Glutaraldehyde PDF
Glutaraldehyde PDF
Glutaraldehyde PDF
FOREWORD INTRODUCTION
GLUTARADEHYDE
CAS N°: 111-30-8
UNEP PUBLICATIONS
OECD SIDS GLUTARALDEHYDE
There is no current priority for further testing, exposure analysis or in-depth assessment.
The principal health effects of glutaraldehyde are irritation of the skin, eye and respiratory tract,
skin sensitisation and occupational asthma. Exposure data indicated that, in some situations,
particularly the health care industry (disinfection), x-ray film processing and the animal health
industry (spray use), health concerns may arise where available control measures such as
ventilation have not been implemented to minimise exposure.
Due to low and intermittent exposure, the public health risk from the industrial use of
glutaraldehyde is minimal. For the use of glutaraldehyde in cosmetics, a safety margin of >400
for extensive use indicated low concern.
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pKa
ENVIRONMENTAL
FATE/BIODEGRADATION
3.1.1 Photodegradation In water, no statistical change after
24h.
ECOTOXICOLOGY
4.1 Acute/Prolonged Toxicity to Bluegill US EPA 660/3- LC50 (24h)= 15 mg/l, LC50 (48h)= 12
Fish sunfish 75-009 mg/l,
LC50 (96h)= 11mg/l, NOEC = 10 mg/l
4.2 Acute Toxicity to Aquatic D. magna US EPA 660/3- LC50 (48h)= 0.35 mg/l
Invertebrates (Daphnia) 75-009 LC50 (48h)= 2.1 mg/l, NOEC = 0.32
mg/l
4.3 Toxicity to Aquatic Plants Sel.caprico US EPA ILm (96h)= 3.9 mg/l
e.g Algae rnutum
Scen.subspi OECD 201 EC50 (96h)= 0.9 mg/l, NOEC (96h)=
catus 0.625 mg/l
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4.5.2 Chronic Toxicity to Aquatic D. magna OECD 201 LC50 (21d) = >4.3 mg/l, NOEC (21d)=
Invertebrates (Daphnia) 2.1 mg/l
4.6.3 Toxicity to Other Non- Mallard n/a LC50 = 466 mg/kg (acute oral)
Mammalian Terrestrial duck LC50 > 5000 mg/kg (21d dietary)
Species (Including Birds) Bobwhite n/a LC50 > 5000 mg/kg (21d dietary)
quail
TOXICOLOGY
5.1.1 Acute Oral Toxicity rat (SD) US EPA CFR40 LD50 = 246 mg/kg (m), 154 mg/kg (f)
rat (SD) OECD 401 LD50 = 316 mg/kg (m), 285 mg/kg (f)
rat (W) US EPA CFR40 LD50 = 362 mg/kg (m), 418 mg/kg (f)
5.1.2 Acute Inhal. Toxicity - vapour rat (F) OECD 403 LC50 = 96 mg/m3 (m), 164 mg/m3 (f)
- aerosol rat (SD) OECD 403 LC50 = 350 mg/m3 (m), 280 mg/m3 (f)
5.1.3 Acute Dermal Toxicity rat (SD) OECD 402 LD50 > 2000 mg/Kg
5.2.1 Skin Irritation rabbit OECD 404 50,45% solution corrosive, 25% severe
irritant, 2% slight irritant, 1% no
effects
5.2.2 Eye Irritation rabbit OECD 405 5% solution severe irritant, 2,1%
irritant, 0.5,0.2% slight irritant, 0.1%
no effects
5.4 Repeat. Dose Tox. - Oral rat (F) OECD 408 90d NOEL = 5 mg/kg (drinking water)
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A Bacterial Test S.typhimur OECD 471 TA100, 102,104: + with and without
(Gene Mutation) . metabolic activation; TA98,1535,1537 -.
- Sister chromatid exchange Ch.hamster OECD 479 + with and without metabolic activation
5.8 Toxicity to Reproduction rat (CD) oral (dr.water) NOEL = 50 ppm (General toxicity)
NOEL = 1000 ppm (Reprotox. parental)
NOEL = 1000 ppm (Reprotox. F1 gen.)
5.9 Developmental Toxicity/ rat (W) OECD 414 NOEL = 5 mg/kg (General toxicity)
Teratogenicity NOEL = 68 mg/kg (Preg. /Litter, Foetal)
rabbit OECD 414 NOEL = 15 mg/kg (General toxicity)
NOEL = 15 mg/kg (Preg. /Litter, Foetal)
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1. IDENTITY
Name: Glutaraldehyde
CAS no.: 111-30-8
Synonyms: 1,5-pentanedial
1,3-diformylpropane
Glutaral
Glutardialdehyde
Glutaric dialdehyde
Glutaraldehyde is a colourless oily liquid which undergoes chemical reactions typical of aldehydes. It
also cross-links with proteins and, in aqueous solutions, it partially polymerises to give oligomers. In the
vapour state, glutaraldehyde has a pungent odour, with an odour threshold of 0.04 ppm.
Glutaraldehyde is manufactured in Germany by BASF and in the USA by Union Carbide Corporation. It
is usually sold commercially as a 45% or 50% aqueous solution.
International production volumes were not available, however, import volumes were available from some
member countries. In Australia, over 100 tonnes per year of glutaraldehyde have been imported in recent
years. Sweden imports approximately 165 tonnes/year, Denmark approximately 50 tonnes/year, France <
1000 tonnes/year, United Kingdom several hundred tonnes/year and Canada 33-333 tonnes/year.
Norway imports approximately 12 700 tonnes of glutaraldehyde-containing products each year.
A summary of use data provided by OECD member countries is tabled in Appendix A. The table also
includes information on classification, occupational exposure limits and occupational exposure data
provided by members.
Cold disinfectant in the health care industry. Glutaraldehyde is used in the form of a 1% or 2% aqueous
solution which has to be activated by an alkaline buffer, for example, sodium bicarbonate. The activated
solution can be used for up to two weeks and it is used in the chemical disinfection of instruments such as
endoscopes, bronchoscopes, dental equipment and other clinical instruments. Disinfection involves
immersion of the instrument in glutaraldehyde solution using either closed troughs, trolley systems or
automated washing units.
Hardener in x-ray film processing. Glutaraldehyde is incorporated into developing solutions for black
and white x-ray photography as a hardening (or cross-linking) agent to shorten the drying cycle in film
processing. The developers containing glutaraldehyde are generally used in high temperature, automated
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film processors, mainly in the medical field and, to a lesser extent, in engineering applications such as the
non-destructive testing of welds. X-ray developers are usually supplied as concentrates containing free
glutaraldehyde or the glutaraldehyde-sodium bisulfite complex, with the concentrate diluted to give a
working strength solution containing less than 1% glutaraldehyde.
Water treatment. Aqueous solutions of glutaraldehyde at 10-50% are used for the treatment of water in
cooling towers, air washers and other water recirculating systems to prevent corrosion and the build-up
of microbial growth. The solution is administered in slugs as shock kill doses, either manually or by use
of automatic dosing equipment, to give 50-100 ppm glutaraldehyde in treated water.
Biocide in the pulp and paper industry. Aqueous solutions of glutaraldehyde at 10-50% are used to
reduce or inhibit the growth of micro-organisms in pulp slurries. The solution is administered in slugs by
use of automatic dosing equipment to give 50-100 ppm glutaraldehyde in pulp stock.
Cleaning agent. Glutaraldehyde is used as a preservative in industrial cleaning agents, for example, in
the food, beverage and tobacco manufacturing industries, and in retail detergents. In France, the
glutaraldehyde content of 8 products used in disinfection, control, cleaning and repairing was in the range
0.024-6.5%. In the United Kingdom, the glutaraldehyde content in retail cleaning agents was 0.05-
0.1%.
Biocide in the petroleum industry. Glutaraldehyde is used in the industry as a drilling mud additive, oil
recovery agent and in treating oil wells. It is also used as a biocide in petroleum products such as
lubricating oils.
Animal health industry. Glutaraldehyde is used in the animal health industry to disinfect animal and bird
houses. Dilute solutions containing 0.1-0.3% glutaraldehyde are sprayed, washed or foamed onto the
walls, floors and other surfaces. Fogging of animal sheds can be conducted with automatic equipment
using a solution containing approximately 400 ppm. Solutions containing approximately 750 ppm are
used to sanitise egg shells to assist in the removal of dirt and debris.
Tanning. Aqueous solutions of glutaraldehyde are used to soften leathers and to improve their resistance
to water, alkalis and mould. The leathers are soaked in a solution containing 0.5-2% glutaraldehyde.
Microscopy/histology. Glutaraldehyde is used as a tissue fixative in histology and electron and light
microscopy, generally as a 1.5-6% aqueous solution.
Aquaculture. Glutaraldehyde is used, generally in conjunction with wetting agents, to control viruses and
other micro-organisms in fish farming.
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. an embalming agent.
The results of a NIOSH (USA) survey detailing numbers of workers and types of workplaces using
glutaraldehyde are listed in Appendix B.
3. ENVIRONMENT
Waste glutaraldehyde solutions are disposed of to sewer. This provides a route for glutaraldehyde to
enter the aquatic environment when residues that may remain in treated sewage effluent are discharged to
receiving waters.
Glutaraldehyde's main application, as a cold disinfectant for use in such facilities as hospitals, surgeries
and medical clinics, entails discharge of significant quantities to sewer as solutions that are disposed of
retain at least 50% of their activity. Such disposal will occur predominantly in metropolitan areas.
Smaller discharges to sewer will occur from formulation and other end-uses such as x-ray film
processing, water cooling treatment and tanning.
Five-day biological oxygen demand and aquatic metabolism studies indicate that glutaraldehyde degrades
readily. Accordingly, significant degradation is expected during passage through sewage treatment
works. Reaction with proteins present in sewage effluent will also remove significant amounts from
aqueous waste streams. Any glutaraldehyde that may enter receiving waters is likely to be rapidly diluted
and undergo further biodegradation.
Small amounts of glutaraldehyde will volatilise to the atmosphere. Glutaraldehyde used as a biocide in
cooling systems will be entrained in water cooling tower drift. However, glutaraldehyde is not expected
to persist in the atmosphere as it would be subject, like other aliphatic aldehydes (for example, propanal,
for which the USA has prepared a SIAR including an estimated half-life of 5.8 hours in air) to
photochemically induced degradation in that compartment. In addition, the hydrophilicity of
glutaraldehyde will ensure its removal through dissolution in rain.
Monitoring studies have been performed in Canada at a paper mill and a de-inking plant. Both studies
showed a rapid decrease in glutaraldehyde concentration in the white water. In the paper mill, the white
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water concentration decreased from 51 mg/L half an hour after dosing to 4 mg/L after 6 hours. In the de-
inking plant, the corresponding concentration decreased from 56 mg/L half an hour after dosing to 5
mg/L after 7 hours. These results were attributed partly to dilution of the white water.
In the paper mill, the glutaraldehyde concentration in white water effluent to the clarifier was below the
detection limit of 1 mg/L throughout the study. In the de-inking plant, the glutaraldehyde concentration
in the clarifier decreased from 14 mg/L half an hour after dosing to 7 mg/L after 3 hours and below the
detection limit of 5 mg/L after 7 hours. In effluent water from the clarifier, the concentration was below
the detection limit of 5 mg/L throughout the study.
In Australia, environmental exposure primarily arises as a result of use as a cold chemical sterilant when
spent solutions are disposed of to sewer. Assuming that 75% of the estimated 50 tonnes per year that is
used for this purpose is so discharged, the average daily discharge across Australia would be 37500/365
= 100 kg. For a population of about 17 million with an average daily per capita wastewater discharge of
150L (a conservative estimate) the concentration in wastewater would be about 40 gµ/L.
Note that the above estimate is a worst case as it takes no account of such factors as reaction with
proteinaceous constituents of raw sewage and biodegradation, which are expected to significantly reduce
concentrations of glutaraldehyde in wastewater before discharge. Any glutaraldehyde remaining in
treated effluent will be further diluted in receiving waters and subject to further biodegradation.
In Australia, glutaraldehyde is also used in x-ray film processing, water treatment, tanning and animal
housing, but in smaller volumes and at lower concentrations than as cold chemical sterilant. Free
glutaraldehyde is not released from x-ray film processing because of reaction with sulfite from the fixer.
Cooling towers discharge to sewer at a maximum concentration of 250 mg/L. Losses from tanning are
estimated as 1-3% of the original charge, and would be expected to react with dissolved proteins in
tannery effluent. Use in animal housing primarily involves atmospheric exposure as glutaraldehyde
solutions are generally applied to surfaces and allowed to dry. These sources of exposure would not be
expected to add significantly to the wastewater load.
Little information was available on antiprotozoal use of glutaraldehyde in aquaculture in Australia, but
concentrations discharged would be expected to be low as higher concentrations may be damaging rather
than therapeutic to aquatic fauna.
PEC values were calculated in Sweden for three different scenarios: a fine paper mill and a newspaper
mill with one or two days retention time. Based on a glutaraldehyde concentration of 50 mg/L in white
water during dosing periods, and assuming a dilution factor of 100, PEC values of 60 gµ/L, 2.9 gµ/L and
Table 1 indicates that glutaraldehyde is slightly toxic to crabs, shrimp and sewage micro-organisms,
slightly to moderately toxic to fish and Daphnia, moderately toxic to oyster larvae, and moderately to
highly toxic to algae. Glutaraldehyde loses its biological activity below about 10 mg/L.
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Acute data for bluegill sunfish, daphnids, oyster larvae, crabs, shrimp and algae are available. These
indicate oyster larvae (48h LC50 = 2.1 mg/L) to be the most sensitive faunal species, disregarding one test
for Daphnia magna in which poorly correlated data returned a 48h LC50 of 0.35 mg/L. For floral
species, the alga Scenedesmus subspicatus is most sensitive (96h EC50 = 0.9 mg/L).
Additional summary data generated in Germany indicates slight to moderate acute toxicities under semi-
static conditions to zebra fish (96h LC50 = 5.8 mg/L) and Daphnia (48h EC50 = 21.9 mg/L).
As a wide selection of species is available, a safety factor of 100 seems most appropriate, giving a PNEC
of 2100/100 = 21 gµ/L for faunal species and 900/100 = 9 gµ/L for algae.
Note that these PNEC values are very much lower than measured no-effect concentrations, for example,
the measured no-effect concentration for the alga Scenedesmus subspicatus is 0.3 mg/L. The no-effect
concentration in 21d testing with Daphnia magna was 2.1 mg/L. Application of an assessment factor of
10 would give a PNEC of 30 gµ/L based on the algal chronic value. [Note that the OECD Provisional
Guidance for the Assessment of Aquatic Effects recommends that the PNEC should be derived using the
chronic value where chronic data are available for the most sensitive species in acute testing.]
Only avian data are available. Acute oral and dietary LD50s for mallard duck are above 400 mg/kg.
With a safety factor of 1000, the PNEC is above 400 gµ/kg.
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The PEC is less than the acute PNEC for aquatic fauna, even without considering losses during sewage
treatment, and also less than the PNEC based on algal chronic values. Therefore, glutaraldehyde is not
expected to present a significant risk to the aquatic environment.
The above PEC values are based on the Australian situation where discharge to sewage treatment works
allows large reductions through dilution. Estimates from Sweden indicate that concentrations in
wastewater from on-site treatment plants (sedimentation and chemical precipitation only) serving fine
paper mills may reach 6 mg/L, more than two orders of magnitude higher than predicted for municipal
sewage treatment works. Hence concentrations of glutaraldehyde leaving specific facilities, such as
paper mill effluents treated only by sedimentation and chemical precipitation, may be higher than
concentrations leaving municipal sewage treatment works because of the absence of dilution by other
waste streams.
For the terrestrial compartment, the PNEC is above 400 gµ/kg, an order of magnitude above the predicted
wastewater concentration. As glutaraldehyde is hydrophilic, biodegradable in soil and water and has no
bioaccumulative properties, there is no apparent risk to the terrestrial compartment.
4. HUMAN HEALTH
Workers may be exposed to aqueous solutions of glutaraldehyde from 50% to less than 1% by skin
contact and by inhalation of the vapours liberated from the solutions. Glutaraldehyde has a low vapour
pressure over its aqueous solutions. The risk of exposure to glutaraldehyde vapours is enhanced at
higher temperatures and/or concentrations and by use in spray form.
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The occupational exposure standard for glutaraldehyde in most OECD member countries is 0.2 ppm
(peak limitation) with a ‘sensitiser’ notation. The standard was recently lowered to 0.1 ppm (peak) in
Australia and a similar reduction is proposed in Germany.
Manufacture of Glutaraldehyde
Exposure data is available for plant workers involved in the manufacture and drumming of
glutaraldehyde. For 88 short-term (15 min.) exposure limit tests conducted between 1989-1992, the
range was 0.01-0.34 ppm, with a mean of 0.06 ppm.
Formulation
The formulation of glutaraldehyde products is carried out by the dilution of aqueous concentrate
(generally 25-50%) with water and the addition of other ingredients. Mixing is usually carried out in a
sealed system, but handling and packaging of the formulated product is usually more open and workers
may be exposed to glutaraldehyde. Atmospheric monitoring during a well-ventilated operation in
Australia resulted in 15 minute glutaraldehyde concentrations in the range 0.02-0.10 ppm.
Cold Disinfection
The majority of exposure data for glutaraldehyde is related to its use in the health care industry. The
number of workers potentially exposed is considerable due to growth in the use of endoscopy as a routine
clinical procedure. A busy endoscopy unit in a general hospital could carry out several thousand
examinations per year with the requirement for cleaning after each procedure. Workers in operating
theatres, clinics, laboratories and dental departments may also be exposed.
Workplace monitoring has been conducted in Australian health care establishments, with glutaraldehyde
concentrations of less than 0.1 ppm generally obtained in well ventilated workplaces. Results of up to
0.11 ppm were obtained with personal monitoring, and up to 0.49 ppm with area monitoring. Workplace
monitoring in 6 Finnish health care establishments gave an average concentration of 0.1 ppm with a
standard deviation of 0.1 ppm. Monitoring of levels in French workplaces found that the majority of
samples were under 0.01 ppm. In the UK, personal monitoring results during endoscopy disinfection
were up to 0.15 ppm, with a mean of 0.02 ppm for one set of results and 0.03 ppm for another.
Published monitoring results are available. In the disinfection of surfaces in operating theatres, use of a
0.5% solution gave personal exposures up to 0.03 ppm with a mean of 0.01 ppm, while use of a 3%
solution resulted in exposures up to 0.57 ppm with a mean of 0.15 ppm. Use of a 2% solution for
disinfection in endoscopy units gave a mean of 0.015 ppm, with the highest readings during decanting
(max. 0.23 ppm).
In the USA, NIOSH has issued several reports on the atmospheric monitoring of glutaraldehyde in
hospitals, with personal monitoring results up to 0.6 ppm and area monitoring results up to 0.3 ppm.
The highest readings were for manual operations, for example, manual cleaning of endoscopes, filling
tanks, cleaning surfaces.
The introduction of automatic film processors has reduced exposure to glutaraldehyde during x-ray film
processing, but it may be significant for those workers involved in manual processing and the mixing of
solutions. Workplace atmospheric monitoring in Australian hospital x-ray facilities found that
glutaraldehyde concentrations were generally less than 0.2 ppm, although concentrations up to 0.4 ppm
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have been recorded. Monitoring in 2 Finnish workplaces found average concentrations of 0.65 ppm, with
a standard deviation of 0.17 ppm.
Water Treatment
For a cooling tower where glutaraldehyde was injected into the sump, atmospheric concentrations during
dosing at levels up to 1200 ppm were all below 0.024 ppm. Similar results were obtained during the
dosing of an air washer at 1000 ppm and in the workplace near the air vent.
A theoretical calculation (by Sweden) showed that, for an initial concentration of 50 or 125 ppm in
process water, the atmospheric concentration of glutaraldehyde would be 7 and 17.5 ppb respectively.
Exposure assessments performed at paper mills in Sweden, Scotland and Canada showed that the air
concentration never exceeded the detection limit of 20 ppb or 1 ppb (Sweden). In Sweden, the initial dose
in process water was 50 ppm glutaraldehyde.
As the glutaraldehyde solution is generally applied in spray form during this use, full body protection is
usually worn.
During the manual spraying of chicken houses with a 2% glutaraldehyde solution, a personal short-term
(10-15 min.) sample gave an exposure measurement of 0.12 ppm and three static short-term readings
were in the range 0.03-0.08 ppm. During automatic spraying, static short-term readings were in the
range 0.02-0.05 ppm.
In Australia, an egg collector was exposed to an atmospheric concentration of < 0.1 ppm while using a
solution containing 0.1-0.3% glutaraldehyde in spray form.
Other uses
Little information was available for occupational exposure to glutaraldehyde for its other uses, however,
in general, exposure is expected to be low, for example, in microscopy, in aircraft and portable toilet
sanitation, in tanning and in the paper and petroleum industries. In an ink formulating process in the UK,
air concentrations up to 0.04 ppm glutaraldehyde were recorded.
In exposure information available for France, most atmospheric concentrations during control,
disinfection, cleaning and repairing activities were < 0.005 ppm, with a peak of 17 ppm obtained for a
non-specified activity. Levels up to 0.03 ppm were obtained in the agriculture/food industry, however,
glutaraldehyde was not detectable in other industry activities monitored, for example, printing, water
treatment, machining.
In general, public exposure to glutaraldehyde is minimal. The public is unlikely to be exposed during its
routine importation, transportation and formulation, and during its use in most industrial applications.
Direct exposure is a possibility in health care establishments if cleaning and rinsing is inadequate and if
spillage occurs in patient areas. In the use of glutaraldehyde in water treatment, infrequent public
exposure may occur from drift emanating from cooling water towers. Public exposure is also a
possibility in premises after air duct disinfection if ventilation after the fogging process is inadequate.
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For non-rinse off cosmetics (face cream, general purpose cream, body lotion, roll-on antiperspirant,
hairstyling product), the mean total estimate of use for an individual was 20.3g (of product)/day,
assuming that the person used all types extensively (rather than average use). The estimate for average
use was 10.8 g/day. For rinse off cosmetics (make-up remover, shower gel, shampoo, hair conditioner),
the corresponding estimate of extensive use was 17 g/day.
Using the EC algorithm method for estimating the average daily dermal exposure (Ed), and assuming that
all products contained 0.1% glutaraldehyde, 10% of rinse off product is retained after rinsing, and 10%
of glutaraldehyde is absorbed through the skin,
Due to relatively short residence time in the environment and a lack of bioaccumulation, indirect exposure
via the environment is considered to be a minor route of exposure for humans.
Human evidence has shown that glutaraldehyde is an irritant to the skin, eyes and respiratory system,
with the effects consistent with those demonstrated in animal testing. Many cases of dermatitis have been
reported for workers exposed to glutaraldehyde solutions, usually 2% or higher. Facial dermatitis has
resulted from the use of glutaraldehyde in spray form. Irritation of the nose and throat and general
tightness of the chest have been experienced by workers exposed to glutaraldehyde vapours. In a study of
Swedish hospital workers, nose and throat irritation was experienced at vapour concentrations below 0.2
ppm. Eye irritation was observed in workers exposed to glutaraldehyde vapours above disinfectant
solutions. Human evidence indicates that skin and respiratory irritant effects are exacerbated on repeated
exposure to glutaraldehyde.
Case reports and patch testing in animals and volunteers have shown that glutaraldehyde is a skin
sensitiser. Photosensitisation testing on volunteers did not produce a phototoxic or photoallergic
response.
A number of reports of occupational asthma and/or rhinitis in workers exposed to glutaraldehyde have
produced concern that glutaraldehyde may be a respiratory sensitiser. In the absence of adequate case
reporting or an identified immune mechanism, it is difficult to say definitively that glutaraldehyde is a
respiratory sensitiser, and there is debate on whether the symptoms are due to an irritant or an allergic
respiratory response. However, in the United Kingdom, glutaraldehyde has been added to the indicative
list of respiratory sensitisers.
Limited epidemiological data is available on the long-term effects of glutaraldehyde. A mortality study
did not reveal any increased incidence of cancer deaths.
Several acute toxicity studies have been carried out in a variety of animal species. The oral LD50 of
glutaraldehyde was 134-820 mg/kg in rats, 100-350 mg/kg in mice and 50 mg/kg in guinea-pigs. The
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dermal LD50 was 640-2000 mg/kg in rabbits and > 2500 mg/kg in rats and mice, with skin absorption
observed at high concentrations. Glutaraldehyde has a high acute inhalational toxicity in rats and mice,
and lung damage has been reported. Four-hour LC50 values of 23.5 and 40.1 ppm have been obtained for
male and female rats respectively, but the glutaraldehyde solution had to be heated in order to generate
glutaraldehyde vapour at high enough concentrations.
Glutaraldehyde was corrosive to the skin and eyes of rabbits at high concentrations, with signs of skin
irritation evident at 2%, and eye irritation at 0.2%. Exposure to glutaraldehyde vapours resulted in nasal
irritation and respiratory difficulty. An RD50 of 13.8 ppm was obtained in mice, with the respiratory
decrease 26% at 1.6 ppm, the lowest dose tested. Joint irritation was seen in rabbits after intra-articular
administration. Glutaraldehyde was a skin sensitiser in guinea pigs.
Short term (9-day or 2-week) repeated dose inhalational rat studies resulted in significant mortality at
approximately 2 ppm, and nasal irritation at levels down to approximately 0.2 ppm. Lesions of the nasal
cavity and larynx were observed at 0.5 ppm and, in the 9-day study, atrophy of the liver was observed at
3.1 ppm. Signs of irritation included laboured breathing and discharge and encrustation around the eyes
and nose.
In two subchronic (13-14 weeks) inhalational rat studies, signs of nasal irritation were observed at lower
concentrations, with a NOAEL for nasal cavity lesions of 125 ppb in one study and a LOAEL of 194
ppb in the other. Slight nasal irritation was observed at 49 ppb in the second study. In corresponding 2-
week and 13-week studies in mice, mortality occurred at 1.6 ppm and 500 ppb respectively, with lesions
of the nasal cavity in females at the lowest dose (62.5 ppb) in the 13-week study.
In a short-term dermal study in male mice, cumulative toxicity and mortality occurred after repeated skin
contact to aqueous solutions containing 25% and 50% glutaraldehyde, but there was no evidence of
cumulative toxicity at 5% or less.
A subchronic drinking water study in rats indicated some toxicity at 1000 ppm, and a physiological
response at 250 ppm. Reductions in food and water consumption and a dose-related effect in kidney
weight were observed, but as drinking water studies at high concentrations are generally hampered by a
natural aversion of the animals to the taste/odour of glutaraldehyde, the significance of these results is
uncertain.
A 2-year drinking water study in rats resulted in an increased incidence of large granular lymphatic
leukaemia (LGLL) in the liver and spleen of females only at all dose levels (50-1000 ppm), but the
finding was not conclusive as the strain of rats used in the study has a high natural susceptibility to
LGLL and variation in control data existed within the study laboratory.
Repeated oral doses given during pregnancy to rabbits, rats and mice caused embryotoxicity and
foetoxicity, but only at maternally toxic doses. From a gavage study in the rabbit, the most sensitive
species, a NOAEL of 15 mg/kg/d can be taken for the maternal and foetal organism. No teratogenic
effects were observed in any of the studies.
Early mutagenicity studies were negative, but more recent studies have indicated that glutaraldehyde is
mutagenic in vitro in bacterial assays and tests in mammalian cells. In vivo genotoxicity tests to date
have proven negative.
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The critical effects are eye, skin and respiratory irritation, skin sensitisation and occupational asthma.
Nose and throat irritation has been observed in humans at vapour concentrations below 0.2 ppm.
Occupational asthma has also been reported in workers exposed to dilute solutions of glutaraldehyde. In
9-day or 2-week rat studies, nasal irritation occurred at levels down to 0.2 ppm, and in 13 or 14-week
sudies, a NOAEL of 125 ppb was obtained for nasal cavity lesions in rats and a LOAEL of 62.5 ppb in
mice.
Atmospheric concentrations of glutaraldehyde > 0.1 ppm (peak) have been recorded during disinfection
and x-ray film processing where control measures such as enclosure and local exhaust ventilation have
not been installed, so the risk of respiratory irritant effects to workers in these situations is significant.
The risk of respiratory irritant effects also may be significant where aerosols are generated, for example,
in animal housing disinfection, however, from exposure information available, the risk is low for other
uses of glutaraldehyde.
Contact dermatitis and eye irritation have been reported in workers using glutaraldehyde solutions,
usually 2% or higher. Skin sensitisation has been confirmed in workers using dilute solutions. In
rabbits, eye irritation was observed with a 0.2% solution and skin irritation with a 2% solution.
Where occupational exposure may be significant, control measures are necessary to reduce the risk of
adverse health effects. Operations involving glutaraldehyde should be enclosed as much as possible. In
the health care industry, local exhaust ventilation is recommended for fixed work stations. Where this is
not practical, mobile units with vapour extactors and adsorption filters can be used.
Recommended personal protective equipment includes safety eyewear, nitrile or butyl rubber gloves and
protective clothing. Where glutaraldehyde is used in spray form, for example, in animal housing
disinfection, a hood and respirator are also required.
Safe use guidelines, particularly for the health care industry, are worthwhile. They should include
information about the health effects of glutaraldehyde and detailed guidance on the control measures
available to minimise exposure.
Due to low and intermittent exposure, the public health risk from the industrial use of glutaraldehyde is
minimal.
For the use of glutaraldehyde in cosmetics, the average daily exposure from extensive use was estimated
at 0.037 mg/kg/day. The critical NOAEL (for maternal toxicity and reproductive effects) is 15
mg/kg/day, giving a safety margin of 15/0.037 = 405, so the use of glutaraldehyde in cosmetics is of
low concern.
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5.1 Conclusions
The health effects of glutaraldehyde in humans and animals are characterised by local irritation of the
skin, eye and respiratory tract and skin sensitisation. The irritant effects are exacerbated by repeated
exposure. Occupational asthma has been reported in workers exposed to glutaraldehyde. Consideration
of the health effects data and current exposure levels indicates that some health concerns may arise
during the use of glutaraldehyde in the health care industry (as a cold disinfectant) and during x-ray film
processing in situations where control measures such as enclosure, local exhaust ventilation and skin and
eye protection have not been implemented to minimise exposure. Similarly, in the use of glutaraldehyde
in spray form during disinfection in the animal health industry, personal protective measures are
necessary. However, it is expected that the necessary risk reduction techniques are available in member
countries to adequately manage the risk.
In most situations, the risk to aquatic organisms is low. However, there may be some risk to aquatic
organisms, specifically algae, under extreme environmental conditions, for example, during drought in
Australia. Also, there may be a risk in situations such as paper mill effluent treated only by
sedimentation and chemical precipitation and not discharged to sewer. The risk to terrestrial organisms is
low.
The use of glutaraldehyde in cosmetics does not give cause for concern at the current maximum
concentration of 0.1%.
5.2 Recommendations
There is no current priority for further testing, exposure analysis or an in-depth assessment. Risk
reduction measures are recommended for the use of glutaraldehyde in a number of occupational settings
to reduce the risk to human health. Further risk management action may be required in some situations to
reduce the risk to the environment.
6. REFERENCES
National Industrial Chemicals Notification and Assessment Scheme, Glutaraldehyde - Full Public
Report, AGPS, Canberra, Australia, July 1994.
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Australia R21-23-25-34- Over 100 te/yr imported. Used mainly in health care industry as disinfectant Exposure standard 0.1 ppm (peak),
43 (55% of total) and in x-ray film processing (20%). Also used in water sens.
treatment (10%), tanning (5%), animal health (5%), and in small quantities in
toilet disinfection, microscopy, aquaculture and air duct disinfection.
Denmark Harmful, More than 50 registered products (most contain 1-5% glutaraldehyde). Total
Corrosive, volume in Danish products is approx 50 te/yr. Mainly used in the following
Sensitiser industries: health sector (mainly hospitals), graphics and paper, film
(skin) processing, agriculture, repair and service, iron and metals, petroleum
processing, transport, food industry, tanning.
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Finland R22/38/41/43 Used in disinfection and x-ray film processing. Workplace monitoring: disinfection
of gastroscopes and
bronchoscopes: mean 0.1 ppm; x-
ray film processing: mean 0.65
ppm.
France No major producer identified. Main importer < 1000 te/yr. Use pattern: 50% Exposure standard 0.2 ppm
disinfection/biocidal control, 40% photographic industry, 5% leather industry, (ceiling value). Monitoring of
5% paper industry. Industrial activities include: disinfection, cleaning, control, disinfection, cleaning,
agriculture, food industry, printing, document reproduction, water treatment, repairing activities gave
and as biocide or preservative in a variety of other activities, eg machining, concentrations mainly < 0.005 ppm
assembling, welding. Glutaraldehyde content of 8 products used in disinfection, (peak 17 ppm). In agriculture and
control, cleaning and repairing was 0.024-6.5%. food industries, levels up to 0.03
ppm. Not detected in other
activities.
Norway R21/22-36-43 12 700 te of product consumed per year. 80% used in industrial cleaning agents Exposure standard 0.2 ppm.
S24-26-39 in food, beverage, tobacco and paper manufacturing industries. 14% used in
photocopying developers for use in the printing and publishing industry.
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Sweden Corrosive Total volume used approx. 165 te/yr. Used mainly in water treatment in the Exposure standard 0.2 ppm
Harmful pulp and paper industry. Also used in photographic chemicals, agriculture, fish (ceiling).
farming, metals industry, and disinfection in the health care industry. In the
agricultural sector, used with high pressure cleaners and fog generators at 2-5%
glutaraldehyde.
Switzerland Toxic 326 products registered, with approx. 50% being consumer products. Mainly MAK 0.2 ppm, sens.
used in disinfection (concentration 0.01-20%). Also used in washing agents for No monitoring data available.
textiles and dishes, and in photographic products.
Consumer exposure expected to be low and intermittent.
UK Used mainly as disinfectant in health care industry and as biocide in off-shore Exposure standard 0.2 ppm (10
operations. Also used in water treatment, animal health, paper manufacture, min.) Monitoring data:
cosmetics, cleaning agents, and in smaller quantities in x-ray film processing disinfection of endoscopes 0.002-
and histology. 0.15 ppm, animal housing 0.02-
0.08 ppm, water treatment < 0.024
ppm, ink formulation 0.04 ppm
(mean).
USA Used in disinfection, oil industry, tissue fixation, tanning, chemical TLV 0.2 ppm C, sens.
manufacture, printing, agriculture, paper manufacture, cleaning.
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APPENDIX B
1
Standard error
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1. GENERAL INFORMATION
A. Cas-number 111-30-8
E. EINECS-Number 203-856-5
H. Substance Group
I. Substance Remark
B. Lead Organisation
Name of Lead Organisation: Worksafe Australia
National Industrial Chemicals Notification and Assessment
Scheme (NICNAS)
Contact person: Ms Lesley Onyon
Address:
Street: 92 Parramatta Road
Town: CAMPERDOWN
SYDNEY
State/Territory: NSW
Postcode: 2050
C. Name of responder
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AGFA-Gevaert Ltd
372 Whitehorse Rd, Nunawading, Victoria 3131
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A. Type of Substance
element [ ]; inorganic [ ]; natural substance [ ]; organic [X];
organometallic [ ]; petroleum product [ ]
1.2 SYNONYMS
glutardialdehyde
glutaral
1,3-diformylpropane
glutaric dialdehyde
1.3 IMPURITIES The dimer and trimer may be present in aqueous solution.
1.4 ADDITIVES Additives such as sodium bicarbonate may be added to commercial preparations.
1.5 QUANTITY
Labelling
Classification
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A. General
Biocide/Disinfection 2% liquid
About 100 tonnes of 12-50% glutaraldehyde are imported into Australia annually.
The largest and most concentrated source of environmental exposure is disposal of spent
cold chemical sterilant solutions. These are disposed of when the concentration in the
sterilant bath drops below about 10-15 000 mg/L. Disposal generally entails flushing to
sewer with copious quantities of water.
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Occupational exposure (to vapours and by skin contact). is mainly during the use of 1%
and 2% aqueous solutions in disinfection in the health care industry. Exposure may also
be significant during the use of x-ray film processing solutions and, to a lesser extent,
during its use as a disinfectant in the animal health industry. Exposure in other
industries is usually minor or sporadic.
Public exposure is minimal, with possible exposure to humans from portable toilet use
and from vapour drift from water cooling towers.
Significant discharge of free glutaraldehyde from X-ray film processors is not expected
because of reaction with sulphite from the fixer.
2. PHYSICAL-CHEMICAL DATA
2.1 MELTING POINT (if more than one, identify the recommended value)
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Temperature: 20°C
Method:
GLP: Yes [ ] No [ ] ? [X]
Remarks; ...............
Reference: Condensed Chemical Dictionary, 1981
A. Solubility
Value: miscible
Temperature: 20-21°C
Description: Miscible [X]; Of very high solubility [ ]; Of high
solubility [ ]; Soluble [ ]; Slightly soluble [ ]; Of low
solubility [ ]; Of very low solubility [ ]; Not soluble [ ]
Method: US FIFRA guidelines 1993
GLP: Yes [X] No [ ] ? [ ]
Remarks: mean of 18 replicates
Reference: SLI report, Feb. 1994
pH Value: ...............
Concentration: ...............
Temperature: ...............°C
Method:
GLP: Yes [ ] No [ ] ? [ ]
pKa value: ............... at 25°C
Remarks: The 50% aqueous solution is mildly acid
Reference: Russell & Hopwood, 1976
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Value: ...............°C
Type of test: Closed cup [ ]; Open cup [ ]; Other [ ]
Method:
GLP: Yes [ ] No [ ] ? [ ]
Remarks: No data available
Reference: ...............
Value: ...............°C
Pressure: ...............hPa
Method:
GLP: Yes [ ] No [ ] ? [ ]
Remarks: No data available
Reference: ...............
2.9 FLAMMABILITY
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Value: ...............mV
Method:
GLP: Yes [ ] No [ ] ? [X]
Remarks: Glutaraldehyde is oxidised to glutaric acid.
Reference: Beauchamp, 1992
Value: ................
Method:
GLP: Yes [ ] No [ ] ? [ ]
Remarks: see 3.3.1
Reference: ...............
Temperature: 20-21°C
Method: US FIFRA guidelines 1993
GLP: Yes [X] No [ ] ? [ ]
Remarks: mean of 6 replicates
Reference: SLI report, Feb. 1994
3.1 STABILITY
3.1.1 PHOTODEGRADATION
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No formal data are available. However, water authorities report that glutaraldehyde has
never impacted on sewage treatment processes.
Because of the use pattern of glutaraldehyde in Australia, the main exposure is aquatic
(sewer) with some atmospheric.
Significant transport is not expected because of limited persistence in air, soil and water.
Concentrations likely to arise in sewage treatment works were estimated by diluting the
average daily disposal from sterilant baths (assumed to be 75% of average daily use) and
assuming dilution in the daily sewage flow, without degradation or sorption. Estimated
concentrations in city and rural treatment works were about 50 and 200 gµ/L, well below
biocidal concentrations. The concentration likely to enter receiving waters is therefore
low.
3.3.1 TRANSPORT
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Soil types: Sandy loam, pH 6.8, 1.0% organic carbon, 10% clay, 23%
silt, 67% sand, cation exchange capacity 5.5 meq/100 g;
Silt loam, pH 6.7, 1.4% organic carbon, 21% clay, 62% silt,
17% sand, cation exchange capacity 16.8 meq/100 g;
3.5 BIODEGRADATION
(a)
Type: Aerobic [X]; anaerobic [ ].
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23% in 6 days
30% in 7 days
35% in 15 days
80% in 15 days (DOC)
(b)
Type: Aerobic [X]; anaerobic [ ]
BOD5
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COD
RATIO BOD5/COD
3.7 BIOACCUMULATION
4 ECOTOXICOLOGICAL DATA
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Duration: 96 hours
A. Daphnia
(a)
Type of test: static [X]; semi-static [ ]; flow-through [ ]; other [ ];
open-system [ ]; closed-system [X]
Duration: 48 hours
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(b)
Type of test: static [X]; semi-static [ ]; flow-through [ ]; other [ ];
open-system [ ]; closed-system [X]
Duration: 48 hours
(a)
Type of test: static [X]; semi-static [ ]; flow-through [ ]; other [ ]; open-system
[ ]; closed-system [X]
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Duration: 48 hours
(b)
Type of test: static [X]; semi-static [ ]; flow-through [ ]; other [ ]; open-system
[ ]; closed-system [X]
Duration: 96 hours
(c)
Type of test: static [X]; semi-static [ ]; flow-through [ ]; other [ ]; open-system
[ ]; closed-system [X]
Duration: 96 hours
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96 h LC50 = 41 mg/L;
(d)
Type of test: static [ ]; semi-static [X]; flow-through [ ]; other [ ]; open-system [ ];
closed-system [ ]
Duration: 96 hours
(a)
Species Selenastrum capricornutum
Duration: 96 hours
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(b)
Species Scenedesmus supspicatus
Duration: 96 hours
Remarks: The biomass was monitored by direct cell count, and the
end-point was determined from the area under the curve.
End-points are expressed as nominal concentrations. Analytical
measurements indicated that actual concentrations were in the
order of 20% of nominal initially, declining to 5% or less after
96 h.
(a)
Type: Aquatic [ ]; Field [ ]; Soil [ ]; Other [X]
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(b)
Type: Aquatic [ ]; Field [ ]; Soil [ ]; Other [X]
Monitoring: Yes [ ]; no [ ]
No tests performed.
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Duration: 21 days
Remarks: Test solutions were renewed three times per week, with
concentrations measured for the initial and final renewal.
Results are expressed as nominal concentrations, and should be
treated with caution as measured concentrations were extremely
erratic, ranging from 99.3% of nominal to below the limit of
detection, and not correlated with nominal concentration or
exposure period. The NOEC and LOEC reflect number of
offspring per adult.
No tests available
No tests available.
(a)
Species Mallard duck
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(b)
Species Mallard duck
(c)
Species Mallard duck
(d)
Species: Bobwhite quail
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(e)
Species: Bobwhite quail
No reports.
None
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5. TOXICITY
(a)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Value: male 246 mg/kg b.w.: female 154 mg/kg
Method: US EPA, 40 CFR, parts 158 & 798
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
(b)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Value: male 316 mg/kg b.w.: female 285 mg/kg
Method: OECD 401
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
(c)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Wistar)
Value: male 362 mg/kg b.w.: female 418 mg/kg
Method: US EPA, 40 CFR 163.81-1
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
(d)
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(e)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Wistar) - males only
Value: male 1.47 g/kg b.w.
Method: ..................
GLP: Yes [ ] No [X] ? [ ]
Test substance: 50% aqueous solution
(f)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Wistar) - males only
Value: male 1.98 g/kg b.w.:
Method: ..................
GLP: Yes [ ] No [X] ? [ ]
Test substance: 25% aqueous solution
(g)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Wistar)
Value: (i) male and female > 16 g/kg b.w. (ii) m 12.3, f 9.85 g/kg; (iii)
m 3.32, f 1.33 g/kg; (iv) m 1.67, f 1.10 g/kg
Method: OECD 401
GLP: Yes [ ] No [ ] ? [X]
Test substance: (i) 0.5% aqueous solution; (ii) 1.0%; (iii) 5.0%; (iv) 10%
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(h)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Wistar)
Value: male 1217 mg/kg b.w.: female 919 mg/kg
Method: US FIFRA 1982 guidelines
GLP: Yes [X] No [ ] ? [ ]
Test substance: 14.5% aqueous solution
(a)
Type: LC0 [ ]; LC100 [ ]; LC50 [X], LCL0 [ ]; Other [ ]
Species/strain: Rat (Fischer 344)
Exposure time: 4 hours
Value: male 96 gµ/L (23.5 ppm v/v); female 164 gµ/L (40.1 ppm)
Method: OECD 403
GLP: Yes [X] No [ ] ? [ ]
Test substance: Vapours generated by metering 5% aqueous solution into
rotating evaporator tube, where hot air (65oC) exhausted into
inhalation chamber.
(b)
Type: LC0 [ ]; LC100 [ ]; LC50 [X], LCL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Exposure time: 4 hours
Value: male 0.35 mg/L; female 0.28 mg/L
Method: OECD 403
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution - aerosol
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(c)
Type: LC0 [ ]; LC100 [ ]; LC50 [X], LCL0 [ ]; Other [ ]
Species/strain: Rat (Wistar)
Exposure time: 4 hours
Value: 0.80 mg/L (male & female)
Method: .................
GLP: Yes [ ] No [ ] ? [X]
Test substance: 25% aqueous solution - aerosol
(d)
Type: LC0 [ ]; LC100 [ ]; LC50 [X], LCL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Exposure time: 4 hours
Value: male 0.52 mg/L; female 0.45 mg/L
Method: ..................
GLP: Yes [ ] No [ ] ? [X]
Test substance: 50% aqueous solution - aerosol
(e)
Type: LC0 [ ]; LC100 [ ]; LC50 [X], LCL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Exposure time: 4 hours
Value: No mortality, so no LC50 determined
Method: OECD 403
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution - open tray for static study, and air
bubbler generation (at ambient temperature) for dynamic
studies
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(a)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (Sprague-Dawley)
Value: > 2000 mg/kg b.w.
Method: OECD 402
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
(b)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rabbit (albino) - males only
Value: (i) 1.80 g/kg b.w.; (ii) 8.5 g/kg; (iii) > 16.3 g/kg
Method: Similar to OECD 402
GLP: Yes [ ] No [ ] ? [X]
Test substance: (i) 50% aqueous solution; (ii) 25%; (iii) 5%
(c)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other [ ]
Species/strain: Rat (New Zealand White)
Value: (i) males 2.24 g/kg b.w., females 3.04 g/kg
(ii) > 16.6 g/kg; (iii) > 16.5 g/kg
Method: OECD 402
GLP: Yes [ ] No [ ] ? [X]
Test substance: (I) 45% aqueous solution; (ii) 15%; (iii) 10%
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(d)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other []
Species/strain: Rabbit (New Zealand albino)
Value: 617 mg/kg b.w.
Method: ..............
GLP: Yes [ ] No [X] ? [ ]
Test substance: 45% aqueous solution
Remarks: 4 animals/dose at approx. 0.6, 1.3 or 2.8 mL
(e)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other []
Species/strain: Rabbit (albino) - males only
Value: 2.87 g/kg b.w.
Method: ..............
GLP: Yes [ ] No [X] ? [ ]
Test substance: 50% aqueous solution
Remarks: 4 animals/dose at 0.90, 1.8, 3.6 or 7.2 g/kg. Gross pathology
observations in victims included damage to lungs, liver, spleen
and kidneys. In survivors, kidneys were mottled.
(f)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other []
Species/strain: Rabbit (albino) - males only
Value: 13.6 g/kg b.w.
Method: .................
GLP: Yes [ ] No [X] ? [ ]
Test substance: 25% aqueous solution
Remarks: 4 animals/dose at 6.8 or 13.6 g/kg, 2 animals at 0.85 or 3.4
g/kg. Only 2/4 deaths at highest dose, so high degree of
uncertainty in value. Gross pathology observations in victims
included mottled liver and congested kidneys.
(g)
Type: LD0 [ ]; LD100 [ ]; LD50 [X], LDL0 [ ]; Other []
Species/strain: Rabbit (New Zealand White)
Value: > 2 g/kg b.w.
Method: US FIFRA 1982 guidelines
GLP: Yes [X] No [ ] ? [ ]
Test substance: 14.5% aqueous solution
Remarks: 1.0 or 2.0 g/kg was applied (under gauze) to the clipped trunk
of 5 animals/sex/dose. Only one male death at 2g/kg occurred.
Gross pathology revealed discoloured lungs in 3 males.
(h)
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No studies available.
5.2 CORROSIVENESS/IRRITATION
(a)
Species/strain: Rabbit (New Zealand White)
Results: 50% aqueous solution: Corrosive [X]
25%: Highly irritating [X]
2%: Slightly irritating [X]
1%: Not irritating [X]
Classification: > 25%: Corrosive (caused burns) [X]
2% and up to 25%: Irritating [X]
Method: OECD 404
GLP: Yes [X] No [ ] ? [ ]
Test substance: 1% to 50% aqueous solutions
Remarks: 3 male and 3 females treated with 0.5 mL solution, which was
kept in contact for 4 hours under an occlusive dressing. 45 and
50% solutions corosive - moderate to severe erythema, slight to
severe oedema and spots of necrosis; 25% solution a severe
irritant; 2% a slight irritant; no significant effects for a 1%
solution.
(b)
Species/strain: Rabbit (New Zealand White)
Results: Highly irritating [X]
Classification: Highly corrosive (causes severe burns) [ ];
Corrosive (caused burns) [ ]; Irritating [X];
Not irritating [ ]
Method: USA FIFRA 1982 guidelines
GLP: Yes [X] No [ ] ? [ ]
Test substance: 14.5% aqueous solution
Remarks: 3 male and 3 females treated with 0.5 mL solution, which was
kept in contact for 4 hours under an occlusive dressing.
Resulted in moderate to severe erythema, moderate oedema and
necrosis.
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(a)
Species/strain: Rabbit (New Zealand White)
Results: 5% solution: Highly irritating [X]
2%: Irritating [X]
1%: Moderate irritating [X]
Classification: Irritating [X]; Not irritating [ ]; Risk of serious damage to
eyes [ ]
Method: OECD 405
GLP: Yes [X] No [ ] ? [ ]
Test substance: 1, 2 and 5% aqueous solutions
(b)
Species/strain: Rabbit (albino) - males only
Results: Slightly irritating [X]
Classification: Iritating [X]
Method: OECD 405
GLP: Yes [X] No [ ] ? [ ]
Test substance: 0.1, 0.2 and 0.5% aqueous solutions
(c)
Species/strain: Rabbit (New Zealand White)
Results: Corrosive [X]
Classification: Iritating [ ]; Not irritating [ ]; Risk of serious damage to eyes
[X}
Method: US FIFRA 1982 guidelines
GLP: Yes [X] No [ ] ? [ ]
Test substance: 14.5% aqueous solution
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(a)
Type: Maximisation
Species/strain: Guinea-pig (Dunkin Hartley)
Results: Sensitising [X]; Not sensitising [ ]; ambiguous [ ]
Classification: Sensitising [X]; Not sensitising [ ]
Method: OECD 406
GLP: Yes [X] No [ ] ? [ ]
Test substance: 2% aqueous solution
(b)
Type: Buehler
Species/strain: Guinea-pig (Hartley)
Results: Sensitising [ ]; Not sensitising [X]; ambiguous [ ]
Classification: Sensitising [ ]; Not sensitising [X]
Method: OECD 406
GLP: Yes [ ] No [ ] ? [X]
Test substance: 0.5% aqueous solution
(c)
Type: Patch Test
Species/strain: Human
Results: Sensitising [ ]; Not sensitising [ ]; ambiguous [X]
Classification: Sensitising [ ]; Not sensitising [ ]
Method: Other
GLP: Yes [ ] No [X] ? [ ]
Test substance: 2% + 5% aqueous solution
(d)
Type: Patch Test
Species/strain: Human
Results: Sensitising [X]; Not sensitising [ ]; ambiguous [ ]
Classification: Sensitising [X]; Not sensitising [ ]
Method: other
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(a)
Species/strain: Rat (Fischer 344)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: Oral feed (drinking water)
Exposure period: 90 days
Frequency of treatment: 7 days/week
Postexposure observ. period: 4 weeks
Dose: males: 0, 5, 25, 100 mg/kg
females: 0, 7, 35, 120 mg/kg
(20m, 20f per group)
Control group: Yes [X]; No [ ]; No data [ ], Concurrent no treatment
[ ]; Concurrent vehicle [X]; Historical [ ]
NOEL: 5 mg/kg
LOEL: 25 mg/kg
(b)
Species/strain: Mouse (C3H/HeJ)
Sex: Female [ ]; Male [X]; Male/Female [ ]
Route of Administration: Dermal
Exposure period: 10 days
Frequency of treatment: one application per day
Postexposure observ. period: ...............
Dose: 50µ L of solution
Control group: Yes [X]; No [ ]; No data [ ]
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Method: ...............
GLP: Yes [X] No [ ] ? [ ]
Test substance: 0.05, 0.25, 0.5, 2.5, 5.0, 25 and 50% aqueous solution
(c)
Species/strain: Rat (Fischer 344)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: Dermal
Exposure period: 28 days
Frequency of treatment: daily
Postexposure observ. period: 4 weeks
Dose: 2.0 mL/kg b.w./day of 0, 2.5, 5.0 or 7.5% of solution
of test substance (0, 50, 100, 150 mg/kg b.w./day)
Control group: Yes [X]; No [ ]; No data [ ]
Concurrent no treatment [ ]; Concurrent
vehicle [X]; Historical [ ]
NOEL: not determined
LOEL: 50 mg/kg b.w./day (lowest dose)
Results: 15 animals/sex/dose for control and high doses, 10 for
low and mid doses.
No treatment-related mortality. Clinical signs of
toxicity during study included slight erythema, little
oedema and persistent skin colour change. Dose-
related incidence of skin lesions confirmed by
microscopic examination at necropsy. Reduced body
weight gain in males, dose-related increase in platelet
count in females.
(d)
Species/strain: Rat (Fischer 344)
Sex: Female [ ]; Male [ ]; Male/Female [X];
Route of Administration: inhalation
Exposure period: 9 days
Frequency of treatment: 6 hours/day
Post-exposure observ. period: ...............
54
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OECD SIDS GLUTARALDEHYDE
(e)
Species/strain: Rat (Fischer 344)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 9 days
Frequency of treatment: 6 hours/day
Post-exposure observ. period: ...............
Dose: 0, 0.3, 1.1, 3.1ppm
Control group: Yes [X]; No [ ]; No data [ ]
oncurrent no treatment [ ]; Concurrent vehicle [ ];
Historical [ ]
NOEL: ...............
LOEL: 0.3 ppm
(f)
Species/strain: Rat (F344/N)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 2 weeks
55
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OECD SIDS GLUTARALDEHYDE
(g)
Species/strain: Mouse (B6C3F1)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 2 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observ. period: ...............
Dose: 0, 0.16, 0.5, 1.6, 5 and 16ppm
Control group: Yes [X]; No [ ]; No data [ ]
Concurrent no treatment [ ]; Concurrent
vehicle [ ]; Historical [ ]
NOEL: 0.16 ppm
LOEL: 0.5 ppm
Results: Five animals per sex were in each group. All mice at
1.6 ppm and above died of respiratory distress. At
necropsy, histological examination of tissues revealed
damage to the nasal cavity at 1.6 ppm and above, and
damage to the larynx at 0.5 ppm and above.
(h)
Species/strain: Rat (Fischer 344)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 14 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observ. period: ...............
Dose: 0, 21, 49, 194ppb
Control group: Yes [X]; No [ ]; No data [ ]
56
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OECD SIDS GLUTARALDEHYDE
(i)
Species/strain: Rat (F344/N)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 13 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observ. period: ...............
Dose: 0, 62.5, 125, 250, 500, 1000 ppb
Control group: Yes [X]; No [ ]; No data [ ]
Concurrent no treatment [ ]; Concurrent
vehicle [ ]; Historical [ ]
NOEL: 125 ppb
LOEL: 250 ppb
Results: Ten animals per sex were in each group, with no
exposure-related mortality. Dose-related lesions of the
nasal cavity were observed at 250 ppb and above. The
body weight gain was reduced in males at 1000 ppb,
and in females at 500 and 1000 ppb.
Histoaudioradiographic studies indicated that the nasal
lesions were different from those observed with
formaldehyde.
(j)
Species/strain: Mouse (B6C3F1)
Sex: Female [ ]; Male [ ]; Male/Female [X]
Route of Administration: inhalation
Exposure period: 13 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observ. period: ...............
Dose: 0, 62.5, 125, 250, 500, 1000ppb
Control group: Yes [X]; No [ ]; No data [ ]
Concurrent no treatment [ ]; Concurrent
vehicle [ ]; Historical [ ]
NOEL: ...............
57
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OECD SIDS GLUTARALDEHYDE
A. BACTERIAL TEST
(a)
Type: Cytogenetic assay
System of testing: Chinese hamster ovary cells
Concentration: 0.03 - 30 gµ/mL
Metabolic activation: With [ ]; Without [ ]; With and Without [X]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: 300 gµ/mL
Without metabolic activation: 30 gµ/mL
58
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OECD SIDS GLUTARALDEHYDE
(b)
Type: Cytogenetic assay
System of testing: Chinese hamster ovary cells
Concentration: 0.3 - 16 gµ/mL
Metabolic activation: With [ ]; Without [ ]; With and Without [X]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: ...............
Without metabolic activation: ...............
Precipitation conc: ...............
Genotoxic effects: + ? -
With metabolic activation: [ ] [ ] [X]
Without metabolic activation: [X] [ ] [ ]
Method: Similar to OECD 473
GLP: Yes [X] No [ ] ? [ ]
Test substance:
Remarks: In these chromosomal aberration assays, one laboratory
obtained negative results with and without S9 metabolic
activation. In the second laboratory, the result was negative
with S9, and positive without S9.
(c)
Type: Sister chromatid exchange assay
System of testing: Chinese hamster ovary cells
Concentration: 0.36 - 16 gµ/mL
Metabolic activation: With [ ]; Without [ ]; With and Without [X]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: ...............
Without metabolic activation: ...............
Precipitation conc: ...............
Genotoxic effects: + ? -
With metabolic activation: [X] [ ] [ ]
Without metabolic activation: [X] [ ] [ ]
Method: Similar to OECD 479
GLP: Yes [X] No [ ] ? [ ]
Test substance:
Remarks: In one laboratory, sister chromatid exchanges were induced,
with and without S9 metabolic activation. In the second
laboratory, the result was negative without S9, and weakly
positive with S9.
59
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OECD SIDS GLUTARALDEHYDE
(d)
Type: Sister chromatid exchange assay
System of testing: Chinese hamster ovary cells
Concentration: 0.01 - 0.3 gµ/mL
Metabolic activation: With [ ]; Without [ ]; With and Without [X]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: 0.30 mg/mL
Without metabolic activation: 0.10 mg/mL
Precipitation conc: ...............
Genotoxic effects: + ? -
With metabolic activation: [ ] [X] [ ]
Without metabolic activation: [ ] [X] [ ]
With metabolic activation, statistically significant increases
were observed at 0.1 and 1 gµ/mL, but not at 0.3 gµ/mL. Without
metabolic activation, statistically significant increases were
observed at 0.03 and 0.1 gµ/mL, but not at 0.3 gµ/mL.
(e)
Type: HGPRT forward mutation assay
System of testing: Chinese hamster ovary cells
Concentration: 0.10 - 30 gµ/mL
Metabolic activation: With [ ]; Without [ ]; With and Without [X]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: 30 gµ/mL
Without metabolic activation: 6 gµ/mL
Precipitation conc: ...............
Genotoxic effects: + ? -
With metabolic activation: [ ] [ ] [X]
Without metabolic activation: [ ] [ ] [X]
Method: ....................
GLP: Yes [X] No [ ] ? [ ]
Test substance: UCARCIDE Antimicrobial 250, a 50% aqueous solution
Remarks: This recent study as not reviewed,
(f)
Type: Mouse lymphoma assay
System of testing: Mouse lymphoma L5178Y cells
Concentration: 0 - 16 gµ/mL
Metabolic activation: With [ ]; Without [X]; With and Without [ ]; No data [ ]
Results:
Cytotoxicity conc:
With metabolic activation: ...............
60
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OECD SIDS GLUTARALDEHYDE
(a)
Type: Micronucleus assay
Species/strain: Mouse (Swiss-Webster)
Sex: Female [ ]; Male [ ]; Male/Female [X]; No data [ ]
Route of Administration: gavage
Exposure period: ...............
Doses: 0, 80, 160, 250 mg/kg
Results:
Effect on mitotic index or P/N ratio: no change in P/N ratio
Genotoxic effects: + ? -
[] [] []
Method: similar to OECD 474
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
Remarks: Five animals per sex per group were dosed except for
250 mg/kg, where 8 per sex were dosed. No females
died, but 2 mice at 250 mg/kg and one each at 80 and
160 mg/kg died. No induction of micronuclei in the
polychromatic erythrocytes in the peripheral blood was
observed.
(b)
Type: Cytogenetic assay
Species/strain: Rat (Sprague-Dawley)
Sex: Female [ ]; Male [ ]; Male/Female [X]; No data [ ]
Route of Administration: gavage
Exposure period: ...............
Doses: males: 0, 25, 60, 120 mg/kg bw; females: 0, 15, 40,
80 mg/kg
Results:
Effect on mitotic index or P/N ratio: ...............
Genotoxic effects: + ? -
[ ] [ ] [X]
Method: similar to OECD 475
GLP: Yes [X] No [ ] ? [ ]
Test substance: 50% aqueous solution
Remarks: Five animals per sex per group were dosed, with one
male at 120 mg/kg dying. The number off aberrant
61
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OECD SIDS GLUTARALDEHYDE
(c)
Type: Drosophila SLRL test
Species/strain: Drosophila melanogaster
Sex: Female [ ]; Male [X]; Male/Female [ ]; No data [ ]
Route of Administration: injection and oral feed
Exposure period: ...............
Doses: ...............
Results:
Effect on mitotic index or P/N ratio: ...............
Genotoxic effects: + ? -
[ ] [ ] [X]
Method: similar to OECD 477
GLP: Yes [ ] No [ ] ? [ ]
Test substance:
Remarks: Male Canton-S wild-type flies were injected with
glutaraldehyde solution, with the number of lethal
mutations from the mating of newly-emerged flies
determined. The results were negative. In a second
series of tests, the eggs of mated Canton-S flies were
exposed to cornmeal containing glutaraldehyde, with
the results also negative.
5.7 CARCINOGENICITY
62
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OECD SIDS GLUTARALDEHYDE
Method: ...............
GLP: Yes [ ] No [ ] ? [X]
Test substance:
Remarks: ...............
Reference: Ballantyne, Bushy Run RC draft report
91U0012, Apr. 1993, and report Mar. 1994
(a)
Type: Fertility [X]; One generation study [ ]; Two
generation study [ ]; Other [ ]
Species/strain: Rat (F344/N)
Sex: Female [ ]; Male [ ]; Male/Female [X]; No
data [ ]
Route of Administration: inhalation
Exposure period: 13 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observation period: ...............
Premating exposure period: male: ..............., female: ...............
Duration of test: ...............
Doses: 0, 62.5, 250, 1000 ppb
Control group: Yes [X]; No [ ]; No data [ ];
Concurrent no treatment [ ]; Concurrent
vehicle [ ]; Historical [ ]
...............
NOEL Parental: ...............
NOEL F1 Offspring: ...............
NOEL F2 Offspring: ...............
Results: Sperm morphology measurements for the males
were normal. Estrous cycle lengths for the
females were normal.
Method: ...............
GLP: Yes [ ] No [ ] ? [X]
Test substance:
Remarks: ...............
Reference: NTP, March 1993
(b)
Type: Fertility [X]; One generation study [ ]; Two
generation study [ ]; Other [ ]
Species/strain: Mouse (B6C3F1)
Sex: Female [ ]; Male [ ]; Male/Female [X]; No
data [ ]
Route of Administration: inhalation
Exposure period: 13 weeks
Frequency of treatment: 6 hours/day, 5 days/week
Postexposure observation period: ...............
Premating exposure period: male: ..............., female: ...............
Duration of test: ...............
63
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OECD SIDS GLUTARALDEHYDE
Method: ...............
GLP: Yes [ ] No [ ] ? [X]
Test substance:
Remarks: ...............
(c)
Type: Fertility [ ]; One generation study [ ]; Two
generation study [X]; Other [ ]
Species/strain: Rat (CD)
Sex: Female [ ]; Male [ ]; Male/Female [X]; No
data [ ]
Route of Administration: oral (drinking water)
Exposure period: 20 weeks
Frequency of treatment: ...............
Postexposure observation period: ...............
Premating exposure period: 10 weeks
Duration of test: 9 months
Doses: 0, 50, 250, 1000 ppm
Control group: Yes [X]; No [ ]; No data [ ];
Concurrent no treatment [ ]; Concurrent
vehicle [X]; Historical [ ]
Method: ...............
GLP: Yes [X] No [ ] ? [ ]
Test substance: UCARCIDE Antimicrobial 250, which is a
50% aqueous solution
Remarks: This recent study was not reviewed. Dose
concentrations expressed as w/v
glutaraldehyde.
64
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OECD SIDS GLUTARALDEHYDE
(a)
Species/strain: Rat (Wistar)
Sex: Female [X]; Male [ ]; Male/Female [ ]; No data [ ]
Route of Administration: Drinking water
Duration of test: sacrifice at 20 days
Exposure period: days 6 to 16 post coitum
Frequency of treatment: ...............
Doses: 0, 5, 36, 68 mg/kg bw (25 per group)
Control group: Yes [X]; No [ ]; No data [ ];
Concurrent no treatment [ ]; Concurrent vehicle [X];
Historical [ ]
NOEL Maternal Toxicity: 5 mg/kg
NOEL teratogenicity: ...............
Results: A dose-related decrease in water consumption occurred
for dams at 26 and 68 mg/kg. For foetuses, no
significant findings were observed in the sex
distribution, placental weight or foetal weight. No
significant malformations or variations were noted in
soft tissue and skeletal examination of the foetuses.
(b)
Species/strain: Rabbit(Himalayan)
Sex: Female [X]; Male [ ]; Male/Female [ ]; No data [ ]
Route of Administration: gavage
Duration of test: sacrifice at day 29
Exposure period: days 7 to 19 post insemination
Frequency of treatment: daily
Doses: 0, 5, 15, 45 mg/kg bw (15 per group)
Control group: Yes [X]; No [ ]; No data [ ];
Concurrent no treatment [ ]; Concurrent vehicle [X];
Historical [ ]
NOEL Maternal Toxicity: 15 mg/kg
NOEL teratogenicity: ...............
Results: Five of the 15 does died at 45 mg/kg, with only 4 live
foetuses produced (from one doe). In the does, food
consumption and body weight gain were reduced, and
at necropsy, irritation of the gastrointestinal tract was
noted. No significant effects were observed for does or
foetuses at 5 and 15 mg/kg. There was no evidence of
teratogenicity at any dose.
A. Specific toxicities
65
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OECD SIDS GLUTARALDEHYDE
(a)
Type: Respiratory irritation
Species/strain: Mouse (Swiss Webster) - males only
Results: Irritating at the lowest dose (1.64 ppm)
RD50 13.8 ppm
Classification: Irritating
Method: ASTM E981-84
GLP: Yes [X] No [ ] ? [ ]
Test substance: Vapour generated by passing air (at ambient temperature)
through a bubbler containing 50% aqueous solution - a second
bubbler required for the higher vapour concentrations
(b)
Type: Respiratory hypersensitivity
Species/strain: Guinea pig (Hartley) - males only
Results: Sensitising [ ]; Not sensitising [X]; ambiguous [ ]
Classification: Sensitising [ ]; Not sensitising [X]
Method: ...................
GLP: Yes [X] No [ ] ? [ ]
Test substance: Vapour generated by passing air (at ambient temperature)
through bubbler containing 50% aqueous solution
Remarks: 8 animals exposed (head only) to 14 ppm for 1h/day for 5 days,
followed by challenge with 4-5 ppm on days 19, 26, 40. No
change in respiratory waveform, and respiratory rate decrease
in exposed animals similar to controls in each challenge phase.
(c)
Type: Phototoxicity
Results: not phototoxic in humans
(d)
Type: Photoallergy
Results: No evidence of photoallergic response in humans
66
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B. Toxicodynamics, toxicokinetics
Type: Toxicokinetics
Results: Dermal and intravenous studies in the rat with dilute aqueous glutaraldehyde
solutions (0.075-7.5%) showed that , in dermal tests, approx 5% was absorbed
in the rat, and 30-50% in the rabbit. In the intravenous injection tests, approx
12% was absorbed in the rat and approx 33% in the rabbit. There were no
significant differences between males and females in the study. The dermal
absorption rate constant was low (0.2-2 hours) in each species. The elimination
times were long for both intravenous injection (t0.5 for the rat 10h, rabbit 15-
30h) and dermal application (t0.5 for the rat 40-110h, rabbit 20-100h), possibly
due to the binding of glutaraldehyde to protein and the slow excretion of
metabolites. The principal metabolite in both species was CO2 with other
metabolites not identified. The report proposed that the metabolism probably
involved initial oxidation to corresponding carboxylic acids by aldehyde
dehydrogenase, and then further oxidation to CO2. (Reference: Ballantyne,
1986)
Other studies:
In vitro studies using human skin tissue showed that glutaraldehyde did not
penetrate the thick skin of the sole, but 3-14% penetrated the stratum corneum
of the chest and abdomen and 3-4% penetrated the epidermis. (Ref. Reifenrath,
1985)
In a study in humans, rats, mice, rabbits and guinea-pigs, less than 1% of
applied glutaraldehyde penetrated the skin. (Ref. Beauchamp, 1992)
(a)
Results: No. of deaths in a mortality study was less than expected, as was the
incidence of cancer deaths.
Remarks: The incidence of death and incidence of cancer deaths in 186 male
employees at a glutaraldehyde production unit were compared to those
of US white males and to 29,000 other chemical workers during the
period 1959 - 1978. All subjects were observed for 10 years.
(b)
Results: The incidence of sensitisation in glutaraldehyde workers was
inconclusive.
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OECD SIDS GLUTARALDEHYDE
Dermatitis of the hands in 18 of 39 (46%) Swedish hospital workers using aq. glutaraldehyde, compared
with 16% in controls. (Ref. Norback, Scand. J. Work Env. Hlth vol 14, 366-371, 1988)
Increased incidence of skin disease in 541 hospital cleaners compared with 157 controls. (Ref. Hansen,
Cont. Derm. vol9, 343-351, 1983)
Facial dermatitis in 3 of 9 staff in an endoscopy unit. (Ref. Jachuck et al, J. Soc. Occup. Med. vol 39,
69-71, 1989)
Skin irritation in 14 of 44 hospital workers exposed to 2% solution. (Ref. NIOSH HETA report 86-226-
1769, Jan. 1987)
Eye irritation in 28 of 44 hospital workers exposed to 2% solution. (Ref. NIOSH HETA report 86-226-
1769, Jan. 1987)
Nose and throat irritation in Swedish hospital workers using aq. glutaraldehyde. (Ref. Norback, Scand.
J. Work Env. Hlth vol 14, 366-371, 1988)
Nose and throat irritation in hospital workers using 2% aq. glutaraldehyde. (Ref. D’Arcy,. J. Pharmac.
Belg. vol 45, 47, 1989)
Dermatitis of hands and fingers and around eyes and mouth in hospital cleaner exposed to 2%
glutaraldehyde solution. Patch testing positive. (Ref. Di Prima et al, Cont. Derm. vol 9 (3), 219-220,
1988)
Dermatitis of hands in hospital nurses. Patch test positive. (Ref. Bardazzi et al, Cont. Derm. vol 14 (5),
319-320, 1986)
Dermatitis of hands, arms face and neck in hospital maintenance employee. Patch testing positive. (Ref.
Fowler, J. Occup. Med. vol 31 (10), 852-853, 1989)
Dermatitis of the hands in 13 health care workers exposed regularly to glutaraldehyde solution. Positive
patch test in 9 workers after 48h and positive in all after 96h. (Ref. Nethercott et al, Cont. Derm. vol 18,
193-196, April 1988)
Dermatitis in funeral service workers; 6/34 tested positive to glutaraldehyde compared 0/38 controls.
(Ref. Nethercott et Holness, Cont. Derm. vol 18, 263-267, May 1988)
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Dermatitis on hands and forearms in 5 hospital workers. Patch testing positive. (Ref. Goncalo et al,
Cont. Derm. vol 10, 183-184, 1984)
Dermatitis on fingers of a radiologist and an x-ray technician. Patch testing positive. (Ref. Fisher, Cutis
vol 28, 113-122, 1981)
Dermatitis of hands and fingers in three dental assistants and two patients being treated therapeutically
with glutaraldehyde. Patch testing positive. (Ref. Jordan et al, Arch. Dermatol. Res. vol 105, 94-95,
1972)
Dermatitis of scalp from hair conditioner containing glutaraldehyde. Positive patch test. (Ref. Jaworsky
et al, Cleveland Clinic J. Med. vol 54 (5), 443-444, 1987)
Asthma-like symptoms in endoscopy unit sister; peak-flow measurements improved over weekend. (Ref.
Benson, J. Soc. Occup. Med. vol 34, 63-64, 1984)
Asthma in 4 endoscopy nurses, including 3 atopics. Adverse reaction in 2 cases on provocation testing
with glutaraldehyde. (Ref. Corrado et al, Human Toxicol. vol 5, 325-327, 1986)
Rhinitis in 6 of 9 staff in an endoscopy unit and one case of asthma; no history of atopy. (Ref. Jachuck
et al, J. Soc. Occup. Med. vol 39, 69-71, 1989)
Asthma in respiratory technologist in bronchoscopy unit. Positive challenge testing. (Ref. J. Allergy
Clin. Immunol. vol 91 (5), 974-978, 1993)
Asthma in two radiographers with history of hay-fever. Only one positive to challenge testing. (Ref.
Cullinan, The Lancet, vol 340, 1477, 12 Dec1992)
Asthma-like symptoms in endoscopy nurse; improved over weekend and holidays. (Ref. Caswell,
Australian Doctor, 10 Sep 1993, 53-54)
Asthma, nasal congestion and watering of eyes in respiratory technician, with frequency and severity
gradually increasing. Delayed response on challenge test, but IgE and IgG levels normal. (Ref. Nicewicz
et al, Immunol. Allergy Pract. vol 8 (8), 272-278, 1986)
Additional information on workplace exposure in Australia and information on human health effects are
detailed in the NICNAS Glutaraldehyde Report 1994.
6. REFERENCES
69
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OECD SIDS GLUTARALDEHYDE
• Howard, "Handbook of Environmental Fate and Exposure Data for Organic Chemicals",
Volume I, Large Production and Priority Pollutants, Lewis Publishers, Michigan, 1989;
Volume IV, Solvents 2, Lewis Publishers, Michigan, 1993.
• Ritter, "Ready Biodegradability: Modified MITI-Test (I) for Piror 850", RCC Project
245327, May 1990.
• Waggy, "Glutaraldehyde Ecological Fate and Effects Studies", Union Carbide Research
and Development Department Project No 515G02, October 1981.
• Vilkas, "The Acute Toxicity of 50% Glutaraldehyde to the Water Flea, Daphnia magna
Straus, Union Carbide Environmental Services Project No 11506-61-04, January 1978.
• "The Acute Toxicity of 25% Aqueous Glutaraldehyde to the Water Flea, Daphnia
magna Straus, Union Carbide Environmental Services Project No 11506-61-03,
December 1977.
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• Adema and Bakker, “Aquatic Toxicity of Compounds that May be Carried Over by
Ships. A Progress Report for 1983 and 1984”, Netherlands Organisation for Applied
Scientific Research, Report no. R 84/59, May 1984
• "Influence of Piror 850 on the Reproduction of Daphnia magna", Cytotest Cell Research
Project No 164002, March 1990.
• Acute Oral LD50 - Mallard Duck: Glutaraldehyde 25%", Wildlife International Ltd
Project No 142-114, January 1978.
• "Acute Oral LD50 - Mallard Duck: Glutaraldehyde 50%", Wildlife International Ltd
Project No 142-111, February 1978.
• "Eight Day Dietary LC50 - Mallard Duck: Glutaraldehyde 50%", Wildlife International
Ltd Project No 142-110, January 1978.
• Bushy Run Research Centre, ‘UCARCIDE Antimicrobial 250, ‘Acute Peroral Toxicity
Study in the Rat’, Project Report 54-145, Pennsylvania, USA, January 1992.
• Product Safety Labs, ‘Glutaraldehyde 50%: EPA Acute Oral LD50’, Report T-2299,
New Jersey, USA, June 1982.
• Mellon Institute, ‘Range Finding Tests on Glutaraldehyde, 45% Aqueous’, Report 27-
137, Pennsylvania, USA, September 1964.
• Bushy Run Research Centre, ‘Aqucar 514 Water Treatment Biocide - Acute Toxicity
and Irritancy Study’, Project Report 47-166, Pennsylvania, USA, November 1984.
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• Bushy Run Research Centre, ‘Ucarcide Antimicrobial 250: Acute Vapour Inhalation
Toxicity Test in Rats’, Project Report 53-8, Pennsylvania, USA, November 1990.
• Bushy Run Research Centre, ‘Glutaraldehyde Dilutions - Percutaneous Toxicity and Eye
Irritation Studies’, Project Report 44-65, Pennsylvania, USA, June 1981.
• Bushy Run Research Centre, ‘Glutaraldehyde Dilutions (45%, 15%, 10%)- Acute
Percutaneous Toxicity Studies’, Project Report 48-51, Pennsylvania, USA, June 1985.
• Bushy Run Research Centre, ‘Glutaraldehyde Dilutions - Primary Skin and Eye
Irritancy Studies’, Project Report 47-33, Pennsylvania, USA, November 1984.
• Pharmaco LSR Inc., ‘Guinea Pig Maximization Test with Glutaraldehyde’, study no.
93-0793, New Jersey, USA, September 1993.
• Product Safety Labs, ‘Glutaraldehyde 50%: ‘Guinea Pig Sensitisation (Buehler)’, Report
no. T-2303, New Jersey, USA, 1 June 1982.
• Shelanski, ‘Glutaraldehyde, 5% Solution - Repeated Insult Patch Test’, I.B.L. No. 4099,
Industrial Biology Laboratories Inc., August 1966.
• Testkit Laboratories Inc., ‘Glutaraldehyde - Repeated Insult Patch Test’, Study no. 80-
39, USA, November 1980.
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No.25, National Institute of Health Publication 93-3348, U.S. Department of Health and
Human Services, March 1993.
• TKL Research Inc., ‘Glutaraldehyde 0.5% - Phototoxicity Test’, Study no. 906001,
New Jersey, USA, April 1990.
73
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• TKL Research Inc., ‘Glutaraldehyde - Photoallergy Test’, Study no. 907001, New
Jersey, USA, April 1990.
74
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systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : ARG type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | MPC |
--------------------------------
8H-TWA : 0.7 MG/M3 (0.2 PPM)
entry date: OCT 1991 effective date: 29MAY1991
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : CAN type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | TLV |
--------------------------------
TWA: ceiling limit - 0.2 ppm, 0.7 mg/m3. Prescribed by the Canada
Occupational Safety and Health Regulations, under the Canada Labour
Code(administered by the Department of Employment and Immigration).
The regulations state that no employee shall be exposed to a
concentration of an airborne chemical agent in excess of the value for
that chemical agent adopted by ACGIH (American Conference of
Governmental Industrial Hygienists) in its publication entitled:
"Threshold Limit Value and Biological Exposure Indices for 1985-86".
The regulations also state that the employer shall, where a person is
about to enter a confined space, appoint a qualified person to verify
by means of tests that the concentration of any chemical agent or
combination of chemical agents will not result in the exposure of the
person to a concentration in excess of the value indicated above.
These regulations prescribe standards whose enforcement will provide a
safe and healthy workplace.
entry date: OCT 1994 effective date: 24MCH1994
*******
systematic name:Pentanedial
common name :glutaraldehyde
76
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OECD SIDS GLUTARALDEHYDE
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : CAN type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| USE | OCC | RQR |
| STORE | | |
| LABEL | | |
--------------------------------
Ingredient Disclosure List - Concentration: 1% weight/weight. The
Workplace Hazardous Materials Information System (WHMIS) is a national
system providing information on hazardous materials used in the
workplace. WHMIS is implemented by the Hazardous Products Act and the
Controlled Products Regulations (administered by the Department of
Consumer and Corporate Affairs). The regulations impose standards on
employers for the use, storage and handling of controlled products.
The regulations also address labelling and identification, employee
instruction and training, as well as the upkeep of a Materials Safety
Data Sheet (MSDS). The presence in a controlled product of an
ingredient in a concentration equal to or greater than specified in
the Ingredient Disclosure List must be disclosed in the Safety Data
Sheet.
entry date: APR 1991 effective date: 31DEC1987
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :Glutardialdehyde
cas no :111-30-8 rtecs no :MA2450000
area : DEU type : REC
77
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OECD SIDS GLUTARALDEHYDE
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AQ | | CLASS |
| USE | INDST | RQR |
--------------------------------
THIS SUBSTANCE IS CLASSIFIED AS HAZARDOUS TO WATER (WATER-HAZARD CLASS:
WGK 2). (THE DIFFERENT CLASSES ARE: WGK 3 = VERY HAZARDOUS; WGK 2 =
HAZARDOUS; WGK 1 = SLIGHTLY HAZARDOUS; WGK 0 = IN GENERAL NOT
HAZARDOUS.) THE CLASSIFICATION FORMS THE BASIS FOR WATER-PROTECTION
REQUIREMENTS FOR INDUSTRIAL PLANTS IN WHICH WATER-HAZARDOUS SUBSTANCES
ARE HANDLED.
entry date: JAN 1995
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :Glutardialdehyde
cas no :111-30-8 rtecs no :MA2450000
area : DEU type : REC
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | MAK |
--------------------------------
8h-TWA: 0.1 ml/m3 (ppm); 0.4 mg/m3 (20C, 101.3 kPa). Local irritant.
5min-STEL: 0.2 ml/m3 (ppm); 0.8 mg/m3; ceiling value; 8x/shift. Danger
of sensitization. Pregnancy group C: There is no reason to fear a risk
of damage to the developing embryo or fetus when MAK and BAT values are
adhered to.
entry date: FEB 1996 effective date: 01JUL1995
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : GBR type : REC
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| SAFTY | INDST | RQR |
| MONIT | | |
--------------------------------
The code of practice gives practical guidance on how to protect workers
from the ill-effects of respiratory sensitisers including
glutaraldehyde. Assessment of risk, control measures, monitoring
78
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OECD SIDS GLUTARALDEHYDE
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : GBR type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| TRNSP | MARIN | RQR |
| AQ | MARIN | RSTR |
| AQ | EMI | RSTR |
--------------------------------
CATEGORY D SUBSTANCE: DISCHARGE INTO THE SEA IS PROHIBITED; DISCHARGE
OF RESIDUAL MIXTURES IS SUBJECT TO RESTRICTIONS. (APPLIES TO
GLUTARALDEHYDE SOLUTIONS OF 50% OR LESS).
entry date: 1992 effective date: 06APR1987
title: THE MERCHANT SHIPPING (CONTROL OF POLLUTION BY NOXIOUS LIQUID
SUBSTANCES IN BULK) REGULATIONS 1987, SCHEDULE 1
original : GBRSI*, STATUTORY INSTRUMENTS, 551 , , 15 , 1987
amendment: GBRSI*, STATUTORY INSTRUMENTS, 2604 , , 2 , 1990
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : MEX type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | MXL |
--------------------------------
AT ANY WORKPLACE WHERE THIS SUBSTANCE IS PRODUCED, STORED OR HANDLED A
CONCENTRATION OF 0.7MG/M3 (0.2PPM) SHOULD NEVER BE EXCEEDED AT ANY
TIME.
entry date: DEC 1991 effective date: 28MAY1984
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
79
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OECD SIDS GLUTARALDEHYDE
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : RUS type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AQ | SURF | MAC |
| | | CLASS |
--------------------------------
0.07MG/L HAZARD CLASS: II
entry date: JUL 1990 effective date: 1JAN1989
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : SWE type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | HLV |
--------------------------------
CLV: 0.8MG/M3 (0.2PPM) (15MIN-TWA). SENSITIZING.
entry date: 1992 effective date: 01JUL1991
*******
systematic name:Pentanedial
common name :glutaraldehyde
80
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OECD SIDS GLUTARALDEHYDE
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : USA type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| FOOD | ADDIT | RSTR |
| TRANS | | RSTR |
| STORE | | RSTR |
| PACK | | RSTR |
--------------------------------
; Summary - THIS SUBSTANCE IS INCLUDED ON A LIST OF SUBSTANCES USED TO
PREPARE ADHESIVES WHICH MAY BE SAFELY USED AS COMPONENTS OF ARTICLES
INTENDED FOR USE IN PACKAGING, TRANSPORTATION, OR HOLDING FOOD IN
ACCORDANCE WITH THE FOLLOWING PRESCRIBED CONDITIONS: SUBSTA NCE MUST BE
SEPARATED FROM THE FOOD BY A FUNCTIONAL BARRIER, MUST NOT EXCEED LIMITS
OF GOOD MANUFACTURING PRACTICE USED WITH DRY FOODS, OR NOT EXCEED TRACE
AMOUNTS AT SEAMS AND EDGE EXPOSURES WHEN USED WITH FATTY AND AQUEOUS
FOODS. ALSO REGULATED BY SEA M INTEGRITY, LABELING STANDARDS, AND ANY
PROVISION UNDER 21 CFR 175
entry date: NOV 1991 effective date: 1977
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
81
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OECD SIDS GLUTARALDEHYDE
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : USA type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| CLASS | PESTI | RQR |
| MANUF | PESTI | PRMT |
| FOOD | ADDIT | RQR |
| AQ | GRND | RQR |
| SAFTY | OCC | RQR |
--------------------------------
CASE NAME GLUTARALDEHYDE; Summary - THIS SUBSTANCE IS INCLUDED ON A
LIST OF ACTIVE INGREDIENTS CONTAINED IN A PRODUCT FIRST REGISTERED
BEFORE NOVEMBER 1, 1984, FOR WHICH A REGISTRATION STANDARD HAS NOT
BEEN ISSUED. PUBLICATION OF THIS LIST INITIATES AN ACCELERATED
REREGISTRATION AND DATA C ALL-IN FOR PRODUCTS CONTAINING THE LISTED
ACTIVE INGREDIENTS. THE STATUTORY CRITERIA THAT EPA MUST INCLUDE IN
SETTING PRIORITIES FOR INCLUSION ON LIST B ARE THOSE ACTIVE
INGREDIENTS RELATING TO FOOD AND FEED USE, GROUNDWATER CONTAMINANTS,
POTENTIAL RESID UES IN SHELLFISH, AND THOSE ACTIVE INGREDIENTS WITH
SIGNIFICANT DATA GAPS AND THOSE OF CONCERN FOR WORKER EXPOSURE BECAUSE
OF AGRICULTURAL, GREENHOUSE, OR NURSERY EXPOSURE.
entry date: JAN 1992 effective date: 1988
*******
82
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OECD SIDS GLUTARALDEHYDE
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : USA type : REC
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| AIR | OCC | TLV |
--------------------------------
Ceiling Limit 0.2 ppm, 0.82 MG/M3; Summary - THIS THRESHOLD LIMIT
VALUE IS INTENDED FOR USE IN THE PRACTICE OF INDUSTRIAL HYGIENE AS A
GUIDELINE OR RECOMMENDATION IN THE CONTROL OF POTENTIAL HEALTH
HAZARDS.
entry date: DEC 1991 effective date: 1989
*******
systematic name:Pentanedial
common name :glutaraldehyde
reported name :GLUTARALDEHYDE
cas no :111-30-8 rtecs no :MA2450000
area : EEC type : REG
--------------------------------
|subject|specification|descriptor|
|-------+-------------+----------|
| GOODS | CSMET | PRMT |
| GOODS | CSMET | RQR |
| GOODS | CSMET | MXL |
--------------------------------
THE SUBSTANCE IS PRESERVATIVE WHICH COSMETIC PRODUCTS MAY CONTAIN
WITHIN THE LIMIT AND UNDER THE CONDITIONS LAID DOWN. MXL: 0.1%. THE
SUBSTANCE IS PROHIBITED IN AEROSOLS. WARNING WHICH MUST BE PRINTED ON
THE LABEL IS GIVEN. MEMBER STATES SHALL TAKE ALL MEASURES NECESSARY TO
ENSURE THAT THE COSMETIC PRODUCTS MAY BE MARKETED ONLY IF THEIR
PACKAGING, CONTAINERS OR LABELS BEAR THE INFORMATION LAID DOWN.
entry date: SEP 1995 effective date: 27MCH1978
83
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