Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012

SECTION 1. PRODUCT AND COMPANY IDENTIFICATION

Product name Substance Number Common Name Chemical Name : : : : ALIMTA 000004273779 Pemetrexed Disodium Heptahydrate for Injection L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5yl)ethyl]benzoyl]-, disodium salt, heptahydrate

Company

Telephone Emergency telephone number

: :

Eli Lilly and Company Lilly Corporate Center Indianapolis, IN 46285 317-276-2000 CHEMTREC: 1-800-424-9300

(Outside U.S. 1-703-527-3887)

Item Code

VL7623, VL7640

SECTION 2. HAZARDS IDENTIFICATION

Emergency Overview
Lilly Lab Labeling Code Health: 2 Fire: 1 Reactivity: 0 Special: Reproductive Hazard Primary Hazards: Mutagen, Irritant (eyes, skin), Blood, Bone Marrow, Reproductive Hazard Summary (Caution): May cause heritable genetic damage. May cause eye and skin irritation. May cause blood effects. May cause bone marrow effects. This product may cause adverse reproductive effects. Emergency Overview Form Colour Odour Special: R

: : :

lyophilized white odourless

Potential Health Effects Eyes Skin

: :

May irritate eyes. May irritate skin. Skin rash has been reported in patients not pretreated with a 1/9

Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 cortiosteroid (dexamethasone). Aggravated Medical Condition Primary Routes of Entry Additional Information : : : None known. Inhalation Skin Absorption Decreased fetal weight and viability have been reported in animal studies with pemetrexed disodium. The active ingredient, pemetrexed, is a folic acid antimetabolite, this class of compounds is known to cause developmental effects. Effects of overexposure to pemetrexed disodium may include bone marrow suppression resulting in decreased blood cell counts, inflammation of mucous membranes, skin rash, fatigue, fetal effects, and reproductive tissue changes. Patients are instructed to take folic acid and vitamin B12 to reduce treatment-related toxicity. Print Date 03/23/2012

Carcinogenicity NTP No component of this product present at levels greater than or equal to 0.1% is identified as a known or anticipated carcinogen by NTP. IARC No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. OSHA No component of this product present at levels greater than or equal to 0.1% is identified as a carcinogen or potential carcinogen by OSHA.

SECTION 3. COMPOSITION/INFORMATION ON INGREDIENTS

Chemical Name Pemetrexed Disodium Heptahydrate Mannitol CAS-No. 357166-29-1 69-65-8 Concentration [%] 50 50

SECTION 4. FIRST AID MEASURES

Inhalation : Remove to fresh air. If breathing is irregular or stopped, administer artificial respiration. Call a physician immediately. Wash off immediately with plenty of water for at least 15 minutes. Take off all contaminated clothing immediately. Get medical attention if irritation develops and persists. Wash contaminated clothing before re-use. In case of eye contact, remove contact lens and rinse immediately with plenty of water, also under the eyelids, for at least 15 minutes. Obtain medical attention. If conscious, give the victim plenty of water to drink. Never give anything by mouth to an unconscious person. Call a physician immediately.

Skin contact

Eye contact

Ingestion

Notes to physician Treatment

Pemetrexed disodium - If overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician. Management of pemetrexed overdose should include consideration of the use of leucovorin or thymidine rescue. 2/9

Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012 Patients are instructed to take folic acid and vitamin B12 to reduce treatment-related toxicity.

SECTION 5. FIRE-FIGHTING MEASURES

Flash point Lower explosion limit : No data available : No data available : : Upper explosion limit : No data available

Suitable extinguishing media Unusual Fire and Explosion Hazard. Special protective equipment for fire-fighters

Water Carbon dioxide (CO2) Dry chemical Dust may form explosive mixture in air. Hazardous decomposition products formed under fire conditions. Wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.

SECTION 6. ACCIDENTAL RELEASE MEASURES

Methods for cleaning up

Use double pairs of latex disposable gloves which must be disposed of within an hour, goggles, impermeable body covering, and approved HEPA-filtered or supplied-air respirator. If material spills occur in production area, use either wet clean-up methods, ensuring that no airborne dusts or aerosols are formed, or appropriate vacuum cleaners having high efficiency particulate air (HEPA) filters. It is recommended that areas handling final finished product have cytotoxic spill kits available. Spill kits should include impermeable body covering, shoe covers, latex and utility latex gloves, goggles, approved HEPA respirator, disposable dust pan and scoop, absorbent towels, spill control pillows, disposable sponges, sharps container, disposable garbage bag, and a hazardous waste label.

SECTION 7. HANDLING AND STORAGE

Storage Requirements for storage areas and containers : Store at 20 to 25 C (68 to 77 F). Excursions permitted from 15 to 30 C (59 to 86 F). [see USP]. Premetrexed is not light sensitive.

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Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012

SECTION 8. EXPOSURE CONTROLS/PERSONAL PROTECTION

Exposure guidelines Components Pemetrexed Disodium Heptahydrate Mannitol Exposure Limit Values LEG: 8 or 12 hour TWA 0.3 g/m3 LEG: 30 min Excursion Limit 3.6 g/m3 EG: TWA 10 mg/m3

For appropriate handling precautions in specific laboratory, manufacturing, or clinical health care operations, consult with a health and safety or technical services representative. In clinical health care settings, follow OSHA Technical Manual, Section VI, Chapter 2 - Controlling Occupational Exposure to Hazardous Drugs. This chapter covers protection of employees during cytotoxic drug preparation, administration, disposal, and the handling of human waste products potentially contaminated with cytotoxic drug substances. GENERAL: For all work environments, wear eye protection and ELIMINATE hand-to-eye contact. Avoid skin contact, wear gloves, and take other appropriate precautions. Engineering measures Extensive local exhaust, ventilated enclosure (HEPA-filtered balance enclosure, fume hood, or Class II or III vertical flow biosafety cabinet), or enclosed process equipment. Personal protective equipment Respiratory protection : When the exposure guidelines may be exceeded, use an approved HEPA-filtered or supplied-air respirator. Goggles Face-shield Chemical-resistant gloves and impermeable body covering to minimize skin contact. If handled in a ventilated enclosure, as in a laboratory setting, respirator and goggles or face shield may not be required. Safety glasses are always required. In production settings, airline-supplied, hood-type respirators are preferred. Shower and change clothing if skin contact occurs.

Eye protection Skin and body protection

: :

Hygiene measures

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Appearance Form Physical state Safety data 4/9 : lyophilized : solid Colour Odour : white : odourless

Material Safety Data Sheet

ALIMTA
Version 1.4 Flash point Lower explosion limit Upper explosion limit : No data available : No data available : No data available Revision Date 02/11/2011 Water solubility Water solubility log Pow Print Date 03/23/2012 : 101.5 g/l(pH 7), (as free acid) : 89.4 g/l(pH 9), (as free acid) : <1

SECTION 10. STABILITY AND REACTIVITY

Materials to avoid Hazardous decomposition products Thermal decomposition : : Incompatible with oxidizing agents. Hazardous decomposition products formed under fire conditions.

Stable under normal conditions.

Hazardous reactions

Hazardous polymerisation does not occur.

SECTION 11. TOXICOLOGICAL INFORMATION

Acute oral toxicity Pemetrexed Disodium Heptahydrate: Acute inhalation toxicity Pemetrexed Disodium Heptahydrate: Acute dermal toxicity Pemetrexed Disodium Heptahydrate: LD50 (rat) > 500 mg/kg (as free base)

No data available

LD50 (rabbit) > 1,000 mg/kg

Acute toxicity (other routes of administration) Intravenous - LD50 (male rat) 1,332 mg/kg Pemetrexed Disodium Convulsions. Heptahydrate: Intravenous - LD50 (female rat) > 1,574 mg/kg Convulsions. Mortality. Skin irritation Pemetrexed Disodium Heptahydrate: Eye irritation Pemetrexed Disodium Heptahydrate: Sensitisation 5/9

rabbit, Irritant

rabbit, Mild eye irritation (cleared within 7 days)

Material Safety Data Sheet

ALIMTA
Version 1.4 Pemetrexed Disodium Heptahydrate: Repeated dose toxicity Pemetrexed Disodium Heptahydrate: Revision Date 02/11/2011 Print Date 03/23/2012 No test data available. Skin rash has been reported in patients not pretreated with a cortiosteroid (dexamethasone).

Decreased testes weights with decreased sperm production and decreased red blood cells were reported in mice with intraperitoneal exposure for 6 weeks. Intravenous exposure in dogs for up to 6 months resulted in mortality, decreased white blood cell counts, mild anemia, and intestinal lesions.

Carcinogenicity Pemetrexed Disodium Heptahydrate: Reproductive toxicity Pemetrexed Disodium Heptahydrate:

This information is not available.

Administration to pregnant mice resulted in decreased fetal weight, incomplete ossification of some skeletal structures, and cleft palate. Male reproductive toxicity characterized by reduced fertility, hypospermia, and testicular atrophy was observed when given to male mice.

Mutagenicity Pemetrexed Disodium Heptahydrate: Further information Pemetrexed Disodium Heptahydrate:

Clastogenic in the in vivo micronucleus assay in the mouse. Results in genetic toxicity assays (in vitro): Negative.

Patients are instructed to take folic acid and vitamin B12 to reduce treatment-related toxicity.

SECTION 12. ECOLOGICAL INFORMATION

Toxicity to fish Pemetrexed Disodium Heptahydrate LC50 / 96 h / Oncorhynchus mykiss (rainbow trout): > 1,099.6 mg/l (highest concentration tested) (as free acid) NOEC / 96 h / Oncorhynchus mykiss (rainbow trout): 1,099.6 mg/l (highest concentration tested) (as free acid) LOEC (embryo + 28 days post hatch) / Pimephales promelas (fathead minnow): > 13 mg/l (highest concentration tested) (as free acid) NOEC (embryo + 28 days post hatch) / Pimephales promelas (fathead minnow): 13 mg/l (highest concentration tested) (as free acid) LOEC / 28 h / C. riparius: > 100,000 g/l (highest concentration tested) NOEC / 28 h / C. riparius: 100,000 g/l (highest concentration tested)

Toxicity to algae Pemetrexed Disodium Heptahydrate

EC50 / 72 h / Pseudokirchneriella subcapitata (green algae): 17 mg/l (yield) (as free acid) NOEC / 72 h / Pseudokirchneriella subcapitata (green algae): 4 mg/l 6/9

Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012 (yield) (as free acid) EC50 / 72 h / Pseudokirchneriella subcapitata (green algae): 63 mg/l (average specific growth rate) (as free acid) NOEC / 72 h / Pseudokirchneriella subcapitata (green algae): 11 mg/l (average specific growth rate) (as free acid) Effects on micro-organisms Pemetrexed Disodium Heptahydrate

EC50 / 3 h / Respiration inhibition of activated sludge: > 1,000 mg/l (highest concentration tested) (as free acid) NOEC / 3 h / Respiration inhibition of activated sludge: 1,000 mg/l (highest concentration tested) (as free acid)

Toxicity to daphnia Pemetrexed Disodium Heptahydrate

EC50 / 48 h/ Daphnia magna (Water flea) : 462.0 mg/l (as free acid) NOEC / 48 h/ Daphnia magna (Water flea) : 91.8 mg/l (as free acid)

Chronic Toxicity to daphnia Pemetrexed Disodium Heptahydrate

EC50/ 21 d / Daphnia magna (Water flea) : 1.8 mg/l (reproduction) (as free acid) LOEC/ 21 d / Daphnia magna (Water flea) : 2.1 mg/l (as free acid) NOEC/ 21 d / Daphnia magna (Water flea) : 1.2 mg/l (as free acid)

Lilly Aquatic Exposure Guideline Drinking Water: 0.045 g/l Pemetrexed Disodium Heptahydrate (as disodium salt) Chronic Exposure of Aquatic Organisms: 1 g/l (as disodium salt) Acute Exposure of Aquatic Organisms: 16 mg/l (as disodium salt)

Biodegradability Pemetrexed Disodium Heptahydrate

Hydrolysis: <10% degradation at 50C for 5 days in pH4, 7, and 9 buffers Ready Biodegradability: 20% of theoretical C was released as CO2 over 29 day incubation Biodegradation (sludge): >99% disappearance when incubated with 1.5 g/L sludge solids (24 hrs) Degradation in sludge: After 1 hr incubation 90% of pemetrexed had disappeared. Numerous degradation peaks were observed by HPLC/RAM. 18.4% applied radioactivity evolved as 14 CO2 over the 28-day study. Degradation in water-sediment systems: DT50 (days): <0.5 7/9

Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012 Over 100 day study, 8.1 to 14.3% AR evolved as 14 CO2 Non extractable radioactive residues at Day 100: 100: 26.9% to 39.8% of applied radioactivity.Three major degradation products observed over 100 day study all of which were degraded over the duration of the study. Bioaccumulation Pemetrexed Disodium Heptahydrate

Refer to Section 9.

SECTION 13. DISPOSAL CONSIDERATIONS

Waste disposal methods : To avoid accidental exposure due to waste handling, place waste residue in a segregated, sealed plastic container. Used syringes, needles, and sharps should not be crushed, clipped, or recapped, but placed directly into an approved sharps container. Dispose of any cleanup materials and waste residue according to all applicable laws and regulations, e.g., secure chemical landfill disposal.

SECTION 14. TRANSPORT INFORMATION

Other information : Not dangerous goods in the meaning of DOT, IMO/IMDG, ICAO/IATA

SECTION 15. REGULATORY INFORMATION

TSCA Status: Not On TSCA Inventory 357166-29-1 Pemetrexed Disodium Heptahydrate DSL Status: This product contains the following components that are not on the Canadian DSL nor NDSL lists. 357166-29-1 Pemetrexed Disodium Heptahydrate

California Prop. 65 This product does not contain any chemicals known to State of California to cause cancer, birth defects, or any other reproductive harm. US. EPA Emergency Planning and Community Right-To-Know Act (EPCRA) SARA Title III Section 313 Toxic Chemicals (40 CFR 372.65) - Supplier Notification Required SARA 313: This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313. US. EPA Emergency Planning and Community Right-To-Know Act (EPCRA) SARA Title III Section 302 Extremely Hazardous Substance (40 CFR 355, Appendix A) SARA 302: No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.

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Material Safety Data Sheet

ALIMTA
Version 1.4 Revision Date 02/11/2011 Print Date 03/23/2012

SECTION 16. OTHER INFORMATION

Further information As of the date of issuance, we are providing available information relevant to the handling of this material in the workplace. All information contained herein is offered with the good faith belief that it is accurate. THIS MATERIAL SAFETY DATA SHEET SHALL NOT BE DEEMED TO CREATE ANY WARRANTY OF ANY KIND (INCLUDING WARRANTY OF MERCHANT ABILITY OR FITNESS FOR A PARTICULAR PURPOSE). In the event of an adverse incident associated with this material, this safety data sheet is not intended to be a substitute for consultation with appropriately trained personnel. Nor is this safety data sheet intended to be a substitute for product literature which may accompany the finished product. For additional information contact: Eli Lilly and Company Hazard Communication 317-651-9533

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