title: Subchronic hepatotoxicity evaluation of 1,2,4-tribromobenzene in Sprague-Dawley rats.
abstract: Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.
authors.affiliation: The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Darol E
authors.initials: DE
authors.lastname: Dodd
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Pluta
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sochaski
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Funk
authors.forename: Russell S
authors.initials: RS
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001969:Bromobenzenes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D059550:Toxicity Tests, Subchronic
chemical_list: D001969:Bromobenzenes; C026924:1,2,4-tribromobenzene