MATERIAL SAFETY DATA SHEET - Pfizer

1 1. IDENTIFICATION OF THE SUBSTANCE/PREPARATION AND THE COMPANY/UNDERTAKINGM aterial Name: Methotrexate Solution for InjectionTrade Name:Methoblastin; Maxtrex; Methotrexat; Lantarel; TrexanChemical Family:MixtureIntended Use:Antineoplastic2. HAZARDS IDENTIFICATIONA ppearance:Clear yellow solutionStatement of Hazard:Non-hazardous in accordance with international standards for workplace Hazard Information:Short Term:May be absorbed through the skin and cause systemic effects. May be harmful if swallowed.(based on components) .Long Term:Animal studies have shown a potential to cause adverse effects on the fetus. The use of thisdrug during pregnancy has resulted in birth Clinical Effects:Adverse effects associated with therapeutic use include gastrointestinal disturbances such asnausea, dyspepsia, and vomiting and gastrointestinal irritation.

2 Effects on blood and blood-forming organs have also Indication of danger:Not classifiedNote:This document has been prepared in accordance with standards for workplace SAFETY , whichrequire the inclusion of all known hazards of the active substance or its intermediatesregardless of the potential risk. The precautionary statements and warnings included may notapply in all cases. Your needs may vary depending upon the potential for exposure in COMPOSITION/INFORMATION ON INGREDIENTSH azardous_____PZ00135 Emergency telephone number:CHEMTREC (24 hours): 1-800-424-9300 Revision date: 29-Mar-2012 Emergency telephone number:ChemSafe (24 hours): +44 (0)208 762 8322 Contact MATERIAL SAFETY data SHEETPage 1 of 7 Pfizer IncPfizer Pharmaceuticals Group 235 East 42nd StreetNew York, New York 100171-212-573-2222 Pfizer LtdRamsgate RoadSandwich, KentCT13 9 NJUnited Kingdom+00 44 (0)1304 616161 MATERIAL SAFETY data SHEET_____3.

3 COMPOSITION/INFORMATION ON INGREDIENTSI ngredientCAS NumberEU EINECS/ELINCS List EU Classification%Methotrexate59-05-2200-41 3-8 Mut. ;R68 Repr. ;R61T; hydroxide1310-73-2215-185-5C;R35###Ingre dientCAS NumberEU EINECS/ELINCS List EU Classification%Sodium chloride7647-14-5231-598-3 Not Listed*Water for Injection7732-18-5231-791-2 Not Listed*Additional Information:* Proprietary### as (s) indicated as hazardous have been assessed under standards for the full text of the R phrases mentioned in this Section, see Section 164. FIRST AID MEASURESEye Contact:Flush with water while holding eyelids open for at least 15 minutes. Seek medical Contact:Remove contaminated clothing. Flush area with large amounts of water. Use soap. Seekmedical :Never give anything by mouth to an unconscious person. Wash out mouth with water. Do notinduce vomiting unless directed by medical personnel.

4 Seek medical attention :Remove to fresh air and keep patient at rest. Seek medical attention and Effects of Exposure:For information on potential signs and symptoms of exposure, See Section 2 - HazardsIdentification and/or Section 11 - Toxicological FIRE FIGHTING MEASURESE xtinguishing Media:Use carbon dioxide, dry chemical, or water Combustion Products:Formation of toxic gases is possible during heating or Fighting Procedures:During all fire fighting activities, wear appropriate protective equipment, including self-contained breathing / Explosion Hazards:Fine particles (such as dust and mists) may fuel ACCIDENTAL RELEASE MEASURESH ealth and SAFETY Precautions:Personnel involved in clean-up should wear appropriate personal protective equipment (seeSection 8). Minimize for Cleaning / Collecting:Contain the source of spill if it is safe to do so.

5 Collect spill with absorbent MATERIAL . Clean spillarea : 2 of 7 Revision date: 29-Mar-2012 MATERIAL Name: Methotrexate Solution for Injection MATERIAL SAFETY data SHEET_____Measures for EnvironmentalProtections:Place waste in an appropriately labeled, sealed container for disposal. Care should be taken toavoid environmental Consideration for LargeSpills:Non-essential personnel should be evacuated from affected area. Report emergencysituations immediately. Clean up operations should only be undertaken by trained HANDLING AND STORAGEG eneral Handling:Avoid contact with eyes, skin and clothing. Avoid breathing vapor or mist. Wash thoroughlyafter handling. Avoid open Conditions:Store as directed by product EXPOSURE CONTROLS / PERSONAL PROTECTIONR efer to available public information for specific member state Occupational Exposure Controls:Engineering controls should be used as the primary means to control exposures.

6 Generalroom ventilation is adequate unless the process generates dust, mist or fumes. Keep airbornecontamination levels below the exposure limits listed above in this Exposure Controls:Refer to specific Member State legislation for requirements under Community Protective Equipment:Refer to applicable national standards and regulations in the selection and use of personalprotective equipment (PPE).Hands:Impervious gloves are recommended if skin contact with drug product is possible and for bulkprocessing :Wear SAFETY glasses or goggles if eye contact is :Impervious protective clothing is recommended if skin contact with drug product is possible andfor bulk processing OEL - TWA2 mg/m3 Hungary OEL - TWA2 mg/m3 Lithuania OEL - TWA5 mg/m3 Japan - OELs - Ceilings2 mg/m3 MethotrexateLatvia OEL - mg/m3 Sodium hydroxideOSHA - Final PELS - TWAs:2 mg/m3 Version: 3 of 7 Poland OEL - mg/m3 ACGIH Ceiling Threshold Limit:Slovakia OEL - TWA2 mg/m32 mg/m3 Slovenia OEL - TWA2 mg/m3 Pfizer OEL TWA-8 Hr:Sweden OEL - TWAs1 mg/m3 Australia PEAK2 mg/m32 g/m3 Austria OEL - MAKs2 mg/m3 Bulgaria OEL - mg/m3 Sodium chlorideCzech Republic OEL - TWA1 mg/m3 Revision date.

7 29-Mar-2012 Estonia OEL - TWA1 mg/m3 Latvia OEL - TWA5 mg/m3 France OEL - TWA2 mg/m3 MATERIAL Name: Methotrexate Solution for Injection MATERIAL SAFETY data SHEET_____8. EXPOSURE CONTROLS / PERSONAL PROTECTIONR espiratory protection :If the applicable Occupational Exposure Limit (OEL) is exceeded, wear an appropriaterespirator with a protection factor sufficient to control exposures to below the PHYSICAL AND CHEMICAL PROPERTIES10. STABILITY AND REACTIVITYC hemical Stability:Stable under normal conditions of to Avoid:Fine particles (such as dust and mists) may fuel Materials:As a precautionary measure, keep away from strong oxidizers11. TOXICOLOGICAL INFORMATIONG eneral Information:The information included in this section describes the potential hazards of the Toxicity: (Species, Route, End Point, Dose)Acute Toxicity Comments:A greater than symbol (>) indicates that the toxicity endpoint being tested was not achievableat the highest dose used in the / Sensitization: (Study Type, Species, Severity)Repeated Dose Toxicity: (Duration, Species, Route, Dose, End Point, Target Organ)_____PZ00135 Rat Oral LD50 3000 mg/kgRevision date: 29-Mar-2012 Molecular Formula:Mouse Oral LD50 4000 mg/kgMixtureSodium hydroxideMaterial Name: Methotrexate Solution for InjectionMethotrexateMouse IP LD50 40 mg/kgMolecular Weight.

8 MixtureRat Oral LD50 135 mg/kgSodium chlorideRat Sub-tenon injection (eye) LD50 6 mg/kgEye Irritation Rabbit ModerateVersion: 4 of 7 Skin Irritation Rabbit MildRat Intravenous LD50 14 mg/kgSodium hydroxidePhysical State:Eye Irritation Rabbit SevereMouse Oral LD50 146 mg/kgSkin Irritation Rabbit SevereSolutionNot Specified Inhalation LC50 > 188 ug/m3 Color:Sodium chlorideClear Yellow MATERIAL SAFETY data SHEET_____11. TOXICOLOGICAL INFORMATIONR eproduction & Developmental Toxicity: (Study Type, Species, Route, Dose, End Point, Effect(s))Genetic Toxicity: (Study Type, Cell Type/Organism, Result)Carcinogen Status:None of the components of this formulation are listed as a carcinogen by IARC, NTP or below12. ECOLOGICAL INFORMATIONE nvironmental Overview:Environmental properties have not been thoroughly investigated.

9 Releases to the environmentshould be DISPOSAL CONSIDERATIONSW aste Treatment Methods:Dispose of waste in accordance with all applicable laws and regulations. Member Statespecific and Community specific provisions must be considered. Considering the relevantknown environmental and human health hazards of the MATERIAL , review and implementappropriate technical and procedural waste water and waste disposal measures to preventoccupational exposure and environmental release. It is recommended that waste minimizationbe practiced. The best available technology should be utilized to prevent environmentalreleases. This may include destructive techniques for waste and TRANSPORT INFORMATIONThe following refers to all modes of transportation unless specified regulated for transport under USDOT, EUADR, IATA, or IMDG : 5 of 7In Vitro Chromosome Aberration Human Lymphocytes PositiveMethotrexateIn Vitro Sister Chromatid Exchange Mouse PositiveMethotrexateUnscheduled DNA Synthesis Human Lymphocytes PositiveEmbryo / Fetal Development Mouse Oral 10 mg/kg/day NOAEL Not teratogenicIn Vivo Micronucleus Mouse PositiveEmbryo / Fetal Development Mouse Oral 25-50 mg/kg/day LOAEL Teratogenic4 Week(s) Rat Oral mg/kg LOAEL Bone marrow, LiverEmbryo / Fetal Development Monkey Intravenous 30 mg/kg/day LOAEL Developmental toxicityMethotrexateRevision date: 29-Mar-2012 IARC.

10 Group 3 (Not Classifiable)Embryo / Fetal Development Rat Intraperitoneal 5 mg/kg LOAEL Fetotoxicity6 Week(s) Rat Oral mg/kg LOAEL Bone Marrow, LiverMaterial Name: Methotrexate Solution for InjectionMethotrexate MATERIAL SAFETY data SHEET_____15. REGULATORY INFORMATIONEU Indication of danger:Not classifiedOSHA Label:Non-hazardous in accordance with international standards for workplace - WHMIS: ClassificationsWHMIS hazard class:D2a very toxic materials16. OTHER INFORMATIONText of R phrases mentioned in Section 3_____PZ00135 PresentSodium hydroxideMaterial Name: Methotrexate Solution for InjectionCERCLA/SARA Hazardous Substancesand their Reportable Quantities:1000 lb454 kgInventory - United States TSCA - Sect. 8(b)PresentAustralia (AICS):PresentAustralia (AICS):PresentVersion: 6 of 7 Standard for the Uniform Schedulingfor Drugs and Poisons:Schedule 5 Schedule 6 Standard for the Uniform Schedulingfor Drugs and Poisons:EU EINECS/ELINCS List215-185-5 Schedule 4 Water for InjectionMethotrexateInventory - United States TSCA - Sect.