Journal of Exposure Science & Environmental Epidemiology

JES publishes research important to exposure assessment for toxic substances, environmental epidemiology and related disciplines that advance the exposure assessment process.

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is used as an alternative for some phthalate plasticizers. In rats, DINCH mostly eliminates in feces as cyclohexane-1,2-dicarboxylic acid (CHDA), mono isononyl ester (MINCH) or in urine as CHDA. However, CHDA is not a specific biomarker of DINCH and measuring MINCH in feces is impractical. To identify additional potential biomarkers, we administered DINCH (500 mg/kg body weight) in a single subcutaneous (SC) or oral dose to four adult female Sprague-Dawley rats. We collected 24-h urine samples before dosing (to be used as controls) and 24-h and 48-h after dosing, and serum at necropsy after 48 h. We positively identified and accurately quantified CHDA and cyclohexane-1,2-dicarboxylic [corrected] acid, mono hydroxyisononyl ester (MHNCH) using authentic standards. Moreover, we tentatively identified MINCH and 12 oxidative metabolites, including 4 cyclohexane ring oxidation products, based on their mass spectrometric-fragmentation patterns. CHDA and MHNCH levels were higher in the urine collected 24 h after oral than SC administration. By contrast, 48-h after dosing, CHDA urinary levels were similar regardless of the exposure route. We detected all but two of the urine metabolites also in serum. Levels of CHDA and MHNCH in serum were lower than in the two post-dose urine collections. Our results suggest that several urinary oxidative metabolites, specifically CHDA, mono oxoisononyl ester and MHNCH may be used as specific biomarkers of DINCH exposure in humans.

The Narodichesky region, Zhitomir Oblast, Ukraine, is situated ∼80 km from the Chernobyl Nuclear Power Plant, which exploded in 1986 and polluted the environment. A previous study found that children living in villages with high activity of (137)Cesium (Cs) in the soil had decreased levels of hemoglobin, erythrocytes and thrombocytes. These findings motivated the present study that used a more comprehensive exposure assessment, including individual whole-body concentrations (WBC) of (137)Cs (Bq/kg). This cross-sectional sample examined between 2008-2010, included 590 children in the age 0-18 years. Children with higher individual log(WBC) activity in the body had significantly decreased hemoglobin, erythrocyte and thrombocyte counts. The effect of log(WBC) on decreased thrombocyte count was only seen in children older than 12 years. The average village activity of (137)Cs (kBq/m(2)) in soil was associated with decreased blood counts only indirectly, through (137)Cs in the body as an intermediate variable. Children in this study were born at least 4 years after the accident and thus exposed to low doses of ionizing radiation from (137)Cs. This cross-sectional study indicates that low levels may be associated with decreased blood counts, but we cannot exclude that these results are due to residual confounding factors.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 September 2013; doi:10.1038/jes.2013.60.

For decades, asbestos-containing gaskets were used in virtually every system that involved the transport of fluids or gases. Prior to the mid-1970s, some automobile exhaust systems contained asbestos gaskets either at flanges along the exhaust pipes or at the exhaust manifolds of the engine. A limited number of automobile mufflers were lined with asbestos paper. This paper describes a simulation study that characterized personal and bystander exposures to asbestos during the removal of automobile exhaust systems (ca. 1945-1975) containing asbestos gaskets. A total of 16 pre-1974 vehicles with old or original exhaust systems were studied. Of the 16 vehicles, 12 contained asbestos gaskets in the exhaust system and two vehicles had asbestos lining inside the muffler. A total of 82 samples (23 personal, 38 bystander, and 21 indoor background) were analyzed by Phase Contrast Microscopy (PCM) and 88 samples (25 personal, 41 bystander, and 22 indoor background) by Transmission Electron Microscopy (TEM). Only seven of 25 worker samples analyzed by TEM detected asbestos fibers and 18 were below the analytical sensitivity limit (mean 0.013 f/cc, range 0.001-0.074 f/cc). Applying the ratio of asbestos fibers:total fibers (including non-asbestos) as determined by TEM to the PCM results showed an average (1 h) adjusted PCM worker exposure of 0.018 f/cc (0.002-0.04 f/cc). The average (1 h) adjusted PCM airborne concentration for bystanders was 0.008 f/cc (range 0.0008-0.015 f/cc). Assuming a mechanic can replace four automobile single exhaust systems in 1 workday, the estimated 8-h time-weighted average (TWA) for a mechanic performing this work was 0.01 f/cc. Under a scenario where a mechanic might repeatedly conduct exhaust work, these results suggest that exposures to asbestos from work with automobile exhaust systems during the 1950s through the 1970s containing asbestos gaskets were substantially below 0.1 f/cc, the current PEL for chrysotile asbestos, and quite often were not detectable.

We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

The Savannah River Site (SRS) is one of the largest facilities in the nation's nuclear weapons complex. To date, little information has been published regarding radiation risk estimates derived from epidemiological studies of SRS workers. As part of an ongoing epidemiological cohort study of SRS workers, we have assessed the suitability of the Site's personnel radiation dosimetry information for use in epidemiological analyses. This paper provides information on historical dosimetry methods, recording practices, and the completeness of computerized dosimetry information for workers employed at SRS during the period 1951-1989, when the site was operated by the du Pont Company. The study includes 18,883 workers hired at SRS between 1951 and 1987 who were employed for at least 90 days. Documents relating to external radiation dosimetry methods were reviewed, recorded doses were examined to evaluate recording practices, and the completeness of monitoring was assessed by comparing employment history and computerized dosimetry records, and by implementing a "nearby" procedure for estimating values for missing annual dosimetry records. Dosimeter technology evolved over this period from two-element film dosimeters to multielement thermoluminescent dosimeters. Dosimetry measurements were recorded consistently in 0.05 millisievert (mSv) increments. Prior to 1973, recording thresholds of 0.10-0.15 mSv were used while from 1973 to 1989 a recording threshold of 0.05 mSv was used. We abstracted nearly 3 person-Sv of dosimetry information that was available in hardcopy but not in computerized format. The collective dose from the computerized and abstracted records totaled 512.1 person-Sv. A "nearby" method was used to estimate dose values for 13,812 employment-years for which dosimetry information was not available. The average estimated value was 0.6 mSv and the assigned collective dose derived via the "nearby" procedure was 8.7 person-Sv. The consistency of dosimetry practices at SRS and the completeness of historical dosimetry records are supportive of their use in epidemiologic research.

The Feed Materials Production Center (FMPC) at Fernald, Ohio produced uranium metal products for use in Department of Energy defense programs. Radium-contaminated waste material was stored on-site in two K-65 silos on the west side of the facility and provided a source of 222Ra. The initial objective of this study was to estimate radon exposures to employees at FMPC working from 1952 to 1988. A modified Gaussian plume model was used to estimate exposures to workers. In an effort to validate these model-based estimates, we used 138 CR-39 film assays from window glass sampled in buildings throughout the site. Results from the CR-39 assays indicated a second substantial source of radon, the smaller Q-11 silos located in the production area. A response-surface regression analysis using a cubic spline model was fit to the CR-39 data to estimate 210Po surface activity levels at geographic coordinates throughout the facility. Knowledge of the age of the glass, the amount of contaminated waste in the Q-11 silos, and 210Po decay rates were used to estimate annual exposures to radon decay products (WLM: working level months). Estimated WLM levels associated with the Q-11 source term indicated that employees working in the vicinity during the period when they were filled with radium-contaminated waste (1952-1958) received substantially higher radon exposures than those from the K-65 source during this period. Results of the two models, corresponding to the K-65 and Q-11 sources, were combined to estimate WLM levels by year for each of the 7143 Fernald workers during the period 1952-1988. Estimated cumulative exposures to individual workers ranged from <0.5 to 751 WLM. Estimated radon exposures from this newly discovered source have important implications for future epidemiologic studies of lung cancer in workers at the Fernald facility.

Although occupational benzene exposure of refinery workers has been studied for decades, no extensive analysis of historical industrial hygiene data has been performed focusing on airborne concentrations at specific refineries and tasks. This study characterizes benzene exposures at the ExxonMobil Baytown, TX, refinery from 1978 to 2006 to understand the variability in workers' exposures over time and during different job tasks. Exposures were grouped by operational status, job title, and tasks. More than 9000 industrial hygiene air samples were evaluated; approximately 4000 non-task (> 3 h) and 1000 task-related (< 3 h) personal samples were considered. Each sample was assigned to one of 27 job titles, 29 work areas, and 16 task bins (when applicable). Process technicians were sampled most frequently, resulting in the following mean benzene concentrations by area: hydrofiner (n=245, mean=1.3 p.p.m.), oil movements (n=286, mean=0.23 p.p.m.), reformer (n=575, mean=0.10 p.p.m.), tank farm (n=9, mean=0.65 p.p.m.), waste treatment (n=446, mean=0.13 p.p.m.), and other areas (n=460, mean=0.062 p.p.m.). The most frequently sampled task was sample collection (n=218, mean=0.40 p.p.m.). Job title and area did not significantly impact task-related exposures. Airborne concentrations were significantly lower after 1990 than before 1990. Results of this task-focused study may be useful when analyzing benzene exposures at other refineries.

The extent to which drinking water turbidity measurements indicate the risk of gastrointestinal illness is not well understood. Despite major advances in drinking water treatment and delivery, infectious disease can still be transmitted through drinking water in the United States, and it is important to have reliable indicators of microbial water quality to inform public health decisions. The objective of our study was to assess the relationship between gastrointestinal illness, quantified through emergency department visits, and drinking water quality, quantified as raw water and filtered water turbidity measured at the treatment plant. We examined the relationship between turbidity levels of raw and filtered surface water measured at eight major drinking water treatment plants in the metropolitan area of Atlanta, Georgia, and over 240,000 emergency department visits for gastrointestinal illness during 1993-2004 among the population served by these plants. We fit Poisson time-series statistical regression models that included turbidity in a 21-day distributed lag and that controlled for meteorological factors and long-term time trends. For filtered water turbidity, the results were consistent with no association with emergency department visits for gastrointestinal illness. We observed a modest association between raw water turbidity and emergency department visits for gastrointestinal illness. Our results suggest that source water quality may contribute modestly to endemic gastrointestinal illness in the study area. The association between turbidity and emergency department visits for gastrointestinal illness was only observed when raw water turbidity was considered; filtered water turbidity may not serve as a reliable indicator of modest pathogen risk at all treatment plants.

Water ingestion estimates are important for the assessment of risk to human populations of exposure to water-borne pollutants. This paper reports mean and percentile estimates of the distributions of daily average per capita water ingestion for a number of age range groups. The age ranges, based on guidance from the US EPA's Risk Assessment Forum, are narrow for younger ages when development is rapid and wider for older ages when the rate of development decreases. Estimates are based on data from the United States Department of Agriculture's (USDA's) 1994-1996 and 1998 Continuing Survey of Food Intake by Individuals (CSFII). Water ingestion estimates include water ingested directly as a beverage and water added to foods and beverages during preparation at home or in local establishments. Water occurring naturally in foods or added by manufacturers to commercial products (beverage or food) is not included. Estimates are reported in milliliters (ml/person/day) and milliliters per kilogram of body weight (ml/kg/day). As a by-product of constructing estimates in terms of body weight of respondents, distributions of self-reported body weights based on the CSFII were estimated and are also reported here.

Human exposure to Bisphenol A (BPA) is omnipresent. Both the extent of the exposure and its toxicological relevance are controversially discussed. We aim to reliably determine and evaluate the extent of BPA body burden in the German population from 1995 to 2009 based on 600 24 h urine samples and corresponding plasma samples from the Environmental Specimen Bank. We determined total and unconjugated BPA in urine and plasma using on-line solid-phase extraction high-performance liquid chromatography coupled to isotope dilution tandem mass spectrometry with a limit of quantification (LOQ) of 0.1 μg/l. In the stored urines, total BPA was quantifiable in >96% (median: 1.49 μg/l; 95th percentile: 7.37 μg/l), whereas unconjugated BPA was quantifiable only in <15% of the samples. Total BPA concentrations decreased over time, but 24 h urine volumes increased. Therefore, daily intakes calculated from the 24 h urines remained rather constant at a median of 0.037 and a 95th percentile of 0.171 μg BPA/kg body weight/day. In 60 corresponding plasma samples, total BPA levels were generally below the LOQ of 0.1 μg/l and, if quantifiable, most BPA was unconjugated, thus hinting to external contamination. We see total BPA in urine as the most appropriate and robust marker for BPA exposure assessment (if controlled for BPA contamination). Unconjugated BPA in urine and unconjugated or total BPA in plasma where contamination or breakdown of the glucuronide cannot be ruled out are of no value for human exposure assessment.

Trihalomethanes (THMs) can form as byproducts during drinking water disinfection, which is crucial for limiting human exposure to disease-causing pathogens. The US Environmental Protection Agency (USEPA), recognizing both the importance of water disinfection for public health protection and potential risks associated with THM exposure, developed disinfection byproduct rules with the parallel goals of ensuring safe drinking water and limiting the levels of THMs in public water systems. The National Health and Nutrition Examination Survey (NHANES) THM blood data can be used as a means for assessing US population exposures to THMs; biomonitoring equivalents (BEs) can provide human health risk-based context to those data. In this paper, we examine the blood THM levels in the 1999-2004 NHANES data to (i) determine weighted population percentiles of blood THMs, (ii) explore whether gender and/or age are associated with blood THM levels, (iii) determine whether temporal trends can be discerned over the 6-year timeframe, and (iv) draw comparisons between population THM blood levels and BEs. A statistically significant decrease in blood chloroform levels was observed across the 1999-2004 time period. Age-related differences in blood chloroform levels were not consistent and no gender-related differences in blood chloroform levels were observed. The concentrations of all four THMs in the blood of US residents from the 2003 to 2004 NHANES dataset are below BEs consistent with the current US EPA reference doses. For bromodichloromethane and dibromochloromethane, the measured median blood concentrations in the United States are within the BEs for the 10(-6) and 10(-4) cancer risk range, whereas measured values for bromoform generally fall below the 10(-6) cancer risk range. These assessments indicate that general population blood concentrations of THMs are in a range considered to be a low to medium priority for risk assessment follow-up, according to the guidelines for interpretation of biomonitoring data using BEs.

Exposure to cadmium, a heavy metal present in cigarettes, can be assessed in both urine and blood. Few studies have compared the properties of concurrent measurements of urine cadmium (uCd) and blood cadmium (bCd) in relation to the duration and timing of a known exposure. In this study, bCd and uCd were modeled with data from the National Health and Nutrition Examination Survey (1999-2010). Adjusted geometric mean bCd and uCd were estimated from regression results. Each 1% higher geometric mean uCd was associated with 0.50% (95% confidence interval: 0.47%-0.54%; R(2)=0.30) higher bCd. In male never-smokers, bCd was 69% (59%-81%) and uCd was 200% (166%-234%) higher at age ≥70 years versus 20-29 years. Ten pack-years (py) of smoking were associated with 13.7% (10.0%-17.4%) higher bCd and 16.8% (12.6%-21.1%) higher uCd in male smokers. The first year after smoking cessation was associated with 53% (48%-58%) lower bCd and 23% (14%-33%) lower uCd in representative males aged 55 years with 20 py smoking. Smoking in the previous 5 days was associated with 55% (40%-71%) higher bCd and 7% (-3%-18%) higher uCd. Results were similar for women. uCd mainly measures long-term exposure and bCd recent exposure, but with noticeable overlap. Epidemiological studies should base the choice of uCd or bCd on the timing of cadmium exposure relevant to the disease under study.Journal of Exposure Science and Environmental Epidemiology advance online publication, 4 September 2013; doi:10.1038/jes.2013.55.

Volunteer studies suggest that showering/bathing with chlorinated tap water contributes to daily chloroform inhalation exposure for the majority of US adults. We used data from the 1999-2000 US National Health and Nutrition Examination Survey (NHANES) and weighted multiple linear regression to test the hypothesis that personal exposure microevents such as showering or spending time at a swimming pool would be significantly associated with chloroform levels in 2-3 day personal air samples. The NHANES data show that eight of 10 US adults are exposed to detectable levels of chloroform. Median (1.13 microg/m(3)), upper percentile (95th, 12.05 microg/m(3)), and cancer risk estimates were similar to those from recent US regional studies. Significant predictors of log personal air chloroform in our model (R(2)=0.34) included age, chloroform concentrations in home tap water, having no windows open at home during the sampling period, visiting a swimming pool during the sampling period, living in a mobile home/trailer or apartment versus living in a single family (detached) home, and being Non-Hispanic Black versus Non-Hispanic White, although the race/ethnicity estimates appear influenced by several outlying observations. Reported showering activity was not a significant predictor of personal air chloroform, possibly due to the wording of the NHANES shower question. The NHANES measurements likely underestimate true inhalation exposures since subjects did not wear sampling badges while showering or swimming, and because of potential undersampling by the passive monitors. Research is needed to quantify the potential difference.

Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.

The impact of the US EPA-required phase-outs starting in 2000-2001 of residential uses of the organophosphate (OP) pesticides chlorpyrifos (CPF) and diazinon (DZN) on preschool children's pesticide exposures was investigated over 2003-2005, in the Raleigh-Durham-Chapel Hill area of North Carolina. Data were collected from 50 homes, each with a child initially of age 3 years (OCh) and a younger child (YCh). Environmental samples (indoor and outdoor air, dust, soil) and child-specific samples (hand surface residue, urine, diet) were collected annually over 24-h periods at each home. Child time-activity diaries and household pesticide use information were also collected. Analytes included CPF and DZN; pentachlorophenol (PCP); 2,4-dichlorophenoxyacetic acid (2,4-D); the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCP); and the DZN metabolite 2-isopropyl-6-methyl-4-pyrimidinol (IMP). Exposures (ng/day) through the inhalation, dietary ingestion, and indirect ingestion were calculated. Aggregate potential doses in ng/kg body weight per day (ng/kg/day) were obtained by summing the potential doses through the three routes of exposure. Geometric mean aggregate potential doses decreased from 2003 to 2005 for both OCh and YCh, with the exception of 2,4-D. Child-specific longitudinal modeling indicated significant declines across time of the potential doses of CPF, DZN, and PCP for both children; declines of IMP for both children, significant only for OCh; a decline of TCP for OCh but an increase of TCP for YCh; and no significant change of 2,4-D for either child. Age-adjusted modeling indicated significant effects of the child's age for all except CPF, and of time for all except PCP and 2,4-D. Within-home variability was small compared with that between homes; variability was smallest for 2,4-D, both within and between homes. The aggregate potential doses of CPF and DZN were well below published reference dose values. These findings show the success of the US EPA restrictions in reducing young children's pesticide exposures.

A subset of private pesticide applicators in the Agricultural Health Study (AHS) epidemiological cohort was monitored around the time of their agricultural use of 2,4-dichlorophenoxyacetic acid (2,4-D) and O,O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate (chlorpyrifos) to assess exposure levels and potential determinants of exposure. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Boom spray or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 microg/l in pre- and post-application urine, respectively (P<0.05 for difference); 0.39 mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 microg/m(3) for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 microg/l in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 microg/m(3) for air concentration. Only 53% of the chlorpyrifos applicators had measurable hand loading results; their median hand loading being 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use, and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the AHS. Results may also be of use in pesticide safety education for reducing exposures to pesticide applicators.

In this study, we investigated the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide exposures of 135 preschool-aged children and their adult caregivers at 135 homes in North Carolina (NC) and Ohio (OH). Participants were randomly recruited from six NC and six OH counties. Monitoring was performed over a 48-h period at the participants' homes. Environmental samples included soil, outdoor air, indoor air, and carpet dust. Personal samples collected by the adult caregivers concerning themselves and their children consisted of solid food, liquid food, hand wipe, and spot urine samples. All samples were analyzed for 2,4-D (free acid form) by gas chromatography/mass spectrometry. 2,4-D was detected in all types of environmental samples but most often in carpet dust samples, with detection frequencies of 83% and 98% in NC and OH, respectively. The median level of 2,4-D in the carpet dust samples was about three times higher in OH homes compared to NC homes (156 vs. 47.5 ng/g, P<0.0002). For personal samples, 2,4-D was more frequently detected in the hand wipe samples from OH participants (>48%) than from NC participants (<9%). Hand wipe levels at the 95th percentile were about five times higher for OH children (0.1 ng/cm(2)) and adults (0.03 ng/cm(2)) than for the NC children (0.02 ng/cm(2)) and adults (<0.005 ng/cm(2)). 2,4-D was detected in more than 85% of the child and adult urine samples in both states. The median urinary 2,4-D concentration was more than twice as high for OH children compared to NC children (1.2 vs. 0.5 ng/ml, P<0.0001); however, the median concentration was identical at 0.7 ng/ml for both NC and OH adults. The intraclass correlation coefficient of reliability for an individual's urinary 2,4-D measurements, estimated from the unadjusted (0.31-0.62) and specific gravity-adjusted (0.37-0.73) values, were somewhat low for each group in this study. The variability in urinary 2,4-D measurements over the 48-h period for both children and adults in NC and OH suggests that several spot samples were needed to adequately assess these participants' exposures to 2,4-D in residential settings. Results from this study showed that children and their adult caregivers in NC and OH were likely exposed to 2,4-D through several pathways at their homes. In addition, our findings suggest that the OH children might have been exposed to higher levels of 2,4-D through the dermal and nondietary routes of exposure than the NC children and the NC and OH adults.

To determine the major factors affecting the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) among county noxious weed applicators in Kansas, we used a regression technique that accounted for multiple days of exposure. We collected 136 12-h urine samples from 31 applicators during the course of two spraying seasons (April to August of 1994 and 1995). Using mixed-effects models, we constructed exposure models that related urinary 2,4-D measurements to weighted self-reported work activities from daily diaries collected over 5 to 7 days before the collection of the urine sample. Our primary weights were based on an earlier pharmacokinetic analysis of turf applicators; however, we examined a series of alternative weighting schemes to assess the impact of the specific weights and the number of days before urine sample collection that were considered. The derived models accounting for multiple days of exposure related to a single urine measurement seemed robust with regard to the exact weights, but less to the number of days considered; albeit the determinants from the primary model could be fitted with marginal losses of fit to the data from the other weighting schemes that considered a different numbers of days. In the primary model, the total time of all activities (spraying, mixing, other activities), spraying method, month of observation, application concentration, and wet gloves were significant determinants of urinary 2,4-D concentration and explained 16% of the between-worker variance and 23% of the within-worker variance of urinary 2,4-D levels. As a large proportion of the variance remained unexplained, further studies should be conducted to try to systematically assess other exposure determinants.

Employment in the manufacture of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) is associated with potential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and elevated serum lipid TCDD concentrations can be measured in workers for decades after terminated occupational exposure. As part of an epidemiological study of 1599 workers employed at a facility in New Plymouth, New Zealand that manufactured 2,4,5-T, serum TCDD concentrations measured in blood samples from 346 workers were used with work history records and a simple pharmacokinetic model in a linear regression to estimate dose rates associated with specific job exposure groups at the facility. The model was used to estimate serum TCDD concentration profiles over time for each individual in the full study group and accounted for 30% of the observed variance in TCDD concentrations in the serum donor subgroup. The model underestimated measured concentrations substantially for eleven individuals in the study group; examination of questionnaire data revealed a variety of activities apart from routine employment at the facility that may have contributed to the measured serum TCDD concentrations. Estimated serum TCDD concentrations were below 300 p.p.t. for all individuals in the cohort over the entire study time period, lower than estimates for other 2,4,5-T worker populations. This finding is consistent with occupational medicine records, which indicated that no cases of chloracne were ever diagnosed among workers employed on the site. The modeled exposures will be used in an evaluation of mortality patterns of workers at this facility.

Para-dichlorobenzene (p-DCB) products are widely used in the home and public buildings, leading to exposure to this chemical in indoor environments. In this study, we explored potential relationships between p-DCB exposure and diabetes in US adults by analyzing a nationally representative subsample of 3063 adult participants aged 20-79 years randomly selected for measurement of urinary concentrations of 2,5-dichlorophenol (2,5-DCP), the major metabolite of p-DCB, in the 2007-2010 National Health and Nutrition Examination Survey. Median urinary 2,5-DCP concentration was 7.0 μg/l (interquartile range: 2.1-29.9). Of the participants, 560 (13.6%) were diabetic. A dose-dependent increase in the prevalence of diabetes was observed in the study participants across quartiles of urinary 2,5-DCP (P-trend<0.0001). After adjusting for potential confounders, individuals in the highest quartile of urinary 2,5-DCP had an increased odds of diabetes (OR=1.59 (95% CI: 1.06, 2.40)) compared with individuals with the lowest quartile. The highest quartile of urinary 2,5-DCP was also positively associated with insulin resistance (adjusted β=0.75; 95% CI: 0.27, 1.24). This study demonstrated a potential association between exposure to p-DCB, measured as urinary concentrations of 2,5-DCP, and diabetes in US adults. Additional epidemiologic and mechanistic studies would further explore these interactions.Journal of Exposure Science and Environmental Epidemiology advance online publication, 1 April 2015; doi:10.1038/jes.2015.19.

Most air pollution and health studies conducted in recent years have examined how a health outcome is related to pollution concentrations from a fixed outdoor monitor. The pollutant effect estimate in the health model used indicates how ambient pollution concentrations are associated with the health outcome, but not how actual exposure to ambient pollution is related to health. In this article, we propose a method of estimating personal exposures to ambient PM(2.5) (particulate matter less than 2.5 microm in diameter) using sulfate, a component of PM(2.5) that is derived primarily from ambient sources. We demonstrate how to use regression calibration in conjunction with these derived values to estimate the effects of personal ambient PM(2.5) exposure on a continuous health outcome, forced expiratory volume in 1 s (FEV(1)), using repeated measures data. Through simulation, we show that a confidence interval (CI) for the calibrated estimator based on large sample theory methods has an appropriate coverage rate. In an application using data from our health study involving children with moderate to severe asthma, we found that a 10 microg/m3 increase in PM(2.5) was associated with a 2.2% decrease in FEV(1) at a 1-day lag of the pollutant (95% CI: 0.0-4.3% decrease). Regressing FEV(1) directly on ambient PM(2.5) concentrations from a fixed monitor yielded a much weaker estimate of 1.0% (95% CI: 0.0-2.0% decrease). Relatively small amounts of personal monitor data were needed to calibrate the estimate based on fixed outdoor concentrations.

Central-site monitors do not account for factors such as outdoor-to-indoor transport and human activity patterns that influence personal exposures to ambient fine-particulate matter (PM(2.5)). We describe and compare different ambient PM(2.5) exposure estimation approaches that incorporate human activity patterns and time-resolved location-specific particle penetration and persistence indoors. Four approaches were used to estimate exposures to ambient PM(2.5) for application to the New Jersey Triggering of Myocardial Infarction Study. These include: Tier 1, central-site PM(2.5) mass; Tier 2A, the Stochastic Human Exposure and Dose Simulation (SHEDS) model using literature-based air exchange rates (AERs); Tier 2B, the Lawrence Berkeley National Laboratory (LBNL) Aerosol Penetration and Persistence (APP) and Infiltration models; and Tier 3, the SHEDS model where AERs were estimated using the LBNL Infiltration model. Mean exposure estimates from Tier 2A, 2B, and 3 exposure modeling approaches were lower than Tier 1 central-site PM(2.5) mass. Tier 2A estimates differed by season but not across the seven monitoring areas. Tier 2B and 3 geographical patterns appeared to be driven by AERs, while seasonal patterns appeared to be due to variations in PM composition and time activity patterns. These model results demonstrate heterogeneity in exposures that are not captured by the central-site monitor.Journal of Exposure Science and Environmental Epidemiology advance online publication, 16 January 2013; doi:10.1038/jes.2012.118.

Although short in duration, air pollutant exposures occurring in non-residential microenvironments (MEs), including restaurants, vehicles and commercial locations, can represent a large fraction of total personal exposures. For the Sources and Composition of Particulate Exposures study, a novel compact sampling system was developed, facilitating simultaneous measurement of highly speciated PM(2.5) mass in a range of commercial and residential locations. This sampler also included 1-min measurements of PM(2.5) mass and ultrafine particle (UFP) counts. Sampling was conducted in a number of MEs (retail stores, restaurants and vehicles) throughout Atlanta. Chemically resolved particulate measurements in these locations are of interest for both exposure scientists and epidemiologists but have typically not been conducted because of logistical constraints associated with sampling these trace constituents. We present measurements from a non-random sample of locations that are limited in their generalizability but provide several promising hypothesis-generating results. PM(2.5) mass concentrations greater than 100  μg/m(3), and UFPs>10(5) particles /cm(3) were measured during several events in the restaurant and vehicle. Somewhat unexpectedly, the grocery store ME, along with the restaurant and vehicle, also had the highest levels of elemental carbon (EC), organic carbon (OC) and most elements. In-vehicle concentrations of soil-related elements (Al, Ca, Fe, K and Ti) and auto-related elements (EC, OC, Zn and Cu) were higher than those measured at a central ambient site. The lowest concentrations for most pollutants were found in the hospital and retail locations. It is questionable whether periodic, high PM concentrations in the grocery store and restaurant pose health risks for customers; however, individuals working in these locations may be exposed to levels of concern.

Personal activity patterns have often been suggested as a source of unexplained variability when comparing personal particulate matter (PM2.5) exposure to modeled data using central site or microenvironmental data. To characterize the effect of personal activity patterns on asthmatic children's personal PM2.5 exposure, data from the Windsor, Ontario Exposure Assessment Study were analyzed. The children spent on an average 67.1±12.7% (winter) and 72.3±22.6% (summer) of their time indoors at home where they received 51.7±14.8% and 66.3±19.0% of their PM2.5 exposure, respectively. In winter, 17.7±5.9% of their time was spent at school where they received 38.6±11.7% of their PM2.5 exposure. In summer, they spent 10.3±11.8% 'indoors away from home', which represented 23.4±18.3% of their PM2.5 exposure. Personal activity codes adapted from those of the National Human Activity Pattern Survey and the Canadian Human Activity Pattern Survey were assigned to the children's activities. Of the over 100 available activity codes, 19 activities collectively encompassed nearly 95% of their time. Generalized estimating equation (GEE) models found that, while indoors at home, relative to daytime periods when sedentary activities were conducted, several personal activities were associated with significantly elevated personal PM2.5 exposures. Indoor playing represented a mean increase in PM2.5 of 10.1 μg/m(3) (95% CI 6.3-13.8) and 11.6 μg/m(3) (95% CI 8.1-15.1) in winter and summer, respectively, as estimated by a personal nephelometer.Journal of Exposure Science and Environmental Epidemiology advance online publication, 1 May 2013; doi:10.1038/jes.2013.20.