Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 67-68-5 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Dimethyl sulfoxide
  • SULFINYLBISMETHANE (9CI)

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Toxicology of topical dimethyl sulfoxide (DMSO) has been investigated ... . In this study, 9 mL of 90% dimethyl sulfoxide were applied twice daily to the entire trunk of 20 healthy volunteers for 3 weeks. The following laboratory tests were done: complete blood count, urinalysis, blood sedimentation rate, and SGOT, BUN, and fasting blood sugar determinations. At the end of the study, all laboratory values had remained normal. Except for the appearance of such cutaneous signs as erythema, scaling, contact urticaria, and stinging and burning sensations, the drug was tolerated well by all but two individuals, who developed systemic symptoms. In one, a toxic reaction developed on the 12th day, characterized by a diffuse erythematous and scaling rash accompanied by severe abdominal cramps; the other had a similar rash and complained of nausea, chills, and chest pains. These signs, however, abated in spite of continued administration of the drug. [Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 360]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: To investigate possible side effects of chronic exposure to dimethyl sulfoxide, ... 20 volunteers were painted with 9 mL of 90% dimethyl sulfoxide over the entire trunk, once daily for a period of 26 weeks. Neither clinical nor laboratory investigations showed adverse effects of the drug. However, most subjects did experience the well known DMSO induced, disagreeable oyster like breath odor, to which they eventually became insensitive. One fatality due to a hypersensitivity reaction has been reported. [Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 360]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Male volunteer subjects, ages 21-55, were treated with DMSO, applied as an 80% gel, to the skin in a single daily dose of 1 g/kg body weight. DMSO was applied daily for 12 weeks. … Dermal exposure and effects on eyes /of/ subjects treated with DMSO exhibited a characteristic respiratory odor, previously identified as dimethyl sulfide, a metabolite. A variable degree of skin reaction was observed, characterized by wheal and erythema, drying and scaling. Other side effects included some sedation, and occasional bouts of insomnia and nausea. With the exception of eosinophilia, no significant abnormalities were observed in blood chemistry, hematology, and urine analysis. DMSO had no significant effect on pulmonary function, EKG or EEG. Subjective eye complaints consisted of mild photophobia and foreign body sensations. Less frequently, tearing, blurring of vision, disturbances in peripheral vision, and tiring of the eyes were mentioned. These symptoms could not be substantiated by ophthalmological examination or testing and did not persist after DMSO was discontinued. There were no differences in accommodation, near point of convergence, ocular tension, cycloplegic retinoscopy, and cycloplegic refraction. Slit lamp examination revealed no abnormal corneal or lens changes. Visual function, and pupillary mydriasis to 1% tropicamide were not altered. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: 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. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Dermal and ocular application 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. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: Two elderly people were given intravenous infusion of dimethylsulphoxide (DMSO) as treatment for arthritis. One became seriously ill, the other remained well. Both had similar changes in aspartate transaminase, hydroxybutyrate dehydrogenase, and creatine kinase and evidence of haemolysis. This is the first report of serum enzyme changes and anaemia after intravenous DMSO in man. [Yellowlees P et al; Lancet 2 (8202): 1004-6 (1980) ]**PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: A 43-year-old Caucasian female applied DMSO to her lower abdomen for treatment of interstitial cystitis. She used 2 treatments separated by 1 1/2 hr consisting of applications of 2 ounces of DMSO mixed with 2 ounces of distilled water on a washcloth over a 6" x 12" skin area, for a total application of 132 g or 1.8 g/kg. ... Within 24 hr the patient developed fatigue and cyanosis, as well as dyspnea with mild exertion which did not worsen over time. Ten days after the DMSO application ... she was mildly dyspneic but fully alert. She /presented/ to the emergency department where her oximetry increased to 54% on oxygen per nasal cannula. ... She had /been/ taking lansoprazole for approximately 2 weeks, starting 11 days prior to onset of the cyanosis, alprazolam for a longer period on an as needed basis, and 200 mg phenazopyridine /three times daily/ starting 3 day after the onset of cyanosis. Her initial laboratory tests were remarkable for a 47% methemoglobin level, a hemoglobin of 9.4 g/dL, a hematocrit of 27.7%, and a reticulocyte count of 5.9%. She received 2 treatments with 1 mg methylene blue/kg iv without significant improvement in either her cyanosis or methemoglobin level. Repeat analysis on a blood sample drawn the day following admission demonstrated a sulfhemoglobin level of 6.2% and a methemoglobin level of < 0.1%. During hospitalization the patient was transfused with 2 units of packed red blood cells. She was discharged on the third hospital day still on oxygen but with continued symptomatic improvement. Her G6PD level was 280 U/ trillion RBC (normal range 146-376). ... Adverse effect: Sulhemoglobinemia after dermal exposure [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: A 63-year-old arthritic patient applied 90% DMSO topically and experienced mixed sensorimotor peripheral neuropathy and segmental demyelination. [Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 1335]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Groups of 4 to 14 unshaven rats (108-182 g) were immersed in a DMSO solution (40, 60, 80 or 100%) until the fur and skin were thoroughly wetted. The animals were then withdrawn from the solution and allow most of the excess solution to run off. From the weights before and after dipping, it was possible to calculate the amount of DMSO. There was no immediate response, but within 24 hours 13/14 rats dipped into 100% DMSO were dead. A complete microscopic examination of tissues revealed no changes. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Three groups of 8 male Sprague-Dawley rats were exposed to an aerosol of 1600 mg DMSO per cubic meter of air for 4 hr. Control rats were exposed to a normal chamber environment. Groups were sacrificed immediately after exposure, another 24 hr after exposure, and the third group was observed for 2 weeks after exposure before sacrifice. There was no mortality and none of the animals displayed outward signs of toxicity during and after exposure to DMSO. After exposure, the hair was damp and slightly yellow, and the animals had a characteristic garlic-like odor. Organs appeared normal at necropsy. Histopathologic examination revealed areas of hemorrhage in lung sections of control and DMSO treated animals. Focal and diffuse collections of clear pneumocytes were noted within lung alveoli in DMSO treated rats; similar edematous changes were not seen in control animals. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Single i.v. injections of undiluted DMSO were administered to groups of 5 male and 5 female Carworth CFN 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. … 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 motor activity and myasthenia. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Slight conjunctivitis in the eyes of rabbits were noted at the 24 hr observation period in the animals undergoing ocular tests. This disappeared by 48 hrs post dosing. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Six pairs (male and female) of young adult beagle dogs received daily oral doses of 0, 2.5, 5, 10, 20 and 40 g/kg/d DMSO, 5 days a week for up to 23 weeks. The 20 and 40 g/kg dose levels were not tolerated by the dogs and were reduced. Changes in the lens of the eye were observed in dogs receiving 5 g/kg after 9 weeks of administration. At lower dose levels by the 18th week all the dogs were affected. Treatment was withheld after 23 weeks and the animals were observed for 31 weeks. The changes persisted after the withdrawal of DMSO but became slightly less pronounced. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Daily i.v. doses of 3 or 2 g/kg DMSO in a 40% solution were given respectively to 4 or 1 male rhesus monkeys for 9 consecutive days. … /Investigators observed a/ rapid fourfold increase in diuresis over the control values in the monkeys receiving 2 or 3 g/kg DMSO. This urine output indicates that DMSO is one of the strongest diuretics known. The absence of any microscopic or gross structural damage to the kidneys suggests that the coffee-colored urine seen after DMSO administration represents a transient erythrocytic hemolysis, possibly caused by an osmotic gradient due to DMSO in the vascular system. Since this effect was short lived and did not significantly alter the red cell count or the hemoglobin and hematocrit values, we believe the coffee-colored urine represented a transient and reversible condition. … The partial thromboplastin time in DMSO treated monkeys decreased from a normal mean of 46 s to a mean of 18.7 s. These values returned to normal when DMSO administration was stopped. Although the PT values in both saline and DMSO Treated monkeys fluctuated slightly before and after Treatment, the values did not significantly differ from the control standard range … An increase in respiratory rate after DMSO was previously reported. It appears from these studies that DMSO acts as a central respiratory stimulant when given iv in bolus form. A rise in minute respiratory volume concomitant with the rise in respiratory rate was also reported. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: A total of 32 male Sprague-Dawley 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. Control rats were exposed to a normal chamber environment. Hemoglobin concentration, packed erythrocyte volume as expressed by the microhematocrit, and total leukocyte and reticulocyte counts were done on all animals. …There were no outward toxic signs noted in any of the exposed animals throughout the experimental period of 6 weeks. The characteristic garlic-like odor was detected in The breath of each of the rats after the first day of exposure, and the hair began to appear slightly yellow after The first week. All animals gained weight normally, showing a mean gain of 95.8 % for the test animals and 92.5 % for the controls. No significant alterations were noted in hemoglobin concentrations, microhematocrit, total leukocyte counts, reticulocyte counts, serum glutamic pyruvic and glutamic-oxalo-acetic transaminase activities, liver alkaline phosphatase activity, or liver lactate concentrations. Gross and histopathologic examinations of organs and tissue were unremarkable except for nonspecific inflammatory changes in the lungs and livers of nearly all animals, including controls. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Medical grade DMSO was applied daily to the shaved backs of rabbits for 30 days at a dose of 1.0 or 5.0 g/kg/day. Rabbits received dermal applications of DMSO to normal and abraded skin for a period of 23 weeks, when ocular changes were observed. Treatment was withheld from animals showing ocular changes; the remaining animals continued to receive DMSO applications for the scheduled 26 weeks (6 months). Mortality was high in all groups, however there was no significant differences in mortality between groups. There were no clinical signs to suggest systemic toxicity. Local dermal reactions of slight erythema and mild edema were observed following each application. The degree of reaction was similar in all groups. Abrasion of the skin did not increase the reaction. Hair growth was normal and there were no dermal reactions observed during the post-treatment observation interval. Water consumption, measured during week 26, was markedly increased in animals receiving 8.1 mg/kg; a lesser increase in water consumption was noted for other groups receiving DMSO. Macroscopic and hematological examinations, organ weight analysis, and histopathology did not reveal any adverse effects. There were no changes in dermal morphology except for random occurrences of inflammatory reaction. Adverse ocular (lenticular) effects were observed. These were restricted to the lens, and consisted of nuclear refractive changes. There was no effect on the peripheral lens, vitreous humor, or retina. Abrasion of the skin had no effect on the incidence of lenticular effects. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 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. Groups of 2 animals of each sex were treated with 1 or 3 mL/kg. Three animals of each sex received 9 mL/kg. Dosages administered were equivalent to 990, 2970, and 8910 mg/kg/day. The principal physical signs seen in the animals given DMSO orally included /SRP: excess salivation/ and emesis. These signs occurred sporadically and did not appear to be related to the dose except in the group receiving 9 mL/kg. ... Anorexia occurred at high oral doses but was not evident at the 2 lower dose levels. ... No DMSO-related changes were found in the treated monkeys during physical examinations. These tests included mean systolic blood pressure, heart rate, respiratory rate, body temperature, 48-hour water consumption, neurological reflexes, and electrocardiograms, performed during weeks 1, 4, 7, 12, 24, 37, 51, and 73 of study. No evidence of refractoriness to tropicamide mydriasis was seen in any of these monkeys. The typical DMSO lenticular changes described in other species were not visible in any monkey during the course of the experiment. No significant differences were found between the DMSO-treated and control monkeys in any of the hematologic or biochemical parameters evaluated. Animals given 1 mL/kg orally responded in a similar manner. ... Further, no significant differences were seen in erythrocyte sedimentation rate (ESR), BSP retention, creatinine clearance, urinalysis, and absolute or relative organ weights between the treated and control animals. No significant lesions attributable to DMSO were found upon gross examination at necropsy. No histologic changes were visible in the lenses of treated animals. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Doses (0, 1, 3, and 9 mL/kg) of a 90 % (v/v) aqueous solution of pharmaceutical grade DMSO were administered dermally to 4 groups of rhesus monkeys 7 days per week. Topical administration was by direct application to the entire abdominal skin. Animals were restrained in a supine position for 1 hour after drug administration to prevent ingestion of the applied solution. Control animals in each group were given water, 9.0 mL/kg body weight. Dosages administered were equivalent to 990, 2970, and 8910 mg/kg/day. All animals treated topically with DMSO exhibited scaling and flaking of the skin in the area of drug application during the initial phases of the study. There were no apparent differences among the various treatment groups. Although several animals had erythema of the skin it did not appear to be related to the dose, and erythema did not occur at regular intervals in any animal. No other adverse behavioral or physical signs were seen that could be attributed to topical application of DMSO. The only ocular abnormality observed was in one animal which had been given 1 mL of DMSO/kg per day dermally for 82 weeks. In the final ocular examination, this animal had a unilateral complete retinal detachment and syneresis of the vitreous humor. There were no biomicroscopically visible changes in the vitreous humor of the remaining animals. There appeared to be several swollen lenticular fibers in the equatorial portion of the lens in the affected eyes. The retina was undergoing cystic changes and the outer limbs of the neuroepithelial cells were sticky. There was no indication of inflammatory activity within the eye although there was an accumulation of inflammatory cells in the periphery of the optic nerve near the globe. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ... Dimethyl sulfoxide ... produces swellings and blisters associated with ionic shifts between compartments in chick embryos by altering permeability of cell membranes and other membranes. [Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 167]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Studies in hamsters, rats, and mice have shown that dimethyl sulfoxide causes teratogenic effects when administered intraperitoneally at high doses of 2.5 to 12 grams per kg of body weight. [Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Studies in rabbits have shown that dimethyl sulfoxide causes teratogenic effects when administered topically at doses of 5 grams per kg of body weight for the first 2 days, then 2.5 grams per kg of body weight for the last 8 days. However, in another study using rabbits, dimethyl sulfoxide was not shown to cause any abnormalities when administered topically at doses of 1.1 grams per kg of body weight on Days 3 through 16 of gestation. [Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Three groups of 25 mated female rats received DMSO by gavage at the dose levels of 200, 1000, and 5000 mg/kg/day as a solution in purified water. DMSO was administered each day from day 6 to day 15 of gestation. A control group of 25 mated females was given the vehicle alone. Day 0 of pregnancy was designated as the day of confirmed mating. Clinical signs including mortality and evidence of abortion were checked daily. Food consumption and body weight were recorded at designated intervals during pregnancy. On day 20 of pregnancy, females were killed. The gravid uterus was weighed and fetuses removed by hysterectomy. Females were examined macroscopically. Litter parameters were recorded: number of corpora lutea, implantation sites, early and late resporptions, and dead and live fetuses. Fetuses were weighed, sexed, and submitted to external examination and then to soft tissue or skeletal examinations. Maternal data: There were no clinical signs observed in treated or control groups. No maternal deaths or abortions occurred in any group. Lower food consumption and body weight gain were noted in females of the 5000 mg/kg group. No macroscopic findings were noted at necropsy in any of the females. Litter data: Pre- and post-implantation losses were similar in all groups. No treatment-related effects were observed on the number of fetuses or the sex ratio. In the 5000 mg/kg/day group, fetal body weights were slightly lower than that of controls, an indirect consequence, at least in part, of decreased maternal food consumption and body weight gain. Fetal examination: No external malformations or anomalies were observed in fetuses from any group. An increased incidence of two soft tissues anomalies were observed: dilated renal pelvis for fetuses in all treated groups, which was associated at 5000 mg/kg/day with an increased incidence of dilated ureter(s). No treatment-related soft tissue malformations were observed. There were no treatment-related skeletal variations or malformations in any group. An increased incidence of reduced or delayed ossification of ribs was observed in fetuses of the 5000 mg/kg group. This skeletal anomaly is considered to be a consequence of the lowered fetal body weights observed for this group. No treatment-related microscopic changes were noted in the kidneys of fetuses with dilated renal pelvis. Dilation of the renal pelvis may be related to the diuretic properties of DMSO. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Pregnant hamsters were administered a single intraperitoneal injection of 0.5 mL undiluted DMSO on day 8 of gestation and the embryos were examined 1 to 3 days later. DMSO was found to be embryotoxic, the embryocidal effect being most marked in litters from mothers weighing less than 110 g at the time of injection. Various degrees of exencephaly and anencephaly were found in those embryos surviving up to 3 days after the injection. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: 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. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: DMSO was tested in the Salmonella typhimurium pre-incubation protocol at concentrations of DMSO (100, 333, 1000, 3333, 10000 ug) /with strains TA97, TA98, TA100, TA102, TA104, TA1537, and TA1538/. The five doses were tested in triplicate; repeat tests were performed after the initial trial. A maximum volume of 0.05 mL was added to each plate. DMSO was negative, in the presence and absence of metabolic activation. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: DMSO was tested in the standard plate incorporation assay using five S. typhimurium tester strains (TA 98, 100, 1535, 1537, 1538). Multiple geometric dilutions were tested in duplicate plates, starting with the maximum non-toxic dose of 500 mg per plate. DMSO was negative, in the presence and absence of metabolic activation, in all strains tested. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: 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. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: Groups of 15 male mice were injected intraperitoneally with 5, 7.5, and 10 g/kg DMSO twice at an interval of about 20 hours. Surviving males were paired with untreated virgin females, which were replaced at weekly intervals for five consecutive weeks. … During the first week of matings, pregnancy rates were reduced in females paired with 10 g/kg males. Rates increased in subsequent weeks, and were comparable to controls by week 5. Pregnancy rates of females paired with males given 5 and 7.5 g/kg were similar to controls. Total implantation rates were reduced in females paired with 7.5 and 10 g/kg males during week 1. There were no significant differences in implantations in subsequent weeks. The number of dead implantations in females mated to DMSO-treated males did not differ from that of controls during the entire test interval. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: DMSO was injected intraabdominally into 1-2-day-old Drosophila melanogaster males at concentrations of 0.1, 1 and 5%; the volume injected was 0.2 µl per fly. Rod-X and ring-X bearing males were used to test for sex-linked recessive lethals and for sex chromosome loss, respectively. Controls consisted of males that were not injected, and males that received saline injections. One day after treatment, each male was individually crossed with three 4-day-old virgin females. In order to collect post meiotic and premeiotic germ cell stages separately, males were mated every two days to a new set of females. Males were mated five times to obtain broods A to E. Mortality and sterility of treated males were recorded during the breeding program. Increased mortality was observed in all injected males; DMSO did not enhance mortality when compared to saline. 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. Data from later broods showed lower frequencies of sex chromosome loss than those from the first brood. This tendency was also observed in untreated controls. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: DMSO increased enzymatic activity of glucagon and guanylylimidodiphosphate. Effect of DMSO on rat hepatic adenylate cyclase reversible and stimulatory effect of DMSO on enzymatic activity was observed in persistent active state induced by preincubation with guanylylimidodiphosphate. [Hynie S et al; Naunyn-Schmiedeberg's Arch Pharmacol 310 (3): 231 (1980) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Human corneal epithelium incubated in organ culture for 20-28 hr and exposed to DMSO 2, 4, 6, 8, 6, 4 and 2% successively for 10 min. Latent cell damage at 31 deg C. Toxic at 4 deg in pure serum and Dulbecco's medium. [Sperling et al; Acta Ophthalmol (copenh) 57 (5): 891 (1979) ]**PEER REVIEWED**
  • IMMUNOTOXICITY: Autoimmune strain MRL/Ipr, C3H/lpr, and male BXSB mice were placed on a continuous treatment regimen with 3% DMSO or 3% DMS02 in the drinking water, ad libitum, commencing at 1 to 2 months of age, before spontaneous autoimmune lymphoproliferative disease development could be detected. This represented doses of 8-10 g/kg/day of DMSO and 6-8 g/kg/day of DMS02. Both compounds were observed to extend the mean life span of MRL/Ipr mice from 5.5 months to over 10 months of age. All strains showed decreased antinuclear antibody responses and significant diminution of lymphadenopathy, splenomegaly, and anemia development. Serum IgG levels and spleen IgM antibody plaque formation, however, did not differ from control values. There was no indication of involvement of systemic immunosuppressive or antiproliferative effects, and treated animals were observed to remain healthy and vigorous with no signs of toxicity. These results demonstrate that high doses of both DMSO and its major in vivo metabolite, DMSO2, provide significant protection against the development of murine autoimmune lymphoproliferative disease. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • IMMUNOTOXICITY: The effect of intraperitoneal DMSO on serum immunoglobulin levels was evaluated for matched groups of 10 animals given daily intraperitoneal injections of 0.1 or 0.2 mL of undiluted DMSO. After three injections of 0.2 mL, only six animals survived and immunoglobulin concentrations were determined on the fourth day. Animals given 0.1 mL received 7 daily injections and their serum immunoglobulin levels were assayed on the 8th day. Surviving animals given 0.2 mL DMSO (8.8g/kg) demonstrated a 60-80% drop in IgG subclasses, a 64% drop in IgA, and a 50% drop in IgM. Animals given 0.1 mL (4.4g/kg) experienced a 30% drop for IgG subclasses and a 21% drop for IgA. IgM levels remained unchanged. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat oral 17.9 mL/kg [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 573]**PEER REVIEWED**
  • LD50 Rat oral 14500 g/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Rat ip 8200 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Rat sc 12000 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 rat iv 5360 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Mouse oral 7920 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Mouse ip 2500 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Mouse iv 3800 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**
  • LD50 Dog iv 2500 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1364]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Following topical application, DMSO is absorbed and widely distributed in tissue and body fluids. DMSO and dimethyl sulfone are excreted in the urine and feces. DMSO is eliminated through the breath and skin and is responsible for the characteristic garlic odor. ... Dimethyl sulfone can persist in serum > 2 weeks after a single intravesical instillation. No residual accumulation of DMSO has occurred after treatment from protracted periods of time. [Novak, K.M. (ed.). Drug Facts and Comparisons 59th Edition 2005. Wolters Kluwer Health. St. Louis, Missouri 2005., p. 720]**PEER REVIEWED**
  • Dimethyl sulfoxide and one of its metabolites, dimethyl sulfone, are excreted in the urine and feces. The other metabolite, dimethyl sulfide, is eliminated via breath and through the skin. [Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. ]**PEER REVIEWED**
  • It is not known whether dimethyl sulfoxide is excreted in breast milk and problems in humans have not been documented [Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. ]**PEER REVIEWED**
  • In man radioactivity of 35S DMSO appeared in blood 5 min after cutaneous application. One hour later, radioactivity could detected in bones. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • DMSO was administered orally /to human volunteers/ at a dose of 1g/kg as a 70% aqueous solution; a dose of 1 g/kg was administered dermally. DMSO was readily absorbed when administered dermally, peak serum levels occurring after 4 to 8 hr. Orally administered DMSO was rapidly absorbed, reaching a peak serum level in 4 hr. Serum levels of DMSO were undetectable after 120 hr. Both unchanged DMSO and a metabolite, dimethylsulfone (DMSO2) were isolated from urine. Dimethylsulfone appeared in serum after about 48 hr and persisted for as long as 400 hr. Urinary excretion of DMSO after dermal and oral administration amounted to approximately 13% and 30-68% of the dose, respectively. Excretion of DMSO2 was about 5 to 10% and 21 to 23%, respectively. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • S35-DMSO was administered to rats orally, animals were killed at various times and the tissues were assayed for total radioactivity. There were appreciable concentrations of radioactivity in all tissues 0.5 hr after an oral dose. Plasma, kidney, spleen, lung,heart and testes appeared to have somewhat higher levels than liver, fat, small intestine, brain, skeletal muscle and red cells. Concentrations in the testes, brain skeletal muscle and heart increased after 0.5 hr, but remained virtually constant in other tissues. Levels had declined to minimal values in all tissues after 24 hr. ... The ratio of DMSO2 to DMSO in rats 4 hr after oral administration of S35-DMSO was found to be virtually constant in liver, testes, kidney, spleen, small intestine, heart and plasma, averaging about 6.5% (range of 4.1-10.6% for tissues of 2 rats). [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • The rate of passage of dermally applied S35-DMSO through the skin was also estimated in rats and rabbits. Eight rats were dosed dermally with 0.55 g/kg of S35-DMSO. Two animals each were sacrificed after 30 min, 1 hr, 2 hr and 24 hr respectively. In rats, after 30 min, 63% (average) of the dose remained at the site of application; after 1 hr, 19% (average) of the dose remained; and, after 2 hr, 14% (average) was left. After 24 hr, the radioactivity at the site of application was the same as that of the surrounding skin. Six rabbits were similarly treated. In 2 animals, sacrificed after 30 min, 85% (average) of the dose remained at the site of application. After 4 hr, 11% (average) remained, and, after 24 hr, the radioactivity was essentially equal to that of the surrounding skin. Radioactivity in respired air was measured from 2 rats given 0.55 g/kg of S35-DMSO (approximately 8 uC) dermally. An average of 6.0% of the dose was found in the respired air. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • Urinary excretion of DMSO /in monkeys/ increased rapidly, reached a steady state level of approximately 9 gms/day after 2 days. The increase in DMSO excretion at 5 days reflected an increased urine volume on that day. DMSO disappeared rapidly from urine after treatment ended and only trace amounts were detected after 72 hrs. About 128 gms, or 60% of the ingested DMSO was excreted in the urine unchanged. ... Urinary excretion of DMSO2 increased slowly and reached a maximum of about 3 gms/day after 5 days of DMSO Administration. Excretion remained between 2-3 gms/day during the remainder of oral DMSO. Once DMSO treatment stopped, urinary DMSO2 declined slowly over the next 5 days. Approximately 33 gms, or about 16% of the ingested DMSO was excreted in urine as DMSO2. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**
  • Plasma concentrations of DMSO, dimethylsulfone (DMSO2), and dimethylsulfide (DMSH2) were assessed in 10 patients who underwent autologous transplants with stem cells, cryopreserved in 10% DMSO (vol/vol). Blood was sampled at multiple times after the stem-cell infusion. Urine was pooled during the 24 hours postinfusion. DMSO, DMSO2, and DMSH2 were assayed simultaneously by gas chromatography. A one-compartment model with saturable elimination proved most suitable for fitting plasma DMSO concentration-versus-time data. Stem-cell volumes infused ranged between 180 and 585 mL (254 to 824 mmol DMSO). Infusions lasted between 20 and 120 minutes. Peak plasma DMSO concentrations were 19.1 +/- 6.3 mmol/L (mean +/- SD). Pharmacokinetic parameters for volume of the central compartment (Vc), maximum velocity (Vmax), and Michaels-Menten constant (Km) were 37.3 +/- 17 L, 0.99 +/- 0.57 mmol/L/hr, and 5.2 +/- 5.0 mmol/L, respectively. Plasma DMSO2 concentrations increased during the first 24 hours, plateaued at 4.4 +/- 1.2 mmol/L, and remained there until 48 hours (the last sample). DMSH2 concentrations were at steady-state by 5 minutes and remained between 3 and 5 mmol/L for 48 hours. Urinary excretion of DMSO and DMSO2 accounted for 44% +/- 4% and 4% +/- 1%, respectively, of the administered DMSO dose. Renal clearance of DMSO was 14.1 +/- 3.4 mL/min. These data (1) document plasma concentrations of DMSO and metabolites in patients following peripheral-blood stem-cell transplants; (2) allow consideration of potential effects of these concentrations on stem-cell engraftment and drug-drug interactions; and (3) can facilitate a concentration-guided phase I trial of DMSO. [Egorin MJ et al; J Clin Oncol. 16(2): 610-5 (1998) ]**PEER REVIEWED**

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Metabolism/Metabolites

  • Dimethyl sulfoxide is metabolized to dimethyl sulfone and dimethyl sulfide. [Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. ]**PEER REVIEWED**
  • In man, DMSO is oxidized into dimethylsulfone DMSO2, metabolite excreted by urine (17-22 %). DMSO is reduced into dimethylsulfide, DMS, a volatile metabolite, responsible for garlic odour of exhaled air (1 %). About 85 % is excreted unchanged, both by urine (50 %) and feces (50 %). [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Dimethyl sulfoxide as of June 7, 2005. ]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008