Comprehensive 26-week subchronic toxicity assessment of perfluoroheptanoic acid in Sprague–Dawley rats: implications for human health

• PFHpA was orally given to rats at 20, 40, and 80 mg/kg/day for 26 weeks. • Microscopic changes in liver & thyroid were observed with altered serum biomarkers. • Forestomach squamous cell hyperplasia occurred as a localized effect of PFHpA. • These PFHpA-induced toxic effects in rats may not directly reflect human health risk. Perfluoroheptanoic acid (PFHpA), a short-chain perfluoroalkyl used in various industrial applications, is highly persistent and raises concerns about ecological and human health. However, in vivo toxicity data are limited. This study evaluated PFHpA toxicity in male and female Sprague-Dawley rats given oral doses of 20, 40, and 80 mg/kg/day for 26 weeks. During administration, body weights, clinical observations, and neurobehavioral assessments were conducted, followed by clinical pathology and histopathology after the final sacrifice. Additionally, PFHpA concentrations were measured in the serum of all rats at week 26. At the end of the dosing period, serum concentrations of PFHpA were higher in male rats than in females. Males receiving 80 mg/kg/d exhibited centrilobular hepatocellular hypertrophy in the liver, follicular cell hypertrophy in the thyroid, increased liver weight, elevated blood urea nitrogen, and decreased total bilirubin levels. Squamous cell hyperplasia in the forestomach, indicative of localized irritant effects, was observed in all PFHpA-treated groups. Thyroid hormone assays revealed lower total thyroxine levels in the high-dose group than in the control group in both sexes (P < 0.001). The main changes observed in PFHpA-treated groups appeared to be rat-specific hepatic adaptations rather than adverse effects, as no mortality, clinical symptoms, or body weight loss occurred. We concluded that the toxicological impact of PFHpA is negligible in standard lab rats. This novel finding can inform stakeholders in the industrial, medical, and political fields, especially regarding public health management.