ASSESSMENT OF THE IN-VIVO GENOTOXICITY OF 2-HYDROXY 4-METHOXYBENZOPHENONE

The genotoxic potential of 2-hydroxy 4-methoxy-benzophenone (benzophen one-3, Bz-3), a commonly used sunscreen, has been evaluated previously with in vitro systems. Data from Salmonella studies (with and without activation) have been predominantly negative, but two reports have sh own weakly positive results in a single bacterial strain under conditi ons of metabolic activation. In addition, Bz-3 has been reported to in duce chromosome aberrations and equivocal results for sister chromatid exchange in Chinese hamster ovary (CHO) cells. We used the Drosophila somatic mutation and recombination test (SMART) and in vivo cytogenet ics in rat bone marrow to define the potential for in vivo expression of this in vitro activity. For the SMART assay, larva from a mating of ''multiple wing hair'' (mwh) females with heterozygous ''flare'' (flr ) males were exposed to 0, 3000, or 3500 ppm Bz-3 or 25 ppm dimethylni trosamine (DMN, positive control) for 72 hr. A recombination between t he mwh and flr genes produces twin wing spots, while events such as de letions produce single spots. None of the Bz-3-treated larva produced flies with significantly more single or multiple wing spots than contr ols. In contrast, DMN-treated larva produced flies with significantly more single or multiple wing spots than controls. The in vivo cytogene tic assay in rat bone marrow cells was conducted to evaluate the clast ogenicity of Bz-3. Sprague-Dawley rats were treated by oral gavage wit h a single administration of 0.0, 0.5, 1.67, or 5 gm/kg Bz-3 or a sing le dose of 5 gm/kg/day Bz-3 for 5 consecutive days. Cyclophosphamide ( CP) was the positive control and was administered at 20 mg/kg with bot h treatment regimens. Colchicine growth-arrested bone marrow cells wer e collected 8 and 12 hr after the single treatment and 12 hr after the last daily treatment. Under either treatment protocol none of the Bz- 3 concentrations caused any significant increase in chromosomal aberra tions. Results from these two studies strongly support the conclusion that Bz-3 is not genotoxic in vivo. (C) 1994 Wiley-Liss, Inc.