Factors affecting variability in the urinary biomarker 1,6-hexamethylene diamine in workers exposed to 1,6-hexamethylene diisocyanate

Gaines, Linda G. Trelles; Fent, Kenneth W.; Flack, Sheila L.; Thomasen, Jennifer M.; Whittaker, Stephen G.; Nylander‐French, Leena A.

doi:10.1039/c0em00122h

Cited by 13 publications

(5 citation statements)

References 25 publications

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“…We were able to use reliable and specific biomarkers to estimate workers’ internal exposure dose by measuring their plasma and urine biomarker levels during the workday. We have previously demonstrated that HDA is excreted in urine with a half-life of ∼2.9 h and that urine HDA levels are correlated with same-day measurements of HDI monomer exposure ( Gaines et al, 2010a , b , 2011 ). For HDI isocyanurate, we have demonstrated that TAHI in urine is a specific biomarker of HDI isocyanurate exposure and that urine TAHI levels are correlated with same-day exposure measurements of HDI isocyanurate exposure ( Robbins et al, 2018 ).…”

Section: Discussionmentioning

confidence: 95%

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate

et al. 2020

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We evaluated the impact of genetic variance on biomarker levels in a population of workers in the automotive repair and refinishing industry who were exposed to respiratory sensitizers 1,6-hexamethylene diisocyanate (HDI) monomer and one of its trimers, HDI isocyanurate. The exposures and respective urine and plasma biomarkers 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) were measured in 33 workers; and genome-wide microarrays (Affymetrix 6.0) were used to genotype the workers' single-nucleotide polymorphisms (SNPs). Linear mixed model analyses have indicated that interindividual variations in both inhalation and skin exposures influenced these biomarker levels. Using exposure values as covariates and a false discovery rate < 0.10 to assess statistical significance, we observed that seven SNPs were associated with HDA in plasma, five were associated with HDA in urine, none reached significance for TAHI in plasma, and eight were associated with TAHI levels in urine. The different genotypes for the 20 significant SNPs accounted for 4-to 16-fold changes observed in biomarker levels. Associated gene functions include transcription regulation, calcium ion transport, vascular morphogenesis, and transforming growth factor beta signaling pathway, which may impact toxicokinetics indirectly by altering inflammation levels. Additionally, in an expanded analysis using a minor allele cutoff of 0.05 instead of 0.10, there were biomarker-associated SNPs within three genes that have been associated with isocyanate-induced asthma: ALK, DOCK2, and LHPP. We demonstrate that genetic variance impacts the biomarker levels in workers exposed to HDI monomer and HDI isocyanurate and that genetics can be used to refine exposure predictions in small cohorts when quantitative personal exposure and biomarker measurements are included in the models.

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Section: Discussionmentioning

confidence: 95%

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate

et al. 2020

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“…Increased airflow and downdraft booths (vs. cross- or semi-draft booths) were associated with reduced polyisocyanate breathing zone concentrations. Gaines et al (37) and Flack et al (38) documented that the type of spray booth was a significant predictor of HDA level (1, 6-hexamethylene diamine, an HDI biomarker) in the urine and blood plasma of autobody spray painters, regardless of the painters’ choice of respiratory protection. Education and outreach are needed to improve respiratory protection and spray booth ventilation in the collision repair industry.…”

Section: Discussionmentioning

confidence: 99%

Airborne Isocyanate Exposures in the Collision Repair Industry and a Comparison to Occupational Exposure Limits

Reeb-Whitaker

Whittaker

Ceballos

et al. 2012

Journal of Occupational and Environmental Hygiene

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Isocyanate exposure was evaluated in 33 spray painters from 25 Washington State autobody shops. Personal breathing zone samples (n = 228) were analyzed for isophorone diisocyanate (IPDI) monomer, 1,6-hexamethylene diisocyanate (HDI) monomer, IPDI polyisocyanate, and three polyisocyanate forms of HDI. The objective was to describe exposures to isocyanates while spray painting, compare them with short-term exposure limits (STELs), and describe the isocyanate composition in the samples. The composition of polyisocyanates (IPDI and HDI) in the samples varied greatly, with maximum amounts ranging from up to 58% for HDI biuret to 96% for HDI isocyanurate. There was a significant inverse relationship between the percentage composition of HDI isocyanurate to IPDI and to HDI uretdione. Two 15-min STELs were compared: (1) Oregon's Occupational Safety and Health Administration (OR-OSHA) STEL of 1000 μg/m3 for HDI polyisocyanate, and (2) the United Kingdom's Health and Safety Executive (UK-HSE) STEL of 70 μg NCO/m3 for all isocyanates. Eighty percent of samples containing HDI polyisocyanate exceeded the OR-OSHA STEL while 98% of samples exceeded the UKHSE STEL. The majority of painters (67%) wore half-face air-purifying respirators while spray painting. Using the OROSHA and the UK-HSE STELs as benchmarks, 21% and 67% of painters, respectively, had at least one exposure that exceeded the respirator's OSHA-assigned protection factor. A critical review of the STELs revealed the following limitations: (1) the OR-OSHA STEL does not include all polyisocyanates, and (2) the UK-HSE STEL is derived from monomeric isocyanates, whereas the species present in typical spray coatings are polyisocyanates. In conclusion, the variable mixtures of isocyanates used by autobody painters suggest that an occupational exposure limit is required that includes all polyisocyanates. Despite the limitations of the STELs, we determined that a respirator with an assigned protection factor of 25 or greater is required to protect against isocyanate exposures during spray painting. Consequently, half-face air-purifying respirators, which are most commonly used and have an assigned protection factor of 10, do not afford adequate respiratory protection.

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“…Dermal exposure to monomeric and polymeric HDI comprises a significant route for exposure to spray painters employed in the automotive refinishing industry. 3,[5][6][7][8][15][16][17][18][19] Although the dermal exposure route has been established to be significant, 8,16,17,20 there are no regulatory limits or standards regarding dermal exposure to isocyanates. Here, we report our investigation on the penetration patterns and rates of monomeric and polymeric HDI in human skin in order to gain insight to the potential contribution of dermal exposure to internal dose received in this worker population.…”

Section: Discussionmentioning

confidence: 99%

Penetration patterns of monomeric and polymeric 1,6-hexamethylene diisocyanate monomer in human skin

Thomasen

Nylander‐French

2012

J. Environ. Monit.

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We investigated penetration patterns of monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI), experimentally and as part of commercial products, in excised full-thickness human skin at 5, 10, 30, or 60 min after exposure. We observed that both monomeric and polymeric HDI were readily absorbed into the skin and that the clearcoat composition affects the penetration rate of the individual isocyanates. The short-term absorption rates for HDI monomer, biuret, and isocyanurate were determined and used to estimate the exposure time required to reach a body burden equal to the American Conference of Governmental Industrial Hygienists (ACGIH) inhalation threshold limit value (TLV) or Oregon State occupational exposure limit (OEL). Oregon is the only government entity in the United States to promulgate a short-term exposure limit (STEL) for HDI-based polyisocyanates biuret and isocyanurate. Based on these absorption rates for a slow-drying clearcoat after 10 min (1.33 μg cm(-2) h(-1)) or 60 min (0.219 μg cm(-2) h(-1)), we calculated that 6.5 and 40 min dermal exposure, respectively, is required to achieve a dose of HDI equivalent to the ACGIH TLV. For biuret, the time to achieve a dose equivalent to the Oregon OEL for slow-drying clearcoat was much shorter (<31 min) than that for fast-drying clearcoat (618 min). Isocyanurate had the shortest skin absorption times regardless of clearcoat formulation (14 s-1.7 min). These results indicate that the dose received through dermal exposure to HDI-containing clearcoats has a significant potential to exceed the dose equivalent to that received through inhalation exposure at established regulatory limits. A critical need exists to monitor dermal exposure quantitatively in exposed workers, to use proper protective equipment to reduce dermal exposure, and to re-evaluate regulatory exposure limits for isocyanates.

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Factors affecting variability in the urinary biomarker 1,6-hexamethylene diamine in workers exposed to 1,6-hexamethylene diisocyanate

Cited by 13 publications

References 25 publications

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate

Airborne Isocyanate Exposures in the Collision Repair Industry and a Comparison to Occupational Exposure Limits

Penetration patterns of monomeric and polymeric 1,6-hexamethylene diisocyanate monomer in human skin

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