Thirteen-week subcutaneous repeated dose toxicity study of butylparaben and its toxicokinetics in rats

Parabens are widely used preservatives in cosmetics and pharmaceutical products and are approved as food additives. These chemicals have been considered safe for many years. However, the literature classifies parabens as endocrine-disrupting chemicals, and an assessment of their influence on the endocrine system and systemic toxicity is important. This study explored long-term systemic toxicity, effects on the endocrine system, and toxicokinetic behavior after repeated subcutaneous administration of butylparaben to Sprague–Dawley rats. Rats were treated with vehicle (4% Tween 80) or butylparaben at dose levels of 2, 10, and 50 mg/kg/day for 13 weeks. Assessment of systemic toxicity and endocrine-disrupting effects was based on mortality; clinical signs; body weight; food and water consumption; ophthalmological findings; urinalysis; hematology and clinical biochemistry; organ weights; necropsy and histopathological findings; regularity and length of the estrous cycle; semen quality; and toxicokinetic behavior. Female uterine weight and estrous cycle, and male semen quality indicated no estrogenic effects. Butylparaben induced local irritation at the injection site in both sexes at a dose of 50 mg/kg/day, but systemic toxicity was not observed. Therefore, the no-observed-adverse-effect level of butylparaben is set at 50 mg/kg/day in rats of both sexes. Butylparaben was without endocrine system effects at this dose. Butylparaben displays dose-dependent systemic exposure up to the maximum dose of 50 mg/kg/day and repeated administration of butylparaben for 13 weeks shows no bioaccumulation.