Urinary 1,6-hexamethylene diamine (HDA) may serve as a biomarker for systemic exposure to 1,6-hexamethylene diisocyanate (HDI) in occupationally exposed populations. However, the quantitative relationships between dermal and inhalation exposure to HDI and urine HDA levels have not been established. We measured acid-hydrolyzed urine HDA levels along with dermal and breathing-zone levels of HDI in 48 automotive spray painters. These measurements were conducted over the course of an entire workday for up to three separate workdays that were spaced approximately 1 month apart. One urine sample was collected before the start of work with HDI-containing paints and subsequent samples were collected during the workday. HDA levels varied throughout the day and ranged from nondetectable to 65.9 microg l(-1) with a geometric mean and geometric standard deviation of 0.10 microg l(-1) +/- 6.68. Dermal exposure and inhalation exposure levels, adjusted for the type of respirator worn, were both significant predictors of urine HDA levels in the linear mixed models. Creatinine was a significant covariate when used as an independent variable along with dermal and respirator-adjusted inhalation exposure. Consequently, exposure assessment models must account for the water content of a urine sample. These findings indicate that HDA exhibits a biphasic elimination pattern, with a half-life of 2.9 h for the fast elimination phase. Our results also indicate that urine HDA level is significantly associated with systemic HDI exposure through both the skin and the lungs. We conclude that urinary HDA may be used as a biomarker of exposure to HDI, but biological monitoring should be tailored to reliably capture the intermittent exposure pattern typical in this industry.

Urine amine levels used as biomarkers of diisocyanate exposure have usually been normalized with creatinine concentration. The suitability of using creatinine concentration or specific gravity for these biomarkers in exposure assessment has not been established. We investigated the effect of creatinine concentration and specific gravity on urine 1,6-hexamethylene diamine (HDA) levels in multiple mixed linear regression models using quantitative dermal and inhalation exposure data derived from a survey of automotive spray painters occupationally exposed to 1,6-hexamethylene diisocyanate (HDI). Painters' dermal and breathing-zone HDI exposure were monitored for an entire workday for up to three workdays spaced approximately one month apart. One urine sample was collected before the start of work with HDI-containing paints, and multiple samples were collected throughout the workday. Both creatinine concentration and specific gravity were highly significant predictors (p < 0.0001) of urine HDA levels. When these two were used together in the same model, creatinine remained highly significant (p < 0.0001), but specific gravity decreased in significance (p-values 0.10-0.17). We used different individual factors to determine which affected creatinine and specific gravity. Urine collection time was a highly significant predictor of specific gravity (p = 0.003) and creatinine concentration (p = 0.001). Smoker status was significant (p = 0.026) in the creatinine model. The findings indicate that creatinine concentration is more appropriate to account for urine water content than specific gravity and that creatinine is best used as an independent variable in HDI exposure assessment models instead of traditional urine normalization with creatinine concentration.

We conducted a repeated exposure-assessment survey for task-based breathing-zone concentrations (BZCs) of monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI) during spray painting on 47 automotive spray painters from North Carolina and Washington State. We report here the use of linear mixed modeling to identify the primary determinants of the measured BZCs. Both one-stage (N = 98 paint tasks) and two-stage (N = 198 paint tasks) filter sampling was used to measure concentrations of HDI, uretidone, biuret, and isocyanurate. The geometric mean (GM) level of isocyanurate (1410 microg m(-3)) was higher than all other analytes (i.e. GM < 7.85 microg m(-3)). The mixed models were unique to each analyte and included factors such as analyte-specific paint concentration, airflow in the paint booth, and sampler type. The effect of sampler type was corroborated by side-by-side one- and two-stage personal air sampling (N = 16 paint tasks). According to paired t-tests, significantly higher concentrations of HDI (P = 0.0363) and isocyanurate (P = 0.0035) were measured using one-stage samplers. Marginal R(2) statistics were calculated for each model; significant fixed effects were able to describe 25, 52, 54, and 20% of the variability in BZCs of HDI, uretidone, biuret, and isocyanurate, respectively. Mixed models developed in this study characterize the processes governing individual polyisocyanate BZCs. In addition, the mixed models identify ways to reduce polyisocyanate BZCs and, hence, protect painters from potential adverse health effects.

Quantification of amines in biological samples is important for evaluating occupational exposure to diisocyanates. In this study, we describe the quantification of 1,6-hexamethylene diamine (HDA) levels in hydrolyzed plasma of 46 spray painters applying 1,6-hexamethylene diisocyanate (HDI)-containing paint in vehicle repair shops collected during repeated visits to their workplace and their relationship with dermal and inhalation exposure to HDI monomer. HDA was detected in 76% of plasma samples, as heptafluorobutyryl derivatives, and the range of HDA concentrations was < or =0.02-0.92 microg l(-1). After log-transformation of the data, the correlation between plasma HDA levels and HDI inhalation exposure measured on the same workday was low (N = 108, r = 0.22, P = 0.026) compared with the correlation between plasma HDA levels and inhalation exposure occurring approximately 20 to 60 days before blood collection (N = 29, r = 0.57, P = 0.0014). The correlation between plasma HDA levels and HDI dermal exposure measured on the same workday, although statistically significant, was low (N = 108, r = 0.22, P = 0.040) while the correlation between HDA and dermal exposure occurring approximately 20 to 60 days before blood collection was slightly improved (N = 29, r = 0.36, P = 0.053). We evaluated various workplace factors and controls (i.e. location, personal protective equipment use and paint booth type) as modifiers of plasma HDA levels. Workers using a downdraft-ventilated booth had significantly lower plasma HDA levels relative to semi-downdraft and crossdraft booth types (P = 0.0108); this trend was comparable to HDI inhalation and dermal exposure levels stratified by booth type. These findings indicate that HDA concentration in hydrolyzed plasma may be used as a biomarker of cumulative inhalation and dermal exposure to HDI and for investigating the effectiveness of exposure controls in the workplace.

We conducted a quantitative dermal and inhalation exposure assessment of monomeric and polymeric 1,6-hexamethylene diisocyanates (HDI) in 47 automotive spray painters from North Carolina and Washington State. We report here the use of linear mixed modeling (LMM) to identify the primary determinants of dermal exposure. Dermal concentrations of HDI, uretidone, biuret, and isocyanurate were significantly higher in 15 painters who did not wear coveralls or gloves (N = 51 paint tasks) than in 32 painters who did wear coveralls and gloves (N = 192 paint tasks) during spray painting. Regardless of whether protective clothing was worn, isocyanurate was the predominant species measured in the skin [geometric mean (GM) = 33.8 ng mm(-3)], with a 95% detection rate. Other polyisocyanates (GM < or = 0.17 ng mm(-3)) were detected in skin during <23% of the paint tasks. According to marginal R(2) statistics, mixed models generated in this study described no <36% of the variability in dermal concentrations of the different polyisocyanates measured in painters who did not wear protective clothing. These models also described 55% of the variability in dermal concentrations of isocyanurate measured in all painters (N = 288 paint tasks). The product of analyte-specific breathing-zone concentration (BZC) and paint time was the most significant variable in all the models. Through LMM, a better understanding of the exposure pathways governing individual polyisocyanate exposures may be achieved. In particular, we were able to establish a link between BZC and dermal concentration, which may be useful for exposure reconstruction and quantitatively characterizing the protective effect of coveralls and gloves. This information can be used to reduce dermal exposures and better protect automotive spray painters from potential adverse health effects.