These data suggest that environmental exposure to lead may delay growth and pubertal development in girls, although confirmation is warranted in prospective studies.

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The concept of model validation is evolving in the scientific community. This paper addresses the comparison of observed and predicted estimates as one component of model validation as applied to the integrated exposure uptake biokinetic (IEUBK) model for lead in children. The IEUBK model is an exposure (dose)-response model that uses children's environmental lead exposures to estimate risk of elevated blood lead (typically > 10 pg/dl) through estimation of lead body burdens in a mass balance framework. We used residence-specific environmental lead measurements from three epidemiologic datasets as inputs for the IEUBK model to predict blood lead levels, and compared these predictions with blood lead levels of children living at these residences. When the IEUBK modeling focused on children with representative exposure measurements, that is, children who spent the bulk of their time near the locations sampled, there was reasonably close agreement between observed and predicted blood lead distributions in the three studies considered. Geometric mean observed and predicted blood lead levels were within 0.7 pg/dl, and proportions of study populations expected to be above 10 pg/dl were within 4% of those observed.

Background: The U.S. Environmental Protection Agency (EPA) completed a toxicological review of tetrachloroethylene (perchloroethylene, PCE) in February 2012 in support of the Integrated Risk Information System (IRIS).Objectives: We reviewed key findings and scientific issues regarding the human health effects of PCE described in the U.S. EPA’s Toxicological Review of Tetrachloroethylene (Perchloroethylene).Methods: The updated assessment of PCE synthesized and characterized a substantial database of epidemiological, experimental animal, and mechanistic studies. Key scientific issues were addressed through modeling of PCE toxicokinetics, synthesis of evidence from neurological studies, and analyses of toxicokinetic, mechanistic, and other factors (tumor latency, severity, and background rate) in interpreting experimental animal cancer findings. Considerations in evaluating epidemiological studies included the quality (e.g., specificity) of the exposure assessment methods and other essential design features, and the potential for alternative explanations for observed associations (e.g., bias or confounding).Discussion: Toxicokinetic modeling aided in characterizing the complex metabolism and multiple metabolites that contribute to PCE toxicity. The exposure assessment approach—a key evaluation factor for epidemiological studies of bladder cancer, non-Hodgkin lymphoma, and multiple myeloma—provided suggestive evidence of carcinogenicity. Bioassay data provided conclusive evidence of carcinogenicity in experimental animals. Neurotoxicity was identified as a sensitive noncancer health effect, occurring at low exposures: a conclusion supported by multiple studies. Evidence was integrated from human, experimental animal, and mechanistic data sets in assessing adverse health effects of PCE.Conclusions: PCE is likely to be carcinogenic to humans. Neurotoxicity is a sensitive adverse health effect of PCE.Citation: Guyton KZ, Hogan KA, Scott CS, Cooper GS, Bale AS, Kopylev L, Barone S Jr, Makris SL, Glenn B, Subramaniam RP, Gwinn MR, Dzubow RC, Chiu WA. 2014. Human health effects of tetrachloroethylene: key findings and scientific issues. Environ Health Perspect 122:325–334; http://dx.doi.org/10.1289/ehp.1307359

The integrated exposure uptake biokinetic model for lead in children was developed to provide plausible blood lead distributions corresponding to particular combinations of multimedia lead exposure. The model is based on a set of equations that convert lead exposure (expressed as micrograms per day) to blood lead concentration (expressed as micrograms per deciliter) by quantitatively mimicking the physiologic processes that determine blood lead concentration. The exposures from air, food, water, soil, and dust are modeled independently by several routes. Amounts of lead absorbed are modeled independently for air, food, water, and soil/dust, then combined as a single input to the blood plasma reservoir of the body. Lead in the blood plasma reservoir, which includes extracellular fluids, is mathematically allocated to all tissues of the body using age-specific biokinetic parameters. The model calculation provides the estimate for blood lead concentration for that age. This value is treated as the geometric mean of possible values for a single child, or the geometric mean of expected values for a population of children exposed to the same lead concentrations. The distribution of blood lead concentrations about this geometric mean is estimated using a geometric standard deviation, typically 1.6, derived from the analysis of well-conducted community blood studies.Environ Health Perspect 106(Suppl 6):1513-1530 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-6/1513-1530white/abstract.html