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The aim of this study was to determine factors influencing observed increased metal biomarkers of exposure levels in a group of 116 Quebec apprentice welders during a longitudinal follow-up of exposure. Analysis of 14 metals was carried out in hair, fingernail, and toenail samples taken from participants over the course of their welding curriculum at 6 different times. Personal and socio-demographic characteristics, lifestyle habits, and other potential confounding factors were documented by questionnaire. Multivariate linear mixed-effect models were used to assess main predictors of metal concentrations in each biological matrix including increasing time of exposure throughout the curriculum (defined as the repeated measure "time" variable"). Significant associations between repeated measure "time" variable and metal levels in hair, fingernails, and toenails were found for chromium, iron, manganese and nickel. Significant associations with "time" were also noted for arsenic levels in hair and fingernails, and for barium, cobalt and vanadium levels in fingernails and toenails. The repeated measure "time" variable, hence increasing time of exposure throughout the curriculum, was the predominant predictor of elevated biological metal levels. Reduced spaces and simultaneous activities such as oxyfuel-cutting and welding in the same welding room were suspected to contribute to higher metal levels. Age, ethnicity, and annual household income exerted an effect on metal levels and considered as confounders in the models. Variations observed in metal levels between hair and nails of apprentice welders also emphasized the relevance and importance of performing multi-matrix and multi-element biomonitoring to assess temporal variations in biological metal concentrations during welding curriculum. [ABSTRACT FROM AUTHOR]

Introduction The US Integrated Management Information System (IMIS) contains workplace measurements collected by Occupational Safety and Health Administration (OSHA) inspectors. Its use for research is limited by the lack of record of a value for the limit of detection (LOD) associated with non-detected measurements, which should be used to set censoring point in statistical analysis. We aimed to remedy this by developing a predictive model of the volume of air sampled (V) for the non-detected results of airborne measurements, to then estimate the LOD using the instrument detection limit (IDL), as IDL/V. Methods We obtained the Chemical Exposure Health Data from OSHA's central laboratory in Salt Lake City that partially overlaps IMIS and contains information on V. We used classification and regression trees (CART) to develop a predictive model of V for all measurements where the two datasets overlapped. The analysis was restricted to 69 chemical agents with at least 100 non-detected measurements, and calculated sampling air flow rates consistent with workplace measurement practices; undefined types of inspections were excluded, leaving 412,201/413,515 records. CART models were fitted on randomly selected 70% of the data using 10-fold cross-validation and validated on the remaining data. A separate CART model was fitted to styrene data. Results Sampled air volume had a right-skewed distribution with a mean of 357 l, a median (M) of 318, and ranged from 0.040 to 1868 l. There were 173,131 measurements described as non-detects (42% of the data). For the non-detects, the V tended to be greater (M = 378 l) than measurements characterized as either 'short-term' (M = 218 l) or 'long-term' (M = 297 l). The CART models were complex and not easy to interpret, but substance, industry, and year were among the top three most important classifiers. They predicted V well overall (Pearson correlation (r) = 0.73, P < 0.0001; Lin's concordance correlation (r c ) = 0.69) and among records captured as non-detects in IMIS (r = 0.66, P < 0.0001l; r c = 0.60). For styrene, CART built on measurements for all agents predicted V among 569 non-detects poorly (r = 0.15; r c = 0.04), but styrene-specific CART predicted it well (r = 0.87, P < 0.0001; r c = 0.86). Discussion Among the limitations of our work is the fact that samples may have been collected on different workers and processes within each inspection, each with its own V. Furthermore, we lack measurement-level predictors because classifiers were captured at the inspection level. We did not study all substances that may be of interest and did not use the information that substances measured on the same sampling media should have the same V. We must note that CART models tend to over-fit data and their predictions depend on the selected data, as illustrated by contrasting predictions created using all data vs. limited to styrene. Conclusions We developed predictive models of sampled air volume that should enable the calculation of LOD for non-detects in IMIS. Our predictions may guide future work on handling non-detects in IMIS, although it is advisable to develop separate predictive models for each substance, industry, and year of interest, while also considering other factors, such as whether the measurement evaluated long-term or short-term exposure. [ABSTRACT FROM AUTHOR]

Objectives The COLCHIC database contains workplace exposure results of chemical samples collected by the French prevention network since 1987. We aimed to investigate potential associations between exposure levels and ancillary variables in COLCHIC across a broad range of chemical agents in order to provide insight into how to best interpret and exploit the information in this national database. Methods We selected personal and area measurements in COLCHIC and collected outside respiratory personal protective equipment (PPE), restricted to chemical agents that had at least 1000 samples available. We used Tobit models to estimate associations between exposure concentrations and sample year, sampling duration, PPE, workforce size, collective protective equipment, origin of request, and reason for request for each chemical agent for the period 1987–2019. Models for period 2002–2019 also included type of process (open/closed) and exposure frequency. We used separate models for each combination of agent, period, and personal or area samples. We then applied Bayesian meta-analytical methods to assess average effects and effect heterogeneity of exposure factors across agents. Results COLCHIC contained 720 282 exposure results (62% personal and 38% area samples) to 77 agents, including 346 766 results for the more recent period 2002–2019 (67% personal and 33% area samples). Sample year and duration, PPE, and process type had the strongest and most consistent associations with exposure levels across agents. Personal and area exposure levels decreased yearly (6% for the entire period and 9% since 2002), and 30-min samples were approximately twice as high as 240-min samples. Workers wearing PPE were exposed to levels 1.7 times higher on average than those without PPE for both area and personal samples. Personal exposure levels associated with enclosed or semi-enclosed processes were approximately 20–30% lower compared with open processes. The associations for the other exposure variables were weaker and more inconsistent between agents. Between-agent heterogeneity of estimated effects, based on 80% prediction intervals, was lowest for sampling duration, time trends, and the presence of PPE. Conclusions Sampling duration, time trends, and the presence of PPE are important factors to take into account when analyzing COLCHIC and had similar associations with exposure levels across agents. Other variables generally showed weaker associations or variable effects. These results will be used to adjust exposure estimates for the French working population from measurements stored in COLCHIC. [ABSTRACT FROM AUTHOR]

Diisocyanates are occupational contaminants and known sensitizers causing irritation (skin and respiratory tract) as well as occupational asthma. Because of their physicochemical properties (semi-volatile and high reactivity) and low occupational limits, diisocyanate exposure evaluation is still a challenge nowadays for industrial hygienists and laboratories. The objective of this study was to compare the methylene diphenyl diisocyanate (MDI) concentrations measured by five methods using different collection or derivatization approaches in an oriented-strand board (OSB) factory. The methods used were: OSHA 47 (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and CIP10 (centrifugation, 1,2-methoxyphenylpiperazine). Real-time monitoring of particle concentration and size distribution was performed to explain the potential bias between methods. The comparison study was performed over 3 consecutive days, generating at least 18 replicates for each of the 5 methods. The results of each methods were compared using linear mixed effect modeling. Compared to Asset, which yielded the highest concentrations overall, the OSHA method provided the smallest bias with −18% (95% CI [-61;24]) (not significant) for MDI monomer and the DAN method provided the smallest bias with −30 (95% CI [–70;9]) (not significant) for Total Reactive Isocyanate Group (TRIG). The CIP10 and Iso-Chek methods provided the largest biases for MDI monomer (–83% (95% CI [–115;–51]) and −78% (95% CI [–110;–46]), respectively) as well as for TRIG (–87% (95% CI [–120;–55]) and −75% (95% CI [–107;–44]), respectively). The underestimations of the CIP10 and Iso-Chek were explained by its inefficient sampling principle for fines particles and the use of a non-impregnated filter to collect aerosol MDI, respectively. This study confirms that impregnated filter, including denuding device such as the Asset EZ4-NCO sampler, collects the MDI-coated wood particles and MDI vapor with similar efficiency. It also demonstrates for the first time in this type of MDI emission a significant agreement for TRIG concentration between the DAN method in the impregnated filter configuration and an international standard one such as Asset. [ABSTRACT FROM AUTHOR]

Objectives The occupational environment represents an important source of exposures to multiplehazards for workers' health. Although it is recognized that mixtures of agents may have differenteffects on health compared to their individual effects, studies generally focus on the assessment ofindividual exposures. Our objective was to identify occupational co-exposures occurring in the United States using the multi-industry occupational exposure databank of the Occupational Safety and Health Administration (OSHA). Methods Using OSHA's Integrated Management Information System (IMIS), measurement data from workplace inspections occurring from 1979 to 2015 were examined. We defined a workplace situation (WS) by grouping measurements that occurred within a company, within the same occupation (i.e. job title) within 1 year. All agents present in each WS were listed and the resulting databank was analyzed with the Spectrosome approach, a methodology inspired by network science, to determine global patterns of co-exposures. The presence of an agent in a WS was defined either as detected, or measured above 20% of a relevant occupational exposure limit (OEL). Results Among the 334 648 detected exposure measurements of 105 distinct agents collected from 14 513 US companies, we identified 125 551 WSs, with 31% involving co-exposure. Fifty-eight agents were detected with others in >50% of WSs, 29 with a proportion >80%. Two clusters were highlighted, one for solvents and one for metals. Toluene, xylene, acetone, hexone, 2-butanone, and N -butyl acetate formed the basis of the solvent cluster. The main agents of the metal cluster were zinc, iron, lead, copper, manganese, nickel, cadmium, and chromium. 68 556 WS were included in the analyses based on levels of exposure above 20% of their OEL, with 12.4% of co-exposure. In this analysis, while the metal cluster remained, only the combinations of toluene with xylene or 2-butanone were frequently observed among solvents. An online web application allows the examination of industry specific patterns. Conclusions We identified frequent co-exposure situations in the IMIS databank. Using the spectrome approach, we revealed global combination patterns and the agents most often implicated. Future work should endeavor to explore the toxicological effects of prevalent combinations of exposures on workers' health to prioritize research and prevention efforts. [ABSTRACT FROM AUTHOR]

Because of the semi-volatile nature of diisocyanates (being airborne in both physical vapor and particulate phases), their high reactivity and low occupational exposure limits, diisocyanate exposure evaluation has been challenging for industrial hygienists and laboratories. The objective of this study was to compare the toluene diisocyanate (2,4 and 2,6 isomers, TDI) concentration measured by five methods in a flexible polyurethane foam factory using different collection or derivatization approaches. The methods used were: OSHA 42 modified (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and CIP10 (centrifugation, 1,2-methoxyphenylpiperazine). Particle real-time monitoring for concentration and size distribution was performed in parallel to improve the understanding of the potential bias between methods. The comparison study was performed over 3 days, providing 18 replicates for each of the 5 methods. Isocyanate concentrations collected for each sampling method were compared using linear mixed effect modeling. Compared to OSHA, which yielded the highest concentrations overall, the Asset and DAN methods provided the smallest biases (−29% (95% CI [−52;−6]) and −45% (95% CI [−67;−23]), respectively), while the CIP10 and Iso-Chek methods provided the largest biases (−82% (95% CI [−105;−66]) and −96% (95% CI [−118;−75]), respectively). The substantial bias of Iso-Chek and CIP10 seemed to be explained by the predominance of TDI in the form of sub-micron particles that were inadequately captured by these two methods due to their sampling principle, which are particle filtration without derivatizing agent and centrifugation respectively. Asset and DAN performance seemed to decrease as the sampling time increased. While DAN's bias could be related to a reagent deficiency on the filter, the disparities between OSHA and Asset, both considered as reference methods, highlight the fact that the mechanisms of collection, derivation and extraction do not seem to be completely controlled. Finally, an upward trend has been observed between concentrations of particles below 300 nm in size and concentration levels of TDI. It has also been observed that TDI levels increased with the TDI foam index produced at the facility. [ABSTRACT FROM AUTHOR]

Objectives: The Integrated Management Information System (IMIS) is the largest multi-industry source of exposure results available in North America. In 2010, the Occupational Safety and Health Administration (OSHA) released the Chemical Exposure Health Data (CEHD) that contains analytical results of samples collected by OSHA inspectors. However, the two databanks only partially overlap, raising suspicion of bias in IMIS data. We investigated the factors associated with selective recording of CEHD results into the IMIS databank. Methods: This analysis was based on personal exposure measurements of 24 agents from 1984 to 2009. The association between nine variables (level of exposure coded as detected versus non-detected (ND), whether a sampling result was part of a panel of chemicals, duration of sampling, issuance of a citation, presence of other detected levels during the same inspection, year, OSHA region, amount of penalty, and establishment size) and a CEHD sampling result being reported in IMIS was analyzed using modified Poisson regression. Results: A total of 461 900 CEHD sampling results were examined. The proportion of CEHD sampling results recorded into IMIS was 38% (51% for detected and 28% for ND measurements). In the models, the detected sampling results were associated with a higher probability of recording into IMIS than ND sampling results, and this difference was similar for panel versus non-panel samples. Probability of recording remained constant from 1984 to 2009 for sampling results measured on panels but increased for sampling results of single determinations of an agent. Some OSHA regions had probability of recording two times higher than others. No other variables that we examined were associated with a CEHD sampling result being reported in IMIS. Conclusions: Our results indicate that the under-reporting of sampling results in IMIS is differential: ND results (especially those determined from the panels) seem less likely to be recorded in IMIS than other results. It is important to consider both IMIS and CEHD data in order to reduce bias in evaluation of exposures in workplaces inspected by OSHA. [ABSTRACT FROM AUTHOR]

DAN is a novel derivatizing agent for isocyanate sampling which targets total reactive isocyanate group (TRIG). Field evaluations have been conducted for 4,4'-Methylene diphenyl diisocyanate (MDI) sampling using DAN as the derivatizing agent in a CIP10. The perimidone formed, selective of TRIG, was analyzed in laboratory by liquid chromatography coupled to tandem mass spectrometry. Workplaces using MDI-based polyurethane spray foam and MDI wood product binder were studied. Each study compared the data obtained between the CIP10/DAN, the CIP10/MP, and a reference method. As a first evaluation, the CIP10/DAN sampled simulated MDI spray foam atmosphere in parallel with impingers (reference method) and CIP10/MP. The mean of the TRIG concentration values measured was 16% (95% confidence interval [CI], [1, 31]) higher for the CIP10/MP samples as compared to the impinger samples, while the mean TRIG concentrations found were 98% (95% CI [63, 133]) higher for the CIP10/DAN samples as compared to the impinger samples. For sampling done in a real workplace using MDI-based spray foam, the CIP10/DAN method showed lower results than the CIP10/MP method. The presence of hygroscopic DMSO used in the DAN approach is a limitation and may prevent obtaining accurate results in the spray foam atmosphere. CIP10/DAN was also studied in MDI wood product binder atmosphere. Mean TRIG concentrations found were 80% (95% CI [51, 110]) and 79% (95% CI [50, 108]) lower for the CIP10/MP and CIP10/DAN method, respectively, as compared to the reference method (a 13-mm filter coated with MP). In this case, the CIP10 may have reached its limit in this last evaluation where vapors and particles below 1 µm were not collected as efficiently as they were with the reference method. [ABSTRACT FROM AUTHOR]

Residues 16-20 of the β-amyloid peptide (Aβ) function as a self-recognition element during Aβ assembly into fibers. Peptides containing this motif retain the ability to interact with Aβ and, in some cases, potently inhibit its assembly. Replacing L- with D-amino acids could stabilize such peptides and permit their evaluation as therapeutic agents for Alzheimer's disease. Here we have assessed the effect that such a chiral reversal has on inhibitory potency. D-enantiomers of five peptides, KLVFFA, KKLVFFA, KFVFFA, KIVFFA, and KVVFFA, were unexpectedly more active as inhibitors in an in vitro fibrillogenesis assay. Circular dichroism showed that D-KLVFFA more effectively prevented Aβ adopting the β-sheet secondary structure correlated with fibrillogenesis. Electron microscopy showed that fiber formation was also more strongly inhibited by D-KLVFFA. Heterochiral inhibition was confirmed using D-Aβ, on the principle that enantiomeric proteins exhibit reciprocal chiral biochemical interactions. With D-Aβ, L-KLVFFA was the more potent inhibitor, rather than D-KLVFFA. Most significantly, D-peptides were more potent at reducing the toxicity of both Aβ[sub 1-40] and Aβ[sub 1-42] toward neuronal cells in culture. This unforeseen heterochiral stereoselectivity of Aβ for D-peptide inhibitors should be considered during future design of peptide-based inhibitors of Aβ neurotoxicity and fibrillogenesis. [ABSTRACT FROM AUTHOR]