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Developmental toxicity of thiodiglycol in Sprague-Dawley rats.
Int J Toxicol. 2007 Jul-Aug; 26(4):365-71.IJ

Abstract

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.

Authors+Show Affiliations

Directorate of Toxicology, U.S. Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17661228

Citation

Houpt, John T., et al. "Developmental Toxicity of Thiodiglycol in Sprague-Dawley Rats." International Journal of Toxicology, vol. 26, no. 4, 2007, pp. 365-71.
Houpt JT, Crouse LC, Angerhofer RA, et al. Developmental toxicity of thiodiglycol in Sprague-Dawley rats. Int J Toxicol. 2007;26(4):365-71.
Houpt, J. T., Crouse, L. C., Angerhofer, R. A., Leach, G. J., & Reddy, G. (2007). Developmental toxicity of thiodiglycol in Sprague-Dawley rats. International Journal of Toxicology, 26(4), 365-71.
Houpt JT, et al. Developmental Toxicity of Thiodiglycol in Sprague-Dawley Rats. Int J Toxicol. 2007 Jul-Aug;26(4):365-71. PubMed PMID: 17661228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental toxicity of thiodiglycol in Sprague-Dawley rats. AU - Houpt,John T, AU - Crouse,Lee C B, AU - Angerhofer,Richard A, AU - Leach,Glenn J, AU - Reddy,Gunda, PY - 2007/7/31/pubmed PY - 2007/10/12/medline PY - 2007/7/31/entrez SP - 365 EP - 71 JF - International journal of toxicology JO - Int J Toxicol VL - 26 IS - 4 N2 - 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. SN - 1091-5818 UR - https://www.unboundmedicine.com/medline/citation/17661228/Developmental_toxicity_of_thiodiglycol_in_Sprague_Dawley_rats_ DB - PRIME DP - Unbound Medicine ER -