Berrin Serdar

Simultaneous determination of urinary 1- and 2-naphthols, 3- and 9-phenanthrols, and 1-pyrenol in coke oven workers

A method was developed for simultaneous quantification of urinary 1- and 2-naphthols, 3- and 9-phenanthrols and 1-pyrenol using gas chromatography with mass spectrometry (GC-MS). This method was applied to urine samples from coke oven workers (n =28) and controls (n =22) from Northern China. Geometric mean levels of urinary 1-naphthol (58.8 μg l−1), 2-naphthol (34.1 μg l−1), 3-phenanthrol (7.35 μg l−1), 9-phenanthrol (1.28 μg l−1) and 1-pyrenol (25.4 μg l−1) were significantly higher among coke oven workers than controls. All the substances tested were highest among top-of-oven workers, who had 15-fold higher 1-naphthol, eight-fold higher 2-naphthol and 20-fold higher 1-pyrenol levels compared with controls. Using multiple linear regression models, 72.5% of the variation in 1- and 2-naphthol and 82.8% of the variation in 1-pyrenol were explained by the concentration of naphthalene or pyrene in the urine, the work category and the smoking intensity. Cigarette consumption significantly contributed to levels of urinary 1-pyrenol and naphthols, particularly 2-naphthol. A negative relationship between work category and the ratio of naphthols/1-pyrenol was observed among smokers. Our results suggest that urinary naphthols and phenanthrols reflect polycyclic aromatic hydrocarbon (PAH) exposure as well as the widely used 1-pyrenol, and that interactions between cigarette smoking and PAH exposure result in different patterns of metabolism for individual PAHs.

Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study

We recently reported associations between urinary 1-naphthol (1N) levels and several intermediate measures of male reproductive health, namely sperm motility, serum testosterone levels, and sperm DNA damage. However, because 1N is a major urinary metabolite of both naphthalene and the insecticide carbaryl, exposure misclassification stemming from differences in exposure source was probable and interpretation of the results was limited. As naphthalene, but not carbaryl, is also metabolized to 2-naphthol (2N), the relationship of urinary 1N to 2N within an individual may give information about source of 1N. Utilizing data from two previous studies that measured both 1N and 2N in urine of men exposed to either carbaryl or naphthalene, the present study employed several methods to differentiate urinary 1N arising from exposures to carbaryl and naphthalene among men in the reproductive health study. When re-evaluating the reproductive health data, techniques for identifying 1N source involved exploring interaction terms, stratifying the data set based on 1N/2N ratios, and performing an exposure calibration using a linear 1N to 2N relationship from a study of workers exposed to naphthalene in jet fuel. Despite some inconsistencies between the methods used to distinguish 1N source, we found that 1N from carbaryl exposure is likely responsible for the previously observed association between 1N and sperm motility, whereas 1N from naphthalene exposure is likely accountable for the association between 1N and sperm DNA damage. We demonstrate that studies of health effects associated with carbaryl should utilize a 1N/2N ratio to identify subgroups in which carbaryl is the primary source of 1N. Conversely, studies of naphthalene-related outcomes may utilize 2N levels to estimate exposure.

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.

Naphthalene and its biomarkers as measures of occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAH) include compounds with two or more fused benzene rings, many of which are carcinogens. Industrial sources produce hundreds of PAH, notably in the coke- and aluminium-producing industries. Because PAH are distributed at varying levels between gaseous and particulate phases, exposure assessment has been problematic. Here, we recommend that occupational exposures to naphthalene be considered as a potential surrogate for occupational PAH exposure for three reasons. Naphthalene is usually the most abundant PAH in a given workplace; naphthalene is present almost entirely in the gaseous phase and is, therefore, easily measured; and naphthalene offers several useful biomarkers, including the urinary metabolites 1- and 2-hydroxynaphthalene. These biomarkers can be used to evaluate total-body exposure to PAH, in much the same way that 1-hydroxypyrene has been applied. Using data from published sources, we show that log-transformed airborne levels of naphthalene are highly correlated with those of total PAH (minus naphthalene) in several industries (creosote impregnation: Pearson r= 0.815, coke production: r= 0.917, iron foundry: r= 0.854, aluminium production: r= 0.933). Furthermore, the slopes of the log-log regressions are close to one indicating that naphthalene levels are proportional to those of total PAH in those industries. We also demonstrate that log-transformed urinary levels of the hydroxynaphthalenes are highly correlated with those of 1-hydroxypyrene among coke oven workers and controls (r= 0.857 and 0.876), again with slopes of log-log regressions close to one. These results support the conjecture that naphthalene is a useful metric for occupational PAH exposure. Since naphthalene has also been shown to be a respiratory carcinogen in several animal studies, it is also argued that naphthalene exposures should be monitored per se in industries with high levels of PAH.

Albumin Adducts of Naphthalene Metabolites as Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons

We investigated the utility of adducts formed by the reaction of the naphthalene metabolites naphthalene-1,2-oxide, 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) with serum albumin (Alb) as biomarkers of exposure to polycyclic aromatic hydrocarbons. Cysteinyl serum Alb adducts of 1,2- and 1,4-NPQ (1,2-NPQ-Alb and 1,4-NPQ-Alb, respectively) but not of naphthalene-1,2-oxide were detected in 28 coke oven workers and 22 controls from the steel industry of northern China. The median level of 1,2-NPQ-Alb in coke oven workers (76.6 pmol/g) was significantly higher than that observed in controls (44.9 pmol/g; P = 0.0027). However, the median level of 1,4-NPQ-Alb in exposed subjects was not significantly different from that of controls (48.6 versus 44.2 pmol/g; P = 0.296). Levels of 1,2-NPQ-Alb were significantly correlated with exposure category (controls, side and bottom workers, and top-of-oven workers) as well as with previously measured levels of urinary naphthalene, 1- and 2-naphthol, and 1-pyrenol in these subjects. Multiple linear regression analysis revealed that 35% of the variation in 1,2-NPQ-Alb could be explained by the work category and age. A negative relationship between 1,2-NPQ-Alb and age was observed, suggesting that cytochrome P450 c metabolism diminished with age at ∼3%/year of life.

Childhood hematologic cancer and residential proximity to oil and gas development

Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.

Predictors Of Occupational Exposure To Styrene And Styrene-7,8-Oxide In The Reinforced Plastics Industry

Objective: To identify demographic and work related factors that predict blood levels of styrene and styrene-7,8-oxide (SO) in the fibreglass reinforced plastics (FRP) industry. Methods: Personal breathing-zone air samples and whole blood samples were collected repeatedly from 328 reinforced plastics workers in the Unuted States between 1996 and 1999. Styrene and its major metabolite SO were measured in these samples. Multivariable linear regression analyses were applied to the subject-specific levels to explain the variation in exposure and biomarker levels. Results: Exposure levels of styrene were approximately 500-fold higher than those of SO. Exposure levels of styrene and SO varied greatly among the types of products manufactured, with an 11-fold range of median air levels among categories for styrene and a 23-fold range for SO. Even after stratification by job title, median exposures of styrene and SO among laminators varied 14- and 31-fold across product categories. Furthermore, the relative proportions of exposures to styrene and SO varied among product categories. Multivariable regression analyses explained 70% and 63% of the variation in air levels of styrene and SO, respectively, and 72% and 34% of the variation in blood levels of styrene and SO, respectively. Overall, air levels of styrene and SO appear to have decreased substantially in this industry over the last 10–20 years in the US and were greatest among workers with the least seniority. Conclusions: As levels of styrene and SO in air and blood varied among product categories in the FRP industry, use of job title as a surrogate for exposure can introduce unpredictable measurement errors and can confound the relation between exposure and health outcomes in epidemiology studies. Also, inverse relations between the intensity of exposure to styrene and SO and years on the job suggest that younger workers with little seniority are typically exposed to higher levels of styrene and SO than their coworkers.

Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002).

Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001–2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution.

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 (pu2009=u20090.061). 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 (pu2009<u20090.0001). 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.