Ann M. Mason

Use of a Physiologically Based Pharmacokinetic Model to Identify Exposures Consistent With Human Biomonitoring Data for Chloroform

Biomonitoring data provide evidence of human exposure to environmental chemicals by quantifying the chemical or its metabolite in a biological matrix. To better understand the correlation between biomonitoring data and environmental exposure, physiologically based pharmacokinetic (PBPK) modeling can be of use. The objective of this study was to use a combined PBPK model with an exposure model for showering to estimate the intake concentrations of chloroform based on measured blood and exhaled breath concentrations of chloroform. First, the predictive ability of the combined model was evaluated with three published studies describing exhaled breath and blood concentrations in people exposed to chloroform under controlled showering events. Following that, a plausible exposure regimen was defined combining inhalation, ingestion, and dermal exposures associated with residential use of water containing typical concentrations of chloroform to simulate blood and exhaled breath concentrations of chloroform. Simulation results showed that inhalation and dermal exposure could contribute substantially to total chloroform exposure. Next, sensitivity analysis and Monte Carlo analysis were performed to investigate the sources of variability in model output. The variability in exposure conditions (e.g., shower duration) was shown to contribute more than the variability in pharmacokinetics (e.g., body weight) to the predicted variability in blood and exhaled breath concentrations of chloroform. Lastly, the model was used in a reverse dosimetry approach to estimate distributions of exposure consistent with concentrations of chloroform measured in human blood and exhaled breath.

Conclusions and Recommendations of the Expert Panel: Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States

We thank the following organizations for generously providing support for the workshop: the AmericanChemistry Council; the Centers for Disease Control and Prevention (C13/CCU323635-01); the Departmentof Health and Human Services, Health Resources and Services Administration (HHSH240200415021P);Health Canada (H405-03-ExSD079/4500078209); 3M; Pennsylvania State University College of Medicine;the Research Foundation for Health and Environmental Effects; and the U.S. Environmental ProtectionAgency, Office of Children’s Health (CH-83213101-0).The opinions expressed in this article are those of the authors and do not necessarily reflect the viewsand/or policies of their affiliations.Address correspondence to Cheston M. Berlin, Jr., MD, Department of Pediatrics Children’s Hospital,Milton S. Hershey Medical Center, Pennsylvania State University College of Medi cine, M.C. HO85, PO Box850, Hershey, PA 17033, USA. E-mail: cmb6@psu.edu

Collection and Use of Exposure Data from Human Milk Biomonitoring in the United States

Human milk is a unique biological matrix that can be used to estimate exposures in both the mother and the breastfed infant. In addition, the presence of environmental chemicals in human milk may act as a sentinel for exposures to a broader population. Several factors play a role in determining the quantity of chemicals transferred to milk and, subsequently, to the breastfeeding infant, including maternal, infant, and chemical characteristics. Exposure to certain environmental chemicals during critical periods can disrupt normal infant development, yet few data exist to quantify the hazards posed by environmental chemicals in human milk. Chemicals measured in human milk may also provide insights to agents suspect in altering breast development and breast-related disease risk. Carefully designed exposure assessment and toxicokinetic studies are needed to elucidate mechanisms and establish relationships between human milk and other biologic matrices. Data from human milk biomonitoring studies can be used to inform and validate models that integrate information about chemical properties, human metabolism, and biomarker concentrations. Additional research is needed to determine the degree to which environmental chemicals enter, are present in, and are excreted from human milk, their impact on the host (mother), and the extent of their bioavailability to breastfeeding infants. This article describes how the collection and use of exposure data from human milk biomonitoring in the United States can be designed to inform future research and policy. We thank the following organizations for generously providing support for the Workshop: the American Chemistry Council; the Centers for Disease Control and Prevention (C13/CCU323635-01); the Department of Health and Human Services, Health Resources and Services Administration (HHSH240200415021P); Health Canada (H405-03-ExSD079/4500078209); 3M; Pennsylvania State University College of Medicine; the Research Foundation for Health and Environmental Effects; and the U.S. Environmental Protection Agency, Office of Children’s Health (CH-83213101-0). The views expressed in this report are those of the authors and do not necessarily reflect the opinions and/or policies of the U.S. Environmental Protection Agency.

A comparative evaluation of five hazard screening tools.

An increasing number of hazard assessment tools and approaches are being used in the marketplace as a means to differentiate products and ingredients with lower versus higher hazards or to certify what some call greener chemical ingredients in consumer products. Some leading retailers have established policies for product manufacturers and their suppliers to disclose chemical ingredients and their related hazard characteristics often specifying what tools to use. To date, no data exists that show a tools reliability to provide consistent, credible screening-level hazard scores that can inform greener product selection. We conducted a small pilot study to understand and compare the hazard scoring of several hazard screening tools to determine if hazard and toxicity profiles for chemicals differ. Seven chemicals were selected that represent both natural and man-made chemistries as well as a range of toxicological activity. We conducted the assessments according to each tool providers guidelines, which included factors such as endpoints, weighting preferences, sources of information, and treatment of data gaps. The results indicate the tools varied in the level of discrimination seen in the scores for these 7 chemicals and that tool classifications of the same chemical varied widely between the tools, ranging from little or no hazard or toxicity to very high hazard or toxicity. The results also highlight the need for transparency in describing the basis for the tools hazard scores and suggest possible enhancements. Based on this pilot study, tools should not be generalized to fit all situations because their evaluations are context-specific. Before choosing a tool or approach, it is critical that the assessment rationale be clearly defined and matches the selected tool or approach. Integr Environ Assess Manag 2017;13:139-154.