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 Nutrition Examination Survey; among the women with endometriosis the values were, respectively, 29% and 6.8 (3.1) years; among those without endometriosis these values were 18% and 5.3 (2.8) years. In simulations, menstrual fluid loss (ml/cycle) in women taking oral contraceptives was assumed to be 56% of loss in non-users. We evaluated the association between simulated plasma PFAS concentration and endometriosis in the simulated population using logistic regression. Based on the simulations, the association between PFAS levels and endometriosis attributable to differential contraceptive use had an odds ratio (95% CI) of 1.05 (1.02, 1.07) for a loge unit increase in PFOA and 1.03 (1.02, 1.05) for PFOS. In comparison, the epidemiologic study reported odds ratios of 1.62 (0.99, 2.66) for PFOA and 1.25 (0.87, 1.80) for PFOS. Our results suggest that the influence of oral contraceptive use on the association between PFAS levels and endometriosis is relatively small.
•We performed a quantitative bias analysis of a study of PFAS and endometriosis•PFAS levels were simulated in women with and without endometriosis.•Simulated levels of PFOS and PFOA were affected by oral contraceptive (OC) use.•Failure to consider OC use caused bias in the PFAS-endometriosis association
In epidemiologic and exposure research, biomonitoring is often used as the basis for assessing human exposure to environmental chemicals. Studies frequently rely on a single urinary measurement per ...participant to assess exposure to non-persistent chemicals. However, there is a growing consensus that single urine samples may be insufficient for adequately estimating exposure. The question then arises: how many samples would be needed for optimal characterization of exposure? To help researchers answer this question, we developed a tool called the Biomarker Reliability Assessment Tool (BRAT). The BRAT is based on pharmacokinetic modeling simulations, is freely available, and is designed to help researchers determine the approximate number of urine samples needed to optimize exposure assessment. The BRAT performs Monte Carlo simulations of exposure to estimate internal levels and resulting urinary concentrations in individuals from a population based on user-specified inputs (e.g., biological half-life, within- and between-person variability in exposure). The BRAT evaluates-through linear regression and quantile classification-the precision/accuracy of the estimation of internal levels depending on the number of urine samples. This tool should guide researchers towards more robust biomonitoring and improved exposure classification in epidemiologic and exposure research, which should in turn improve the translation of that research into decision-making.
Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), ...which is related to PFAS concentration and birth weight.
We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS-birth weight association observed in epidemiologic studies might be attributable to GFR.
We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data.
The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: -3.40, -2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: -8.46, -5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR-birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: -21.66, -7.78) and 14.72 g (95% CI: -8.92, -1.09) reductions in birth weight, respectively.
Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy.
Human exposure to pesticides commands the implementation of food safety control, but few studies have provided a comparative assessment of conventional and organic products. This study set out to ...examine 22 pesticides in four distinct commodities (lettuce, apples, grapes, and tomatoes) from conventional and organic agriculture available to consumers. A multiresidue procedure based on QuEChERS extraction and ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was first validated for its robustness. Suitable determination coefficients (R2 > 0.99) and recoveries generally between 70 and 110% were obtained. Intraday and interday variations were <20% and low matrix effects were noted with sample-to-sample variation. Method limits of detection (LOD) in the overall range of 0.05–2 μg kg−1 were obtained. The validated method was applied to 133 fruit and vegetable samples purchased in Canada, including conventional and organic culture samples. Overall, 47% of the 133 samples had levels above the LOD for at least one pesticide. Neonicotinoid insecticides were detected in all four product types. Imidacloprid (0.08–29 μg kg−1), acetamiprid (0.11–108 μg kg−1), and clothianidin (0.13–141 μg kg−1) were the most recurrent. Atrazine was reported in approximately a third of the lettuce samples (0.25–7.5 μg kg−1). For varieties with samples available from both organic and conventional agriculture, the proportion of insecticide levels > LOD was significantly higher (p < 0.05) for samples from conventional agriculture (9.7%) than from organic agriculture (2.0%). Measured levels were compliant to Canadian Maximum Residue Limits (MRLs), but a thorough human health risk assessment has yet to be conducted for many of these pesticides.
•Multiclass pesticides were analyzed by QuEChERS–LC-MS/MS in fruits and vegetables.•Testing of 133 real samples indicated 47% of positives to at least one pesticide.•Multiple pesticide residues were detected in about half of these positive samples.•Recurrent pesticides were imidacloprid, acetamiprid, clothianidin, and atrazine.•Higher pesticide occurrence was noted in varieties of conventional vs. organic culture.
Despite 20 y of biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) in both serum and urine, we have an extremely limited understanding of PFAS concentrations in breast milk of women ...from the United States and Canada. The lack of robust information on PFAS concentrations in breast milk and implications for breastfed infants and their families were brought to the forefront by communities impacted by PFAS contamination.
The objectives of this work are to:
) document published PFAS breast milk concentrations in the United States and Canada;
) estimate breast milk PFAS levels from maternal serum concentrations in national surveys and communities impacted by PFAS; and
) compare measured/estimated milk PFAS concentrations to screening values.
We used three studies reporting breast milk concentrations in the United States and Canada We also estimated breast milk PFAS concentrations by multiplying publicly available serum concentrations by milk:serum partitioning ratios for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Measured and estimated breast milk concentrations were compared to children's drinking water screening values.
Geometric means of estimated breast milk concentrations ranged over approximately two orders of magnitude for the different surveys/communities. All geometric mean and mean estimated and measured breast milk PFOA and PFOS concentrations exceeded drinking water screening values for children, sometimes by more than two orders of magnitude. For PFHxS and PFNA, all measured breast milk levels were below the drinking water screening values for children; the geometric mean estimated breast milk concentrations were close to-or exceeded-the children's drinking water screening values for certain communities. Exceeding a children's drinking water screening value does not indicate that adverse health effects will occur and should not be interpreted as a reason to not breastfeed; it indicates that the situation should be further evaluated. It is past time to have a better understanding of environmental chemical transfer to-and concentrations in-an exceptional source of infant nutrition. https://doi.org/10.1289/EHP10359.
Oil and gas exploitation can release several contaminants in the environment, including trace elements, with potentially deleterious effects on exposed pregnant individuals and their developing ...fetus. Currently, there is limited data on pregnant individuals’ exposure to contaminants associated with oil and gas activity.
We aimed to 1)measure concentrations of trace elements in biological and tap water samples collected from pregnant individuals participating in the EXPERIVA study; 2)compare with reference populations and health-based guidance values; 3)assess correlations across matrices; and 4)evaluate associations with the density/proximity of oil and gas wells.
We collected tap water, hair, nails, and repeated urine samples from 85pregnant individuals, and measured concentrations of 21trace elements. We calculated oil and gas well density/proximity (Inverse Distance Weighting IDW) for 4buffer sizes (2.5 km, 5 km, 10 km, no buffer). We performed Spearman’s rank correlation analyses to assess the correlations across elements and matrices. We used multiple linear regression models to evaluate the associations between IDWs and concentrations.
Some study participants had urinary trace element concentrations exceeding the 95th percentile of reference values; 75% of participants for V, 29% for Co, 22% for Ba, and 20% for Mn. For a given trace element, correlation coefficients ranged from −0.23 to 0.65 across matrices; correlations with tap water concentrations were strongest for hair, followed by nails, and urine. Positive (e.g., Cu, Cr, Sr, U, Ga, Ba, Al, Cd) and negative (e.g., Fe) associations were observed between IDW metrics and the concentrations of certain trace elements in water, hair, and nails.
Our results suggest that pregnant individuals living in an area of oil and gas activity may be more exposed to certain trace elements (e.g., Mn, Sr, Co, Ba) than the general population. Association with density/proximity of wells remains unclear.
BACKGROUND: Despite experimental evidence, most epidemiologic studies to date have not supported an association between exposure to persistent organic pollutants (POP) and breast cancer incidence in ...humans. This may be attributable to difficulties in estimating blood/tissue POP concentration at critical time periods of carcinogenesis. OBJECTIVES: In this work we aimed to develop a tool to estimate lifetime POP blood/tissue exposure and levels during any hypothesized rime window of susceptibility in breast cancer development. METHODS: We developed a physiologically based pharmacokinetic (PBPK) model that can account for any given physiologic lifetime history. Using data on pregnancies, height, weight, and age, the model estimates the values of physiologic parameters (e.g., organ volume, composition, and blood flow) throughout a woman's entire life. We assessed the lifetime toxicokinetic profile (LTP) for various exposure scenarios and physiologic factors (i.e., breast-feeding, growth, pregnancy, lactation, and weight changes). RESULTS: Simulations for three POPs hexachlorobenzene, polychlorinated biphenyl (PCB)-153, PCB-180 using different lifetime physiologic profiles showed that the same blood concentration at 55 years of age can be reached despite totally different LTP. Aside from exposure levels, lactation periods and weight profile history were shown to be the factors that had the greatest impact on the LTP. CONCLUSIONS: This new lifetime PBPK model, which showed the limitations of using a single sample value obtained around the time of diagnosis for lifetime exposure assessment, will enable researchers conducting environmental epidemiology studies to reduce uncertainty linked to past POP exposure estimation and to consider exposure during time windows that are hypothesized to be mechanistically critical in carcinogenesis.
► In line with Self-Determination Theory, the Gaming Motivation Scale (GAMS) was developed. ► Results confirmed the internal consistency of the six subscales. ► The factorial and construct validity ...of the GAMS was supported.
The purpose of the present research was to develop and validate a measure of gaming motivation. In line with Self-Determination Theory, the Gaming Motivation Scale (GAMS) is designed to assess intrinsic motivation, integrated, identified, introjected, and external regulation, as well as amotivation. Results confirmed the internal consistency of the six subscales. In addition, the six-factor structure of the GAMS was confirmed, as was the presence of a simplex-like structure underlying the GAMS subscales. Finally, the construct validity of the GAMS was supported by correlations with need satisfaction as postulated by Self-Determination Theory. The importance of this new multidimensional scale for the development of research programs on gaming motivation is discussed.
► We put forward a framework to optimize biomonitoring using population PBPK modeling. ► The optimal time to measure styrene in venous blood is at the end of shift. ► Styrene in exhaled air should be ...measured 15min after the end of shift. ► Our results support the BEI® of 0.2mg/l in venous blood at the end of shift. ► We propose a BLV of 0.3ppm in exhaled air 15min after the end of shift.
Biomonitoring of chemicals in the workplace provides an integrated characterization of exposure that accounts for uptake through multiple pathways and physiological parameters influencing the toxicokinetics.
We used the case of styrene to (i) determine the best times to sample venous blood and end-exhaled air, (ii) characterize the inter-individual variability in biological levels following occupational exposure and (iii) propose biological limit values using a population physiologically based pharmacokinetic (PBPK) model.
We performed Monte Carlo simulations with various physiological, exposure and workload scenarios. Optimal sampling times were identified through regression analyses between levels in biological samples and 24-h area under the arterial blood concentration vs. time curve. We characterized the variability in levels of styrene in biological samples for exposures to a time weighted average (TWA) of 20ppm.
Simulations suggest that the best times to sample venous blood are at the end of shift in poorly ventilated workplaces and 15min after the shift in highly ventilated workplaces. Exhaled air samples are most informative 15min after the shift. For a light workload, simulated styrene levels have a median (5th–95th percentiles) of 0.4mg/l (0.2–0.6) in venous blood at the end of shift and 0.5ppm (0.3–0.8) in exhaled air 15min after the end of shift.
This study supports the current BEI® of the ACGIH of 0.2mg/l of styrene in venous blood at the end of shift and indicates a biological limit value of 0.3ppm in end-exhaled air 15min after the end of shift.
In our recent paper (Verner et al. 2013), we suggested that gestational weight gain (GWG) confounded the association between prenatal PCB-153 (polychlorinated biphenyl-153) exposure and birth weight ...observed in the meta-analysis by Govarts et al.
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