The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure.

We investigated the association between biomarkers of dermal exposure, naphthyl-keratin adducts (NKA), and urine naphthalene biomarker levels in 105 workers routinely exposed to jet-fuel. A moderate correlation was observed between NKA and urine naphthalene levels (p = 0.061). The NKA, post-exposure breath naphthalene, and male gender were associated with an increase, while CYP2E1*6 DD and GSTT1-plus (++/+-) genotypes were associated with a decrease in urine naphthalene level (p < 0.0001). The NKA show great promise as biomarkers for dermal exposure to naphthalene. Further studies are warranted to characterize the relationship between NKA, other exposure biomarkers, and/or biomarkers of biological effects due to naphthalene and/or PAH exposure.

Quantifying the relative importance of predictors in multiple linear regression analyses for public health studies.

Multiple linear regression analysis is widely used in many scientific fields, including public health, to evaluate how an outcome or response variable is related to a set of predictors. As a result, researchers often need to assess "relative importance" of a predictor by comparing the contributions made by other individual predictors in a particular regression model. Hence, development of valid statistical methods to estimate the relative importance of a set of predictors is of great interest. In this research, the authors considered the relative importance of a predictor when defined by that portion of the squared multiple correlation explained by the contribution of each predictor in the final model of interest. Here, a number of suggested relative importance indices motivated by this definition are reviewed, including the squared zero-order correlation, squared semipartial correlation, Product Measure (i.e., Pratt's Index), General Dominance Index, and Johnson's Relative Weight. The authors compared these indices using data sets from an occupational health study in which human inhalation exposure to styrene was measured and from a laboratory animal study on risk factors for atherosclerosis, and statistical properties using bootstrap methods were examined. The analysis suggests that the General Dominance Index and Johnson's Relative Weight are preferred methods for quantifying the relative importance of predictors in a multiple linear regression model. Johnson's Relative Weight involves significantly less computational burden than the General Dominance Index when the number of predictors in the final model is large.

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

BACKGROUND: Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. OBJECTIVE: Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. METHODS: The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. RESULTS: The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). CONCLUSIONS: PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

Dermal exposure to jet fuel (JP-8) in US Air Force personnel.

Limited research has been conducted on dermal exposure and risk assessment, owing to the lack of reliable measurement techniques and data for quantitative risk assessment. We investigated the magnitude of dermal exposure to jet propulsion fuel 8 (JP-8), using naphthalene as a surrogate, on the US Air Force fuel-cell maintenance workers. Dermal exposure of 124 workers routinely working with JP-8 was measured using a non-invasive tape-strip technique coupled with gas chromatography-mass spectrometry analysis. The contribution of job-related factors to dermal exposure was determined using multiple linear regression analyses. Average whole body dermal exposure to naphthalene (as a marker for JP-8) was 7.61 +/- 2.27 ln(ng m(-2)). Significant difference (P < 0.0001) between the high-exposure group [8.34 +/- 2.23 ln(ng m(-2))] and medium- and low-exposure groups [6.18 +/- 1.35 ln(ng m(-2)) and 5.84 +/- 1.34 ln(ng m(-2)), respectively] was observed reflecting the actual exposure scenarios. Skin irritation, use of booties, working inside the fuel tank and the duration of JP-8 exposure were significant factors explaining the whole body dermal exposure. This study clearly demonstrates the efficiency and suitability of the tape-strip technique for the assessment of dermal exposure to JP-8 and that naphthalene can serve as a useful marker of exposure and uptake of JP-8 and its components. It also showed that the skin provides a significant route for JP-8 exposure and that actions to reduce exposure are required. Studies to investigate the relative contribution of dermal uptake of JP-8 on total body dose and the toxicokinetics of dermal exposure to JP-8 are underway.

Determination of keratin protein in a tape-stripped skin sample from jet fuel exposed skin.

Chemical contaminants or their metabolites may bind to and react with keratin proteins in the stratum corneum of the skin. Here, we present a tape-stripping method for the removal and quantification of keratin from the stratum corneum for normalization of extracted concentrations of naphthalene (as a marker for jet fuel exposure) from 12 human volunteers before and after exposure to jet fuel (JP-8). Due to the potential for removal of variable amounts of squamous tissue from each tape-strip sample, keratin was extracted and quantified using a modified Bradford method. Confirmation of the extraction of keratin was verified by western blotting using a monoclonal mouse anti-human cytokeratin antibody. Naphthalene was quantified in the sequential tape strips collected from the skin between 10 and 25 min after a single dose of JP-8 was initially applied. The penetration of jet fuel into the stratum corneum was demonstrated by the fact that the average mass of naphthalene recovered by a tape strip decreased with increased exposure time and subsequent tape strips and that the evaporation of naphthalene was observed to be negligible. There were no significant differences in the amount of keratin or naphthalene removed by tape strips between males and females, between age groups, races or degrees of skin pigmentation. We conclude that (i) the amount of keratin removed with tape strips was not affected by up to a 25 min exposure to JP-8 and (ii) there was a substantial decrease in the amount of keratin removed with consecutive tape strips from the same site, thus, adjusting the amount of naphthalene by the amount of keratin measured in a tape-strip sample should improve the interpretation of the amount of this analyte using this sampling approach. Although we found that normalization of the naphthalene to the amount of keratin in the tape-strip samples did not affect the ability of this method to quantify the dermal exposure to JP-8 under these laboratory conditions, the actual concentration of naphthalene (as a marker for JP-8 exposure) per unit of keratin in a tape-strip sample can be determined using this method and may prove to be required when measuring occupational exposures under field conditions.