Evaluation of Exposure Assessment Tools under REACH: Part I-Tier 1 Tools.

Tier 1 occupational exposure assessment tools recommended for use under the Registration, Evaluation, Authorization, and restriction of CHemicals (REACH) were evaluated using newly collected measurement data. Evaluated tools included the ECETOC TRAv2 and TRAv3, MEASEv1.02.01, and EMKG-EXPO-TOOL. Fifty-three exposure situations (ESs) based on tasks/chemicals were developed from National Institute for Occupational Safety and Health field surveys. During the field surveys, high quality contextual information required for evaluating the tools was also collected. For each ES, applicable tools were then used to generate exposure estimates using a consensus approach. Among 53 ESs, only those related to an exposure category of liquids with vapor pressure (VP) > 10 Pa had sufficient numbers of exposure measurements (42 ESs with n = 251 for TRAv2 and TRAv3 and 40 ESs with n = 243 for EMKG-EXPO-TOOL) to be considered in detail. The results for other exposure categories (aqueous solutions, liquids with VP ≤ 10 Pa, metal processing, powders, and solid objects) had insufficient measurement to allow detailed analyses (results listed in the Supplementary File). Overall, EMKG-EXPO-TOOL generated more conservative results than TRAv2 and TRAv3 for liquids with high VP. This finding is at least partly due to the fact that the EMKG-EXPO-TOOL only considers pure substances and not mixtures of chemical agents. For 34 out of 40 ESs available for chemicals with VP > 10 Pa, the liquid was a mixture rather than a pure substance. TRAv3 was less conservative than TRAv2, probably due to additional refinement of some input parameters. The percentages of exposure measurement results exceeding the corresponding tool estimates for liquids with VP > 10 Pa by process category and by input parameters were always higher for TRAv3 compared to those for TRAv2. Although the conclusions of this study are limited to liquids with VP > 10 Pa and few process categories, this study utilized the most transparent contextual information compared to previous studies, reducing uncertainty from assumptions for unknown input parameters. A further validation is recommended by collecting sufficient exposure data covering other exposure categories and all process categories under REACH

Evaluation of Exposure Assessment Tools under REACH: Part II-Higher Tier Tools.

Stoffenmanager®v4.5 and Advanced REACH Tool (ART) v1.5, two higher tier exposure assessment tools for use under REACH, were evaluated by determining accuracy and robustness. A total of 282 exposure measurements from 51 exposure situations (ESs) were collected and categorized by exposure category. In this study, only the results of liquids with vapor pressure (VP) > 10 Pa category having a sufficient number of exposure measurements (n = 251 with 42 ESs) were utilized. In addition, the results were presented by handling/activity description and input parameters for the same exposure category. It should be noted that the performance results of Stoffenmanager and ART in this study cannot be directly compared for some ESs because ART allows a combination of up to four subtasks (and nonexposed periods) to be included, whereas the database for Stoffenmanager, separately developed under the permission of the legal owner of Stoffenmanager, permits the use of only one task to predict exposure estimates. Thus, it would be most appropriate to compare full-shift measurements against ART predictions (full shift including nonexposed periods) and task-based measurements against task-based Stoffenmanager predictions. For liquids with VP > 10 Pa category, Stoffenmanager®v4.5 appeared to be reasonably accurate and robust when predicting exposures [percentage of measurements exceeding the tool's 90th percentile estimate (%M > T) was 15%]. Areas that could potentially be improved include ESs involving the task of handling of liquids on large surfaces or large work pieces, allocation of high and medium VP inputs, and absence of local exhaust ventilation input. Although the ART's median predictions appeared to be reasonably accurate for liquids with VP > 10 Pa, the %M > T for the 90th percentile estimates was 41%, indicating that variance in exposure levels is underestimated by ART. The %M > T using the estimates of the upper value of 90% confidence interval (CI) of the 90th percentile estimate (UCI90) was considerably reduced to 18% for liquids with VP > 10 Pa. On the basis of this observation, users might be to consider using the upper limit value of 90% CI of the 90th percentile estimate for predicting reasonable worst case situations. Nevertheless, for some activities and input parameters, ART still shows areas to be improved. Hence, it is suggested that ART developers review the assumptions in relation to exposure variability within the tool, toward improving the tool performance in estimating percentile exposure levels. In addition, for both tools, only some handling/activity descriptions and input parameters were considered. Thus, further validation studies are still necessary

A nationwide follow-up study of occupational organic dust exposure and risk of chronic obstructive pulmonary disease (COPD)

Objectives To study exposure-response relations between cumulative organic dust exposure and incident chronic obstructive pulmonary disease (COPD) among subjects employed in the Danish farming and wood industry. Methods We studied exposure-response relations between cumulative organic dust exposure and incident COPD (1997–2013) among individuals born during 1950–1977 in Denmark ever employed in the farming or wood industry (n=1 75 409). Industry-specific employment history (1964–2007), combined with time-dependent farming and wood industry-specific exposure matrices defined cumulative exposure. We used logistic regression analysis with discrete survival function adjusting for age, sex and calendar year. Adjustment for smoking status was explored in a subgroup of 4023 with smoking information available. Results Cumulative organic dust exposure was inversely associated with COPD (adjusted rate ratios (RRadj (95% CIs) of 0.90 (0.82 to 0.99), 0.76 (0.69 to 0.84) and 0.52 (0.47 to 0.58) for intermediate-low, intermediatehigh and high exposure quartiles, respectively, compared with the lowest exposure quartile). Lagging exposure 10 years was not consistently suggestive of an association between cumulative exposure and COPD; RRadj (95% CI): 1.05 (0.94 to 1.16), 0

A principal factor analysis to characterize agricultural exposures among Nebraska veterans

Agricultural workers are at an increased risk of developing chronic respiratory disorders. Accurate estimation of long-term agricultural exposures based on questionnaires has been used to improve the validity of epidemiologic investigations and subsequent evaluation of the association between agricultural exposures and chronic diseases. Our aim was to use principal factor analysis (PFA) to distill exposure data into essential variables characterizing long-term agricultural exposures. This is a crosssectional study of veterans between the ages of 40 and 80 years and who worked on a farm for ≥ 2 years. Participant characteristics were: 98.1% were white males with a mean age 65 ± 8 (SD) years and 39.8% had chronic obstructive pulmonary disease. The final model included four factors and explained 16.6% of the variance in the exposure data. Factor 1 was a heterogeneous factor; however, Factor 2 was exclusively composed of exposure to livestock such as hogs, dairy and poultry. Factor 3 included exposures from jobs on or off the farm such as wood dust, mineral dust, asbestos and spray paint. Crop exposure loaded exclusively in Factor 4 and included lifetime hours of exposure and maximum number of acres farmed in the participants’ lifetime. The factors in the final model were interpretable and consistent with farming practices

Activation of inflammatory responses in human U937 macrophages by particulate matter collected from dairy farms: an in vitro expression analysis of pro-inflammatory markers

Abstract Background The purpose of the present study was to investigate activation of inflammatory markers in human macrophages derived from the U937 cell line after exposure to particulate matter (PM) collected on dairy farms in California and to identify the most potent components of the PM. Methods PM from different dairies were collected and tested to induce an inflammatory response determined by the expression of various pro-inflammatory genes, such as Interleukin (IL)-8, in U937 derived macrophages. Gel shift and luciferase reporter assays were performed to examine the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like-receptor 4 (TLR4). Results Macrophage exposure to PM derived from dairy farms significantly activated expression of pro-inflammatory genes, including IL-8, cyclooxygenase 2 and Tumor necrosis factor-alpha, which are hallmarks of inflammation. Acute phase proteins, such as serum amyloid A and IL-6, were also significantly upregulated in macrophages treated with PM from dairies. Coarse PM fractions demonstrated more pro-inflammatory activity on an equal-dose basis than fine PM. Urban PM collected from the same region as the dairy farms was associated with a lower concentration of endotoxin and produced significantly less IL-8 expression compared to PM collected on the dairy farms. Conclusion The present study provides evidence that the endotoxin components of the particles collected on dairies play a major role in mediating an inflammatory response through activation of TLR4 and NF-κB signaling