Metabolism of [14C]trichloroethylene to14CO2and interaction of a metabolite with liver DNA in rats and mice

Abstract

Male Sprague‐Dawley rats and male B6C3F1 mice excreted 5–15% of a tracer dose of [ ¹⁴ C]trichloroethylene as ¹⁴ CO ₂ within 24 h after ip injection of a single dose in a corn‐oil vehicle. The proportion of the dose excreted as CO ₂ was greater in mice than in rats, but increased in the rats after starvation or pretreatment with phenobarbital. As the dose was increased toward the LD50 level, the proportion excreted as ¹⁴ CO ₂ decreased slightly, but this was largely due to increased loss of unchanged trichloroethylene. The excretion of ¹⁴ CO ₂ was thus correlated with the expected level of microsomal metabolism of trichloroethylene to an electrophilic intermediate capable of binding to glutathione or macromolecules. Liver protein labeling was observed to be relatively high (10,000–23,000 cpm/mg in the mouse), while DNA labeling was consistently observed to be very low, not allowing identification of any adducts by high‐performance liquid chromatography (HPLC). Also, no effect on DNA fragmentation was seen by alkaline sucrose gradient centrifugation after injection of an LD50 dose of trichloroethylene. The ability of trichloroethylene to interact with DNA in vivo was thus observed to be very slight.