Material Safety Data Sheet

1. PRODUCT IDENTIFICATION
Product Name Product Use Manufacturer Address Alprostadil Injection, USP Maintain patency of ductus arteriosus in neonates Teva Parenteral Medicines, Inc. 11 Hughes Irvine, CA 92618-1902 1-800-424-9300 (United States) 1-202-483-7617 (International Collect) 1-800-729-9991 http://www.newsicor.com PGE-1, Prostandin, Prostaglandin E1 (11-, 13E, 15S) 11, 15-Dihydroxy-9-oxoprost-13-en-1-oic Acid C20H34O5 Agent used for vasodilation and muscle stimulation 1 mL vial containing 1 mL of Alprostadil November 29, 2005

Alprostadil Injection, USP

Chemtrec Emergency No. Business Phone Website Address Common Names Chemical Name Chemical Formula Chemical Family How Supplied Date of Preparation:

2. COMPOSITION AND INGREDIENTS

CHEMICAL NAME CAS# Wt% Alprostadil Ethanol 745-65-3 64-17-5 0.05 Balance ACGIH TLV NE 1000 ppm STEL NE NE NE 1000 ppm EXPOSURE LIMITS IN AIR OSHA PEL STEL NE NE 0.5 g/m3 TWA* NE Other

NE - Not Established C - Ceiling Limit

* Innovators Exposure Limit

NOTE: All WHMIS required information is included. It is located in appropriate sections based on the ANSI Z400.1 format CHEMTREC NUMBER: Use only in the event of a chemical emergency involving a spill, leak, fire, exposure or accident involving this drug.

3. HAZARD IDENTIFICATION EMERGENCY OVERVIEW: Material is a clear, colorless liquid. Flammable liquid and vapor. Vapor can cause flash fire. Eye irritant. Harmful to the fetus. Avoid contact with eyes, skin and clothing. Avoid exposure during pregnancy and while breastfeeding. Do not taste or swallow. Wash thoroughly after handling. Keep away from heat, sparks, flames, or other sources of ignition (e.g., static electricity, pilot lights, mechanical/electrical equipment).

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3. HAZARD IDENTIFICATION cont

Symptoms of Overexposure by Route of Exposure: This material is intended for injection under the supervision of physicians. Inhalation: Inhalation of significant amounts of the product is not anticipated to occur because of the small size of individual containers.

Alprostadil Injection, USP

Contact with Skin or Eyes: Contact may cause irritation. Effects may include stinging, watering, redness and swelling of the eyes and redness, itching, and a burning sensation on the skin. Ingestion: Ingestion is not an anticipated route of occupational exposure. However, it is considered slightly toxic based on animal data. Symptoms similar to those identified under injection may occur. Injection: Local redness and pain are the primary symptoms of accidental injection in an occupational setting. Medical personnel are not anticipated to experience over-exposures to the therapeutic doses of this product. However, effects including vomiting, flushing, central nervous system effects (e.g., headache, drowsiness, dizziness disorientation and fatigue), increased or decreased heart rate and increased pulse rate may occur. See package insert for other adverse reactions associated with therapeutic doses of this product. Health Effects or Risks From Exposure (An explanation in lay terms): Acute: The primary health effects anticipated in an occupational setting include irritation of eyes and skin as well as redness and local swelling after accidental injection. In case of over-exposure by injection, effects such as vomiting, flushing, central nervous system effects (e.g., headache, drowsiness, dizziness disorientation and fatigue), breathing difficulties, increased or decreased heart rate and increased pulse rate may occur. Cancer: No long-term carcinogenicity studies were identified. information for the non-active ingredient. See Section 11 for carcinogenicity

Chronic: Potential hazard to the fetus and reproductive toxicant (see Section 11). Other Comments: Most adverse health effects associated with ethanol, a component of this material, are related to the chronic ingestion of alcoholic beverages. Alcoholism has been associated with liver, stomach, heart and nervous system damage, cancer, adverse reproductive effects and effects on the developing fetus. Many of these effects may be related to metabolic changes that result from constantly high blood levels of alcohol. This exposure pattern is significantly different from that of persons handling ethanol in the workplace or a medical setting. Pre-Existing Medical Conditions: Conditions aggravated by exposure may include skin and respiratory (asthma-like) disorders.

4. FIRST-AID MEASURES
Skin Exposure: Remove contaminated shoes and clothing and cleanse affected area(s) thoroughly by washing with mild soap and water. If irritation or redness develops and persists, seek medical attention. Eye Exposure: Move victim away from exposure and into fresh air. If irritation or redness develops, flush eyes with clean water and seek medical attention. For direct contact, hold eyelids apart and flush the affected eye(s) with clean water for at least 15 minutes. Seek medical attention.

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4. FIRST-AID MEASURES cont

Inhalation: If respiratory symptoms develop, move victim away from source of exposure and into fresh air. If symptoms persist, seek medical attention. If victim is not breathing, clear airway and immediately begin artificial respiration. If breathing difficulties develop, oxygen should be administered by qualified personnel. Seek immediate medical attention. Ingestion: If swallowed, seek emergency medical attention. If victim is drowsy or unconscious and vomiting, place on the left side with the head down and DO NOT give anything by mouth. If not vomiting and professional advice is not available, DO NOT induce vomiting. If possible, do not leave victim unattended and observe closely for adequacy of breathing. Victims of chemical exposure must be taken for medical attention. Take a copy of the MSDS to the physician or health professional with victim. Physicians should refer to Section 11 (Toxicological Information) as well as the Physicians Desk Reference for additional treatment information.

Alprostadil Injection, USP

5. FIRE-FIGHTING MEASURES (The following is for Ethanol, the main component)

Flash Point: 13C/55F Autoignition Temperature: 363C/685F Flammable Limits (in air by volume, %): Lower: 3.3% Upper: 19% Fire Extinguishing Equipment: Water may be ineffective for extinguishment, unless used under favorable conditions by experienced fire fighters. Carbon dioxide can displace oxygen. Use caution when applying carbon dioxide in confined spaces Water Spray: OK (for Cooling) Foam: OK Carbon Dioxide: OK Dry Chemical: OK Halon: OK Other: Any "ABC" Class

Unusual Fire and Explosion Hazards: This material is extremely flammable and can be ignited by heat, sparks, flames, or other sources of ignition (e.g., static electricity, pilot lights, or mechanical/electrical equipment). Vapors may travel considerable distances to a source of ignition where they can ignite, flashback, or explode. May create vapor/air explosion hazard indoors, outdoors, or in sewers. Vapors are heavier than air and can accumulate in low areas. If container is not properly cooled, it can rupture in the heat of a fire. Explosion Sensitivity to Mechanical Impact: Not sensitive. Explosion Sensitivity to Static Discharge: Not sensitive. Special Fire Fighting Procedures: For fires beyond the incipient stage, emergency responders in the immediate hazard area should wear bunker gear. When the potential chemical hazard is unknown, in enclosed or confined spaces, or when explicitly required by DOT, a self-contained breathing apparatus should be worn. In addition, wear other appropriate protective equipment as conditions warrant (see Section 8). Isolate immediate hazard area and keep unauthorized personnel out. Contain spill if it can be done with minimal risk. Move undamaged containers from immediate hazard area if it can be done with minimal risk. Cool equipment exposed to fire with water, if it can be done with minimal risk. Water spray may be useful in minimizing or dispersing vapors. Avoid spreading burning liquid with water used for cooling purposes. NFPA HAZARD CLASS: Health: Flammability: Reactivity: 1 (Slight) 3 (Severe) 0 (Least)

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6. ACCIDENTAL RELEASE MEASURES

Spill and Leak Response: For small releases of this product, wear latex or nitrile gloves and safety glasses. For large or uncontrolled releases, stay away from spill. Extremely flammable. Keep all sources of ignition and hot metal surfaces away from spill/release. The use of explosion-proof equipment is recommended. Stay upwind and away from spill/release. Isolate immediate hazard area and keep unauthorized personnel out. Contain spill if it can be done with minimal risk. Wear appropriate protective equipment including respiratory protection as conditions warrant (see Section 8). Prevent spilled material from entering sewers, storm drains, other unauthorized treatment drainage systems, and natural waterways. Immediate cleanup of any spill is recommended. Spilled material may be absorbed into an appropriate absorbent material. Notify fire authorities and appropriate federal, state, and local agencies.

Alprostadil Injection, USP

7. HANDLING and STORAGE

Work and Hygiene Practices: As with all chemicals, avoid getting this product ON YOU or IN YOU. Do not eat, drink, smoke or apply cosmetics while handling the product. Wash hands thoroughly after handling. Particular care in working with this product must be practiced in pharmacies and other preparation areas, during manufacture of this product, and during patient administration. Precautions should be taken during the following activities: Withdrawal of needles from drug vials. Drug transfers using syringes and needles or filter straws. Expulsion of air from drug-filled syringes.

Storage and Handling Practices: Employees must be trained to properly use the product. Ensure vials are properly labeled. Store only in approved containers. Use and store this material in cool, dry, wellventilated areas away from heat, direct sunlight, hot metal surfaces, and all sources of ignition. Post area No Smoking or Open Flame. Keep away from any incompatible materials or conditions (see Section 10). Store at temperatures between 2-8C (36-46F). . Protective Practices During Maintenance of Contaminated Equipment: When cleaning non-disposable equipment, wear latex or nitrile gloves (double gloving is recommended), goggles, and lab coat. Wash equipment with soap and water. All needles, syringes, vials and other disposable items contaminated with this product should be disposed of properly.

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8. EXPOSURE CONTROLS - PERSONAL PROTECTION

Ventilation and Engineering Controls: Use with adequate ventilation. Follow standard medical product handling procedures. Respiratory Protection: Not normally required for routine, medical administration of this product. A NIOSH certified air-purifying respirator with an organic vapor cartridge may be used under conditions where airborne concentrations are expected to be excessive. Protection provided by air purifying respirators is limited (see manufacturers respirator selection guide). Use a positive pressure air supplied respirator if there is potential for uncontrolled release, exposure levels are not known, or any other circumstances where air-purifying respirators may not provide adequate protection. A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements must be followed whenever workplace conditions warrant a respirator's use. Eye Protection: Approved eye protection to safeguard against potential eye contact, irritation or injury is recommended. Depending on conditions of use, a face shield may be necessary. Hand Protection: Use latex, nitrile, or rubber gloves. Check gloves for leaks. Wash hands before and after using gloves. Body Protection: No special body protection required for routine, medical administration of this product. Wear lab coat, gown, or smock, as appropriate for procedure. Product Preparation Instructions for Medical Personnel: Follow standard procedure for handling pharmaceutical materials and recommendations presented on the Package Insert.

Alprostadil Injection, USP

9. PHYSICAL and CHEMICAL PROPERTIES (The following is for Ethanol, the main component)
Relative Vapor Density (air = 1): Specific Gravity (water = 1): Solubility in Water: Vapor Pressure, mm Hg @ 20C. Odor Threshold: Alcohol-like . Appearance and Color: Clear, colorless liquid
ND = No Data

1.6 0.789 Soluble 43

Evaporation Rate (n-BuAc=1): Melting/Freezing Point: Boiling Point: pH:

2.4 -114C (-173F) 78C (172F) No data

10. STABILITY and REACTIVITY

Stability: Stable under normal conditions of storage and handling. Materials With Which Substance is Incompatible: This product is generally compatible with other common materials in a medical facility. Keep away from strong oxidizing agents, strong acids, peroxides, acid chlorides, alkali metals and ammonia. Hazardous Polymerization: Will not occur. Hazardous Combustion Products: Heat may cause product to decompose, destroying the product or producing toxic fumes.

Material Safety Data Sheet

11. TOXICOLOGICAL INFORMATION

Toxicity Data: The following information is for Alprostadil, the active ingredient Oral LD50(rat) = 228 mg/kg Oral LD50 (mouse) = 186 mg/kg IV LD50(rat) = 19200 ug/kg IV LD50(mouse) = 21 mg/kg Subcutaneous LD50(rat) = 18600 ug/kg Subcutaneous LD50(mouse) = 26400 ug/kg IP LD50(rat) = 24900 ug/kg IP LD50 (mouse) = 19800 ug/kg

Alprostadil Injection, USP

Suspected Cancer Agent: No long-term animal studies were identified. It is not listed as carcinogenic by NTP, IARC or OSHA. However, ingestion of alcoholic beverages has been classified by IARC as carcinogenic to humans (Group1). Occupational or medical exposure to ethanol and exposures other than by ingestion (i.e., dermal and inhalation) have not been associated with cancer in humans. Irritancy of Product: This product is expected to be irritating to eyes. Sensitization to the Product: No data to indicate it is a sensitizer. Reproductive Toxicity Information: Listed below is information concerning the effects of Alprostadil on human and animal reproductive systems. This material is not intended for use in pediatric patients or women. Mutagenicity: Not genotoxic in a battery of short-term screening tests. . Embryotoxicity/Teratogenicity/Reproductive Toxicity: Did not increase malformations in rats when given continuously by intravenous infusion up to 28 times the recommended human dose or by a single subcutaneous injection up to 7 times the recommended human dose. Alprostadil caused malformations in rats when given by a single subcutaneous injection at 14 times the recommended human dose. Likely to be an abortifacient in animals and humans. Analogues of alprostadil such as misoprostol and dinoprost have been used to induce abortions in women. Did not impair spermatogenesis in rats administered up to 0.2 mg/kg/day (up to 200-fold higher than the recommended human dose). ACGIH Biological Exposure Indices: Currently there are no Biological Exposure Indices (BEIs) associated with the components of this product.

12. ECOLOGICAL INFORMATION

All work practices must be aimed at eliminating environmental contamination. Environmental Stability: This product will be relatively stable under ambient environmental conditions. Effect of Materials on Plants or Animals: No specific information is available on the effect on plants or animals in the environment. Effect of Chemicals on Aquatic Life: No specific information is available on the effect on plants or animals in the aquatic environment.

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13. DISPOSAL CONSIDERATIONS

Preparing Wastes for Disposal: This material, if discarded as produced, would be a RCRA "characteristic" hazardous waste due to the characteristic(s) of ignitability (D001) Use resulting in chemical or physical change or contamination may subject it to further regulation as a hazardous waste. Along with properly characterizing all waste materials consult state and local regulations regarding the proper disposal of this material. U.S. EPA Waste Number: D001 (Characteristic/Ignitability)

Alprostadil Injection, USP

14. TRANSPORTATION INFORMATION

This Material is Hazardous as Defined by 49 CFR 172.101 by the U. S. Department of Transportation. The following is a list of options for shipping this drug: Proper Shipping Name: Ethanol solutions, Hazard Class Number and Description: 3 UN Identification Number: UN1170 Packing Group: II DOT Label(s) Required: Flammable liquid North American Emergency Response Guidebook Number (1996) 128 MARINE POLLUTANT: No component of this product is listed as a Marine Pollutant (49 CFR 172.101, Appendix B) Proper Shipping Name: Consumer commodity ORM-D Hazard Class Number and Description: None UN Identification Number: None Packaging Group: None DOT label(s) Required: None DOT Exemption 9275 Teva Sicor is party to this exemption which permits shipment of certain limited quantities of ethanol containing materials. The exemption authorizes a person who is not a holder of this exemption to reoffer it for transportation provided no modifications or changes are made to the package and it is reoffered for transportation in conformance with this exemption and the Hazardous Materials Regulations. A copy of Teva Sicors exemption must be maintained at each facility where this drug is offered or reoffered for transportation. Transport Canada Transportation of Dangerous Goods Regulations: This material is considered as dangerous goods. See above.

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15. REGULATORY INFORMATION

U.S. REGULATIONS: U.S. SARA Reporting Requirements: The components of this product are not subject to the reporting requirements of Sections 302, 304 and 313 of Title II of the Superfund Amendments and Reauthorization Act.

Alprostadil Injection, USP

U.S. SARA Threshold Planning Quantity: Not applicable U.S. TSCA Inventory Status: Alprostadil, a drug as defined by the Federal Food, Drug and Cosmetic Act and is therefore not a chemical substance under TSCA. California Safe Drinking Water and Toxic Enforcement Act (Proposition 65): This product does not contain chemicals known to the State of California to cause cancer or reproductive effects. However, ethyl alcohol (in alcoholic beverages) is on the list as known to the State of California to cause birth defects and other reproductive harm. Other U.S. Federal Regulations: Based on this products use, the requirements of the OSHA Bloodborne pathogen Standard (29 CFR 1910.1030) are applicable. CANADIAN REGULATIONS: Canadian DSL/NDSL Status: Alprostadil is regulated by the Food and Drug Administration of Health Canada and is therefore exempt from the requirements of CEPA. ANSI Labeling (Based on 129.1, Provided to Summarize Occupational Exposure Hazards): Flammable liquid and vapor. Vapor can cause flash fire. Eye irritant. Harmful to the fetus. Avoid contact with eyes, skin and clothing. Avoid exposure during pregnancy and while breastfeeding. Wash thoroughly after handling. Keep away from heat, sparks, flames, or other sources of ignition (e.g., static electricity, pilot lights, mechanical/electrical equipment). Avoid accidental injection. Do not eat, drink or smoke when handling. Clean up spills promptly.

16. OTHER INFORMATION

Issue Date: 11/29/05 Previous Issue Date: 11/18/02 The information in this document is believed to be correct as of the date issued. HOWEVER, NO WARRANTY OF MERCHANTABILITY, FITNESS FOR ANY PARTICULAR PURPOSE, OR ANY OTHER WARRANTY IS EXPRESSED OR IS TO BE IMPLIED REGARDING THE ACCURACY OR COMPLETENESS OF THIS INFORMATION, THE RESULTS TO BE OBTAINED FROM THE USE OF THIS INFORMATION OR THE PRODUCT, THE SAFETY OF THIS PRODUCT, OR THE HAZARDS RELATED TO ITS USE. This information and product are furnished on the condition that the person receiving them shall make his own determination as to the suitability of the product for his particular purpose and on the condition that he assume the risk of his use thereof.