Comparison of biomarker for diagnosis of nitrous oxide abuse: challenge of cobalamin metabolic parameters, a retrospective study.

BACKGROUND: Recreational use of nitrous oxide (N2O) leads to neurological disorders including combined subacute degeneration of spinal cord, psychological disorders, and thrombosis. Serum or urine N2O assays could not be routinely performed. Hence, it is necessary to investigate other biological markers such as metabolic markers. We aimed here to challenge the three main biological markers used for the diagnosis of nitrous oxide abuse as total vitamin B12, homocysteine, and methylmalonic acid. METHODS: We retrospectively collected clinical and biological data from 52 patients with known, documented chronic N2O abuse and associated clinical signs (peripheral neuropathy disability score or thrombosis event). Sera and plasma total vitamin B12, methylmalonic acid (MMA), and homocysteine were performed to identify the most specific marker of chronic N2O intoxication and related clinical outcomes. RESULTS: Plasma homocysteine was almost consistently increased in case of N2O chronic consumption, whereas MMA increase and total vitamin B12 decrease are not systematically found. Our results showed that none of the markers are correlated with levels of N2O consumptions. However, homocysteine and MMA are correlated with clinical severity, but MMA seems to be a better marker of clinical severity. CONCLUSION: There is no specific marker of nitrous oxide abuse according to levels of consumption, total vitamin B12 decrease could not be used either as consumption or as severity marker. However, we showed that homocysteine is consistently increased and could be used as marker of recent N2O consumption. On the other hand, we showed that MMA could be used as a marker of clinical gravity.

On-site comparison of the OSHA 47, Asset EZ4-NCO, Iso-Chek, DAN, and CIP10 methods for measuring methylene diphenyl diisocyanate (MDI) at an oriented-strand board (OSB) factory.

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.

On site comparison of the OSHA 42, Asset EZ4-NCO, Iso-Chek, DAN and CIP10 methods for measuring toluene diisocyanate (TDI) at a polyurethane foam factory.

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.