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The influence of exposure duration on chemical toxicity has important implications for risk assessment. Although a default 10-fold extrapolation factor is commonly applied when the toxicological dataset includes a subchronic (90-day) study but lacks studies of chronic duration, little consensus has been reached on an appropriate extrapolation factor to apply when the dataset includes a 28-day study but lacks studies of longer durations. The goal of the present assessment was to identify a 28-day to 90-day extrapolation factor by analyzing distributions of ratios of No-Observed-Adverse-Effect Levels (NOAELs) and Benchmark Doses (BMDs) derived from 28-day and 90-day studies. The results of this analysis suggest that a default 10-fold extrapolation factor in chemical risk assessment applications is sufficient to account for the uncertainty associated with evaluating human health risk based on results from a 28-day study in the absence of results from a 90-day study. This analysis adds significantly to the growing body of literature interpreting the influence of exposure duration on chemical toxicity that will likewise facilitate discussions on the future state of testing requirements in the international regulatory community., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Serum concentrations of 35 ortho-substituted polychlorinated biphenyl congeners (PCBs) were measured in 765 adults from Anniston, Alabama, where PCBs were manufactured between 1929 and 1971. As part of the Anniston Community Health Survey (ACHS), demographic data, questionnaire information, and blood samples were collected from participants in 2005-2007. Forty-six percent of study participants were African-American, 70% were female, and the median age was 56 years. The median concentration of the sum of 35 PCB congeners (ΣPCBs) was 528 ng/g lipid, with a 90th percentile of 2,600 ng/g lipid, minimum of 17.0 ng/g lipid, and maximum of 27,337 ng/g lipid. The least square geometric mean ΣPCBs was more than 2.5 times higher for African-American participants than for White participants (866 ng/g lipid vs. 331 ng/g lipid); this difference did not change materially after adjustment for age, sex, body mass index (BMI) and current smoking. In spite of large differences in absolute PCB levels, relative contributions of individual congeners to ΣPCBs were quite similar between race groups. Nevertheless, while percent contributions to ΣPCBs for most of the most abundant penta- to heptachlorobiphenyls were higher among African-Americans, the percentages were higher in Whites for the lower-chlorinated PCBs 28 and 74 and for octa- to decachlorinated PCBs. No major differences were observed in geometric mean ΣPCBs between women and men when adjusted for age, race, BMI and current smoking (516 ng/g lipid vs. 526 ng/g lipid). Principal component analysis revealed groups of co-varying congeners that appear to be determined by chlorine substitution patterns. These congener groupings were similar between ACHS participants and the National Health and Nutrition Examination Survey (NHANES) 2003-04 sample of the general United States population, despite ACHS participants having serum concentrations of ΣPCBs two to three times higher than those in comparable age and race groups from NHANES., (Published by Elsevier B.V.)

Background: There is limited research examining the relationship between lead (Pb) exposure and medically diagnosed attention deficit hyperactivity disorder (ADHD) in children. The role of mercury (Hg) and cadmium (Cd) exposures in ADHD development is even less clear., Objectives: To examine the relationship between Pb, Hg, and Cd and ADHD in children living inside and outside a Lead Investigation Area (LIA) of a former lead refinery in Omaha, NE., Methods: We carried out a case-control study with 71 currently medically diagnosed ADHD cases and 58 controls from a psychiatric clinic and a pediatric clinic inside and outside of the LIA. The participants were matched on age group (5-8, 9-12 years), sex, race (African American or Caucasians and others), and location (inside or outside LIA). We measured whole blood Pb, total Hg, and Cd using inductively coupled plasma mass spectrometry., Results: Inside the LIA, the 27 cases had blood Pb geometric mean (GM) 1.89 µg/dL and the 41 controls had 1.51 µg/dL. Outside the LIA, the 44 cases had blood Pb GM 1.02 µg/dL while the 17 controls had 0.97 µg/dL. After adjustment for matching variables and maternal smoking, socioeconomic status, and environmental tobacco exposure, each natural log unit blood Pb had an odds ratio of 2.52 with 95% confidence interval of 1.07-5.92. Stratification by the LIA indicated similar point estimate but wider CIs. No associations were observed for Hg or Cd., Conclusions: Postnatal Pb exposure may be associated with higher risk of clinical ADHD, but not the postnatal exposure to Hg or Cd., (© 2013 Published by Elsevier Inc.)