The distribution excretion and biotransformation of p-dichloro[14C]benzene in rats after repeated inhalation, oral and subcutaneous doses.
1. Following repeated daily whole-body exposure (3 h/day) of rats to atmospheres containing p-dichloro[14C]benzene (10000p.p.m.), or administration of oral or subcutaenous 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 (less than 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 24 h. 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-dichlorphenol was the major 14C component in bile (30-42%).
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
D000336:Aerosols; D002722:Chlorobenzenes; D007306:Insecticides; C018511:4-dichlorobenzene