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Exposure to high levels of manganese (Mn) in occupational settings is known to lead to adverse neurological effects. Since Mn is an essential nutrient, there are mechanisms that maintain its homeostatic control in the body, and there is some level of Mn in air that does not perturb Mn homeostasis. However, the Mn exposure concentrations at which no adverse effects are expected in occupational settings vary considerably across regulatory agencies. We set out to derive a Mn Occupational Exposure Level (OEL) for welders based on a review of studies that evaluated Mn exposure concentrations from welding fumes and: (1) neurological effects in welders; (2) levels of Mn in the brains of welders (via pallidal index [PI] estimated from magnetic resonance imaging [MRI]); (3) other biomarkers of Mn exposure in welders (i.e., blood and urine); and (4) Mn brain concentrations, PI, and corresponding neurological effects in non-human primates. Our analysis suggests uncertainty in quantifying dose-response associations for Mn from many of the occupational welding studies. The few welding studies that adequately estimate exposure suggest a possible OEL of 100-140μg/m 3 for respirable Mn. This range is consistent with other epidemiology studies, studies of biomarkers of Mn exposure in welders, and with studies in non-human primates, though future studies could provide a stronger basis for deriving a Mn occupational guideline for welders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Human exposure to toluene diisocyanate (TDI) occurs mainly through inhalation of vapors in occupational settings where TDI is produced or used, but dermal exposure to TDI is also possible during some operations. Because of a recent epidemiology study reporting a possible association with lung cancer risk in workers with potential dermal exposure to TDI, we evaluated the evidence from epidemiological, toxicological, and toxicokinetic studies to assess whether it is likely that dermal exposure to TDI can cause human respiratory cancers. We found that the reported associations with respiratory cancers in the epidemiology studies do not support TDI as a causal factor, as there are other explanations that are more likely than causation, such as confounding by smoking and low socioeconomic status. Experimental animal and genotoxicity studies indicate that the carcinogenic potential of TDI depends on its conversion to toluene diamine (TDA), and there is no evidence of systemic availability of TDA after dermal or inhalation exposure to TDI. Also, systemic uptake of TDI is very low after dermal exposure, and any absorbed TDI is more likely to react with biomolecules on or below the skin surface than to form TDA. Even if some TDA formation occurred after dermal exposure to TDI, TDA does not induce respiratory tract tumors in experimental animals after either dermal or oral exposure. We conclude that the available evidence indicates that dermal TDI exposure does not cause respiratory cancers in humans., (Copyright © 2017 Gradient. Published by Elsevier Ltd.. All rights reserved.)

Background: Short-term exposure to ozone has been associated with asthma hospital admissions (HA) and emergency department (ED) visits, but the shape of the concentration-response (C-R) curve is unclear., Methods: We conducted a time series analysis of asthma HAs and ambient ozone concentrations in six metropolitan areas in Texas from 2001 to 2013. Using generalized linear regression models, we estimated the effect of daily 8-hour maximum ozone concentrations on asthma HAs for all ages combined, and for those aged 5-14, 15-64, and 65+years. We fit penalized regression splines to evaluate the shape of the C-R curves., Results: Using a log-linear model, estimated risk per 10ppb increase in average daily 8-hour maximum ozone concentrations was highest for children (relative risk [RR]=1.047, 95% confidence interval [CI]: 1.025-1.069), lower for younger adults (RR=1.018, 95% CI: 1.005-1.032), and null for older adults (RR=1.002, 95% CI: 0.981-1.023). However, penalized spline models demonstrated significant nonlinear C-R relationships for all ages combined, children, and younger adults, indicating the existence of thresholds. We did not observe an increased risk of asthma HAs until average daily 8-hour maximum ozone concentrations exceeded approximately 40ppb., Conclusion: Ozone and asthma HAs are significantly associated with each other; susceptibility to ozone is age-dependent, with children at highest risk. C-R relationships between average daily 8-hour maximum ozone concentrations and asthma HAs are significantly curvilinear for all ages combined, children, and younger adults. These nonlinear relationships, as well as the lack of relationship between average daily 8-hour maximum and peak ozone concentrations, have important implications for assessing risks to human health in regulatory settings., (Copyright © 2017. Published by Elsevier Ltd.)

Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D(2) (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37°C, the wild-type enzyme lost 15% of its activity in 1h, whereas the Val187Ile form remained >95% active. At 50°C, the half life of native HPGDS was 9min, compared to 42 min for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75-1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model., (Copyright © 2011 Elsevier Inc. All rights reserved.)