Alternative Approaches to Dose–Response Modeling of Toxicological Endpoints for Risk Assessment: Nonmonotonic Dose Responses for Endocrine Disruptors

Vandenberg, Laura N.; Blumberg, Bruce

doi:10.1016/b978-0-12-801238-3.64298-8

Cited by 4 publications

(5 citation statements)

References 140 publications

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“…This type of relationship suggests that physiological adaptations to high exposure may protect from the detrimental effects of nickel and is commonly observed in epidemiological studies of endocrine disruptors (Vandenberg et al 2012 ), for which nickel is classified (Stinson et al 1992 ). Several underlying mechanisms have been explored to explain non-monotonic dose responses (Vandenberg and Blumberg 2018 ), such as the one observed in this study; however, the exact mechanism remains elusive for nickel. Corroborating the non-monotonic effects of nickel are two studies among adults in China and the U.S. that observed a plateau in the relationship between environmental nickel exposure and diabetes (Liu et al 2015 ; Titcomb et al 2021 ).…”

Section: Discussionmentioning

confidence: 98%

Environmental Nickel Exposure and Cardiovascular Disease in a Nationally Representative Sample of U.S. Adults

et al. 2023

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Background Laboratory studies have linked nickel with the pathogenesis of cardiovascular disease (CVD); however, few observational studies in humans have confirmed this association. Objective This study aimed to use urinary nickel concentrations, as a biomarker of environmental nickel exposure, to evaluate the cross-sectional association between nickel exposure and CVD in a nationally representative sample of U.S. adults. Methods Data from a nationally representative sample ( n = 2702) in the National Health and Nutrition Examination Survey 2017–20 were used. CVD ( n = 326) was defined as self-reported physicians’ diagnoses of coronary heart disease, angina, heart attack, or stroke. Urinary nickel concentrations were determined by inductively coupled plasma mass spectrometry. Logistic regression with sample weights was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. Results Urinary nickel concentrations were higher in individuals with CVD (weighted median 1.34 μg/L) compared to those without CVD (1.08 μg/L). After adjustment for demographic, socioeconomic, lifestyle, and other risk factors for CVD, the ORs (95% CIs) for CVD compared with the lowest quartile of urinary nickel were 3.57 (1.73–7.36) for the second quartile, 3.61 (1.83–7.13) for the third quartile, and 2.40 (1.03–5.59) for the fourth quartile. Cubic spline regression revealed a non-monotonic, inverse U-shaped, association between urinary nickel and CVD (P nonlinearity < 0.001). Conclusions Nickel exposure is associated with CVD in a non-monotonic manner among U.S. adults independent of well-known CVD risk factors. Supplementary Information The online version contains supplementary material available at 10.1007/s12403-023-00579-4.

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Section: Discussionmentioning

confidence: 98%

Environmental Nickel Exposure and Cardiovascular Disease in a Nationally Representative Sample of U.S. Adults

et al. 2023

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“…The lack of studies in the area indicate the need for developing better approaches for evaluating the evidence, together with improved methods for risk assessment [14]. Traditional risk assessments may not always be appropriate when considering unresolved issues, including low-dose or non-threshold effects [53], or in determining how non-monotonic dose responses influence the way risk assessments are performed for chemicals with endocrine disrupting activities [54].…”

Section: Discussionmentioning

confidence: 99%

Presence and Natural Treatment of Organic Micropollutants and their Risks after 100 Years of Incidental Water Reuse in Agricultural Irrigation

Chávez-Mejía

Navarro-González

Magaña-López

et al. 2019

Water

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The aim of the research was to show the presence of micropollutants contained in the wastewater of Mexico City within the distribution canals of the Mezquital Valley (MV), as well as their retention in agricultural soil and aquifers. This system constitutes the world's oldest and largest example of the use of untreated wastewater for agricultural irrigation. The artificial recharge associated with the MV aquifers, with groundwater extracted for human consumption showing its importance as a water resource for Mexico City. The results of sampling show the presence of 18 compounds, with 10 of these considered as endocrine disruptor compounds (EDCs). The concentration of these pollutants ranged from 2 ng/L for 17 β-estradiol to 99 ng/L for DEHP, with these values decreasing throughout the course of the canals due to the wastewater dilution factor, their retention in agricultural soil, and their accumulation in the local aquifer. The main mechanisms involved in natural attenuation are adsorption, filtration, and biodegradation. Drinking water equivalent levels (DWELs) were estimated for 11 compounds with regard to acceptable daily intakes (ADIs), by assuming local exposure parameters for a rural Mexican population. These were compared with the maximum groundwater concentrations (Cgw) to screen the potential risks. The very low ratios of Cgw to DWELs indicate no appreciable human health risk from the presence of trace concentrations of these compounds in the source of drinking water in the MV. Despite this, far from being exceeded after more than 100 years of irrigation with residual water, the natural soil attenuation seems to remain stable.

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“…This concept is relevant given the varying effects induced by endogenous hormones at different pre- or postnatal stages or ages [ 106 ]. Interestingly, the primary impact of hormones on adult cells is thought to be “activational” because they typically induce transcriptional activation of certain sets of genes in target cells, and the resulting gene expression then ceases when the exposure terminates [ 107 ]. In contrast, endocrine effects during development are often termed “organizational” because they can permanently alter the organization (specification, differentiation, proliferation, morphology, and/or function) of cells within developing tissues and organ systems.…”

Section: Developmental Timing Of Exposure Modulates Edc-induced Epimumentioning

confidence: 99%

“…In contrast, endocrine effects during development are often termed “organizational” because they can permanently alter the organization (specification, differentiation, proliferation, morphology, and/or function) of cells within developing tissues and organ systems. Disruptions of either of these types of effects can potentially lead to development of disease in the adult [ 107 ].…”

Section: Developmental Timing Of Exposure Modulates Edc-induced Epimumentioning

confidence: 99%

Differential susceptibility to endocrine disruptor-induced epimutagenesis

Lehle

McCarrey

2020

Environmental Epigenetics

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There is now considerable evidence indicating the potential for endocrine disrupting chemicals to alter the epigenome and for subsets of these epigenomic changes or “epimutations” to be heritably transmitted to offspring in subsequent generations. While there have been many studies indicating how exposure to endocrine disrupting chemicals can disrupt various organs associated with the body’s endocrine systems, there is relatively limited information regarding the relative susceptibility of different specific organs, tissues, or cell types to endocrine disrupting chemical-induced epimutagenesis. Here we review available information about different organs, tissues, cell types, and/or cell lines which have been shown to be susceptible to specific endocrine disrupting chemical-induced epimutations. In addition, we discuss possible mechanisms that may be involved, or impacted by this tissue- or cell type-specific, differential susceptibility to different endocrine disrupting chemicals. Finally, we summarize available information indicating that certain periods of development display elevated susceptibility to endocrine disrupting chemical exposure and we describe how this may affect the extent to which germline epimutations can be transmitted inter- or transgenerationally. We conclude that cell type-specific differential susceptibility to endocrine disrupting chemical-induced epimutagenesis is likely to directly impact the extent to, or manner in, which endocrine disrupting chemical exposure initially induces epigenetic changes to DNA methylation and/or histone modifications, and how these endocrine disrupting chemical-induced epimutations can then subsequently impact gene expression, potentially leading to the development of heritable disease states.

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Alternative Approaches to Dose–Response Modeling of Toxicological Endpoints for Risk Assessment: Nonmonotonic Dose Responses for Endocrine Disruptors

Cited by 4 publications

References 140 publications

Environmental Nickel Exposure and Cardiovascular Disease in a Nationally Representative Sample of U.S. Adults

Environmental Nickel Exposure and Cardiovascular Disease in a Nationally Representative Sample of U.S. Adults

Presence and Natural Treatment of Organic Micropollutants and their Risks after 100 Years of Incidental Water Reuse in Agricultural Irrigation

Differential susceptibility to endocrine disruptor-induced epimutagenesis

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