Studies of acute nephrotoxic potential of trichloroethylene in Fischer 344 rats.
Group of male Fischer 344 rats, after pretreatment with phenobarbital (80 mg/kg, ip, 3 d), were treated ip in corn oil with 0, 5.5, 11.0, and 22.0 mmol trichloroethylene (TRI) per kg body weight. Urines were collected 24 h after the treatment and the animals were then sacrificed. The nephrotoxicity of TRI was then studied by measuring certain biochemical parameters characteristic of renal injury and its in vivo metabolism by quantitating the TRI principal urinary metabolites. Treatment of rats with TRI up to 11 mmol/kg did not influence any of the measured biochemical parameters of nephrotoxicity. On the other hand, significant increases in the urinary level of N-acetyl-beta-glucose-D-aminidase (NAG) and glucose as well as serum urea nitrogen were observed at 24 h only at the highest dose level (22 mmol/kg) or TRI. Urinary excretions of both trichloroethanol and trichloroacetic acid reached an apparent saturation at the highest dose level of TRI. In inhalation studies, urinary levels of gamma-glutamyltranspeptidase, NAG, glucose, proteins, and serum urea nitrogen were significantly increased at 24 h when rats were exposed to either 1000 or 2000 ppm TRI for 6 h. The capacity of renal cortical slices to accumulate p-aminohippurate was significantly reduced 24 h after the exposure to 22 mmol TRI/kg (ip), or to 1000 or 2000 ppm TRI. These results have demonstrated that TRI exerts its acute nephrotoxic potential at a very high dose level and produces nephrotoxic insult at the proximal tubular and possibly glomerular regions of the rat kidney, whether exposed by inhalation or by an ip route. These data further indicate an involvement of a capacity-limited metabolism in the expression of acute nephrotoxicity due to TRI in Fischer 344 rats.
Chakrabarti
S K
SK
Médecine du Travail et Hygiène du Milieu, Faculté de Médecine, Université de Montréal, Québec, Canada.
Tuchweber
B
B
D000284:Administration, Oral; D000818:Animals; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008452:Maximum Allowable Concentration; D051381:Rats; D011916:Rats, Inbred F344; D014241:Trichloroethylene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
D014241:Trichloroethylene