Association of perfluorinated chemical exposure in utero with maternal and infant thyroid hormone levels in the Sapporo cohort of Hokkaido Study on the Environment and Children’s Health

Kato, Shinichi; Itoh, Shinji; Yuasa, Motoyuki; Baba, Toshiaki; Miyashita, Chihiro; Sasaki, Seiko; Nakajima, Sachiko; Uno, Atsushi; Nakazawa, Hiroyuki; Iwasaki, Yusuke; Okada, Emiko; Kishi, Reiko

doi:10.1007/s12199-016-0534-2

Cited by 55 publications

(52 citation statements)

References 41 publications

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“…In humans, however, the situation is less clear. For the compounds considered in the present study, some studies have reported negative associations with T 4 levels in blood (DH Makey et al 2016;Zheng et al 2017;Zota et al 2011), but other studies have reported positive associations (EFSA 2011a;Shrestha et al 2017;Stapleton et al 2011), concentration-dependent associations (Zhao et al 2015), or a lack of associations (Audet-Delage et al 2013;Kato et al 2016;Olsen et al 2003). The observed difference between rodent and human studies is attributed to the fact that humans have a reserve of T 4 stably bound to TBG.…”

Section: Discussionmentioning

confidence: 60%

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

Hamers

Kortenkamp

Scholze

et al. 2020

Environ Health Perspect

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BACKGROUND: House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine (T 4 ) for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR in vitro relates to in vivo T 4 -TTR binding is unknown. OBJECTIVES: Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the in vitro TTRbinding potency to in vivo inhibition levels of T 4 -TTR binding in maternal and infant serum. METHODS: Twenty-five contaminants were tested for their in vitro capacity to compete for TTR-binding with a fluorescent FITC-T 4 probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration-response curves were compared with concentration-response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor-TTR dissociation constant (K i ) was used to estimate inhibition levels of T 4 -TTR binding in human blood. RESULTS: The TTR-binding potency of the mixtures was well predicted by concentration addition. The ∼ 20% inhibition in FITC-T 4 binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of T 4 -TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively. DISCUSSION: The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTRbinding compounds and circulating T 4 levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of T 4 -TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.

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Section: Discussionmentioning

confidence: 60%

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

Hamers

Kortenkamp

Scholze

et al. 2020

Environ Health Perspect

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“…Some studies also reported similar inconsistent observations224041). In Hokkaido cohort with matched mother and child pairs (n=39), PFOS levels measured in 24 weeks of pregnancy showed a negative association with maternal TSH, but a positive association with cord serum TSH.…”

Section: Pfass Exposure and Thyroid Hormone Disruption In Susceptiblementioning

confidence: 81%

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

Lee

Choi

2017

Ann Pediatr Endocrinol Metab

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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.

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“…Several important potential covariates, including smoking, fish intake and environmental contaminants such as PFOS and mercury were considered. Our previous reports on the same cohort showed that PFOA, Mono-2-ethylhexyl phthalate, Bisphenol A are not associated with maternal or neonatal TH levels (Kato et al, 2016;Minatoya et al, 2016;Minatoya et al, 2017).…”

Section: Strengths and Limitationsmentioning

confidence: 88%

“…The models were adjusted for variables that were significantly associated with TSH or FT4 levels at p < 0.05 level in the univariate analysis (data not shown). PFOS was included in the model for maternal THs becauseKato et al (2016) previously reported that, in multivariate analyses, PFOS were significantly associated with maternal TSH in the same cohort. Mercury was associated with total TEQ/PCBs, but not with THs, therefore it was not adjusted for in the multivariate model.…”

mentioning

confidence: 99%

Association of prenatal exposure to PCDD/Fs and PCBs with maternal and infant thyroid hormones: The Hokkaido Study on Environment and Children's Health

Baba

Ito

Yuasa

et al. 2018

Science of The Total Environment

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Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are persistent organic pollutants that are universally detected. Some congeners of PCDDs, PCDFs or PCBs have dioxin-like toxicity, whereas non-dioxin-like PCBs are considered to have different toxicity. Reports of the relationships between prenatal exposure to PCDDs, PCDFs or PCBs and thyroid homeostasis in pregnant women and infants have been inconsistent. The aim of this study was to investigate the effect of maternal serum PCDD/F or PCB levels on maternal and neonatal thyroid hormone (TH) levels in a prospective cohort. Of the 514 subjects in the prospective cohort, 386 mothers and 410 infants were included for analysis. Fifteen dioxins and seventy PCBs in maternal blood collected between 23 and 41weeks of gestation were measured using high-resolution gas chromatography and high-resolution mass spectrometry. Blood samples to measure thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers at an early gestational stage (median ten weeks), and from infants between four and seven days of age, respectively. Multiple linear regression analysis was conducted. Median concentration of total PCBs, PCB 153 were 104,700, and 20,500pg/g lipid, respectively. Median total dioxin-TEQ was 13.8pg/g lipid. Total dioxin-TEQ, coplanar PCBs were positively associated with neonatal FT4 (beta=0.224, 0.206, respectively). The association was stronger in boys (beta=0.299, 0.282, respectively). Several PCDD/F and PCB isomers were also positively associated with neonatal FT4. Total PCBs or non-dioxin-like PCBs were not associated with any maternal or neonatal THs. No DLC grouping or congeners were associated with neonatal TSH. Non-ortho PCBs were positively associated with maternal FT4. Three PCB congeners had significant positive association(s) with maternal THs. In conclusion, the results of our study suggest that perinatal exposure to background-level DLCs increases neonatal FT4, especially in boys.

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Association of perfluorinated chemical exposure in utero with maternal and infant thyroid hormone levels in the Sapporo cohort of Hokkaido Study on the Environment and Children’s Health

Abstract: These findings suggest that PFOS may independently affect the secretion and balances of maternal and infant TSH even at low levels of environmental exposure.

Cited by 55 publications

References 41 publications

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

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

Association of prenatal exposure to PCDD/Fs and PCBs with maternal and infant thyroid hormones: The Hokkaido Study on Environment and Children's Health

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