title: Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.
abstract: Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.
authors.affiliation: Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
authors.forename: M A
authors.initials: MA
authors.lastname: Valentovic
authors.forename: J G
authors.initials: JG
authors.lastname: Ball
authors.forename: D K
authors.initials: DK
authors.lastname: Anestis
authors.forename: K W
authors.initials: KW
authors.lastname: Beers
authors.forename: E
authors.initials: E
authors.lastname: Madan
authors.forename: J L
authors.initials: JL
authors.lastname: Hubbard
authors.forename: G O
authors.initials: GO
authors.lastname: Rankin
mesh_terms: D000208:Acute Disease; D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D000814:Aniline Compounds; D006846:Hydrocarbons, Halogenated; C066212:2-fluoroaniline; C025257:2-chloroaniline; C023650:aniline