Long-Term Repeated Exposure Assessment of PFHpA Shows No Serious Toxicity

"Species and Sex Differences Should Be Considered When Assessing Human Health Risk"

As regulations on perfluoroalkyl substances (PFAS), commonly referred to as "Forever Chemicals," become more stringent, the use of alternative substances is increasing. Amidst this trend, a Korean research team has, for the first time, verified the long-term safety of a next-generation alternative PFAS compound.


The National Research Institute of Toxicology (KIT) announced on July 27 that a team led by Dr. Byungseok Lee and Dr. Jiseok Han at the Biomarker Research Center performed a 26-week repeated-dose toxicity study using perfluoroheptanoic acid (PFHpA), an alternative PFAS substance. Although some physiological changes were observed, the team reported that no serious toxicological effects related to human health risk were identified. The findings have been published in the international journal of environmental toxicology, Environment International.

Schematic Diagram of 26-Week Repeated Dose Toxicity Evaluation of PFHpA Using Rats. Following 26 weeks of repeated oral administration of PFHpA to male and female rats, significant changes were observed including histopathological lesions in the liver and thyroid, localized irritative changes in the stomach, and hematobiochemical alterations. Courtesy of the research team

Schematic Diagram of 26-Week Repeated Dose Toxicity Evaluation of PFHpA Using Rats. Following 26 weeks of repeated oral administration of PFHpA to male and female rats, significant changes were observed including histopathological lesions in the liver and thyroid, localized irritative changes in the stomach, and hematobiochemical alterations. Courtesy of the research team

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PFHpA is a short-chain PFAS that is increasingly being used to replace conventional long-chain PFAS compounds. However, most studies have focused on short-term exposure, so there has been a lack of evidence regarding its long-term safety.


Following the Organisation for Economic Co-operation and Development (OECD) test guidelines and Good Laboratory Practice (GLP) standards, the research team administered repeated oral doses of PFHpA to male and female rats for 26 weeks and comprehensively analyzed factors such as body weight, blood tests, neurobehavioral responses, and organ changes.


As a result, the high-dose group showed hepatocellular hypertrophy, changes in the thyroid, and decreased thyroid hormone levels; however, there were no decreases in body weight, deaths, notable neurobehavioral abnormalities, or severe organ damage. The research team explained that these changes are attributable to the physiological characteristics of rodents and adaptive metabolic responses of the liver, making it difficult to interpret these results as indicating direct risk to humans.

Research team at the National Institute for National Defense Science. (From left) Byungseok Lee, Heejin Park, Jiseok Han, and Seongae Hyun, principal researchers. Provided by KIT

Research team at the National Institute for National Defense Science. (From left) Byungseok Lee, Heejin Park, Jiseok Han, and Seongae Hyun, principal researchers. Provided by KIT

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Furthermore, the blood concentration of PFHpA was found to be higher in males than in females, and some tissue changes were also more pronounced, confirming sex-based differences in toxicity. The research team plans to carry out follow-up studies on reproductive toxicity, inhalation and skin exposure, and other diverse routes of exposure, as well as risk assessments that reflect actual human exposure levels.



Dr. Byungseok Lee stated, "Although the use of alternative substances is increasing due to PFAS regulations, there are still insufficient data on long-term safety. We hope that the findings of this study will serve as a scientific basis for future risk assessments and regulatory policymaking."


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