Leena A. Nylander-French

Association of Silica Exposure with Anti–Neutrophil Cytoplasmic Autoantibody Small-Vessel Vasculitis: A Population-Based, Case-Control Study

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.

Case-cohort analysis of brain cancer and leukemia in electric utility workers using a refined magnetic field job-exposure matrix

BACKGROUNDnThe potential association between occupational electric and magnetic field exposure and cancer is well documented in the literature, but there is uncertainty regarding a causal relation.nnnMETHODSnUsing data from a completed cohort study, we sought to refine the job-exposure matrix in a case-cohort analysis by regrouping jobs into more homogeneous groups, but without making additional measurements. From the original cohort, we selected the 164 men who died of leukemia, 145 men who died of brain cancer, and a random subcohort of 800 men (0.6% of the cohort). Erroneous job assignments were corrected and job groups were subdivided based on differences in work environments or tasks performed.nnnRESULTSnMagnetic field exposure remained unrelated to leukemia mortality and positively associated with brain cancer mortality based on both cumulative and average magnetic field indices. Although not monotonic across the middle intervals, increased risk of brain cancer was found in relation to career exposure, with risk ratios of 1.8 (95% CI = 0.7-4.7) and 2.5 (95% CI = 1.0-6.3) in the uppermost categories for cumulative and average exposure, stronger for exposure 2-10 years past.nnnCONCLUSIONSnImprovements in exposure assignment based only on reassignment of job titles to occupational categories had little impact on the measured associations of magnetic fields with leukemia or brain cancer.

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.

An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry

Abstract During the manufacturing of reinforced plastics, large amounts of styrene and trace quantities of styrene-7,8-oxide (SO) are released. Since previous work suggests that inhalation of even small amounts of SO might be an important health risk, we investigated several possible factors contributing to styrene and SO exposure during the manufacture of reinforced plastics. Factors related to job type, worker and the type and quantity of styrene-containing resins were investigated using mixed-effects multiple linear regression models. Overall, SO exposure levels were positively correlated with styrene exposure levels. However, this correlation was statistically significant only among hand laminators who had the highest exposures to both styrene and SO. An important factor for predicting both styrene and SO concentrations was the type of resin used, while the quantity of resin consumed was predictive of styrene but not of SO exposure. Since SO exposure appears to be associated with factors other than coexposure to styrene, more effort should be placed on investigating emissions of SO per se. The type of mixed-models regression analysis employed in this study can be used for clarifying the underlying patterns for exposures to styrene and SO as well as for evaluating preventive measures. 1999 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved.

Comparing Urinary Biomarkers of Airborne and Dermal Exposure to Polycyclic Aromatic Compounds in Asphalt-Exposed Workers

When working with hot mix asphalt, road pavers are exposed to polycyclic aromatic hydrocarbons (PAHs) through the inhalation of vapors and particulate matter (PM) and through dermal contact with PM and contaminated surfaces. Several PAHs with four to six rings are potent carcinogens which reside in these particulate emissions. Since urinary biomarkers of large PAHs are rarely detectable in asphalt workers, attention has focused upon urinary levels of the more volatile and abundant two-ring and three-ring PAHs as potential biomarkers of PAH exposure. Here, we compare levels of particulate polycyclic aromatic compounds (P-PACs, a group of aromatic hydrocarbons containing PAHs and heterocyclic compounds with four or more rings) in air and dermal patch samples from 20 road pavers to the corresponding urinary levels of naphthalene (U-Nap) (two rings), phenanthrene (U-Phe) (three rings), monohydroxylated metabolites of naphthalene (OH-Nap) and phenanthrene (OH-Phe), and 1-hydroxypyrene (OH-Pyr) (four rings), the most widely used biomarker of PAH exposure. For each worker, daily breathing-zone air (n = 55) and dermal patch samples (n = 56) were collected on three consecutive workdays along with postshift, bedtime, and morning urine samples (n = 149). Measured levels of P-PACs and the urinary analytes were used to statistically model exposure-biomarker relationships while controlling for urinary creatinine, smoking status, age, body mass index, and the timing of urine sampling. Levels of OH-Phe in urine collected postshift, at bedtime, and the following morning were all significantly associated with levels of P-PACs in air and dermal patch samples. For U-Nap, U-Phe, and OH-Pyr, both air and dermal patch measurements of P-PACs were significant predictors of postshift urine levels, and dermal patch measurements were significant predictors of bedtime urine levels (all three analytes) and morning urine levels (U-Nap and OH-Pyr only). Significant effects of creatinine concentration were observed for all analytes, and modest effects of smoking status and body mass index were observed for U-Phe and OH-Pyr, respectively. Levels of OH-Nap were not associated with P-PAC measurements in air or dermal patch samples but were significantly affected by smoking status, age, day of sample collection, and urinary creatinine. We conclude that U-Nap, U-Phe, OH-Phe, and OH-Pyr can be used as biomarkers of exposure to particulate asphalt emissions, with OH-Phe being the most promising candidate. Indications that levels of U-Nap, U-Phe, and OH-Pyr were significantly associated with dermal patch measurements well into the evening after a given work shift, combined with the small ratios of within-person variance components to between-person variance components at bedtime, suggest that bedtime measurements may be useful for investigating dermal PAH exposures.

Population-based case-control study of occupational exposure to electromagnetic fields and breast cancer.

PURPOSEnThis population-based case-control study examined occupational exposure to electromagnetic fields in relation to female breast cancer incidence among 843 breast cancer cases and 773 controls.nnnMETHODSnExposure was classified based on work in the two longest-held jobs, and indices of cumulative exposure to magnetic fields based on a measurement survey.nnnRESULTSnFemale breast cancer was not associated with employment as an office or industrial worker. For the total study population, cumulative exposure over the entire career, and in the past 0-10 and 10-20 years generally showed odds ratios (ORs) close to the null. Moderately elevated risks were found for intermediate but not high levels of cumulative exposure accumulated 20 or more years ago (OR = 1.5; 95% CI = 1.1-2.0). Associations were stronger for premenopausal women (OR = 1.7; 95% CI = 1.1-2.7) in the past 10-20 years, and those with estrogen-receptor positive (ER+) breast tumors (OR = 2.06; 95% CI = 1.1-4.0). No consistent dose-response patterns were observed.nnnCONCLUSIONSnThese findings give little support to the hypothesis that electromagnetic fields cause cancer of the female breast.

A tape-stripping method for measuring dermal exposure to multifunctional acrylates

Current methods for measuring dermal exposure to skin irritants and allergens, such as acrylates, have significant drawbacks for exposure assessment. A noninvasive sampling method has been developed and tested for measuring dermal exposure to a multifunctional acrylate employing a tape stripping of the nonviable epidermis (stratum corneum). Samples were subsequently extracted and a gas chromatographic method was employed for quantitative analysis of tripropylene glycol diacrylate (TPGDA). This method was tested in 10 human volunteers exposed to an a priori determined amount of TPGDA or a UV-radiation curable acrylate coating containing TPGDA (UV-resin) at different sites on hands and arms. On the average, the first tape stripping removed 94% (coefficient of variation 16%) of the theoretical quantity of deposited TPGDA and 89% (coefficient of variation 15%) of the theoretical quantity of deposited TPGDA in UV-resin 30min after exposure. Quantities of TPGDA recovered from two consecutive tape strippings accounted for all of the test agent, demonstrating both the efficiency of the method to measure dermal exposure and the potential to determine the rate of absorption with successive samples over time. In general, the amount removed by the first stripping was greater for TPGDA than for UV-resin while the second stripping removed approximately 6 and 21% of TPGDA and UV-resin, respectively. However, when the amounts removed with the first tape stripping for TPGDA or UV-resin from the five different individual sites were compared, no significant differences were observed (P=0.111 and 0.893, respectively). No significant difference was observed in recovery between TPGDA and UV-resin for the first tape stripping when calculated as a percentage of the theoretical amount (P=0.262). The results indicate that this tape-stripping technique can be used to quantify dermal exposure to multifunctional acrylates.

Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers

Respiratory sensitization and occupational asthma are associated with exposure to 1,6-hexamethylene diisocyanate (HDI) in both monomeric and oligomeric forms. The monomer and polymers of diisocyanates differ significantly in their rates of absorption into tissue and their toxicity, and hence may differ in their contribution to sensitization. We have developed and evaluated a liquid chromatography/mass spectrometry (LC-MS) method capable of quantifying HDI and its oligomers (uretidone, biuret, and isocyanurate) in air, tape-stripped skin, and paint samples collected in the automotive refinishing industry. To generate analytical standards, urea derivatives of HDI, biuret, and isocyanurate were synthesized by reaction with 1-(2-methoxyphenyl)piperazine and purified. The urea derivatives were shown to degrade on average by less than 2% per week at -20 degrees C over a 2 month period in occupational samples. The average recovery of HDI and its oligomers from tape was 100% and the limits of detection were 2 and 8 fmol microl(-1), respectively. Exposure assessments were performed on 13 automotive spray painters to evaluate the LC-MS method and the sampling methods under field conditions. Isocyanurate was the most abundant component measured in paint tasks, with median air and skin concentrations of 2.4 mg m(-3) and 4.6 microg mm(-3), respectively. Log-transformed concentrations of HDI (r = 0.79, p < 0.0001) and of isocyanurate (r = 0.71, p < 0.0001) in the skin of workers were correlated with the log-transformed product of air concentration and painting time. The other polyisocyanates were detected on skin for less than 25% of the paint tasks. This LC-MS method provides a valuable tool to investigate inhalation and dermal exposures to specific polyisocyanates and to explore relative differences in the exposure pathways.

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., Pratts Index), General Dominance Index, and Johnsons 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 Johnsons Relative Weight are preferred methods for quantifying the relative importance of predictors in a multiple linear regression model. Johnsons Relative Weight involves significantly less computational burden than the General Dominance Index when the number of predictors in the final model is large.

Dermal and Inhalation Exposure to Methylene Bisphenyl Isocyanate (MDI) in Iron Foundry Workers

Diisocyanates are a group of chemically reactive agents, which are used in the production of coatings, adhesives, polyurethane foams, and parts for the automotive industry and as curing agents for cores in the foundry industry. Dermal and inhalation exposure to methylene bisphenyl isocyanate (MDI) is associated with respiratory sensitization and occupational asthma. However, limited research has been performed on the quantitative evaluation of dermal and inhalation exposure to MDI in occupationally exposed workers. The objective of this research was to quantify dermal and inhalation exposure levels in iron foundry workers. Workers involved in mechanized moulding and mechanized production of cores were monitored: 12 core makers, 2 core-sand preparers, and 5 core installers. Personal breathing-zone levels of MDI were measured using impregnated filter sampling. Dermal exposure to MDI was measured using a tape-strip technique. Three or five consecutive tape-strip samples were collected from five exposed skin areas (right and left forefingers, left and right wrists, and forehead). The average personal air concentration was 0.55 microg m(-3), 50-fold lower than the Swedish occupational exposure limit of 30 microg m(-3). The core makers had an average exposure of 0.77 microg m(-3), which was not significantly different from core installers and core-sand preparers average exposure of 0.16 microg m(-3) (P = 0.059). Three core makers had a 10-fold higher inhalation exposure than the other core makers. The core makers mean dermal exposure at different skin sites varied from 0.13 to 0.34 microg while the two other groups exposure ranged from 0.006 to 0.062 microg. No significant difference was observed in the MDI levels between the skin sites in a pairwise comparison, except for left forefinger compared to left and right wrist (P < 0.05). In addition, quantifiable but decreasing levels of MDI were observed in the consecutive tape strip per site indicating MDI penetration into the skin. This study indicates that exposure to MDI can be quantified on workers skin even if air levels are close to unquantifiable. Thus, the potential for uncured MDI to deposit on and penetrate into the skin is demonstrated. Therefore, dermal exposure along with inhalation exposure to MDI should be measured in the occupational settings where MDI is present in order to shed light on their roles in the development of occupational isocyanate asthma.