JP8 exposure and neurocognitive performance among US Air Force personnel.

Petroleum-based fuels such as jet propellant (JP) 4, JP5, JP8, and jet A1 (JetA) are among the most common occupational chemical exposures encountered by military and civilian workforces. Although acute toxicity following high-level exposures to JP8 and similar chemical mixtures has been reported, the relationship between persistent low-level occupational exposures to jet fuels and both acute and longer-term central nervous system (CNS) function has been comparatively less well characterized. This paper describes results of neurocognitive assessments acquired repeatedly across a work week study design (Friday to Friday) as part of the Occupational JP8 Exposure Neuroepidemiology Study (OJENES) involving U.S. Air Force (AF) personnel with varying levels of exposure to jet fuel (JP8). JP8 exposure levels were quantified using both personal air monitoring and urinary biomarkers of exposure. Neurocognitive performance was evaluated using an objective, standardized battery of tests. No significant associations with neurocognitive performances were observed between individuals having regular contact and those with minimal/no direct contact with JP8 (measured by average work week levels of personal breathing zone exposure). Also, no significant findings were noted between repeated measures of absorbed dose (multi-day pre-shift urinary 1- and 2-naphthol) and reduced proficiency on neurocognitive tasks across the work week. Results suggest that occupational exposure to lower (than regulated standards) levels of JP8 do not appear to be associated with acute, measurable differences or changes in neurocognitive performance.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

BACKGROUND: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. OBJECTIVE: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). METHODS: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. RESULTS: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. CONCLUSIONS: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. CITATION: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760.

Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic.

Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben, propyl-paraben, mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston, MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 h and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval (CI): 41%, 216%) than non-users, whereas their MBP concentrations were only 28% higher (CI: 2%, 62%). Women using cologne/perfume had MEP concentrations 167% (CI: 98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy.

The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments.

In this prospective cohort of women undergoing infertility treatments, we measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used regression models to evaluate the association of BPA with antral follicle count (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume (OV). BPA, detected in >80% of women, had a geometric mean (±GSD) of 1.6±2.0, 1.7±2.1, and 1.5±1.8µg/L for the women contributing to the AFC (n=154), day-3 FSH (n=120), and OV (n=114) analyses, respectively. There was an average decrease in AFC of 12% (95% CI: -23%, -0.6%), 22% (95% CI: -31%, -11%), and 17% (95% CI: -27%, -6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st quartile, respectively (p-trend: <0.001). No association of SG-BPA with FSH or OV was observed. Among women from an infertility clinic, higher urinary BPA concentrations were associated with lower AFC, raising concern for possible accelerated follicle loss and reproductive aging.

Urinary paraben concentrations and ovarian aging among women from a fertility center.

BACKGROUND: Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure. OBJECTIVE: We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts. METHODS: Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures. RESULTS: Of the women enrolled in 2004-2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0-46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were -5.0% (-23.7, 18.4) and -16.3% (-30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (-0.26, 2.57) and 1.02 IU/L (-0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume. CONCLUSIONS: PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies.

Postural sway and exposure to jet propulsion fuel 8 among US Air Force personnel.

OBJECTIVE: To determine whether short-term jet propulsion fuel 8 (JP-8) exposure is associated with balance measurements in JP-8-exposed air force personnel. METHODS: As part of a larger neuroepidemiology study, balance tasks were completed by JP-8-exposed individuals (n = 37). Short-term JP-8 exposure was measured using personal breathing zone levels and urinary biomarkers. Multivariate linear regression analyses were conducted to examine the relationship between workday JP-8 exposure and postural sway. RESULTS: Balance control decreased as the task became more challenging. Workday exposure to JP-8, measured by either personal air or urinary metabolite levels, was not significantly related to postural sway. Increases in workday postural sway were associated with demographic variables, including younger age, being a current smoker, and higher body mass index. CONCLUSION: Results suggest that short-term workday JP-8 exposure does not significantly contribute to diminished balance control.

Predictors and variability of urinary paraben concentrations in men and women, including before and during pregnancy.

BACKGROUND: Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. OBJECTIVE: We evaluated predictors and variability of urinary paraben concentrations. METHODS: We measured urinary concentrations of methyl (MP), propyl (PP), and butyl paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). RESULTS: Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 µg/L (MP), 24.2 µg/L (PP), and 0.70 µg/L (BP). Urinary MP and PP concentrations were 4.6 and 7.8 times higher in women than men, respectively, and concentrations of both MP and PP were 3.8 times higher in African Americans than Caucasians. MP and PP concentrations were slightly more variable in women (ICC = 0.42, 0.43) than men (ICC = 0.54, 0.51), and were weakly correlated between partners (r = 0.27-0.32). Among 129 pregnant women, urinary paraben concentrations were 25-45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). CONCLUSIONS: Urinary paraben concentrations were more variable in women compared with men, and during pregnancy compared with before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual's exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure.

Characterization of inhalation exposure to jet fuel among U.S. Air Force personnel.

BACKGROUND: Jet propulsion fuel-8 (JP-8) is the primary jet fuel used by the US military, collectively consuming ~2.5 billion gallons annually. Previous reports suggest that JP-8 is potentially toxic to the immune, respiratory, and nervous systems. The objectives of this study were to evaluate inhalation exposure to JP-8 constituents among active duty United States Air Force (USAF) personnel while performing job-related tasks, identify significant predictors of inhalation exposure to JP-8, and evaluate the extent to which surrogate exposure classifications were predictive of measured JP-8 exposures. METHODS: Seventy-three full-time USAF personnel from three different air force bases were monitored during four consecutive workdays where personal air samples were collected and analyzed for benzene, ethylbenzene, toluene, xylenes, total hydrocarbons (THC), and naphthalene. The participants were categorized a priori into high- and low-exposure groups, based on their exposure to JP-8 during their typical workday. Additional JP-8 exposure categories included job title groups and self-reported exposure to JP-8. Linear mixed-effects models were used to evaluate predictors of personal air concentrations. RESULTS: The concentrations of THC in air were significantly different between a priori exposure groups (2.6 mg m(-3) in high group versus 0.5 mg m(-3) in low, P < 0.0001), with similar differences observed for other analytes in air. Naphthalene was strongly correlated with THC (r = 0.82, P < 0.0001) and both were positively correlated with the relative humidity of the work environment. Exposures to THC and naphthalene varied significantly by job categories based on USAF specialty codes and were highest among personnel working in fuel distribution/maintenance, though self-reported exposure to JP-8 was an even stronger predictor of measured exposure in models that explained 72% (THC) and 67% (naphthalene) of between-worker variability. In fact, both self-report JP-8 exposure and a priori exposure groups explained more between-worker variability than job categories. CONCLUSIONS: Personal exposure to JP-8 varied by job and was positively associated with the relative humidity. However, self-reported exposure to JP-8 was an even stronger predictor of measured exposure than job title categories, suggesting that self-reported JP-8 exposure is a valid surrogate metric of exposure when personal air measurements are not available.

Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy.

BACKGROUND: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy. OBJECTIVE: We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure. METHODS: We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure. RESULTS: Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA. CONCLUSIONS: Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended.

Urinary biomarkers of occupational jet fuel exposure among Air Force personnel.

There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8.

The Occupational JP8 Exposure Neuroepidemiology Study (OJENES): repeated workday exposure and central nervous system functioning among US Air Force personnel.

One of the most prevalent workplace chemical exposures historically and currently confronting the global military and civilian workforce is jet propellant (JP) fuel (e.g., JP4, JP5, JP8, jet A1), a complex mixture of numerous hydrocarbon compounds and additives. To date, numerous protective and preventive strategies (e.g., federal exposure limits, workplace procedure protocols, protective gear such as goggles, respirator use, gloves, and coveralls) have been put in place to minimize acutely toxic exposure levels. However, questions remain regarding the effect of repeated exposures at lower (than regulated) levels of JP fuel. The Occupational JP8 Exposure Neuroepidemiology Study (OJENES) was designed to examine the relationships between occupational JP8 exposure over multiple, repeated workdays and specific aspects of central nervous system (CNS) functioning among Air Force (AF) personnel. In this report, we present the OJENES methodology, descriptive findings related to participant characteristics, JP8 exposure levels observed over a work week among higher and lower exposure groups, and neuropsychological task performances at the first study assessment. Results indicated minimal differences between participants in the high and lower exposure groups in terms of descriptive characteristics, other than daily JP8 exposure levels (p<0.001). In addition, neuropsychological task performances for most task measures were not found to be significantly different from reported reference ranges. These findings demonstrated that confounding and misclassification of exposure and outcome status are not major concerns for the study. Therefore, future OJENES analyses targeting the more focused research questions regarding associations between JP8 exposure and CNS functioning are likely to provide valid conclusions, as they will be less influenced by these research biases.

Inhalation exposure to jet fuel (JP8) among U.S. Air Force personnel.

As jet fuel is a common occupational exposure among military and civilian populations, this study was conducted to characterize jet fuel (JP8) exposure among active duty U.S. Air Force personnel. Personnel (n = 24) were divided a priori into high, moderate, and low exposure groups. Questionnaires and personal air samples (breathing zone) were collected from each worker over 3 consecutive days (72 worker-days) and analyzed for total hydrocarbons (THC), benzene, toluene, ethylbenzene, xylenes, and naphthalene. Air samples were collected from inside the fuel tank and analyzed for the same analytes. Linear mixed-effects models were used to evaluate the exposure data. Our results show that the correlation of THC (a measure of overall JP8 inhalation exposure) with all other analytes was moderate to strong in the a priori high and moderate exposure groups combined. Inhalation exposure to all analytes varied significantly by self-reported JP8 exposure (THC levels higher among workers reporting JP8 exposure), a priori exposure group (THC levels in high group > moderate group > low group), and more specific job task groupings (THC levels among workers in fuel systems hangar group > refueling maintenance group > fuel systems office group > fuel handling group > clinic group), with task groupings explaining the most between-worker variability. Among highly exposed workers, statistically significant job task-related predictors of inhalation exposure to THC indicated that increased time in the hangar, working close to the fuel tank (inside > less than 25 ft > greater than 25 ft), primary job (entrant > attendant/runner/fireguard > outside hangar), and performing various tasks near the fuel tank, such as searching for a leak, resulted in higher JP8 exposure. This study shows that while a priori exposure groups were useful in distinguishing JP8 exposure levels, job task-based categories should be considered in epidemiologic study designs to improve exposure classification. Finally, the strong correlation of THC with naphthalene suggests that naphthalene may be an appropriate surrogate of JP8 exposure. [Supplementary materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a pdf file containing a table detailing concentrations of JP8 components.].