Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.
Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.
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Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Dow
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Foster
J R
JR
Hext
P M
PM
D000280:Administration, Inhalation; D000284:Administration, Oral; D000641:Ammonia / Q000652:urine; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002118:Calcium / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005561:Formates / Q000652:urine*; D006490:Hemostatics; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000652:urine*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine
D018685:Anesthetics, Inhalation; D015415:Biomarkers; D005561:Formates; D006490:Hemostatics; C030544:formic acid; D014241:Trichloroethylene; D000641:Ammonia; D002118:Calcium