MATERIAL SAFETY DATA SHEET

Revision date: 22-May-2012 Version: 1.2 Page 1 of 10

1. IDENTIFICATION OF THE SUBSTANCE/PREPARATION AND THE COMPANY/UNDERTAKING

Greenstone LLC Emergency telephone number:

100 Route 206 North CHEMTREC (24 hours): 1-800-424-9300
Peapack, NJ 07977
800-435-7095

Material Name: Bisoprolol Fumarate Tablets (Greenstone LLC)

Trade Name: Not applicable
Synonyms: None
Chemical Family: Not determined
Intended Use: Pharmaceutical product used as, antihypertensive

2. HAZARDS IDENTIFICATION

Appearance: Pink or White Tablet

Signal Word: WARNING

Statement of Hazard: Suspected of damaging the unborn child.

Additional Hazard Information:

Short Term: Active ingredient may be harmful if swallowed. Antihypertensive drug: has blood pressure-
lowering properties

Long Term: Animal studies have shown a potential to cause adverse effects on the fetus. May be harmful
to aquatic organisms. May have long-term toxic effects on the aquatic environment. (based on
components) .
Known Clinical Effects: The most frequent adverse effects seen during clinical use are headache, chest pain, and
dizziness. Due to intended use, dangerous lowering of blood pressure can occur.
EU Indication of danger: Toxic to Reproduction: Category 3

EU Hazard Symbols:

EU Risk Phrases:
R63 - Possible risk of harm to the unborn child.
Australian Hazard Classification Hazardous Substance. Non-Dangerous Goods.
(NOHSC):

Note: This document has been prepared in accordance with standards for workplace safety, which
require the inclusion of all known hazards of the active substance or its intermediates
regardless of the potential risk. The precautionary statements and warnings included may not
apply in all cases. Your needs may vary depending upon the potential for exposure in your
workplace.

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 2 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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3. COMPOSITION/INFORMATION ON INGREDIENTS

Hazardous
Ingredient CAS Number EU EINECS/ELINCS List EU Classification %
Bisoprolol fumarate 104344-23-2 Not Listed Xn;R22 5 or 10 mg***
Repr.Cat.3;R63
R52/53
Calcium phosphate dibasic, anhydrous 7757-93-9 231-826-1 Not Listed *
Colloidal silicon dioxide 7631-86-9 231-545-4 Not Listed *
418-260-2
Polyethylene glycol 25322-68-3 Not Listed Not Listed *
Microcrystalline cellulose 9004-34-6 232-674-9 Not Listed *
Titanium dioxide 13463-67-7 236-675-5 Not Listed *
Magnesium stearate 557-04-0 209-150-3 Not Listed *

Ingredient CAS Number EU EINECS/ELINCS List EU Classification %

Crospovidone 9003-39-8 Not Listed Not Listed *
Polysorbate 80 9005-65-6 Not Listed Not Listed *
Hydroxypropyl methylcellulose 9004-65-3 Not Listed Not Listed *

Additional Information: * Proprietary

*** per tablet/capsule/lozenge/suppository
Ingredient(s) indicated as hazardous have been assessed under standards for workplace
safety.

For the full text of the R phrases mentioned in this Section, see Section 16

4. FIRST AID MEASURES

Eye Contact: Flush with water while holding eyelids open for at least 15 minutes. Seek medical attention
immediately.

Skin Contact: Remove contaminated clothing. Flush area with large amounts of water. Use soap. Seek
medical attention.

Ingestion: Never give anything by mouth to an unconscious person. Wash out mouth with water. Do not
induce vomiting unless directed by medical personnel. Seek medical attention immediately.

Inhalation: Remove to fresh air and keep patient at rest. Seek medical attention immediately.

Symptoms and Effects of Exposure: For information on potential signs and symptoms of exposure, See Section 2 - Hazards
Identification and/or Section 11 - Toxicological Information.

5. FIRE FIGHTING MEASURES

Extinguishing Media: Use carbon dioxide, dry chemical, or water spray.

Hazardous Combustion Products: Carbon monoxide, carbon dioxide, and oxides of nitrogen may be generated in a fire.

Fire Fighting Procedures: During all fire fighting activities, wear appropriate protective equipment, including self-
contained breathing apparatus.

Fire / Explosion Hazards: Fine particles (such as dust and mists) may fuel fires/explosions.

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 3 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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6. ACCIDENTAL RELEASE MEASURES

Health and Safety Precautions: Personnel involved in clean-up should wear appropriate personal protective equipment (see
Section 8). Minimize exposure.

Measures for Cleaning / Collecting: Contain the source of spill if it is safe to do so. Collect spilled material by a method that
controls dust generation. A damp cloth or a filtered vacuum should be used to clean spills of
dry solids. Clean spill area thoroughly.

Measures for Environmental Place waste in an appropriately labeled, sealed container for disposal. Care should be taken to
Protections: avoid environmental release.

Additional Consideration for Large Non-essential personnel should be evacuated from affected area. Report emergency
Spills: situations immediately. Clean up operations should only be undertaken by trained personnel.

7. HANDLING AND STORAGE

General Handling: Minimize dust generation and accumulation. If tablets or capsules are crushed and/or broken,
avoid breathing dust and avoid contact with eyes, skin, and clothing. When handling, use
appropriate personal protective equipment (see Section 8). Wash hands and any exposed skin
after removal of PPE. Review and implement appropriate technical and procedural waste water
and waste disposal measures to prevent occupational exposure or environmental releases.
Potential points of process emissions of this material to the atmosphere should be controlled
with dust collectors, HEPA filtration systems or other equivalent controls. Releases to the
environment should be avoided.
Storage Conditions: Store as directed by product packaging.

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 4 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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8. EXPOSURE CONTROLS / PERSONAL PROTECTION

Refer to available public information for specific member state Occupational Exposure Limits.

Bisoprolol fumarate
Manufacturer OEL: 25ug/m3

Calcium phosphate dibasic, anhydrous

Latvia OEL - TWA 10 mg/m3

Colloidal silicon dioxide

Australia TWA 2 mg/m3
Austria OEL - MAKs 4 mg/m3
Czech Republic OEL - TWA 0.1 mg/m3
4.0 mg/m3
Estonia OEL - TWA 2 mg/m3
Germany - TRGS 900 - TWAs 4 mg/m3
Germany (DFG) - MAK 4 mg/m3 inhalable fraction
Ireland OEL - TWAs 6 mg/m3
2.4 mg/m3
Latvia OEL - TWA 1 mg/m3
OSHA - Final PELs - Table Z-3 Mineral D: 20 mppcf
Listed
Slovakia OEL - TWA 4.0 mg/m3
Slovenia OEL - TWA 4 mg/m3

Polyethylene glycol
Austria OEL - MAKs 1000 mg/m3
Germany - TRGS 900 - TWAs 1000 mg/m3
Germany (DFG) - MAK 1000 mg/m3 inhalable fraction
Slovakia OEL - TWA 1000 mg/m3
Slovenia OEL - TWA 1000 mg/m3

Microcrystalline cellulose
ACGIH Threshold Limit Value (TWA) 10 mg/m3
Australia TWA 10 mg/m3
Belgium OEL - TWA 10 mg/m3
Estonia OEL - TWA 10 mg/m3
France OEL - TWA 10 mg/m3
Ireland OEL - TWAs 10 mg/m3
4 mg/m3
Latvia OEL - TWA 2 mg/m3
OSHA - Final PELS - TWAs: 15 mg/m3
Portugal OEL - TWA 10 mg/m3
Romania OEL - TWA 10 mg/m3
Spain OEL - TWA 10 mg/m3

Titanium dioxide
ACGIH Threshold Limit Value (TWA) 10 mg/m3
Australia TWA 10 mg/m3
Austria OEL - MAKs 5 mg/m3
Belgium OEL - TWA 10 mg/m3
Bulgaria OEL - TWA 10.0 mg/m3

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Revision date: 22-May-2012 Version: 1.2
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Denmark OEL - TWA 6 mg/m3

Estonia OEL - TWA 5 mg/m3
France OEL - TWA 10 mg/m3
Greece OEL - TWA 10 mg/m3
5 mg/m3
Ireland OEL - TWAs 10 mg/m3
4 mg/m3
Latvia OEL - TWA 10 mg/m3
Lithuania OEL - TWA 5 mg/m3
OSHA - Final PELS - TWAs: 15 mg/m3
Poland OEL - TWA 10.0 mg/m3
Portugal OEL - TWA 10 mg/m3
Romania OEL - TWA 10 mg/m3
Spain OEL - TWA 10 mg/m3
Sweden OEL - TWAs 5 mg/m3

Magnesium stearate
ACGIH Threshold Limit Value (TWA) 10 mg/m3
Lithuania OEL - TWA 5 mg/m3
Sweden OEL - TWAs 5 mg/m3

Engineering Controls: Engineering controls should be used as the primary means to control exposures. General
room ventilation is adequate unless the process generates dust, mist or fumes. Keep airborne
contamination levels below the exposure limits listed above in this section.

Personal Protective Equipment: Refer to applicable national standards and regulations in the selection and use of personal
protective equipment (PPE).
Hands: Impervious gloves are recommended if skin contact with drug product is possible and for bulk
processing operations.
Eyes: Wear safety glasses or goggles if eye contact is possible.
Skin: Impervious protective clothing is recommended if skin contact with drug product is possible and
for bulk processing operations.
Respiratory protection: If the applicable Occupational Exposure Limit (OEL) is exceeded, wear an appropriate
respirator with a protection factor sufficient to control exposures to below the OEL.

9. PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Tablet Color: Pink or White

Molecular Formula: Mixture Molecular Weight: Mixture

10. STABILITY AND REACTIVITY

Chemical Stability: Stable under normal conditions of use.

Conditions to Avoid: Fine particles (such as dust and mists) may fuel fires/explosions.
Incompatible Materials: As a precautionary measure, keep away from strong oxidizers

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 6 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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11. TOXICOLOGICAL INFORMATION

General Information: The information included in this section describes the potential hazards of the individual
ingredients.

Acute Toxicity: (Species, Route, End Point, Dose)

Microcrystalline cellulose
Rat Oral LD50 > 5000 mg/kg
Rabbit Dermal LD50 > 2000 mg/kg

Magnesium stearate
Rat Oral LD50 > 2000 mg/kg
Rat Inhalation LC50 > 2000 mg/m3

Hydroxypropyl methylcellulose
Rat Oral LD50 > 10,000 mg/kg

Titanium dioxide
Rat Oral LD50 > 7500 mg/kg
Rat Subcutaneous LD 50 50 mg/kg

Polysorbate 80
Rat Intravenous LD 50 1790 mg/kg
Mouse Oral LD 50 25 g/kg

Bisoprolol fumarate
Rat Oral LD50 940 mg/kg
Acute Toxicity Comments: A greater than symbol (>) indicates that the toxicity endpoint being tested was not achievable
at the highest dose used in the test.

Irritation / Sensitization: (Study Type, Species, Severity)

Microcrystalline cellulose
Skin Irritation Rabbit Non-irritating
Eye Irritation Rabbit Non-irritating

Polyethylene glycol
Eye Irritation Rabbit Mild
Skin Irritation Rabbit Mild

Repeated Dose Toxicity: (Duration, Species, Route, Dose, End Point, Target Organ)

Bisoprolol fumarate
4 Week(s) Rat Intravenous 5 mg/kg/day NOAEL None identified
4 Week(s) Dog Intravenous 10 mg/kg/day NOAEL None identified
6 Month(s) Rat Oral 150 mg/kg/day NOAEL None identified
12 Month(s) Rat Oral 75 mg/kg/day NOAEL None identified

Reproduction & Developmental Toxicity: (Study Type, Species, Route, Dose, End Point, Effect(s))

Bisoprolol fumarate
Reproductive & Fertility Rat Oral 150 mg/kg/day NOAEL Negative

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 7 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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11. TOXICOLOGICAL INFORMATION

Embryo / Fetal Development Rat No route specified 40 mg/kg/day NOAEL Not Teratogenic, Maternal Toxicity,
Fetotoxicity
Embryo / Fetal Development Rabbit No route specified 6.25 mg/kg/day NOAEL Not Teratogenic, Fetotoxicity, Maternal
Toxicity

Genetic Toxicity: (Study Type, Cell Type/Organism, Result)

Bisoprolol fumarate
In Vitro Bacterial Mutagenicity (Ames) Not specified Negative
In Vitro Chromosome Aberration Hamster Negative
In Vitro Unscheduled DNA Synthesis Not specified Negative
In Vivo Micronucleus Mouse Negative
In Vitro Cytogenetics Rat Negative

Carcinogenicity: (Duration, Species, Route, Dose, End Point, Effect(s))

Bisoprolol fumarate
26 Month(s) Rat Oral, in feed 125 mg/kg/day NOAEL Not carcinogenic
24 Month(s) Mouse Oral, in feed 240 mg/kg/day NOAEL Not carcinogenic

Carcinogen Status: None of the components of this formulation are listed as a carcinogen by IARC, NTP or OSHA.

Crospovidone
IARC: Group 3 (Not Classifiable)

Titanium dioxide
IARC: Group 2B (Possibly Carcinogenic to Humans)
OSHA: Listed

Colloidal silicon dioxide

IARC: Group 3 (Not Classifiable)

12. ECOLOGICAL INFORMATION

Environmental Overview: Environmental properties have not been thoroughly investigated. Releases to the environment
should be avoided.
Mobility, Persistence and Not readily biodegradable ( 4 % after 28 days). (bisoprolol fumarate)
Degradability:
Aquatic Toxicity: (Species, Method, End Point, Duration, Result)

Bisoprolol fumarate
Daphnia magna (Water Flea) EC50 48 Hours 90 mg/L
Fish LC50 96 Hours > 100 mg/L

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 8 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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13. DISPOSAL CONSIDERATIONS

Waste Treatment Methods: Dispose of waste in accordance with all applicable laws and regulations. Member State
specific and Community specific provisions must be considered. Considering the relevant
known environmental and human health hazards of the material, review and implement
appropriate technical and procedural waste water and waste disposal measures to prevent
occupational exposure and environmental release. It is recommended that waste minimization
be practiced. The best available technology should be utilized to prevent environmental
releases. This may include destructive techniques for waste and wastewater.

14. TRANSPORT INFORMATION

The following refers to all modes of transportation unless specified below.

Not regulated for transport under USDOT, EUADR, IATA, or IMDG regulations.

15. REGULATORY INFORMATION

EU Symbol: Xn
EU Indication of danger: Toxic to Reproduction: Category 3

EU Risk Phrases:
R63 - Possible risk of harm to the unborn child.

EU Safety Phrases:
S22 - Do not breathe dust.
S36/37 - Wear suitable protective clothing and gloves.
S53 - Avoid exposure - obtain special instructions before use.

OSHA Label:
WARNING
Suspected of damaging the unborn child.

Canada - WHMIS: Classifications

WHMIS hazard class:
Class D, Division 2, Subdivision A

Calcium phosphate dibasic, anhydrous

Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 9 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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15. REGULATORY INFORMATION

EU EINECS/ELINCS List 231-826-1

Crospovidone
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present

Polysorbate 80
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present

Colloidal silicon dioxide

Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 231-545-4
418-260-2

Polyethylene glycol
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present

Microcrystalline cellulose
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 232-674-9

Hydroxypropyl methylcellulose
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
Standard for the Uniform Scheduling Schedule 4
for Drugs and Poisons:

Titanium dioxide
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 236-675-5

Magnesium stearate
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 209-150-3

16. OTHER INFORMATION

Text of R phrases mentioned in Section 3

R63 - Possible risk of harm to the unborn child.

R22 - Harmful if swallowed.
R52/53 - Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

Data Sources: Publicly available toxicity information.

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Material Name: Bisoprolol Fumarate Tablets (Greenstone Page 10 of 10

LLC)
Revision date: 22-May-2012 Version: 1.2
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Reasons for Revision: Updated Section 1 - Identification of the Substance/Preparation and the Company/Undertaking.
Updated Section 9 - Physical and Chemical Properties. Updated Section 2 - Hazard
Identification.

Prepared by: Product Stewardship Hazard Communication

Global Environment, Health, and Safety Operations

It is believed that the information contained in this Material Safety Data Sheet is accurate, and while it is provided in good faith, it is
without a warranty of any kind, expressed or implied. If data for a hazard are not included in this document there is no known
information at this time

End of Safety Data Sheet

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