Urine 1,6-hexamethylene diamine (HDA) levels among workers exposed to 1,6-hexamethylene diisocyanate (HDI)

Abstract

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.

Fig. 1.

Level of HDA in urine samples from a painter in Washington state throughout the workday on Visit 1 (filled circles), Visit 2 (filled diamonds), and Visit 3 (filled squares).

Fig. 2.

Level of HDA in urine samples from painter in Washington State throughout the workday on Visit 1 (filled circles), Visit 2 (filled diamonds), and Visit 3 (filled squares). Worker did not paint on Visit 1.

Fig. 3.

The relationship between natural log-transformed BZC–APF exposure and natural log-transformed urine HDA levels adjusted for creatinine in samples collected from 48 spray painters exposed to HDI in North Carolina and Washington State. The line indicates the best-fit linear regression (R² = 0.10). (Note: Since multiple imputation creates 10 different datasets, for this figure, all nondetectable levels of urine HDA and BZC were assigned a value of the LOD/√2 instead of multiple imputation used for the models.)