Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

Abstract

Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs) are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.

Associations of Exposure to Perfluoroalkyl Substances With Thyroid Hormone Concentrations and Birth Size

“…Main sources of exposure in the general population include consumer products, seafood, house dust, and drinking water (3)(4)(5)(6). Early life stages are particularly vulnerable to PFAS exposure (7), and current evidence suggests that PFAS exposures negatively impact the regulation and development of metabolic, immune, and neurological systems in pregnant women and infants (8)(9)(10).…”

“…Recent systematic reviews have found that PFAS can potentially impact both maternal TH levels during gestation and newborn TH levels at birth (8,9,28). In particular, PFOS and PFOA have been found to be positively associated with maternal and cord TSH levels (29)(30)(31)(32).…”

Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

“…Since VD is reported to regulate osteoblast proliferation and differentiation, bone mineralization and gene transcription of importance for the bone and calcium homeaostasis [40][41][42] , our results showing PFOA inhibition of VD-induced gene expression and reduced bone mineralization would provide the first biological explanation of the epidemiological reports indicating PFAS endocrine disruption on bone health. Together with computational and in silico evidence indicating a competition of PFOA on the same binding site of 1,25(OH)D on the VDR, and subsequent alteration of receptors flexibility, this study adds further knowledge to the range of steroid pathways disrupted by PFAS [20][21][22][23][24] . However, in a small cohort of young healthy men from PFAS-exposed community, we did not observed a reduction of 25(OH)D levels, despite a raise in PTH levels www.nature.com/scientificreports/ that could suggest a compensatory mechanism by parathyroid glands to maintain calcium homeostasis in front of a functional defect of VD action.…”

“…Epidemiological studies have reported an inverse relationship between PFAS exposure and bone health [14][15][16][17][18][19] , suggesting a possible role of PFAS in the onset of osteoporosis, however the associated mechanisms are still unexplored. Because different PFASs, including PFOA, have been associated with altered sex steroid 20,21 and thyroid hormone levels [22][23][24] we hypothesized that they may also affect vitamin D metabolism. Vitamin D (VD) is a key regulator of bone mineralization and calcium homeostasis in both men and women 25 , and low levels of VD are typically associated with reduced bone mass.…”

Thyroid Disrupting Chemicals

“…Perfluoroalkyl substances (PFASs) have been widely used as surface coating in several industrial production settings, from textile and food packaging to cosmetic and photography. The correlation between different PFASs with thyroid hormones have been evaluated in several human studies, showing different trend depending on the sex and the age of the cohort [ 45 ]. The CHIrP (Chemicals, Health and Pregnancy) study, conducted in Canada among a population of 152 euthyroid pregnant women, assessed the levels of different PFASs (perfluorohexanesulfonate (PFHxS) median concentration detected 1.0 ng/mL, perfluorononanoate (PFNA) median concentration detected 0.6 ng/mL, perfluorooctanoate (PFOA) median concentration detected 1.7 ng/mL and perfluorooctanesulfonate (PFOS) median concentration detected 4.8 ng/mL) in the maternal serum together with thyroid hormones, TSH and TPOAb.…”