Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace - Part II adjustments to the adult exposure model, confirmation of Leggett+, and modeling of workplace exposure.

California's Office of Environmental Health Hazard Assessment has updated the comprehensive age-specific model of lead metabolism in humans published by Richard W. Leggett in 1993. The updated model, called Leggett+, was introduced in a peer-reviewed report in 2013. The Leggett + model simulates the relationship between blood lead and exposure in the workplace. Leggett + includes a workplace exposure model comprising respiratory tract intake (workplace lead inhaled by a worker) and uptake (lead absorbed into the blood from the respiratory tract plus uptake from ambient air and diet). The latter is calculated as intake times an inhalation transfer coefficient plus background uptake. An adjusted adult systemic model describes the metabolism of the absorbed lead. This paper provides details about the workplace exposure and uptake elements of Leggett+, an updated approach to calibrating an inhalation transfer coefficient, confirmation of the model's performance in predicting blood lead levels from workplace studies, and predictions of blood lead levels from simulated exposures to workplace airborne lead over a working lifetime. Blood lead relative to airborne lead concentrations in a standard workplace scenario predicted by Leggett + was similar to corresponding relationships from four published workplace studies. Leggett + predictions displayed a good fit to regression equations when other key factors were considered such as pre-employment blood lead and ongoing background intake of lead, workplace air concentration, lead aerosol characteristics, and worker activity levels. The comprehensive Leggett + model can simulate plausible workplace air-blood lead relationships from a broad range of worker exposures. The inhalation transfer coefficient of 0.30, derived from empirical data described in the 2013 report has been reexamined. The original estimate continues to represent a plausible mid-point for a coefficient derived from an expanded range of theoretical particle size distributions deposited in the upper and lower regions of the respiratory tract considering intake during sedentary and outdoor activity breathing scenarios. This coefficient is slightly lower than the value of 0.35 estimated for unknown forms of lead by Leggett in 1993.

Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace - Part I adjustments to the adult systemic model.

California's Division of Occupational Safety and Health has initiated a process to update its standards for exposure to lead in workplaces. In support of this effort, the state's Office of Environmental Health Hazard Assessment evaluated the age-specific, bio-kinetic model of lead metabolism in humans, originally published by R.W. Leggett in 1993. This model was ultimately chosen for its physiologic realism and practicality in characterizing the relationship between air lead concentrations and blood lead levels in chronically exposed worker and its practicality in making necessary adjustments. Leggett's original model systematically under-predicts bone and blood levels in workers such that several adjustments to the parameters are needed to improve predictions for occupational exposure scenarios. The aim of this work is to incorporate new information about the bio-kinetics of lead in workers and to adjust the Leggett model to improve its predictions.The Leggett model was evaluated by comparing its predictions with information on lead concentrations in bone, blood, and urine from workers and other chronically exposed adults. Key model parameters were identified based upon a review of the relevant exposure assessment and modeling literature. Adjustments to the model parameters were made based on empirical evidence. They included reducing the level of lead in blood (BLL) where the rate of decrease in red blood cell binding begins and ends, lead accumulation rate in cortical bone, the rate of lead elimination in trabecular bone, and rate of lead transferred from diffusible plasma to urine. Regression methods and visual inspection of plotted data were used to assess the effect of adjustments on model predictions. When compared with the original, the adjusted Leggett model more accurately predicted lead concentrations observed in active and retired workers. Also, the adjusted Leggett model required less lead uptake to reach the same BLLs for BLLs less than 25 µg/dL and more time for BLLs to decline than the original Leggett model. These findings are important for defining an adequately protective occupational standard for lead exposure.

Developing asthma in childhood from exposure to secondhand tobacco smoke: insights from a meta-regression.

OBJECTIVE: Studies have identified associations between household secondhand tobacco smoke (SHS) exposure and induction of childhood asthma. However, the true nature and strength of this association remains confounded in many studies, producing inconsistent evidence. To look for sources of potential bias and try to uncover consistent patterns of relative risk estimates (RRs), we conducted a meta-analysis of studies published between 1970 and 2005. DATA SOURCES: Through an extensive literature search, we identified 38 epidemiologic studies of SHS exposure and the development of childhood asthma (that also controlled for atopy history) from 300 potentially relevant articles. DATA SYNTHESIS: We observed substantial heterogeneity within initial summary RRs of 1.48 [95% confidence interval (CI), 1.32-1.65], 1.25 (1.21-1.30), and 1.21 (1.08-1.36), for ever, current, and incident asthma, respectively. Lack of control for type of atopy history (familial or child) and child's own smoking status within studies and age category altered summary RRs in separate meta-regressions. After adjusting for these confounding characteristics, consistent patterns of association emerged between SHS exposure and childhood asthma induction. Our summary RR of 1.33 (95% CI, 1.14-1.56) from studies of incident asthma among older children (6-18 years of age) is 1.27 times the estimate from studies of younger children and higher than estimates reported in earlier meta-analyses. CONCLUSIONS: This new finding indicates that exposure duration may be a more important factor in the induction of asthma than previously understood, and suggests that SHS could be a more fundamental and widespread cause of childhood asthma than some previous meta-analyses have indicated.

Lessons learned from "the skeptical environmentalist": an environmental health perspective.

Few books about the environment have generated as much heated debate as Bjørn Lomborg's 'The Skeptical Environmentalist: Measuring the Real State of the World', published by Cambridge University Press in 2001. A flavor of the controversy can be gleaned from a series of reviews and rebuttals published in 'Scientific American' (Rennie 2002). In general, most positive reviews appeared in the popular press (e.g., 'The Economist', 'Washington Post Book Review', 'The Wall Street Journal') and most negative reviews appeared in the scientific press (e.g., 'Science', 'Nature', 'Bioscience'). Although 'The Skeptical Environmentalist' (TSE) addresses a number of environmental health issues, voices from the environmental health community have not been prominent among the participants in this debate. Now that the dust from the initial stampede to praise and condemn the book has settled, we will explore lessons to be learned from TSE and the associated debate from an environmental health perspective.