Dimethyl Sulfoxide

CAS RN:67-68-5

Toxicity Summary

IDENTIFICATION AND USE: Dimethyl sulfoxide (DMSO) is a colorless, very hygroscopic, liquid. It is a molecule with a long history in pharmaceutics and is now well established as a penetration enhancer in topical pharmaceutical formulations. It is currently prescribed as medication for this purpose in diclofenac sodium topical solution (approved in the United States to treat signs and symptoms of osteoarthritis) and idoxuridine topical solution (approved in Europe for the treatment of herpes zoster). DMSO is used as a medication for symptomatic relief of interstitial cystitis. DMSO is not a nutritional supplement, it is metabolized to methylsulfonylmethane (MSM), which is available as a nutritional supplement. DMSO is used in the cryopreservation of cell populations including stem cells, embryos, and various cell cultures. It is also used as an Industrial solvent and as antifreeze or hydraulic fluid when mixed with water. HUMAN EXPOSURE AND TOXICITY: Dermal exposure to DMSO causes skin reactions, erythema and pruritis, which appear immediately after contact with the undiluted substance; 70% solutions are usually tolerated without symptoms. In very sensitive individuals, however, reactions have been seen after contact with 10% solutions. In humans, topical and intradermal application of DMSO produced garlic breath, mast cell degranulation, an increase in polymorphonuclear leukocytes and perivascular eosinophils, itching, and histamine mediated and non-histamine dependent whealing and erythematous flare. Two drops of >50% DMSO in the eye caused a temporary burning sensation and vasodilatation; concentrations of <50% exhibited no effects. A case of sulhemoglobinemia after dermal exposure to DMSO has been described. ANIMAL STUDIES: To study the effects of acute DMSO exposure unshaven rats were immersed in a DMSO solution. There was no immediate response, but within 24 hours 13/14 rats dipped into 100% DMSO were dead. Single i.v. injections of undiluted DMSO were administered to groups of 5 male and 5 female rats. Dose levels were 2.5, 5.0, and 10 g/kg. Each dose was administered over a 1-minute interval. Animals were observed for 14 days following DMSO administration and with one exception, deaths occurred within the first 24 hours. Death was preceded by tremors, myasthenia, dyspnea, and occasionally, convulsions. Non-lethal doses of DMSO produced decreased motoractivity and myasthenia. A total of 32 male rats were exposed to 200 mg DMSO per cubic meter of air for 7 hr/day, 5 days a week, for 6 weeks for 30 exposures. There were no outward toxic signs noted in any of the exposed animals throughout the experimental period of 6 weeks. A garlic-like odor, characteristic of DMSO exposure, was detected in the breath of each of the rats after the first day of exposure. Pharmaceutical-grade DMSO was administered as a 90% solution to 4 groups of rhesus monkeys by gastric intubation, 7 days a week for up to 87 weeks. Dosages administered were equivalent to 990, 2970, and 8910 mg/kg/day. The principal physical signs seen in the animals given DMSO orally included sporadic excess salivation and emesis. Anorexia only occurred at high oral doses. No DMSO-related changes were found in the treated monkeys during physical examinations. No significant lesions attributable to DMSO were found upon gross examination at necropsy. No histologic changes were visible in the lenses of treated animals. In developmental studies groups of 5 -6 pregnant golden hamsters were injected with dilutions of DMSO ranging from 50 to 5500 mg/kg iv or 5500 and 8250 mg/kg ip on the eighth day of gestation. Examination of the embryos 3 days later revealed that no embryocidal or teratogenic effects were noted until levels of 2500 mg/kg were reached. At higher levels, malformations, including exencephaly, rib fusions, microphthalmia, limb abnormalities and cleft lip were found. There was no appreciable effect of DMSO on maternal weight gain or health. DMSO was tested in Chinese hamster ovary cells to a maximum concentration of 5000 ug/mL with and without metabolic activation. DMSO did not induce cell toxicity or cell cycle delay, and did not induce an increase in the incidence of SCEs. Intraabdominal injection of DMSO did not induce sex-linked recessive lethals and did not raise the frequency of sex chromosome loss above the spontaneous level in Drosophila melanogaster. DMSO was tested in five S. typhimurium tester strains (TA 98, 100, 1535, 1537, 1538). DMSO was negative, in the presence and absence of metabolic activation. ECOTOXICITY STUDIES: The acute toxicity (g/kg bw) of i.p. DMSO injection to chinook salmon (Oncorhynchus tshawytscha): LD50 = 12.0, sockeye salmon (Oncorhynchus nerka): LD50 = 13.0, coho salmon (Oncorhynchus kisutch): LD50 = 16.0 and rainbow trout (Salmo gardneri): LD50 = 17.0. Fish usually died within 24 hr; however, a few died between 24 and 48 hours.
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