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

The chlorinated acetic acids monochloroacetic acid (MCA) and trichloro acetic acid (TCA) are found as chlorine disinfection by-products in fi nished drinking-water supplier. TCA has been demonstrated to be a mous e liver carcinogen. A chronic study in which male Fischer 344/N rats w ere exposed for 104 wk to TCA and MCA in the drinking water is describ ed. Animals, 28 d old, were exposed to 0.05, 0.5, or 2 g/L MCA, or 0.0 5, 0.5, or 5 g/L TCA. The 2.0 g/L MCA was lowered in stages to 1 g/L w hen the animals began to exhibit signs of toxicity. A time-weighted me an daily MCA concentration (MDC) of 1.1 g/L was calculated over the 10 4-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 spontane ous 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. Drinking water concentrations of greater than or equal to 0.5 g/L MCA produced a mod erate to severe toxicity as reflected by a depressed water consumption and growth rate. A no-observed-effects level (NOEL) for carcinogenici ty of 0.5 g/L (26.1 mg/kg/d) MCA was calculated. TCA at drinking water levels as high as 5 g/L produced only minimal toxicity and growth inh ibition and provided a NOEL of 364 mg/kg/d. Our results demonstrate th at under the conditions of this bioassay, MCA and TCA were not tumorig enic in the male F344/N rat.