Effects of tris(4-chlorophenyl)methanol on the rat following short-term oral exposure

The systemic toxicity of tris(4-chlorophenyl)methanol (TCPM) was studied in male and female rats following 4 weeks dietary exposure dosed at 1, 10 and 100 ppm. An increased spleen to body weight ratio was observed in males at 10 and 100 ppm and in females at 100 ppm. An increased liver to body weight ratio was detected in both sexes at 100 ppm. Dose-related increases in hepatic Phase-I (AH, APDM, EROD and PROD) and Phase-II (UDPGT, GST) enzyme activities were observed generally at 10 and 100 ppm, with the elevation in PROD activity being the most marked. Increased urinary ascorbic acid was detected in both males and females after 1 week of treatment at 100 ppm and after 4 weeks of treatment at 10 and 100 ppm. At 10 and 100 ppm, elevated % lymphocytes were found in males, and higher white blood cell and lymphocyte counts were observed in females. In the liver, mild to moderate cytoplasmic changes consistent with proliferation of smooth endoplasmic reticulum were present in rats of both sexes at 10 and 100 ppm, and increased number of hepatocytes undergoing apoptosis were observed in male rats at 100 ppm. Mild splenic changes consisting of sinus hyperplasia in males and females at 100 ppm and mantle zone atrophy in males at 100 ppm were also observed. It was concluded that TCPM at a dietary concentration of 10 ppm (equivalent to 1.2 mg/kg/day) produced systemic changes in rats that included various hepatic effects, increased splenic weight, and modulations in white blood cells and lymphocyte counts.