Exposure to Contemporary and Emerging Chemicals in Commerce among Pregnant Women in the United States: The Environmental influences on Child Health Outcome (ECHO) Program

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This article references 79 other publications.

1. 1

   Braun, J. M. Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat. Rev. Endocrinol. 2017, 13, 161– 173,  DOI: 10.1038/nrendo.2016.186

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   Early-life exposure to EDCs: role in childhood obesity and neurodevelopment

   Braun, Joseph M.

   Nature Reviews Endocrinology (2017), 13 (3), 161-173CODEN: NREABD; ISSN:1759-5029. (Nature Publishing Group)

   Endocrine-disrupting chems. (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are crit. for growth and development during gestation, infancy and childhood. The fetus, infant and child might have enhanced sensitivity to environmental stressors such as EDCs due to their rapid development and increased exposure to some EDCs as a consequence of development-specific behavior, anatomy and physiol. In this Review, I discuss epidemiol. studies examg. the relationship between early-life exposure to bisphenol A (BPA), phthalates, triclosan and perfluoroalkyl substances (PFAS) with childhood neurobehavioural disorders and obesity. The available epidemiol. evidence suggest that prenatal exposure to several of these ubiquitous EDCs is assocd. with adverse neurobehaviour (BPA and phthalates) and excess adiposity or increased risk of obesity and/or overweight (PFAS). Quantifying the effects of EDC mixts., improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability and elucidating the presence and nature of sexually dimorphic EDC effects would enable stronger inferences to be made from epidemiol. studies than currently possible. Ultimately, improved ests. of the causal effects of EDC exposures on child health could help identify susceptible subpopulations and lead to public health interventions to reduce these exposures.

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   Braun, J. M.; Sathyanarayana, S.; Hauser, R. Phthalate exposure and children’s health. Curr. Opin. Pediatr. 2013, 25, 247– 254,  DOI: 10.1097/MOP.0b013e32835e1eb6

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   Phthalate exposure and children's health

   Braun, Joseph M.; Sathyanarayana, Sheela; Hauser, Russ

   Current Opinion in Pediatrics (2013), 25 (2), 247-254CODEN: COPEE9; ISSN:1040-8703. (Lippincott Williams & Wilkins)

   Purpose of review: Phthalates are multifunctional chems. used in personal care products, medications, and plastics. We reviewed the epidemiol. literature examg. the relationship between early life phthalate exposure and pediatric health outcomes. Recent findings: Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-Bu phthalate (DBP), and di-Et phthalate (DEP) exposures are assocd. with alterations in infant/toddler phys. development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure. Summary: Several epidemiol. studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.

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3. 3

   Dodson, R. E.; Nishioka, M.; Standley, L. J.; Perovich, L. J.; Brody, J. G.; Rudel, R. A. Endocrine disruptors and asthma-associated chemicals in consumer products. Environ. Health Perspect. 2012, 120, 935– 943,  DOI: 10.1289/ehp.1104052

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   Endocrine disruptors and asthma-associated chemicals in consumer products

   Dodson, Robin E.; Nishioka, Marcia; Standley, Laurel J.; Perovich, Laura J.; Brody, Julia Green; Rudel, Ruthann A.

   Environmental Health Perspectives (2012), 120 (7), 935-943CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)

   Background: Lab. and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chems. in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. Objectives: We anal. quantified endocrine disruptors and asthma-related chems. in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chems. Methods: We selected 213 com. products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and UV filters. Results: We detected 55 compds., indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concns. and nos. of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-Pr phthalate; also endocrine-disrupting compds.), suggesting a substitution. Many detected chems. were not listed on product labels. Conclusions: Common products contain complex mixts. of EDCs and asthma-related compds. Toxicol. studies of these mixts. are needed to understand their biol. activity. Regarding epidemiol., our findings raise concern about potential confounding from co-occurring chems. and misclassification due to variability in product compn. Consumers should be able to avoid some target chems.-synthetic fragrances, BPA, and regulated active ingredients-using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chems.

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   Woodruff, T. J.; Zota, A. R.; Schwartz, J. M. Environmental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ. Health Perspect. 2011, 119, 878– 885,  DOI: 10.1289/ehp.1002727

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   Environmental chemicals in pregnant women in the United States: NHANES 2003-2004

   Woodruff Tracey J; Zota Ami R; Schwartz Jackie M

   Environmental health perspectives (2011), 119 (6), 878-85 ISSN:.

   BACKGROUND: Exposure to chemicals during fetal development can increase the risk of adverse health effects, and while biomonitoring studies suggest pregnant women are exposed to chemicals, little is known about the extent of multiple chemicals exposures among pregnant women in the United States. OBJECTIVE: We analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. METHODS: We analyzed data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003-2004, a nationally representative sample of the U.S. population. For each chemical analyte, we calculated descriptive statistics. We calculated the number of chemicals detected within the following chemical classes: polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), organochlorine pesticides, and phthalates and across multiple chemical classes. We compared chemical analyte concentrations for pregnant and nonpregnant women using least-squares geometric means, adjusting for demographic and physiological covariates. RESULTS: The percentage of pregnant women with detectable levels of an individual chemical ranged from 0 to 100%. Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons, and perchlorate were detected in 99-100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes. We found, generally, that levels in pregnant women were similar to or lower than levels in nonpregnant women; adjustment for covariates tended to increase levels in pregnant women compared with nonpregnant women. CONCLUSIONS: Pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy making.

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   Wang, A.; Padula, A.; Sirota, M.; Woodruff, T. J. Environmental influences on reproductive health: the importance of chemical exposures. Fertil. Steril. 2016, 106, 905– 929,  DOI: 10.1016/j.fertnstert.2016.07.1076

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   Environmental influences on reproductive health: the importance of chemical exposures

   Wang, Aolin; Padula, Amy; Sirota, Marina; Woodruff, Tracey J.

   Fertility and Sterility (2016), 106 (4), 905-929CODEN: FESTAS; ISSN:0015-0282. (Elsevier)

   Chem. exposures during pregnancy can have a profound and life-long impact on human health. Because of the omnipresence of chems. in our daily life, there is continuous contact with chems. in food, water, air, and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chems. In this review we provide a summary of current data on maternal and fetal exposure, as well as health consequences from these exposures. We review several chem. classes, including polychlorinated biphenyls, perfluoroalkyl substances, polybrominated di-Ph ethers, phenols, phthalates, pesticides, and metals. Addnl., we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chem. exposure and its adverse reproductive health consequences.

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   Blum, A.; Behl, M.; Birnbaum, L.; Diamond, M. L.; Phillips, A.; Singla, V.; Sipes, N. S.; Stapleton, H. M.; Venier, M. Organophosphate Ester Flame Retardants: Are They a Regrettable Substitution for Polybrominated Diphenyl Ethers?. Environ. Sci. Technol. Lett. 2019, 6, 638– 649,  DOI: 10.1021/acs.estlett.9b00582

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   Organophosphate Ester Flame Retardants: Are They a Regrettable Substitution for Polybrominated Diphenyl Ethers?

   Blum, Arlene; Behl, Mamta; Birnbaum, Linda S.; Diamond, Miriam L.; Phillips, Allison; Singla, Veena; Sipes, Nisha S.; Stapleton, Heather M.; Venier, Marta

   Environmental Science & Technology Letters (2019), 6 (11), 638-649CODEN: ESTLCU; ISSN:2328-8930. (American Chemical Society)

   A review to det. whether organophosphate ester flame retardants (OPFR) are a better choice (better alternative) than polybrominated di-Ph ether flame retardants (PBDE) by comparing the two over a range of properties is given. OPFR exposure is ubiquitous to humans and indoor/outdoor; they now often occur at higher concns. than PBDE peak exposure concns. Toxicity testing, epidemiol. study, and risk assessment data all suggest there are health concerns at current exposure levels for halogenated and non-halogenated OPFR. With the large no. of OPFR in use, producers can move toward healthier, safer products by developing innovative ways to reduce fire risks for electronics enclosures, upholstered furniture, building materials, and other consumer products with no added flame retardants. Topics discussed include: introduction; environmental behavior; indoor behavior and human exposure; toxicity and health effects; epidemiol. evidence; looking forward; supporting information (plasma bio-equiv. using high through-put toxicokinetic modeling).

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   Rochester, J. R.; Bolden, A. L.; Bisphenol, S. and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes. Environ. Health Perspect. 2015, 123, 643– 650,  DOI: 10.1289/ehp.1408989

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   Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol a substitutes

   Rochester, Johanna R.; Bolden, Ashley L.

   Environmental Health Perspectives (2015), 123 (7), 643-650CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

   BACKGROUND: Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chem. and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled "BPA-free." Some of the chem. replacements, however, are also bisphenols and may have similar physiol. effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes. OBJECTIVES: This review was carried out to evaluate the physiol. effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA. METHODS: We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol. RESULTS: We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examd. the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, anti-estrogenic, androgenic, and anti androgenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ wts., reproductive end points, and enzyme expression. CONCLUSIONS: Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.

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    Buckley, J. P.; Barrett, E. S.; Beamer, P. I.; Bennett, D. H.; Bloom, M. S.; Fennell, T. R.; Fry, R. C.; Funk, W. E.; Hamra, G. B.; Hecht, S. S.; Kannan, K.; Iyer, R.; Karagas, M. R.; Lyall, K.; Parsons, P. J.; Pellizzari, E. D.; Signes-Pastor, A. J.; Starling, A. P.; Wang, A.; Watkins, D. J.; Zhang, M.; Woodruff, T. J.; program collaborators for ECHO Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program. J. Exposure Sci. Environ. Epidemiol. 2020, 30, 397– 419,  DOI: 10.1038/s41370-020-0211-9

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    Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program

    Buckley Jessie P; Buckley Jessie P; Barrett Emily S; Beamer Paloma I; Bennett Deborah H; Bloom Michael S; Fennell Timothy R; Fry Rebecca C; Funk William E; Iyer Ramsunder; Hamra Ghassan B; Zhang Mingyu; Hecht Stephen S; Kannan Kurunthachalam; Parsons Patrick J; Kannan Kurunthachalam; Parsons Patrick J; Karagas Margaret R; Signes-Pastor Antonio J; Lyall Kristen; Pellizzari Edo D; Starling Anne P; Wang Aolin; Woodruff Tracey J; Watkins Deborah J

    Journal of exposure science & environmental epidemiology (2020), 30 (3), 397-419 ISSN:.

    The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.

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    Pellizzari, E. D.; Woodruff, T. J.; Boyles, R. R.; Kannan, K.; Beamer, P. I.; Buckley, J. P.; Wang, A.; Zhu, Y.; Bennett, D. H. Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research. Environ. Health Perspect. 2019, 127, 126001  DOI: 10.1289/EHP5133

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    Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

    Pellizzari Edo D; Woodruff Tracey J; Wang Aolin; Boyles Rebecca R; Kannan Kurunthachalam; Beamer Paloma I; Buckley Jessie P; Zhu Yeyi; Zhu Yeyi; Bennett Deborah H

    Environmental health perspectives (2019), 127 (12), 126001 ISSN:.

    BACKGROUND: The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133.

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    Zhu, H.; Chinthakindi, S.; Kannan, K. A method for the analysis of 121 multi-class environmental chemicals in urine by high-performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 2021, 1646, 462146  DOI: 10.1016/j.chroma.2021.462146

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    A method for the analysis of 121 multi-class environmental chemicals in urine by high-performance liquid chromatography-tandem mass spectrometry

    Zhu, Hongkai; Chinthakindi, Sridhar; Kannan, Kurunthachalam

    Journal of Chromatography A (2021), 1646 (), 462146CODEN: JCRAEY; ISSN:0021-9673. (Elsevier B.V.)

    Biomonitoring of human exposure to environmental chems. has gained momentum in recent years. Biomonitoring methods often include anal. of a single class of chems. with similar chem. properties. In this study, we describe a method that involves solid-phase extn. (SPE) coupled with liq. chromatog.-tandem mass spectrometry (LC-MS/MS) and capable of measuring 121 environmental chems. comprising plasticizers (PMs; n = 45), environmental phenols (EPs; n = 45), and pesticides (n = 31) through a single extn. of urine. Urine samples were incubated with 20 μL of β-glucuronidase/arylsulfatase (4000 units/mL urine) (from Helix pomatia) buffered at pH 5.5 for 2 h at 37 °C for optimal deconjugation conditions. We compared two extn. methods, namely liq.-liq. extn. and SPE, and the latter with ABS Elut NEXUS cartridges was optimized to yield best extn. efficiencies. For increased resoln. and chromatog. sepn., two methods involving Ultra AQ C18 and Betasil C18 columns were used. The MS/MS analyses were performed under both neg. and pos. ionization modes. The optimized method yielded excellent intra- and inter-day variabilities (relative std. deviation: 0.40-11%) and satisfactory recoveries (80-120%) for >95% of the analytes. The limits of detection were ≤ 0.1 ng/mL for 101 analytes and between 0.1 and 1.0 ng/mL for 18 analytes. The optimized SPE LC-MS/MS method was validated through the anal. of std. ref. materials and proficiency test urine samples and further applied in the anal. of 21 real urine samples to demonstrate simultaneous detn. of 121 environmental chems. in urine samples.

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    Kannan, K.; Stathis, A.; Mazzella, M. J.; Andra, S. S.; Barr, D. B.; Hecht, S. S.; Merrill, L. S.; Galusha, A. L.; Parsons, P. J. Quality assurance and harmonization for targeted biomonitoring measurements of environmental organic chemicals across the Children’s Health Exposure Analysis Resource laboratory network. Int. J. Hyg. Environ. Health 2021, 234, 113741  DOI: 10.1016/j.ijheh.2021.113741

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    15

    Quality assurance and harmonization for targeted biomonitoring measurements of environmental organic chemicals across the Children's Health Exposure Analysis Resource laboratory network

    Kannan, Kurunthachalam; Stathis, Alexa; Mazzella, Matthew J.; Andra, Syam S.; Barr, Dana Boyd; Hecht, Stephen S.; Merrill, Lori S.; Galusha, Aubrey L.; Parsons, Patrick J.

    International Journal of Hygiene and Environmental Health (2021), 234 (), 113741CODEN: IJEHFT; ISSN:1438-4639. (Elsevier GmbH)

    A consortium of labs. established under the Children's Health Exposure Anal. Resource (CHEAR) used a multifaceted quality assurance program to promote measurement harmonization for trace orgs. analyses of human biospecimens that included: (1) participation in external quality assurance (EQA)/proficiency testing (PT) programs; (2) analyses of a urine-based CHEAR common quality control (QC) pool with each anal. batch across all participating labs.; (3) method validation against NIST Std. Ref. Materials (SRMs); and (4) analyses of blinded duplicates and other project-specific QC samples. The capability of five CHEAR labs. in org. chem. anal. increased across the 4-yr period, and performance in the external PT program improved over time - recent challenges reporting >90% analytes with satisfactory performance. The CHEAR QC pools were analyzed for several classes of org. chems. including phthalate metabolites and environmental phenols by the participating labs. with every batch of project samples, which provided a rich source of measurement data for the assessment of intra- and inter-lab. variance. Within-lab. and overall variabilities in measurements across labs. were calcd. for target chems. in urine QC pools; the coeff. of variation (CV) was generally below 25% across batches, studies and labs. and indicated acceptable anal. imprecision. The suite of org. chems. analyzed in the CHEAR QC pool was broader than those reported for com. available ref. materials. The accuracy of each of the labs. methods was verified through the anal. of several NIST SRMs and was, for example, 97 ± 5.2% for environmental phenols and 95 ± 11% for phthalates. Anal. of blinded duplicate samples showed excellent agreement and reliability of measurements. The intra-class correlation coeffs. (ICC) for phthalate metabolites analyzed in various batches across three CHEAR labs. showed excellent reliability (typically >0.90). Overall, the multifaceted quality assurance protocols followed among the CHEAR labs. ensured reliable and reproducible data quality for several classes of org. chems. Increased participation in external PT programs through inclusion of addnl. target analytes will further enhance the confidence in data quality.

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    Barr, D. B.; Silva, M. J.; Kato, K.; Reidy, J. A.; Malek, N. A.; Hurtz, D.; Sadowski, M.; Needham, L. L.; Calafat, A. M. Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. Environ. Health Perspect. 2003, 111, 1148– 1151,  DOI: 10.1289/ehp.6074

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    Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers

    Barr Dana B; Silva Manori J; Kato Kayoko; Reidy John A; Malek Nicole A; Hurtz Donald; Sadowski Melissa; Needham Larry L; Calafat Antonia M

    Environmental health perspectives (2003), 111 (9), 1148-51 ISSN:0091-6765.

    Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in 2,541 persons in the United States were lower than we anticipated, especially when compared with urinary metabolite levels of other commonly used phthalates. This finding raised questions about the sensitivity of this biomarker for assessing DEHP exposure. We explored the utility of two other DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), as additional DEHP biomarkers. These metabolites are formed by oxidative metabolism of MEHP. In urine from 62 people, both the range and the mean urinary levels of MEOHP and MEHHP were on average 4-fold higher than those of MEHP; the mean of the individual ratios of MEHHP/MEOHP, MEHHP/MEHP, and MEOHP/MEHP were 1.4, 8.2, and 5.9, respectively. These data suggest that MEOHP and MEHHP are more sensitive biomarkers of exposure to DEHP than is MEHP. These findings also suggest a predominant human metabolic route for DEHP hydrolysis to MEHP followed by oxidation of MEHP; they also imply that a similar mechanism may be relevant for other high-molecular-weight phthalates, such as di-n-octyl, di-isononyl, and di-isodecyl phthalates.

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17. 17

    Wolff, M. S.; Engel, S. M.; Berkowitz, G. S.; Ye, X.; Silva, M. J.; Zhu, C.; Wetmur, J.; Calafat, A. M. Prenatal phenol and phthalate exposures and birth outcomes. Environ. Health Perspect. 2008, 116, 1092– 1097,  DOI: 10.1289/ehp.11007

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    17

    Prenatal phenol and phthalate exposures and birth outcomes

    Wolff, Mary S.; Engel, Stephanie M.; Berkowitz, Gertrud S.; Ye, Xiaoyun; Silva, Manori J.; Zhu, Chenbo; Wetmur, James; Calafat, Antonia M.

    Environmental Health Perspectives (2008), 116 (8), 1092-1097CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)

    Many phthalates and phenols are hormonally active and are suspected to alter the course of development. We investigated prenatal exposures to phthalate and phenol metabolites and their assocns. with body size measures of the infants at birth. We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. Median urinary concns. were > 10 μg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concns. of low-mol.-wt. phthalate monoesters (low-MWP) were approx. 5-fold greater than those of high-mol.-wt. metabolites. Low-MWP metabolites had a pos. assocn. with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth wt. in boys (-210 g av. birth wt. difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concns. were assocd. with a similar decrease in birth wt. among girls but with greater birth wt. in boys. We obsd. a range of phthalate and phenol exposures during pregnancy in our population, but few were assocd. with birth size. The assocn. of 2,5-DCP and BP3 with reduced or increased birth wt. could be important in very early or small-size births. In addn., pos. assocns. of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.

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18. 18

    Braun, J. M.; Bellinger, D. C.; Hauser, R.; Wright, R. O.; Chen, A.; Calafat, A. M.; Yolton, K.; Lanphear, B. P. Prenatal phthalate, triclosan, and bisphenol A exposures and child visual-spatial abilities. Neurotoxicology 2017, 58, 75– 83,  DOI: 10.1016/j.neuro.2016.11.009

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    18

    Prenatal phthalate, triclosan, and bisphenol A exposures and child visual-spatial abilities

    Braun, Joseph M.; Bellinger, David C.; Hauser, Russ; Wright, Robert O.; Chen, Aimin; Calafat, Antonia M.; Yolton, Kimberly; Lanphear, Bruce P.

    NeuroToxicology (2017), 58 (), 75-83CODEN: NRTXDN; ISSN:0161-813X. (Elsevier Inc.)

    During fetal development, sex steroids influence sexually dimorphic behaviors, such as visual-spatial abilities. Thus, endocrine disrupting chems. that impact sex steroids during gestation may affect these behaviors. We investigated the relationship between prenatal urinary phthalate metabolite, triclosan, and BPA concns. and visual-spatial abilities in a prospective cohort of 198 mother-child dyads. Data are from a prospective cohort in Cincinnati, OH (HOME Study). We measured nine phthalate metabolites, triclosan, and BPA in maternal urine samples collected at 16 and 26 wk of gestation. We assessed children's visual-spatial abilities at 8 years of age using the Virtual Morris Water Maze (VMWM), a computerized version of the rodent Morris Water Maze. We quantified the covariate-adjusted change in the time or distance to complete the VMWM and time spent in the correct quadrant during a probe trial with an interquartile range increase in chem. concns. using linear mixed models and linear regression, resp. Boys completed the VMWM faster (4.1 s; 95% CI:-7.1, -1.2) and in less distance (1.4 units; 95% CI:-2.8, 0) than girls. Overall, children with higher mono-Bu (MnBP), mono-benzyl (MBzP), and mono-carboxypropyl phthalate concns. completed the VMWM in less time and distance than children with lower concns. For example, children with higher MnBP concns. completed the VMWM in 0.9 less distance units (95% CI:-1.8, -0.0). Child sex modified the assocn. between MnBP and VMWM performance. In girls, higher MnBP concns. were assocd. with longer time (1.7 s; 95% CI: -0.7, 4.1) and shorter distance (-1.7 units; 95% CI: -2.8, -0.5), whereas in boys, it was assocd. with shorter time (-3.0 s; 95% CI:-5.6, -0.4), but not distance (-0.1 units; 95% CI:1.4, 1.0). Other phthalate metabolites, triclosan, and BPA were not assocd. with VMWM performance, and sex did not consistently modify these assocns. In this cohort, greater prenatal urinary concns. of some phthalate metabolites were assocd. with improved VMWM performance, particularly among boys. Future studies should confirm these findings and det. if phthalates affect other hormonally sensitive aspects of child neurobehavior.

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19. 19

    Lubin, J. H.; Colt, J. S.; Camann, D.; Davis, S.; Cerhan, J. R.; Severson, R. K.; Bernstein, L.; Hartge, P. Epidemiologic evaluation of measurement data in the presence of detection limits. Environ. Health Perspect. 2004, 112, 1691– 1696,  DOI: 10.1289/ehp.7199

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    19

    Epidemiologic evaluation of measurement data in the presence of detection limits

    Lubin, Jay H.; Colt, Joanne S.; Camann, David; Davis, Scott; Cerhan, James R.; Severson, Richard K.; Bernstein, Leslie; Hartge, Patricia

    Environmental Health Perspectives (2004), 112 (17), 1691-1696CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)

    Quant. measurements of environmental factors greatly improve the quality of epidemiol. studies but can pose challenges because of the presence of upper or lower detection limits or interfering compds., which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of "fill-in" values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5-10%). The fill-in approach generally produces unbiased parameter ests. but may produce biased variance ests. and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for addnl. anal., such as relative risk regression or graphical display, then multiple imputation produces unbiased ests. and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case-control study of non-Hodgkin lymphoma.

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20. 20

    Hornung, R. W.; Reed, L. D. Estimation of Average Concentration in the Presence of Nondetectable Values. Appl. Occup. Environ. Hyg. 1990, 5, 46– 51,  DOI: 10.1080/1047322X.1990.10389587

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    20

    Estimation of average concentration in the presence of nondetectable values

    Hornung, Richard W.; Reed, Laurence D.

    Applied Occupational and Environmental Hygiene (1990), 5 (1), 46-51CODEN: AOEHE9; ISSN:1047-322X.

    To est. the av. concn. of a particular contaminant during some period of time, a certain proportion of the collected samples is often reported to be below the limit of detection. The statistical terminol. for these results is censored data, i.e., nonzero values which cannot be measured but are known to be below some threshold. Samples taken over time are assumed to follow a lognormal distribution. Given this assumption, several techniques are presented for estn. of the av. concn. from data contg. nondetectable values. The techniques proposed include three methods of estn. with a left-censored lognormal distribution: a max. likelihood statistical method and two methods involving the limit of detection. Each method is evaluated using computer simulation with respect to the bias assocd. with estn. of the mean and std. deviation. The max. likelihood method produced unbiased ests. of both the mean and std. deviation under a variety of conditions. However, this method is somewhat complex and involves laborious calcns. and use of tables. Two simpler alternatives involve the substitution of L/2 and a new proposal of L/√‾2 for each nondetectable value, where L = the limit of detection. The new method provided more accurate estn. of the mean and std. deviation than the L/2 method when the data are not highly skewed. The L/2 method should be used when the data are highly skewed (geometric std. deviation ≥3.0 or greater).

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21. 21

    Barr, D. B.; Wang, R. Y.; Needham, L. L. Biologic monitoring of exposure to environmental chemicals throughout the life stages: requirements and issues for consideration for the National Children’s Study. Environ. Health Perspect. 2005, 113, 1083– 1091,  DOI: 10.1289/ehp.7617

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    Biologic monitoring of exposure to environmental chemicals throughout the life stages: requirements and issues for consideration for the National Children's Study

    Barr, Dana B.; Wang, Richard Y.; Needham, Larry L.

    Environmental Health Perspectives (2005), 113 (8), 1083-1091CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)

    Biomonitoring of exposure is a useful tool for assessing environmental exposures. The matrixes available for analyses include blood, urine, breast milk, adipose tissue, and saliva, among others. The sampling can be staged to represent the particular time period of concern: preconceptionally from both parents, from a pregnant woman during each of the three trimesters, during and immediately after childbirth, from the mother postnatally, and from the child as it develops to 21 years of age. The appropriate sample for biomonitoring will depend upon matrix availability, the time period of concern for a particular exposure or health effect, and the different classes of environmental chems. to be monitored. This article describes the matrixes available for biomonitoring during the life stages being evaluated in the National Children's Study; the best biol. matrixes for exposure assessment for each individual chem. class, including consideration of alternative matrixes; the anal. methods used for anal., including quality control procedures and less costly alternatives; the costs of anal.; optimal storage conditions; and chem. and matrix stability during long-term storage.

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22. 22

    O’Brien, K. M.; Upson, K.; Cook, N. R.; Weinberg, C. R. Environmental Chemicals in Urine and Blood: Improving Methods for Creatinine and Lipid Adjustment. Environ. Health Perspect. 2016, 124, 220– 227,  DOI: 10.1289/ehp.1509693

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    Environmental chemicals in urine and blood: Improving methods for creatinine and lipid adjustment

    O'Brien, Katie M.; Upson, Kristen; Cook, Nancy R.; Weinberg, Clarice R.

    Environmental Health Perspectives (2016), 124 (2), 220-227CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

    Background: Investigators measuring exposure biomarkers in urine typically adjust for creatinine to account for diln.-dependent sample variation in urine concns. Similarly, it is std. to adjust for serum lipids when measuring lipophilic chems. in serum. However, there is controversy regarding the best approach, and existing methods may not effectively correct for measurement error. OBjectives: We compared adjustment methods, including novel approaches, using simulated case -control data. Methods: Using a directed acyclic graph framework, we defined six causal scenarios for epidemiol. studies of environmental chems. measured in urine or serum. The scenarios include variables known to influence creatinine (e.g., age and hydration) or serum lipid levels (e.g., body mass index and recent fat intake). Over a range of true effect sizes, we analyzed each scenario using seven adjustment approaches and estd. the corresponding bias and confidence interval coverage across 1,000 simulated studies. RESULTS: For urinary biomarker measurements, our novel method, which incorporates both covariate-adjusted standardization and the inclusion of creatinine as a covariate in the regression model, had low bias and possessed 95% confidence interval coverage of nearly 95% for most simulated scenarios. For serum biomarker measurements, a similar approach involving standardization plus serum lipid level adjustment generally performed well. CONCLUSIONS: To control measurement error bias caused by variations in serum lipids or by urinary diluteness, we recommend improved methods for standardizing exposure concns. across individuals.

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23. 23

    Boeniger, M. F.; Lowry, L. K.; Rosenberg, J. Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am. Ind. Hyg. Assoc. J. 1993, 54, 615– 627,  DOI: 10.1080/15298669391355134

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    23

    Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review

    Boeniger, Mark Frederick; Lowry, Larry K.; Rosenberg, Jon

    American Industrial Hygiene Association Journal (1958-1999) (1993), 54 (10), 615-27CODEN: AIHAAP; ISSN:0002-8894.

    A review, with 122 refs., leading to the conclusions that creatinine (CRE) excretion is subject to wide fluctuations due to specific internal and external factors; the use of CRE to correct chem. concns. in urine will not necessarily improve the correlation to the exposure dose for all chems. (it may, in fact, worsen the result); and other means of expressing urine concn. may offer greater accuracy towards estg. individually absorbed dose.

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24. 24

    Kuiper, J. R.; O’Brien, K. M.; Ferguson, K. K.; Buckley, J. P. Urinary specific gravity measures in the U.S. population: Implications for the adjustment of non-persistent chemical urinary biomarker data. Environ. Int. 2021, 156, 106656  DOI: 10.1016/j.envint.2021.106656

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    24

    Urinary specific gravity measures in the U.S. population: Implications for the adjustment of non-persistent chemical urinary biomarker data

    Kuiper, Jordan R.; O'Brien, Katie M.; Ferguson, Kelly K.; Buckley, Jessie P.

    Environment International (2021), 156 (), 106656CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Urinary biomarkers are often cor. for sample diln. using creatinine, which is influenced by sociodemog. factors and certain health conditions. We assessed predictors of urinary sp. gr. and creatinine among NHANES 2007-2008 participants (n = 7257). We cor. concns. of mono-Bu phthalate (MnBP) for diln. using two methods, each applied to both sp. gr. and creatinine: correction using a sample mean of the diln. indicator (i.e., sp. gr. or creatinine) and covariate-adjusted standardization. We compared distributions and assessed the agreement of uncorrected or cor. concns. visually using Bland-Altman plots and statistically by Kendall's τa. We stratified all analyses by age category (i.e., 6-19 or 20+ years of age). Gender, race/ethnicity, body mass index, and height were assocd. with urinary sp. gr. and creatinine. Distributions of cor. MnBP concns. were comparable for both methods and diln. indicators, but agreement between methods was greater for sp. gr. Addnl., sp. gr.- and creatinine-cor. MnBP concns. had slightly greater agreement with each other when cor. using a covariate-adjusted standardization method. Sp. gr., like creatinine, is assocd. with sociodemog. and body compn. variables. Accounting for these factors as part of the diln. correction method may be important to minimize bias.

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    Shelby, M. D. NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP) NTP CERHR MON , 2006, 18.

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    Office of Environmental Health Hazard Assessment Safe Drinking Water and Toxic Enforcement Act of 1986. Chemicals Known to the State to Cause Cancer or Reproductive Toxicity. March 19, 2021 Proposition 65 List https://oehha.ca.gov/proposition-65/proposition-65-list (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Evaluation of New Scientific Evidence Concerning DINP and DIDP: In Relation to Entry 52 of Annex XVII to REACH Regulation (EC) No 1907/2006 https://echa.europa.eu/documents/10162/31b4067e-de40-4044-93e8-9c9ff1960715 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Inclusion of substances of very high conern in the candidate list (Decision by the Executive Director). https://www.echa.europa.eu/documents/10162/78d8ecfd-5e83-4299-9f16-15681ee11bbb (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: acetamiprid. https://echa.europa.eu/substance-information/-/substanceinfo/100.111.622 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: 6-chloronicotinic acid. https://echa.europa.eu/substance-information/-/substanceinfo/100.023.819 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: 2,2’,4,4’-tetrahydroxybenzophenone https://echa.europa.eu/substance-information/-/substanceinfo/100.004.573 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: 4-hydroxybenzophenone. https://echa.europa.eu/substance-information/-/substanceinfo/100.013.188 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: Diheptyl phthalate https://echa.europa.eu/substance-information/-/substanceinfo/100.020.806 (accessed Aug 30, 2021).

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    European Chemicals Agency (ECHA) Substance Infocard: Dipentyl phthalate. https://echa.europa.eu/substance-information/-/substanceinfo/100.004.563 (accessed Aug 30, 2021).

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    Office of Environmental Health Hazard Assessment (OEHHA) Proposition 65 Fact Sheets: Phthalates https://www.p65warnings.ca.gov/fact-sheets/phthalates (accessed Aug 30, 2021).

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    Ospina, M.; Wong, L. Y.; Baker, S. E.; Serafim, A. B.; Morales-Agudelo, P.; Calafat, A. M. Exposure to neonicotinoid insecticides in the U.S. general population: Data from the 2015-2016 national health and nutrition examination survey. Environ. Res. 2019, 176, 108555  DOI: 10.1016/j.envres.2019.108555

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    Exposure to neonicotinoid insecticides in the U.S. general population: Data from the 2015-2016 national health and nutrition examination survey

    Ospina, Maria; Wong, Lee-Yang; Baker, Samuel E.; Serafim, Amanda Bishop; Morales-Agudelo, Pilar; Calafat, Antonia M.

    Environmental Research (2019), 176 (), 108555CODEN: ENVRAL; ISSN:0013-9351. (Elsevier)

    Neonicotinoids are used for insect control in agriculture, landscaping, and on household pets. Neonicotinoids have become popular replacements for organophosphate and carbamate insecticides, and use is on the rise. To assess human exposure to neonicotinoid insecticides in a representative sample of the U. S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examn. Survey (NHANES). We used online solid-phase extn. coupled to isotope diln. high-performance liq. chromatog.-tandem mass spectrometry after enzymic hydrolysis of conjugates to quantify in 3038 samples the urinary concns. of six neonicotinoid biomarkers: four parent compds. (acetamiprid, clothianidin, imidacloprid, thiacloprid) and two metabolites (N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid). We calcd. distribution percentiles, and used regression models to evaluate assocns. of various demog. parameters and fasting time with urinary concns. above the 95th percentile (a value selected to represent higher than av. concns.) of neonicotinoid biomarkers. Weighted detection frequencies were 35% (N-desmethyl-acetamiprid), 19.7% (5-hydroxy imidacloprid), 7.7% (clothianidin), 4.3% (imidacloprid), and <0.5% (acetamiprid, thiacloprid). The weighted frequency of having detectable concns. of at least one of the six biomarkers examd. was 49.1%.

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37. 37

    Casida, J. E. Neonicotinoids and Other Insect Nicotinic Receptor Competitive Modulators: Progress and Prospects. Annu. Rev. Entomol. 2018, 63, 125– 144,  DOI: 10.1146/annurev-ento-020117-043042

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    37

    Neonicotinoids and Other Insect Nicotinic Receptor Competitive Modulators: Progress and Prospects

    Casida, John E.

    Annual Review of Entomology (2018), 63 (), 125-144CODEN: ARENAA; ISSN:0066-4170. (Annual Reviews)

    A review. Neonicotinoids (neonics) are remarkably effective as plant systemics to control sucking insects and for flea control on dogs and cats. The nitroimines imidacloprid, clothianidin, thiamethoxam, and dinotefuran are the leaders among the seven com. neonics that also include the nitromethylene nitenpyram, the nitromethylene-derived cycloxaprid, and the cyanoimines acetamiprid and thiacloprid. Honey bees are highly sensitive to the nitroimines and nitromethylenes, but the cyanoimines are less toxic. All neonics are nicotinic acetylcholine receptor (nAChR) agonists with a common mode of action, target-site cross-resistance, and much higher potency on insect than mammalian nAChRs at defined binding sites. The structurally related sulfoximine sulfoxaflor and butenolide flupyradifurone are also nAChR agonists, and the mesoionic triflumezopyrim is a nAChR competitive modulator with little or no target-site cross-resistance. Some neonics induce stress tolerance in plants via salicylate-assocd. systems. The neonics in general are readily metabolized and, except for pollinators, have favorable toxicol. profiles.

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    Douglas, M. R.; Tooker, J. F. Large-scale deployment of seed treatments has driven rapid increase in use of neonicotinoid insecticides and preemptive pest management in US field crops. Environ. Sci. Technol. 2015, 49, 5088– 5097,  DOI: 10.1021/es506141g

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    Large-Scale Deployment of Seed Treatments Has Driven Rapid Increase in Use of Neonicotinoid Insecticides and Preemptive Pest Management in U.S. Field Crops

    Douglas, Margaret R.; Tooker, John F.

    Environmental Science & Technology (2015), 49 (8), 5088-5097CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    A review. Neonicotinoids are the most widely used class of insecticides worldwide, but patterns of their use in the U.S. are poorly documented, constraining attempts to understand their role in pest management and potential nontarget effects. We synthesized publicly available data to est. and interpret trends in neonicotinoid use since their introduction in 1994, with a special focus on seed treatments, a major use not captured by the national pesticide-use survey. Neonicotinoid use increased rapidly between 2003 and 2011, as seed-applied products were introduced in field crops, marking an unprecedented shift toward large-scale, preemptive insecticide use: 34-44% of soybeans and 79-100% of maize ha were treated in 2011. This finding contradicts recent analyses, which concluded that insecticides are used today on fewer maize ha than a decade or two ago. If current trends continue, neonicotinoid use will increase further through application to more ha of soybean and other crop species and escalation of per-seed rates. Alternatively, our results, and other recent analyses, suggest that carefully targeted efforts could considerably reduce neonicotinoid use in field crops without yield declines or economic harm to farmers, reducing the potential for pest resistance, nontarget pest outbreaks, environmental contamination, and harm to wildlife, including pollinator species.

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39. 39

    Jeschke, P.; Nauen, R.; Schindler, M.; Elbert, A. Overview of the status and global strategy for neonicotinoids. J. Agric. Food Chem. 2011, 59, 2897– 2908,  DOI: 10.1021/jf101303g

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    Overview of the Status and Global Strategy for Neonicotinoids

    Jeschke, Peter; Nauen, Ralf; Schindler, Michael; Elbert, Alfred

    Journal of Agricultural and Food Chemistry (2011), 59 (7), 2897-2908CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)

    A review. In recent years, neonicotinoid insecticides have been the fastest growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors (nAChRs), their mol. target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and greatly facilitates the understanding of functional properties of the insect nAChRs. In this context, the crystal structure of the acetylcholine-binding proteins provides the theor. foundation for designing homol. models of the corresponding receptor ligand binding domains within the nAChRs, a useful basis for virtual screening of chem. libraries and rational design of novel insecticides acting on these practically relevant channels. Because of the relatively low risk for nontarget organisms and the environment, the high target specificity of neonicotinoid insecticides, and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programs. Innovative concepts for life-cycle management, jointly with the introduction of generic products, have made neonicotinoids the most important chem. class for the insecticide market.

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40. 40

    Simon-Delso, N.; Amaral-Rogers, V.; Belzunces, L. P.; Bonmatin, J. M.; Chagnon, M.; Downs, C.; Furlan, L.; Gibbons, D. W.; Giorio, C.; Girolami, V.; Goulson, D.; Kreutzweiser, D. P.; Krupke, C. H.; Liess, M.; Long, E.; McField, M.; Mineau, P.; Mitchell, E. A.; Morrissey, C. A.; Noome, D. A.; Pisa, L.; Settele, J.; Stark, J. D.; Tapparo, A.; Van Dyck, H.; Van Praagh, J.; Van der Sluijs, J. P.; Whitehorn, P. R.; Wiemers, M. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites. Environ. Sci. Pollut. Res. Int. 2015, 22, 5– 34,  DOI: 10.1007/s11356-014-3470-y

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    Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites

    Simon-Delso N; Amaral-Rogers V; Belzunces L P; Bonmatin J M; Chagnon M; Downs C; Furlan L; Gibbons D W; Giorio C; Girolami V; Goulson D; Kreutzweiser D P; Krupke C H; Liess M; Long E; McField M; Mineau P; Mitchell E A D; Morrissey C A; Noome D A; Pisa L; Settele J; Stark J D; Tapparo A; Van Dyck H; Van Praagh J; Van der Sluijs J P; Whitehorn P R; Wiemers M

    Environmental science and pollution research international (2015), 22 (1), 5-34 ISSN:.

    Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time-depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

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41. 41

    Goulson, D. An overview of the environmental risks posed by neonicotinoid insecticides. J. Appl. Ecol. 2013, 50, 977– 987,  DOI: 10.1111/1365-2664.12111

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    Tomizawa, M.; Casida, J. E. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu. Rev. Pharmacol. Toxicol. 2005, 45, 247– 268,  DOI: 10.1146/annurev.pharmtox.45.120403.095930

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    Neonicotinoid insecticide toxicology: mechanisms of selective action

    Tomizawa, Motohiro; Casida, John E.

    Annual Review of Pharmacology and Toxicology (2005), 45 (), 247-268, 1 plateCODEN: ARPTDI; ISSN:0362-1642. (Annual Reviews Inc.)

    A review. The neonicotinoids, the newest major class of insecticides, have outstanding potency and systemic action for crop protection against piercing-sucking pests, and they are highly effective for flea control on cats and dogs. Their common names are acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam. They generally have low toxicity to mammals (acute and chronic), birds, and fish. Biotransformations involve some activation reactions but largely detoxification mechanisms. In contrast to nicotine, epibatidine, and other ammonium or iminium nicotinoids, which are mostly protonated at physiol. pH, the neonicotinoids are not protonated and have an electroneg. nitro or cyano pharmacophore. Agonist recognition by the nicotinic receptor involves cation-π interaction for nicotinoids in mammals and possibly a cationic subsite for interaction with the nitro or cyano substituent of neonicotinoids in insects. The low affinity of neonicotinoids for vertebrate relative to insect nicotinic receptors is a major factor in their favorable toxicol. profile.

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43. 43

    Mach, B. M.; Bondarenko, S.; Potter, D. A. Uptake and dissipation of neonicotinoid residues in nectar and foliage of systemically treated woody landscape plants. Environ. Toxicol. Chem. 2018, 37, 860– 870,  DOI: 10.1002/etc.4021

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    Uptake and dissipation of neonicotinoid residues in nectar and foliage of systemically treated woody landscape plants

    Mach, Bernadette M.; Bondarenko, Svetlana; Potter, Daniel A.

    Environmental Toxicology and Chemistry (2018), 37 (3), 860-870CODEN: ETOCDK; ISSN:0730-7268. (Wiley-Blackwell)

    Systemic neonicotinoid insecticides used in urban arboriculture could pose a risk to bees and other pollinators foraging on treated plants. We measured uptake and dissipation of soil-applied imidacloprid and dinotefuran in nectar and leaves of 2 woody plant species, a broadleaf evergreen tree (Ilex × attenuata) and a deciduous shrub (Clethra alnifolia), to assess concns. to which pollinators and pests might be exposed in landscape settings. Three application timings, autumn (postbloom), spring (prebloom), and summer (early postbloom), were evaluated to see if taking advantage of differences in the neonicotinoids' systemic mobility and persistence might enable pest control while minimizing transference into nectar. Nectar and tissue samples were collected from in-ground plants and analyzed for residues by high-performance liq. chromatog.-tandem mass spectrometry (HPLC-MS/MS) in 2 successive years. Concns. found in nectar following autumn or spring applications ranged from 166 to 515 ng/g for imidacloprid and from 70 to 1235 ng/gg for dinotefuran, depending on plant and timing. These residues exceed concns. shown to adversely affect individual- and colony-level traits of bees. Summer application mitigated concns. of imidacloprid (8-31 ng/g), but not dinotefuran (235-1191 ng/g), in nectar. Our data suggest that dinotefuran may be more persistent than is generally believed. Implications for integrated pest and pollinator management in urban landscapes are discussed. Environ Toxicol Chem 2017;9999:1-11. © 2017 SETAC.

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44. 44

    Frank, S. D. Reduced risk insecticides to control scale insects and protect natural enemies in the production and maintenance of urban landscape plants. Environ. Entomol. 2012, 41, 377– 386,  DOI: 10.1603/EN11230

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    Reduced risk insecticides to control scale insects and project natural enemies in the production and maintenance of urban landscape plants

    Frank, Steven D.

    Environmental Entomology (2012), 41 (2), 377-386CODEN: EVETBX; ISSN:0046-225X. (Entomological Society of America)

    Armored scale insects are among the most difficult to manage and economically important arthropod pests in the prodn. and maintenance of urban landscape plants. This is because of morphol. traits that protect them from contact insecticides. I compared initial and season-long control of euonymus scale, Unaspis euonymi Comstock (Hemiptera: Diaspidae), by reduced-risk insecticides (insect growth regulators [IGRs], neonicotinoids, spirotetramat) to det. if they controlled scale as well as more toxic insecticides such as the organophosphate, acephate, and pyrethroid, bifenthrin. I also evaluated how these insecticides affected natural enemy abundance on exptl. plants and survival when exposed to insecticide residue. All insecticides tested reduced first generation euonymus scale abundance. In 2009, reinfestation by second generation euonymus scale was highest on plants treated with acetamiprid and granular dinotefuran. In 2010, systemic neonicotinoids and spirotetramat prevented cottony cushion scale infestation 133 d after treatment whereas scale readily infested plants treated with bifenthrin and horticultural oil. Encarsia spp. and Cybocephalus spp. abundance was related to scale abundance. These natural enemies were generally less abundant than predicted by scale abundance on granular dinotefuran treated plants and more abundant on granular thiamethoxam treated plants. Bifenthrin residue killed 90-100% of O. insidiosus and E. citrina within 24 h. My results indicate that reduced risk insecticides can provide season-long scale control with less impact on natural enemies than conventional insecticides. This could have economic and environmental benefits by reducing the no. of applications necessary to protect nursery and landscape plants from scale.

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45. 45

    Han, W.; Tian, Y.; Shen, X. Human exposure to neonicotinoid insecticides and the evaluation of their potential toxicity: An overview. Chemosphere 2018, 192, 59– 65,  DOI: 10.1016/j.chemosphere.2017.10.149

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    Human exposure to neonicotinoid insecticides and the evaluation of their potential toxicity: An overview

    Han, Wenchao; Tian, Ying; Shen, Xiaoming

    Chemosphere (2018), 192 (), 59-65CODEN: CMSHAF; ISSN:0045-6535. (Elsevier Ltd.)

    Neonicotinoid insecticides have become the fastest growing class of insecticides over the past few decades. The insecticidal activity of neonicotinoids is attributed to their agonist action on nicotinic acetylcholine receptors (nAChRs). Because of the special selective action on nAChRs in central nervous system of insects, and versatility in application methods, neonicotinoids are used to protect crops and pets from insect attacks globally. Although neonicotinoids are considered low toxicity to mammals and humans in comparison with traditional insecticides, more and more studies show exposure to neonicotinoids pose potential risk to mammals and even humans. In recent years, neonicotinoids and their metabolites have been successfully detected in various human biol. samples. Meanwhile, many studies have focused on the health effects of neonicotinoids on humans. Our aims here are to review studies on human neonicotinoid exposure levels, health effect, evaluation of potential toxicity and to suggest possible directions for future research.

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46. 46

    Chen, M.; Tao, L.; McLean, J.; Lu, C. Quantitative analysis of neonicotinoid insecticide residues in foods: implication for dietary exposures. J. Agric. Food Chem. 2014, 62, 6082– 6090,  DOI: 10.1021/jf501397m

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    Quantitative Analysis of Neonicotinoid Insecticide Residues in Foods: Implication for Dietary Exposures

    Chen, Mei; Tao, Lin; McLean, John; Lu, Chensheng

    Journal of Agricultural and Food Chemistry (2014), 62 (26), 6082-6090CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)

    This study quant. measured neonicotinoids in various foods that are common to human consumption. All fruit and vegetable samples (except nectarine and tomato) and 90% of honey samples were detected pos. for at least one neonicotinoid; 72% of fruits, 45% of vegetables, and 50% of honey samples contained at least two different neonicotinoids in one sample, with imidacloprid having the highest detection rate among all samples. All pollen samples from New Zealand contained multiple neonicotinoids, and five of seven pollens from Massachusetts detected pos. for imidacloprid. These results show the prevalence of low-level neonicotinoid residues in fruits, vegetables, and honey that are readily available in the market for human consumption and in the environment where honeybees forage. In light of new reports of toxicol. effects in mammals, the results strengthen the importance of assessing dietary neonicotinoid intakes and the potential human health effects.

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    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslegurk%253D&md5=5d368918eb05485950db0e090972c527
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    Consumer Products Safety Commission. Chronic Hazard Advisory Panel on Phthalates and Phthalate Alternatives Final Report , July, 2014.

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    California Safe Cosmetics Act of 2005. In 2005; p Chapter 729.

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    Consumer Product Safety Improvement Act of 2008. In 2008; pp 122 STAT. 3016-122 STAT. 3077.

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    Food and Drug Administration, Indirect Food Additives: Polymers. In 2012; Vol. 77 41,899.

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51. 51

    Pelch, K.; Wignall, J. A.; Goldstone, A. E.; Ross, P. K.; Blain, R. B.; Shapiro, A. J.; Holmgren, S. D.; Hsieh, J. H.; Svoboda, D.; Auerbach, S. S.; Parham, F. M.; Masten, S. A.; Walker, V.; Rooney, A.; Thayer, K. A. A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives. Toxicology 2019, 424, 152235  DOI: 10.1016/j.tox.2019.06.006

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    A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives

    Pelch, Katherine; Wignall, Jessica A.; Goldstone, Alexandra E.; Ross, Pam K.; Blain, Robyn B.; Shapiro, Andrew J.; Holmgren, Stephanie D.; Hsieh, Jui-Hua; Svoboda, Daniel; Auerbach, Scott S.; Parham, Fredrick M.; Masten, Scott A.; Walker, Vickie; Rooney, Andrew; Thayer, Kristina A.

    Toxicology (2019), 424 (), 152235CODEN: TXCYAC; ISSN:0300-483X. (Elsevier Ltd.)

    A review. Recent studies report widespread usage or exposure to a variety of chems. with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogs or derivs. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogs of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to Jan. 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicol. Program's Research Report 4 (NTP RR-04), "Biol. Activity of Bisphenol A (BPA) Structural Analogs and Functional Alternatives". Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through Jan. 2019. In total, there are 22, 117, and 221 human epidemiol., exptl. animal, or in vitro studies included. The most frequently studied BPA analogs are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiol. studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a crit. need for better exposure information to prioritize exptl. studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA to consider BPA structural and functional analogs.

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    Rosenmai, A. K.; Dybdahl, M.; Pedersen, M.; Alice van Vugt-Lussenburg, B. M.; Wedebye, E. B.; Taxvig, C.; Vinggaard, A. M. Are structural analogues to bisphenol a safe alternatives?. Toxicol. Sci. 2014, 139, 35– 47,  DOI: 10.1093/toxsci/kfu030

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    Are Structural Analogues to Bisphenol A Safe Alternatives?

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Mikael; van Vugt-Lussenburg, Barbara Medea Alice; Wedebye, Eva Bay; Taxvig, Camilla; Vinggaard, Anne Marie

    Toxicological Sciences (2014), 139 (1), 035-047CODEN: TOSCF2; ISSN:1096-0929. (Oxford University Press)

    Bisphenol A (BPA) is a chem. with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogs of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives, there is a risk of effects similar to BPA. The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA. Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well as Quant. Structure-Activity Relationship (QSAR) modeling. Results: All test compds. caused the same qual. effects on estrogen receptor and androgen receptor activities, and most of the alternatives exhibited potencies within the same range as BPA. Hormone profiles for the compds. indicated a specific mechanism of action on steroidogenesis which generally lead to decreased androgen, and increased estrogen and progestagen levels. Differential effects on corticosteroid synthesis were obsd. suggesting a compd.-specific mechanism. Overall, BPS was less estrogenic and antiandrogenic than BPA, but BPS showed the largest efficacy on 17α-hydroxyprogesterone (17α-OH progesterone). Finally, there were indications of DNA damage, carcinogenicity, oxidative stress, effects on metab., and skin sensitization of one or more of the test compds. Conclusions: Interference with the endocrine system was the predominant effect of the test compds. A substitution of BPA with these structural analogs should be carried out with caution.

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53. 53

    Rodríguez-Carmona, Y.; Ashrap, P.; Calafat, A. M.; Ye, X.; Rosario, Z.; Bedrosian, L. D.; Huerta-Montanez, G.; Velez-Vega, C. M.; Alshawabkeh, A.; Cordero, J. F.; Meeker, J. D.; Watkins, D. Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico. J. Exposure Sci. Environ. Epidemiol. 2020, 30, 56– 69,  DOI: 10.1038/s41370-019-0168-8

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    Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico

    Rodriguez-Carmona, Yanelli; Ashrap, Pahriya; Calafat, Antonia M.; Ye, Xiaoyun; Rosario, Zaira; Bedrosian, Leah D.; Huerta-Montanez, Gredia; Velez-Vega, Carmen M.; Alshawabkeh, Akram; Cordero, Jose F.; Meeker, John D.; Watkins, Deborah

    Journal of Exposure Science & Environmental Epidemiology (2020), 30 (1), 56-69CODEN: JESEBS; ISSN:1559-0631. (Nature Research)

    Methods: We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concns. over time and linear mixed models to identify predictors of exposure (sociodemog. characteristics, drinking water sources, diet, product use). Results: Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (mol. sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were assocd. with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concns. remained low throughout the study period. Conclusion: Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Addnl. studies are needed to further characterize sources of phthalate replacement chems. and potential exposure-related health effects among vulnerable populations.

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    Silva, M. J.; Jia, T.; Samandar, E.; Preau, J. L., Jr; Calafat, A. M. Environmental exposure to the plasticizer 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) in U.S. adults (2000-2012). Environ. Res. 2013, 126, 159– 163,  DOI: 10.1016/j.envres.2013.05.007

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    Environmental exposure to the plasticizer 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) in US adults (2000-2012)

    Silva, Manori J.; Jia, Tao; Samandar, Ella; Preau, James L.; Calafat, Antonia M.

    Environmental Research (2013), 126 (), 159-163CODEN: ENVRAL; ISSN:0013-9351. (Elsevier)

    1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a complex mixt. of nine carbon branched-chain isomers. It has been used in Europe since 2002 as a plasticizer to replace phthalates such as di(2-ethylhexyl)phthalate (DEHP) and diisononyl phthalate (DINP). Urinary concns. of the oxidative metabolites of DINCH, namely cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (MCOCH); cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (MONCH); and cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (MHNCH), can potentially be used as DINCH exposure biomarkers. The concns. of MCOCH, MONCH and MHNCH were measured by online solid phase extn.-high performance liq. chromatog.-tandem mass spectrometry in urine collected in 2000 (n=114), 2001 (n=57), 2007 (n=23), 2009 (n=118), 2011 (n=94) and 2012 (n=121) from convenience groups of anonymous U.S. adult volunteers with no known DINCH exposure. None of the DINCH metabolites were detected in samples collected in 2000 and 2001. Only one sample collected in 2007 had measureable concns. of DINCH metabolites. The detection rate for all three metabolites increased from 2007 to 2012. The presence of oxidative metabolites of DINCH in urine suggests that these oxidative metabolites can be used as DINCH biomarkers for exposure assessment even at environmental exposure levels.

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55. 55

    Gyllenhammar, I.; Glynn, A.; Jonsson, B. A.; Lindh, C. H.; Darnerud, P. O.; Svensson, K.; Lignell, S. Diverging temporal trends of human exposure to bisphenols and plastizisers, such as phthalates, caused by substitution of legacy EDCs?. Environ. Res. 2017, 153, 48– 54,  DOI: 10.1016/j.envres.2016.11.012

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    55

    Diverging temporal trends of human exposure to bisphenols and plastizisers, such as phthalates, caused by substitution of legacy EDCs?

    Gyllenhammar, Irina; Glynn, Anders; Joensson, Bo A. G.; Lindh, Christian H.; Darnerud, Per Ola; Svensson, Kettil; Lignell, Sanna

    Environmental Research (2017), 153 (), 48-54CODEN: ENVRAL; ISSN:0013-9351. (Elsevier)

    Phthalates and phenolic substances were investigated in urine samples from first-time mothers in Uppsala, Sweden, collected between 2009 and 2014. These substances have a comparably fast metab. and urinary metabolites are predominantly analyzed. The main aim was to investigate if measures to decrease prodn. and use of certain phthalates and bisphenol A (BPA) have resulted in decreased human exposure, and to det. if exposures to replacement chems. have increased. Temporal trends were evaluated for metabolites (n=13) of seven phthalates, a phthalate replacer, four different bisphenols, triclosan, one organophosphate-based flame retardant, and for two pesticides. The results showed downward trends of several phthalates which are in the process of being regulated and phased out. Concomitantly, an increasing trend was seen for a metabolite of the phthalate replacer Di-iso-nonylcyclohexane 1,2-dicarboxylate (DiNCH). Bisphenol A (BPA) showed a downward trend, whereas bisphenol F, identified as one of the substitutes for BPA, showed an increasing trend. The decreasing trend of triclosan is likely due to declining use within the EU. Temporal trend studies of urine samples make it possible to investigate human exposure to rapidly metabolised substances and study how measures taken to regulate and replace problematic chems. affect human exposure.

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56. 56

    Kasper-Sonnenberg, M.; Koch, H. M.; Apel, P.; Ruther, M.; Palmke, C.; Bruning, T.; Kolossa-Gehring, M. Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB). Int. J. Hyg. Environ. Health 2019, 222, 1084– 1092,  DOI: 10.1016/j.ijheh.2019.07.011

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    Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

    Kasper-Sonnenberg, Monika; Koch, Holger M.; Apel, Petra; Ruether, Maria; Paelmke, Claudia; Bruening, Thomas; Kolossa-Gehring, Marike

    International Journal of Hygiene and Environmental Health (2019), 222 (8), 1084-1092CODEN: IJEHFT; ISSN:1438-4639. (Elsevier GmbH)

    From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concns. of OH-MINCH rapidly increased from 0.15μg/L in 2010 to twice the concn. in 2011 (0.31μg/L) with further increases in 2013 (0.37μg/L), 2015 (0.59μg/L) and 2017 (0.70μg/L). Similar increases, albeit at lower detection rates and concn. levels, could be obsd. for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other. For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calcd. for 2017 was 0.23μg/kg bw/d, thus 4,310-times lower than the TDI. The max. DI calcd. for one individual in 2012 (42.60μg/kg bw/d) was a factor of more than 20 below the TDI. The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk redn. measures if exposures reached crit. levels, or if new toxicol. data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.

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57. 57

    Doherty, B. T.; Hammel, S. C.; Daniels, J. L.; Stapleton, H. M.; Hoffman, K. Organophosphate Esters: Are These Flame Retardants and Plasticizers Affecting Children’s Health?. Curr. Environ. Health Rep. 2019, 6, 201– 213,  DOI: 10.1007/s40572-019-00258-0

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    57

    Organophosphate Esters: Are These Flame Retardants and Plasticizers Affecting Children's Health

    Doherty, Brett T.; Hammel, Stephanie C.; Daniels, Julie L.; Stapleton, Heather M.; Hoffman, Kate

    Current Environmental Health Reports (2019), 6 (4), 201-213CODEN: CEHRB3; ISSN:2196-5412. (Springer International Publishing AG)

    A review. Purpose of Review: Organophosphate esters (OPEs) are applied to a variety of consumer products, primarily as flame retardants and plasticizers. OPEs can leach out of products over time and are consequently prevalent in the environment and frequently detected in human biomonitoring studies. Exposure during pregnancy is of particular concern as OPEs have recently been detected in placental tissues, suggesting they may be transferred to the developing infant. Also, studies have now shown that children typically experience higher exposure to several OPEs compared with adults, indicating they may be disproportionately impacted by these compds. This review summarizes the current literature on reproductive and child health outcomes of OPE exposures and highlights areas for future research. Recent Findings: Exptl. animal studies demonstrate potential for OPEs to adversely impact health, and a limited no. of epidemiol. studies conducted in adult cohorts suggest that OPEs may interfere with the endocrine system. Assocns. have also been reported with reproductive outcomes (e.g., fertilization and pregnancy loss) and with the timing of parturition and preterm birth. Cross-sectional studies also demonstrate assocns. between OPEs and respiratory health outcomes, allergic disease, and measures of adiposity.

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58. 58

    Dodson, R. E.; Perovich, L. J.; Covaci, A.; Van den Eede, N.; Ionas, A. C.; Dirtu, A. C.; Brody, J. G.; Rudel, R. A. After the PBDE phase-out: a broad suite of flame retardants in repeat house dust samples from California. Environ. Sci. Technol. 2012, 46, 13056– 13066,  DOI: 10.1021/es303879n

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    58

    After the PBDE Phase-Out: A Broad Suite of Flame Retardants in Repeat House Dust Samples from California

    Dodson, Robin E.; Perovich, Laura J.; Covaci, Adrian; Van den Eede, Nele; Ionas, Alin C.; Dirtu, Alin C.; Brody, Julia Green; Rudel, Ruthann A.

    Environmental Science & Technology (2012), 46 (24), 13056-13066CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    Higher house dust polybrominated di-Ph ether (PBDE) flame retardant (FR) concns. have been reported in California vs. other parts of the world due to the state furniture flammability std.; however, changing concns. of these and other FR have not been evaluated following the 2004 US phase-out of PentaBDE and OctaBDE. This work analyzed dust collected in 16 California homes in 2006 and again in 2011 for 62 FR and organohalogens; this represents the broadest in-home FR investigation. A total of 55 compds. were detected in at least one sample; 41 in at least 50% of samples. Chlorinated organophosphate flame retardants concns., including 2 (TCEP, TDCIPP) listed as carcinogens under California Proposition 65, were obsd. up to 0.01% in dust, higher than previously reported in the US. In 75% of homes, TDBPP (brominated Tris) was detected; this compd. was banned in sleep-wear for children due to carcinogenicity. This is the first report on TDBPP in house dust. Concns. of Firemaster 550 components (EH-TBB, BEH-TEBP, TPHP) were higher in 2011 than 2006, consistent with its use as a PentaBDE replacement. Results highlighted the evolving nature of FR exposure and suggested manufacturers continue to use hazardous chems. and replace chems. of concern with chems. with uncharacterized toxicity.

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59. 59

    van der Veen, I.; de Boer, J. Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis. Chemosphere 2012, 88, 1119– 1153,  DOI: 10.1016/j.chemosphere.2012.03.067

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    59

    Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis

    van der Veen, Ike; de Boer, Jacob

    Chemosphere (2012), 88 (10), 1119-1153CODEN: CMSHAF; ISSN:0045-6535. (Elsevier Ltd.)

    A review. Since the ban on some brominated flame retardants (BFRs), phosphorus flame retardants (PFRs), which were responsible for 20% of the flame retardant (FR) consumption in 2006 in Europe, are often proposed as alternatives for BFRs. PFRs can be divided in three main groups, inorg., org. and halogen contg. PFRs. Most of the PFRs have a mechanism of action in the solid phase of burning materials (char formation), but some may also be active in the gas phase. Some PFRs are reactive FRs, which means they are chem. bound to a polymer, whereas others are additive and mixed into the polymer. The focus of this report is limited to the PFRs mentioned in the literature as potential substitutes for BFRs. The physico-chem. properties, applications and prodn. vols. of PFRs are given. Non-halogenated PFRs are often used as plasticisers as well. Limited information is available on the occurrence of PFRs in the environment. For tri-Ph phosphate (TPhP), tricresylphosphate (TCP), tris(2-chloroethyl)phosphate (TCEP), tris(chloropropyl)phosphate (TCPP), tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) a no. of studies have been performed on their occurrence in air, water and sediment, but limited data were found on their occurrence in biota. Concns. found for these PFRs in air were up to 47 μg m-3, in sediment levels up to 24 mg kg-1 were found, and in surface water concns. up to 379 ng L-1. In all these matrixes TCPP was dominant. Concns. found in dust were up to 67 mg kg-1, with TDCPP being the dominant PFR. PFR concns. reported were often higher than polybrominated diphenylether (PBDE) concns., and the human exposure due to PFR concns. in indoor air appears to be higher than exposure due to PBDE concns. in indoor air.Only the Cl-contg. PFRs are carcinogenic. Other neg. human health effects were found for Cl-contg. PFRs as well as for TCP, which suggest that those PFRs would not be suitable alternatives for BFRs. TPhP, diphenylcresylphosphate (DCP) and TCP would not be suitable alternatives either, because they are considered to be toxic to (aquatic) organisms. Diethylphosphinic acid is, just like TCEP, considered to be very persistent. From an environmental perspective, resorcinol-bis(diphenylphosphate) (RDP), bisphenol-A di-Ph phosphate (BADP) and melamine polyphosphate, may be suitable good substitutes for BFRs.Information on PFR anal. in air, water and sediment is limited to TCEP, TCPP, TPhP, TCP and some other organophosphate esters. For air sampling passive samplers have been used as well as solid phase extn. (SPE) membranes, SPE cartridges, and solid phase micro-extn. (SPME).For extn. of PFRs from water SPE is recommended, because this method gives good recoveries (67-105%) and acceptable relative std. deviations (RSDs) (<20%), and offers the option of online coupling with a detection system. For the extn. of PFRs from sediment microwave-assisted extn. (MAE) is recommended. The recoveries (78-105%) and RSDs (3-8%) are good and the method is faster and requires less solvent compared to other methods.For the final instrumental anal. of PFRs, gas chromatog.-flame photometric detection (GC-FPD), GC-nitrogen-phosphorus detection (NPD), GC-at. emission detection (AED), GC-mass spectrometry (MS) as well as liq. chromatog. (LC)-MS/MS and GC-Inductively-coupled plasma-MS (ICP-MS) are used. GC-ICP-MS is a promising method, because it provides much less complex chromatograms while offering the same recoveries and limits of detection (LOD) (instrumental LOD is 5-10 ng mL-1) compared to GC-NPD and GC-MS, which are frequently used methods for PFR anal. GC-MS offers a higher selectivity than GC-NPD and the possibility of using isotopically labeled compds. for quantification.

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60. 60

    Young, A. S.; Allen, J. G.; Kim, U. J.; Seller, S.; Webster, T. F.; Kannan, K.; Ceballos, D. M. Phthalate and Organophosphate Plasticizers in Nail Polish: Evaluation of Labels and Ingredients. Environ. Sci. Technol. 2018, 52, 12841– 12850,  DOI: 10.1021/acs.est.8b04495

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    60

    Phthalate and Organophosphate Plasticizers in Nail Polish: Evaluation of Labels and Ingredients

    Young, Anna S.; Allen, Joseph G.; Kim, Un-Jung; Seller, Stephanie; Webster, Thomas F.; Kannan, Kurunthachalam; Ceballos, Diana M.

    Environmental Science & Technology (2018), 52 (21), 12841-12850CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    In the 2000s, nail polish manufacturers started promoting "3-Free" products, phasing out three widely publicized toxic chems.: toluene, formaldehyde, and di-Bu phthalate (DnBP). However, DnBP was sometimes replaced by another endocrine-disrupting plasticizer, tri-Ph phosphate (TPHP). Many new "n-Free" labels have since appeared, without any standardization on which n chems. are excluded. This study aimed to compare measured plasticizer content against nail polish labels. First, we summarized definitions of labels. Then, we measured 12 phthalate and 10 organophosphate plasticizers in 40 nail polishes from 12 brands selected for popularity and label variety. We found labels ranging from 3- to 13-Free; 10-Free was the most inconsistently defined (six definitions). Our samples contained TPHP and bis(2-ethylhexyl) phthalate (DEHP) at up to 7940 and 331 μg/g, resp. The 5- to 13-Free samples had lower TPHP levels than unlabeled or 3-Free samples (median <0.002 vs. 3730 μg/g, p < 0.001). The samples that did not contain TPHP had higher DEHP levels (median 68.5 vs. 1.51 μg/g, p < 0.05). We measured plasticizers above 100 μg/g in five brands that did not disclose them and in two that excluded them in labels. This study highlights inconsistencies in nail polish labels and identifies TPHP and DEHP as ingredient substitutes for DnBP.

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61. 61

    Ingle, M. E.; Watkins, D.; Rosario, Z.; Velez Vega, C. M.; Huerta-Montanez, G.; Calafat, A. M.; Ospina, M.; Cordero, J. F.; Alshawabkeh, A.; Meeker, J. D. The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Rico. Environ. Res. 2019, 179, 108756  DOI: 10.1016/j.envres.2019.108756

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    The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Rico

    Ingle, Mary E.; Watkins, Deborah; Rosario, Zaira; Velez Vega, Carmen M.; Huerta-Montanez, Gredia; Calafat, Antonia M.; Ospina, Maria; Cordero, Jose F.; Alshawabkeh, Akram; Meeker, John D.

    Environmental Research (2019), 179 (Part_A), 108756CODEN: ENVRAL; ISSN:0013-9351. (Elsevier)

    Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been assocd. with adverse reproductive health outcomes. More research is needed to investigate assocns. with OPEs and personal care products (PCP) use. Pregnant women (18-40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n = 148 women) between 2011 and 2015. Concns. of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-Bu phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Assocns. among products and metabolite concns. (n = 296 observations) were assessed using linear mixed models. BCEtP, BCPP, BDCPP and DPHP were detected frequently (≥77%). Correlations among metabolites (0.16 ≤ r ≤ 0.35) and Intraclass correlation coeffs. (ICCs) (0.03 ≤ ICC≤0.34) were weak-to-moderate. Suntan lotion was assocd. with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home. Assocns. with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted.

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62. 62

    Cordner, A.; Richter, L.; Brown, P. Can Chemical Class Approaches Replace Chemical-by-Chemical Strategies? Lessons from Recent U.S. FDA Regulatory Action on Per- And Polyfluoroalkyl Substances. Environ. Sci. Technol. 2016, 50, 12584– 12591,  DOI: 10.1021/acs.est.6b04980

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    62

    Can Chemical Class Approaches Replace Chemical-by-Chemical Strategies? Lessons from Recent U.S. FDA Regulatory Action on Per- And Polyfluoroalkyl Substances

    Cordner, Alissa; Richter, Lauren; Brown, Phil

    Environmental Science & Technology (2016), 50 (23), 12584-12591CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    Concern about the toxicity and exposure of per- and polyfluoroalkyl substances (PFASs) is growing among scientists, regulators, and residents of contaminated communities. In 2016, the United States Food and Drug Administration (FDA) removed three food contact substances (FCSs) contg. perfluorinated chems. from the list of approved FCSs due to concerns regarding chem. safety. To investigate the significance and limitations of the FDA's regulatory action for environmental health research, advocacy, and regulation, we conducted a media anal. and qual. interviews with a range of involved stakeholders. We find that the FDA's regulatory action represents a potential shift from chem.-by-chem. regulation toward class-based regulation, where groups of chems. can be identified as sharing properties and risks, and are thus evaluated and regulated together. The FDA decision sets an important precedent of using a petition process to delist chems. based on a safety std. However, the narrow reach of this action also highlights the need for more comprehensive, precautionary chem. regulation capable of thoroughly evaluating classes of chems., and raises important questions about how classes of chems. are delimited in environmental health science and regulation.

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63. 63

    Chan, M.; Mita, C.; Bellavia, A.; Parker, M.; James-Todd, T. Racial/Ethnic Disparities in Pregnancy and Prenatal Exposure to Endocrine-Disrupting Chemicals Commonly Used in Personal Care Products. Curr. Environ. Health Rep. 2021, 8, 98– 112,  DOI: 10.1007/s40572-021-00317-5

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    63

    Racial/Ethnic Disparities in Pregnancy and Prenatal Exposure to Endocrine-Disrupting Chemicals Commonly Used in Personal Care Products

    Chan Marissa; Bellavia Andrea; Parker Michaiah; James-Todd Tamarra; Mita Carol; James-Todd Tamarra; James-Todd Tamarra

    Current environmental health reports (2021), 8 (2), 98-112 ISSN:.

    PURPOSE OF REVIEW: Endocrine-disrupting chemical (EDC) exposure during pregnancy is linked to adverse maternal and child health outcomes that are racially/ethnically disparate. Personal care products (PCP) are one source of EDCs where differences in racial/ethnic patterns of use exist. We assessed the literature for racial/ethnic disparities in pregnancy and prenatal PCP chemical exposures. RECENT FINDINGS: Only 3 studies explicitly examined racial/ethnic disparities in pregnancy and prenatal exposure to PCP-associated EDCs. Fifty-three articles from 12 cohorts presented EDC concentrations stratified by race/ethnicity or among homogenous US minority populations. Studies reported on phthalates and phenols. Higher phthalate metabolites and paraben concentrations were observed for pregnant non-Hispanic Black and Hispanic women. Higher concentrations of benzophenone-3 were observed in non-Hispanic White women; results were inconsistent for triclosan. This review highlights need for future research examining pregnancy and prenatal PCP-associated EDCs disparities to understand and reduce racial/ethnic disparities in maternal and child health.

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64. 64

    James-Todd, T. M.; Meeker, J. D.; Huang, T.; Hauser, R.; Ferguson, K. K.; Rich-Edwards, J. W.; McElrath, T. F.; Seely, E. W. Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors. Environ. Int. 2016, 96, 118– 126,  DOI: 10.1016/j.envint.2016.09.009

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    Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors

    James-Todd, Tamarra M.; Meeker, John D.; Huang, Tianyi; Hauser, Russ; Ferguson, Kelly K.; Rich-Edwards, Janet W.; McElrath, Thomas F.; Seely, Ellen W.

    Environment International (2016), 96 (), 118-126CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Epidemiol. studies suggest phthalate metabolite concns. are assocd. with type 2 diabetes. GDM is a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors [i.e. 1st trimester body mass index (BMI), gestational wt. gain (GWG), and 2nd trimester glucose levels]. A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concns. Nine sp. gr.-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess assocns. between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concns. and categorized GWG and impaired glucose tolerance defined as glucose ≥140 mg/dL based on a 50-g glucose load test. Models were adjusted for potential confounders. There were no assocns. between 1st trimester urinary phthalate metabolite concns. and 1st trimester BMI. Mono-Et phthalate concns. averaged across pregnancy were assocd. with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester mono-Et phthalate was assocd. with increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). A summary measure of di-2-ethylhexyl phthalate metabolite concns. were inversely assocd. with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). Higher exposure to mono-Et phthalate, a metabolite of the parent compd. of di-Et phthalate, may be assocd. with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was assocd. with reduced odds of impaired glucose tolerance.

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65. 65

    Nguyen, V. K.; Kahana, A.; Heidt, J.; Polemi, K.; Kvasnicka, J.; Jolliet, O.; Colacino, J. A. A comprehensive analysis of racial disparities in chemical biomarker concentrations in United States women, 1999-2014. Environ. Int. 2020, 137, 105496  DOI: 10.1016/j.envint.2020.105496

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    65

    A comprehensive analysis of racial disparities in chemical biomarker concentrations in United States women, 1999-2014

    Nguyen, Vy Kim; Kahana, Adam; Heidt, Julien; Polemi, Katelyn; Kvasnicka, Jacob; Jolliet, Olivier; Colacino, Justin A.

    Environment International (2020), 137 (), 105496CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Compared to non-Hispanic White women, the highest disparities were obsd. for non-Hispanic Black, Mexican American, Other Hispanic, and Other Race/Multi-Racial women with higher levels of pesticides and their metabolites, including 2,5-dichlorophenol, o,p'-DDE, beta-hexachlorocyclohexane, and 2,4-dichlorophenol, along with personal care and consumer product compds., including parabens and monoethyl phthalate, as well as several metals, such as mercury and arsenic. Exposure levels for Me and Pr parabens, however, were the highest in non-Hispanic black compared to non-Hispanic white children with av. differences exceeding 4-fold. Exposure disparities for Me and Pr parabens are increasing over time in Other Race/Multi-racial women while fluctuating for non-Hispanic Black, Mexican American, and Other Hispanic. Cotinine levels are among the highest in Non-Hispanic White women compared to Mexican American and Other Hispanic women with disparities plateauing and increasing, resp. We systematically evaluated differences in chem. exposures across women of various race/ethnic groups and across age groups and time. Our findings could help inform chem. prioritization in designing epidemiol. and toxicol. studies. In addn., they could help guide public health interventions to reduce environmental and health disparities across populations.

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66. 66

    Buckley, J. P.; Kim, H.; Wong, E.; Rebholz, C. M. Ultra-processed food consumption and exposure to phthalates and bisphenols in the US National Health and Nutrition Examination Survey, 2013-2014. Environ. Int. 2019, 131, 105057  DOI: 10.1016/j.envint.2019.105057

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    66

    Ultra-processed food consumption and exposure to phthalates and bisphenols in the US National Health and Nutrition Examination Survey, 2013-2014

    Buckley, Jessie P.; Kim, Hyunju; Wong, Eugenia; Rebholz, Casey M.

    Environment International (2019), 131 (), 105057CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Ultra-processed food has low nutritional quality, is assocd. with development of chronic diseases, and may increase exposure to chems. used in food packaging and prodn. To assess assocns. of ultra-processed food consumption with exposure to phthalates and bisphenols, including newer replacements, in the general U. S. population. Among 2212 National Health and Nutrition Examn. Survey (NHANES) 2013-2014 participants (≥6 years), we classified items reported in a 24-h dietary recall according to the NOVA food processing classification system and calcd. energy intake from ultra-processed food. Urinary concns. of mono-benzyl (MBzP), mono-(3-carboxypropyl) (MCPP), mono-(carboxyisononyl) (MCNP), mono-(carboxyisoctyl) (MCOP), and four metabolites of di(2-ethylhexyl) (.sum.DEHP) phthalates and bisphenols A, F, and S were measured in spot urine samples. We estd. percent changes in natural log creatinine-standardized concns. per 10% higher energy from ultra-processed food in covariate-adjusted multivariable linear regression models. We examd. effect measure modification by age group, race/ethnicity, and poverty:income ratio and assessed assocns. with minimally processed food intake. In adjusted models, higher energy from ultra-processed food was assocd. with higher urinary concns. of MCPP, MCNP, and MCOP but not MBzP, .sum.DEHP, or bisphenols. Each 10% higher energy from ultra-processed food was assocd. with 8.0% (95% CI: 5.6%, 10.3%) higher urinary MCOP concns., with a stronger assocn. among children than adolescents or adults. Ultra-processed sandwiches/hamburgers, French fries/other potato products, and ice cream/pops were assocd. with higher concns. of multiple chems. Higher energy from minimally processed food was assocd. with lower concns. of MCPP, MCNP, MCOP, and bisphenols A and F. Ultra-processed food consumption may increase exposure to currently used phthalates. Addnl. research is needed to det. whether minimally processed food diets or changes in food prodn. practices can reduce phthalate and bisphenol exposures and related health effects, particularly among children who are more vulnerable to toxicants and tend to consume more ultra-processed food than adults.

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    Zota, A. R.; Phillips, C. A.; Mitro, S. D. Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010. Environ. Health Perspect. 2016, 124, 1521– 1528,  DOI: 10.1289/ehp.1510803

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    Recent fast food consumption and bisphenol a and phthalates exposures among the U.S. population in NHANES, 2003-2010

    Zota, Ami R.; Phillips, Cassandra A.; Mitro, Susanna D.

    Environmental Health Perspectives (2016), 124 (10), 1521-1528CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

    BACKGROUND: Phthalates and bisphenol A (BPA) are widely used industrial chems. that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food. OBJECTIVE: To examine assocns. between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S. population. METHODS: We combined data on 8,877 participants from the National Health and Nutrition Examn. Survey (NHANES 2003-2010). Using 24-h dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examd. assocns. between dietary exposures and urinary chem. concns. using multivariate linear regression. RESULTS: We obsd. evidence of a pos., dose-response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, resp., than nonconsumers. Fast food-derived fat intake was also pos. assocd. with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was assocd. with grain and other intake, and DiNPm was assocd. with meat and grain intake. CONCLUSION: Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure redn. strategies.

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    Payne-Sturges, D. C.; Gee, G. C.; Cory-Slechta, D. A. Confronting Racism in Environmental Health Sciences: Moving the Science Forward for Eliminating Racial Inequities. Environ. Health Perspect. 2021, 129, 55002  DOI: 10.1289/EHP8186

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    Confronting Racism in Environmental Health Sciences: Moving the Science Forward for Eliminating Racial Inequities

    Payne-Sturges Devon C; Gee Gilbert C; Cory-Slechta Deborah A

    Environmental health perspectives (2021), 129 (5), 55002 ISSN:.

    BACKGROUND: The twin pandemics of COVID-19 and systemic racism during 2020 have forced a conversation across many segments of our society, including the environmental health sciences (EHS) research community. We have seen the proliferation of statements of solidarity with the Black Lives Matter movement and commitments to fight racism and health inequities from academia, nonprofit organizations, governmental agencies, and private corporations. Actions must now arise from these promises. As public health and EHS scientists, we must examine the systems that produce and perpetuate inequities in exposure to environmental pollutants and associated health effects. OBJECTIVES: We outline five recommendations the EHS research community can implement to confront racism and move our science forward for eliminating racial inequities in environmental health. DISCUSSION: Race is best considered a political label that promotes inequality. Thus, we should be wary of equating race with biology. Further, EHS researchers should seriously consider racism as a plausible explanation of racial disparities in health and consider structural racism as a factor in environmental health risk/impact assessments, as well as multiple explanations for racial differences in environmental exposures and health outcomes. Last, the EHS research community should develop metrics to measure racism and a set of guidelines on the use and interpretation of race and ethnicity within the environmental sciences. Numerous guidelines exist in other disciplines that can serve as models. By taking action on each of these recommendations, we can make significant progress toward eliminating racial disparities. https://doi.org/10.1289/EHP8186.

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69. 69

    Stanfield, Z.; Addington, C. K.; Dionisio, K. L.; Lyons, D.; Tornero-Velez, R.; Phillips, K. A.; Buckley, T. J.; Isaacs, K. K. Mining of Consumer Product Ingredient and Purchasing Data to Identify Potential Chemical Coexposures. Environ. Health Perspect. 2021, 129, 67006  DOI: 10.1289/EHP8610

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    69

    Mining of consumer product ingredient and purchasing data to identify potential chemical coexposures

    Stanfield, Zachary; Addington, Cody K.; Dionisio, Kathie L.; Lyons, David; Tornero-Velez, Rogelio; Phillips, Katherine A.; Buckley, Timothy J.; Isaacs, Kristin K.

    Environmental Health Perspectives (2021), 129 (6), 067006CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

    Background: Chems. in consumer products are a major contributor to human chem. coexposures. Consumers purchase and use a wide variety of products contg. potentially thousands of chems. There is a need to identify potential real-world chem. coexposures to prioritize in vitro toxicity screening. However, due to the vast no. of potential chem. combinations, this identification has been a major challenge. Objectives: We aimed to develop and implement a data-driven procedure for identifying prevalent chem. combinations to which humans are exposed through purchase and use of consumer products. Methods: We applied frequent itemset mining to an integrated data set linking consumer product chem. ingredient data with product purchasing data from 60,000 households to identify chem. combinations resulting from co-use of consumer products. Results: We identified co-occurrence patterns of chems. over all households as well as those specific to demog. groups based on race/ethnicity, income, education, and family compn. We also identified chems. with the highest potential for aggregate exposure by identifying chems. occurring in multiple products used by the same household. Last, a case study of chems. active in estrogen and androgen receptor in silico models revealed priority chem. combinations co-targeting receptors involved in important biol. signaling pathways. Discussion: Integration and comprehensive anal. of household purchasing data and product-chem. information provided a means to assess human near-field exposure and inform selection of chem. combinations for high-throughput screening in in vitro assays.

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    Zeng, D.; Kang, Y.; Chen, J.; Li, A.; Chen, W.; Li, Z.; He, L.; Zhang, Q.; Luo, J.; Zeng, L. Dermal bioaccessibility of plasticizers in indoor dust and clothing. Sci. Total Environ. 2019, 672, 798– 805,  DOI: 10.1016/j.scitotenv.2019.04.028

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    70

    Dermal bioaccessibility of plasticizers in indoor dust and clothing

    Zeng, Diya; Kang, Yuan; Chen, Junheng; Li, Anyao; Chen, Wanyu; Li, Zhumei; He, Lintao; Zhang, Qiuyun; Luo, Jiwen; Zeng, Lixuan

    Science of the Total Environment (2019), 672 (), 798-805CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    Several studies indicated human exposure to plasticizers by a dermal pathway is not negligible, but dermal bioaccessibility of phthalates and alternative plasticizers from important environmental matrixes (indoor dust, clothing) and the importance wt. of dermal exposure to those pollutants have been poorly studied. An in-vitro physiol.-based extn. test was used to assess dermal bioaccessibility of target phthalates and alternative plasticizers from indoor dust and clothing. Temp., incubation time, and sweat:sebum and solid:liq. ratios were selected to examine their effect on bioaccessibility. Bioaccessibility of di-Et phthalate (DEP), di-Bu phthalate (DBP), bis-2-ethylhexyl phthalate (DEHP), acetyl tri-Bu citrate (ATBC), bis-2-ethylhexyladipate (DEHA), and bis-2-ethylhexyl terephthalate (DEHT) in indoor dust were 66.20 ± 1.93, 94.27 ± 1.31, 80.37 ± 8.09, 75.02 ± 2.12, 94.50 ± 3.42, and 74.09 ± 3.79%, resp., under 1:1 sweat:sebum ratio, 1:100 solid:liq. ratio (indoor dust), 1:1 area:area ratio (1:1, clothing), and 90 min incubation time at 36.3° conditions, selected based on exptl. results and human phys. DBP displayed the highest bioaccessibility in all samples. The time course of plasticizer release was fitted to a first-order, one-compartment model. DBP showed the highest model-calcd. release rate (k1), consistent with bioaccessibility results. A risk assessment indicated DBP dermal exposure was an important exposure route, accounting for ∼21.58% of total intake. Indoor dust was an important exposure media when considering dermal bioaccessibility.

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    Hou, M.; Shi, Y.; Na, G.; Cai, Y. A review of organophosphate esters in indoor dust, air, hand wipes and silicone wristbands: Implications for human exposure. Environ. Int. 2021, 146, 106261  DOI: 10.1016/j.envint.2020.106261

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    71

    A review of organophosphate esters in indoor dust, air, hand wipes and silicone wristbands: Implications for human exposure

    Hou, Minmin; Shi, Yali; Na, Guangshui; Cai, Yaqi

    Environment International (2021), 146 (), 106261CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    A review. The ubiquity of organophosphate esters (OPEs) in various environmental matrixes inevitably pose human exposure risks. Numerous studies have investigated human exposure pathways to OPEs, including air inhalation, dust ingestion, dermal contact, and dietary and drinking water intake, and have indicated that indoor dust and indoor air routes are frequently the two main human exposure pathways. This article reviews the literature on OPE contamination in indoor air and dust from various microenvironments and on OPE particle size distributions and bioavailability in dust conducted over the past 10 years. Ways in which sampling strategies are related to the uncertainty of exposure assessment results and comparability among different studies in terms of sampling tools, sampling sites, and sample types are addressed. Also, the assocns. of OPEs in indoor dust/air with human biol. samples were summarized. Studies on two emerging matrixes, hand wipes and silicone wristbands, are demonstrated to be more comprehensive and accurate in reflecting personal human exposure to OPEs in microenvironments and are summarized. Given the direct application of some diester OPEs (di-OPEs) in numerous products, research on their existence in indoor dust and food and on their effects on human urine are also discussed. Finally, related research trends and avenues for future research are prospected.

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    Karrer, C.; Andreassen, M.; von Goetz, N.; Sonnet, F.; Sakhi, A. K.; Hungerbuhler, K.; Dirven, H.; Husoy, T. The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels. Environ. Int. 2020, 136, 105397  DOI: 10.1016/j.envint.2019.105397

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    72

    The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels

    Karrer, Cecile; Andreassen, Monica; von Goetz, Natalie; Sonnet, Friederike; Sakhi, Amrit Kaur; Hungerbuhler, Konrad; Dirven, Hubert; Husoey, Trine

    Environment International (2020), 136 (), 105397CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concns. were compared to source-to-dose calcns. for source allocation and plausibility test of the model. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amts. of canned food consumed, the no. of PCPs used, or the no. of TP handling events and levels of BPA, BPS, or BPF. The good agreement between the ranges of modeled BPA exposure and measured BPA amts. indicates that available concns., esp. from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amts. and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concns. in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the resp. exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concn. and occurrence data.

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73. 73

    Husøy, T.; Andreassen, M.; Hjertholm, H.; Carlsen, M. H.; Norberg, N.; Sprong, C.; Papadopoulou, E.; Sakhi, A. K.; Sabaredzovic, A.; Dirven, H. The Norwegian biomonitoring study from the EU project EuroMix: Levels of phenols and phthalates in 24-hour urine samples and exposure sources from food and personal care products. Environ. Int. 2019, 132, 105103  DOI: 10.1016/j.envint.2019.105103

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    73

    The Norwegian biomonitoring study from the EU project EuroMix: Levels of phenols and phthalates in 24-hour urine samples and exposure sources from food and personal care products

    Husoy T; Andreassen M; Hjertholm H; Papadopoulou E; Sakhi A K; Sabaredzovic A; Dirven H A A M; Carlsen M H; Norberg N; Sprong C

    Environment international (2019), 132 (), 105103 ISSN:.

    BACKGROUND: Exposure to multiple chemicals occurs daily through several routes; diet, inhalation and dermal contact. Real-life exposure assessment is needed to understand the risk. Therefore, a human biomonitoring (BM) study was performed to examine the plausibility of source-to-dose calculations for chemical mixtures in the Horizon 2020 EuroMix project. OBJECTIVES: To provide a detailed description of the design of the EuroMix BM study, and to present the initial results for urinary phenols and phthalates and to describe their exposure determinants from foods and personal care products (PCPs). METHOD: Adults (44 males and 100 females) kept detailed diaries on their food consumption, PCP use and handling of cash receipts. Urine samples were collected over the same 24-hour period. Urinary levels of four parabens, five bisphenols, oxybenzone/benzophenone-3 (OXBE), triclosan (TCS), triclocarban (TCC) and metabolites of eight phthalates and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were analysed by ultra-high-performance liquid chromatography and tandem mass spectrometry. Multivariable linear regressions were performed between PCPs/food categories and each dependent chemical variable separately, and were only sex-stratified when an interactions between sex and the independent variable was significant. RESULTS: The detection rate for the metabolites of phthalates and DINCH, and bisphenol A (BPA) and TCS in urine was 88-100%, while bisphenol S (BPS) and bisphenol F (BPF) were only found in 29% and 4% of the urine samples, respectively. Bisphenol B (BPB), bisphenol AF (BPAF) and TCC were not detected. Food groups associated with phenol exposure were meat, bread, beverages and butter and oil. Food determinants for phthalate exposure were sweets, butter and oil, fruit and berries and other foods. The only positive association between the use of PCPs and phenols was found between BPA and lip gloss/balm. Phthalate exposure was associated with the use of shower gel, hand cream (females), toothpaste, anti-wrinkle cream (females) and shaving products (males). CONCLUSION: The participants in the EuroMix BM study were exposed to a mixture of phenols and phthalates. A variety of food categories and PCPs were found to be possible sources of these chemicals. This indicates a complex pattern of exposure to numerous chemicals from multiple sources, depending on individual diet and PCP preferences.

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    Mitro, S. D.; Dodson, R. E.; Singla, V.; Adamkiewicz, G.; Elmi, A. F.; Tilly, M. K.; Zota, A. R. Consumer Product Chemicals in Indoor Dust: A Quantitative Meta-analysis of U.S. Studies. Environ. Sci. Technol. 2016, 50, 10661– 10672,  DOI: 10.1021/acs.est.6b02023

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    74

    Consumer Product Chemicals in Indoor Dust: A Quantitative Meta-analysis of U.S. Studies

    Mitro, Susanna D.; Dodson, Robin E.; Singla, Veena; Adamkiewicz, Gary; Elmi, Angelo F.; Tilly, Monica K.; Zota, Ami R.

    Environmental Science & Technology (2016), 50 (19), 10661-10672CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    Indoor dust is a reservoir for com. consumer product chems., including many compds. with known or suspected health effects; however, most dust exposure studies measure few chems. in small samples. This work systematically searched the US indoor dust literature on phthalates, replacement flame retardants (RFR), perfluoroalkyl substances (PFAS), synthetic fragrances, and environmental phenols, and estd. pooled geometric means (GM) and 95% confidence intervals for 45 chems. measured in ≥3 datasets. Pooled GM calcd. residential intake from dust ingestion, inhalation, and dermal uptake from air, then hazard traits from the Safer Consumer Products Candidate Chem. List were identified to rank and contextualize these results. Results indicated US indoor dust consistently contains chems. from multiple classes. Phthalates occurred in the highest concns., followed by phenols, RFR, fragrance, and PFAS; several phthalates and RFR had the highest residential intakes. Many chems. in dust share hazard traits, e.g., reproductive and endocrine toxicity. Recommendations are made to maximize study comparability and advance indoor exposure science. This information is crit. in shaping future exposure and health studies, particularly related to cumulative exposure, and providing evidence for intervention development and public policy.

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    Shin, H. M.; Moschet, C.; Young, T. M.; Bennett, D. H. Measured concentrations of consumer product chemicals in California house dust: Implications for sources, exposure, and toxicity potential. Indoor Air 2020, 30, 60– 75,  DOI: 10.1111/ina.12607

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    75

    Measured concentrations of consumer product chemicals in California house dust: Implications for sources, exposure, and toxicity potential

    Shin, Hyeong-Moo; Moschet, Christoph; Young, Thomas M.; Bennett, Deborah H.

    Indoor Air (2020), 30 (1), 60-75CODEN: INAIE5; ISSN:1600-0668. (Wiley-Blackwell)

    Household dust is a reservoir of various consumer product chems. Thus, characterizing comprehensive chem. profiles of house dust may help improve our understanding of residential chem. exposure. We have previously developed a method for detecting a broad spectrum of chems. in dust by applying a combination of target, suspect screening, and non-target methods with mass spectrometry preceded by liq. chromatog. and gas chromatog. Building upon a previous study that detected 271 compds. in 38 dust samples, we presented concns. of 144 compds. that were confirmed and quantified by stds. in the same set of samples. Ten compds. were measured with median concns. greater than 10 000 ng/g of dust: cis-hexadec-6-enoic acid, squalene, cholesterol, vitamin E, bis(2-ethylhexyl) phthalate, dioctyl terephthalate, linoleic acid, tricaprylin, tris(1-chloroisopropyl) phosphate, and oxybenzone. We also reviewed in vitro toxicity screening data to identify compds. that were not previously detected in indoor dust but have potential for adverse health effects. Among 119 newly detected compds., 13 had endocrine-disrupting potential and 7 had neurotoxic potential. Toxicity screening data were not available for eight biocides, which may adversely affect health. Our results strive to provide more comprehensive chem. profiles of house dust and identified information gaps for future health studies.

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    Centers for Disease Control and Prevention, Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, March 2021.

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77. 77

    Calafat, A. M.; Longnecker, M. P.; Koch, H. M.; Swan, S. H.; Hauser, R.; Goldman, L. R.; Lanphear, B. P.; Rudel, R. A.; Engel, S. M.; Teitelbaum, S. L.; Whyatt, R. M.; Wolff, M. S. Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology. Environ. Health Perspect. 2015, 123, A166– A168,  DOI: 10.1289/ehp.1510041

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    77

    Optimal exposure biomarkers for nonpersistent chemicals in environmental epidemiology

    Calafat, Antonia M.; Longnecker, Matthew P.; Koch, Holger M.; Swan, Shanna H.; Hauser, Russ; Goldman, Lynn R.; Lanphear, Bruce P.; Rudel, Ruthann A.; Engel, Stephanie M.; Teitelbaum, Susan L.; Whyatt, Robin M.; Wolff, Mary S.

    Environmental Health Perspectives (2015), 123 (7), A166-A168CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

    We discuss considerations that are essential when evaluating exposure to nonpersistent, semivolatile environmental chems. such as phthalates and phenols (e.g., bisphenol A). A biomarker should be chosen to best represent usual personal exposures and not recent, adventitious, or extraneous exposures. Biomarkers should be selected to minimize contamination arising from collection, sampling, or anal. procedures. Pharmacokinetics should be considered; for example, nonpersistent, semivolatile chems. are metabolized quickly, and urine is the compartment with the highest concns. of metabolites. Because these chems. are nonpersistent, knowledge of intraindividual reliability over the biol. window of interest is also required. In recent years researchers have increasingly used blood as a matrix for characterizing exposure to nonpersistent chems. However, the biol. and tech. factors noted above strongly support urine as the optimal matrix for measuring nonpersistent, semivolatile, hydrophilic environmental agents.

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    Kwiatkowski, C. F.; Andrews, D. Q.; Birnbaum, L. S.; Bruton, T. A.; DeWitt, J. C.; Knappe, D. R. U.; Maffini, M. V.; Miller, M. F.; Pelch, K. E.; Reade, A.; Soehl, A.; Trier, X.; Venier, M.; Wagner, C. C.; Wang, Z.; Blum, A. Scientific Basis for Managing PFAS as a Chemical Class. Environ. Sci. Technol. Lett. 2020, 7, 532– 543,  DOI: 10.1021/acs.estlett.0c00255

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    Scientific Basis for Managing PFAS as a Chemical Class

    Kwiatkowski, Carol F.; Andrews, David Q.; Birnbaum, Linda S.; Bruton, Thomas A.; DeWitt, Jamie C.; Knappe, Detlef R. U.; Maffini, Maricel V.; Miller, Mark F.; Pelch, Katherine E.; Reade, Anna; Soehl, Anna; Trier, Xenia; Venier, Marta; Wagner, Charlotte C.; Wang, Zhanyun; Blum, Arlene

    Environmental Science & Technology Letters (2020), 7 (8), 532-543CODEN: ESTLCU; ISSN:2328-8930. (American Chemical Society)

    A scientific basis to manage one chem. class, PFAS (per- and polyfluoroalkyl substances) is discussed. This class includes perfluoroalkyl acids, perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochem., environmental, and toxicol. properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS examd. to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. It concludes with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential PFAS uses, and how to further develop safer alternatives and methods to remove existing PFAS from the environment.

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    Bălan, S. A.; Mathrani, V. C.; Guo, D. F.; Algazi, A. M. Regulating PFAS as a Chemical Class under the California Safer Consumer Products Program. Environ. Health Perspect. 2021, 129, 25001  DOI: 10.1289/EHP7431

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    79

    Regulating PFAS as a Chemical Class under the California Safer Consumer Products Program

    Balan Simona Andreea; Mathrani Vivek Chander; Guo Dennis Fengmao; Algazi Andre Maurice

    Environmental health perspectives (2021), 129 (2), 25001 ISSN:.

    BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of manmade chemicals containing at least one fully fluorinated carbon atom. The widespread use, large number, and diverse chemical structures of PFAS pose challenges to any sufficiently protective regulation, emissions reduction, and remediation at contaminated sites. Regulating only a subset of PFAS has led to their replacement with other members of the class with similar hazards, that is, regrettable substitutions. Regulations that focus solely on perfluoroalkyl acids (PFAAs) are ineffective, given that nearly all other PFAS can generate PFAAs in the environment. OBJECTIVES: In this commentary, we present the rationale adopted by the State of California's Department of Toxic Substances Control (DTSC) for regulating PFAS as a class in certain consumer products. DISCUSSION: We at the California DTSC propose regulating certain consumer products if they contain any member of the class of PFAS because: a) all PFAS, or their degradation, reaction, or metabolism products, display at least one common hazard trait according to the California Code of Regulations, namely environmental persistence; and b) certain key PFAS that are the degradation, reaction or metabolism products, or impurities of nearly all other PFAS display additional hazard traits, including toxicity; are widespread in the environment, humans, and biota; and will continue to cause adverse impacts for as long as any PFAS continue to be used. Regulating PFAS as a class is thus logical, necessary, and forward-thinking. This technical position may be helpful to other regulatory agencies in comprehensively addressing this large class of chemicals with common hazard traits. https://doi.org/10.1289/EHP7431.

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