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Analytical determination of specific 4,4′-methylene diphenyl diisocyanate hemoglobin adducts in human blood

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Abstract

4,4′-Methylene diphenyl diisocyanate (MDI) is one of the most important isocyanates in the industrial production of polyurethane and other MDI-based synthetics. Because of its high reactivity, it is known as a sensitizing agent, caused by protein adducts. Analysis of MDI is routinely done by determination of the nonspecific 4,4′-methylenedianiline as a marker for MDI exposure in urine and blood. Since several publications have reported specific adducts of MDI and albumin or hemoglobin, more information about their existence in humans is necessary. Specific adducts of MDI and hemoglobin were only reported in rats after high-dose MDI inhalation. The aim of this investigation was to detect the hemoglobin adduct 5-isopropyl-3-[4-(4-aminobenzyl)phenyl]hydantoin (ABP-Val-Hyd) in human blood for the first time. We found values up to 5.2 ng ABP-Val-Hyd/g globin (16 pmol/g) in blood samples of workers exposed to MDI. Because there was no information available about possible amounts of this specific MDI marker, the analytical method focused on optimal sensitivity and selectivity. Using gas chromatography–high-resolution mass spectrometry with negative chemical ionization, we achieved a detection limit of 0.02 ng ABP-Val-Hyd/g globin (0.062 pmol/g). The robustness of the method was confirmed by relative standard deviations between 3.0 and 9.8 %. Combined with a linear detection range up to 10 ng ABP-Val-Hyd/g globin (31 pmol/g), the enhanced precision parameter demonstrates that the method described is optimized for screening studies of the human population.

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Acknowledgments

The development of this method of analyzing MDI-specific hemoglobin adducts found in the human body was funded by the German chemicals industry. The method was developed during an ongoing 10-year project on human biomonitoring. The project is a cooperation agreed in 2010 between the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) and the Verband der chemischen Industrie (German Chemical Industry Association—VCI) and is administered by the Federal Environment Agency (UBA). Experts from public authorities, industry, and science support the project in selecting substances and developing methods. We would like to thank the International Isocyanate Institute for sponsoring the syntheses of the calibration standards.

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  1. Health Protection, Institute of Biomonitoring, Currenta GmbH & Co. OHG, 51368, Leverkusen, Germany

    Wolfgang Gries & Gabriele Leng

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  1. Wolfgang Gries
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  2. Gabriele Leng
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Correspondence to Wolfgang Gries.

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Gries, W., Leng, G. Analytical determination of specific 4,4′-methylene diphenyl diisocyanate hemoglobin adducts in human blood. Anal Bioanal Chem 405, 7205–7213 (2013). https://doi.org/10.1007/s00216-013-7171-z

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  • DOI: https://doi.org/10.1007/s00216-013-7171-z

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