Safety evaluation of benzophenone-3 after dermal administration in rats

Benzophenone-3 (BZ-3) is a category 1 (over-the-counter) product approved by the US Food and Drug Administration (FDA) for use as a sunscreen agent in medicine, cosmetics, industry, and agriculture. This is due to its ability to absorb and dissipate ultraviolet light in a harmless manner, thus protecting human skin and products from UV irradiation. This study investigated the safety of BZ-3 after repeated administration. BZ-3 in ointment base was applied at a dose of 100 mg/kg body wt. twice daily, for 4 weeks to the skin of male Sprague-Dawley rats. Body weight, organ to body weight ratios, hematological, and clinical chemistry parameters were not effected. Pathological examination revealed no significant changes between control and treated animals. No gross external abnormalities were observed. Both in vivo and in vitro blood glutathione (GSH) levels were effected by BZ-3 treatment. However, after 60 min of incubation, a reversal of this effect was observed in the treatment group as blood GSH levels approached normal levels. Furthermore, investigation of GSH-reductase and peroxidase with time indicated an increase in GSH-reductase activity at 60 and 90 min with no effect on GSH-peroxidase. Pre-treatment with phenobarbital modulated the metabolic disposition of BZ-3. There was an increase in the formation of the hydroxy metabolites but not the O-dealkylated form. This study suggests that BZ-3 is not toxic to rats when applied dermally at a dose of 100 mg/kg body wt. for 4 weeks.