Tissue distribution of monochloroacetic acid and its binding to albumin in rats

Abstract

Distribution of monochloroacetic acid (CA) was studied in rats given a single oral dose of 0.1 mmole/kg body weight [1-14C]CA, by gavage. The animals were sacrificed at 4, 8, 12, 24 and 48 hr following the treatment. The distribution of 14C-label, determined in different tissues, suggests that CA is rapidly absorbed and eliminated from the body. The elimination phase appears to be fast for intestine and kidney as compared to other tissues. Maximum radioactivity was detected in intestine and kidney at 4 and 8 hr following the treatment which was followed by liver, spleen, testes, lung, brain and heart in a decreasing order. A group of rats treated with a single oral dose of 1 mmole/kg [1-14C]CA, by gavage, was also sacrificed at 24 hr following the exposure to study the effect of a higher dose on distribution of [1-14C]CA. The distribution of 14C-label at both dose levels indicates that toxicokinetic properties of CA are dose-dependent. Another group of rats administered 1 mmole/kg [1-14C] CA daily for three days was also sacrificed at 24 hr following the last dose to evaluate the bioaccumulating properties of CA and/or its metabolites in the tissues. As compared to the number of doses given, the accumulation of 14C-label was not as large as expected. 14C-Label determined in the dialyzed plasma, suggests an in vivo binding of 14C-label to plasma proteins where albumin accounted for about 65% as determined by affinity chromatography. Isolation and identification of the adducts of amino acids will help in understanding the mechanism of CA toxicity and development of a suitable biomarker of CA exposure.