Incorporating regulatory guideline values in analysis of epidemiology data

• Published in: Environment international 2018-11, Vol.120, p.535-543
• Main Authors: Gennings, Chris, Shu, Huan, Rudén, Christina, Öberg, Mattias, Lindh, Christian, Kiviranta, Hannu, Bornehag, Carl-Gustaf
• Format: Article
• Language: English
• Subjects: Arbetsmedicin och miljömedicin; Birth Weight; Child, Preschool; Complex Mixtures - analysis; Complex Mixtures - standards; Cumulative risk assessment; Endocrine Disruptors - analysis; Endocrine Disruptors - standards; Environmental chemicals; Environmental Exposure - analysis; Environmental Exposure - standards; Environmental Health and Occupational Health; Environmental Monitoring - methods; Female; Folkhälsovetenskap; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Government Regulation; Hazardous Substances - analysis; Hazardous Substances - standards; Health Sciences; Humans; Hälsovetenskap; Infant, Newborn; Language Development Disorders - epidemiology; Male; Maternal-Fetal Exchange; Medical and Health Sciences; Medicin och hälsovetenskap; Mixtures; Models, Statistical; Pregnancy; Public Health Science; Public Health, Global Health, Social Medicine and Epidemiology; Risk Assessment; Uncertainty
• ISSN: 0160-4120; 1873-6750; 1873-6750
• DOI: 10.1016/j.envint.2018.08.039

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. •We introduce a new class of models that include the regulatory concept of “acceptable concentration range” (ACR).•These ACR models complement current risk assessment methods by estimating guideline values using human biomonitoring data.•We illustrate the strategy using prenatal concentrations from 11 environmental chemicals and two health outcomes.•We determine that the published HBM values are orders of magnitude higher than those estimated using human data.•The r