Time course of enzyme induction in liver and kidneys and absorption, distribution and elimination of 1,4-dichlorobenzene in rats

Time course of enzyme induction was measured in Fischer344 rats treated daily at 150 and 600 mg 1,4-dichlorobenzene (1,4-DCB)/kg p.o. up to 28 days. The monoxygenases 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O-deethylase (EROD) and aldrin epoxidase (ALD) as well as the phase II enzymes; epoxide hydrolase (EH), glutathione S-transferase (GS-T) and glucuronyl transferase (GLU-T) were dose-dependently induced in the liver of males and females. A pronounced induction in the kidneys was measured at 600 mg/kg only for ECOD. After single oral administration of 100 and 1000 mg/kg bw and feeding of 100 and 1000 ppm (corresponding to approximate to 10 and 100 mg/kg btv) to male Wistar rats for 28 days, the time course of I,4-DCB and 2,5-DCP concentrations was investigated in plasma, adipose, hepatic and renal tissue. In addition, total urinary excretion of 2,5-DCP was determined. After single application, 1,4-DCB and 2,5-DCP were rapidly eliminated from the plasma and tissues, 40-60% of the dose administered was excreted as 2,5-DCP in the urine. There were no indications of cumulative effects after a feeding period of 28 days. The concentrations decreased in all tissues until the 7th day of study. Thereafter, there seems to be a steady state until the 28th day. A total of 7 days after the end of exposure, no more residues could be detected. Following long-term inhalation (450 and 3000 mg/m(3)) 1,4-DCB concentrations were highest in adipose tissues at 6 months followed by a marked decline at 18 months. I,4-DCB and 2,5-DCP concentrations in plasma and liver were much lower but again with a peak at 6 months. When compared with published human data on measurements in plasma, urine, liver and adipose tissue the results suggest that there should be no hazard for the general population. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.