Apel et al., 2020
Apel, P., Rousselle, C., Lange, R., Sissoko, F., Kolossa-Gehring, M., & Ougier, E.; “Human biomonitoring initiative (HBM4EU) – Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment;” International Journal of Hygiene and Environmental Health, 2020, 230, 113622; DOI: 10.1016/j.ijheh.2020.113622.
ABSTRACT:
The European Joint Program “HBM4EU” is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission’s Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values – named HBM guidance values or HBM-GVs – can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values’ proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative. FULL TEXT
Andersen et al., 2008
Andersen, H. R., Schmidt, I. M., Grandjean, P., Jensen, T. K., Budtz-Jorgensen, E., Kjaerstad, M. B., Baelum, J., Nielsen, J. B., Skakkebaek, N. E., & Main, K. M.; “Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy;” Environmental Health Perspectives, 2008, 116(4), 566-572; DOI: 10.1289/ehp.10790.
ABSTRACT:
OBJECTIVES: The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants.
DESIGN AND MEASUREMENTS: Pregnant women employed in greenhouses in Denmark were consecutively recruited, and 113 mother-son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized techniques. Concentrations of reproductive hormones in serum from the boys were analyzed.
RESULTS: The prevalence of cryptorchidism at 3 months of age was 6.2% [95% confidence interval (CI), 3.0-12.4]. This prevalence was considerably higher than among Danish boys born in the Copenhagen area (1.9%; 95% CI, 1.2-3.0) examined by the same procedure. Boys of pesticide-exposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone: testosterone ratio were increased compared with boys of nonexposed mothers. For individual parameters, only the decreased penile length was statistically significant (p = 0.04). However, all observed effects were in the anticipated direction, and a joint multivariate test showed that this finding had a p-value of 0.012.
CONCLUSIONS: Our findings suggest an adverse effect of maternal occupational pesticide exposure on reproductive development in the sons despite current greenhouse safeguards and special measures to protect pregnant women.
Alberto et al., 2016
Alberto, D., Serra, A. A., Sulmon, C., Gouesbet, G., & Couee, I.; “Herbicide-related signaling in plants reveals novel insights for herbicide use strategies, environmental risk assessment and global change assessment challenges;” Science of The Total Environment, 2016, 569-570, 1618-1628; DOI: 10.1016/j.scitotenv.2016.06.064.
ABSTRACT:
Herbicide impact is usually assessed as the result of a unilinear mode of action on a specific biochemical target with a typical dose-response dynamics. Recent developments in plant molecular signaling and crosstalk between nutritional, hormonal and environmental stress cues are however revealing a more complex picture of inclusive toxicity. Herbicides induce large-scale metabolic and gene-expression effects that go far beyond the expected consequences of unilinear herbicide-target-damage mechanisms. Moreover, groundbreaking studies have revealed that herbicide action and responses strongly interact with hormone signaling pathways, with numerous regulatory protein-kinases and -phosphatases, with metabolic and circadian clock regulators and with oxidative stress signaling pathways. These interactions are likely to result in mechanisms of adjustment that can determine the level of sensitivity or tolerance to a given herbicide or to a mixture of herbicides depending on the environmental and developmental status of the plant. Such regulations can be described as rheostatic and their importance is discussed in relation with herbicide use strategies, environmental risk assessment and global change assessment challenges. FULL TEXT
Gillezeau et al., 2020
Gillezeau, C., Lieberman-Cribbin, W., & Taioli, E.; “Update on human exposure to glyphosate, with a complete review of exposure in children;” Environmental Health, 2020, 19(1), 115; DOI: 10.1186/s12940-020-00673-z.
ABSTRACT:
BACKGROUND: Glyphosate, a commonly used pesticide, has been the topic of much debate. The effects of exposure to glyphosate remains a contentious topic. This paper provides an update to the existing literature regarding levels of glyphosate exposure in occupationally exposed individuals and focuses or reviewing all the available published literature regarding glyphosate exposure levels in children.
METHODS: A literature review was conducted and any articles reporting quantifiable exposure levels in humans published since January 2019 (the last published review on glyphosate exposure) were reviewed and data extracted and standardized.
RESULTS: A total of five new studies reporting exposure levels in humans were found including 578 subjects. Two of these studies focused on occupationally exposed individuals while three of them focused on glyphosate exposure levels in children. Given the sparse nature of the new data, previously identified studies on exposure to glyphosate in children were included in our analysis of children’s exposure. The lowest average level of glyphosate exposure reported was 0.28 μg/L and the highest average exposure levels reported was 4.04 μg/L.
CONCLUSION: The literature on glyphosate exposure levels, especially in children, remains limited. Without more data collected in a standardized way, parsing out the potential relationship between glyphosate exposure and disease will not be possible. FULL TEXT
Haas et al., 2015
Haas, D. M., Parker, C. B., Wing, D. A., Parry, S., Grobman, W. A., Mercer, B. M., Simhan, H. N., Hoffman, M. K., Silver, R. M., Wadhwa, P., Iams, J. D., Koch, M. A., Caritis, S. N., Wapner, R. J., Esplin, M. S., Elovitz, M. A., Foroud, T., Peaceman, A. M., Saade, G. R., Willinger, M., Reddy, U. M., & NuMo, M. b study; “A description of the methods of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b);” American Journal of Obstetrics & Gynecology, 2015, 212(4), 539 e531-539 e524; DOI: 10.1016/j.ajog.2015.01.019.
ABSTRACT:
OBJECTIVE: The primary aim of the “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, and environmental factors that predict adverse pregnancy outcomes.
STUDY DESIGN: Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks’ gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction.
RESULTS: We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported.
CONCLUSION: The “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” cohort study methods and procedures can help investigators when they plan future projects.
Hantsoo et al., 2019
Hantsoo, L., Jasarevic, E., Criniti, S., McGeehan, B., Tanes, C., Sammel, M. D., Elovitz, M. A., Compher, C., Wu, G., & Epperson, C. N.; “Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy;” Brain, Behavior, and Immunity, 2019, 75, 240-250; DOI: 10.1016/j.bbi.2018.11.005.
ABSTRACT:
BACKGROUND: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women.
METHODS: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34weeks gestation; plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated.
RESULTS: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q=5.7×10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-alpha and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p=0.03) and eicosapentaenoic acid (EPA) (p=0.05).
DISCUSSION: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of omega-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.
Scholze et al., 2020
Scholze, M., Taxvig, C., Kortenkamp, A., Boberg, J., Christiansen, S., Svingen, T., Lauschke, K., Frandsen, H., Ermler, S., Hermann, S. S., Pedersen, M., Lykkeberg, A. K., Axelstad, M., & Vinggaard, A. M.; “Quantitative in Vitro to in Vivo Extrapolation (QIVIVE) for Predicting Reduced Anogenital Distance Produced by Anti-Androgenic Pesticides in a Rodent Model for Male Reproductive Disorders;” Environ Health Perspect, 2020, 128(11), 117005; DOI: 10.1289/EHP6774.
ABSTRACT:
BACKGROUND: Many pesticides can antagonize the androgen receptor (AR) or inhibit androgen synthesis in vitro but their potential to cause reproductive toxicity related to disruption of androgen action during fetal life is difficult to predict. Currently no approaches for using in vitro data to anticipate such in vivo effects exist. Prioritization schemes that limit unnecessary in vivo testing are urgently needed.
OBJECTIVES: The aim was to develop a quantitative in vitro to in vivo extrapolation (QIVIVE) approach for predicting in vivo anti-androgenicity arising from gestational exposures and manifesting as a shortened anogenital distance (AGD) in male rats.
METHODS: We built a physiologically based pharmacokinetic (PBK) model to simulate concentrations of chemicals in the fetus resulting from maternal dosing. The predicted fetal levels were compared with analytically determined concentrations, and these were judged against in vitro active concentrations for AR antagonism and androgen synthesis suppression.
RESULTS: We first evaluated our model by using in vitro and in vivo anti-androgenic data for procymidone, vinclozolin, and linuron. Our PBK model described the measured fetal concentrations of parent compounds and metabolites quite accurately (within a factor of five). We applied the model to nine current-use pesticides, all with in vitro evidence for anti-androgenicity but missing in vivo data. Seven pesticides (fludioxonil, cyprodinil, dimethomorph, imazalil, quinoxyfen, fenhexamid, o-phenylphenol) were predicted to produce a shortened AGD in male pups, whereas two (lambda-cyhalothrin, pyrimethanil) were anticipated to be inactive. We tested these expectations for fludioxonil, cyprodinil, and dimethomorph and observed shortened AGD in male pups after gestational exposure. The measured fetal concentrations agreed well with PBK-modeled predictions.
DISCUSSION: Our QIVIVE model newly identified fludioxonil, cyprodinil, and dimethomorph as in vivo anti-androgens. With the examples investigated, our approach shows great promise for predicting in vivo anti-androgenicity (i.e., AGD shortening) for chemicals with in vitro activity and for minimizing unnecessary in vivo testing. FULL TEXT
Pellizzari et al., 2019
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;” Environmental Health Perspectives, 2019, 127(12), 126001; DOI: 10.1289/EHP5133.
ABSTRACT:
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. FULL TEXT
Buckley et al., 2020
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;” Journal of exposure science & environmental epidemiology, 2020, 30(3), 397-419; DOI: 10.1038/s41370-020-0211-9.
ABSTRACT:
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. FULL TEXT
Franke et al., 2020
Franke, A. A., Li, X., & Lai, J. F.; “Analysis of glyphosate, aminomethylphosphonic acid, and glufosinate from human urine by HRAM LC-MS;” Analytical and Bioanalytical Chemistry, 2020; DOI: 10.1007/s00216-020-02966-1.
ABSTRACT:
Aminomethylphosphonic acid (AMPA) is the main metabolite of glyphosate (GLYP) and phosphonic acids in detergents. GLYP is a synthetic herbicide frequently used worldwide alone or together with its analog glufosinate (GLUF). The general public can be exposed to these potentially harmful chemicals; thus, sensitive methods to monitor them in humans are urgently required to evaluate health risks. We attempted to simultaneously detect GLYP, AMPA, and GLUF in human urine by high-resolution accurate-mass liquid chromatography mass spectrometry (HRAM LC-MS) before and after derivatization with 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl) or 1-methylimidazole-sulfonyl chloride (ImS-Cl) with several urine pre-treatment and solid phase extraction (SPE) steps. Fmoc-Cl derivatization achieved the best combination of method sensitivity (limit of detection; LOD) and accuracy for all compounds compared to underivatized urine or ImS-Cl-derivatized urine. Before derivatization, the best steps for GLYP involved 0.4 mM ethylenediaminetetraacetic acid (EDTA) pre-treatment followed by SPE pre-cleanup (LOD 37 pg/mL), for AMPA involved no EDTA pre-treatment and no SPE pre-cleanup (LOD 20 pg/mL) or 0.2-0.4 mM EDTA pre-treatment with no SPE pre-cleanup (LOD 19-21 pg/mL), and for GLUF involved 0.4 mM EDTA pre-treatment and no SPE pre-cleanup (LOD 7 pg/mL). However, for these methods, accuracy was sufficient only for AMPA (101-105%), while being modest for GLYP (61%) and GLUF (63%). Different EDTA and SPE treatments prior to Fmoc-Cl derivatization resulted in high sensitivity for all analytes but satisfactory accuracy only for AMPA. Thus, we conclude that our HRAM LC-MS method is suited for urinary AMPA analysis in cross-sectional studies. FULL TEXT