title: Toxicity assessment of thiodiglycol.
abstract: Sulfur mustard (HD) undergoes hydrolysis to form various products such as thiodiglycol (TG) in biological and environmental systems. TG is a precursor in the production of HD and it is also considered as a "Schedule 2" compound (dual-use chemicals with low to moderate commercial use and high-risk precursors). Several toxicological studies on TG were conducted to assess environmental and health effects. The oral LD(50) values were >5000 mg/kg in rats. It was a mild skin and moderate ocular irritant and was not a skin sensitizer in animals. It was not mutagenic in Ames Salmonella, Escherichia coli, mouse lymphoma, and in vivo mouse micronucleus assays, but it induced chromosomal aberrations in Chinese hamster ovarian (CHO) cells. A 90-day oral subchronic toxicity study with neat TG at doses of 0, 50, 500, and 5000 mg/kg/day (5 days/week) in Sprague-Dawley rats results show that there are no treatment-related changes in food consumption, hematology, and clinical chemistry in rats of either sex. The body weights of both sexes were significantly lower than controls at 5000 mg/kg/day. Significant changes were also noted in both sexes in absolute weights of kidneys, kidney to body weight ratios, and kidney to brain weight ratios, in the high-dose group. The no-observed-adverse-effect level (NOAEL) for oral toxicity was 500 mg/kg/day. The developmental toxicity conducted at 0, 430, 1290, and 3870 mg/kg by oral gavage showed maternal toxicity in dams receiving 3870 mg/kg. TG was not a developmental toxicant. The NOAEL for the developmental toxicity in rats was 1290 mg/kg. The provisional oral reference dose (RfD) of 0.4 mg/kg/day was calculated for health risk assessments. The fate of TG in the environment and soil showed biological formation of thiodiglycalic acid with formation of an intermediate ((2-hydroxyethyl)thio)acetic acid. It was slowly biodegraded under anaerobic conditions. It was not toxic to bluegill sunfish at 1000 mg/L and its metabolism and environmental and biochemical effects are summarized.
authors.affiliation: Directorate of Toxicology, U.S. Army Center for Health Promotion and Preventive Medicine, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403, USA. gunda.reddy@us.army.mil
authors.forename: Gunda
authors.initials: G
authors.lastname: Reddy
authors.forename: Michael A
authors.initials: MA
authors.lastname: Major
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Leach
mesh_terms: D000818:Animals; D017753:Ecosystem; D004781:Environmental Exposure; D004791:Enzyme Inhibitors / Q000633:toxicity; D006801:Humans; D007928:Lethal Dose 50; D009151:Mustard Gas / Q000737:chemistry; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D012869:Skin Absorption; D012997:Solvents / Q000633:toxicity; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D004791:Enzyme Inhibitors; D012997:Solvents; D013438:Sulfhydryl Compounds; C047519:2,2'-thiodiethanol; D009151:Mustard Gas