Ninety day toxicity study of chloroacetic acids in rats.
Chloroacetic acids are produced in drinking water as a result of disinfection processes. Chloroacetic acids are also metabolites of widely used and toxic halogenated hydrocarbons. Thus, chronic human exposure to these chemicals is likely to occur. The objective of the present study was to examine the toxic effects of monochloroacetic acid (MCA), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) in a 90-day subchronic study in rats via oral exposure by drinking water. Chloroacetic acid solutions were prepared at concentrations which provided an approximate intake of 1/4 the LD50 dose per day: MCA, 1.9 mM; DCA, 80.5 mM; TCA, 45.8 mM. Control rats received distilled water only. After 90 days, major organs were removed, fixed, paraffin embedded, and stained. Light microscopic examination of the major organs revealed variable degrees of alterations in the lung and liver of all three treated groups. In the liver, morphological changes were predominantly localized to the portal triads, which were mildly to moderately enlarged with random bile duct proliferation, extension of portal veins, fibrosis, edema, and occasional foci of inflammation. In the lungs, minimal alterations were observed as foci of perivascular inflammation on small pulmonary veins. Morphological changes in the testes and brain were seen only in the DCA treated group. Testes were atrophic with few spermatocytes and no mature spermatozoa. Focal vacuolation and gliosis were present in the forebrain and brainstem. The results of these studies indicate that, relative to their respective LD50 values, DCA given at 80.5 mM is more toxic than TCA given at 45.8 mM and MCA at 1.9 mM is least toxic.
Bhat
H K
HK
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Kanz
M F
MF
Campbell
G A
GA
Ansari
G A
GA
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D003999:Dichloroacetic Acid / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000473:pathology; D014238:Trichloroacetic Acid / Q000633:toxicity*
D000085:Acetates; C006972:chloroacetic acid; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid