P,P'-DICHLORODIPHENYL SULFONE METABOLISM AND DISPOSITION IN RATS

p,p'-Dichlorodiphenyl sulfone (DDS) is a lipophilic monomer used exten sively in the synthesis of high temperature plastics. Studies of the f ate of uniformly labeled [C-14]DDS in the rat have established that it is readily absorbed from the gastrointestinal tract, distributed to a ll tissues examined, and concentrated in adipose tissue, After intrave nous administration of 10 mg/kg and determination of the time course o f DDS distribution, increasing accumulation of DDS in adipose was obse rved up to 24 hr, followed by slow elimination with a half-life of sim ilar to 12 days. DDS equivalents in tissues were primarily (>90%) pare nt compound, whereas excreted DDS equivalents were primarily (>80%) pr esent as metabolites. On repeat oral dosing at 10 mg/kg, levels of DDS in tissues seemed to reach steady state after similar to 2 weeks, at which time the concentrations in adipose reached 265 mu g/g tissue, He patic cytochrome P450 (CYP) content, ethoxyresorufin O-deethylase acti vities, and levels of metabolites arising from phase I metabolism were doubled after repeat oral administration of DDS, but benzphetamine N- demethylase activity was unchanged, Thus, it seems that DDS induces CY P1A forms, but not CYP2B isozymes. DDS-derived radioactivity was excre ted primarily in feces and to a lesser extent in urine as a phenolic m etabolite and its glucuronide, The aglycone of this glucuronide was is olated and characterized by NMR and MS as 3-hydroxy-4,4'-dichlorodiphe nyl sulfone.