Procter & Gamble MATERIAL SAFETY DATA SHEET Macrobid® Page 1 of 5 SECTION 1 – CHEMICAL / PRODUCT AND COMPANY IDENTIFICATION PROCTER & GAMBLE PHARMACEUTICALS, INC. Hazard Rating PO BOX 191 NORWICH, NY 13815 EMERGENCY PHONE: 24 HOUR SPILL RESPONSE PHONE: 800-424-9300 CHEMTREC Chemical Nitrofurantoin monohydrate: 1-[[(5- Macrobid® Capsules Nitro-2-furanyl)methylene]amino]-2,4- Marketed Drug Product imidazolidinedione monohydrate Intended Pharmaceutical Nitrofurantoin macrocrystals: 1-[[(5- Nitro-2-furanyl)methylene]amino]-2,4- imidazolidinedione Chemical Nitrofuran Formula: Monohydrate: C 8H6N4O5 H2O Macrocrystals: C SECTION II - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW: Macrobid® is a 100 mg opaque black and yellow gelatin capsule. It contains 2 plugs, one yellow, the second a mottled off-white to light yellow in color. Material is intended for use as a human pharmaceutical. Accidental excessive ingestion may cause gastrointestinal effects, skin, hypersensitivity reactions, hematological , neurological, liver and pulmonary effects. Hazard and Toxicological information is based on the active pharmaceutical ingredients. Eye: As a capsule, unlikely to come into contact with eye. If powder from crushed or pulverized capsule cores contacts eyes, unknown effect from direct contact by material. Skin: As a capsule, unlikely to come into prolonged contact with skin. Prolonged contact with powder from crushed or pulverized capsule cores may cause skin irritation. Ingestion: Accidental excessive ingestion may cause gastrointestinal effects, skin, hypersensitivity reactions, hematological , neurological, liver and pulmonary effects. Inhalation: As a capsule, unlikely to be inhaled. If powder from crushed or pulverized capsule core is inhaled, may be irritating to upper respiratory tract. Reproductive Hazard? Reversible alterations in spermatogenesis in male rats. Refer to Toxicological Section XI. Carcinogenic Hazard? IARC classifies nitrofurantoin as a Group 3 carcinogen (not classifiable as to its carcinogenicity in humans) based on “inadequate” data in humans and “limited” data in animals (IARC, 1990). See Section XI for additional carcinogenicity information. Medical Conditions Aggravated by Gastrointestinal, pulmonary, hypersensitivity reaction, skin, Exposure or Target Organ Systems: hemolytic anemia. Cases of hemolytic anemia of the primaquine- sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. Hemolysis is an indication for discontinuing nitrofurantoin; hemolysis ceases when the drug is withdrawn. Target Organ Systems: Liver, lungs, nervous system. Procter & Gamble
PROCTER & GAMBLE Page 2 of 5 MSDS Identifier: Macrobid® SECTION III – COMPOSITION AND INGREDIENTS Principal Hazardous Components CAS 1-[[[5-Nitro-2-furanyl]methylene]amino]-2,4-imidazolidinedione 1-[[[5-Nitro-2-furanyl]methylene]amino]-2,4-imidazolidinedione monohydrate 17140-81-7 Excipients: carbomer 934P, corn starch, compressible sugar, D&C yellow No. Various 77.2% 10, edible gray ink, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lactose, magnesium stearate, povidone, talc, and titanium dioxide. NOTE: This MSDS is written to address potential worker health and safety issues associated with the handling of the formulated final product which is a capsule, e.g., during the transportation, distribution, and use by medical personnel. For worker health and safety information during the manufacture of Macrobid®, please refer to the MSDS on each component. SECTION IV - FIRST AID MEASURES Eye: If powder contacts eye, flush with plenty of water for at least 15 minutes. Do not put oil or oinment in eyes. Get immediate medical attention. Skin: If powder contacts skin, flush with plenty of water for at least 15 minutes. Get immediate medical attention. Inhalation: As a capsule, not expected. If powder from crushed or pulverized capsule core is inhaled, remove to fresh air. Call a physician. Provide supportive symptomatic care. Ingestion: If swallowed, wash out mouth with water provided person is conscious. Do not induce vomiting. Call a physician. Provide supportive symptomatic care. Additional First Aid Measures: Not available
SECTION V - FIRE FIGHTING MEASURES Flash Point: Not applicable Not available Flash Point test Not Available Auto-ignition Not applicable Not available Flammable Limits Not applicable Temperature: (% by volume in air) LEL % UEL % Extinguishing Media This material is assumed to be combustible, and should be treated as such. Water spray, CO2, dry chemical or appropriate foam. Explosion Hazards This material is assumed to be combustible and may emit toxic fumes, under fire conditions. Special Instructions As with all fires, evacuate personnel to safe area. Firefighters should use self- contained breathing apparatus and protective clothing to prevent contact with skin and eyes. SECTION VI - ACCIDENTAL RELEASE MEASURES Personnel Safeguards: Wear gloves to avoid contact with skin and eyes when handling/counting large amounts of capsules. Wash thoroughly after handling. Environmental Precautions: Dispose of all collected material in accordance with applicable local, state and federal waste disposal regulations (see Section XIII). Spill Clean-up Procedures: If capsules are broken and the core is crushed or pulverized, cordon off the area. Take proper precautions to minimize exposure by using appropriate personal protective equipment. Wet material with water to reduce potential for dust generation and soak up material with absorbent, e.g., paper towels. Wash spill area thoroughly with soap and water. Procter & Gamble PROCTER & GAMBLE Page 3 of 5 MSDS Identifier: Macrobid® SECTION VII - HANDLING AND STORAGE Recommended Storage Temperature Not available None 59-86 Personnel Precautions: Avoid contact with skin and eyes. Conditions for Safe Storage: Store in dry location, minimize exposure to light. Other Precautions: N/A SECTION VIII - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Not applicable for capsules. Eye Protection: Not applicable for capsules. Respiratory Protection: Not applicable for capsules. Skin Protection: Rubber gloves are recommended to minimize potential for skin contact when handling/counting large amounts of capsules. Exposure Limits: Active Ingredient Exposure Limit: 0.5 mg/m3 (Active Pharmaceutical Ingredient) P&GP Internal OEL SECTION IX - PHYSICAL AND CHEMICAL PROPERTIES Appearance / Color: Not available Solubility in Not available Opaque black and yellow Water: <0.1 mg/ml at 19oC gelatin capsule. 2 plugs: one yellow, the second a mottled off-white to light yellow in color. Not available Vapor Pressure Not available Odor Threshold: Not available Vapor Density: Not available Physical State: Not available Specific Gravity Not available (H2O=1): Molecular Weight: Not available Percent Volatile by Not available Macrocrystals: 238.16 Volume (%): Monohydrate: 256.17 Not available Evaporation Rate: Not available Boiling or Melting Not available Other Not Available Point of Active 270-272 Miscellaneous Pharmaceutical Melting Point Properties Ingredient: SECTION X – STABILITY AND REACTIVITY Stability: Unstable Hazardous Will Not Occur May Occur Polymerization: Polymerization: Not Available Incompatibility: Oxidizing agents (Materials to avoid) Hazardous CO2, CO, nitrogen oxides Decomposition Products: Procter & Gamble PROCTER & GAMBLE Page 4 of 5 MSDS Identifier: Macrobid® SECTION XI - TOXICOLOGICAL INFORMATION Eye Effects: Not available Acute Oral Effects: The oral LD50 of nitrofurantoin in rats and mice was reported to be 604 and 360 mg/kg, respectively. Acute Inhalation Effects: Not available Chronic Effects: Pulmonary, liver, and nervous system. Sub-Chronic Effects: Pulmonary, liver, and nervous system. Reproductive and Doses of 10 mg/kg/day or greater, higher than therapeutic doses, in Birth Effects: healthy human males may produce a slight to moderate decrease in sperm count. The administration of high doses (10 mg/kg/day) of nitrofurantoin to rats causes reversible spermatogenic arrest. Several reproduction studies have been performed in rabbits and rats at doses up to six times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to nitrofurantoin. In a single published study conducted in mice at 68 times the human dose, growth retardation and a low incidence of minor and common malformations were observed. However, at 25 times the human dose, fetal malformations were not observed; the relevance of these findings to humans is uncertain. Genetic Toxicity: Nitrofurantoin has produced positive results in Ames Assay in the presence and absence of a liver activating system. Nitrofurantoin induced increased numbers of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells but not in human cells in culture. Results of the sex-linked recessive lethal assay in Drosphila were negative after administration of nitrofurantoin by feeding or by injection. Nitrofurantoin did not induce heritable mutation in the rodent models examined. Carcinogenicity: Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F1 mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulose cell tumors of the ovary. In male F344/N rats, there were increased incidences of uncommon kidney tubular cell neoplasms, osteosarcomas of the bone, and neoplasms of the subcutaneous tissue. In one study involving subcutaneous administration of 75 mg/kg nitrofurantoin to pregnant female mice, lung papillary adenomas of unknown significance were observed in the F1 generation. SECTION XII -ECOLOGICAL INFORMATION No environmental fate studies have been conducted to date. Agency Agency Requirement N/A SECTION XIII - DISPOSAL CONSIDERATIONS All wastes containing the material should be properly labeled. Dispose of any waste residues according to prescribed federal, state and local guidelines, e.g., appropriately permitted chemical waste incinerator. Rinse waters resulting from spill cleanups should be discharged in an environmentally safe manner, e.g., appropriately permitted municipal or on-site wastewater treatment facility. Procter & Gamble PROCTER & GAMBLE Page 5 of 5 MSDS Identifier: Macrobid® SECTION XIV – TRANSPORTATION Transport according to all local, state and federal regulations. Agency Parameter Requirement Proper Shipping Name Not applicable/not regulated Hazard Class or Division Not applicable/not regulated UN or NA Number Not applicable/not regulated Packing Group Not applicable/not regulated Hazardous Waste Number Not regulated under RCRA SECTION XV - ADDITIONAL REGULATORY INFORMATION Observe all federal, state and local environmental regulations. Not covered by WHMIS – cosmetics, drugs, food or devices (as defined by the FDA). SECTION XVI - OTHER INFORMATION DISCLAIMER: This MSDS is intended to provide a brief summary of our knowledge and guidance regarding the use of this material. It is not meant to be an all-inclusive document on worldwide hazard communication regulations. All P&G operations must comply with applicable local and national MSDS/Hazard Communication Regulations. This information is offered in good faith. Each user of this material needs to evaluate the conditions of use and design the appropriate protective mechanisms to prevent employee exposures, property damage or release to the environment.
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