Evaluation of subchronic toxicity, genotoxicity, and blood kinetics of 1,2-benzisothiazolin-3-one following oral administration.

Biocides are widely used as household preservatives, with 1,2-benzisothiazolin-3-one (BIT) being among the most common. However, toxicological data for risk assessment of BIT remain limited. To address this gap, general toxicity, genotoxicity, and time-course blood kinetic studies were conducted. In an acute oral toxicity study, 4 of 6 animals died at 300 mg/kg, indicating an LD50 of 50-300 mg/kg and a GHS Category 3 classification. In a 4-week oral toxicity study in rats, female mortality and male body weight loss occurred at 180 mg/kg, while gastric hyperkeratosis and squamous cell hyperplasia appeared at ≥30 mg/kg. In a 13-week oral toxicity study in rats (5, 15, and 50 mg/kg bw/day), histopathological changes were confined to the stomach, with dose-dependent forestomach squamous cell hyperplasia and hyperkeratosis observed from 15 mg/kg bw/day and persisting with reduced severity during the recovery period, resulting in a NOAEL of 5 mg/kg bw/day. BIT was negative in bacterial reverse mutation, chromosomal aberration, and in vivo micronucleus assays. Following a single oral dose of 50 mg/kg, BIT was rapidly and almost completely absorbed, with higher systemic exposure in female rats. These results provide a robust toxicological basis for the human health risk assessment of BIT following oral exposure.