Effects of Legacy PFAS and Novel Alternatives on Thyroid Function in Mother‒Child Populations: A Systematic Review.
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Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in industrial and consumer applications, such as firefighting foams, textiles, electronics, industrial coatings, food packaging, and household consumer products, due to their excellent chemical stability. However, legacy long-chain PFAS are prohibited because of their endocrine-disrupting properties, bioaccumulative nature, and potential carcinogenicity, followed by the emergence of new alternatives, such as short-chain congeners and novel PFAS alternatives. PFAS are known to disrupt endocrine function, and the thyroid gland, a critical endocrine organ, is particularly vulnerable to their effects. Mother‒child populations are more likely to be affected by PFAS due to their specific physiological characteristics, metabolic differences, and developmental stages. This paper reviews the exposure levels of legacy PFAS and their alternatives in maternal and infant blood and breast milk, and the relationship between PFAS exposure and thyroid hormone (TH) levels. It also examines the similarities and differences in the mechanisms by which different PFAS affect thyroid function. Research has revealed that both legacy and PFAS alternatives have been detected in maternal blood, infant blood, and breast milk. While legacy PFAS exhibit higher exposure levels with notable regional variations, the concentrations of PFAS alternatives, although lower, remain a concern. PFAS exposure affects TH in mothers and infants, with legacy PFAS having a more significant effect. The mechanisms underlying thyroid disruption caused by different PFAS are largely similar. However, PFAS alternatives are characterized by high protein affinity, ability to disrupt fatty acid metabolism, and high hydrophilicity, and may also increase the risk of thyroid cancer (TC). This study provides critical evidence for evaluating the safety of PFAS alternatives and provides a scientific foundation for developing preventive and regulatory measures.