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Material Safety Data Sheet

ALIMTA

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

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SECTION 1. PRODUCT AND COMPANY IDENTIFICATION

Product name : ALIMTA

Substance Number : 000004273779

Common Name : Pemetrexed Disodium Heptahydrate for Injection

Chemical Name : L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, disodium salt, heptahydrate

Company : Eli Lilly and Company

Lilly Corporate Center

Indianapolis, IN 46285

Telephone : 317-276-2000

Emergency telephone number : 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 CodeHealth: 2

Fire: 1

Reactivity: 0

Special: Reproductive Hazard

Special:R

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 bloodeffects. May cause bone marrow effects. This product may cause adverse reproductive effects.

Emergency OverviewForm : lyophilized

Colour : white

Odour : odourless

Potential Health Effects

Eyes : May irritate eyes.

Skin : May irritate skin. Skin rash has been reported in patients not pretreated with a

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cortiosteroid (dexamethasone).

Aggravated Medical Condition : None known.

Primary Routes of Entry : Inhalation Skin Absorption

Additional Information : 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 acidand vitamin B12 to reduce treatment-related toxicity.

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 CAS-No. Concentration [%]

Pemetrexed Disodium Heptahydrate 357166-29-1 50

Mannitol 69-65-8 50

SECTION 4. FIRST AID MEASURESInhalation : Remove to fresh air. If breathing is irregular or stopped, administer artificial

respiration. Call a physician immediately.

Skin contact : 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.

Eye contact : 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.

Ingestion : If conscious, give the victim plenty of water to drink. Never give anything by mouth

to an unconscious person. Call a physician immediately.

Notes to physician

Treatment : Pemetrexed disodium - If overdose occurs, general supportive measures should be

instituted as deemed necessary by the treating physician. Management of pemetrexedoverdose should include consideration of the use of leucovorin or thymidine rescue.

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

SECTION 5. FIRE-FIGHTING MEASURES

Flash point : No data availableLower explosion limit : No data available

Upper explosion limit : No data available

Suitable extinguishing media : Water Carbon dioxide (CO2) Dry chemical

Unusual Fire and Explosion

Hazard.

: Dust may form explosive mixture in air. Hazardous decomposition products formed

under fire conditions.

Special protective equipment for

fire-fighters

: 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 areashandling 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 areasand 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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SECTION 8. EXPOSURE CONTROLS/PERSONAL PROTECTION

Exposure guidelines

Components Exposure Limit Values

Pemetrexed Disodium

Heptahydrate

LEG: 8 or 12 hour TWA 0.3 g/m3

LEG: 30 min Excursion Limit 3.6 g/m3

Mannitol EG: TWA 10 mg/m3

For appropriate handling precautions in specific laboratory, manufacturing, or clinical health care operations, consult with a healthand 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.

Eye protection : Goggles Face-shield

Skin and body protection : Chemical-resistant gloves and impermeable body covering to minimize skin contact. Ifhandled in a ventilated enclosure, as in a laboratory setting, respirator and goggles or

face shield may not be required. Safety glasses are always required.

Hygiene measures : In production settings, airline-supplied, hood-type respirators are preferred. Shower

and change clothing if skin contact occurs.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Appearance

Form : lyophilizedPhysical state : solid

Colour : whiteOdour : odourless

Safety data

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Flash point : No data availableLower explosion limit : No data available

Upper explosion limit : No data available

Water solubility : 101.5 g/l(pH 7), (as free acid)Water solubility : 89.4 g/l(pH 9), (as free acid)

log Pow : < 1

SECTION 10. STABILITY AND REACTIVITY

Materials to avoid : Incompatible with oxidizing agents.

Hazardous decompositionproducts

: Hazardous decomposition products formed under fire conditions.

Thermal decomposition : Stable under normal conditions.

Hazardous reactions : Hazardous polymerisation does not occur.

SECTION 11. TOXICOLOGICAL INFORMATION

Acute oral toxicity

Pemetrexed Disodium

Heptahydrate:

LD50 (rat) > 500 mg/kg

(as free base)

Acute inhalation toxicity

Pemetrexed DisodiumHeptahydrate:

No data available

Acute dermal toxicity

Pemetrexed Disodium

Heptahydrate:

LD50 (rabbit) > 1,000 mg/kg

Acute toxicity (other routes of administration)

Pemetrexed Disodium

Heptahydrate:

Intravenous - LD50 (male rat) 1,332 mg/kg

Convulsions.

Intravenous - LD50 (female rat) > 1,574 mg/kg

Convulsions. Mortality.

Skin irritation


rabbit, Irritant

Eye irritation

Pemetrexed Disodium

Heptahydrate:

rabbit, Mild eye irritation

(cleared within 7 days)

Sensitisation

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Pemetrexed Disodium

Heptahydrate:

No test data available. Skin rash has been reported in patients not pretreated with acortiosteroid (dexamethasone).

Repeated dose toxicity


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, mildanemia, and intestinal lesions.

Carcinogenicity

Pemetrexed Disodium

Heptahydrate:

This information is not available.

Reproductive toxicity


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 observedwhen given to male mice.

Mutagenicity

Pemetrexed Disodium

Heptahydrate:

Clastogenic in the in vivo micronucleus assay in the mouse. Results in genetic toxicity

assays (in vitro): Negative.

Further information

Pemetrexed DisodiumHeptahydrate: Patients are instructed to take folic acid and vitamin B12 to reduce treatment-relatedtoxicity.

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 DisodiumHeptahydrate

EC50 / 72 h / Pseudokirchneriella subcapitata (green algae): 17 mg/l

(yield) (as free acid)

NOEC / 72 h / Pseudokirchneriella subcapitata (green algae): 4 mg/l

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(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


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


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

(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 DisodiumHeptahydrate Hydrolysis: 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):

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Over 100 day study, 8.1 to 14.3% AR evolved as 14 CO2Non 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 DisodiumHeptahydrate 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 lawsand 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. 65This 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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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 OFMERCHANT 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 finishedproduct.For additional information contact:

Eli Lilly and Company

Hazard Communication

317-651-9533

Documents

ALIMTA_VL7640