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Biological Monitoring
A Practical Field Manual
2nd edition
By the AIHA® Biological Monitoring Committee

Biological Monitoring: A Practical Field Manual,
2nd edition
By the AIHA Biological Monitoring Committee
bit.ly/BiologicalMonitoringPPT
Published by AIHA®
Falls Church, VA
Disclaimer
This publication was developed by experts with background, training, and experience in various aspects of
industrial hygiene (IH) and occupational and environmental health and safety (OEHS), working with information
that was available at the time of publication. AIHA, as publisher, and the author(s) have been diligent in ensuring
that the material and methods addressed in this book reflect prevailing IH and OEHS practices. It is possible,
however, that certain policies or procedures discussed will require modification because of changing federal,
state, local, or international regulations.
AIHA and the author(s) disclaim any liability, loss, or risk resulting directly or indirectly from use of the practices
and/or theories presented in this publication. Moreover, it is the user’s responsibility to stay informed of any
changing federal, state, local, or international regulations that might affect the material contained herein, as well
as the policies adopted specifically in the user’s workplace.
Specific mention of manufacturers and products in this book does not represent an endorsement by AIHA or the
author(s).
Copyright © 2022 by AIHA
All rights reserved. No part of this publication may be reproduced in any form or by any other means (graphic,
electronic, or mechanical, including photocopying, taping, or information storage or retrieval systems) without
written permission from the publisher.
Book design by Jim Myers

Editorial support provided by Lisa Lyubomirsky
Stock Number: EBMG22-654

ISBN: 978-1-950286-11-9
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Biological Monitoring: A Practical Field Manual, 2nd edition
Table of Contents
Editors/Contributing Authors..................................................................................................................................................................... vii

Foreword/How to Read This Guide.......................................................................................................................................................... ix
Acknowledgments.......................................................................................................................................................................................... x
1. Purpose.........................................................................................................................................................................................................1
2. Scope.............................................................................................................................................................................................................1
3. Definitions and Abbreviations............................................................................................................................................................1
4. Significance and Uses............................................................................................................................................................................5
5. Elements of a Biological Monitoring Program in an Occupational and Environmental Hygiene Program........5
5.1 Objective............................................................................................................................................................................................5
5.2 Defining Biological Monitoring..................................................................................................................................................6
5.3 When Is Biological Monitoring Appropriate?.......................................................................................................................6
5.4 Cautionary Notes on Biological Monitoring..........................................................................................................................7
5.5 Roles and Responsibilities..........................................................................................................................................................7
5.6 Developing a Process to Create a Biological Monitoring Program..............................................................................8
5.7 Elements of a Written Biological Monitoring Protocol......................................................................................................9
5.7.1 Objective............................................................................................................................................................................9
5.7.2 Process Summary...........................................................................................................................................................9
5.7.3 Participants.......................................................................................................................................................................9
5.7.4 Collection Schedule..................................................................................................................................................... 10
5.7.5 Collection Procedure................................................................................................................................................... 11
5.7.6 Questionnaire Administration................................................................................................................................. 11
5.7.7 Quality Control.............................................................................................................................................................. 11
5.7.8 Documentation............................................................................................................................................................. 11
5.7.9 Analytical Procedures................................................................................................................................................. 12
5.7.10 Reviewing and Reporting Results......................................................................................................................... 12
5.7.11 Follow-Up Actions....................................................................................................................................................... 12
5.8 Sampling and Analytical Method Issues............................................................................................................................ 12
5.9 Implementation of a Biological Monitoring Program...................................................................................................... 13
5.10 Data Analyses, Reporting, and Periodic Review............................................................................................................. 13
5.11 Reports to Participants and Management........................................................................................................................ 13
5.12 Stopping a Program................................................................................................................................................................... 13
Copyright AIHA® For personal use only. Do not distribute. iii

6. Sampling and Analysis....................................................................................................................................................................... 14

6.1 Introduction to Sampling.......................................................................................................................................................... 14
6.1.1 Sampling Personnel......................................................................................................................................................... 14
6.1.2 Sample Collection and Shipping................................................................................................................................. 14
6.1.3 Field Blanks and Other Blanks.................................................................................................................................... 15
6.1.4 Labels................................................................................................................................................................................... 15
6.1.5 Baseline Sampling........................................................................................................................................................... 15
6.1.6 Sampling Other Than for Biological Monitoring.................................................................................................... 16
6.1.7 Documentation.................................................................................................................................................................. 16
6.1.8 Safety................................................................................................................................................................................... 16
6.2 Urine Collection............................................................................................................................................................................ 16
6.2.1 Trace Metals....................................................................................................................................................................... 17
6.2.2 Organic Analytes.............................................................................................................................................................. 17
6.3 Blood Collection........................................................................................................................................................................... 18
6.3.1 Metals................................................................................................................................................................................... 18
6.3.2 Organics.............................................................................................................................................................................. 18
6.4 Breath Collection......................................................................................................................................................................... 19
6.5 Saliva Collection.......................................................................................................................................................................... 19
6.6 Hair Collection.............................................................................................................................................................................. 19
6.7 Laboratory QA/QC...................................................................................................................................................................... 19
6.7.1 Definitions and Basics.................................................................................................................................................... 19
6.7.2 Analytical Chemistry Laboratories and Biological Monitoring........................................................................ 22
6.7.2.1 Identifying Laboratories Initially................................................................................................................ 22
6.7.2.2 Selecting the Marker...................................................................................................................................... 23
6.7.2.3 Availability of Standard Reference Materials....................................................................................... 24
6.7.2.4 Proficiency Testing.......................................................................................................................................... 25
6.7.2.5 Preparation of Spiked Samples................................................................................................................. 25
6.7.2.6 Frequency of QC Samples........................................................................................................................... 26
6.7.2.7 Corrective Actions........................................................................................................................................... 26
7. Using Results........................................................................................................................................................................................... 26
7.1 Control Programs........................................................................................................................................................................ 26
7.1.1 Exposure Assessment.................................................................................................................................................... 27
7.1.1.1 The Exposing Chemical and the Physical State of Its Challenge (Solid, Liquid, or Gas)....... 27
7.1.1.2 Whether Physical Activity (Workload) and Heat Stress Are Factors for Each Worker......... 29
7.1.1.3 PPE, Local Emission Source Controls, General Workplace Controls, and Worker
Training in Their Use...................................................................................................................................... 30
7.1.1.4 Validity of Sampling, Storage, Transport, and Analytical Procedures for the Marker.............. 30
7.1.2 Health Surveillance and Medical Surveillance....................................................................................................... 32
7.1.2.1 Scientific Definitions....................................................................................................................................... 32
7.1.2.2 OSHA Medical Screening and Medical Surveillance.......................................................................... 33
iv Copyright AIHA® For personal use only. Do not distribute.

8. Ethical and Legal Aspects of Biological Monitoring............................................................................................................... 38

8.1 Ethical and Legal Basics........................................................................................................................................................... 38
8.2 Ethical and Legal Considerations for Implementing Biological Monitoring............................................................ 40
8.2.1 Before Biological Monitoring........................................................................................................................................ 41
8.2.2 Performing Biological Monitoring............................................................................................................................... 41
8.2.3 After Biological Monitoring........................................................................................................................................... 41
8.2.3.1 Timely Notification.......................................................................................................................................... 41
8.2.3.2 Right to Know................................................................................................................................................... 42
8.2.3.3 Confidentiality of Results............................................................................................................................. 42
8.2.3.4 Administrative Removal............................................................................................................................... 42
8.2.3.5 Responsible Employer Use of Biological Monitoring Data............................................................... 42
8.2.3.6 Preemployment Testing................................................................................................................................ 42
8.2.4 Sensitized Individuals and Biological Monitoring................................................................................................. 42
9. References................................................................................................................................................................................................ 43
Appendix I: Introduction to Biological Monitoring; Questions and Answers......................................................................... 45
Appendix II: Case Studies......................................................................................................................................................................... 73
Case Study 1: Importance of Biological Monitoring for Urinary 1-Hydroxypyrene (1HP) in Assessing Dermal
Exposure for Coke Oven Workers: Biological Monitoring to Represent a Class of Compounds................................ 73
Case Study 2: Biological Monitoring for Estrogens and Progestins as Indicators of Occupational
Exposure in the Reformulation of Hormone Replacement Therapy Products: Saliva Biological
Monitoring................................................................................................................................................................................................. 74
Case Study 3: 4,4’-Methylene Dianiline Spill at a Large Chemical Manufacturing Facility in the Southwestern
United States: Urine Monitoring as an Index of Exposure...................................................................................................... 75
Case Study 4: Protectiveness of Negative and Positive Pressure Respirators and Contribution of
Dermal Exposure to Carbon Disulfide Exposure in the Viscose Rayon Industry: Urine Monitoring for
TTCA in Tandem With Personal Air Sampling............................................................................................................................. 76
Case Study 5: N,N-Dimethylacetamide Dermal Exposure to Workers in the Acrylic Fiber
Manufacturing Industry........................................................................................................................................................................ 78
Case Study 6: Cadmium and Past Exposures.............................................................................................................................. 79
Case Study 7: Workplace Protection Factors for Lead Fume for Powered Air-Purifying Respirators
in a Brass Foundry: Blood Lead Must Be Used to Ascertain True Protectiveness of Respirators............................. 79
Case Study 8: 2-Butoxyethanol Exposure for Window Cleaners: Urine Monitoring as a Means
to Gauge Noninhalation Exposure................................................................................................................................................... 80
Case Study 9: Urine Biological Monitoring After Hexamethylene Diisocyanate Exposure During
Motor Vehicle Repair Spray Painting to Test Personal Protective Equipment Protectiveness.................................... 81
Case Study 10: Effect of Respirator Use on Exposure to 2-Methoxyethanol.................................................................... 82
Case Study 11: Death by Dimethylmercury Poisoning in a Laboratory Researcher:
The Utility of Hair Analysis to Reconstruct Metal Exposures.................................................................................................. 83
Case Study 12: Exhaled Breath Measurements for Tetrachloroethylene Exposures in
Dry-Cleaning Shops.............................................................................................................................................................................. 84
Case Study 13: Breath Analysis for Freon-113 as a Tool for Evaluating Respirator Performance.......................... 85
Case Study 14: Personal Exposure to JP-8 Jet Fuel at Air Force Bases: Exhaled Breath
Analysis Versus Breathing Zone Air Sampling Results for a Relatively Nonvolatile Fuel............................................. 86
Copyright AIHA® For personal use only. Do not distribute. v

Case Study 15: Air and Biological Monitoring of Solvent Exposure During Graffiti Removal..................................... 87
Case Study 16: Biological Monitoring and Air Sampling for Thorium for Mineral Sands Workers:
Biological Monitoring and Radioactive Elements........................................................................................................................ 88
Case Study 17: Organocarbamate Pesticide Exposure Assessment: Carbaryl Exposure to Farmer
Applicators and Their Families.......................................................................................................................................................... 89
Case Study 18: Organophosphate Intoxication of a Worker in a Plastic Bottle Recycling Plant:
Unexpected Events Can Lead to Health Problems..................................................................................................................... 90
Case Study 19: Methylene Chloride, Carbon Monoxide, and Carboxyhemoglobin:
The Same Marker but Different Kinetics......................................................................................................................................... 91
Case Study 20: Aplastic Anemia in a Petrochemical Factory Worker................................................................................. 92
Case Study 21: Dental Worker Mercury in Nails, Hair, and Urine......................................................................................... 93
Case Study 22: 1,3-Butadiene Exposures in Butadiene Polymer Manufacturing........................................................... 93
Case Study 23: Urinary Cotinine and Smoking Stoppage After a Smoking Ban............................................................. 94
Case Study 24: Tungsten and Cobalt in the Hard Metal Industry......................................................................................... 95
Case Study 25: The Use of Plasma Indium Concentration as a Biomarker of Cumulative
Indium Exposure..................................................................................................................................................................................... 96
Case Study 26: Biological Monitoring of Pyrethroid Exposure of Pest Control Workers in Japan............................. 97
Case Study 27: Behavior of Aluminum in Aluminum Welders and Manufacturers of
Aluminum Sulfate—Impact on Biological Monitoring................................................................................................................ 98
Case Study 28: Biological Monitoring of Blood Naphthalene Levels as a Marker of Occupational
Exposure to PAHs Among Auto Mechanics and Spray Painters in Rawalpindi.............................................................. 99
Case Study 29: Study of Urinary Concentrations of Mandelic Acid in Employees Exposed to Styrene................100
Case Study 30: Biological Monitoring of Occupational Exposure to Dichloromethane by Means of Urinalysis for
Unmetabolized Dichloromethane...................................................................................................................................................101
Case Study 31: A Pilot Biomonitoring Study of Cumulative Phthalates Exposure Among Vietnamese American
Nail Salon Workers..............................................................................................................................................................................101
Appendix III: Background Concentrations for Biological Monitoring of Environmental Chemicals..............................103
Appendix IV: Consent Forms for Biological Monitoring...............................................................................................................105
Appendix V: Some Important Internet URLs for Biological Monitoring..................................................................................113
Appendix VI: Biological Monitoring for Evaluating Occupational Exposure to Toxic Chemicals Slide
Presentation: An Introduction..........................................................................................................................................................115
Appendix VII: Overview: Intake, Internal Movement, Metabolism, and Excretion of Exposing Chemicals
in the Body..............................................................................................................................................................................................117
vi Copyright AIHA® For personal use only. Do not distribute.

Editors
1st Edition
• Shane S. Que Hee, MS, PhD, RPIH, FAIC, FAIHA; Department of Environmental Health Sciences and UCLA
Center for Occupational and Environmental Health, Fielding School of Public Health, University of California
at Los Angeles
2nd Edition
• Lee Brum, PhD, F-ABFT, FAIHA; NMS Labs, Horsham, PA
• Kim Diep, CIH, BSc, MEng
• Shane S. Que Hee, MS, PhD, RPIH, FAIC, FAIHA; Department of Environmental Health Sciences and UCLA
at Los Angeles
Contributing Authors
This guideline is sponsored and maintained by the AIHA Biological Monitoring Committee. Present and former
committee members who contributed (in parentheses) include the following.
For the 1st Edition:

• Mark Boeniger, CIH; NIOSH (Appendix VII)
• Tim Buckley, PhD, CIH; Johns Hopkins University SPH, Department of Environmental Health Sciences
(Appendix VII)
• James Calpin, CIH; Analytics Corporation (Appendix IV)
• Kevin Cummins, CIH; OSHA Health Response Team (Section 5; Case Studies 1–3)
• Jean Grassman, PhD; Brooklyn College CUNY (Section 8.2)
• Larry K. Lowry, PhD, ABCC; Occupational Health Sciences, University Texas Health Center at Tyler
(Appendix VII)
• Paul R. Michael, PhD, CIH; Monsanto Company (Section 6)
• Dan Napier, MS, CIH, CSP; DNA Industrial Hygiene (Appendix VII)
• Shane Que Hee, MS, PhD, RPIH, FAIC, FAIHA; Department of Environmental Health Sciences and UCLA
Center for Occupational and Environmental Health, School of Public Health, University of California at
Los Angeles (Sections 5–8; Case Studies; Appendices I, III, and VI)
• P. Jenny E. Quintana, MPH, PhD; Graduate School of Public Health, San Diego State University (Appendix VI)
• Garry Spies, CIH, CSP; Pharmacia (Section 5; Case Studies 5 and 6)
• Reggie Suga, SC, CIH, CHMM; Tetra Tech NUS (Sections 6 and 7)
• Glenn Talaska, PhD, CIH; Department of Environmental Health, University of Cincinnati Medical Center
(Appendix VII)
• Paul Ullucci; ESA Laboratories (Section 6)
• Albert M. Zielinski, CIH; GE Lighting (Section 6)
Copyright AIHA® For personal use only. Do not distribute. vii

For 2nd Edition:

(Appendix III from the 1st edition was deleted and the following Appendix numbers decreased by 1)
• Lee Blum, PhD, F-ABFT, FAIHA; NMS Labs, Horsham, PA (Sections: Foreword to the second edition; 1
Purpose; 2 Scope; 3 Definitions [with Kim Diep]; 4 Significances and Uses; Appendices I [with Shane Que
Hee] and III; Case Studies 24 and 25).
• Pamela Burda, MS, DHP, CIH, CSP (Sections 6 and 7; Case Studies 27, 28, 29, 30, and 31).
• Kim Diep, BSc, MEng, CIH (Section 3 Definitions [with Lee Blum], edited overall changes)
• Shane Que Hee, MS, PhD, RPIH, FAIC, FAIHA; Department of Environmental Health Sciences and UCLA
at Los Angeles (Sections 5 [with Sheldon Rabinovitz], 7, 8, 9; Case Studies 4, 7–23; Appendices I [with Lee
Blum] and VI)
• Sheldon Rabinovitz, PhD, CIH, FAIHA (Section 5 [with Shane Que Hee], Case Study 26 [with Pamela Burda];
Appendix VII).
Staff Liaisons
1st Edition
• Margaret A. Breida, MS; AIHA
• Mili Mavely; AIHA
2nd Edition
• Thursa Pecorado; AIHA
• Janice Allen; AIHA
• Gouhar Nayeem; AIHA
viii Copyright AIHA® For personal use only. Do not distribute.

Foreword
The Biological Monitoring Committee prepared this document to be used as a guide and reference for entry-level
industrial hygienists and occupational health specialists. The committee worked for several years preparing
this text. The contributing authors are recognized individually, but many other volunteers spent countless hours
assisting and working with the listed authors.
We hope industrial hygienists and occupational health specialists, those intending to become occupational
safety and health personnel, practicing public health professionals, and informed members of the general public
will use this manual to orient themselves relative to the practice and theory of biological monitoring. Although
it is impossible to have all the answers, the Biological Monitoring Committee tried to address many of the major
issues according to the perspective of the industrial hygienist with as little technical content as possible at a level
also appropriate for students studying for Bachelor of Science degrees.
Foreword to the Second Edition

The second edition of this Practical Field Manual has the same purpose and scope as that of the first edition.
The members of the current Biological Monitoring Committee recognize the original authors for their expertise
in the field of biological monitoring and their commitment to creating the first edition of this manual. It is on their
shoulders that we updated and revised this manual for today’s practicing industrial hygienists and occupational
health professionals. We also acknowledge all the volunteers and professionals for their contributions to this
second edition, in the hope of ensuring the health and safety of workers in the workplace.
How to Read This Guide

Readers with various levels of experience can use this manual.
The PowerPoint slideshow (see enclosed QR code) can be used as an introduction for entry-level industrial
hygienists and occupational health specialists or for experienced occupational health professionals as a review
or for training purposes. Entry-level industrial hygienists should also attempt their own answers to the questions
posed in Appendix I, which provides an introduction and answers to some of the most commonly asked questions
in biological monitoring. They should compare their answers with those provided in Appendix I and then read the
applications of each question to the biological monitoring of benzene and lead. The same set of questions should
then be applied to another exposing chemical for familiarization with the basics of biological monitoring and the
kinds of documentation necessary for each chemical.
Industrial hygienists familiar with the basics of biological monitoring may wish to begin with how a biological
monitoring program is conceptualized, developed, and implemented in the workplace (Section 5). Others with specific
questions may wish to consult specific sections directly—for example, how to do sampling (Section 6) or how to
interpret results (Section 7). In each case, it is important that each section be read through from the beginning.
Staff note: This guideline was developed using AIHA’s guideline procedures, which include peer review by AIHA
technical committees and outside experts.
Comments are welcome and should be directed to AIHA Scientific and Technical Initiatives Staff at 3141 Fairview
Park Drive, Suite 777, Falls Church, VA 22042.
Lee Brum, Kim Diep, Shane Que Hee, Editors
Diana Larson, John Snawder, Craig Willey, Peer Reviewers
Copyright AIHA® For personal use only. Do not distribute. ix

Acknowledgments
Thanks to all who helped create this guide:
1st Edition
• To Jenny Quintana, who did the early heavy lifting.
• To the committee chairpersons―Paul Ullucci, Kevin Cummins, Tim Buckley, Jim Calpin, Jean Grassman, and
Dan Napier―who must have wondered if the project would ever be completed.
• To AIHA’s Margie Breida, who patiently listened to all of our excuses.
• To AIHA for its support.
• To all the contributing authors.
• To all the production people.
• To all spouses and significant others who had to support their partners.
• To Mark Boeniger of NIOSH for his indefatigable optimism.
The editor and authors acknowledge and thank everyone who helped, assisted, or otherwise aided and abetted
them. Special thanks go to Margie Breida of AIHA who was indispensable in facilitating the task. We also thank
AIHA for having faith in our committee.
2nd Edition
• To all the team members contributing their efforts to the revision.
• To our colleagues who reviewed and provided comments.
• To all the committee chairpersons since 2014 who expectantly placed this revision in their work plans.
• To all AIHA staff who helped.
• To all their family members and friends who helped the contributing authors and the AIHA production team
survive the rigors of this revision.
• To Kim Diep, who kept us on the straight and narrow.
x Copyright AIHA® For personal use only. Do not distribute.

1. Purpose Administrative rotation: The process that reassigns

the worker through different job descriptions to
reduce exposure.
This guide is written as both a text for undergraduate Aerodynamic diameter for an aerosol: The
courses in industrial hygiene and a practical field diameter of the spherical water droplet that has
manual for entry-level and experienced practicing the equivalent volume at the same conditions of a
industrial hygienists. This guide, along with the most solid or liquid aerosol particle.
current methods for specific biological monitoring Aerosol: The airborne particles that are solid or liquid.
protocols and more theoretical texts, will enable the Alveoli: The anatomical sites in the lungs where
practicing professional to further excel in the conduct oxygen and carbon dioxide exchange occur.
of good science in the field. Analysis: The procedure applied to identify and
quantify an element, compound, or material.
2. Scope Antibody: The protein that a living organism is

stimulated to make from B lymphocytes when a
foreign antigen is present.
This guide covers the general basics of biological Antigen: A large macromolecule that triggers an
monitoring from the perspective of a field industrial immune response.
hygienist and also constitutes a field manual for the Baseline sampling: Sampling of a biological
trainee industrial hygienist. The guide is also suitable specimen prior to worker exposure.
for undergraduate students because it contains a Behavioral change: A condition that describes a
slide presentation and a question-and-answer section change in attitude, nervous state, or behavior.
(Appendix I). The guide cannot answer advanced Biochemical epidemiology: The correlation of
questions about the entirety of biological monitoring, chemical markers measured in bodily media with
but many books and scientific articles are available for epidemiologic variates.
that purpose. Such advanced topics include analytical Biologically effective dose: The amount (mass or
methods, advanced toxicological mechanisms, moles) of an exposing compound that actually
toxicokinetics, and advanced risk assessment for reaches a target organ.
specific chemicals. Biological equivalent values: The values of
biological markers that correlate to external
guidelines.
3. Definitions and Biological exposure index (BEI®): A guidance value
Abbreviations that is published by ACGIH for assessing biological
monitoring results.
Biological monitoring: The measurement of
For the purposes of this guideline document, the chemical markers in bodily media that are
following terms and definitions apply. The AIHA indicative of external exposure to chemical,
Glossary of Occupational Hygiene Terms should be physical, or biological agents.
referenced for any terms not defined in this section. Biomarker: The determinant or marker that is
measured in a biological system.
Absorbed dose: The amount (mass or moles) of Blank: A sample that does not contain the analyte;
exposing chemical that actually enters into the there are many possible blanks.
bloodstream through any external routes of Blood: The red-colored fluid contained in arteries
exposure. and veins that is pumped by the heart, providing
Accuracy: The term that describes how close the the body with nutrition, oxygen, and waste
data are to the true values. Accuracy is usually removal.
expressed as the percent (%) relative error and is Boiling point: The temperature at which a liquid
positive or negative. completely changes into the gaseous state at
ACGIH: The abbreviation for the American a specified external pressure and at which the
Conference of Governmental Industrial Hygienists. vapor pressure of an analyte becomes equal to the
Action level: The value that triggers an action to start external pressure.
control procedures, which varies with agencies. Breathing zone air sampling: The air sampling that
Adduct: The product of a reaction that occurs is collected near the worker’s lapel.
between a macromolecule of the body and the Cancer: The condition where cells grow and divide
exposing chemical or a metabolite. without control.
Copyright AIHA® For personal use only. Do not distribute. 1

Chelate: The compound formed when a metal bonds End-of-shift sampling: Sampling that takes place at
with organic functional groups. the end of the work shift or time of exposure.
Chromatography: A technique used to separate Endogenous: A substance found naturally in the
components of a mixture. living system under study.
Circadian rhythm: Unique cycling of a process in Engineering controls: Controls that manipulate the
a living organism that could be on the scale of physical work environment and do not involve
minutes to decades. personal protection equipment.
Coefficient of variation: The result derived from the EPA: The abbreviation for the United States
standard deviation divided by the representative Environmental Protection Agency.
value (often the arithmetic mean). Enzyme: An agent that catalyzes a biological
Conjugate: The product of a reaction between reaction and is not itself consumed in the reaction.
the exposing chemical or a metabolite with an Ethics: The discipline of conduct for a person or the
endogenous biochemical substrate. members of a profession dealing with what is
Control chart: A plot of marker concentration good and bad based on a written code.
compared to the time for a worker or a group of Excretion: A biomarker that appears outside of the
workers. body.
Detection: The procedure used for the qualitative Exposure: The amount or concentration of a material
analysis of a chemical compound, element, or that contacts the body.
material. Field blank: A sampling container (and any
Detection limit: The concentration that is needed presampling contents) that is subjected to the
to yield an instrument response discernible from same operational sampling procedures in the field
the background signal. It is often calculated as the as the real sample in parallel without actually
arithmetic mean of the background signal plus 3 taking the sample.
times its standard deviation and is also called the Fluids: A state of matter that flows under pressure;
limit of detection (LOD). that is, gas and liquid states.
Dimensions: the length or width. Common units are Formulation: A mixture of compounds used for
meters (m), foot (ft), inches (in). The metric units specific industrial or user purposes.
are often preceded by the prefixes: M- = mega- = Gas: The standard state of matter that a material
one million; k- = kilo- = one thousandth; c- = centi- or compound has that is wholly gaseous at a
= one hundred; d- = deci- = one-tenth; m- = milli- = specified temperature and pressure.
one thousandth; u- = micro- = one millionth; n- = Genetic factors: Traits that are determined by the
nano- = one thousandth of a millionth; p- = pico- = genes (DNA).
one millionth of a millionth. Also, 12 inches = one Glutathione: The tripeptide Glu-Cys-Gly, where Glu
foot; 3 feet = one yard; 480 yards = one mile. is glutamic acid, Cys is cysteine, and Gly is glycine.
Dipstick: An impregnated stick that changes color A substrate in conjugation reactions.
when exposed to the analyte of interest at a Hair: The flexible shaft of distinct coloring that
designated concentration. protrudes from the skin surface.
Direct-reading instruments: Instruments that give Half-life: The time needed for a reactant to be
almost instantaneous readings on site. reduced to half of its original concentration; t0.5 =
Dose response: The correlation that compares a 0.693/k, where k is the rate constant in units of
biological effect or biological parameter with time–1.
exposure dose. Health surveillance: The periodic monitoring of
Dynamic air sampling: Air sampling that is collected health used to assess risk and detect health
with a pump. effects of exposures to chemical, physical, and
Edema: The swelling that occurs from fluid biological agents.
accumulation in tissues, either within cells or in Homeostasis: The state that describes the normal
interstitial spaces. stable control of various body parameters, such as
Element: An atom that is characterized with an temperature and osmotic pressure.
assigned atomic number (number of protons). Hormone: A chemical agent secreted by one gland
Elimination: The process that occurs for the internal to act on another gland or organ.
clearance of a biomarker from an internal organ. Hydrolysis: The reaction that occurs between a
End-exhaled breath (alveolar exhaled breath): The molecule and water.
exhaled breath forced from the lungs after natural Hypersensitivity: A state of susceptibility in the
exhalation. immune system that occurs above the norm.
2 Copyright AIHA® For personal use only. Do not distribute.

Immune response: Chemical/cellular response of the Macromolecules: High molecular weight

body to an antigen or invading microorganism. biochemicals (e.g., proteins, phospholipids,
Informed consent: Permission given by the worker glycosides, and nucleic acids) and their mixed
for procedures that will involve the worker before analogs such as glycolipids, lipoproteins, and
the procedures are instituted. chromatin (nuclear protein/DNA complex).
Inhalation: The inspiration or breathing in that Marker: The determinant that is measured in human
brings air into the body. body media.
Inorganic: A compound that does not contain Matrix spike: A known amount of analyte added
carbon. to a sample that is to be analyzed. The process is
Interindividual variation: The variation of biomarker also called spiking.
concentrations that occurs among individuals Medical monitoring: The performance of medical
exposed to the same concentration of an exposing tests and physical examinations used to evaluate
agent. an individual’s ongoing exposure to a factor that
Internal dose: The amount of an exogenous could negatively impact that person’s health.
substance that is actually absorbed by the body. Medical removal: The removal of the worker from
Internal standard method: A standard curve that the workplace for medical reasons.
is constructed by plotting the ratio of the analyte Medical screening: A method for detecting disease
response relative to that of a specific amount of a or body dysfunction before medical care is sought
reference compound added to all samples versus (OSHA).(1)
analyte concentration. Medical surveillance: The analysis of health
Intrinsically safe: Conditions for 30 minutes (NIOSH) information to look for workplace problems that
that are not immediately dangerous to life and require targeted prevention (OSHA, NIOSH).(2)
health. Metabolite: A byproduct of the biochemical
Ionizing radiation: Radiation with sufficient energy alteration of an exposing chemical that is typically
to remove electrons from atoms or molecules, e.g., catalyzed by cellular enzymes.
ionization of oxygen in air. Midstream urine: A urine sample taken that involves
Kidneys: The pair of organs that is responsible for discarding the first couple of milliliters to eliminate
conserving body macromolecules, excreting low- potential contamination from microorganisms or
molecular weight end products of metabolism and sperm.
catabolism in the urine, and maintaining body salt Mixed exhaled breath: The breath that is naturally
balance. exhaled without force.
Label: (1) The identifiers used on an individual Molecular epidemiology: Population studies that
sample container; (2) an identifier that is inserted involve molecular biologic and genetic markers.
into an atom or molecule that allows detection. Molecular weight: The weight that consists of all the
Lean body mass: Total body weight measured atoms in a molecule relative to carbon 12C6.
without the fat weight. Mutagenicity: Transmissible changes that occur in
Limit of detection (LOD): See detection limit. the genes; altered DNA.
Limit of quantitation (LOQ): See lower quantifiable Negative interference: An interference that causes
limit. the observed value to be decreased relative to its
Liver: The major organ of metabolism, catabolism, true value.
and anabolism of the body and the major one for NIOSH: The abbreviation for the National Institute
conjugation; it eliminates high molecular weight for Occupational Safety and Health.
conjugates in the bile. It also stores glycogen. Occupational illness: An abnormal health condition
Lower quantifiable limit (LQL): The lowest caused or contributed to by a noninstantaneous
concentration at which an analyte can be detected event or exposure in the work environment
and reliably measured using predefined criteria for (OSHA).(3)
inaccuracy and imprecision. It is often calculated Octanol/water coefficient: The ratio of the solubility
as the arithmetic mean of the background blank of analyte in octanol compared to that in water at
plus 10 times its standard deviation and is also the same temperature.
called the limit of quantitation (LOQ). Odor threshold: The air concentration at which an
Lungs: The pair of organs responsible for oxygen odor can be perceived.
and carbon dioxide exchange for the blood of the OSHA: The abbreviation for the Occupational Safety
body through inhalation and exhalation. and Health Administration.

Oxidation: The process where oxygen is gained Replicate analysis: The analysis performed with
or hydrogen is lost in a compound or the loss of split samples, or a sample analyzed multiple times.
electrons or gain in oxidation number for an atom. Respirable aerosol: Aerosols that have an
Oxide: The compound that results after reaction of a aerodynamic diameter of < 10 µm.
metal element with oxygen. Sampling: The act of collecting or taking a portion of
Passive air sampling: Air sampling that occurs the whole.
without a pump. This is also called diffusive air Sebum: The waxy excretion on the skin surface that
sampling. is secreted by sebaceous glands.
Pathogen: An agent that causes disease. Selectivity: The degree to which an analytical
Personal breathing zone air sampling: The sampler method can determine specific substances in a
is located on the lapel of the worker during mixture.
integrated air sampling. Semen: The viscous, creamy fluid obtained from the
Personal protective equipment (PPE): Materials or penis on ejaculation.
equipment that are worn to protect the worker Serum (blood): The clear liquid that appears on
from health and safety hazards. blood coagulation/clotting.
Pesticide: An agent that controls or kills pests. Skin: The outer solid layers of the body that consist
pH: The value represented by minus logarithm to of the stratum corneum, the epidermis, and the
base 10 of the hydrogen ion activity (which for the dermis.
pH range 1‒11 at 25°C is equal to the hydrogen Solubility: The maximum (saturation) amount of a
ion molar concentration in aqueous solution). solid that a specified solution volume can contain
Phase I process: Biotransformation that results in without a precipitate being evident.
reduction, oxidation, or hydrolysis of an exogenous Specific gravity: The density of a material or
substance. compound relative to the density of water at the
Phase II process: The bioconjugation that occurs same conditions.
between an exogenous substance and its Spectroscopy: The use of electromagnetic radiation
Phase I metabolites with a nonmacromolecule for the detection and quantitation of matter.
biochemical. Sperm: The cells found in semen that contain the
Plasma (blood): The liquid that does not contain male contribution to genetic inheritance.
the cellular components of blood on sitting or Spot urine sample: A urine sample collected as a
mild centrifugation of a blood sample; however, single void at a designated time.
it contains electrolytes, nutrients, and proteins of Sputum: Watery fluid with solids excreted from the
blood. throat and upper lungs on expectoration.
Positive interference: An interference that causes Standard operating procedures (SOPs): The
the observed value to be increased over its true written procedures that are used and referred to
value. for routine operations.
Precision: The determination of a measurement’s Standard reference material (SRM): A bulk material
reproducibility that is usually expressed as the that has been analyzed by several different
coefficient of variation (CV) of the data. Intra- analytical techniques and can be used in quality
assay precision is the CV of samples tested assurance.
multiple times within the same batch. Inter-assay Symbiotic: A state of being in mutual association.
precision is the CV of replicates of samples tested Threshold limit values (TLVs®): Quantitative
between batches. guideline(s) for healthy workers developed by
Preservative: A substance that is added to a ACGIH to assist in the control of health hazards.
sampling container to preserve the analyte and its Time-and-motion study: A study that is used to
concentration. It can also prevent microbial growth assess how much time and how much motion a
in aqueous or biological media. worker expends during the work shift or during
Quality assurance: The written program or set of unit processes.
operating procedures used to achieve control of Trace metals: The metals that are not in high
the measurement process. concentrations in the body.
Quality control: The proof that verifies the accuracy Twenty-four-hour urine sample: A cumulative urine
and precision of the measurement process. sample that is taken (all voids collected) over a
Relative response factor: The detector response period of 24 hr.
that is used for a determinant relative to that of a Unit process: A sequence of steps that is
reference compound. characterized.

Uptake: The movement of substances into the body • The manual contains information pertinent to the
from the environment. The rate is determined by interaction of the health professional, the worker,
the analyte mass absorbed divided by analyte unions, and corporate administration relative to a
mass exposed to over a specific time period. biological monitoring program.
Urine: The yellowish, watery, nonviscous fluid • Case studies are provided to illustrate the practical
containing bodily waste products that is filtered use of biological monitoring.
from the blood by the kidneys. It is stored in the • The manual contains a question-and-answer
bladder and voided through the penis in males section on biological monitoring that focuses on
and the urethra in females. lead and benzene, two major toxicants with which
Vapor: The gaseous state of a compound that all occupational health professionals must be able
is above its liquid or solid standard state at a to cope.
specified temperature and pressure. • The manual contains an example of consent forms
Vapor pressure: The pressure exerted by a solid as models.
or liquid compound at a specific temperature • The manual contains pictorial material in the form
and external pressure when the headspace air is of slides to enable beginners to grasp the essential
saturated with the compound. scientific principles of biological monitoring. It then
Volume: A parameter that has the units of tests this knowledge as it applies to benzene and
dimension to the cube exponent. Some important lead in a question-and-answer format.
volume equivalencies include: one thousand liters • The manual contains essential knowledge for
= one cubic meter; one thousand milliliters = one industrial hygienists to help them communicate
liter. See also the entry for "dimensions." with industrial hygiene chemists.
WEELs®: The abbreviation for workplace
environmental exposure levels.
5. Elements of a Biological
4. Significance and Uses Monitoring Program in
Significance an Occupational and
• This is an updated field manual for biological Environmental Hygiene
monitoring intended for use by industrial hygienists
and other occupational health professionals. Program
• Previous books on biological monitoring have
concentrated on the science associated with the 5.1 Objective
field. This manual considers management, policy,
Biological monitoring is the measurement of
ethics, legal issues, and other issues germane to
chemicals, their metabolites, and markers of affected
the practice of industrial hygiene and occupational
body systems in biological matrices (urine, blood, or
health.
breath) after occupational exposure to workplace
• The language in this manual is as nontechnical
stressors. Although applicable to all exposure
as possible to allow for use by many different
stressors, such as chemical, physical, biological,
professionals at varying levels of education.
mechanical, psychological, and ergonomic agents,
• The manual applies a multidisciplinary and
this section will focus only on exposure to chemical
interdisciplinary holistic approach.
agents.
• The manual contains illustrative case studies of
Biological monitoring after chemical exposure is an
biological monitoring.
important tool in an occupational and environmental
• The manual contains an updated slide
hygiene program. Under certain exposure scenarios,
presentation on the principles of biological
such as when a chemical agent is absorbed through
monitoring.
the skin, air monitoring results are not adequately
related to inhalation (lung) exposure or health risk.
Uses However, because biological monitoring involves
• The manual contains information to enable a field unique ethical issues, more planning and more re-
industrial hygienist or an occupational health sources are required to ensure valid results than are
professional to set up, run, and terminate a necessary for air monitoring. For these reasons and
biological monitoring program. others, the occupational and environmental health

program within an organization must define the role It is important to place biological monitoring in
of biological monitoring before program development. perspective relative to health monitoring and medical
Among the issues that should be resolved prior to im- monitoring. The latter two can be defined as periodic
plementing biological monitoring programs is defining assessment of the health status of workers to detect
the position of an organization’s top management on early effects (health) or clinical effects (medical). Bio-
biological monitoring. Very few workplace regulations logical monitoring is generally not intended to detect
in the United States require biological monitoring. These the early medical signs or effects of chemical expo-
include benzene,(4) lead,(5,6) and cadmium.(7) Under most sure and is considered part of health monitoring. This
circumstances, biological monitoring is considered distinction can have implications on recordkeeping,
because it will provide a more accurate measurement confidentiality, worker rights, and information access
of health risk than air sampling will. Management may for industrial hygienists.
wish to limit the role of biological monitoring in an Frequently, industrial hygienists and occupation-
occupational and environmental hygiene program to al health professionals are not given access to the
a certain set of circumstances to ensure that ethical results of medical monitoring (clinical chemistry
issues are addressed, to limit legal liabilities that might results) because of patient confidentiality. To imple-
arise from the data, and to deploy scarce resources ment exposure controls, industrial hygienists must
wisely. It will be necessary for the occupational and have access to exposure monitoring results, which
environmental hygiene professional to explain the value include data from biological monitoring. Unfortu-
of biological monitoring to facility management in terms nately, the situation is not necessarily clear-cut in the
of worker productivity, costs, benefits, and company cases of blood acetylcholinesterase activity, methe-
aims and to help define the potential role of biological moglobin content, carboxyhemoglobin content, and
monitoring within the existing occupational and envi- ß2-microglobulin urine concentration. These markers
ronmental hygiene program. of adverse effect are also used in biological monitor-
If the workforce of a facility has a union, the union ing programs and have ACGIH biological exposure
leadership should be consulted in the planning phase index (BEI)® guidance.(8,9) The ß2-microglobulin urine
to verify that adequate measures are in place to concentration after cadmium exposure is also under
protect the confidentiality of the worker. The under- direct OSHA regulation.
standing and support of a union can help to enlist the Like air monitoring results, biological monitoring
cooperation of the workforce in a biological monitoring results of occupational exposure to a specific chemi-
program. It will be necessary for occupational health cal are considered exposure monitoring, not medical
professionals to explain the value of biological mon- results.(10) As such, they can be communicated to per-
itoring to union leadership in terms of worker health sonnel who were not monitored but similarly exposed.
and union aims. However, some parameters that are measured in a
Proposed training programs at all administrative and biological monitoring program, such as ß2-microglobu-
worker levels must also be integrated within the biolog- lin in the case of cadmium exposure, are not unique to
ical monitoring program during the planning stages. a specific exposure and may be a result of a preexist-
ing medical condition. Therefore, careful consideration
5.2 Defining Biological Monitoring must be given when communicating results to employ-
ees who were not monitored, taking care to protect
A clear definition of biological monitoring must be the privacy of those who were monitored.
developed to explain the explicit role of biological
monitoring within the occupational and environmental
5.3 When Is Biological Monitoring
hygiene program. Additionally, this definition will
describe to management and workers what biological Appropriate?
monitoring is and what it is not. The definition of biological monitoring adopted
Generally, biological monitoring after chemical expo- by the organization and the role of biological
sure is defined as the assessment of human exposure monitoring in the occupational hygiene program will
through the measurement of internal chemical mark- determine which exposure scenarios are selected for
ers of exposure, such as the chemical agent itself, its further evaluation using biological monitoring. The
metabolites, or an exposure-related biochemical or justifications must be in-house ones.
body fluid component change, either unrelated or re- Biological monitoring may be necessary by govern-
lated to disease, in human biological samples. Biologi- ment regulation.(4–7) In the United States, biological
cal monitoring is not air, soil, water, or food monitoring monitoring for lead,(5,6) cadmium,(7) and benzene(4) is
for microbes. required by OSHA under certain conditions. See the

question-and-answer section in Appendix I for re- of results and communication to workers challenging.
quirements for lead and benzene. The industrial hygienist’s task is to assess the contri-
In the industrial setting, biological monitoring is often bution of the workplace exposures and recommend
an adjunct exposure assessment tool to air monitoring. control and prevention measures.
For exposure scenarios in which air monitoring does The sampling and analytical procedures of a biolog-
not adequately measure exposure from all routes, bio- ical monitoring program can be more complicated and
logical monitoring should be considered. critical to the interpretation of the results than those of
Exposure scenarios in which air monitoring is inade- an air monitoring program. For some chemical agents,
quate include the following: the timing of sample collection relative to exposure
can affect the validity of the interpretation. The media
• when the chemical agent is known to pass sampled, generally urine or blood, are complex. This
through the skin or is ingested places unique demands on the analytical method and
• when the chemical agent possesses a long increases the need for an effective program of quality
biological half-life assurance/quality control (QA/QC). Lastly, analytical
• when respiratory protection or other personal costs generally are higher. Combined, these factors
protective equipment (PPE) such as gloves or other highlight the need to plan a biological monitoring pro-
protective garments are used gram carefully to achieve the objectives.
Major instances in which biological monitoring is 5.5 Roles and Responsibilities

justified occur when symptoms of overexposure are
evident or are experienced by the worker at the same Biological monitoring requires input from a number
time that air monitoring results imply that inhalation of technical disciplines. The industrial hygienist is
exposure is not hazardous. required to define the objectives of the program and
To ensure that scenarios justifying biological moni- the sampling strategy and recommend control and
toring are effectively and consistently identified, field preventive measures. Having a capable occupational
industrial hygienists should be trained in the role of physician as a resource is essential. Other resource
biological monitoring in their specific occupational and personnel may be necessary depending on the task at
environmental hygiene programs. hand.
Questions that should be addressed prior to the de-
velopment of a program include the following:
5.4 Cautionary Notes on Biological
Monitoring • How will situations justifying biological
Biological monitoring must be approached with monitoring be identified? If the organization
greater care than air monitoring. Because the data intends to place the responsibility on field
are direct measures of the intakes or biological effects industrial hygienists to identify exposure scenarios
of absorption of chemicals after exposure, biological for which biological monitoring is justified,
monitoring results are generally more relevant to work- training and guidance will be required to ensure
er health than are air monitoring data. The sampling a consistent approach is applied throughout the
procedures are more invasive. Urine, breath, or blood organization.
sampling are generally involved in a biological monitor- • Who will be involved in program development?
ing program. Workers may be concerned that the sam- Some organizations may choose to centralize
ples might be used for drug testing or other purposes the process of biological monitoring program
unrelated to workplace chemical biological monitoring. development to ensure that ethical issues are
Biological monitoring data can be highly variable, adequately addressed, that the approach is
with elevated concentrations one day followed by low consistent companywide, and that resources are
ones the next. This may be caused by differences in effectively used. A central steering team may
exposure time; exposure frequency; exposure inten- coordinate and approve biological monitoring
sity during work shifts; work practices; the protection programs and new biological monitoring requests.
afforded by PPE; occurrence of spills and accidents; A consulting team may need to be assembled,
and differences in each worker’s absorption, metab- consisting of an analytical chemist, toxicologist,
olism, and excretion of the exposing chemical—or a epidemiologist, biostatistician, and occupational
mixture of all these factors. The effects of confound- physician. Team members should have the
ing exposures, both on and off the job, must also be appropriate technical abilities for electronic
considered. This variability makes the interpretation communication, which is often essential.

• Who will review and approve the program? In 5.6 Developing a Process to Create a
addition to an industrial hygienist or occupational Biological Monitoring Program
health professional (and an occupational
physician or nurse, if available), it is useful to Before any sampling is conducted, the exposure
include representatives from human resources conditions and biological monitoring index,
and the legal department as well as a respected determinant, or marker must be carefully evaluated
high administrator. Another alternative is to seek to determine whether biological monitoring is
biological monitoring program accreditation scientifically justified for the exposure scenario. It is
on important activities from accrediting bodies absolutely necessary that management be supportive
outside the organization. of the program. If management has already taken
• What is management's role? Management a position on the role of biological monitoring in the
facility’s occupational and environmental hygiene
must be intimately involved in all phases of the
program, this position should be reviewed and used
biological monitoring program.
as a basis for starting or expanding other biological
• Who pays for method development and sample
monitoring programs.
analysis? Resources should not be a limiting factor
All in-house exposure data should be reviewed.
for those scenarios in which biological monitoring
If air monitoring data have been adequate and low
is justified and necessary to answer key questions
relative to the exposure limit, and dermal absorption
about exposure. Consultation with an analytical
or ingestion are not relevant routes of entry, biological
chemistry resource may be required to choose,
monitoring may not provide additional useful expo-
evaluate, or develop the sampling and analytical
sure information unless clinical symptoms and health
methods and design the QA/QC procedures.
complaints have occurred. The current exposure as-
High method development costs may delay
sessment methodologies should, in some way, require
the implementation of a biological monitoring
biological monitoring to provide a more complete
program. It is useful to find other entities who exposure assessment.
are doing what is proposed to establish program The source of the request for biological monitoring
viability relative to cost. A cost-benefit analysis is should also be considered. If a group of workers or
usually crucial for obtaining management support. a workers’ union expresses concern about an expo-
• Who interprets the results? A consulting team is sure scenario, biological monitoring might be a good
helpful. A physician may be needed to interpret technique to reinforce the existing exposure assess-
the results for legal purposes. To communicate ment. Because biological monitoring is a more direct
the results effectively to the worker, the aid measure of chemical intake from all routes, the results
of industrial hygienists or occupational health might be more persuasive than air monitoring results.
professionals is essential, and nurses may also be The current biological monitoring indices/determi-
effective. The help of toxicologists, biostatisticians, nants and analytical methods should also be read and
and epidemiologists may also be necessary. evaluated. The index/determinant should be appropri-
Analytical chemists are useful to ensure that ate to the exposure scenario. For example, the ACGIH
sampling and analytical results are adequate. BEI for chromium is currently applicable to only a
Results must be communicated to the appropriate specific type of chromium exposure: manual metal arc
parties as soon as practical, but those results stainless steel welding. Certain BEIs require a month
must be accurate and readily understandable. Any or two of exposure prior to biological monitoring to
supporting data and information such as for QC, build up the body burden to a steady-state level.
questionnaires, and observations from the field Likewise, the analytical method referenced in the BEI
must be reviewed to ensure an accurate, thorough, documentation or other source should be evaluated,
and balanced interpretation. and a laboratory capable of performing the method
• How will results be reported to participants? should be identified. If possible, the laboratory should
To management? How will confidentiality be be accredited. An initial determination should be per-
assured? Biological monitoring data should be formed to assess whether the sampling and analytical
communicated in a manner that protects individual methods in the BEI documentation are feasible in the
confidentiality but allows everyone to understand facility and for the actual workplace exposure scenario.
the impact of work practices on exposure levels. If these evaluations conclude that biological moni-
Exposure assessment data, including biological toring is justified for the exposure scenario, it is recom-
monitoring data, can motivate good workplace mended that a team be assembled to develop, review,
hygiene practices. and implement the biological monitoring program. The

team must include representatives from the facility’s to be gained by biological monitoring. Some crucial
occupational and environmental hygiene and occu- questions to be answered relative to conditions in the
pational medicine functions as well as from upper specific workplace include the following:
management. An analytical chemist is necessary to
consult on the sampling and analytical chemistry • Is the index/determinant appropriate for the
methods and the QA/QC procedures. Other personnel, exposure scenario?
such as toxicologists, biostatisticians, epidemiologists, • Are sample collection and the analytical method
and medical specialists, might be valuable. feasible and cost effective?
The exposure scenario must be thoroughly evaluat- • Can potential confounding exposures or medical
ed. A summary of the work process should be done to conditions or treatments be controlled or
reveal the degree of dermal contact and the metabolic determined?
load or work required to complete the tasks. Groups of
workers who appear to be similarly exposed should be The critical decision at this point is to determine
defined. Exposure variability within each apparently whether the current exposure scenario justifies biolog-
similar group should be assessed. For example, expo- ical monitoring and whether biological monitoring is
sure of maintenance personnel who perform many dif- feasible.
ferent tasks may vary greatly. In contrast, the exposure
of a group of workers who perform a single set of sim-
5.7 Elements of a Written Biological
ple tasks on a continuous process may vary little during
the work shift or even from day to day. Variability of Monitoring Protocol
exposure during the work shift and workweek should If the exposure scenario justifies biological moni-
be assessed and used to define a sampling strategy. toring and the program is feasible, a written protocol
Monitoring the most exposed worker first can also indi- should be developed. This protocol will guide all facets
cate whether it is cost effective to monitor others. of the sampling and analytical method. It will be used
If exposure to other compounds is possible during as the basis to inform management and employees
work, the exposure potential to these other com- about the program and its results.
pounds must also be assessed. The type and efficacy The following elements should be included in a pro-
of PPE should be recorded. It is desirable to observe tocol.
the work to judge whether PPE is being used properly.
The number of workers involved in the process and the 5.7.1 Objective
length of the work shift and workweek schedule must
be obtained. Workers should be categorized based on The protocol should define why biological monitoring
their production responsibilities (such as maintenance, is being conducted and what questions the program
production, or supervision). will answer. Defining the purpose of the biological
Information on the relevant biological monitor- monitoring program is essential, both to ensure the
ing index or marker should be assembled. The most program answers the proper exposure questions and
common source for biological monitoring indices is the to know when the program can be stopped.
documentations of the ACGIH BEIs and the German
Biologische Arbeitsstoff Toleranz—Werte (BATs). The 5.7.2 Process Summary
documentation that describes both the justification for This describes the process and the exposure scenario,
the index and the key parameters on how the index including the activities of each group of similarly
is to be applied must be thoroughly reviewed. The exposed workers, the potential for dermal contact or
documentation will include a review of the absorption, ingestion, and the PPE used. Information collected on
toxicokinetics, metabolism, and excretion of the chem- the degree and duration of exposure to the compound
ical agent. Other issues that can be found in the doc- of interest as well as any compounds that can
umentation include information on compounds that potentially confound the results should be summarized
can confound the results from occupational, nonoccu-
in the protocol.
pational, and endogenous sources; medical conditions
and medical remedies that can influence the results;
background concentrations; and the requirements and
5.7.3 Participants
interferences of the analytical methods. The workers to be included in the biological monitoring
The information assembled should be reviewed to program must be clearly defined. Among the
determine whether biological monitoring is neces- questions to address include: How many participants
sary. The team must determine whether anything is are necessary to answer the purpose for biological

monitoring? Will every worker in an exposure group training on the topic should help maximize the number
participate or only a portion of the group? Will workers of participants. The industrial hygienist will usually
from all shifts and work groups be included? Will be the person to do worker training and must be able
participation be voluntary? Is a no-exposure negative to articulate the concepts in language, symbols, and
control group needed? Will baseline samples be terms the workers understand. It is also important to
taken? A checklist approach will be valuable. communicate to workers what will happen to their
The cost of the program will increase with the individual and group results as well as the ultimate
number of analyses and number of sample containers. impact of the program. Ideally, understanding the
However, there will be no major extra costs such as for reasons behind the program and its objectives will
sampling pumps—the number of workers sampled is improve workers’ knowledge of the procedures for
not limited by that of the sampling pumps available, handling hazardous chemicals. This may also lead to
for example. greater productivity.
The number of participants included in the program Industrial hygienists may also have to educate their
from each similarly exposed group is a function of superiors on the topic. This process could begin with
the expected variability within each group. Everyone collecting any standard operating procedures and
within groups that perform highly variable tasks from written management policies and assessing the poli-
day to day or week to week, such as maintenance tics of the situation. Committees need to recruit allies
workers, should be included. All workers exposed to who can pose the hard questions and should include
unknown amounts of many chemicals should also be at least one respected member of upper management.
included—hazardous waste workers, for example.
Workers who perform similar tasks day in and day out 5.7.4 Collection Schedule
could be represented by a random sample. Because of
individual differences in personal hygiene, absorption/ The hygienist will be required to define the monitoring
metabolism/elimination of exposing compound, and strategy. Will participants be sampled every day,
nonoccupational confounding exposures, the usual every week, or every 6 months? How many weeks
practice is to include everyone who initially was within or years will the program last? When will it end? A
the exposure group in the biological monitoring proto- checklist for each marker and worker monitored is
col. All work shifts should be included in the program. helpful for defining confounders and interferences
Once it is determined who absorbs the most of the such as smoking, medicinal drugs, alcohol, health
exposing compound and whether these exposures are status, hobbies, and transit mode.
near any guidelines, some changes can be made as to A permanent biological monitoring program is very
which workers need continued sampling. rare. The sampling strategy should be designed to effi-
These considerations then lead to the question of ciently accomplish the objectives of biological monitor-
whether participation should be voluntary. In the ing. The number of samples and length of the program
United States, OSHA and the courts have generally should take into account the variability expected in the
said that worker participation in occupational hygiene sample results. If variability is low, meaning exposure
and occupational medicine programs is voluntary. U.S. is consistent throughout the work shift and work-
regulations require that the employer make certain week, a lower number of samples will be required to
hygiene and occupational medicine programs avail- complete the exposure assessment. Characterizing
able to the employee. However, the regulations do not exposure in a worker population with widely variable
require that workers participate in these programs biological monitoring results will require more samples
unless the employer requires participation as a condi- and more time and will be more expensive.
tion of employment. A full discussion of these issues A collection schedule for a work group with little ex-
is not within the scope of this guideline. Any employer posure variability may involve collecting samples every
considering requiring worker participation in a biologi- work shift from every worker for 2 weeks. If exposure
cal monitoring program should obtain a qualified legal variability from the work tasks performed by the group
opinion to ensure that the proper documentation and is higher, the duration of the program may need to be
communications are made. See Section 8.2 on Ethical extended.
and Legal Considerations. It is often useful to analyze samples obtained pre-
If participation in the biological monitoring program shift or at the beginning of the workweek to establish
is voluntary, there is a risk that workers with the high- a baseline for measuring a rise of the determinant
est exposures may elect not to participate for fear of during the work shift or workweek. A preexposure
losing their jobs. Effective communication of the value sample is useful to show that nonoccupational expo-
of the program to the participants through in-depth sure is contributing to the biological monitoring results.

Such a sample is also useful to demonstrate holdover imize degradation? How long can samples be stored
from the previous day’s work shift exposure for mark- before degradation is significant? Sample labeling
ers of half-time greater than 5 hr. and chain-of-custody procedures should be defined.
The timing of sample collection is a key parameter of To preserve the confidentiality of the participants, it is
the biological monitoring program. The documentation good practice to code the samples rather than mark
of the biological monitoring index will include the rec- them with the name of the participant.
ommended timing of sample collection. Generally, sam-
ples are collected immediately at the end of the work 5.7.6 Questionnaire Administration
shift for biological monitoring indices with elimination
half-times less than 5 hr. For markers with elimination To document the effects of confounding exposures,
half-times between 5 and 20 hr, some accumulation the tasks performed during the exposure period, the
during the workweek is likely, and samples are collected time course of the participant's day, any observations
at the end of the work shift at the end of the workweek of participants, and PPE used during the work shift,
or prior to the last shift of the workweek. The timing of it is effective to ask the participant to complete a
sample collection is less critical for markers with elimi- questionnaire or checklist at the time of sampling. For
nation half-times longer than 20 hr, although adequate a determinant with a short elimination half-time less
sensitivity could then become a problem. Coordinating than 5 hr, it is necessary to document when during the
biological monitoring sample collection with air mon- work shift the exposure occurred. For example, if the
itoring is desirable to allow direct comparison of air majority of exposure occurred in the first hours of the
monitoring and biological monitoring data. work shift and sample collection occurred at the end of
the work shift, urine marker results will underestimate
5.7.5 Collection Procedure exposure unless no urination has occurred. Also,
exposures in the second half of an 8-hr shift may also
The sample collection procedure must be developed.
cause exposure underestimation for urine markers
Will samples be collected in a clinic or in another
of half-lives greater than 5 hr because there has not
location? How will contamination of the sample
been time for metabolism or excretion.
be prevented? If the biological monitoring index
compound is the marker of interest, such as cadmium
or lead, strict procedures must be in place to prevent 5.7.7 Quality Control
the contamination of the biological monitoring sample. The procedures to be used to assess confidence
If the marker is a metabolite, the risk of contamination in the analytical results should be documented.
is reduced. Quality control (QC) can be assessed throughout the
Instructions to participants should be developed program using blanks, samples from personnel who
on how to collect the sample. If contamination of the are not known to be exposed to the agent of interest,
sample is a concern, it might be desirable to have the duplicates (where a sample is split into two samples
workers shower, or at least wash their hands, prior to and analyzed separately), and spiked samples (where
sample collection. Markers with very fast elimination a known concentration of the analyte is added
half-times might require participants to refrain from to one sample of a split). The quality assurance
urine voiding for a period up to 4 hr prior to sample program should describe how the QC results are to be
collection to permit a time-weighted average (TWA) interpreted and the actions that will be taken if results
measurement. The alternative is to collect all voids are not acceptable.
during the work shift. Some markers may require 24-
hr urine sampling. Generally, the worker should empty
5.7.8 Documentation
the bladder just before the work shift. This sample can
be retained as a baseline sample. The protocol should describe the documentation to be
The collection vessel must be specified, along with created and retained from the program. At a minimum,
how the sample is to be collected and documented. analytical results and reports to the participants
Certain blood collection tubes contain stabilizers that should be retained during the employment period
can affect the concentration of the determinant. These of each worker. OSHA requires that exposure
should be avoided (see Section 6.3). Sample pre- monitoring records be retained for the length of
servatives may be required for certain determinants the employment plus another 30 years. Computer
to prevent degradation. Storage requirements and skills are now essential for industrial hygienists in
shipping conditions must be specified. Is refrigeration the documentation, review, and reporting results
adequate, or will storage at ‒70°C be required to min- segments as well as for organizational purposes.

5.7.9 Analytical Procedures Elements of a prequalification program include the

following:
The analytical procedures to be used to find the
concentration of the index/determinant in the sample
• The prequalification samples must be of the same
should be documented. The limit of quantification
media to be sampled in the biological monitoring
(LOQ) should be determined for the fluid involved and
program. Spiked samples of water or solvent
included in the procedures.
will not result in an adequate challenge of the
laboratory.
5.7.10 Reviewing and Reporting Results • The analyte sent to the lab should be the chemical
Prior to implementing the program, the process should form of the analyte seen in the biological medium.
be defined for evaluating the QC, questionnaire, and For example, if the analyte is excreted conjugated,
raw exposure analytical data. The protocol should method development and validation should use
also describe how results will be reported to the the conjugated analyte. However, this may not
participants. For biological monitoring programs always be possible.
that will be completed in a matter of weeks, it might • The sampling and analytical method should
be acceptable to report all results to participants always be the method referenced in the
at one time at the completion of the study. If the documentation for the index/determinant. The
program is to last for several months or years, index was based on the analytical results obtained
participants should receive their results periodically in studies referenced in the documentation.
but at specified intervals. If results are to be collected Different analytical methods might yield different
and reported at the end of the program, it might be analytical results. If a new method is developed, it
necessary to define a trigger value for immediate must be compared with the method referenced in
reporting to the participant. The protocol should the documentation on a performance basis.
both describe the method by which results will be • The analytical method should be validated to at
reported to participants and supervisors and define least 10% of the index. The LOQ and accuracy
how confidentiality of participants will be assured. of the methods should be determined. The intra-
If a biological monitoring marker concentration run precision coefficient of variation should never
regarded as cause for medical attention is exceeded, exceed 10% in the working range.
the physician who is to examine the worker should • If the medium is urine and the creatinine
be named (along with contact information). Similar corrections are used, the creatinine analytical
information should be provided for the threshold for method must also be validated on the same
medical removal. sample. If urine volume is to be utilized, a specific
gravity correction must be applied—meaning that
5.7.11 Follow-Up Actions the method of measurement of specific gravity
The protocol should address when continued biological must be validated and that the specific gravity
monitoring is justified. Programs involving compounds must be measured on the fresh urine sample.
on the EPA Toxic Substances Control Act (TSCA) 8E list Samples outside the reference range of creatinine
may need to be reported to a regulatory agency. and specific gravity are not valid and must be
The protocol should be at least annually reviewed resampled. Dipsticks and portable instruments are
and approved by appropriate worker representatives, available to assess this in the field.
technical resources, and management. • The stability of the analyte in the storage
conditions expected in the study should also be
assessed and controlled.
5.8 Sampling and Analytical Method Issues • Pretreatment of the sample with citric acid or
Contract laboratories generally are not as proficient another preservative might be required. The
with biological monitoring samples as with samples efficacy of the pretreatment procedures should
from air monitoring. Media sampled for biological be assessed on the same types of samples to be
monitoring, generally blood or urine, are complex. This analyzed.
can place demands on the analytical method and
the analyst. Additionally, there are few proficiency A large potential source of variability in a biological
test programs for biological monitoring indices (Pb monitoring program is the sampling and analytical meth-
in blood and Cd in urine have such programs). To od combination. With proper prequalification and ongo-
assure confidence in the results, laboratories must be ing QC, this variability can nearly be eliminated so that
prequalified. the observed variability arises from the person sampled

and not the methods used to sample and analyze the with results discounted if the creatinine concentration
person’s sample. This becomes an important factor to is less than 0.5 g/L or greater than 3 g/L. Urine-specif-
decide the extent of interindividual variability and wheth- ic gravity results should be 1.003–1.030. The NIOSH
er the biological monitoring program should be modified. Manual of Analytical Methods(11)* recommends nor-
malization to 1.024 specific gravity. Data outside of
5.9 Implementation of a Biological these reference ranges mean the urine sampling must
Monitoring Program be repeated. If values outside the reference range are
again obtained, the worker should be referred to a
Prior to taking the first sample, the protocol and physician to ascertain whether kidney and liver func-
results of method development should be presented tions are adequate. If the person is healthy, then the
to appropriate worker representatives, technical use of out-of-reference-range values is appropriate.
resource personnel, and management. Thorough Good judgment should prevail in such cases.
communication at this early stage will minimize
controversy and variability.
5.11 Reports to Participants and
The first step in implementing a protocol is to ed-
ucate the participants and address their concerns. Management
The participants must understand the purpose of the All of a participant's results should be reported to
program and the advantages of biological monitoring the participant. For samples that are discounted, an
over air monitoring in this circumstance. They need to explanation of the reasons for discounting the sample
be familiar with the sample collection and analytical should be provided.
procedures and assured of confidentiality. It might be To assist the participant in interpreting the result,
necessary to develop a procedure covering the dispo- include the reference value (for example, the BEI) or
sition of unused portions of samples, including assur- thresholds for medical attention and medical removal
ances that additional analyses will not be performed with the report. If there is no reference value, each
without the individual's approval. If the latter instance worker should be told the range of values in their
arises, the industrial hygienist may have to develop a workplace.
consent form. (See Appendix IV for examples.) Providing an anonymous summary of all results
The communication sessions should allow questions from the monitoring project may also help a particular
to ensure that the expectations and concerns of par- participant interpret their results and place them in
ticipants are understood and to facilitate trust. context. For this step, the individuals reported on must
be coded to preserve confidentiality. Alternatively,
5.10 Data Analyses, Reporting, and some statistics or graphics should be provided that
Periodic Review guarantee individual confidentiality.
Anonymous summary reports of the project can be
OSHA regulations require that, at a minimum, provided to plant and company management as an
participants need to have access to their results. element of the industrial and environmental hygiene
OSHA's lead and cadmium standards require that status of the plant.
employees be informed of their results. It is good Another effective reporting method for employees
practice to notify each individual of their results as monitored over time is to present past and present
soon as possible. For projects that are limited to a results as a control chart (for example, urine marker
few weeks, reporting cumulative results for the entire concentration vs. time), with reference values clearly
study period may be desirable. indicated.
Data from QC samples and information about con-
founding exposures should be reviewed. The effect
these data may have on an individual's results should 5.12 Stopping a Program
be evaluated and reported to the participant. The The program should be stopped when the reason for
creatinine levels of urine samples should be reviewed, initiating the program has been fulfilled. The reason
*There are very few surface-sampling methods in the NIOSH Manual of Analytical Methods, 4th edition: Method 9100 for lead
surface and hand wipes; Method 2017 for surface wipes and skin badges for aromatic amines; Method 9200 for chlorinated
and organonitrogen herbicides (hand wash); and Method 9201 for chlorinated and organonitrogen herbicides (patch). The 5th
edition contains methamphetamine and illicit drugs on surface wipes by liquid/liquid extraction (Method 9106) or by solid-
phase extraction (Method 9109), followed by analysis by LC-MS (Method 9111). Beryllium on surface wipes by fluorimetry is
Method 9110.

for doing biological monitoring should be articulated must be able to perform the stated aspects of the ap-
as part of the protocol. When that justification is no propriate standard. See also question 5 in Appendix I
longer valid, stop the program. relative to the requirements for lead(5,6) and benzene.(4)
Some biological monitoring programs need to be Often the only specialist on site, the industrial hy-
open ended because the purpose is surveillance. For gienist or occupational health professional needs to
these programs, the data should be summarized at ensure that the worker understands what they have to
least annually as part of the overall exposure assess- do in the sampling scheme and why. The consent pro-
ment process and the results should be compared cess is an effective way to inform the worker of what
against the justification and purpose of the program. A is to happen and allow questions before the sampling
permanent biological monitoring program is rare. occurs. (Appendix IV contains sample consent forms
for unregulated and regulated chemicals.) Because
6. Sampling and Analysis such a form usually has to be approved by the compa-
ny’s lawyers, the process will also help the administra-
tion understand the need for biological monitoring.
6.1 Introduction to Sampling If the worker has already given blanket consent at
Sample collection is a most important part of the the initial time of employment to provide whatever
sampling-analysis chain and, like traditional air samples the employer requests, the sampling proce-
sampling, can be a major responsibility of the dure information in the appropriate consent form, BEI
industrial hygienist. documentation, or laboratory directions can be provid-
ed to generate questions before the sampling begins.
6.1.1 Sampling Personnel
6.1.2 Sample Collection and Shipping
Because biological monitoring involves biological
fluids, only properly accredited personnel can take Because sample contamination and shipping are
blood, urine, and breath samples. Blood sampling, always concerning, it is best to contact your analytical
being invasive of the body, must be left to physicians, laboratory, which will inform you of the correct
nurses, and phlebotomists for legal reasons. The containers, preservatives, labeling, holding times,
training of an industrial hygienist facilitates exhaled shipping containers, and insulation. Some laboratories
breath sampling methods. However, there are few even provide the sampling containers/preservatives,
numerical guidelines for exhaled breath(8) (see labels, insulation, and shipping containers as part
questions 13 and 14 in Appendix I), unlike urine of the analysis price. Some laboratories provide free
sampling (see questions 8–12 in Appendix I). preservatives when requested. The laboratory should
An informed-consent approach under the supervi- also supply detailed written instructions concerning
sion of an on-call clinician, together with the industrial the proper use of the sample containers, timing of the
hygienist, is the best method to prepare the worker for sample, and shipping precautions. The appropriate
urine and breath sampling. Also see Section 5 for the training in all the above may be necessary.
broad overall elements of a biological monitoring pro- Immediately before collecting samples, it is import-
gram to see where the sampling and analysis efforts ant to make adequate preparations such as removing
fit in. contaminated clothing, washing hands or skin, and
At present, the major sampling and analytical showering. It is important to collect samples using only
concerns of industrial hygiene personnel in biological the specified container(s), avoiding any intermediate
monitoring relate to the following: collection vessels or sample transfers that have not
been specifically designated in the sampling plan. Ex-
• training and educating the worker and the tra steps or apparatus increase the possibility of sam-
administration on the need for the sampling ple contamination, especially in the case of metals.
• procuring and managing the sampling containers Sources of metal contamination include the environ-
for use for biological monitoring ment in which the sample is collected; the worker from
• sending the collected sample for analysis in the whom the sample is drawn; sample collection devices
appropriate containers and with the appropriate used for blood collection, such as needles, sample col-
labeling lection containers, and preservatives; and the hands
(including gloves) of the person collecting the sample.
If there is an OSHA-mandated regulation that is For organic analytes, environmental contamination is
applicable (for benzene,(4) lead,(5,6) and cadmium(7)) the a concern when testing for nonmetabolized organic
industrial hygienist or occupational health specialist compounds but is generally not a problem if testing for

metabolites. The analytical laboratory should always analysis in smaller companies. The best way to ad-
be asked for any recommended sampling procedure dress this situation is to take the blank samples but
guidelines because the laboratory is usually up to date not send them for analysis right away. Instead, wait
on the latest requirements or may have further opti- until results from the real sample indicate a problem
mized its procedures. relative to worker exposure that requires confirmation
Holding times (the maximum time from sample that the results are not artifacts of the chain of custo-
collection to sample analysis that assures accurate dy. This would mean that adequate storage conditions
results) and storage conditions may differ for each at the workplace facility must be present, such as a
marker. Metabolites and organic analytes generally refrigerator or freezer dedicated to sample holding
have shorter holding times than metals. Some markers (not food!) and a storage cabinet used only for sample
may require refrigeration immediately after sample storage. Such a strategy may be effective for small
collection. Storage conditions also apply to the time companies.
the samples spend in shipment to the analytical lab,
as they sometimes require overnight shipment on ice 6.1.4 Labels
or dry ice. The specific regulation or documentation The final general consideration during field sampling is
supporting the BEIs usually has guidance on holding to decide what information should be on the label. You
times and storage conditions. Breath samples can will need to plan ahead if no worker names are to be
present special problems because of the possibility of on the sample. How will you code the sample, and who
the analyte’s condensing or reacting with the walls of will have access to the code? How you will store and
the sample container. These difficulties can be de- use the results are also important considerations. Are
creased by minimizing sample holding time or analyz- you going to use control charts to show the progress
ing the samples immediately, if possible. To account of the sampling relative to time and personal breathing
for the possible effect of storage times and conditions, zone exposures? Are you going to use computerized
QC samples should be prepared or obtained at the data management (with backup)? Are computer
same time the samples are collected and should be barcodes to be used, and what aspects need to be on
stored and shipped with the samples. hard copy (such as labels and reports to workers and
Sources of metal contamination include the sample management)? Be sure to double-check all information
collection device (needles for blood collection), sample appearing on labels and entered in computers as part
collection containers, the environment in which the of the written quality assurance program.
sample was collected, and the hands of the person
collecting the sample. For organic analytes, contam- 6.1.5 Baseline Sampling
ination is generally not as much of a problem, but
sample preservation and shipping take on added con- One difficulty with biological monitoring that is
cern. Thus, a written QA program should specify what different from airborne exposure monitoring is
blanks are to be sampled and why, what is to be done that biological monitoring reflects all exposures―
with them, and how their results are to be used in the nonoccupational as well as occupational. Therefore,
QC documentation. exposure to chemicals also present in the home,
recreational, or transport vehicle environments can
complicate the interpretation of results. The analytical
6.1.3 Field Blanks and Other Blanks
chemist can provide a result, but how is it to be
A field blank (a container with the appropriate interpreted? Heavy metals, for example, can be found
preservative that is opened, manipulated, and closed in nonoccupational settings, causing exposures that
in parallel with the sample containers to contain the may result in elevated concentrations in the blood or
real samples) is essential for each type of sample to urine of workers. Elevated concentrations of lead in
detect any problems in the sampling chain of custody. blood can be a result of exposure to lead from water
The field blank constitutes the field method blank or in residential plumbing, leaded paint dust, ammunition
negative control. An unopened sampler can also be from firearms used recreationally, or even ceramic
sent for analysis to ascertain container cleanliness vessels that contained acidic materials such as
(container blank). When preservatives are used, an tomatoes, strawberries, vinegar, or carbonated soda.
extra preservatives blank in its unopened container Elevated mercury levels have been found to correlate
can also be sent for analysis if it is made up off site with consumption of seafood or from taking folk
before field sampling. medicine remedies. Mercury has also been found to
Although the field blank is the chief QC measure in be elevated above its reference range following dental
sampling, analytical costs may preclude any blank work with mercury amalgams.

To assess the true occupational exposure, samples Measuring other routes of exposure (such as the skin
need to be collected prior to exposure to establish surface or saliva in the mouth) can be attempted, but
baseline data. The sample to clear the bladder before procedures for doing so are much less developed than
the shift will suffice for a baseline urine. For rapidly for air monitoring and are beyond the scope of this
metabolized markers (for example, urine and blood guideline.
half-times ≤ 5 hr), this can be accomplished simply
by sampling immediately prior to the beginning of the 6.1.7 Documentation
work shift. Baseline samples can reflect holdover from
Documentation of the sampling conditions and
the previous workday or recent nonworkplace expo-
the work environment is required to allow for a
sures. Baseline data for slowly metabolized materials
meaningful interpretation of the data. It is especially
may be available only by sampling at the beginning
important to note whether the sampling was
of employment or prior to a new work assignment.
done as part of a routine effort to monitor normal
The baseline sample needs to be analyzed only if the
working conditions or if unusual events occurred
sample reflecting exposure is above a reference value.
during the work period. Any pre- or postsampling
Thus, baseline samples need to be stored appropriate-
questionnaires, shipping documents, and analytical
ly in the interim.
lab reports are considered records. They must
No employer wants to have a worker absent from
be managed according to the company’s record
the workforce for exposures that occurred outside
management program and need to reflect any
the workplace, nor pay workers’ compensation for
regulatory or certification requirements. Many testing
this cause if medical removal occurs. Thus, periodic
laboratories are also medical labs and provide an
baseline samples should be taken, and they certainly
analysis request form with spaces for the following:
should be taken when a change of process or work
patient information, sample collection information,
routine occurs. An annual baseline sample is part of
name of the representing physician, specimen
the BEI protocol for assessing occupational exposures
description, name of the person collecting the
to cholinesterase-inhibiting pesticides. The baseline
specimen, and descriptions of the tests requested.
cholinesterase activity measurements in both red
In lieu of preprinted laboratory forms, a custom form
blood cells and serum or plasma, respectively, taken
can be developed, which should include the above
with no prior exposure to enzyme-inhibiting pesticides
items and address sample chain of custody.
for at least 30 days, are used to compare end-of-shift
cholinesterase activity measurements following work-
place exposures. 6.1.8 Safety
All personnel involved with the biological monitoring
6.1.6 Sampling Other Than for Biological program—employees as well as employers, chemists,
Monitoring or health professionals—must be familiar with OSHA
regulations on bloodborne pathogens.(12) Hazards
Concurrent personal breathing zone air monitoring associated with handling of biological fluids must be
should always be conducted when collecting samples
explained to each employee during training sessions.
for biological monitoring. The timing of the air
Methods to minimize exposure, such as engineering
monitoring may vary, however, depending on whether
and work practice controls, PPE, housekeeping, and
the exposure is short (acute) or long term (chronic). For
proper labeling, must be part of the overall bloodborne
instances in which biological monitoring is a measure
pathogens program.
of acute exposure (marker half-times ≤ 5 hr), it is
important that air monitoring be done very close in
time to the biological monitoring, preferably covering 6.2 Urine Collection
the identical exposure period. When the marker being When ACGIH developed the BEIs using the German
evaluated reflects a chronic exposure (for example, BATs as the model, timed spot urine collections with
for the BEIs designated “not critical” in sampling time, 200‒300 mL volume containers were used because all
such as for cadmium in urine and blood for cadmium, the urine collections could be done on the workplace
lead in blood for lead), the time overlap between site and only one sample was necessary. Spot
biological and air monitoring is not as critical. In this samples are typically collected at preshift, postshift
case, air monitoring must be sufficiently detailed, end-of-day, and postshift end-of-week, depending
both to adequately characterize the overall level of on the marker to be measured (see question 8 in
exposure and to be able to differentiate between Appendix I). Containers should be wide mouth to
dissimilar employee exposure populations. enable women to be sampled.

The disadvantage of a spot urine as a specimen is laboratory to ensure sample integrity during storage,
the variation in the concentration of its constituents transport, and analytical laboratory reception. If urine
due to variable worker fluid intake and sweating. This samples need to be frozen, ensure that the bottom
has necessitated the use of normalization procedures part of the sample is cooled first to prevent contain-
(see question 9 in Appendix I). er breakage, especially for glass and low-density
The most common approach to normalization is a polyethylene containers. Creatinine concentration or
creatinine correction. Creatinine is a normal constit- specific gravity do change after freezing relative to
uent of urine that is excreted at a constant rate in fresh urine. Because labels tend to fall off at or below
people of about constant muscle mass (“lean weight”). freezing, the label should be taped securely in a way
The concentration of the marker is divided by the con- that does not obscure the label.
centration of creatinine in the same sample:
6.2.1 Trace Metals
Amt. of marker Vol. of urine Amt. of marker For trace metals in urine, samples are collected in
——————— x ————————— = ————————— plastic cups or bottles that have been acid washed
Vol. of urine Amt. of creatinine Amt. of creatinine or previously analyzed to ensure that they are free of
trace metals. Preservation of urine samples for trace
Common units are milligrams of marker per gram metals usually involves acidification of the sample with
of creatinine; micrograms of creatinine per milligram dilute nitric acid. Acidification should never be done in
of creatinine; and micromole of marker per millimole the field because of the possibility of contamination
creatinine. and acid burns. An alternative is to send the samples
There are limits to the use of this correction. It can- to the laboratory refrigerated overnight and for
not be used if body weight is not relatively constant the acidification to be done at the lab. Refer to the
or if the worker has kidney damage, such as excess analytical laboratory for shipping instructions, such as
protein in the urine (proteinuria). The correction should whether samples should be shipped with cold pack or
be used when creatinine concentration is within the with dry ice to maintain the desired temperature. If dry
range of 0.5–3.0 g/L, but not outside this range. For ice (‒70°C) is specified, special shipping requirements
instance, in the case of a dilute urine of 0.2 g/L, the and documentation are necessary. Express mail or
uncorrected marker concentration will be multiplied by delivery services that involve a signed receipt at the
a factor of 5, often resulting in a falsely elevated result. sample destination are recommended.
It is advisable to use a creatinine dipstick just after Another approach is for the laboratory to provide
sample collection at the sampling site to determine two containers: a wide-mouth acid-washed container
whether the fresh urine sample is valid or if another for sample collection and a leakproof transport bottle
sample needs to be collected on another exposure containing an acid preservative for shipping that the
day. There is no point to an expensive marker analysis collected sample is poured into for storage and trans-
when the sample is invalid. port. Samples should be packed in a cooler with cold
Another normalization procedure is by specific gravi- packs, using an appropriate shipping container that
ty: the density of the urine relative to that of water at meets the regulations covering shipping of biological
the same temperature. samples. Samples should be sent off by next-day or
It is advisable to check the specific gravity at the site second-day delivery.
and time of collection with a dipstick, just as for the
creatinine concentration above. If the urine specific 6.2.2 Organic Analytes
gravity is greater than 1.015, the creatinine concentra- Urine collection procedures for organic analytes vary
tion is usually greater than 0.5 g/L. This procedure also depending on the marker of interest. For organic solvent
avoids inconsistent results and unnecessary expense metabolites such as trichloroacetic acid, o-Cresol,
from invalid urine samples. The specific gravity cor- methylhippuric acid, phenol, pentachlorophenol,
rection is not applicable below a value of 1.010. The mandelic acid, N-methylacetamide, hexanedione,
NIOSH reference specific gravity is 1.024, and: and so forth, samples are collected in plastic
containers unpreserved. Samples should be frozen
Corrected specific gravity = (observed value × 24) / last two as recommended and then sent to the laboratory by
digits of the observed specific gravity overnight carrier.
For the determination of volatile organics in urine,
Samples that are not frozen should have their cre- the sample is collected in a urine cup and promptly
atinine or specific gravity checked by the analytical transferred to two clean 40-mL, Teflon®-lined, screw-

cap vials. The vials are filled to near overflow level and suitable for all elements at the concentration needed
the caps replaced and tightened firmly. It is essential for biological monitoring. For example, antimony
that there are no bubbles present. Vials should be well (Sb), used in the production of plastics, can result in
protected from breakage and sent to the laboratory contamination of plastic collection tubes designated
in coolers with cold packs by next-day service. Do not as trace metal-free by certain manufacturers. If a
allow freezing. manufacturer’s certification does not list the metal
Urine samples for aromatic amines determination— of interest at the desired concentration, notify the
aniline, o-toluidine, methylene dianiline, ß-naphthyl- testing laboratory about testing a representative
amine, and so forth—are stabilized by the addition of number of collection tubes as blanks from a
citric acid to the urine sample at approximately 1 g to manufacturer’s production lot. Because the presence
every 100 mL of urine. The citric acid should be added and concentrations of elements may vary between
to the transport bottle by the laboratory or in an on- production lots, each lot needs to be assessed
site laboratory, but not in the field. Urine samples for individually.
the analysis of alkoxy acetic acid metabolites of glycol Evacuated tubes containing ethylene diamine
ethers should be preserved and acidified with hydro- tetraacetic acid (EDTA) disodium salt as an anticoag-
chloric acid. Numerous other collection methods are ulant are routinely used. Dipotassium EDTA salt is the
possible, depending on the nature of the analyte. Us- favored anticoagulant for plastic tan-top Vacutainers
ers should consult the laboratory for specific details on for blood lead analysis. EDTA provides longer anti-
sample collection, preservation, and shipping. Alter- coagulant action than heparin and is recommended
natively, the written guidelines that cover this process when there is a delay between sample collection and
should be followed meticulously. analysis. Although stability is usually not an issue for
these metals, contact the testing laboratory to rec-
6.3 Blood Collection ommend storage and shipping conditions. Samples
Collection of blood is usually by venipuncture should always be shipped in insulated containers to
into a vacuum-collection tube (Vacutainer®) with avoid temperature extremes. For metals such as alu-
an approximate volume of 15 mL that contains minum, cobalt, chromium, nickel, tin, manganese, and
anticoagulant to prevent clotting. As a rule of thumb, zinc, extreme caution must be taken to avoid contami-
the volume of blood drawn should be equal to 2.5 nation in all aspects of sample collection.
times the volume required for analysis. After the blood Contamination of the blood sample with metals from
is sampled, it must be rocked 10–20 times to mix the needles is also an issue of concern. For occupational
blood thoroughly with the anticoagulant. Whole-blood exposure purposes, flushing of the needle by taking
samples generally are not frozen. Blood for serum a preliminary blood sample before taking the actual
samples is metered into two tubes (for example, red- trace metal sample is effective in limiting needle con-
top Vacutainers) with no anticoagulant and allowed to tamination.
clot for 30 min. The tubes are then centrifuged at 1500 For determinations requiring plasma or serum, an
g for 15–20 min. The clear top layer is transferred additional source of contamination must be dealt
by pipet (plastic for metals) to a clean glass vial or with. After being collected in an appropriate tube, the
centrifuge tube, which is closed with a Teflon-lined sample is centrifuged and the plasma/serum layer
screw cap. The sample is cooled for 1 hr at 4°C, then transferred to another tube. This step must be done in
frozen at –20°C, with shipping at –20°C. Industrial a laboratory environment (not the field) using a plastic
hygienists need to check for the proper shipping transfer pipet and a plastic tube known to be metal
requirements for their samples. free. Glass transfer pipets and glass tubes should
never be used unless precleaned in a dilute nitric acid
6.3.1 Metals solution.
All containers, evacuated tubes, transfer pipets,
The most convenient method for the collection of
transport tubes, and other sampling accessories
trace metals in blood is the use of evacuated trace
should be checked for metal contamination regularly
metal-free blood collection tubes. These tubes are
by analysis of several samples from each lot as blanks.
available from several manufacturers that certify their
use for specific elements at verified concentrations.
Careful attention must be made to the manufacturer’s 6.3.2 Organics
certifying documentation of the metals tested and The most common organic analyses performed
their respective specified concentration. Not all blood on whole blood is the determination of volatile
collection tubes designated as trace metal-free are organic compounds such as benzene, toluene,

trichloroethylene, xylene, perchloroethylene, and Some other methods that could be used, depending
similar industrial solvents. For this determination, on the analyte, include collecting the sample with a
whole blood is collected in glass Vacutainers with solid sorbent that is independent of relative humidity
anticoagulant and transferred to Teflon-lined, screw- (for example, Tenax® polymers and XAD® resins) in an
cap glass vials. The blood is added to the vial until it evacuated Summa™ canister or in an evacuated glass
almost overflows, and the cap is screwed on tightly. container. The solid sorbent method would require
Ensure that no air bubbles remain in the vial. Samples the use of an instrument such as a wet-test meter to
should be kept cold (but not frozen) and shipped measure breath volume.
cold to the laboratory. When shipping, take every
precaution to prevent breakage of the glass vials.
6.5 Saliva Collection
For the determination of polychlorinated biphenyls
(PCBs) and pesticides, blood serum is used. For this Teflon preweighed containers (10‒25 mL) are
determination, blood should be collected in glass preferred for whole saliva collection. The worker sits
red-top Vacutainers. Samples are allowed to clot for with the head tilted forward so that the saliva moves
15–30 min and are then centrifuged. The serum layer anteriorly in the mouth. After an initial swallow, the
is removed with a glass transfer pipet and placed in a saliva should be allowed to drain continuously for 5
glass transport tube. Plastic should be avoided for or- min from the lower lip into a clean funnel sitting in
ganic analytes. Glass should be handled with extreme the container neck. The worker then expectorates the
caution. residual mouth saliva into the funnel. This particular
Biological monitoring of organophosphorus com- method is called the draining method. Other methods
pounds usually also requires the determination of cho- can also be applied but using foreign objects in the
linesterase activity in red cells and serum or plasma. mouth for the stimulated sampling methods can
For this determination, the plasma must be separated introduce contamination.
from the red cells. Samples are collected in Vacutainer
tubes containing EDTA. After collection, the samples 6.6 Hair Collection
are centrifuged at 2500 rev/min for 5–7 min. The upper
yellow plasma layer is completely removed from the Hair is collected from the back of the head at the nape
red cells. Red cell and plasma samples should be re- of the neck. Stainless-steel scissors should be used,
frigerated and not frozen. Send samples on cold packs and the hair should be cut as close to the scalp as
by overnight delivery. possible. The hair length should be no longer than
1–2 in., with the end closest to the scalp being
6.4 Breath Collection retained. About 0.5–1.0 g hair (1–2 tablespoons)
should be cut and placed into a clean envelope or
The most convenient breath collection container is a
a zip-top plastic bag (if metals are being analyzed)
clean 5–10 L Tedlar® gas bag that has been filled and
for shipping in an appropriate container, such as
evacuated at least 3 times with medical-grade air. The
a plastic bottle. If organics are to be analyzed, the
sample can be taken after the end of the shift or after
container should be Teflon or acid-washed Pyrex®. As
worker exposure for 15 min to an uncontaminated
shampoos, hair tinters, conditioners, suntan lotions, or
atmosphere, or, preferably, to pure medical air breathed
in under a Tyvek® hood. The sampling procedure is to other hair cosmetics affect trace metal analysis, the
exhale normally and then blow the end-exhaled air of use of these agents should also be ascertained, along
the lungs through a Teflon or polyethylene 0.5-in. or with specific brand names.
0.25-in. connector attached to the bag by 0.25-in. inner
diameter Teflon tubing that is as short as possible. 6.7 Laboratory QA/QC
Tygon® butt-to-butt collars need to be used to ensure 6.7.1 Definitions and Basics
there are no leaks. (Test with soap solution.) Fill the bag
at least half full. If the worker feels there is too much • Quality assurance (QA) is the overall program by
resistance to blowing, a wider diameter Teflon tubing which accurate and precise results are obtained.
is required. Any other collection device that features The QA program is a written set of standard
valves will require medical certification of worker operating procedures (SOPs).
lung function. The carbon dioxide concentration is • Quality control (QC) is the means by which to
measured with a detector tube, both to ensure the end- demonstrate that each assay or process works
exhaled sample is a valid one and to normalize breath properly. Documentation shows that the QA
concentrations, if desired. program works.

Both QA and QC are essential parts of any deter- analyte and matrix involved. The LOQ is the more im-
mination, no matter which matrix is being analyzed portant parameter to ascertain.
or which chemical or hazard is being measured. The industrial hygienist should ask for the latest
Every laboratory, whether it is analyzing air or water version of the laboratory’s QA/QC plan and docu-
or dirt or blood, must have a formal written QA/QC mentation. Safety concerns should be recognized
program in place to ensure the validity of the data. by all laboratory personnel, such as the technicians
Although QA/QC falls under the primary responsibili- and laboratory analysts being trained on the OSHA
ty of the laboratory, industrial hygienists, occupation- requirements for bloodborne pathogens.(12) Meth-
al physicians, nurses, and others who rely on contract ods to minimize exposure, such as engineering and
laboratories for biological monitoring determinations work-practice controls, personal protective equipment,
should be aware of basic QA/QC and should use ba- housekeeping, and proper labeling, must be part of the
sic QA/QC in their sampling protocols, as discussed in overall program. Compliance with OSHA’s laboratory
Section 6.1. standard(17) is useful in meeting such objectives.
Laboratory SOPs provide the formal documentation Laboratory analytical QA/QC can be divided into
of how the laboratory functions, including the following: two major areas: preanalytical and analytical. Prean-
alytical parameters deal with the QA/QC that must be
• Sample collection; labeling; sample log-in; sample in place before a laboratory can perform any analyses,
storage; holding times; preservation measures; whereas analytical parameters deal with the determi-
sample analysis and data reduction; archiving nation itself. The first part of any QA/QC program is
data; disposal of biological waste and hazardous the preparation of SOPs, which cover every aspect of
chemicals; and so forth laboratory operation. The preanalytical QC plan may
• SOPs must be regularly reviewed by the laboratory be very similar to that outlined for field sampling by
QA/QC manager and laboratory director and the
health professionals in Section 6.1. However, many
formal program revised whenever a change or
laboratories also have personnel who go into the field
update is required.
to sample, and their QA/QC is generally more complex
than used by field-only personnel because the field
The QA manual should describe the procedures used
actions have corresponding laboratory analytical pro-
to assure high-quality data (e.g., personnel qualifi-
cedures. Their QA/QC may also include evaluations of
cations and training, documentation of laboratory
new sampling container products and direct-reading
procedures, instrument calibration and maintenance).
device development—for example, field immunoas-
The manual also describes the control measures
say and colorimetric kits. Direct-reading devices will
taken to monitor, and when necessary, to improve the
laboratory’s results (e.g., QC samples, control charts, become more important in the future.
resolution of deficient performance).(13–16) A laboratory Analytical method SOPs provide the step-by-step
should be able to specify its criteria for accuracy and procedures to determine a particular substance in a
precision of results and how the criteria are applied to particular matrix. They include standardization pro-
each set of samples analyzed. To allow for meaning- cedures, QC measures, sample analysis, LOQs, LODs,
ful interpretation, the data must have accuracy and working ranges, data reduction/calculations, and data
precision sufficient to allow samples from unexposed acceptance/rejection criteria. The most important part
individuals to be clearly distinguished from regulatory of a method SOP is the method validation study. This
levels or BEI concentrations. is the initial demonstration by the laboratory that the
The limit of detection (LOD) and the limit of quanti- method does indeed work, that it is both accurate and
tation (LOQ) depend on the method being used for the precise, and that it will give reproducible results in an
analysis. They can vary from laboratory to laboratory. intra-run and inter-run manner.
The usual definition of LOD is the concentration that A QA/QC system is the formal program that a labo-
causes 3 times the signal-to-noise ratio or 4 times ratory establishes to monitor quality. The major steps,
the total response-to-noise ratio. The usual definition in order, are as follows:
of LOQ is the concentration that causes 10 times the
signal-to-noise ratio or 11 times the total response-to- 1. Document all methods and procedures;
noise ratio. The latter can be defined operationally as 2. Establish an analyst’s training program that sets
the concentration that causes an intra-run coefficient qualification standards and the training as well
of variation (100 x [standard deviation/mean]) of 10%, as requirements for all analysts; and
for example. Consult the laboratory for its LOD and 3. Certify or accredit the laboratory, as appropriate
LOQ and how they are determined for the particular for each analyte.

The most important function of a QA/QC system is cadmium program, which comprises blood and urine
to monitor quality. Quality can be monitored by the cadmium, urine ß2-microglobulin, and urine creatinine;
following: and the trace metal program that assesses aluminum
(Al), chromium (Cr), copper (Cu), selenium (Se), and
• the various inter- and intra-laboratory QC Zinc (Zn) in plasma. Laboratories are encouraged to
programs participate in proficiency testing programs even if not
• QC charts (plots of detector responses to known required by law to do so.
concentrations of analytes over time) The final preanalytical parameter is sample col-
• QA audits (usually at least one a year) lection, which is discussed at length in Sections 6.1
through 6.6. Sample and reagent blank determinations
All laboratory testing falls under the jurisdiction are necessary for any analysis, but especially for trace
of some certifying or accrediting organization. The metal analyses, in which sample collection containers
same is true of laboratories performing biological (particularly needles and blood collection tubes) can
monitoring. Under the Clinical Laboratory Improve- be a source of contamination. It is up to the industrial
ment Act (CLIA) of 1988 (42 CFR § 493, Laboratory hygienist, by taking field blanks in parallel with the
Requirements), any laboratory analyzing biological sample, to ensure that the environment is not a source
samples must obtain a CLIA certificate. Laboratories of contamination.
performing biological monitoring analyses require a Calibration standards are important because quan-
high-complexity testing certificate. Laboratories can titative determinations are only as accurate as the
be accredited by the College of American Patholo- standard on which they are based. In the area of trace
gists (CAP), individual states, or any other accrediting metal determinations, the National Institute of Stan-
agency approved by CLIA. Additionally, laboratories dards and Technology (NIST) provides many different
must be licensed in their individual states or any state standard reference materials (SRMs) consisting of
where they obtain samples. For example, laboratories individual certified metal standard solutions as well
analyzing samples from New York state must be li- as mixtures that are used as primary metal standards.
censed by New York state. Industrial hygienists should Additionally, standard solutions of most metals are
always ask a prospective laboratory whether it has a available from a number of manufacturers at various
CLIA certificate. concentrations that are certified against these NIST
If there is a need to analyze biological samples for SRMs. NIST also provides a blood lead SRM consisting
drugs, Substance Abuse and Mental Health Services of four whole-blood calibrators that can be used as
Administration (SAMSHA) certification may be re- calibration standards or QC samples.
quired for drug testing of certain occupations (such In the case of organic analytes such as organic
as truck drivers, airline pilots) but is not necessary for solvents, pesticides, phenols, and other organics,
all situations. In many circumstances, accreditation by standard solutions in methanol/methylene chloride
CAP for drug testing assures that laboratories conduct are available from a number of suppliers. Most an-
quality testing. The laboratory must be licensed by the alytes have a certificate of analysis provided by the
Federal Nuclear Regulatory Commission to analyze for manufacturer or supplier. For solvent metabolites and
radioactive material. Some state regulatory agencies most organics, the pure compound is the only material
may also require licenses. available for standardization. Thus, the issues of puri-
An important requirement of certification/accredi- ty, stability, and solubility must be considered.
tation is proficiency testing. Industrial hygienists are A calibration verification standard is a standard
familiar with the Proficiency Analytical Testing (PAT) obtained from a different source of material than that
program run by NIOSH. AIHA-accredited laboratories used for the calibration standard. It is a single-point
are required to participate. OSHA requires laborato- standard that verifies the primary standard. A number
ries to participate successfully in a CLIA-approved of manufacturers provide individual standards and
blood lead proficiency program. (Since 2018, OSHA mixed standards for both metals and organics created
no longer has its own list of laboratories approved for this purpose. All the standard materials mentioned
for blood lead analysis. See https://www.osha.gov/ previously could be used too. The idea here is that if
blood-lead-laboratories.) CLIA-registered laboratories the calibration standard is purchased from a manu-
are required to participate in an approved proficiency facturer, the calibration verification standard should
test program for every determination that the labo- be prepared internally or purchased from a different
ratory performs. In the case of biological monitoring, manufacturer, and vice versa. If the pure chemical is
examples of proficiency test programs in which a the only standard material available, the chemical
laboratory may participate include blood lead; the could be purchased from two different manufacturers.

One source would be the calibration standard and the normal in an analysis day, for highly critical analyses
other the verification standard. it is not unusual to perform 20% spikes (every fifth
Matrix-matched QC materials provide the best means sample). As mentioned in the calibration verification
to assess the overall accuracy of a biological monitoring section, a different source of material should be used
determination and should be included in every analyt- for the spike from that used for the calibration stan-
ical run. Disguised as samples, these materials can be dard. However, in many cases this also is not possible.
sent to contract laboratories to check the accuracy of Matrix spike values are plotted also, using the same
the values reported. A number of QC materials (espe- procedure as for QC materials.
cially from NIST) are available for the determination of
trace metals in blood, urine, serum, and plasma. 6.7.2 Analytical Chemistry Laboratories and
In addition to the NIST blood lead standards and Biological Monitoring
controls mentioned earlier, urine-based standards are
available for a number of metals and fluoride. NIST Currently, nearly all markers in urine, breath, and
materials are the gold standard and can be used with blood require analysis by analytical chemistry
confidence. The bi-level controls include a normal laboratories because sensitivity, selectivity, accuracy,
control and an elevated control. For any other level, and precision can only be attained by such means.
the elevated control can be diluted with the normal Development of direct-reading methods or near-
control to obtain the desired concentration. Many com- real-time biological monitoring methods will occur in
mercial QCs are available for blood lead, urine metals, the future: this will allow biological monitoring to be
whole-blood metals, and serum metals. Most of these used in much the same way as detector tubes are
controls are also bi-level (that is, they include an unex- used for directly measuring air samples. For example,
posed reference and elevated level). dipsticks are available for measuring urinary
Documentation of analysis of QC materials is done creatinine and glucose.
through QC charts. Every time the analysis is per-
formed, the value is recorded on a statistical chart that 6.7.2.1 Identifying Laboratories Initially. Identifying
displays high and low acceptance levels for the partic- and choosing a laboratory or laboratories is a critical
ular analyte sample. From these charts, the laboratory part of the project and should be completed before
determines if an assay is “in control” or not. Results samples are collected from the employees. Many
that are not within the upper and lower acceptable laboratories, when approached with a request
limits must be further investigated. for analysis, will receive the samples and provide
Replicate analysis is the process of running a sam- results. However, if the samples are unusual or the
ple twice from the first step of the analysis. Duplicate analyses requested are not frequently performed
analysis refers to running the final prepared sample by the laboratory, the primary laboratory may
twice. Replicate analyses should be done at a fre- subcontract samples to another laboratory more
quency of 10% or more of the sample load, or at least familiar with the analysis. Although this may not be
every 10 samples. Replicate analyses are plotted on a problem, and in fact may improve the reliability of
a different type of QC chart so that a laboratory can the results, the submitter should be aware that this
monitor precision. Replicate analysis is a simple way is happening because the sublaboratory may not be
that contract laboratory users check on laboratory CLIA accredited.
performance. A general rule for the industrial hygienist Most commercial laboratories that analyze biologi-
would be to split one sample in every batch of urine or cal samples are familiar with urine, blood, tissue, and
blood samples into two equal aliquots and then send so forth. Many are not prepared to deal with breath
them to the laboratory for analysis. Results of the rep- samples. Because of handling, shipping, and storage
licate analyses should be recorded. problems, breath sample analysis is probably best
Matrix spike analysis is a valuable method to check performed by an in-house or on-site laboratory.
on the accuracy of any analytical method. A matrix Commercial laboratories and, when possible, in-
spike is a sample to which a known amount of the house industrial laboratories should participate in a
analyte of interest is added. For biological monitoring variety of proficiency testing programs, both internal
markers, this must be the marker itself, which is not and external. Although formal programs are not
necessarily the same as the chemical that exposes the available for all analytes, the participation in some
worker. The original sample and this “spiked” sample aspects of a formal program provides an indication
are then analyzed. The difference should correspond that the appropriate QA and QC procedures are in
to the amount spiked. Acceptable recovery rang- place at the laboratory to support the reliability of
es from 75%–125%. Although using 10% spikes is the data.

The laboratory review should include a discussion with an aliquot of the unspiked sample. Consult with
of issues such as the following: your chosen laboratory on how to do matrix spiking.
Most laboratories would be happy to show you how,
• Does the laboratory provide sampling and as well as provide you with the appropriate stan-
shipping containers, along with any needed dard. In the laboratory, matrix spike analysis is very
preservatives and instructions? important for methods in which matrix-matched QC
• Have chain-of-custody procedures been materials are not available. Unfortunately for most
established for handling of samples? organic analyses, this is the usual case, and matrix
• Does the laboratory provide adequate spike analysis provides the major measure of accu-
turnaround of samples? racy available.
• Are rush analyses available? In the laboratory, matrix spiking is also often
• Can the laboratory provide results by fax, done at 2–3 different concentration levels within
telephone, email, or cell phone? the linear dynamic range of the analyte; that is, the
• Will the laboratory provide summary reports original sample is split into 3 or 4 equal aliquots
monthly, quarterly, or annually, as desired? before spiking with various masses of the analyte.
• Will the laboratory provide reports of excursions The technique is then called the method of standard
above your preset limits? additions when the sample content is defined as the
• Is technical support available for discussion of negative intercept on the axis after extrapolation
results? of the straight line that results. Time and economic
• How responsive is the laboratory to efforts to constraints often limit the application of this tech-
resolve problems? nique, but when all else fails, its result is defined
• Will the laboratory provide a list of references, as “acceptable.” Laboratories must be able to use
analytical methods used, QA/QC procedures, this technique for the most intractable quantitation
and internal QC data, such as control charts? cases.
• What outside proficiency testing programs does Once a laboratory has been selected, it should be
the laboratory participate in, and how have their considered an integral part of the biological monitor-
results been? ing program. Collaboration with laboratory person-
• Does the laboratory have a written QA/QC nel regarding the scope and objectives will lead to
system? Will it allow you to read it? significant improvements in the overall biological
• Are the laboratory and its subcontractor monitoring program. If deficiencies are found, correc-
laboratories CLIA accredited? tive action can be taken, such as working with the
• Is the laboratory’s computer system secure, and laboratory to improve results. If you are not satisfied,
does it have a backup? select and test another laboratory.
Another consideration, of course, is cost, including 6.7.2.2 Selecting the Marker. To an analytical
volume discounts, multi-site discounts, and the cost chemist, accurate and precise identification and
of an expedited analysis. quantification of the marker or analyte is the sole
The ultimate test is laboratory performance. If pos- scientific goal for a laboratory’s analysis and QA/
sible, before the final laboratory selection is made, a QC program. From the industrial hygienist’s point
set of samples having known concentrations in the of view (as discussed in Section 5), the analytical
desired biological matrix or a matrix spike (and its chemistry is but one of the variables, albeit one
unspiked counterpart) should be submitted to the of great importance, that must be considered in a
laboratory disguised as actual biological monitoring biological monitoring program. Most occupational
samples. Another method is to combine samples of health professionals really only want to have the
known content in the same matrix, accounting for result, rather than be required to understand the
dilution effects. Sample stability is the major vari- basis of the result. Such thinking causes the role of an
able that must be assessed for this method. These analytical chemist to be devalued. For the industrial
procedures allow the accuracy of the laboratory’s hygienists to make an appropriate interpretation
analyses to be evaluated prior to the start of the bio- about workplace exposures, the formal biological
logical monitoring program. Although sometimes dif- monitoring program must include accurate results
ficult to perform, matrix spiking is another way that of laboratory analysis to assure that the biological
contract laboratory users can check on laboratory monitoring program proves accurate data.
performance. A sample from an unexposed worker However, the industrial hygienist has to know
could be spiked and sent to the laboratory along enough either to select the appropriate marker or

to understand the advice of others, including lab- • total 1,2–cyclohexanediol and total cyclohexanol
oratory personnel experienced in the analyses. For in urine for cyclohexanol and cyclohexanone
biological monitoring data to be meaningful, detailed • all metals in urine and blood
understanding of a chemical’s metabolism and elimi-
nation kinetics in the human body is also required. The markers are analyzed by a hydrolysis proce-
Fortunately, this information already exists for dure that converts all conjugates to the free form for
chemicals that have established BEIs(8,9) or regulato- organics and by a digestive procedure that converts
ry biological monitoring requirements.(4–7) The diffi- all organometallics to metal nitrates before analysis
culty of choosing a marker is much greater when the for metals. You should ask what the recovery of the
literature is contradictory or insufficient or if other laboratory method is for a spiked conjugate for the
chemicals can be metabolized to the same marker. above organics. This is not to say that BEIs specify
In general, the exposing chemical is always the most “total” always. For example, free trichloroethanol
selective and specific marker, whereas metabolites in blood for trichloroethylene is a BEI marker, as is
may have many possible precursors. free 5-hydroxy-N-ethyl-2-pyrrolidone in urine for
Although knowing the specific marker to be mea- N-ethyl-2-pyrrolidone and free 2,5-hexanedione in
sured may seem too simple in defining the scope urine for n-hexane. The health professional must be
of the actual analytical chemistry program, there is specific about what is asked for, which means that a
an intimate tie between which information needs basic knowledge of the terms involved is essential.
to be obtained from the monitoring, which marker In some cases, the biological monitoring marker is
to monitor, and how to obtain the information. In not specific for a particular chemical but may be for
some cases, it is possible to evaluate a combination a metabolite or an indicator of the chemical’s effect.
of acute, intermediate, and chronic exposures. This An example is the testing required under the OSHA
can be done by appropriately selecting the specific standard for cadmium,(7) which includes a test for
markers and sample types, with an understanding of ß2-microglobulin in urine as well as cadmium in urine
the biological and metabolic half-lives. An excellent and blood. The ß2-microglobulin is a protein that is
discussion of this can be found in the Introduction used as an indicator of adverse effect on the kid-
to the biological exposure indices in ACGIH’s Docu- neys. It is not, however, specific to an effect on the
mentation of the TLVs® and BEIs®.(9) kidneys by cadmium and may be the result of other
Another aspect of selecting a marker is whether kidney problems. Other similar tests evaluate the
the free marker, conjugate, or both together (“total”) impact on an organ or tissue where the effect may
should be measured. Usually in the BEIs, the latter is be from more than one cause. For example, cholin-
meant. Examples include the following: esterase activity in red blood cells for pesticides that
inhibit acetylcholinesterase can also be inhibited by
• total aniline in urine for aniline the anesthetic succinyl choline.
• total butoxyacetic acid in urine for Another important concern is to decide which
2-butoxyethanol marker value takes precedence when guidelines
• total 4-chlorocatechol and total 4-chlorophenol are not the same—for example, for lead, the OSHA
in urine for chlorobenzene medical removal threshold of 50 µg/dL blood or
• total furoic acid in urine for furfural the BEI of 20 µg/dL. Another example is for urinary
• total 4,4′-methylenebis(2-chloroaniline) in urine cadmium: the OSHA threshold is 3 µg/g creatinine
for 4,4′-methylenebis(2-chloroaniline) compared with the BEI of 5 µg/g creatinine, although
• total 1,6-hexamethylene diamine in urine for the blood cadmium guidelines are the same. OSHA
1,6-hexamethylene diisocyanate regulations have primacy.
• total 1- and 2-naphthol in urine for naphthalene
• total p-nitrophenol in urine for parathion 6.7.2.3 Availability of Standard Reference
• total 1-hydroxypyrene and 3-hydroxybenzo(a) Materials. The NIST website (https://www-s.nist.
pyrene in urine for polycyclic aromatic gov/srmors/) provides several biological standards
hydrocarbons containing a variety of toxic materials of known
• total pentachlorophenol in urine for concentrations.(18) These materials are all certified
pentachlorophenol and include acceptable ranges around the reference
• total phenol in urine for phenol; total o-Cresol in value. The SRMs for urine are normally supplied
urine for toluene as a dried material, requiring only the addition
• total 2,4- and 2,6-toluene diamine in urine for of high-purity water to reconstitute the sample.
toluene diisocyanate Once in liquid form, they can then be submitted to

the laboratory as if they were a routine sample. In fluorides, cadmium, and other analytes. Samples
some cases, dried blood and serum specimens are are provided bimonthly. The participating labora-
similarly available. tory is provided with both a bimonthly and annual
In addition to NIST, the following locations, among report of the laboratory’s results. Another example
others, provide urine and blood containing known of an interlaboratory testing program is The German
concentrations of contaminants, either as part of an in- External Quality Assessment Scheme (G-EQUAS) for
terlaboratory proficiency test program or as a service. analysis in biological materials. The interlaboratory
program offers samples twice a year for assessing
• Accurate Chemical & Scientific Corporation, 554 various elements and organic substances typical-
Westbury Ave., Carle Place, NY 11514. Phone: ly encountered in the workplace. It also provides a
(516) 333-2221. https://accuratechemical.com/ report of findings.
products. It is a requirement that laboratories in a program
• Bio-Rad, 1000 Alfred Nobel Drive, Hercules, CA participate in those areas in which they routinely do
94547. Phone: (510) 741-1000. https://www. analyses. Similarly, a laboratory conducting biolog-
bio-rad.com/en-us/contact-us. ical monitoring should also participate in a profi-
• Centre de Toxicologie du Québec, Centre ciency test program for those materials for which it
hospitalier de l’Université Laval, 2705 Blvd. routinely conducts analyses. Customers of a labo-
Laurier, Québec, QC GIV 4G2, Canada. Phone: ratory should request summaries of the laboratory’s
(418) 654-2100. https://ctqvente.inspq.qc.ca/ performance in the testing program to help assess
produits.asp?Lg=ang. the laboratory’s accuracy and precision. If not done
• The German External Quality Assessment Scheme as a matter of course by the laboratory, participation
(G-EQUAS) for Analyses in Biological Materials in proficiency testing should be included as part of
Institute and Out-Patient Clinic for Occupational, your contract for services, where available.
Social and Environmental Medicine of the
University Erlangen-Nuremberg, Schillerstrasse 6.7.2.5 Preparation of Spiked Samples. Because of
25, 91054 Erlangen, Germany. Phone: +49-9131- difficulties involved in accurately spiking biological
8522374. https://app.g-equas.de/web/. samples with known concentrations of biomarkers,
• UTAK Laboratories, Inc., 25020 Ave. Tibbitts, it is usually preferable to purchase samples of
Valencia, CA 91355. Phone: (661) 294-3935. known purity or composition. If samples of known
https://utak.com/. concentration are not available, then spikes should
be prepared only by qualified laboratory personnel,
Reference materials for breath analysis are not such as analytical chemists. Spiked biological
commercially available. Standard gas mixtures can samples should be generated with routines similar
be purchased, but they do not contain the potentially to those used for preparing spikes of other liquid
interfering species in human breath. Standard gas media. The form present in the biological medium
samples can be used to spike breath samples by must be the chemical species that is spiked. This
standard additions, which can provide an indication means that spiking tetrachloroethylene instead of
of the accuracy of the analysis. 1,1,1-trichloroethanol or trichloroacetic acid and
their glucuronides is a systematic error for urine
6.7.2.4 Proficiency Testing. Participation in analysis unless tetrachloroethylene is the marker.
an approved proficiency program (run by CAP, Similarly, the recovery of spiked lead chloride
New York State Department of Health, or the in blood may not be the same as for the lead
Wisconsin State Laboratory of Hygiene) for blood organometallic form actually in red blood cells.
lead is mandatory for laboratories conducting The least difficult medium to handle is breath, fol-
analyses in support of the requirements for testing lowed by urine. Standard concentrations of metals
under OSHA’s lead standard.(5,6) There are many in urine can be prepared from commercial concen-
interlaboratory testing programs available for trated standards for atomic absorption or inductively
analytes other than lead. The CAP has proficiency coupled plasma spectrometry, using urine as the
testing for several trace metals in urine, serum, and final diluent. If possible, the volume of the spiking
blood. However, not all compounds or markers are solution added should be less than 1% of total
the objects of proficiency testing. solution volume. In some cases, it will be necessary
The Centre de Toxicologie du Québec, referenced to choose the contaminant species carefully to be
in Section 6.7.2.3, conducts interlaboratory stud- sure it remains soluble at the urine’s pH. Solubility
ies on arsenic, lead, mercury, chromium, selenium, is usually not a problem if an aliquot of the spiked

urine is transferred to a standard sample container used on a less frequent basis. However, the rou-
with preservative immediately after it is spiked. The tine submittal of either known spikes or purchased
sample must be mixed. standard reference materials should be a part of a
Because of the limited volume of available materi- periodic evaluation of the laboratory. Depending on
al, at least in comparison to urine, the techniques for the numbers of samples submitted and the criticality
spiking blood samples are somewhat different. To of the analytical results, the submission of spikes
calculate the quantity of analyte to add, the amount may be done at a frequency that varies from month-
of blood in the tube can be estimated to within 5% ly to annually.
by filling a spare tube with water to an equivalent
level and then measuring the amount of water in a 6.7.2.7 Corrective Actions. If some data points are
graduated cylinder. To have the minimum effect on suspected to be erroneous, it may be possible for the
the sample, the spiking solution should be of mini- laboratory to reanalyze the sample(s) in question.
mum volume with a correspondingly higher concen- This might not be possible if the lab discards samples
tration, for example, 10‒20 µL spiked into 5‒10 mL soon after analysis or if the sample is totally consumed
of blood. The sample must be mixed. in the analysis. If the parameter being measured is
In any event, the actual concentration of the mate- used to assess chronic exposure, and the half-life of
rial of interest should be determined for a portion of the parameter is very long compared with the time
unspiked sample as well. This allows the determina- elapsed since the sample was taken, another sample
tion of the recovery from the spiked sample. Ideally, can be collected from the individual for analysis.
spikes should be submitted in duplicate unless the Poor results on QC samples or unexpected results
reproducibility of the analysis is known. from the control population may require the basic
Spiked samples should be prepared over a range design of the biological monitoring effort to be re-
of concentrations, for example, 0.1, 0.5, 1.0, and 2.0 considered. Consult the documentation for the BEIs
times the regulatory level or BEI guideline. To be a or the analytical lab for “reference” (nonoccupation-
reliable indicator of method performance, the spiked ally exposed) concentration ranges.
sample concentration should be at least 2–5 times Elevated control values can be caused by con-
greater than the unspiked sample. Spikes at low taminated sampling equipment, inadequate an-
levels (0.1) are best prepared using samples from alytical methodology and method, exposure from
the control population for which the background unanticipated sources, or, especially in the case of a
concentration is expected to be lowest. nonspecific parameter such as ß2-microglobulin for
All handling of potentially infectious biological flu- cadmium, confounding effects possibly unrelated to
ids must be done in compliance with OSHA’s blood- the compound of interest. Recoveries from reference
borne pathogens standard.(12) or spiked samples should generally fall in the range
of 75%–125% of the nominal value. Intra-run coeffi-
6.7.2.6 Frequency of QC Samples. The frequency of
cients of variation should be less than 10%.
submitting samples of known concentration, blanks,
Values outside these ranges can be caused by in-
and duplicates normally reflects the availability
adequate analytical method, sample decomposition
of the samples and the ease and expense of
(especially if the analyte is an organic compound), or
obtaining them. Duplicates will normally be most
inadequate spiking and mixing techniques.
easily obtained, followed by blanks. Commercially
available or specially prepared spikes can be difficult
to obtain and are more expensive, so they might not
be utilized as frequently.
7. Using Results
On a routine basis, at least one set of duplicates
and preferably a blank as well should accompany
7.1 Control Programs
each set of samples submitted to the laboratory. The results of biological monitoring reflect exposure
This allows an ongoing evaluation of the repro- from all routes, such as inhalation, oral ingestion, and
ducibility of the laboratory’s testing. Generally, the skin absorption, as tempered through marker half-
quantitative results of the duplicate samples should times that are dependent on(19) the following:
agree within 10%–20% of one another; however, the
reproducibility of an analysis is method dependent. • exposing a chemical and the physical state of its
Therefore, consult with the laboratory for the ex- challenge (solid, liquid, or gas)
pected method variation. Because of the difficulties • physical activity (workload) and whether heat
involved in preparing the samples, spikes may be stress is present for the worker

• PPE, local emission source controls, general • an understanding of the physical and chemical
workplace controls, and general worker training properties on the safety data sheets for the
regarding their use chemicals used in the unit process and whether
• validity of sampling, storage, transport, and they are known to permeate the skin (Refer to
analytical procedures for the marker the PubChem website of the National Library of
Medicine, https://pubchem.ncbi.nlm.nih.gov/. The
These specific areas are under the control of indus- NIOSH Pocket Guide and skin notation guides
trial hygienists. Other factors that may be important also provide information on skin permeation.)
include the following:
Some generalizations include the following:
• genetic factors of the worker, including gender,
race, ethnicity, and family traits • Unenclosed hot processes usually signal a great
• homeostatic factors such as body temperature, potential for inhalation exposure, as do dusty
pH of blood and urine, circadian rhythms, type workplaces and the use of solvents with vapor
of symbiotic microorganisms in the body, and pressures >10–3 mmHg at 25°C. The major role
integrities of the immune and endocrine systems of biological monitoring would be to confirm
• controllable lifestyle factors such as diet; inhalation exposure as obtained concurrently by
tobacco usage, alcohol, caffeine, and drug personal breathing zone air sampling.
intake; and chemical exposures in the home, • Handling solvents without PPE or using
during commuting, and during recreation incompatible gloves or chemical-resistant
• uncontrollable factors such as medications, clothing that do not provide adequate resistance
medical conditions, shock, depression, from the specific chemical can result in the
schizophrenia, trauma, oxygen lack, aging, potential for chemical contact with skin. When
seasonal factors, and injury; also, environmental performing dermal sampling, the industrial
factors such as geography, altitude, local hygienist must observe the exposure situation to
temperature and humidity, indoor air pollution, identify potential sampling sites on the exposed
home pollution, commuting mode, types of or ill-protected skin for skin patch placement(21)
recreation, and past workplace exposures or direct sampling of the exposed skin(21) using
NIOSH methods, if possible.(11) The major role
The practicing industrial hygienist should seek the of biological monitoring in this case would be
help of physicians, chemists, toxicologists, epidemiolo- to show whether the lack of PPE contributed
gists, biostatisticians, and experienced professionals to to skin absorption after skin exposure through
best understand all factors that influence biomarkers. solvent splashes in addition to the known
The industrial hygienist must know how to ask for help inhalation exposure. Even if PPE is worn,
in the way that is best understood by other experts as biological monitoring would show whether the
well as by workplace management and workers. PPE is an effective barrier to exposure.
• The chemicals that expose the skin will
probably have a much longer body half-time
7.1.1 Exposure Assessment
(t0.5) than the same chemical that is inhaled.
The specific areas under the control of industrial This is unless skin absorption occurs fast, as,
hygienists are the first four bullets in 8.1.1—that is, for example, for dimethyl sulfoxide that is in
exposure assessment. The following paragraphs either its pure state or a mixture. Some time is
consider each bullet with the role of biological usually necessary to permeate the skin layer
monitoring specified. consisting of the outer cuticle (epidermis or
stratum corneum); the underlying dermis, which
7.1.1.1 The Exposing Chemical and the Physical contains sweat glands, hair roots, fat glands,
State of Its Challenge (Solid, Liquid, or Gas). and blood capillaries in a matrix of collagen
Determination as to whether inhalation or skin and elastin; and then, through the next layer,
exposure might dominate as exposure routes may the hypodermis, which contains connective
be determined by the following: tissue, fat, arterioles, capillaries, and venules.
The t0.5 is longer for water-soluble neutral and
• reference to the appropriate current weakly acidic compounds that are resisted by
documentation of the threshold limit values(5) the cuticle. In contrast, exposure to organic
• knowledge of the specific unit processes(20) bases such as aniline; basic aqueous solutions

Table 7-1. Workload Contributions Suggested by the International Organization for Standardization
Metabolic Rate Cumulative Workload Workload Above Resting
Work Type (watt/m )
2
(watt)a (watt)a (watt)a
Resting (basal) 44 79 79 0
Sitting 10 18 97 18
Kneeling 20 36 115 36
Crouching 20 36 115 36
Standing 25 45 124 45
Handwork
Light 15 (< 20) 27 (< 36) 106–151b 27–72
Average 30 (20–35) 54 (36–63) 133–178b 54–99
Heavy 40 (> 35) 72 (> 63) 151–196b 72–117
One-arm work
Light 35 (< 45) 63 (< 81) 142–187b 63–108
Average 55 (45–65) 99 (81–117) 178–223b 99–144
Heavy 75 (> 65) 135(>117) 214–259b 135–180
Two-arm work
Light 65 (< 75) 117 (< 135) 196–241b 117–162
Average 85 (75–95) 153 (135–171) 232–277b 153–198
Heavy 105 (> 95) 189 (> 171) 268–313b 189–234
Trunk work
Light 125 (< 155) 225(< 279) 304–349b 225–270
Average 190 (155–230) 342 (279–414) 421–466b 342–387
Heavy 280 (230–330) 504 (414–594) 583–628b 504–549
Very heavy 390 (> 330) 702 (> 594) 781–826b 702–747
Work speed as to distance, walking
2–5 km/hr 110 198 277–322b 198–243
Walking uphill 2-5 km/hr
Inclination 5° 210 378 457–502b 378–423
Inclination 10° 360 648 727–772b 648–693
Walking downhill 5 km/hr
Declination 5° 60 108 187–232b 108–153
Declination 10° 50 90 169–214b 90–135
Walking 4 km/hr, backroad
10 kg 125 225 304–349b 225–270
30 kg 185 333 412–457b 333–378
50 kg 285 513 592–637b 513–558
Work speed as to height
Walking upstairs 1725 3105 3184–3229b 3105–3150
Walking downstairs 480 864 943–988b 864–909

Table 7-1. Workload Contributions Suggested by the International Organization for Standardization (continued)
Metabolic Rate Cumulative Workload Workload Above Resting
Work Type (watt/m )2
(watt)a (watt)a (watt)a
Mounting inclined ladder
Without load 1660 2988 3067–3112b 2988–3033
With 10-kg load 1870 3366 3445–3490b 3366–3411
With 50-kg load 3320 5976 6055–6100b 5976–6021
Mounting vertical ladder
Without 2 3 3733 365
With 10 2 4 4282 420
With 50 4 8 8629 855
a
Assuming a 70-kg reference man of 1.8 m2 skin area.
b
Assuming mean values between basal rate and standing are additive, with mean values for body posture, type of work, and work speed.
Source: Ergonomics of the Thermal Environment—Determination of Metabolic Rate (ISO 8996:2004).(22)
such as alkali salts of organic carboxylic acids; There are two major semiquantitative scales of
strong detergents; desiccant chemicals such workload, one developed by the International Or-
as acetone and concentrated sulfuric acid; ganization for Standardization (ISO) in 1990(22) and
and organic solvents such as benzene causes another that dates from 1982.(23) Table 7-1 shows
breaching and abrading of the cuticle, allowing what internal metabolic energy was formulated by
penetration and permeation into the inner ISO, as apportioned for a 70-kg standard man, as-
skin layers and thus showing shorter body t0.5. suming a 1.8-m2 skin surface area. Each of the work
The major role of biological monitoring for this contributions is additive.
situation would be to assess whether such The other major metabolic energy scheme is the
chemicals could be detected in the baseline following:
sample of the next workday. An end-of-shift
sample might not reflect the skin absorption • Resting, < 117 watt or a level of 0 relative to
contribution because of the long half-time. resting
• Light, 117–232 watt (a midpoint of 175 watt or
7.1.1.2 Whether Physical Activity (Workload) and a level of 58 watt relative to resting)
Heat Stress Are Factors for Each Worker. Increases • Moderate, 233–348 watt (a midpoint of 291
in both physical activity and heat stress cause watt or a level of 174 watt relative to resting)
increases of absorbed dose breathed in and hence • Heavy, 349–465 watt (a midpoint of 407 watt or
biological monitoring marker concentrations in urine, a level of 290 watt relative to resting)
blood, and exhaled breath. This is essentially an • Very heavy, > 465 watt or a level of > 290 watt
observational task for an industrial hygienist. relative to resting
The following qualitative scheme has been found:
To complicate matters, workers who do the same
• Resting: Sedentary, with little physical activity apparent external work at the same work rate may
for < 30% of the time over the work shift experience different body workloads and, hence,
• Light: No sweating, with physical activity at different absorbed doses of the chemicals to which
least 70% of the time over the work shift they are exposed. Each worker should be classified
• Average or moderate: Sweating just begins, as to average body workload in defined-exposure
without puffing and panting situations with the classification system specified.
• Heavy: Puffing and panting; profuse sweating Individual body workload can also be calibrated by
• Very heavy: Wheezing and gulping air; copious blood oxygen or by individual noninvasive blood
sweating pressure measurements (finger cuff or arm cuff).

Heat stress from exposure to workplace hot pro- Training may be in any or various combinations of
cesses and from wearing PPE also contributes to the following:
body workload. Wet/dry bulb assessment of heat
stress is recommended for hot workplaces, and • PPE cleaning and maintenance
similar type measurements within PPE encasing the • donning, doffing, and disposing of PPE
body at the end of shifts.(24) If real heat stress is sus- • local exhaust and building ventilation
pected, the worker should be sent to a physician. • workplace sanitation/cleaning
Workload and heat stress scales are heavily influ- • personal air sampling program
enced by personal factors such as pulmonary func- • personal biological monitoring program
tion, personal fitness, and healthiness. Such factors
are assessed in a conventional medical examina- 7.1.1.4 Validity of Sampling, Storage, Transport,
tion that is part of the health surveillance program. and Analytical Procedures for the Marker. In the
Worker personal factors, such as sleep and diet absence of a physician or an occupational nurse
adequacy, personal relationships, and psychosocial (the case in the vast majority of workplaces), the
stress, and their influence on biological monitoring industrial hygienist must identify the appropriate
results are still unknown. biological monitoring marker, its collection in the
appropriate biological medium, its safe storage,
7.1.1.3 PPE, Local Emission Source Controls, and its safe transport to an identified analytical
General Workplace Controls, and Worker Training chemistry laboratory that will do the analysis as
in Their Use. The biological monitoring data, in outlined in Appendix I. Beforehand, the worker must
conjunction with observational data, may suggest provide consent and be told why the monitoring
which of these factors should be tried first to control is necessary and what the results may mean. This
any overexposure, as signaled by biological marker procedure could be short-circuited by referring the
concentrations that are greater than those expected worker to a medical clinic, which has to follow the
from the inhalation exposure alone. same procedure when the sample is taken. The
The industrial hygienist’s traditional job is to per- industrial hygienist still must justify to the worker
form exposure assessment as follows: why the sampling is necessary and what the
results may mean in conjunction with air sampling
• identify the need for personal and environmental and ventilation results and any skin and surface
controls; exposure sampling.
• institute such measures, along with the The major role of the industrial hygienist in skin
appropriate worker training; and sampling is to identify the most exposed site of the
• test whether these measures are effective and skin. This is often the face, neck, wrists, arms, and
communicate the findings to the worker and hands in workers with long-sleeved shirts, long trou-
supervisors. sers, socks, and chemical-permeable shoes. Table
7-2 shows the accepted surface areas of body parts
Personal controls may include any or various com- for a 70-kg reference man and for a 60-kg reference
binations of the following: woman.(25)
The major tasks for the hygienist are the following:
• respirators
• gloves • Sampler placement must be ascertained by
• chemically protective clothing, especially with close observation and/or by using a visualization
long sleeves technique such as fluorescence, reflectance,
• face shields or chemical spot tests. Use of fluorescence
• personal showering is possible for aromatic compounds, and if
• hand and face washing at breaks compounds are not aromatic, by use of a
• intake of fluids at breaks fluorescent tracer such as uranine or fluorescein.
• personalized break intervals • The skin should be inspected before sampling for
• daily changing of clothing cuts, abrasions, and eczema. These conditions
invalidate the use of organic solvents for pads,
Personal breathing zone air sampling and person- wipes, or hand washes. According to the
al biological monitoring programs are beneficial in California EPA, no organic solvents should be
evaluating the effectiveness of personal and envi- used for skin sampling, even if the skin surface is
ronmental controls and for training. healthy.

Table 7-2. Mean Skin Surface Areas and 90% Confidence the appropriate blank should be analyzed and
Ranges for 70-kg Reference Man and 60-kg Reference its mean analyte content corrected for in the
Woman actual sample.
Body Region Men (cm2) Women (cm2) • Skin or surface area sampled must be
measured—or better, defined beforehand.
Arms 2280 (1090–2920) 2100 (1930–2350)
Repetitive skin sampling with pads and filters
Upper 1430 (1220–1560) NA should be at constant speed (with pressure)
Forearms 1140 (945–1360) NA from the outside margins of any sampling
template into its center, not the reverse. Multiple
Feet 1120 (611–1560) 975 (834–1150)
sampling passes may be necessary depending
Hands 840 (596–1130) 746 (639–824) on the hand pressure.
Head 1180 (900–1610) 1100 (953–1270) • Any exposed side of any filter or pad used
Legs 6360 (2830–8680) 4880 (4230–5850) for sampling should be folded inward before
placement inside the sample container. Multiple
Thighs 1980 (1280–4030) 2580 (2580–3600) wipes of the same surface area should be
Lower legs 2070 (930–2960) 1940 (1650–2290) placed in the same sampling container unless
Trunk 5690 (3060–8930) 5420 (4370–8670) wipe efficiency needs to be determined.
• The sample container should be an acid-
19,400 16,900
Total washed Pyrex screw-cap tube or jar, the cap
(16,600–22,800) (14,500–20,900) of which is Teflon lined. Plastic bag or plastic
NA, not available. tube containers should be avoided for organics,
Source: Modified from Development of Statistical Distributions but they are adequate for inorganic analytes
or Ranges of Standard Factors Used in Exposure Assessments such as lead and cadmium. In case of breakage,
(EPA 600/8-85/010).(25) In public domain. secondary containment by materials of the same
type as used for the sample container should be
used.
• The worker should be asked whether they • The storage and transport container must be
have any known allergy to any organic labeled appropriately and insulated properly for
solvent used in the sampling and whether that transport at the correct temperature.
solvent coexposure is contraindicated for any • The initial survey should involve separate
medication that is being taken. analysis of each pass filter, gauze, or hand
wash to assess recovery for each method. That
The important points for industrial hygienists are analysis should involve at least five sampling
the following: passes to assess whether more than one pass is
necessary for adequate recovery.(27)
• The industrial hygienist must wear the
There are few NIOSH methods for skin sampling.(15)
appropriate gloves during sampling to prevent
Four such methods are presented below.
sample contamination. Glove manufacturers’
permeation/chemical degradation charts should
1. For aniline, o-toluidine, and nitrobenzene
be used for specific instructions; however, these (Method 2017)(28): gauze wipes (4 × 4-in.)
resistance tests are generally done at around are used for surface and wipe sampling, and
room temperature and therefore overestimate the passive skin sampler is 1 g of silica gel
resistance. Alternatively, the industrial hygienist contained in a cotton pouch. Recoveries for
should reference either books of data on glove the passive dermal sampler spiked with 27–31
permeation(26) or their internet equivalent. µg nitrobenzene, aniline, and o-toluidine and
• Filters and gauze pads must not drip solvent equilibrated for 1 hr varied between 88% and
during wetting or sampling. NIOSH recommends 100%. Recoveries for similarly spiked gauze
that at least 80% of the central surface of the wipes after equilibration for about 8 hr varied
wipe or pad be moistened, with no excess liquid. between 83% and 88%. Ultrasonication in 2
• After being moistened with the appropriate mL ethanol for 60 min is the desorption step
solvent, two samples are exposed to the air before capillary gas chromatography/flame
environment by being cradled in the glove type ionization detection. The industrial hygienist
worn for the duration of sampling. Of the two, should wear chemical protective clothing (CPC)

butyl gloves or a laminated glove such as Silver [2,4-D] nonsalt derivatives)(32): The dermal
Shield during sampling.(29) The wipes should be patch here is a 10 × 10-cm polyurethane foam
moistened with distilled water before sampling. pad, 3–4 mm thick, placed in an aluminized
2. For lead in surface wipe samples (Method card holder with a 7.6-cm diameter circle cut
9100)(30): 2 × 2-in. sterile cotton gauze (Curity™, in one side and then affixed to the skin or the
Johnson & Johnson, or equivalent) or ashless worker’s clothing. The pads are transferred with
quantitative filter paper (for example, Whatman 2-propanol-washed forceps to wide-mouth
40) are recommended using a minimum 100 acid-washed 120-mL Pyrex jars with Teflon-
cm2 surface area sampled to detect at least lined screw caps. The caps are closed, then the
2 µg Pb by flame atomic absorption (AAS) jars are labeled and insulated for 4°C transport
or inductively coupled plasma (ICP)-atomic and sent to the laboratory for analysis. Sample
emission spectroscopy. If graphite furnace solubilization in the laboratory is with 20 mL
AAS or ICP-mass spectrometry are used, the isopropanol, and then subsequent methylation
minimum amount to be sampled decreases to is with 20 mL methylating agent in the same
about 100 ng and smaller surface areas can sample treatment and analysis as for Method
be sampled. The gauze pad or paper should be 9200. The method has been validated (> 90%
moistened with 1–2 mL distilled water. Wearing recovery) for 30-day storage, except for the
dustless disposable latex gloves is adequate. 2,4-D acid (80% recovery) and metolachlor
In the laboratory, sample treatment involves (86% recovery). Industrial hygienists should
digestion in concentrated nitric acid before wear CPC nitrile, Teflon, or laminated gloves for
spectroscopic analysis. protection against the pesticides.(29)
3. Hand-wash method for chlorinated and
organonitrogen herbicides (Method 9200 for These basic field sampling methods can be adapted
alachlor, atrazine, cyanazine, metolachlor, for almost any nonvolatile chemical with judicious se-
simazine, and 2,4-dichlorophenoxyacetic acid lection of patch, wipe, or filter types and their solvents.
[2,4-D] nonsalt derivatives)(31): A volume of The NIOSH Manual of Analytical Methods contains
150-mL isopropanol is poured into a 12 x 8-in., many sampling techniques, such as skin wipes,
4-mL polyethylene bag (Scienceware™ or hand-washing, and direct-reading devices that can
equivalent). The hand is then inserted into the be placed on the skin. The industrial hygienist should
bag, and the bag is wrapped securely around consult with the chemist who will quantify the analyte.
the forearm several inches above the wrist.
The hand is shaken for about 30 seconds. The 7.1.2 Health Surveillance and Medical
hand is then removed and dried. If the hand
Surveillance
appears dry, apply hand lotion. The solution is
transferred to an acid-washed 250-mL Pyrex 7.1.2.1 Scientific Definitions. Health surveillance
jar with a Teflon-lined screw-cap lid, the lid and medical surveillance are interlinked and are
secured, and the container labeled and packed often thought of as being the same. The basic
for storage and transport to the laboratory. difference is that medical surveillance involves
A 150-mL blank poured into a plastic bag, clinical markers that physicians use to detect
shaken, and transferred to its Pyrex container adverse effects of exposure in individuals based
must also be analyzed. In the laboratory an on a biomarker reference range, whereas health
aliquot is methylated, the solution is cleaned surveillance concerns all other biomarkers, including
up on a silica gel column and filtered, and biological monitoring markers of dose, effect
the pesticides are quantified in an aliquot by (nonclinical), susceptibility, and predictive effect.
capillary gas chromatography with an electron When there is a definite adverse health effect, the
capture detector. The sample must be analyzed process of medical surveillance becomes medical
within 30 days of the sampling. The hygienist monitoring or medical screening, after which
should wear CPC nitrile, Teflon, or laminated physicians start a diagnosis. The biomarker of
gloves during sampling and transfer operations health surveillance may or may not have a reference
involving these pesticides and isopropanol.(29) range or be dose related.
4. Patch method for chlorinated and Medical surveillance comprises the procedures
organonitrogen herbicides (Method 9201 for involved with the panel of biomarkers that physi-
alachlor, atrazine, cyanazine, metolachlor, cians utilize for blood, urine, and other body fluids
simazine, and 2,4-dichlorophenoxyacetic acid and tissues to gauge whether a person is healthy

via evaluating the function of the vital organs. This status. Surveillance can also be conducted on a
is the examination that physicians do before worker single employee over time. Review of group results
employment and to end employment, and it is the helps to identify potential problem areas and
examination that physicians perform on industri- the effectiveness of existing worksite preventive
al hygienists and any layperson to ascertain their strategies.(2)
health.
Health surveillance involves the procedures with This definition of medical surveillance therefore
biomarkers that are not used clinically to assess involves single cases, single sentinel events, or pro-
health. A biomarker of health surveillance may be- spective epidemiology-type studies at one point in
come classified as a medical surveillance biomarker time or through time. OSHA adds: “The fundamental
when it proves its clinical worth through time. These purpose of surveillance is to detect and eliminate
markers are therefore medical surveillance markers the underlying causes such as hazards or exposures
at their research (validation) stage. NIOSH describes of any discovered trends and thus has a preven-
health surveillance as “efforts to identify and track tion focus.”(35) This purpose broadens the scope
workplace injuries, illnesses, hazards, deaths and of medical surveillance to the whole program that
exposures” and notes that “research goals focus prevents, identifies, controls, and manages health
on new surveillance methods, tools, and analytical effects in the workplace, even though prevention is
techniques.”(33) stated to be the supposed focus. This broadened
Each government has its own definitions of scope for medical surveillance is also utilized by
medical surveillance and health surveillance. In- NIOSH (https://www.cdc.gov/niosh/index.htm). Thus,
dustrial hygienists in every country must abide by personal air sampling, ventilation, hygiene, training,
the regulations (and legal definitions) that govern safety, and administrative issues are included, in
their activities. The rest of this section discusses the
addition to specific clinical and health issues related
requirements in the United States.
to chemical, physical, and biological exposures. This
purpose of medical surveillance enables industrial
7.1.2.2 OSHA Medical Screening and Medical
hygienists and safety engineers to be the primary
Surveillance. In the United States, OSHA
decision-makers relative to preventive measures in
distinguishes(34) between medical screening and
the workplace.
medical surveillance in its own manner (https://
Interestingly, OSHA provides the major medi-
www.osha.gov/medical-surveillance).
cal screening and surveillance endpoints together
Medical screening, according to OSHA, is “a meth-
in its guidance.(34) Table 7-3 summarizes these
od for detecting disease or body dysfunction before
an individual would normally seek medical care. markers for the 14 specific chemical hazards that
Screening tests are usually administered to individ- are relevant to biological monitoring. The tabulat-
uals without current symptoms, but who may be ed endpoints are for medical screening, with two
at high risk for certain adverse health outcomes.”(1) exceptions: the ones required for fitness to wear res-
This is very close to the previously stated definition pirators (“Pulmonary function tests” and “Evaluation
for medical surveillance used in its predictive guide of ability to wear respirators”) and “Additional tests
for supposedly healthy people. OSHA further states: if deemed necessary.” The category “Other required
“The fundamental purpose of screening is early tests” often also contains specific biomarkers for the
diagnosis and treatment of the individual and thus exposure chemical. The category “Additional tests if
has a clinical focus.”(35) This purpose reinforces the deemed necessary” allows the full range of health
primacy of the physician in the testing and brings surveillance markers, including markers for biological
into effect physician-patient confidentiality. monitoring, to be used by a physician.
Medical surveillance, according to OSHA, is “the OSHA also provides general medical screening
analysis of health information to look for problems and medical surveillance guidance (Table 7-4) for
that may be occurring in the workplace that require general chemical exposure in the following situa-
targeted prevention. Thus, surveillance serves as a tions related to chemical exposures:
feedback loop to the employer.”(2) OSHA elaborates:
• Asbestos in general industry (29 CFR
Surveillance may be based on a single case or 1910.1001[l]) and in construction and shipyards
sentinel event, but more typically uses screening (29 CFR 1926.1191[m]/1915.1001)
results from the group of employees being • Hazardous wastes in HAZWOPER (29 CFR
evaluated to look for abnormal trends in health 1910.120[f]/1926.65)

Table 7-3. Major Nonconstruction Industry Medical Screening and Surveillance Endpoints Recommended by OSHA for
Chemical Hazards That Cause Systemic Effects
Chemical
Endpoint 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Preplacement
+a +a +a,k,l +a,k,l +a,k,l + +a + +a +a,l + +a,k,l +a,l +a
exam
Periodic exam +a,b +a +b,l +b,l +b,l +b +a +a +b +a,l +a,l +a,b,l +a,l +a
Emergency/
exposure + + +b,l,m +b,l,r +b,l +a,z – +F +a +l +a,l +a,l +a,l +
examination/tests
Termination exam + +h – +s +a – +h – +a – – – +h –
Exam emphasis c i n t w A C G I K L P R T
Work and medical
+d +b,j +o +b,d +d +d +a +d +d +d +d,M +d +d +d,U
history
Chest X-ray + + – – + – + – – – – – – –
Pulmonary
– – +p – + – + – – + – – – –
function tests
Other required
e – q u x – D H J – N Q S V
tests
Evaluation of
ability to wear + + + + + + + + + + + + + +
respirators
Additional tests
if deemed + + + + + + + + + + + + + +
necessary
Written medical
+f +f +f +g,v +f +B +f +f +f +f +f +f +g,v +f
opinion
Counseling +g +g +g +g,v +g,y – +g,E +g +g +g +g,O +g +g,v –
Medical removal
– – + – + – – – – + + + + +
plan
Key:
1 = Acrylonitrile. 29 CFR § 1910.1045(n)/1926.1145/1915.1045
2 = Arsenic. 29 CFR § 1910.1018(n)/ 1926.1118(n)/1915.1018
3 = Benzene. 29 CFR §1910.1028(i)/1926.1128/1915.1028
4 = 1,3-Butadiene. 29 CFR § 1910.1051(k)/1926.1151
5 = Cadmium. 29 CFR § 1910.1027(l)/1926.1127/ 1915.1027/1928.1027
6 = Carcinogens (Suspect). 29 CFR § 1910.1003-1016(g)/1926.1103/1915.1003-1016
7 = Coke Oven Emissions. 29 CFR § 1910.1029(j)
8 = 1,2-Dibromo-3-chloropropane 29. CFR § 1910.1044(m)/1926.1144/1915.1044
9 = Ethylene Oxide. 29 CFR § 1910.1047(i)/1926.1147
10 = Formaldehyde. 29 CFR § 1910.1048(l)/1926.1148/1915.1048
11 = Lead. 29CFR § 1910.1025(j)/1926.62
12 = Methylenedianiline. 29 CFR § 1910.1050(m)
13 = Methylene chloride. 29 CFR § 1910.1052(j)/1926.1152
14 = Vinyl Chloride. 29 CFR § 1910.1017(k)/ 1926.1117

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ray of light: in another house as poor and as squalid as his own,
there lives a girl, a distant relation of his, who is also in hard and
humble circumstances, and who has nothing in the world save the
affection and friendship of this poor clerk. They write to each other
daily. In the man’s letters a discreet unselfishness is revealed, a rare
delicacy of feeling, which is in sharp contrast to the awkwardness of
his everyday actions and ideas, which verge on the grotesque. At the
office, he has to cringe and sacrifice his honour in order not to forfeit
the favour of his superiors. He stints himself, and makes every kind
of small sacrifice, in order that this woman may be relieved of her
privations. He writes to her like a father or brother; but it is easy for
us to see in his simple phrases that he is in love with her, although
she does not realise it. The character of the woman is equally clear
to us: she is superior to him in education and mind, and she is less
resigned to her fate than he is. In the course of their correspondence
we learn all that is to be known about their past, their melancholy
history and the small incidents of their everyday life, the struggle that
is continually working in the mind of the clerk between his material
want and his desire not to lose his personal honour. This
correspondence continues day by day until the crisis comes, and the
clerk loses the one joy of his life, and learns that his friend is
engaged to be married. But she has not been caught up or carried
off in a brilliant adventure: she marries a middle-aged man, very rich
and slightly discredited, and all her last letters are full of
commissions which she trusts to her devoted old friend to
accomplish. He is sent to the dress-makers about her gowns, and to
the jeweller about her rings; and all this he accepts and does with
perfect self-sacrifice; and his sacrifice seems quite accidental, a
matter of course: there is not the slightest pose in it, nor any fuss,
and only at the end, in his very last letter, and even then only in a
veiled and discreet form, does he express anything of the immense
sorrow which the blow is bringing to him.
The woman’s character is as subtly drawn as the man’s; she is
more independent than he, and less resigned; she is kind and good,
and it is from no selfish motives that she grasps at the improvement
in her fortunes. But she is still young, and her youth rises within her
and imperatively claims its natural desires. She is convinced that by
accepting the proposal which is made to her she will alleviate her
friend’s position as much as her own; moreover, she regards him as
a faithful friend, and nothing more. But we, the outsiders who read
his letters, see clearly that what he feels for her is more than
friendship: it is simply love and nothing else.
The second important book which Dostoievsky wrote (for the
stories he published immediately after Poor Folk were not up to his
mark) was the Letters from a Dead House, which was published on
his return to Russia in 1861. This book may not be his finest artistic
achievement, but it is certainly the most humanly interesting book
which he ever wrote, and one of the most interesting books which
exist in the whole of the world’s literature. In this book he told his
prison experiences: they were put forward in the shape of the
posthumous records of a nobleman who had committed murder out
of jealousy, and was condemned to spend some years in the convict
prison. The book is supposed to be the papers which this nobleman
left behind him. They cover a period of four years, which was the
term of Dostoievsky’s sentence. The most remarkable characteristic
of the book is the entire absence of egotism in the author. Many
authors in similar circumstances would have written volumes of self-
analysis, and filled pages with their lamentations and in diagnosing
their sensations. Very few men in such a situation could have
avoided a slight pose of martyrdom. In Dostoievsky there is nothing
of this. He faces the horror of the situation, but he has no grievance;
and the book is all about other people and as little as possible about
himself. And herein lies its priceless value, for there is no other book
either of fiction or travel which throws such a searching light on the
character of the Russian people, and especially on that of the
Russian peasants. Dostoievsky got nearer to the Russian peasant
than any one has ever done, and necessarily so, because he lived
with them on equal terms as a convict. But this alone would not
suffice to produce so valuable a book; something else was
necessary, and the second indispensable factor was supplied by
Dostoievsky’s peculiar nature, his simplicity of mind, his kindness of
heart, his sympathy and understanding. In the very first pages of this
book we are led into the heart of a convict’s life: the milieu rises
before us in startling vividness. The first thing which we are made
aware of is that this prison life has a peculiar character of its own.
The strange family or colony which was gathered together in this
Siberian prison consisted of criminals of every grade and description,
and in which not only every class of Russian society, but every
shade and variety of the Russian people was represented; that is to
say, there were here assassins by profession, and men who had
become assassins by chance, robbers, brigands, tramps, pick-
pockets, smugglers, peasants, Armenians, Jews, Poles,
Mussulmans, soldiers who were there for insubordination and even
for murder; officers, gentlemen, and political prisoners, and men who
were there no one knew why.
Now Dostoievsky points out that at a first glance you could detect
one common characteristic in this strange family. Even the most
sharply defined, the most eccentric and original personalities, who
stood out and towered above their comrades, even these did their
best to adopt the manners and customs, the unwritten code, the
etiquette of the prison. In general, he continues, these people with a
very few exceptions (innately cheerful people who met with universal
contempt) were surly, envious, extraordinarily vain, boastful, touchy,
and in the highest degree punctilious and conventional. To be
astonished at nothing was considered the highest quality; and in all
of them the one aim and obsession was outward demeanour and the
wish to keep up appearances. There were men who pretended to
have either great moral or great physical strength and boasted of it,
who were in reality cowards at heart, and whose cowardice was
revealed in a flash. There were also men who possessed really
strong characters; but the curious thing was, Dostoievsky tells us,
that these really strong characters were abnormally vain. The main
and universal characteristic of the criminal was his vanity, his desire,
as the Italians say, to fare figura at all costs. I have been told that
this is true of English prisons, where prisoners will exercise the most
extraordinary ingenuity in order to shave. The greater part of these
people were radically vicious, and frightfully quarrelsome. The
gossip, the backbiting, the tale-bearing, and the repeating of small
calumnies were incessant; yet in spite of this not one man dared to
stand up against the public opinion of the prison, according to whose
etiquette and unwritten law a particular kind of demeanour was
observed. In other words, these prisoners were exactly like private
schoolboys or public schoolboys. At a public school, boys will create
a certain etiquette, which has its unwritten law; for instance, let us
take Eton. At Eton you may walk on one side of the street but not on
the other, unless you are a person of sufficient importance. When
you wear a great-coat, you must always turn the collar up, unless
you are a person of a particular importance. You must likewise never
go about with an umbrella unrolled; and, far more important than all
these questions, there arrives a psychological moment in the career
of an Eton boy when, of his own accord, he wears a stick-up collar
instead of a turned-down collar, by which act he proclaims to the
world that he is a person of considerable importance. These rules
are unwritten and undefined. Nobody tells another boy not to walk on
the wrong side of the road; no boy will ever dream of turning down
his collar, if he is not important enough; and in the third and more
special case, the boy who suddenly puts on a stick-up collar must
feel himself by instinct when that psychological moment has arrived.
It is not done for any definite reason, it is merely the expression of a
kind of atmosphere. He knows at a given moment that he can or
cannot go into stick-ups. Some boys can go into stick-ups for almost
nothing, if they have in their personality the necessary amount of
imponderable prestige; others, though the possessors of many
trophies and colours, can only do so at the last possible minute. But
all must have some definite reason for going into stick-ups: no boy
can go into stick-ups merely because he is clever and thinks a lot of
himself,—that would not only be impossible, but unthinkable.
Dostoievsky’s account of the convicts reminds me so strongly of
the conduct of private and public schoolboys in England, that, with a
few slight changes, his Letters from a Dead House might be about
an English school, as far as the mere etiquette of the convicts is
concerned. Here, for instance, is a case in point: Dostoievsky says
that there lived in this prison men of dynamic personalities, who
feared neither God nor man, and had never obeyed any one in their
lives; and yet they at once fell in with the standard of behaviour
expected of them. There came to the prison men who had been the
terror of their village and their neighbourhood. Such a “new boy”
looked round, and at once understood that he had arrived at a place
where he could astonish no one, and that the only thing to do was to
be quiet and fall in with the manners of the place, and into what
Dostoievsky calls the universal etiquette, which he defines as
follows: “This etiquette,” he says, “consisted outwardly of a kind of
peculiar dignity with which every inhabitant of the prison was
impregnated, as if the fact of being a convict was, ipso facto, a kind
of rank, and a respectable rank.” This is exactly the point of view of a
schoolboy at a private school. A schoolboy prefers to be at home
rather than at school. He knows that he is obliged to be at school, he
is obliged to work against his will, and to do things which are often
disagreeable to him; at the same time his entire efforts are strained
to one object, towards preserving the dignity of his status. That was
the great ambition of the convicts, to preserve the dignity of the
status of a convict. Throughout this book one receives the
impression that the convicts behaved in many ways like schoolboys;
in fact, in one place Dostoievsky says that in many respects they
were exactly like children. He quotes, for instance, their delight in
spending the little money they could get hold of on a smart linen shirt
and a belt, and walking round the whole prison to show it off. They
did not keep such finery long, and nearly always ended by selling it
for almost nothing; but their delight while they possessed it was
intense. There was, however, one curious item in their code of
morals, which is singularly unlike that of schoolboys in England, in
Russia, or in any other country: they had no horror of a man who told
tales to the authorities, who, in schoolboy language, was a sneak.
“The Sneak” did not expose himself to the very smallest loss of
caste. Indignation against him was an unthinkable thing: nobody
shunned him, people were friends with him; and if you had explained
in the prison the whole odiousness of his behaviour, they would not
have understood you at all.
“There was one of the gentlemen prisoners, a vicious and mean
fellow, with whom from the first moment I would have nothing to do.
He made friends with the major’s orderly, and became his spy; and
this man told everything he heard about the prisoners to the major.
We all knew this, and nobody ever once thought of punishing or
even of blaming the scoundrel.”
This is the more remarkable from the fact that in Russian schools,
and especially in those schools where military discipline prevails,
sneaking is the greatest possible crime. In speaking of another man
who constantly reported everything to the authorities, Dostoievsky
says that the other convicts despised him, not because he sneaked,
but because he did not know how to behave himself properly.
The convicts, although they never showed the slightest signs of
remorse or regret for anything they had done in the past, were
allowed by their etiquette to express, as it were officially, a kind of
outward resignation, a peaceful logic, such as, “We are a fallen
people. We could not live in freedom, and now we must break
stones.... We could not obey father and mother, and now we must
obey the beating of the drum.” The criminals abused each other
mercilessly; they were adepts in the art, more than adepts, artists.
Abuse in their hands became a science and a fine art; their object
was to find not so much the word that would give pain, as the
offensive thought, the spirit, the idea, as to who should be most
venomous, the most razor-like in his abuse.
Another striking characteristic which also reminds one of
schoolboys, was that the convict would be, as a rule, obedient and
submissive in the extreme. But there were certain limits beyond
which his patience was exhausted, and when once this limit was
overstepped by his warders or the officer in charge, he was ready to
do anything, even to commit murder, and feared no punishment.
Dostoievsky tells us that during all the time he was in prison he
never noticed among the convicts the slightest sign of remorse, the
slightest burden of spirit with regard to the crimes they had
committed; and the majority of them in their hearts considered
themselves perfectly justified. But the one thing they could not bear,
not because it roused feelings of emotion in them, but because it
was against the etiquette of the place, was that people should dwell
upon their past crimes. He quotes one instance of a man who was
drunk—the convicts could get wine—beginning to relate how he had
killed a child of five years old. The whole prison, which up till then
had been laughing at his jokes, cried out like a man, and the
assassin was obliged to be silent. They did not cry out from
indignation, but because it was not the thing to speak of that,
because to speak of that was considered to be violating the
unwritten code of the prison. The two things which Dostoievsky
found to be the hardest trials during his life as a convict were, first,
the absolute absence of privacy, since during the whole four years
he was in prison he was never for one minute either by day or night
alone; and, secondly, the bar which existed between him and the
majority of the convicts, owing to the fact that he was a gentleman.
The convicts hated people of the upper class; although such men
were on a footing of social equality with them, the convicts never
recognised them as comrades. Quite unconsciously, even sincerely,
they regarded them as gentlemen, although they liked teasing them
about their change of circumstance. They despised them because
they did not know how to work properly, and Dostoievsky says that
he was two years in prison before he won over some of the convicts,
though one can see from his accounts of what they said to him, how
much they must have liked him, and he admits that the majority of
them recognised, after a time, that he was a good fellow. He points
out how much harder such a sentence was on one of his own class
than on a peasant. The peasant arrives from all ends of Russia, no
matter where it be, and finds in prison the milieu he is accustomed
to, and into which he falls at once without difficulty. He is treated as a
brother and an equal by the people who are there. With a gentleman
it is different, and especially, Dostoievsky tells us, with a political
offender, whom the majority of the convicts hate. He never becomes
an equal; they may like him, as they obviously did in Dostoievsky’s
case, but they never regard him as being on a footing of equality with
themselves. They preferred even foreigners, Germans for instance,
to the Russian gentlemen; and the people they disliked most of all
were the gentlemen Poles, because they were almost exaggeratedly
polite towards the convicts, and at the same time could not conceal
their innate hatred of them. With regard to the effect of this difference
of class, Dostoievsky, in the course of the book, tells a striking story.
Every now and then, when the convicts had a grievance about their
food or their treatment, they would go on strike, and assemble in the
prison yard. Dostoievsky relates that one day there was a strike
about the food. As all the convicts were gathered together in the
yard, he joined them, whereupon he was immediately told that that
was not his place, that he had better go to the kitchen, where the
Poles and the other gentlemen were. He was told this kindly by his
friends, and men who were less friendly to him made it plain by
shouting out sarcastic remarks to him. Although he wished to stay,
he was told that he must go. Afterwards the strike was dispersed and
the strikers punished, and Dostoievsky asked a friend of his, one of
the convicts, whether they were not angry with the gentlemen
convicts.
“Why?” asked this man.
“Why, because we did not join in the strike.”
“Why should you have joined in the strike?” asked the convict,
trying to understand, “You buy your own food.”
“Many of us eat the ordinary food,” answered Dostoievsky, “but I
should have thought that apart from this we ought to have joined, out
of fellowship, out of comradeship.”
“But you are not our comrade,” said the other man quite simply;
and Dostoievsky saw that the man did not even understand what he
meant. Dostoievsky realised that he could never be a real comrade
of these men; he might be a convict for a century, he might be the
most experienced of criminals, the most accomplished of assassins,
the barrier existing between the classes would never disappear: to
them he would always be a gentleman, it would always be a case of
“You go your way, we go ours.” And this, he said, was the saddest
thing he experienced during the whole of his prison life.
The thing which perhaps caused him the most pleasure was the
insight he gained into the kindness shown to convicts by outsiders.
Alluding to the doctors in the prison hospital, he says: “It is well
known to prisoners all over Russia that the men who sympathise
with them the most are the doctors: they never make the slightest
difference in their treatment of prisoners, as nearly all outsiders do,
except perhaps the Russian poor. The Russian poor man never
blames the prisoner for his crime, however terrible it may be; he
forgives him everything for the punishment that he is enduring, and
for his misfortune in general. It is not in vain that the whole of the
Russian people call crime a misfortune and criminals ‘unfortunates.’
This definition has a deep meaning; it is all the more valuable in that
it is made unconsciously and instinctively.”
It is an incident revealing this pity for the unfortunate which gave
Dostoievsky more pleasure than anything during his stay in prison. It
was the first occasion on which he directly received alms. He relates
it thus:
“It was soon after my arrival in the prison: I was coming back from
my morning’s work, accompanied only by the guard. There met me a
mother and her daughter. The little girl was ten years old, as pretty
as a cherub; I had already seen them once; the mother was the wife
of a soldier, a widow; her husband, a young soldier, had been under
arrest, and had died in the hospital in the same ward in which I had
lain ill. The wife and the daughter had come to say good-bye to him,
and both had cried bitterly. Seeing me, the little girl blushed,
whispered something to her mother, and she immediately stopped
and took out of her bundle a quarter of a kopeck and gave it to the
little girl. The child ran after me and called out, ‘Unfortunate! For the
sake of Christ, take this copper.’ I took the piece of money, and the
little girl ran back to her mother quite contented. I kept that little piece
of money for a very long time.”
What is most remarkable about the book, are the many and
various discoveries which Dostoievsky made with regard to human
nature: his power of getting behind the gloomy mask of the criminal
to the real man underneath, his success in detecting the “soul of
goodness” in the criminals. Every single one of the characters he
describes stands out in startling relief; and if one began to quote
these one would never end. Nevertheless I will quote a few
instances.
There is Akim Akimitch, an officer who had earned his sentence
thus: He had served in the Caucasus, and been made governor of
some small fortress. One night a neighbouring Caucasian prince
attacked his fortress and burnt it down, but was defeated and driven
back. Akim Akimitch pretended not to know who the culprit was. A
month elapsed, and Akim Akimitch asked the prince to come and
pay him a visit. He came without suspecting any evil. Akim Akimitch
marched out his troops, and in their presence told him it was
exceedingly wrong to burn down fortresses; and after giving him
minute directions as to what the behaviour of a peaceful prince
should be, shot him dead on the spot, and reported the case to his
superiors. He was tried and condemned to death, but his sentence
was commuted to twelve years’ hard labour. Akim Akimitch had thus
once in his life acted according to his own judgment, and the result
had been penal servitude. He had not common sense enough to see
where he had been guilty, but he came to the conclusion that he
never under any circumstances ought to judge for himself. He
thenceforth renounced all initiative of any kind or sort, and made
himself into a machine. He was uneducated, extremely accurate,
and the soul of honesty; very clever with his fingers, he was by turn
carpenter, bootmaker, shoemaker, gilder, and there was no trade
which he could not learn. Akim Akimitch arranged his life in so
methodical a manner in every detail, with such pedantic accuracy,
that at first he almost drove Dostoievsky mad, although Akim
Akimitch was kindness itself to him, and helped him in every possible
way during the first days of his imprisonment. Akim Akimitch
appeared to be absolutely indifferent as to whether he was in prison
or not. He arranged everything as though he were to stay there for
the rest of his life; everything, from his pillow upwards, was arranged
as though no change could possibly occur to him. At first
Dostoievsky found the ways of this automaton a severe trial, but he
afterwards became entirely reconciled to him.
Then there was Orlov, one of the more desperate criminals. He
was a soldier who had deserted. He was of small stature and slight
build, but he was absolutely devoid of any sort of fear. Dostoievsky
says that never in his life had he met with such a strong, such an
iron character as this man had. There was, in this man, a complete
triumph of the spirit over the flesh. He could bear any amount of
physical punishment with supreme indifference. He was consumed
with boundless energy, a thirst for action, for revenge, and for the
accomplishment of the aim which he set before him. He looked down
on everybody in prison. Dostoievsky says he doubts whether there
was any one in the world who could have influenced this man by his
authority. He had a calm outlook on the world, as though there
existed nothing that could astonish him; and although he knew that
the other convicts looked up to him with respect, there was no trace
of swagger about him: he was not at all stupid, and terribly frank,
although not talkative. Dostoievsky would ask him about his
adventures. He did not much like talking about them, but he always
answered frankly. When once he understood, however, that
Dostoievsky was trying to find out whether he felt any pangs of
conscience or remorse for what he had done, he looked at him with
a lofty and utter contempt, as though he suddenly had to deal with
some stupid little boy who could not reason like grown-up people.
There was even an expression of pity in his face, and after a minute
or two he burst out in the simplest and heartiest laugh, without a
trace of irony, and Dostoievsky was convinced that when left to
himself he must have laughed again time after time, so comic did the
thought appear to him.
One of the most sympathetic characters Dostoievsky describes is
a young Tartar called Alei, who was not more than twenty-two years
old. He had an open, clever, and even beautiful face, and a good-
natured and naïve expression which won your heart at once. His
smile was so confiding, so childlike and simple, his big black eyes so
soft and kind, that it was a consolation merely to look at him. He was
in prison for having taken part in an expedition made by his brothers
against a rich Armenian merchant whom they had robbed. He
retained his softness of heart and simplicity and his strict honesty all
the time he was in prison; he never quarrelled, although he knew
quite well how to stand up for himself, and everybody liked him. “I
consider Alei,” writes Dostoievsky, “as being far from an ordinary
personality, and I count my acquaintance with him as one of the
most valuable events of my life. There are characters so beautiful by
nature, so near to God, that even the very thought that they may
some day change for the worse seems impossible. As far as they
are concerned you feel absolutely secure, and I now feel secure for
Alei. Where is he now?”
I cannot help quoting two incidents in Dostoievsky’s prison life
which seem to me to throw light on the characteristics of the people
with whom he mixed, and their manner of behaviour; the first is a
story of how a young soldier called Sirotkin came to be a convict.
Here is the story which Dostoievsky gives us in the man’s own
words:
“My mother loved me very much. When I became a recruit, I have
since heard, she lay down on her bed and never rose again. As a
recruit I found life bitter. The colonel did not like me, and punished
me for everything. And what for? I was obedient, orderly, I never
drank wine, I never borrowed, and that, Alexander Petrovitch, is a
bad business, when a man borrows. All round me were such hard
hearts, there was no place where one could have a good cry.
Sometimes I would creep into a corner and cry a little there. Once I
was standing on guard as a sentry; it was night. The wind was
blowing, it was autumn, and so dark you could see nothing. And I
was so miserable, so miserable! I took my gun, unscrewed the
bayonet, and laid it on the ground; then I pulled off my right boot, put
the muzzle of the barrel to my heart, leaned heavily on it and pulled
the trigger with my big toe. It was a miss-fire. I examined the gun,
cleaned the barrel, put in another cartridge and again pressed it to
my breast. Again a miss-fire. I put on my boot again, fixed the
bayonet, shouldered my gun, and walked up and down in silence;
and I settled that whatever might happen I would get out of being a
recruit. Half an hour later the colonel rode by, at the head of the
patrol, right past me.
“‘Is that the way to stand on guard?’ he said.
“I took the gun in my hand and speared him with the bayonet right
up to the muzzle of the gun. I was severely flogged, and was sent
here for life.”
The second story is about a man who “exchanged” his sentence. It
happened thus: A party of exiles were going to Siberia. Some were
going to prison, some were merely exiled; some were going to work
in factories, but all were going together. They stopped somewhere
on the way in the Government of Perm. Among these exiles there
was a man called Mikhailov, who was condemned to a life sentence
for murder. He was a cunning fellow, and made up his mind to
exchange his sentence. He comes across a simple fellow called
Shushilov, who was merely condemned to a few years’
transportation, that is to say, he had to live in Siberia and not in
European Russia for a few years. This latter man was naïve,
ignorant, and, moreover, had no money of his own. Mikhailov made
friends with him and finally made him drunk, and then proposed to
him an exchange of sentences. Mikhailov said: “It is true that I am
going to prison, but I am going to some special department,” which
he explained was a particular favour, as it was a kind of first class.
Shushilov, under the influence of drink, and being simple-minded,
was full of gratitude for the offer, and Mikhailov taking advantage of
his simplicity bought his name from him for a red shirt and a silver
rouble, which he gave him on the spot, before witnesses. On the
following day Shushilov spent the silver rouble and sold the red shirt
for drink also, but as soon as he became sober again he regretted
the bargain. Then Mikhailov said to him: “If you regret the bargain
give me back my money.” This he could not do; it was impossible for
him to raise a rouble. At the next étape at which they stopped, when
their names were called and the officer called out Mikhailov,
Shushilov answered and Mikhailov answered to Shushilov’s name,
and the result was that when they left Tobolsk, Mikhailov was sent
somewhere to spend a few years in exile, and Shushilov became a
“lifer”; and the special department which the other man talked of as a
kind of superior class, turned out to be the department reserved for
the most desperate criminals of all, those who had no chance of ever
leaving prison, and who were most strictly watched and guarded. It
was no good complaining; there was no means of rectifying the
mistake. There were no witnesses. Had there been witnesses they
would have perjured themselves. And so Shushilov, who had done
nothing at all, received the severest sentence the Russian
Government had power to inflict, whereas the other man, a
desperate criminal, merely enjoyed a few years’ change of air in the
country. The most remarkable thing about this story is this:
Dostoievsky tells us that the convicts despised Shushilov, not
because he had exchanged his sentence, but because he had made
so bad a bargain, and had only got a red shirt and a silver rouble.
Had he exchanged it for two or three shirts and two or three roubles,
they would have thought it quite natural.
The whole book is crammed with such stories, each one of which
throws a flood of light on the character of the Russian people.
These Letters from a Dead House are translated into French, and
a good English translation of them by Marie von Thilo was published
by Messrs. Longmans in 1881. But it is now, I believe, out of print.
Yet if there is one foreign book in the whole world which deserves to
be well known, it is this one. Not only because it throws more light on
the Russian people than any other book which has ever been
written, but also because it tells in the simplest possible way
illuminating things about prisoners and prison life. It is a book which
should be read by all legislators; it is true that the prison life it
describes is now obsolete. It deals with convict life in the fifties, when
everything was far more antiquated, brutal and severe than it is now.
Yet although prisoners had to run the gauntlet between a regiment of
soldiers, and were sometimes beaten nearly to death, in spite of the
squalor of the prison and in spite of the dreariness and anguish
inseparable from their lives, the life of the prisoners stands out in a
positively favourable contrast to that which is led by our convicts in
what Mr. Chesterton calls our “clean and cruel prisons,” where our
prisoners pick oakum to-day in “separate” confinement. The proof of
this is that Dostoievsky was able to write one of the most beautiful
studies of human nature that have ever been written out of his prison
experience. In the first place, the prisoners enjoyed human
fellowship. They all had tobacco; they played cards; they could
receive alms, and, though this was more difficult, they could get
wine. There were no rules forbidding them to speak. Each prisoner
had an occupation of his own, a hobby, a trade, in which he occupied
all his leisure time. Had it not been for this, Dostoievsky says, the
prisoners would have gone mad. One wonders what they would think
of an English prison, where the prisoners are not even allowed to
speak to each other. Such a régime was and is and probably always
will be perfectly unthinkable to a Russian mind. Indeed this point
reminds me of a startling phrase of a Russian revolutionary, who had
experiences of Russian prisons. He was a member of the second
Russian Duma; he had spent many years in prison in Russia. In the
winter of 1906 there was a socialistic conference in London which he
attended. When he returned to Russia he was asked by his fellow-
politicians to lecture on the liberty of English institutions. He refused
to do so. “A Russian,” he said, “is freer in prison than an Englishman
is at large.”
The secret of the merit of this extraordinary book is also the secret
of the unique quality which we find in all Dostoievsky’s fiction. It is
this: Dostoievsky faces the truth; he faces what is bad, what is worst,
what is most revolting in human nature; he does not put on blinkers
and deny the existence of evil, like many English writers, and he
does not, like Zola, indulge in filthy analysis and erect out of his
beastly investigations a pseudo-scientific theory based on the belief
that all human nature is wholly bad. Dostoievsky analyses, not in
order to experiment on the patient and to satisfy his own curiosity,
but in order to cure and to comfort him. And having faced the evil
and recognised it, he proceeds to unearth the good from underneath
it; and he accepts the whole because of the good, and gives thanks
for it. He finds God’s image in the worst of the criminals, and shows
it to us, and for that reason this book is one of the most important
books ever written. Terrible as it is, and sad as it is, no one can read
it without feeling better and stronger and more hopeful. For
Dostoievsky proves to us—so far from complaining of his lot—that
life in the Dead House is not only worth living, but full of unsuspected
and unexplored riches, rare pearls of goodness, shining gems of
kindness, and secret springs of pity. He leaves prison with something
like regret, and he regards his four years’ experience there as a
special boon of Providence, the captain jewel of his life. He goes out
saved for ever from despair, and full of that wisdom more precious
than rubies which is to be found in the hearts of children.
V
Crime and Punishment
Crime and Punishment was published in 1866. It is a book which
brought Dostoievsky fame and popularity, and by which, in Europe at
any rate, he is still best known. It is the greatest tragedy about a
murderer that has been written since Macbeth.
In the chapter on Tolstoy and Tourgeniev, I pointed out that the
Russian character could roughly be divided into two types, which
dominate the whole of Russian fiction, the two types being Lucifer,
the embodiment of invincible pride, and Ivan Durak, the wise fool.
This is especially true with regard to Dostoievsky’s novels. Nearly all
the most important characters in his books represent one or other of
these two types. Raskolnikov, the hero of Crime and Punishment, is
the embodiment of the Lucifer type, and the whole motive and
mainspring of his character is pride.
Raskolnikov is a Nihilist in the true sense of the word, not a
political Nihilist nor an intellectual Nihilist like Tourgeniev’s Bazarov,
but a moral Nihilist; that is to say, a man who strives to act without
principle and to be unscrupulous, who desires to put himself beyond
and above human moral conventions. His idea is that if he can
trample on human conventions, he will be a sort of Napoleon. He
goes to pawn a jewel at an old woman pawnbroker’s, and the idea
which is to affect his whole future vaguely takes root in his mind,
namely, that an intelligent man, possessed of the fortune of this
pawnbroker, could do anything, and that the only necessary step is
to suppress this useless and positively harmful old woman. He thus
expresses the idea later:
“I used to put myself this question: If Napoleon had found himself
in my position and had not wherewith to begin his career, and there
was neither Toulon, nor Egypt, nor the passage of the Alps, and if
there were, instead of these splendid and monumental episodes,
simply some ridiculous old woman, a usurer whom he would have to
kill in order to get her money, would he shrink from doing this if there
were no other alternative, merely because it would not be a fine
deed and because it would be sinful? Now I tell you that I was
possessed by this problem for a long time, and that I felt deeply
ashamed when I at last guessed, suddenly as it were, that not only
would he not be frightened at the idea, but that the thought that the
thing was not important and grandiose enough would not even enter
into his head: he would not even understand where the need for
hesitation lay; and if there were no other way open to him, he would
kill the woman without further reflection. Well, I ceased reflecting,
and I killed her, following the example of my authority.”
Raskolnikov is obsessed by the idea, just as Macbeth is obsessed
by the prophecy of the three witches, and circumstances seem to
play the part of Fate in a Greek tragedy, and to lead him against his
will to commit a horrible crime. “He is mechanically forced,” says
Professor Brückner in his History of Russian Literature, “into
performing the act, as if he had gone too near machinery in motion,
had been caught by a bit of his clothing, and cut to pieces.” As soon
as he has killed the old woman, he is fatally led into committing
another crime immediately after the first crime is committed. He
thinks that by committing this crime he will have trampled on human
conventions, that he will be above and beyond morality, a Napoleon,
a Superman. The tragedy of the book consists in his failure, and in
his realising that he has failed. Instead of becoming stronger than
mankind, he becomes weaker than mankind; instead of having
conquered convention and morality, he is himself vanquished by
them. He finds that as soon as the crime is committed the whole of
his relation towards the world is changed, and his life becomes a
long struggle with himself, a revolt against the moral consequences
of his act. His instinct of self-preservation is in conflict with the horror
of what he has done and the need for confession. Raskolnikov, as I
have said, is the embodiment of pride; pride is the mainspring of his
character. He is proud enough to build gigantic conceptions, to foster
the ambition of placing himself above and beyond humanity, but his
character is not strong enough to bear the load of his ideas. He
thinks he has the makings of a great man in him, and in order to
prove this to himself he commits a crime that would put an ordinary
man beyond the pale of humanity, because he thinks that being an
extraordinary man he will remain within the pale of humanity and not
suffer. His pride suffers a mortal blow when he finds that he is weak,
and that the moral consequences of his act face him at every turn.
He fights against this, he strives not to recognise it; he deliberately
seeks the company of detectives; he discusses murder and
murderers with them minutely, and with a recklessness which leads
him to the very brink of the precipice, when it would need but a word
more for him to betray himself. The examining magistrate, indeed,
guesses that he has committed the crime, and plays with him as a
cat plays with a mouse, being perfectly certain that in the long-run he
will confess of his own accord. The chapters which consist of the
duel between these two men are the most poignant in anguish which
I have ever read. I have seen two of these scenes acted on the
stage, and several people in the audience had hysterics before they
were over. At last the moment of expiation comes, though that of
regeneration is still far distant. Raskolnikov loves a poor prostitute
named Sonia. His act, his murder, has affected his love for Sonia, as
it has affected the rest of his life, and has charged it with a sullen
despair. Sonia, who loves him as the only man who has never
treated her with contempt, sees that he has some great load on his
mind, that he is tortured by some hidden secret. She tries in vain to
get him to tell her what it is, but at last he comes to her with the
intention of telling her, and she reads the speaking secret in his
eyes. As soon as she knows, she tells him that he must kiss the
earth which he has stained, and confess to the whole world that he
has committed murder. Then, she says, God will send him a new life.
At first he refuses: he says that society is worse than he, that greater
crimes than his are committed every day; that those who commit
them are highly honoured. Sonia speaks of his suffering, and of the
torture he will undergo by keeping his dread secret, but he will not
yet give in, nor admit that he is not a strong man, that he is really a
louse—which is the name he gives to all human beings who are not
“Supermen.” Sonia says that they must go to exile together, and that
by suffering together they will expiate his deed. This is one of
Dostoievsky’s principal ideas, or rather it is the interpretation and
conception of Christianity which you will most frequently meet with
among the Russian people,—that suffering is good in itself, and
especially suffering in common with some one else.
After Raskolnikov has confessed his crime to Sonia, he still hovers
round and round the police, like a moth fatally attracted by a candle,
and at last he makes open confession, and is condemned to seven
years’ penal servitude. But although he has been defeated in the
battle with his idea, although he has not only failed, but failed
miserably, even after he has confessed his crime and is paying the
penalty for it in prison, his pride still survives. When he arrives in
prison, it is not the hardships of prison life, it is not the hard labour,
the coarse food, the shaven head, the convict’s dress, that weigh on
his spirit; nor does he feel remorse for his crime. But here once more
in prison he begins to criticise and reflect on his former actions, and
finds them neither foolish nor horrible as he did before. “In what,” he
thinks, “was my conception stupider than many conceptions and
theories which are current in the world? One need only look at the
matter from an independent standpoint, and with a point-of-view
unbiased by conventional ideas, and the idea will not seem so
strange. And why does my deed,” he thought to himself, “appear so
ugly? In what way was it an evil deed? My conscience is at rest.
Naturally I committed a criminal offence, I broke the letter of the law
and I shed blood. Well, take my head in return for the letter of the
law and make an end of it! Of course, even many of those men who
have benefited mankind and who were never satiated with power,
after they had seized it for themselves, ought to have been executed
as soon as they had taken their first step, but these people
succeeded in taking further steps, and therefore they are justified: I
did not succeed, and therefore perhaps I had not the right to take the
first step.”
Raskolnikov accordingly considered that his crime consisted solely
in this, that he was not strong enough to carry it through to the end,
and not strong enough not to confess it. He also tortured himself with
another thought: why did he not kill himself as soon as he
recognised the truth? Why did he prefer the weakness of
confession?
The other convicts in the prison disliked him, distrusted him, and
ended by hating him. Dostoievsky’s own experience of convict life
enables him in a short space to give us a striking picture of
Raskolnikov’s relations with the other convicts. He gradually
becomes aware of the vast gulf which there is between him and the
others. The class barrier which rises between him and them, is more
difficult to break down than that caused by a difference in nationality.
At the same time, he noticed that in the prison there were political
prisoners, Poles, for instance, and officers, who looked down on the
other convicts as though they were insects, ciphers of ignorance,
and despised them accordingly. But he is unable to do this, he
cannot help seeing that these ‘ciphers’ are far cleverer in many
cases than the men who look down on them. On the other hand, he
is astonished that they all love Sonia, who has followed him to the
penal settlement where his prison is, and lives in the town. The
convicts rarely see her, meeting her only from time to time at their
work; and yet they adore her, because she has followed
Raskolnikov. The hatred of the other convicts against him grows so
strong that one day at Easter, when he goes to church with them,
they turn on him and say: “You have no right to go to church: you do
not believe in God, you are an atheist, you ought to be killed.” He
had never spoken with them of God or of religion, and yet they
wished to kill him as an atheist. He only narrowly escaped being
killed by the timely interference of a sentry. To the truth of this
incident I can testify by personal experience, as I have heard
Russian peasants and soldiers say that such and such a man was
religious and that such and such a man was “godless,” although
these men had never mentioned religion to them; and they were
always right.
Then Raskolnikov fell ill and lay for some time in delirium in the
hospital. After his recovery he learns that Sonia has fallen ill herself,
and has not been near the prison, and a great sadness comes over
him. At last she recovers, and he meets her one day at his work.
Something melts in his heart, he knows not how or why; he falls at
her feet and cries; and from that moment a new life begins for him.
His despair has rolled away like a cloud: his heart has risen as
though from the dead.
Crime and Punishment, the best known of all Dostoievsky’s works,
is certainly the most powerful. The anguish of mind which
Raskolnikov goes through tortures the reader. Dostoievsky seems to
have touched the extreme limit of suffering which the human soul
can experience when it descends into hell. At the same time, he
never seems to be gloating over the suffering, but, on the contrary, to

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Foreword to the Second Edition

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1. Purpose Administrative rotation: The process that reassigns

2. Scope Antibody: The protein that a living organism is

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Immune response: Chemical/cellular response of the Macromolecules: High molecular weight

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Major instances in which biological monitoring is 5.5 Roles and Responsibilities

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5.7.9 Analytical Procedures Elements of a prequalification program include the

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