Effect of creatinine and specific gravity normalization on urinary biomarker 1,6-hexamethylene diamine

Abstract

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.

(2-Methoxyethoxy)acetic acid: a urinary biomarker of exposure for jet fuel JP-8

“…Therefore, the use of MEAA for a biomarker of exposure for JP-8 is valid either as concentration in urine with or without the creatinine adjustment. Although other researchers (Gaines et al 2010) have suggested that other urine level normalization schemes are better than creatinine adjustment, the differences in the MEAA levels between exposure workgroup categories are so large that it would not change the statistical significance of this study. Some additional comments about the statistics used in this presentation and its obvious limitations are necessary.…”

Evaluation and Comparison of Urinary Metabolic Biomarkers of Exposure for the Jet Fuel JP-8

“…This was not an unexpected result; the use of creatinine to normalize urinary analyte concentrations has been extensively reported to not necessarily improve correlation of dose to exposure for other urinary components (Allessio et al 1985;Boeniger et al 1993;Carrieri et al 2001). Gaines et al (2010) suggested the use of urine specific gravity for biomarker normalization as an alternative to creatinine. However, for the current JP-8 exposure study, creatinine-adjusted and nonadjusted values were the only normalization schemes investigated.…”

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

“…3 We further concluded that creatinine should be used as an independent variable in exposure modeling to account for the water content in the urine sample collected from a worker exposed to HDI. 3,8 However, in our exposure models relating inhalation and dermal HDI exposure to urine HDA levels, considerable intra- and inter-person variability was observed, 3 which would compromise the use of urine HDA as a biomarker for occupational exposure to HDI. To effectively use individual urine HDA levels in monitoring exposure, evaluating personal protection, and establishing regulatory compliance, determining the cause(s) of the variability is critical.…”