Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.
Chronic therapy with sulindac is associated with a low rate of serum aminotransferase elevations, which are rarely severe and usually self-limited. Clinically apparent acute liver injury from sulindac is well known, but rare (~5 cases in 100,000 prescriptions and ~0.1% of users). Sulindac hepatotoxicity typically presents with fever, rash, nausea and vomiting and abdominal pain arising within a few days or weeks of starting the medication and followed shortly thereafter by jaundice. Occasionally, the onset may be delayed, particularly if therapy is intermittent. The clinical pattern suggests an allergic hepatitis and is somewhat similar to the hepatotoxicity of the sulfonamides. The pattern of serum enzyme elevations is usually hepatocellular or mixed at the onset, but may then become cholestatic. However, recovery is usually rapid once sulindac is stopped. Histology is consistent with an allergic hepatitis with spotty necrosis and marked inflammatory cell infiltration with prominence of eosinophils. In many instances, the features of hypersensitivity (such as facial swelling, desquamating rash, pharyngitis, stomatitis, lymphadenopathy, and hypotension) overshadow the liver injury and are more commonly the cause of death. Sulindac can also cause acute liver injury with a more delayed latency with few or no features of hypersensitivity. These cases are usually cholestatic and can be prolonged and lead to vanishing bile duct syndrome.
Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name : Sulindac CAS-No. : 38194-50-2 Relevant identified uses of the substance or mixture and uses advised against Identified uses : Laboratory chemicals, Manufacture of substances Section 2. HAZARDS IDENTIFICATION Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP] Acute toxicity, Oral (Category 3) Respiratory sensitization (Category 1) Skin sensitization (Category 1) Reproductive toxicity (Category 2) Classification according to EU Directives 67/548/EEC or 1999/45/EC Harmful if swallowed. Harmful if swallowed. May cause sensitization by inhalation and skin contact. Possible risk of harm to the unborn child. Label elements Labelling according Regulation (EC) No 1272/2008 [CLP] Pictogram Signal word Danger Hazard statement(s) H301 Toxic if swallowed. H317 May cause an allergic skin reaction. H334 May cause allergy or asthma symptoms or breathing difficulties if inhaled. H361 Suspected of damaging fertility or the unborn child. Precautionary statement(s) P261 Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray. P280 Wear protective gloves. P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/ physician. P342 + P311 If experiencing respiratory symptoms: Call a POISON CENTER or doctor/ physician. Supplemental Hazard none Statements According to European Directive 67/548/EEC as amended. Hazard symbol(s) R-phrase(s) R22 Harmful if swallowed. R42/43 May cause sensitization by inhalation and skin contact. R63 Possible risk of harm to the unborn child. S-phrase(s) none Other hazards - none Section 3. COMPOSITION/INFORMATION ON INGREDIENTS Substances Synonyms : (Z)-5-Fluoro-2-methyl-1-[p-(methylsulfinyl)benzylidene]indene-3-acetic acid Formula : C20H17FO3S Molecular Weight : 356,41 g/mol Component Concentration Sulindac CAS-No. 38194-50-2 - EC-No. 253-819-2 Section 4. FIRST AID MEASURES Description of first aid measures General advice Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Take victim immediately to hospital. Consult a physician. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician. Most important symptoms and effects, both acute and delayed Indication of any immediate medical attention and special treatment needed no data available Section 5. FIREFIGHTING MEASURES Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Carbon oxides, Sulphur oxides, Hydrogen fluoride Advice for firefighters Wear self contained breathing apparatus for fire fighting if necessary. Further information no data available Section 6. ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. Section 7. HANDLING AND STORAGE Precautions for safe handling Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire protection. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Specific end uses no data available Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. Personal protective equipment Eye/face protection Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Section 9. PHYSICAL AND CHEMICAL PROPERTIES Information on basic physical and chemical properties a) Appearance Form: solid b) Odour no data available c) Odour Threshold no data available d) pH no data available e) Melting point/freezing no data available point f) Initial boiling point and no data available boiling range g) Flash point no data available h) Evaporation rate no data available i) Flammability (solid, gas) no data available j) Upper/lower no data available flammability or explosive limits k) Vapour pressure no data available l) Vapour density no data available m) Relative density no data available n) Water solubility insoluble o) Partition coefficient: n- no data available octanol/water p) Autoignition no data available temperature q) Decomposition no data available temperature r) Viscosity no data available s) Explosive properties no data available t) Oxidizing properties no data available Other safety information no data available Section 10. STABILITY AND REACTIVITY Reactivity no data available Chemical stability no data available Possibility of hazardous reactions no data available Conditions to avoid no data available Incompatible materials Strong oxidizing agents Hazardous decomposition products Other decomposition products - no data available Section 11. TOXICOLOGICAL INFORMATION Information on toxicological effects Acute toxicity LD50 Oral - rat - 264 mg/kg Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization no data available May cause allergic respiratory and skin reactions Germ cell mutagenicity no data available Carcinogenicity 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. Reproductive toxicity Possible risk of congenital malformation in the fetus. Suspected human reproductive toxicant Developmental Toxicity - mouse - Oral Specific Developmental Abnormalities: Craniofacial (including nose and tongue). Developmental Toxicity - mouse - Intramuscular Specific Developmental Abnormalities: Craniofacial (including nose and tongue). Specific target organ toxicity - single exposure no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Potential health effects Inhalation May be harmful if inhaled. May cause respiratory tract irritation. Ingestion Toxic if swallowed. Skin May be harmful if absorbed through skin. May cause skin irritation. Eyes May cause eye irritation. Additional Information RTECS: NK8226000 Section 12. ECOLOGICAL INFORMATION Toxicity no data available Persistence and degradability no data available Bioaccumulative potential no data available Mobility in soil no data available Results of PBT and vPvB assessment no data available Other adverse effects no data available Section 13. DISPOSAL CONSIDERATIONS Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging Dispose of as unused product. Section 14. TRANSPORT INFORMATION UN number ADR/RID: 2811 IMDG: 2811 IATA: 2811 UN proper shipping name ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (Sulindac) IMDG: TOXIC SOLID, ORGANIC, N.O.S. (Sulindac) IATA: Toxic solid, organic, n.o.s. (Sulindac) Transport hazard class(es) ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1 Packaging group ADR/RID: III IMDG: III IATA: III Environmental hazards ADR/RID: no IMDG Marine pollutant: no IATA: no Special precautions for user no data available Section 15. REGULATORY INFORMATION This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006. Safety, health and environmental regulations/legislation specific for the substance or mixture no data available Chemical Safety Assessment no data available Section 16. OTHER INFORMATION Further information Copyright 2012 Co. LLC. License granted to make unlimited paper copies for internal use only. The above information is believed to be correct but does not purport to be all inclusive and shall be used only as a guide. The information in this document is based on the present state of our knowledge and is applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee of the properties of the product. Corporation and its Affiliates shall not be held liable for any damage resulting from handling or from contact with the above product. See and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.
