The distribution, excretion and biotransformation of p-dichloro[¹⁴C]benzene in rats after repeated inhalation, oral and subcutaneous doses

Abstract

1. Following repeated daily whole-body exposure (3h/day) of rats to atmospheres containing p-dichloro[¹⁴C]benzene (1000p.p.m.), or administration of oral or subcutaneous doses (250 mg/kg/day), 24-h tissue concn. of ¹⁴C were similar and did not increase after six days dosing, but tended to decrease.

2. After repeated daily atmospheric exposures or oral doses, highest concn. of ¹⁴C occurred in fat, kidneys, liver and lungs. Concn. declined rapidly to near or below limits of detection (< 0.2 p.p.m.) in plasma and tissues at 5 days. After similar subcutaneous doses, tissue concn. declined more slowly.

3. During five days after repeated dosing, most excreted ¹⁴C(91–97%) was in the urine. Little was excreted in faeces or expired air. Excretion was more prolonged following subcutaneous administration. After single doses to bile duct-cannulated animals, 46–63% of the excreted ¹⁴C was in the bile during 24h.

4. The pattern of metabolites in urine and bile was similar after each route of administration although there were quantitative differences. Urine extracts contained two major ¹⁴C-components, namely a sulphate and a glucuronide of 2,5-dichlorophenol, representing 46–54% and 31–34% of the urinary ¹⁴C respectively. Two minor components were identified by mass spectrometry as a dihydroxydichlorobenzene and a mercapturic acid of p-dichlorobenzene.

5. The glucuronide of 2,5-dichlorophenol was the major ¹⁴C component in bile (30–42%).