Dose response effects of 4,4-methylenebis(o-chloroaniline) (101144) (MOCA) were investigated in protein adequate (PA) and protein deficient (PD) male rats. Rats were fed either 0, 250, 500, or 1,000 parts per million (ppm) MOCA in PA groups, or 0, 125, 250, or 500ppm in PD groups for 18 months. Correlations between the amounts of urinary MOCA excreted at various dosages and tumor production were calculated. Survival of all rats decreased with increasing MOCA doses, and mean weight gains in PD rats were less than in PA rats. Mean hematocrit and hemoglobin values of the 1,000ppm PA and 500ppm PD groups differed significantly from controls. Neoplasms were observed, particularly in the lungs of rats on either diet. There also was a high incidence of liver tumors in rats fed 1,000ppm MOCA in a PD diet. A linear dose response relationship was observed for lung cancers. Three other types of tumors were observed (mammary adenocarcinoma, Zymbal gland carcinoma, and hemangiosarcoma). Total number of rats with neoplasms and the number of multiple neoplasms increased with increasing MOCA doses in both groups. Mean MOCA urinary concentrations did not vary directly with MOCA diet concentrations. The largest increases in MOCA urine values correlated with hepatocellular carcinoma. The authors conclude that the mechanisms of lung and liver cancer induction by MOCA were different and mutually suppressive.
Journal of Environmental Pathology and Toxicology. Toxicological and Carcinogenic Health Hazards in the Workplace: proceedings of the First Annual NIOSH Scientific Symposium, Cincinnati, Ohio, April 1978
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