DISPOSITION OF BENZOPHENONE-3 AFTER DERMAL ADMINISTRATION IN MALE-RATS

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, BZ-3) is a UV absorber that is used extensively in medicine, cosmetics and industry as a sunscreen and color fastener. Exposure to the chemical is through the dermal and oral route. Bioavailability of the chemical absorbed through the skin is different from that seen through the oral route. The disposition of BZ-3 was investigated after dermal administration of 100 mg/kg body weight (body wt.) in Sprague-Dawley rats. Blood samples were collected at various intervals and the parent compound and its metabolites were analyzed by HPLC. Absorption was rapid as the parent compound and its metabolites were detected in plasma 5 min post-administration. The half-life (t(1/2)) of absorption was 3.45 h corresponding to an absorption rate constant of 0.2 h(-1). Peak plasma concentration of 35 +/- 4.5 mu g/ml (mean +/- standard error of the mean, S.E.) was attained at 2.5 h post-administration Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 h. for beta phase), the area under the plasma concentration versus time curve was 211.1 +/- 38.2 mu g/ml/h (mean +/- S.E). There was also extensive binding of BZ-3 and its metabolites to plasma proteins. Three metabolites were identified in plasma, 2,4-dihydroxybenzophenone (DHB) and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) were the major metabolites detected in the plasma, while 2,3,4-trihydroxybenzophenone (THB) was detected in trace amounts. Tissue distribution studies revealed that THB was the major metabolite followed by DHB (both free and conjugated) in all tissues examined. The liver contained the highest amount followed by the kidney, spleen and testes, respectively.