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Incorporating regulatory guideline values in analysis of epidemiology data
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Stockholm University.
Stockholm University.
Karolinska Institutet.
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 120, p. 535-543Article in journal (Refereed) Published
Abstract [en]

Fundamental to regulatory guidelines is to identify chemicals that are implicated with adverse human health effects and inform public health risk assessors about “acceptable ranges” of such environmental exposures (e.g., from consumer products and pesticides). The process is made more difficult when accounting for complex human exposures to multiple environmental chemicals. Herein we propose a new class of nonlinear statistical models for human data that incorporate and evaluate regulatory guideline values into analyses of health effects of exposure to chemical mixtures using so-called ‘desirability functions’ (DFs). The DFs are incorporated into nonlinear regression models to allow for the simultaneous estimation of points of departure for risk assessment of combinations of individual substances that are parts of chemical mixtures detected in humans. These are, in contrast to published so-called biomonitoring equivalent (BE) values and human biomonitoring (HBM) values that link regulatory guideline values from in vivo studies of single chemicals to internal concentrations monitored in humans. We illustrate the strategy through the analysis of prenatal concentrations of mixtures of 11 chemicals with suspected endocrine disrupting properties and two health effects: birth weight and language delay at 2.5 years. The strategy allows for the creation of a Mixture Desirability Function i.e., MDF, which is a uni-dimensional construct of the set of single chemical DFs; thus, it focuses the resulting inference to a single dimension for a more powerful one degree-of-freedom test of significance. Based on the application of this new method we conclude that the guideline values need to be lower than those for single chemicals when the chemicals are observed in combination to achieve a similar level of protection as was aimed for the individual chemicals. The proposed modeling may thus suggest data-driven uncertainty factors for single chemical risk assessment that takes environmental mixtures into account.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 120, p. 535-543
Keywords [en]
Cumulative risk assessment, Environmental chemicals, Mixtures
National Category
Health Sciences
Research subject
Public Health Science
Identifiers
URN: urn:nbn:se:kau:diva-69130DOI: 10.1016/j.envint.2018.08.039ISI: 000448688500055Scopus ID: 2-s2.0-85052311282OAI: oai:DiVA.org:kau-69130DiVA, id: diva2:1246431
Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-11-23Bibliographically approved

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Bornehag, Carl-Gustaf

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