Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies

Toxicology. 1998 May 15;127(1-3):39-47. doi: 10.1016/s0300-483x(98)00020-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Ammonia / urine
  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Inhalation / toxicity*
  • Anesthetics, Inhalation / urine
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Calcium / urine
  • Dose-Response Relationship, Drug
  • Formates / urine*
  • Hemostatics
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / urine*
  • Male
  • Rats
  • Rats, Inbred F344
  • Trichloroethylene / administration & dosage
  • Trichloroethylene / toxicity*
  • Trichloroethylene / urine

Substances

  • Anesthetics, Inhalation
  • Biomarkers
  • Formates
  • Hemostatics
  • formic acid
  • Trichloroethylene
  • Ammonia
  • Calcium