Implications of Early Menopause in Women Exposed to Perfluorocarbons

Abstract

These data suggest that PFC are associated with endocrine disruption in women and that further research on mechanisms is warranted.

Biotransformation of 8:2 fluorotelomer alcohol by recombinant human cytochrome P450s, human liver microsomes and human liver cytosol

“…27 PFAAs, especially PFOA, have been reported to cause a wide range of toxic effects including hepatotoxicity, developmental toxicity, immunotoxicity and neonatal toxicity. [28][29][30] Epidemiological studies have also found signicant or suggestive associations between PFAA exposure and biochemical or physiological end points.…”

Extensive literature search and provision of summaries of studies related to the oral toxicity of perfluoroalkylated substances (PFASs), their precursors and potential replacements in experimental animals and humans. Area 1: Data on toxicokinetics (absorption, distribution, metabolism, excretion) in in vitro studies, experimental animals and humans. Area 2: Data on toxicity in experimental animals. Area 3: Data on observations in humans

“…The HR was 1.23 for serum concentrations in the 2 nd (> 9-180.4 ng/mL) vs. 1 st (0.14-9 ng/mL) tertile, and 1.16 for serum concentrations in the 3 rd (> 18.4 ng/mL) vs. 1 st tertile. Knox et al (2011b) also reported among 25 957 women in the C8 Health Project that PFOS exposure significantly increased the risk of menopause in all exposure categories compared to the lowest in those aged over 43-years. A similar association was also observed for the rate of hysterectomy (HRs were 1.44 and 2.56, respectively) (Taylor et al, 2013).…”

“…However, Melzer et al (2010) found that in NHANES men with ≥ 36.8 mg/mL exposure versus those with ≤ 25.5 mg/mL exposure the OR for treated thyroid disease was 2.68 (95 % CI = 1.03-6.98), although no difference was observed in women. Knox et al (2011b) also reported that exposure levels in the C8 Health Project were associated with a significant increase in serum thyroxine (regression coefficient = 0.14, p < 0.0001) and a decrease in T3 uptake (Coeff ranging from -0.21 to 0.009 in men/women aged ≤ 50 and > 50). Gallo et al (2012) also reported that in PFOS-exposed individuals in the C8 Health Project, levels of ALT (OR 22 = 1.13, 95 % CI = 1.07-1.18), GGT (OR 13 = 0.98, 95 % CI = 0.94-1.02) and bilirubin (OR 13 = 1.11, 95 % CI = 0.96-1.28) (indicators of liver function) were significantly increased, with significant dose-response relationships (p < 0.05).…”

“…See subsequent sections for data on other PFASs. Knox et al (2011b) also reported that among older women (> 42 years) in the C8 Health Project the OR for menopause was significantly higher in all quintiles compared to the lowest.…”

Per- and polyfluorinated substances in the Nordic Countries

“…The following associations have been seen for PFOA in the "C8 Health Project": increased total cholesterol and low-density lipoprotein in children and adolescents (Frisbee et al, 2010); increased blood lipid levels in relation to elevated PFOA (and PFOS) concentrations in the blood ; no associations to HDL cholesterol; positive associations with serum and liver enzymes (transaminase; a marker of hepatocellular damage) indicating hepatotoxic effect in humans (Gallo et al, 2012); positive association to serum uric acid (Steenland et al, 2010); no association between PFOA and TSH (n = 371) (Emmett et al, 2006); significant positive elevation in serum T4 and a significant reduction in T3 uptake in adults (Knox et al, 2011a); no associations with preterm birth and fetal growth restrictions (Savitz et al, 2012), positive association with hypothyroidism in children (Odds ratio (OR): 1.54; 95% confidence interval (CI): 1.00, 2.37) ; associations with Attention Deficit Hyperactivity Disorder (ADHD) in children 5-18 years of age, with a small increase in prevalence for the second quartile of exposure and a decrease for the highest versus lowest quartile (Stein and Savitz, 2011); more likely to have experienced menopause among perimenopausal women with higher level of PFOA (and PFOS), suggesting endocrine disrupting effects (Knox et al, 2011b); association with lower serum concentrations of IgA and IgE (for IgE in females only) (C8 Science Panel, 2009).…”