Carcinogenicity assessment of PFOS based on weight of evidence and dose-response analysis

ObjectiveTo assess the quality of the literature related to the carcinogenicity of perfluorooctane sulfonic acid （PFOS） using the weight of evidence method， and to evaluate its carcinogenic risk through the dose-response analysis.MethodsA systematic search for relevant literature on human epidemiologic studies related to PFOS and cancer up to June 2024 was conducted. After evaluation and secondary screening， based on the guidelines for evaluating the relevance and reliability of toxicological data developed by the China National Center for Food Safety Risk Assessment， the dose-response for breast cancer risk analysis was performed using the cancer slope factor （CSF） method in conjunction with the results of meta-analyses of population-based epidemiological studies.ResultsFrom the 2 532 retrieved human epidemiological articles， 35 valid ones were screened， of which 22 were of high quality and 13 were of moderate quality in terms of the reliability. Thirty-two articles were graded as “A/B” or “B” in terms of the relevance. Meta-analysis showed that both low serum PFOS levels （<4.77 ng/mL； OR=1.46， 95% CI： 1.18-1.80） and moderate serum PFOS levels （>4.77 ng/mL and ≤15.67 ng/mL； OR=1.07， 95% CI： 1.04-1.10） were positively associated with the risk of breast cancer. The CSF results indicated that for every 1 ng/kg BW/d increment in external PFOS exposure， the attributable risk of breast cancer incidence increased by 1.64×10-3.ConclusionEvidence from the weight-of-evidence evaluation integrated with meta-analysis confirmed a significant dose-response association between PFOS exposure and population-level breast cancer incidence， suggesting that PFOS exposure may be associated with an increased risk of breast cancer.