Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA)

Coperchini, Francesca; Awwad, Oriana; Rotondi, Mario; Santini, Ferruccio; Imbriani, Marcello; Chiovato, Luca

doi:10.1007/s40618-016-0572-z

Cited by 144 publications

(63 citation statements)

References 81 publications

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“…TH play a critical role in neurodevelopment (de Escobar et al 2004;Porterfield 1994). PFAS are well-documented thyroid disrupters in humans (Coperchini et al 2017;Webster et al 2016), including in pregnant women (Ballesteros et al 2017;Berg et al 2015;Wang et al 2014;Webster et al 2014). Generally, maternal PFAS levels during pregnancy are associated with shifts in TH levels consistent with hypothyroidism (e.g., elevated thyroidstimulating hormone), which is associated with increased risk for low birth weight (Alexander et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Maternal, Embryo, and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

Blake

Cope

Hall

et al. 2020

Environ Health Perspect

173

113

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BACKGROUND: Perfluorooctanoic acid (PFOA) is a poly-and perfluoroalkyl substance (PFAS) associated with adverse pregnancy outcomes in mice and humans, but little is known regarding one of its replacements, hexafluoropropylene oxide dimer acid (HFPO-DA, referred to here as GenX), both of which have been reported as contaminants in drinking water. OBJECTIVES: We compared the toxicity of PFOA and GenX in pregnant mice and their developing embryo-placenta units, with a specific focus on the placenta as a hypothesized target. METHODS: Pregnant CD-1 mice were exposed daily to PFOA (0, 1, or 5 mg=kg) or GenX (0, 2, or 10 mg=kg) via oral gavage from embryonic day (E) 1.5 to 11.5 or 17.5 to evaluate exposure effects on the dam and embryo-placenta unit. Gestational weight gain (GWG), maternal clinical chemistry, maternal liver histopathology, placental histopathology, embryo weight, placental weight, internal chemical dosimetry, and placental thyroid hormone levels were determined. RESULTS: Exposure to GenX or PFOA resulted in increased GWG, with increase in weight most prominent and of shortest latency with 10 mg=kg=d GenX exposure. Embryo weight was significantly lower after exposure to 5 mg=kg=d PFOA (9.4% decrease relative to controls). Effect sizes were similar for higher doses (5 mg=kg=d PFOA and 10 mg=kg=d GenX) and lower doses (1 mg=kg=d PFOA and 2 mg=kg=d GenX), including higher maternal liver weights, changes in liver histopathology, higher placental weights and embryo-placenta weight ratios, and greater incidence of placental abnormalities relative to controls. Histopathological features in placentas suggested that PFOA and GenX may exhibit divergent mechanisms of toxicity in the embryo-placenta unit, whereas PFOA-and GenX-exposed livers shared a similar constellation of adverse pathological features. CONCLUSIONS: Gestational exposure to GenX recapitulated many documented effects of PFOA in CD-1 mice, regardless of its much shorter reported half-life; however, adverse effects toward the placenta appear to have compound-specific signatures.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Maternal, Embryo, and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

Blake

Cope

Hall

et al. 2020

Environ Health Perspect

173

113

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“…PFASs are reported to disrupt thyroid hormone balances by increasing metabolic excretion and inhibiting synthesis of the hormones9). Unlike other persistent organic compounds which preferentially partition into lipid, PFASs are unique as these compounds can resist both water and oil.…”

Section: Perfluoroalkyl Substancesmentioning

confidence: 99%

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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“…However, not all epidemiological studies have found a negative correlation with PFOS levels in serum (Olsen et al 2003), nor all animal studies (Chang et al 2017). Nevertheless, PFOS has been identified as a thyroid hormone disruptor (ATSDR 2018;Coperchini et al 2017).…”

Section: Introductionmentioning

confidence: 99%

A Probabilistic Approach to Evaluate the Risk of Decreased Total Triiodothyronine Hormone Levels following Chronic Exposure to PFOS and PFHxS via Contaminated Drinking Water

Silva

Ringblom

Lindh

et al. 2020

Environ Health Perspect

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BACKGROUND: Extensive exposure to per-and polyfluoroalkyl substances (PFAS) have been observed in many countries. Current deterministic frameworks for risk assessment lack the ability to predict the likelihood of effects and to assess uncertainty. When exposure exceeds tolerable intake levels, these shortcomings hamper risk management and communication. OBJECTIVE: The integrated probabilistic risk assessment (IPRA) combines dose-response and exposure data to estimate the likelihood of adverse effects. We evaluated the usefulness of the IPRA for risk characterization related to decreased levels of total triiodothyronine (T 3) in humans following a real case of high exposure to PFAS via drinking water. METHODS: PFAS exposure was defined as serum levels from residents of a contaminated area in Ronneby, Sweden. Median levels were 270 ng=mL [perfluorooctane sulfonic acid (PFOS)] and 229 ng=mL [perfluorohexane sulfonic acid (PFHxS)] for individuals who resided in Ronneby 1 y before the exposure termination. This data was integrated with data from a subchronic toxicity study in monkeys exposed daily to PFOS. Benchmark dose modeling was employed to describe separate dose-effect relationship for males and females, and extrapolation factor distributions were used to estimate the corresponding human benchmark dose. The critical effect level was defined as a 10% decrease in total T 3. RESULTS: The median probability of critical exposure, following a combined exposure to PFOS and PFHxS, was estimated to be [2.1% (90% CI: 0:4%-13:1%)]. Gender-based analysis showed that this risk was almost entirely distributed among women, namely [3.9% (90% CI: 0:8%-21:6%)]. DISCUSSION: The IPRA was compared with the traditional deterministic Margin of Exposure (MoE) approach. We conclude that probabilistic risk characterization represents an important step forward in the ability to adequately analyze group-specific health risks. Moreover, quantifying the sources of uncertainty is desirable, as it improves the awareness among stakeholders and will guide future efforts to improve accuracy.

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Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA)

Cited by 144 publications

References 81 publications

Evaluation of Maternal, Embryo, and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

Evaluation of Maternal, Embryo, and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

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

A Probabilistic Approach to Evaluate the Risk of Decreased Total Triiodothyronine Hormone Levels following Chronic Exposure to PFOS and PFHxS via Contaminated Drinking Water

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