Pharmacokinetic and toxicological evaluation of dogs fed 1,2,4,5-tetrachlorobenzene in the diet for two years.
1,2,4,5-Tetrachlorobenzene (TCB), an intermediate in several industrial processes, was administered in the diet to dogs at 5 mg/kg . d for 2 yr, followed by a 20-mo recovery phase. The animals were examined periodically for toxicity; the concentration of TCB in the plasma and fat was measured during the 2 yr of exposure and 20 mo of recovery. After 18 mo of exposure, all clinical chemistry parameters were normal; however, after 24 mo, serum alkaline phosphatase activity and total bilirubin levels were slightly elevated in the dogs dosed with TCB. Both clinical chemistry parameters returned to normal levels within 3 mo of the cessation of exposure. After the 20-mo recovery, gross and histopathologic examination of tissues revealed no morphological changes considered related to the ingestion of TCB. At the end of 2 yr of exposure, TCB had reached 98 and 97% of the calculated steady-state concentrations in fat and plasma, respectively. TCB was eliminated from the fat and plasma with half-life values of 111 and 104 d, respectively. Although there were only small differences in the approach to steady state, differences in the rate of elimination of TCB from fat and plasma resulted in dramatic changes in the fat/plasma ratio of TCB throughout the entire study.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002722:Chlorobenzenes / Q000378:metabolism / Q000633:toxicity*; D004032:Diet; D004285:Dogs; D005260:Female; D007700:Kinetics; D008297:Male; D013997:Time Factors
D002722:Chlorobenzenes