Response to Comment on "Enhanced Elimination of Perfluorooctane Sulfonic Acid by Menstruating Women: Evidence from Population-based Pharmacokinetic Modeling (original) (raw)
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Environmental Science & Technology, 2014
Human biomonitoring studies have shown that concentrations of perfluorooctane sulfonic acid (PFOS) in men are higher than in women. We investigate sex differences in elimination of PFOS by fitting a populationbased pharmacokinetic model to six cross-sectional data sets from 1999 to 2012 from the US National Health and Nutrition Examination Survey (NHANES) and derive human first-order elimination rate constants (k E ) and corresponding elimination half-lives (t 1/2 ) for PFOS, where t 1/2 = ln 2/k E . We use a modified version of the Ritter population-based pharmacokinetic model and derive elimination rate constants separately for men and women. The model accounts for population-average lifetime changes in PFOS intake, body weight, and menstruation rate. We compare the model-derived elimination rate constant for hypothetical nonmenstruating women to the elimination rate constant for men and women when menstruation is included as a loss process to evaluate the hypothesis that loss of PFOS by menstruation is an important process for women. The modeled elimination halflife for men is 4.7 years, and the modeled elimination half-life for women when excluding losses from menstruation is 3.7 years. The elimination half-life for women when menstruation is included in the model is 4.0 years. Thus, menstruation accounts for 30% of the discrepancy in elimination of PFOS between men and women. The remaining discrepancy is likely due to other sexspecific elimination routes that are not considered in our modeling.
Environment international, 2017
An association between serum levels of perfluoroalkyl substances (PFAS) and endometriosis has recently been reported in an epidemiologic study. Oral contraceptive use to treat dysmenorrhea (pelvic pain associated with endometriosis) could potentially influence this association by reducing menstrual fluid loss, a route of excretion for PFAS. In this study, we aimed to evaluate the influence of differential oral contraceptive use on the association between PFAS and endometriosis. We used a published life-stage physiologically based pharmacokinetic (PBPK) model to simulate plasma levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from birth to age at study participation (range 18-44years). In the simulated population, PFAS level distributions matched those for controls in the epidemiologic study. Prevalence and geometric mean duration (standard deviation [SD]) of oral contraceptive use in the simulated women were based on data from the National Health and Nutr...
Environmental health : a global access science source, 2015
We previously demonstrated an association between plasma perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and longer time to pregnancy (TTP) in a sample from the Danish National Birth Cohort (DNBC, 1996-2002). In this study we investigated this association in a new sample from the same cohort. Sample 1 consisted of 440 women, and Sample 2 consisted of 1161 women from whom we previously published the associations between PFOS or PFOA and TTP. We performed sample-specific and pooled analyses using discrete-time survival analyses to estimate fecundability ratios according to PFOS and PFOA quartiles, adjusted for potential confounders chosen guided by a directed acyclic graph. We also estimated odds ratios for infertility (TTP > 12 months or infertility treatment) according to PFOS and PFOA by multivariable logistic regression. In Sample 1 PFOS was not associated with lower fecundability ratios or infertility, and there was a tendency towards longer TTP with increasing ...
Pharmacokinetic modeling of perfluorooctanoic acid during gestation and lactation in the mouse
Reproductive Toxicology, 2009
Perfluorooctanoic acid (PFOA) is a processing aid for the polymerization of commercially valuable fluoropolymers. Its widespread environmental distribution, presence in human blood, and adverse effects in animal toxicity studies have triggered attention to its potential adverse effects to humans. PFOA is not metabolized and exhibits dramatically different serum/plasma half-lives across species. Estimated half-lives for humans, monkeys, mice, and female rats are 3-5 years, 20-30 days, 12-20 days, and 2-4 h, respectively. Developmental toxicity is one of the most sensitive adverse effects associated with PFOA exposure in rodents, but its interpretation for risk assessment is currently hampered by the lack of understanding of the inter-species pharmacokinetics of PFOA. To address this uncertainty, a biologically supported dynamic model was developed whereby a two-compartment system linked via placental blood flow described gestation and milk production linked a lactating dam to a growing pup litter compartment. Postnatal serum levels of PFOA for 129S1/SvImJ mice at doses of 1 mg/kg or less were reasonably simulated while prenatal and postnatal measurements for CD-1 mice at doses of 1 mg/kg or greater were simulated via the addition of a biologically based saturable renal resorption description. Our results suggest that at low doses a linear model may suffice for describing the pharmacokinetics of PFOA while a more complex model may be needed at higher doses. Although mice may appear more sensitive based on administered dose of PFOA, the internal dose metrics estimated in this analysis indicate that they may be equal or less sensitive than rats.
Environmental science & technology, 2016
To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184 colostrum samples collected from women participating in a cohort study in eastern Slovakia between 2002 and 2004. During their hospital delivery stay, mothers completed a food frequency questionnaire, and demographic and reproductive data were also collected. PFOS and PFOA predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). The geometric mean concentration in colostrum was 35.3 pg/ml for PFOS and 32.8 pg/ml for PFOA., In multivariable models, parous women had 40% lower PFOS (95% CI: -56 to -17%) and 40% lower PFOA (95% CI: -54 to -23%) concentrations compared with nulliparous women. Moreover, fresh/frozen fish consumption, lo...
Chemosphere, 2019
Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances (PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor. The aim of this study was to investigate PFAS interference on hormonal endometrial regulation. This study was performed within a screening protocol to evaluate reproductive health in high schools. We studied a cohort of 146 exposed females aged 18-21 from the Veneto region in Italy, one of the four areas worldwide heavily polluted with PFAS, and 1080 non-exposed controls. In experiments on Ishikawa cells included UV-Vis spectroscopy, microarray analysis and qPCR. We report a significant dysregulation of the genetic cascade leading to embryo implantation and endometrial receptivity. The most differentially-expressed genes upon PFOA coincubation were ITGB8, KLF5, WNT11, SULT1E1, ALPPL2 and G0S2 (all p < 0.01). By qPCR, we confirmed an antagonistic effect of PFOA on all these genes, which was reversed at higher progesterone levels. Molecular interference of PFOA on progesterone was confirmed by an increase in the intensity of absorption spectra at 250 nm in a dose-dependent manner, but not in the presence of β-estradiol. Age at menarche (+164 days, p = 0.006) and the frequency of girls with irregular periods (29.5% vs 21.5%, p = 0.022) were significantly higher in the exposed group. Our results are indicative of endocrine-disrupting activity of PFAS on progesterone-mediated endometrial function.
Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies
Environmental research, 2015
The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than...