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Introduction: While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration., Method: This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France). Nine PFAS were measured in umbilical cord blood, and the children attended a clinical examination at age 12. Anthropometry, blood metabolic markers, and blood pressure were measured and used to build an internal cardiometabolic score. Linear regression and Quantile G-computation models were used to evaluate individual and mixture PFAS effects, adjusting for confounders and stratifying by sex and pubertal stage., Results: No statistically significant association was observed between prenatal exposure to PFAS and cardiometabolic score at age 12. In post-menarche girls, perfluorohexane sulfonate (PFHxS) and perfluorodecanoic acid (PFDA) were statistically significantly associated with a decrease in a number of adiposity parameters (e.g., Body mass index z-score: beta [95%CI] = -0.37 [-0.67; -0.07]), as well as a decrease in low-density lipoproteins (LDL) and leptin levels. Similar results were observed with PFAS mixture, with statistically significantly decreased tricipital skinfolds (beta [95%CI] = -1.30 [(-2.54;-0.06)]). Isolated associations, including higher systolic blood pressure, changes in cholesterol levels, and lower adiponectin levels were observed in specific subgroups., Conclusion: There is no clear evidence of an association between prenatal exposure to PFAS and the cardiometabolic health at earlier stage of pubertal development. However, inverse associations between PFAS and anthropometric measures have been observed in post-menarche girls. While the literature on this topic is scarce in pre-adolescents, these results suggest the importance of considering sex and pubertal stage in these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although the ovarian reserve is constituted in utero, the literature on the effects of persistent organic pollutants (POPs) during this vulnerable period on the ovarian reserve later in life is limited. We investigated whether cord blood concentrations of POPs were associated with decreased anti-Müllerian hormone (AMH, a marker of the ovarian reserve) levels in girls at the age of 12. We included 239 girls from the French mother-child PELAGIE cohort. POP concentrations of 14 organochlorine pesticides, 17 polychlorinated biphenyls (PCBs), 5 polybrominated diphenyl ethers, and 9 per-polyfluoroalkyl substances were measured on cord blood sampled at birth. During a follow-up study at 12 years old, blood samples were collected to measure AMH levels. Single-exposure associations were examined with multivariable linear regression models adjusted a priori for potential confounders. Stratification on menarche status was also performed. Mixture effects were investigated using quantile g-computation and Bayesian kernel machine regression. Overall, 16 POPs were measured in at least 30% of samples. No significant associations were found in multivariable linear regressions, except for the third tercile of exposure to PCB 180 which was statistically significantly associated with an increase in AMH levels at 12 years old (Tercile 2 v. Tercile 1: 0.13 ng/mL, 95% CI = -0.29, 0.56; Tercile 3 v. Tercile 1: 0.51 ng/mL, 95% CI = 0.02, 0.99). Additionally, in post-menarcheal girls (N = 104) only, the second tercile of p,p'-DDE was statistically significantly associated with decreased AMH levels at 12 years old (Tercile 2 v. Tercile 1: -0.61 ng/mL, 95% CI = -1.16, -0.05, Tercile 3 v. Tercile 1: 0.02 ng/mL, 95% CI = -0.51, 0.54). Both mixture models returned null associations. Despite the limited associations observed in this study, we recommend exploring these associations in larger mother-child cohorts and at older ages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Halogenated organophosphate esters (OPEs) are increasingly used as flame retardants to replace polybrominated diphenyl ethers (PBDEs), which have been phased out due to their confirmed persistence, toxicity, and ability to undergo long range atmospheric transport. Non-halogenated OPEs are primarily used as plasticizers. While human exposure to PBDEs in the Canadian Arctic is well documented, it is not the case for OPEs. To assess the exposure to OPEs in Inuit living in Nunavik (northern Québec, Canada), we measured 16 metabolites of halogenated and non-halogenated OPEs in pooled urine samples from the last population health survey conducted in Nunavik, the Qanuilirpitaa? 2017 Inuit Health Survey (Q2017). Urine samples (n = 1266) were pooled into 30 pools by sex (female; male), age groups (16-19; 20-29; 30-39; 40-59; 60+ years old) and regions (Hudson Bay; Hudson Strait; Ungava Bay). Q2017 geometric means and 95 % confidence intervals were compared with data from the Canadian Health Measures Survey Cycle 6 (2018-2019) (CHMS). Halogenated OPEs were systematically detected and generally found at higher concentrations than non-halogenated OPEs in both Q2017 and CHMS. Furthermore, urinary levels of BCIPP and BDCIPP (halogenated) were lower in Q2017 compared to CHMS while concentrations of DPhP, DpCP and DoCP (non-halogenated) were similar between Q2017 and CHMS. Across the 16 metabolites measured in Q2017, BCIPHIPP (halogenated) had the highest levels (geometric mean: 1.40 μg/g creatinine). This metabolite was not measured in CHMS and should be included in future surveys. Overall, our results show that Inuit in Nunavik are exposed to lower or similar OPEs levels than the rest of the general Canadian population suggesting that the main current exposure to OPEs may be from consumer goods containing flame retardants and imported from the south rather than long-range atmospheric transport to the Arctic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of the Esteban study was to describe levels of various biomarkers of exposure to several environmental pollutants, including metals and metalloids, among the French population. This paper describes the distribution of concentrations of 28 metals and metalloids in two different populations, and estimates the main determinants of exposure to total arsenic, the sum of inorganic arsenic (iAs) and its two metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), cadmium, chromium, copper, mercury and nickel., Methods: Esteban is a cross-sectional study conducted between 2014 and 2016 on a random sample of 2503 adults (18-74 years old) and 1104 children (6-17 years old) from the general population. The data collected included biological samples (blood, hair, and urines), socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors and lifestyle. The geometric mean and percentiles of the distribution were estimated for each metal. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model., Results: Only four metals had a quantification rate below 90% in adults (beryllium, iridium, palladium, and platinum), and three metals in children (beryllium, iridium, and platinum). The concentrations of total arsenic, cadmium, chromium and mercury were higher than those found in most international studies. The determinants significantly associated with exposure were mainly diet and smoking., Conclusions: Esteban provided a nationwide description of 28 metal and metalloid exposure levels for adults (some never measured before) and for the first time in children. The study results highlighted widespread exposure to several metals and metalloids. These results could be used to advocate public health decisions for continued efforts to reduce harmful exposure to toxic metals. The Reference values (RV 95 ) built from Esteban could also be used to support future government strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dioxins, furans, and dioxin-like polychlorinated biphenyls (PCBs) are a group of persistent and toxic chemicals that are known to have human health effects at low levels. These chemicals have been produced for commercial use (PCBs) or unintentionally as by-products of industry or natural processes (PCBs, dioxins, and furans). Additionally, dioxin-like PCBs were formerly used in electrical applications before being banned internationally (2004). These chemicals are widely dispersed in the environment as they can contaminate air and travel hundreds to thousands of kilometers before depositing on land or water, thereafter, potentially entering food chains. Community concerns surrounding the safety of traditional foods prompted a human biomonitoring project in Old Crow, Yukon Territory (YT), Canada (2019). Through collaborative community engagement, dioxins and like compounds were identified as a priority for exposure assessment from biobanked samples. In 2022, biobanked plasma samples (n = 54) collected in Old Crow were used to measure exposures to seven dioxins, ten furans, and four dioxin-like PCBs. 1,2,3,6,7,8-HxCDD, 1,2,3,7,8,9-HxCDD, 1,2,3,4,6,7,8-HpCDD, OCDD, 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF, PCB 126, and PCB 169 were detected in at least 50 % of samples. Among these analytes, the only congener at elevated levels was PCB 169, which was approximately ∼2-fold higher than the general population of Canada. No significant sex-based or body mass index (BMI) differences in biomarker concentrations were observed. Generally, the concentrations of the detected congeners increased with age, except for 1,2,3,4,6,7,8-HpCDD. For the first time, this research measures dioxin and like-compound exposures in Old Crow, advancing the information available on chemical exposures in the Arctic. Further research could be directed towards the investigation of PCB 169 exposure sources and temporal monitoring of exposures and determinants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Clinical dosage of toxic and essential elements in blood is well established and the collection method is still by venipuncture. This method has drawbacks and is not suited for everyone. Volumetric absorptive microsampling (VAMS) has been shown to have advantages over venipuncture. Materials & methods: Using inductively coupled plasma tandem mass spectrometry, a method for quantifying elements in whole blood sampled on VAMS was developed/validated. Method's performance was assessed by comparison with whole blood results. Results: Validation and performance assessment tests tend to show that most of the targeted elements provides accurate and reproducible results comparing to a method of reference. Conclusion: Overall, VAMS presents good preliminary results to eventually become an alternative to venipuncture for blood sampling for some trace elements analysis purposes.

Introduction: Studies have documented high levels of pesticide exposure among men farmworkers; however, few have examined exposures or the experiences of women farmworkers. Data gaps also exist regarding farmworkers' perceived risk and control related to pesticides, information that is critical to develop protective interventions., Objective: We aimed to compare urinary pesticide biomarker concentrations between Latino and Latina farmworkers and examine associations with occupational characteristics, risk perceptions, perceived control, and protective behaviors., Methods: We enrolled a convenience sample of 62 farmworkers (30 men and 32 women) during the pesticide spray season from April-July 2022 in southwestern Idaho. Participants were asked to complete two visits within a seven-day period; at each visit, we collected a urine sample and administered a questionnaire assessing demographic and occupational information. Urine samples were composited and analyzed for 17 biomarkers of herbicides and of organophosphate (OP) and pyrethroid insecticides., Results: Ten pesticide biomarkers (TCPy, MDA, PNP, 3-PBA, 4-F-3-PBA, cis- and trans-DCCA, 2,4-D, Glyphosate, AMPA) were detected in >80% of samples. Men and women had similar urinary biomarker concentrations (p = 0.19-0.94); however, women worked significantly fewer hours than men (p = 0.01), wore similar or greater levels of Personal Protective Equipment (PPE), and were slightly more likely to report having experienced an Acute Pesticide Poisoning (26% of women vs. 14% of men; p = 0.25). We observed inconsistencies in risk perceptions, perceived control, and protective behaviors among men., Discussion: Our study is one the first to examine pesticide exposure and risk perceptions among a cohort of farmworkers balanced on gender. Taken with previous findings, our results suggest that factors such as job tasks, biological susceptibility, or access to trainings and protective equipment might uniquely impact women farmworkers' exposure and/or vulnerability to pesticides. Women represent an increasing proportion of the agricultural workforce, and larger studies are needed to disentangle these findings., Competing Interests: Declaration of conflicts of interest The authors declare they have no actual or potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The commercialization in 2016 of genetically engineered seeds tolerant to dicamba and/or 2,4-dichlorophenoxyacetic acid (2,4-D) has caused a rapid increase in the use of these herbicides. New questions about the reproductive and chronic health effects of long-term exposure to these herbicides have been raised. To assess exposure to dicamba and other pesticides of interest in the Heartland Study, a birth cohort study based in the United States, a new analytical method was needed. The present study describes the development and validation of this new solid phase extraction and liquid chromatography-tandem mass spectrometry method that detects simultaneously 13 pesticides or their metabolites in 250 μL of urine. More specifically, the method allows the analysis of dicamba, 2,4-D and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), which are herbicides, of malathion dicarboxylic acid (MDA), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY) and 2-isopropyl-6-methyl-4-pyrimidinol (IMPY), which are metabolites of organophosphate insecticides, and finally of cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA), 3-Phenoxybenzoic acid (3-PBA), 4-Fluoro-3-phenoxybenzoic acid (4-F-3-PBA) and cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA), which are metabolites of synthetic pyrethroids insecticides. The method was validated under ISO/IEC 17025 guidance. The limit of detection (LOD) in urine samples was 0.10 μg/L for dicamba, while the LOD for other analytes ranged between 0.0038 μg/L and 0.091 μg/L. Accuracy was evaluated by analyzing samples from two External Quality Assessment Schemes, namely G-EQUAS and OSEQAS. Preliminary results obtained following the analysis of 91 urine samples taken from pregnant women enrolled in the Heartland Study are presented here. This method is suitable for human biomonitoring studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are chemical substances spread throughout the environment worldwide. Exposure during pregnancy represents a specific window of vulnerability for child health., Objective: Our objective was to assess the impact of prenatal exposure to multiple PFAS on emotional and behavioral functions in 12-y-old children., Method: In the PELAGIE mother-child cohort (France), prenatal exposure to nine PFAS was measured from concentrations in cord serum samples. Behavior was assessed at age 12 y using the parent-reported Strengths and Difficulties Questionnaire (SDQ) and the self-reported Dominic Interactive for Adolescents (DIA) for 444 children. Associations were estimated using negative binomial models for each PFAS. Bayesian kernel machine regression (BKMR) models were performed to assess the exposure mixture effect on children's behavior., Results: In our study population, 73% of mothers had spent more than 12 y in education. Higher scores on SDQ externalizing subscale were observed with increasing cord-serum concentration of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) [adjusted mean ratio ( aMR ) = 1.18 , 95% confidence interval (CI): 1.03, 1.34, and aMR = 1.14 (95% CI: 1.00, 1.29) for every doubling of concentration, respectively]. Results for the hyperactivity score were similar [ aMR = 1.20 (95% CI: 1.04, 1.40) and aMR = 1.18 (95% CI: 1.02, 1.36), respectively]. With regard to major depressive disorder and internalizing subscales, perfluorodecanoic acid (PFDA) was associated with higher self-reported DIA scores [ aMR = 1.14 (95% CI: 1.01, 1.27) and aMR = 1.11 (95% CI: 1.02, 1.21), respectively]. In terms of the anxiety subscale, PFDA and PFNA were associated with higher scores [ aMR = 1.11 (95% CI: 1.02, 1.21) and aMR = 1.10 (95% CI: 1.01, 1.19), respectively]. Concurrent increases in the PFAS concentrations included in the BKMR models showed no change in the SDQ externalizing and DIA internalizing subscales scores., Conclusion: Prenatal exposure to PFNA and PFOA were associated with increasing scores for measures of externalizing behaviors, specifically hyperactivity. We also identified associations between PFNA and PFDA prenatal exposure levels and increasing scores related to internalizing behaviors (general anxiety and major depressive disorder), which adds to the as yet sparse literature examining the links between prenatal exposure to PFAS and internalizing disorders. https://doi.org/10.1289/EHP12540.

Phthalates are non-persistent chemicals measured as metabolites in urine. Over time, new metabolites have been identified. In the original Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured 11 phthalate metabolites in first trimester urine samples. The goal of the present study was to develop a method to measure new metabolites, to increase the sensitivity for some previously measured metabolites, and to measure these new metabolites in biobanked urine samples from MIREC participants. Using Ultra Performance Liquid Chromatography with a tandem mass spectrometer, we developed a method to measure 24 metabolites from 10 different parent phthalates. Chromatographic interpretation of some of the di-iso-decyl phthalate metabolites (mono-(2-propyl-6oxoheptyl) phthalate (MOiDP), mono-(2,7-methyl-7-carboxyheptyl) phthalate (MCiNP), mono-(2-propyl-6-hydroxy-heptyl) phthalate (MHiDP)) and di-iso-nonyl phthalate metabolites (mono(oxo-isononyl) phthalate (MOiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxy-isononyl) phthalate (MHiNP) and mono-isononyl phthalate (MiNP)) was challenging as these are complex isomeric mixtures. To validate and confirm our quantitation peaks, an assay using a high-resolution detection technique was developed on a Quadrupole Time-of-Flight (QToF) system. This system has a mass resolution of at least 0.005 amu, compared to 0.5 amu for the MS/MS detector. Using the QToF system, the distinction between an isomer and possible interference was achieved with the use of the exact mass. In about 1800 MIREC samples, mono-cyclo-hexyl phthalate (MCHP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), mono-iso-decyl phthalate (MiDP), and mono-n-octyl phthalate (MnOP) were rarely detected, while detection of MMP was improved. MCiOP, MiNP and MCiNP had to be reported semi-quantitatively. Given the complexity of isomeric mixtures of some phthalates, researchers must be careful in their determination of the analytes and the approach used in their quantification when generating biomonitoring data. This study produced biomonitoring data for a large population of pregnant people that can be used in risk assessment of phthalates. Future work will examine associations with birth and child outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Exceptional episodes of exposure to high levels of persistent organic pollutants have already been associated with developmental defects of enamel among children, but knowledge is still scarce concerning the contribution of background levels of environmental contamination., Methods: Children of the French PELAGIE mother-child cohort were followed from birth, with collection of medical data and cord blood samples that were used to measure polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), and perfluorinated alkyl substances (PFASs). At 12 years of age, molar-incisor hypomineralization (MIH) and other enamel defects (EDs) were recorded for 498 children. Associations were studied using logistic regression models adjusted for potential prenatal confounders., Results: An increasing log-concentration of β-HCH was associated with a reduced risk of MIH and EDs (OR = 0.55; 95% CI, 0.32-0.95, and OR = 0.65; 95% CI, 0.43-0.98, respectively). Among girls, intermediate levels of p,p'-DDE were associated with a reduced risk of MIH. Among boys, we observed an increased risk of EDs in association with intermediate levels of PCB 138, PCB 153, PCB 187, and an increased risk of MIH with intermediate levels of PFOA and PFOS., Conclusions: Two OCs were associated with a reduced risk of dental defects, whereas the associations between PCBs and PFASs and EDs or MIH were generally close to null or sex-specific, with an increased risk of dental defects in boys. These results suggest that POPs could impact amelogenesis. Replication of this study is required and the possible underlying mechanisms need to be explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Several studies have reported that prenatal exposure to some persistent organic pollutants (POPs) is associated with higher adiposity in childhood. Few studies have assessed whether this finding persists into adolescence, and few have considered exposure to POPs as a mixture. This study aims to assess the association between prenatal exposure to multiple POPs and adiposity markers and blood pressure in preadolescents., Methods: This study included 1667 mother-child pairs enrolled in the PELAGIE (France) and the INMA (Spain) mother-child cohorts. Three polychlorobiphenyls (PCB 138, 153 and 180, treated as a sum of PCBs) and three organochlorine pesticides (p,p'-Dichlorodiphenyldichloroethylene [p,p'-DDE], β-hexachlorocyclohexane [β-HCH], and hexachlorobenzene [HCB]) were assessed in maternal or cord serum. Body mass index z-score (zBMI), abdominal obesity (waist-to-height ratio > 0.5), percentage of fat mass, and blood pressure (mmHg) were measured at around 12 years of age. Single-exposure associations were studied using linear or logistic regressions, and the POP mixture effect was evaluated using quantile G-computation (qgComp) and Bayesian Kernel Machine Regression (BKMR). All models were adjusted for potential confounders and performed for boys and girls together and separately., Results: Prenatal exposure to the POP mixture was associated with higher zBMI (beta [95 % CI] of the qgComp = 0.15 [0.07; 0.24]) and percentage of fat mass (0.83 [0.31; 1.35]), with no evidence of sex-specific association. These mixture effects were also statistically significant using BKMR. These associations were driven mainly by exposure to HCB and, to a lesser extent, to β-HCH. In addition, the single-exposure models showed an association between β-HCH and p,p'-DDE and higher systolic blood pressure, especially in girls (p,p'-DDE for girls = 1.00 [0.15; 1.86]). No significant associations were found for PCBs., Conclusion: This study suggests that prenatal exposure to POPs, particularly organochlorine pesticides, remains associated with unfavorable cardiometabolic health up to the age of 12., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Lead is harmful for humans by having adverse effects on different biological systems. Venepuncture is the gold standard for blood lead level analysis, but this method has many flaws. The goal of this research was to develop and validate a more practical approach for blood sampling. Materials & methods: Mitra ® devices based on VAMS ® and inductively coupled plasma-MS/MS technologies were employed. Performance evaluation of the newly developed method was also performed by comparing it versus a commonly used method at the Centre de Toxicologie du Québec for blood lead level analysis. Results: Comparison showed no signs of significant difference between the two methods. Conclusion: VAMS may be a useful alternative sampling approach for further research on blood lead analysis and possibly for many other trace elements.

Introduction: Polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs) having numerous toxicological properties, including thyroid endocrine disruption. Our aim was to assess the impact of POPs on thyroid hormones among 12-year-old children, while taking puberty into consideration., Methods: Exposure to 7 PCBs, 4 OCPs, and 6 PFASs (in µg/L), and free tri-iodothyronine (fT3, pg/mL), free thyroxine (fT4, ng/dL), and thyroid-stimulating hormones (TSH, mIU/L) were assessed through blood-serum measurements at age 12 years in 249 boys and 227 girls of the PELAGIE mother-child cohort (France). Pubertal status was clinically rated using the Tanner stages. For each POP, associations were estimated using linear regression, adjusted for potential confounders., Results: Among boys, hexachlorobenzene and perfluorodecanoic acid were associated with decreased fT3 (log-scale; β [95% confidence interval] = -0.07 [-0.12,-0.02] and β = -0.03 [-0.06,-0.00], respectively). Intermediate levels of perfluorohexanesulfonic acid (PFHxS) and PCB180 were associated, respectively, with increased and decreased fT4. After stratification on pubertal status, PCBs and OCPs were associated with decreased TSH only in the more advanced Tanner stages (3-5) and with decreased fT3 among early Tanner stages (1-2). Among girls, PFHxS was associated with decreased TSH (log-scale; β = -0.15 [-0.29,-0.00]), and perfluorooctanoic acid was associated with decreased fT3 (β2nd_tercile = -0.06 [-0.10,-0.03] and β3rd_tercile = -0.04 [-0.08,-0.00], versus. 1st tercile)., Discussion: This cross-sectional study highlights associations between some POPs and thyroid function disruption, which appears consistent with the literature. Considering that the associations were sex-specific and moderated by pubertal status in boys, complex endocrine interactions are likely involved., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Bisphenol A (BPA), a phenolic chemical incorporated into many plastic products, has been found to act as an endocrine disruptor that potentially is linked to adverse neurodevelopmental outcomes. Prenatal BPA concentration levels were assessed in 10 English-speaking Caribbean countries by randomly selecting 15 maternal urine samples from approximately 50 pregnant women samples collected in each island and then comparing the findings with comparable data from Canada and the U.S. BPA was detected in all samples ranging from a low geometric mean of 1.46 μg/L (St. Lucia) to a high of 4.88 μg/L (St. Kitts & Nevis). All of the Caribbean islands sampled had geometric mean concentration levels that were higher than those recorded in two Canadian biomonitoring surveys (1.26 μg/L and 0.80 μg/L) and the U.S. NHANES survey (1.39 μg/L). This first biomonitoring survey of BPA concentration levels in maternal urine samples taken from Caribbean countries clearly points to the need for Caribbean governments and public health officials to first engage in legislative and regulatory efforts to ban or minimize the importation and use of BPA products used the Caribbean and, second, to continue to conduct biomonitoring surveys so as to ensure that these laws and regulations are indeed leading to a decrease of BPA concentrations in Caribbean populations., Competing Interests: The authors declare no conflict of interest.

Background: Despite the increasing trend of cutaneous malignant melanoma (CMM) incidence in Canada, especially among females, few risk factors other than ultraviolet radiation exposure, have been identified., Aim: We conducted a case-control study of 406 CMM cases and 181 controls to evaluate the potential impact of body burdens of various persistent organic pollutants on CMM risk., Methods: Detailed data on potential confounding factors, including lifetime repeated sun exposure and skin reaction to repeated sun exposure, were collected. Gas chromatography tandem mass spectrometry was used to assay plasma levels of 14 polychlorinated biphenyl (PCB) congeners and 11 organochlorine (OC) pesticides among cases and controls., Results: Statistically significant trends of increased CMM risk were observed with increasing plasma concentrations of multiple PCB congeners, including PCBs 138, 153, 170, 180, 183 and 187. For example, compared to lowest plasma concentration quartile of PCB-138, the second, third and fourth quartiles were associated with 1.7 (95% CI: 0.9-2.9), 2.3 (95% CI: 1.3-4.1) and 2.4 (95% CI: 1.3-4.5) -fold increased risks of CMM, respectively. Similarly, increasing plasma concentrations of several OC pesticides (i.e., β-HCH, HCB, Mirex, oxychlordane and trans-Nonachlor) showed statistically significant trends with increased CMM risk. For example, compared to lowest plasma concentration quartile of β-HCH, the second, third and fourth quartiles were associated with 1.3 (95% CI: 0.7-2.3), 2.1 (95% CI: 1.2-3.7) and 2.3 (95% CI: 1.2-4.4) -fold increased risks of CMM, respectively., Conclusion: Plasma levels of several persistent organic pollutants were highly correlated, suggesting that observed associations were not necessarily independent of each other. Given the highly correlated nature of exposure to PCB and OC analytes, sophisticated analyses that consider complex mixtures should be considered in future studies., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Bisphenol A (BPA) is typically measured in urine using an indirect method that involves enzymatic deconjugation and extraction. In contrast, the direct method measures free and conjugated BPA concurrently and sums them to estimate urinary BPA concentrations. Statistical comparison of total BPA results using the direct and indirect methods is necessary to accurately interpret biomonitoring data for risk assessments., Objectives: To compare urinary BPA concentrations estimated from the indirect and direct methods in duplicate first trimester urine samples collected from 1879 pregnant women from the MIREC Study., Methods: For the indirect method, we measured urinary BPA concentrations using GC-MS/MS. For the direct method, we summed free and conjugated BPA concentrations measured using LC-MS/MS. We evaluated deviation between the two methods using the Bland-Altman analysis in the total sample and stratified (1) by specific gravity and (2) at the limit of quantification (LOQ)., Results: Median urinary BPA concentrations for the direct and indirect methods were 0.89 µg BPA equivalents/L and 0.81 µg/L respectively. Concentrations from the direct method were, on average, 8.6% (95% CI: 6.7%, 10.5%) higher than the indirect method in a Bland-Altman analysis. The percent differences between the two methods was 4.0% in urines with specific gravities < 1.02 (n = 1348, 72%) and 20.3% in urine with specific gravity ≥ 1.02. In values below the LOQ (n = 663, 35%), we observed smaller average percent deviation (4.8%) between the two methods but wider limits of agreement., Discussion: Results from this study, based on the largest statistically rigorous comparison of the direct and indirect methods of BPA measurement, contrast previous findings reporting that the indirect method underestimates total BPA exposure. The difference in urinary BPA concentrations we observed with the indirect and direct methods is unlikely to alter the interpretation of health outcome data., (Copyright © 2021. Published by Elsevier Ltd.)

Polyfluoroalkyl substances and perfluoroalkyl substances (PFAS) are a family of anthropogenic chemicals that are used in food packaging, waterproof clothing, and firefighting foams for their water and oil resistant properties. Though levels of some PFAS appear to be decreasing in Canada's south, environmental levels have been increasing in the Arctic due to long-range transport. However, the implications of this on human exposures in sub-Arctic and Arctic populations in Canada have yet to be established. To address this data gap, human biomonitoring research was completed in Old Crow, Yukon, and the Dehcho region, Northwest Territories. Blood samples were collected from adults residing in seven northern First Nations and were analyzed by liquid chromatography mass spectrometry. A total of nine PFAS were quantified: perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOS), perfluorohexane sulphonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA), perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulphonic acid (PFBS). In the Dehcho (n = 124), five PFAS had a detection rate greater than 50% including PFOS, PFOA, PFHxS, PFNA, and PFDA. In addition to these PFAS, PFUdA was also detected in at least half of the samples collected in Old Crow (n = 54). Generally, male participants had higher concentrations of PFAS compared to female participants, and PFAS concentrations tended to increase with age. For most PFAS, Old Crow and Dehcho levels were similar or lower to those measured in the general Canadian population (as measured through the Canadian Health Measures Survey or CHMS) and other First Nations populations in Canada (as measured through the First Nations Biomonitoring Initiative or FNBI). The key exception to this was for PFNA which, relative to the CHMS (0.51 μg/L), was approximately 1.8 times higher in Old Crow (0.94 μg/L) and 2.8 times higher in Dehcho (1.42 μg/L) than observed in the general Canadian population. This project provides baseline PFAS levels for participating communities, improving understanding of human exposures to PFAS in Canada. Future research should investigate site-specific PFNA exposure sources and monitor temporal trends in these regions., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The preoccupation concerning glyphosate (GLYP) has rapidly grown over recent years, and the availability of genetically modified crops that are resistant to GLYP or glufosinate (GLUF) has increased the use of these herbicides. The debate surrounding the carcinogenicity of GLYP has raised interest and the desire to gain information on the level of exposure of the population. GLYP and aminomethylphosphonic acid (AMPA) are commonly simultaneously analysed. GLUF is sometimes also monitored, but its major metabolite, 3-[hydroxy(methyl)phosphinoyl]propionic acid (3MPPA), is rarely present in the method. Using a pentafluorobenzyl derivative to extract the analytes from human urine, we present a method that contains four important analytes to monitor human exposure to GLYP and GLUF. The use of the flash freeze technique speeds up the extraction process and requires less organic solvent than conventional liquid-liquid extraction. The limits of detection in the low μg/L range enable the use of this method for epidemiological studies. The results obtained for 35 volunteers from the Quebec City area are presented with the results from multiple interlaboratory comparisons (G-EQUAS, HBM4EU and OSEQAS). This methodology is currently being used in the Maternal-Infant Research on Environmental Chemicals (MIREC-ENDO) study and in the Canadian Health Measures Survey (CHMS).

Background: As part of the French Human Biomonitoring (HBM) programme, the Esteban study described, among other things, biomarkers levels of various chemicals in adults (18-74 years old) and children (6-17 years old). This paper describes the design of the study and provides, for the first time, data on the biological exposure of the general French population to a wide range of contaminants posing a threat to human health which are currently found in domestic environments., Methods: Esteban is a cross-sectional study conducted on a nationwide sample of the French general population. Exposure biomarkers of six families of contaminants deemed detrimental to adults' and children's health were measured in biological samples collected either at participants' homes by a nurse, or brought to a National Health Insurance examination centre. All participants were randomly selected (2503 adults and 1104 children). The geometric mean and percentiles of the distribution of levels were estimated for each biomarker. Most of the descriptive statistical analyses were performed taking into account the sampling design., Results: Results provided a nationwide description of biomarker levels. Bisphenols (A, S and F), and some metabolites of phthalates and perfluorinated compounds (PFCs) (specifically, PFOS and PFOA) were quantified in almost all the biological samples analysed. Higher levels were observed in children (except for PFCs). Levels were coherent with international studies, except for bisphenols S and F, brominated flame retardants (BFRs) and parabens (with higher levels reported in the USA than in France)., Conclusion and Perspectives: This study is the first to provide a representative assessment of biological exposure to domestic contaminants at the French population level. Our results show that the French general population was exposed to a wide variety of pollutants in 2014-2016, and identify the determinants of exposure. These findings will be useful to stakeholders who wish to advocate an overall reduction in the French population's exposure to harmful substances. Similar future studies in France will help to measure temporal trends, and enable public policies focused on the reduction of those chemicals in the environment to be evaluated., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Phthalates and bisphenol A (BPA) are used in some personal care products (PCPs) and containers for food processing and packaging. The Plastics and Personal-Care Product use in Pregnancy (P4) Study (2009-10) explored the association between PCP use during pregnancy and the postpartum period among 80 pregnant women and 55 infants and BPA and phthalate concentrations in multiple maternal and infant urine specimens collected throughout the study ( n = 1260 samples). The type, frequency, and timing of PCP and food packaging use 24 h before and during the urine collection period was collected at 5 time points for the mother using prospective diaries. Infant urine was collected up to 2 times before 3 months of age, and mothers answered questions about infant feeding and PCP use on their baby. In mothers, monoethyl phthalate (MEP) metabolite concentrations were significantly higher when women reported using makeup or body lotion in the last 24 h. MEP concentrations were consistently higher when the usage occurred within 0-6 h before the urine sample collection for almost all of the PCP categories. Infant lotion or baby powder application in the previous 24 h was associated with higher phthalate metabolite concentrations in infants. Total BPA metabolite concentrations were lower in exclusively breastfed infants compared to those who were exclusively formula fed or breastfed with supplementation. Given that PCPs tend to undergo frequent formulation changes, which could impact the relative importance of a certain product type as a source of exposure, continued research of this type is warranted.

Cadmium (Cd), lead (Pb) and mercury (Hg) are known nephrotoxicants that have been associated with the risk of developing type-2 diabetes (T2D). The aim of this pilot study was to explore relations between biomarkers of Cd, Pb and Hg exposure, early urinary biomarkers of renal dysfunction (kidney-injured molecule-1 (KIM-1), N-acetylglucosaminidase and retinol-binding protein (RBP)) and plasma biomarkers deemed predictive of the risk of developing T2D (adiponectin, leptin, branched-chain and aromatic amino acids), among 70 participants (age range: (46-87 yrs)) from the Canadian Longitudinal Study on Aging (CLSA) with normal glycemic control (glycated haemoglobin ≤ 6.5%) in all but four of them. Significant (p < 0.05) Spearman correlation coefficients were obtained between: plasma adiponectin and RBP (r = 0.42), urinary Cd (r = 0.32), blood Cd (r = 0.36); KIM-1 and CdU (r = 0.33) as well as HgU (r = 0.37); RBP and isoleucine (r = -0.28), leucine (r = -0.33), tyrosine (r = -0.3) and valine (r = -0.44); CdU and isoleucine and valine (r = -0.27 for both). Multiple linear regression analyses showed that some T2D-related biomarkers are confounders of associations between RBP and Hg or Cd biomarkers. Path analyses support a mediating effect of adiponectin on the relation between urinary Cd and RBP. Concluding, this pilot study originally investigated a comprehensive set of biomarkers on complex interactions between toxic metal exposure, renal function and T2D in a group of aging Canadians. Its findings warrant further investigation of longitudinal data in a greater number of participants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the observed inconsistencies between epidemiological studies, we conducted a systematic review of 95 studies retrieved from three main electronic databases. While no clear pattern of associations between blood POPs and breast cancer incidence could be drawn, POPs measured in breast adipose tissue were more clearly associated with higher breast cancer incidence. POPs were more consistently associated with worse breast cancer prognosis whether measured in blood or breast adipose tissue. In contrast, POPs measured in adipose tissue other than breast were inversely associated with both breast cancer incidence and prognosis. Differences in biological tissues used for POPs measurement and methodological biases explain the discrepancies between studies results. Some individual compounds associated with both breast cancer incidence and progression, deserve further investigation.

In the search for improved laboratory methods for the diagnosis of ethylene glycol poisoning, the in vivo formation of a glucuronide metabolite of ethylene glycol was hypothesized. Chemically pure standards of the β-O-glucuronide of ethylene glycol (EG-GLUC) and a deuterated analog (d 4 -EG-GLUC) were synthesized. A high-performance liquid chromatography and tandem mass spectrometry method for determination of EG-GLUC in serum after ultrafiltration was validated. Inter-assay precision (%RSD) was 3.9% to 15.1% and inter-assay %bias was -2.8% to 12.2%. The measuring range was 2-100 μmol/L (0.48-24 mg/L). Specificity testing showed no endogenous amounts in routine clinical samples (n = 40). The method was used to analyze authentic, clinical serum samples (n = 31) from patients intoxicated with ethylene glycol. EG-GLUC was quantified in 15 of these samples, with a mean concentration of 6.5 μmol/L (1.6 mg/L), ranging from 2.3 to 15.6 μmol/L (0.55 to 3.7 mg/L). In five samples, EG-GLUC was detected below the limit of quantification (2 μmol/L) and it was below the limit of detection in 11 samples (1 μmol/L). Compared to the millimolar concentrations of ethylene glycol present in blood after intoxications and potentially available for conjugation, the concentrations of EG-GLUC found in clinical serum samples are very low, but comparable to concentrations of ethyl glucuronide after medium dose ethanol intake. In theory, EG-GLUC has a potential value as a biomarker for ethylene glycol intake, but the pharmacokinetic properties, in vivo/vitro stability and the biosynthetic pathways of EG-GLUC must be further studied in a larger number of patients and other biological matrices., (© 2019 The Authors Drug Testing and Analysis Published by John Wiley & Sons Ltd.)

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.toxlet.2019.05.020. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2019 Elsevier Ireland Ltd. All rights reserved.)

Bisphenols and phthalates leach from medical devices, and this exposure is likely to increase in postcardiac surgery patients. Previous studies suggest that such chemical exposure may impact recovery and wound healing, yet the direct effects of bisphenols and phthalates are unknown in this context. To study the direct effect of clinically based chemical exposures, we measured the metabolites representative of 6 bisphenols and 10 phthalates in men before and after cardiac surgery and then replicated this exposure in a mouse model of cardiac surgery and assessed survival, cardiac function and inflammation. Bisphenol A (BPA), di-ethyl hexyl phthalate (DEHP), butylbenzyl phthalate, di-isodecyl phthalate, and di-n-butyl phthalate metabolites were increased after surgery. DEHP exposure predominated, was positively correlated with duration on the cardiopulmonary bypass machine and exceeded its tolerable daily intake limit by 37-fold. In vivo, C57bl/6 N male mice treated with BPA+phthalates during recovery from surgery-induced myocardial infarction had reduced survival, greater cardiac dilation, reduced cardiac function and increased infiltration of neutrophils, monocytes and macrophages suggesting impaired recovery. Of interest, genetic ablation or estrogen receptor beta (ERβ) antagonism did not improve recovery and replacement of DEHP with tri-octyl trimellitate or removal of BPA from the mixture did not ameliorate these effects. To examine the direct effects on inflammation, treatment of human THP-1 macrophages with BPA and phthalates induced a dysfunctional proinflammatory macrophage phenotype with increased expression of M1-type macrophage polarization markers and MMP9 secretion, yet reduced phagocytic activity. These results suggest that chemicals escape from medical devices and may impair patient recovery., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The matrix effects (MEs) on the quantification of an analyte can be significant and should not be neglected during development and validation of an analytical method. According to this premise, we developed a standardized procedure based on a set of six tests performed on six different sample matrices to detect and characterize the effects of the matrix for single and multiple analytes methods. The link between the matrix effect, recovery, process efficiency, accuracy, precision, and calibration curve was underscored by calculations performed with peak areas, ratios of standard/internal standard peak area, and concentrations. The terms instrumental ME and global ME were introduced, and the term recovery was subdivided for clarity. The test accounts for the presence of ubiquitous and endogenous analytes through background subtraction. The results showed the necessity for using samples with an original concentration in the same range and that the concentration selected for the addition had a definite impact on the results. The use of six-sample matrices provided a standard deviation on the results, and this information could be inserted in a method performance result to show precision. The tool also allows for testing of different analytes/internal standard combinations, which helps with the selection of the association with minimum MEs. A UPLC-MS/MS method for the quantification of several phthalate metabolites in urine was developed and validated with this test. This methodology responds to a scientific need for homogeneity, clarity, and understanding of the results and facilitates the decision-making process while lowering the required costs and time.

Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n-octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates., (Copyright © 2016. Published by Elsevier B.V.)

Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.

Background: Results of recent national surveys have shown the high prevalence of exposure to bisphenol A (BPA) and triclosan (TCS) among the general population; however biomonitoring data for pregnant women and infants are limited., Methods: Women (n=80) were recruited from early prenatal clinics and asked to collect urine samples multiple times during pregnancy and once 2-3 months post-partum. Samples of infant urine and meconium as well as breast milk and infant formula were also collected. Biospecimens were analyzed by GC-MS/MS for BPA, TCS and triclocarban (TCC)., Results: Triclosan was detected in over 80% of the maternal urines (geometric mean (GM): 21.61 μg/L), 60% of the infant urines (GM: 2.8 μg/L), 46% of the breast milk and 80% of the meconium samples. Triclocarban was rarely detected in any of the biospecimens. Median total BPA concentrations were 1.21 and 0.24 μg/L in maternal and infant urines, respectively. Free BPA was detected in only 11% of infant urine samples. The meconium of female infants had significantly higher concentrations of total BPA and TCS than those of males, while no differences were observed in infant urine concentrations by sex., Conclusions: We found widespread exposure among pregnant women and infants to environmental phenols, with large inter-individual variability in exposure to triclosan. These data will contribute to the risk assessment of these chemicals, especially in susceptible sub-populations., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Phthalate metabolites are often measured in biomonitoring studies to evaluate a population's exposure to ubiquitous phthalates. During the course of national biomonitoring studies in Canada, we identified an issue with the accuracy of several commercial phthalate metabolite standards that are commonly used in such studies. The validity of the results from these studies was then questioned. Altogether, three (3) large studies were affected, involving a total of 9302 samples and 105000 individual phthalate metabolite measurements. Data from our previous investigation suggested that the inaccuracies in the commercially-available phthalate metabolite standards were compound- and lot-specific. Therefore, an approach was developed to derive correction factors for each lot of phthalate metabolite standard and was applied to the previously-acquired measurements with the goal of obtaining accurate and comparable data. A statistical analysis was performed to support the approach. It is expected that the corrected phthalate metabolite data from all three Canadian biomonitoring studies are comparable to one another. However, caution is still advised when comparing data obtained from biomonitoring studies for which the calibration standards have not been investigated for their accuracy. Suggestions are made based on quality assurance aspects to improve the validity of phthalate metabolite measurements., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Phthalates are ubiquitous compounds whose metabolites are usually determined in urine for biomonitoring studies. Following suspect and unexplained results from our laboratory in an external quality-assessment scheme, we investigated the accuracy of all phthalate metabolite standards in our possession by comparing them with those of several suppliers. Our findings suggest that commercial phthalate metabolite certified solutions are not always accurate and that lot-to-lot discrepancies significantly affect the accuracy of the results obtained with several of these standards. These observations indicate that the reliability of the results obtained from different lots of standards is not equal, which reduces the possibility of intra-laboratory and inter-laboratory comparisons of results. However, agreements of accuracy have been observed for a majority of neat standards obtained from different suppliers, which indicates that a solution to this issue is available. Data accuracy of phthalate metabolites should be of concern for laboratories performing phthalate metabolite analysis because of the standards used. The results of our investigation are presented from the perspective that laboratories performing phthalate metabolite analysis can obtain accurate and comparable results in the future. Our findings will contribute to improving the quality of future phthalate metabolite analyses and will affect the interpretation of past results.