Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)

Chang, Shu Ching; Thibodeaux, Julie; Eastvold, Mary L.; Ehresman, David J.; Bjork, James A.; Froehlich, John W.; Lau, Christopher; Singh, Ravinder J.; Wallace, Kendall B.; Butenhoff, John L.

doi:10.1016/j.tox.2007.01.020

Cited by 60 publications

(28 citation statements)

References 61 publications

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“…This is opposite the observation in the present study. Finally, a negative bias in thyroidrelated analog methods, using another perfluoroalkyl acid (PFOS), has recently been reported by Chang et al (2007).…”

Section: Discussionmentioning

confidence: 99%

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

Olsen

Zobel

2007

Int Arch Occup Environ Health

255

178

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Objectives Perfluorooctanoic acid (PFOA) results in peroxisome proliferator mediated effects in rats and mice resulting in hypolipidemia but not in monkeys. Counterintuitive modestly positive associations between PFOA and cholesterol levels in production workers have been inconsistently reported. The purpose of this assessment was to examine this association in male workers who manufactured or used PFOA at three facilities. Methods Subjects were male employee voluntary participants of a fluorochemical medical surveillance program who provided blood samples for serum measurement of PFOA (perfluorooctanoate) and various lipid, hepatic, and thyroid parameters. Statistical analyses included multiple and logistic regression and analysis of covariance. Results A total of 506 employees, who did not take cholesterol-lowering medications (93% of all male participants), were analyzed. Serum PFOA concentrations ranged from 0.007 to 92.03 lg/ml [arithmetic mean 2.21 lg/ml (95% confidence interval 1.66-2.77), median 1.10 lg/ml]. Adjusted for age, body mass index, and alcohol usage in regression analyses, PFOA was not statistically significantly (P > 0.05) associated with total cholesterol or low-density lipoproteins (LDL). High-density lipoproteins (HDL) were significantly negatively (P < 0.01) associated with PFOA for the three facilities combined but not by individual sites, indicating the overall result was likely a consequence of residual confounding due to different demographic profiles at these sites. Serum triglycerides were significantly positively associated with PFOA but not consistently by locations. There were no statistically significant associations observed between PFOA and hepatic enzymes for the three facilities combined although some modest positive associations were observed between PFOA and hepatic enzymes at one of the three facilities. Analyses of all locations showed no associations with TSH or T4 and PFOA. A negative association was observed for free T4 and positive association for T3; however, the findings were well within these assays' normal reference ranges. Conclusion There was no evidence that employees' serum PFOA concentrations were associated with total cholesterol or LDL. A negative association with HDL was explained by demographic differences across the three locations. Several explanations are offered for the inconsistent triglyceride associations with PFOA including both methodological as well as biological possibilities.

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Section: Discussionmentioning

confidence: 99%

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

Olsen

Zobel

2007

Int Arch Occup Environ Health

255

178

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“…In humans as well as in animals, perfluorooctanoate adversely affects fT 4 (52,53). In the National Health and Nutrition Examination Survey carried out in the United States (54), individuals with high levels of perfluorooctanoic acid more frequently reported treated thyroid disease.…”

Section: Endocrine Disrupting Chemicalsmentioning

confidence: 99%

Epidemiological trends of iodine-related thyroid disorders: an example from Slovenia

Gaberšček

Zaletel

2016

Archives of Industrial Hygiene and Toxicology

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The epidemiology of thyroid disorders is significantly associated with iodine supply. In 1999, Slovenia increased iodine content in kitchen salt from 10 mg to 25 mg of potassium iodide per kg of salt. According to the WHO criteria, Slovenia shifted from a mildly iodine-deficient country to a country with adequate iodine intake. Ten years after the increase in iodine intake, the incidence of diffuse goitre and thyroid autonomy decreased. Now patients with diffuse goitre and thyroid autonomy reach older age than the patients before the increase in iodine intake. In addition, patients with thyroid autonomy are less frequently hyperthyroid than ten years ago and iodine-induced hyperthyroidism is less severe. The incidence of highly malignant thyroid carcinoma has also dropped. However, the incidence of Hashimoto's thyroiditis increased, most probably in genetically predisposed individuals. Over the last ten years, many animal and in vitro studies evaluated the effects of endocrine disrupting chemicals (EDC) on various aspects of the thyroid function. They mostly studied the effects of polychlorinated biphenyls (PCBs) and dioxins, brominated flame retardants, phthalates, bisphenol A, perfluorinated chemicals, and perchlorate. However, human studies on the effects of EDCs on the thyroid function are very scarce, especially the long-term ones. What they do suggest is that PCBs and dioxins interfere with the transport of thyroid hormones and adversely affect the thyroid function. Many authors agree that iodine deficiency predisposes the thyroid gland to harmful effects of EDCs. Therefore the effects of EDCs in iodine-deficient areas could be more severe than in areas with adequate iodine intake.

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“…Depression of serum triiodothyronine (T 3 ) and/or thyroxine (T 4 ) in PFOA- and PFOS-exposed rats and monkeys has been reported (Butenhoff et al 2002; Lau et al 2007), but without an expected corresponding elevation of thyroid-stimulating hormone (TSH) through feedback stimulation of the hypothalamic–pituitary–thyroid axis. However, it has been hypothesized these associations could be an artifact of the use of analog methods for assessment of free thyroid hormones and are absent if the equilibrium dialysis method is used (Chang et al 2007; Lau et al 2007). …”

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confidence: 99%

Epidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)

Steenland

Fletcher

Savitz

2010

Environ Health Perspect

555

363

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Objective and sourcesWe reviewed the epidemiologic literature for PFOA.Data synthesisPerfluorooctanoic acid (PFOA) does not occur naturally but is present in the serum of most residents of industrialized countries (U.S. median, 4 ng/mL). Drinking water is the primary route of exposure in some populations, but exposure sources are not well understood. PFOA has been used to manufacture such products as Gore-Tex and Teflon. PFOA does not break down in the environment; the human half-life is estimated at about 3 years. PFOA is not metabolized in the body; it is not lipophilic. PFOA is not directly genotoxic; animal data indicate that it can cause several types of tumors and neonatal death and may have toxic effects on the immune, liver, and endocrine systems. Data on the human health effects of PFOA are sparse. There is relatively consistent evidence of modest positive associations with cholesterol and uric acid, although the magnitude of the cholesterol effect is inconsistent across different exposure levels. There is some but much less consistent evidence of a modest positive correlation with liver enzymes. Most findings come from cross-sectional studies, limiting conclusions. Two occupational cohort studies do not provide consistent evidence for chronic disease; both are limited by sample size and reliance on mortality data. Reproductive data have increased recently but are inconsistent, and any observed adverse effects are modest.ConclusionsEpidemiologic evidence remains limited, and to date data are insufficient to draw firm conclusions regarding the role of PFOA for any of the diseases of concern.

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Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)

Cited by 60 publications

References 61 publications

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

Epidemiological trends of iodine-related thyroid disorders: an example from Slovenia

Epidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)

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