FAILURE OF MONOCHLOROACETIC ACID AND TRICHLOROACETIC ACID ADMINISTERED IN THE DRINKING WATER TO PRODUCE LIVER CANCER IN MALE F344/N RATS

Abstract

The chlorinated acetic acids monochloroacetic acid (MCA) and trichloroacetic acid (TCA) are found as chlorine disinfection by-products in finished drinking-water supplies. TCA has been demonstrated to be a mouse liver carcinogen. A chronic study in which male Fischer 344/N rats were exposed for 104 wk to TCA and MCA in the drinking water is described. Animals, 28 d old, were exposed to 0.05, 0.5, or 2 g/L MCA, or 0.05, 0.5, or 5 g/L TCA. The 2.0 g/L MCA was lowered in stages to 1 g/L when the animals began to exhibit signs of toxicity. A time-weighted mean daily MCA concentration (MDC) of 1.1 g/L was calculated over the 104-wk exposure period. Time-weighted mean daily doses (MDD) based upon measured water consumption were 3.5, 26.1, and 59.9 mg/kg/d for 0.05, 0.5, and 1.1 g/L MCA, respectively; TCA MDD were 3.6, 32.5, and 363.8 mg/kg/d. Nonneoplastic hepatic changes were for the most part spontaneous and age related. No evidence of hepatic neoplasia was found at any of the MCA or TCA doses. The incidence of neoplastic lesions at other sites was not enhanced over that in the control group.