Developmental toxicity of thiodiglycol in Sprague-Dawley rats.
Thiodiglycol (TG), a hydrolysis product of sulfur mustard (HD), is a potential contaminant of soil and water at certain military sites. To establish developmental toxicity criteria for TG, an oral developmental toxicity study was conducted in Sprague-Dawley rats. Neat thiodiglycol (99.9 %) was administered orally to mated female rats from gestation days (GDs) 5 through 19. The day of positive mating was considered day 0. A pilot study was conducted with TG at dose levels 250, 500, 1,000, 2,000, or 5,000 mg/kg to select suitable doses for the main study. In the main study, three groups of rats (25/group) received TG by gavage at dose levels of 430, 1,290, or 3,870 mg/kg/day. A fourth group served as a sham control. On day 20 of gestation, all females were euthanized and a cesarean section performed. Litters were examined for soft tissue and skeletal alterations. Maternal toxicity was limited to dams receiving TG at 3,870 mg/kg/day. At this dose, body weights and food consumption were reduced during certain periods of gestation. Fetuses derived from those dams exhibited a nonstatistically significant increased incidence of variations when compared to controls. Fetal body weights in the 3,870 mg/kg/day group were significantly lower than controls. There was no increased incidence of anomalies when thiodiglycol-treated fetuses were compared to controls. It was concluded that TG did not produce terata. Developmental toxicity (decreased fetal weights and associated delays in development) occurred only at the maternally toxic dose of 3,870 mg/kg. It appears that 1,290 mg/kg/day could be considered no observed adverse effect level (NOAEL) for oral developmental toxicity. The lowest observed adverse effect level (LOAEL) was 3,870 mg/kg for maternal toxicity.
Directorate of Toxicology, U.S. Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, Maryland, USA.
John T
JT
Houpt
Lee C B
LC
Crouse
Richard A
RA
Angerhofer
Glenn J
GJ
Leach
Gunda
G
Reddy
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*
D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D013723:Teratogens; C047519:2,2'-thiodiethanol