Comparison of sulfolane effects in Sprague Dawley rats, B6C3F1/N mice, and Hartley guinea pigs after 28 days of exposure via oral gavage

Graphical abstract
Highlights • Sulfolane was evaluated in mice, rat, and guinea pig 28-day toxicity studies. • The rat was more sensitive compared to mice and guinea pigs. • Rats generally had the highest plasma concentrations at 24 h after the last dose.
Sulfolane is a solvent used in industrial refining with identified environmental exposure in drinking water. Due to potential large species differences, the National Toxicology Program (NTP) conducted 28-day toxicity studies in male and female Hsd:Sprague Dawley® SD® rats, B6C3F1/N mice, and Hartley guinea pigs. A wide dose range of 0, 1, 10, 30, 100, 300, and 800 mg/kg was administered via gavage. Histopathology, clinical pathology, and organ weights were evaluated after 28 days of exposure. In addition, plasma concentrations of sulfolane were evaluated 2 and 24 h after the last dose. Increased mortality was observed in the highest dose group of guinea pigs and mice while decreased body weight was observed in rats compared to controls. Histopathological lesions were observed in the kidney (male rat), stomach (male mice), esophagus (male and female guinea pigs), and nose (male guinea pigs). Plasma concentrations were generally higher in rats and guinea pigs compared to mice with evidence of saturated clearance at higher doses. Male rats appear to be the most sensitive with hyaline droplet accumulation occurring at all doses, although the human relevance of this finding is questionable.