Acute renal and hepatic effects induced by 3-haloanilines in the Fischer 344 rat.
Haloanilines are commonly used as chemical intermediates in the manufacture of a wide range of products. The purpose of this study was to examine the in vivo nephrotoxic and hepatotoxic potentials of the 3-haloanilines. The in vitro effects of the 3-haloanilines on renal function were also examined. In the in vivo experiments, male Fischer 344 rats (four rats/group) were administered a single intraperitoneal (i.p.) injection of an aniline hydrochloride (1.0 or 1.25 mmol kg-1) or vehicle. Renal and hepatic function were monitored at 24 and/or 48 h post-treatment. None of the 3-haloanilines were potent nephrotoxicants at either dose level. The greatest effects on renal function were observed following administration of 3-chloroaniline at a dose of 1.25 mmol kg-1 (oliguria, glucosuria, hematuria, decreased p-aminohippurate accumulation by renal cortical slices and increased blood urea nitrogen concentration). 3-Chloroaniline also was the only aniline compound to increase plasma ALT/GPT activity at 48 h. In the in vitro experiments, the ability of an aniline (10(-5) - 10(-3) M) to decrease organic ion accumulation in renal cortical slices from untreated rats was examined. The decreasing order of in vitro nephrotoxic potential was 3-iodoaniline > 3-bromoaniline > 3-chloroaniline > aniline > 3-fluoroaniline. These results indicate that the 3-haloanilines are not potent nephrotoxicants or hepatotoxicants at sublethal doses. In addition, the reasons why the 3-haloanilines have different orders of nephrotoxic potential in vivo and in vitro are not clear at this time.
Rankin
G O
GO
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310, USA.
Valentovic
M A
MA
Nicoll
D W
DW
Ball
J G
JG
Anestis
D K
DK
Brown
P I
PI
Hubbard
J L
JL
D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D004435:Eating; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced; D008099:Liver / Q000187:drug effects*; D008297:Male; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014554:Urination / Q000187:drug effects
D000814:Aniline Compounds; D002273:Carcinogens; C023650:aniline