Acute toxicity, subchronic dermal toxicity, and delayed contact sensitization evaluations of dicyclopentenyloxyethyl methacrylate in rabbits and guinea pigs

Abstract

The subchronic dermal toxicity of dicyclopentenyloxethyl methacrylate (DPOMA) was evaluated in young adult New Zealand White rabbits, and its potential to produce delayed contact sensitization was evaluated in Harley guinea pigs by a modified Buehier's closed patch technique. In addition, studies were conducted to evaluate the acute systemic toxicity of DPOMA in rats (oral) and rabbits (dermal), and its eye and skin irritancy in rabbits. In the subchronic dermal toxicity study, 4 groups of rabbits were treated percutaneously with DPOMA at 0 (acetone), 10, 107, and 1067 (undiluted) mg/kg‐day in a volume of 1 ml/kg, over a 4‐wk period. The application sites were unoccluded. No deaths occurred, and no signs of systemic toxicity were observed. No treatment‐related effects were seen on body weights, hematology, clinical chemistry, urinalysis, organ weights, or histopathology (except the treated skin). The only treatment‐related effect was slight to moderate skin irritation in the mid‐ and high‐dose groups. The severity of skin irritaton was dependent on the number of applications and the concentration of DPOMA. Maximal skin irritation occurred after 1 wk. No skin irritation was seen in the control and low‐dose group. In the DCS study, guinea pigs received 6 induction doses of 0.5 ml 100% DPOMA and were challenged with 0.5 ml of 50% (w/v) DPOMA in acetone 2 wk after the last induction treatment. No erythema or edema was observed in any of the challenged guinea pigs in either the treated and control groups. These acute toxicity studies indicate that DPOMA is practically nontoxic by a single exposure via both oral and dermal routes (the oral LD50 in rat and dermal LD50 in rabbits were greater than 5.0 g/kg body weight), slightly irritating to the skin, and inconsequentially irritating to the eyes. The no‐observed‐effect level (NOEL) for systemic toxicity of DPOMA applied repeatedly to rabbits skin is at least 1067 mg/kg‐d. DPOMA is not a strong or moderate skin sensitizer in guinea pigs.