Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.
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.
Valentovic
M A
MA
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
Ball
J G
JG
Anestis
D K
DK
Beers
K W
KW
Madan
E
E
Hubbard
J L
JL
Rankin
G O
GO
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
D000814:Aniline Compounds; D006846:Hydrocarbons, Halogenated; C066212:2-fluoroaniline; C025257:2-chloroaniline; C023650:aniline