Incorporating regulatory guideline values in analysis of epidemiology data

Gennings, Chris; Shu, Huan; Rudén, Christina; Öberg, Mattias; Lindh, Christian; Kiviranta, Hannu; Bornehag, Carl‐Gustaf

doi:10.1016/j.envint.2018.08.039

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…Thus, the estimated chemical exposure level could be 70 times above a theoretical safe level. This is in line with the conclusion by Gennings et al, that a chemical-by-chemical assessment underestimates the risk of chemical mixtures by a factor of up to 100 (Gennings et al 2018).…”

Section: Discussionsupporting

confidence: 92%

Anthropogenic Organic Contaminants Analysed in Human Blood and Combined Risk

2022

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The number of chemicals in the anthroposphere is increasing and some of them end up in humans. A literature search was made to assess which anthropogenic organic contaminants (OCs) that have been analysed in blood from the general population. The reviewed articles were used to create a database of studies [human blood database (HBDB), containing 559 OCs] reporting blood analyses made worldwide. All studies analysing blood from the Swedish population were compiled into a second database [Swedish exposure database (SEDB), containing 166 OCs] listing blood concentrations of OCs. Data from the SEDB showed decreasing levels of regulated chemicals in blood over time, indicating that regulation had made an impact. The Hazard Index (HI) approach was used as a qualitative mixture risk assessment of the OCs with established human biomonitoring guidance values (HBM-GVs) and blood levels in the SEDB. Nine HBM-GVs were found and the HI of the corresponding OCs/groups of OCs showed that a risk of adverse effects in the general population could not be excluded, which is a cause for concern considering that only a fraction of the analysed OCs in the SEDB were included. This study presents the OCs identified in human blood and concentration time trends. The study highlights the lack of HBM-GVs needed for mixture risk assessments to assess the combined risk of chemical exposure to the general population.

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Section: Discussionsupporting

confidence: 92%

Anthropogenic Organic Contaminants Analysed in Human Blood and Combined Risk

2022

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“…An important challenge of mixtures research is direct translation to regulatory decision making. To address this, Gennings et al recently described a new class of models that include the regulatory concept of acceptable concentration range (ACR) [21]. ACR is a new class of nonlinear statistical models for human data that incorporate and evaluate regulatory guideline values into analyses of the health effects of exposure to chemical mixtures.…”

Section: Risk Assessment and Regulatory Relevancementioning

confidence: 99%

Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods

Joubert

Kioumourtzoglou

Chamberlain

et al. 2022

IJERPH

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Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.

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“…Only steps 1, 2 and 5 are fulfilled for PPPs. Current risk assessment cannot integrate specific endpoints and mixture effects, though innovative approaches have been developed to overcome these limitations for compounds other than pesticides (230).…”

Section: Risk Assessmentmentioning

confidence: 99%

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

et al. 2019

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Plant Protection Products, more commonly referred to as pesticides and biocides, are used to control a wide range of yield-reducing pests including insects, fungi, nematodes, and weeds. Concern has been raised that some pesticides may act as endocrine disrupting chemicals (EDCs) with the potential to interfere with the hormone systems of non-target invertebrates and vertebrates, including humans. EDCs act at low doses and particularly vulnerable periods of exposure include pre-and perinatal development. Of critical concern is the number of pesticides with the potential to interfere with the developing nervous system and brain, notably with thyroid hormone signaling. Across vertebrates, thyroid hormone orchestrates metamorphosis, brain development, and metabolism. Pesticide action on thyroid homeostasis can involve interference with TH production and its control, displacement from distributor proteins and liver metabolism. Here we focused on thyroid endpoints for each of the different classes of pesticides reviewing epidemiological and experimental studies carried out both in in vivo and in vitro. We conclude first, that many pesticides were placed on the market with insufficient testing, other than acute or chronic toxicity, and second, that thyroid-specific endpoints for neurodevelopmental effects and mixture assessment are largely absent from regulatory directives.

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Incorporating regulatory guideline values in analysis of epidemiology data

Cited by 7 publications

References 26 publications

Anthropogenic Organic Contaminants Analysed in Human Blood and Combined Risk

Anthropogenic Organic Contaminants Analysed in Human Blood and Combined Risk

Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

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