Bisphenol a affects neurodevelopmental gene expression, cognitive function, and neuromuscular synaptic morphology in Drosophila melanogaster.

Bisphenol A (BPA) is an environmentally prevalent endocrine disrupting chemical that can impact human health and may be an environmental risk factor for neurodevelopmental disorders. BPA has been associated with behavioral impairment in children and a variety of neurodevelopmental phenotypes in model organisms. We used Drosophila melanogaster to explore the consequences of developmental BPA exposure on gene expression, cognitive function, and synapse development. Our transcriptome analysis indicated neurodevelopmentally relevant genes were predominantly downregulated by BPA. Among the misregulated genes were those with roles in learning, memory, and synapse development, as well as orthologs of human genes associated with neurodevelopmental and neuropsychiatric disorders. To examine how gene expression data corresponded to behavioral and cellular phenotypes, we first used a predator-response behavioral paradigm and found that BPA disrupts visual perception. Further analysis using conditioned courtship suppression showed that BPA impairs associative learning. Finally, we examined synapse morphology within the larval neuromuscular junction and found that BPA significantly increased the number of axonal branches. Given that our findings align with studies of BPA in mammalian model organisms, this data indicates that BPA impairs neurodevelopmental pathways that are functionally conserved from invertebrates to mammals. Further, because Drosophila do not possess classic estrogen receptors or estrogen, this research suggests that BPA can impact neurodevelopment by molecular mechanisms distinct from its role as an estrogen mimic.

Assessing lead-contaminated drinking water in a large academic institution: a case study.

Drinking water is an important source of lead exposure, and definitively characterizing the sources of lead in drinking water, particularly in large institutional settings, can be time-consuming and costly. This study examined lead concentrations in drinking water at a large university, focusing on variability in first-draw samples and variability with dispensed volume. Over 350 sources were sampled twice by independent groups, and while 78% of these samples were within 2.5 µg/L, almost 10% differed by >10 µg/L. In both sampling events, approximately 50% of sources had lead concentrations >1 µg/L, 6% were >15 µg/L, and 30% were between 1 and 15 µg/L. The highest lead concentration detected was 400 µg/L, with five sources >100 µg/L. Nine sources were sampled more intensively and six had first-draw sample ranges >5 µg/L. Lead concentration versus dispensed volume profiles indicated that while most sources had decreasing lead concentrations after the first draw, others had maximum lead concentrations at higher dispensed volumes. The variability observed suggests that assessments using only one or two samples per source may not identify all sources with elevated lead concentrations, and management strategies should account for this possibility.

Nitro-PAH exposures of occupationally-exposed traffic workers and associated urinary 1-nitropyrene metabolite concentrations.

The assessment of occupational exposure to diesel exhaust (DE) is important from an epidemiological perspective. Urinary biomarkers of exposure have been proposed as a novel approach for measuring exposure to DE. In this study, we measured the concentrations of two urinary metabolites of 1-nitropyrene (1NP), a nitrated polycyclic aromatic hydrocarbon that has been suggested as a molecular marker of diesel particulate matter. These two metabolites, 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were determined in urine samples (10mL) from a small group of workers who were occupationally-exposed to vehicle exhaust in Trujillo, Peru, before and after their workshifts. Workshift exposures to 1NP, as well as PM2.5, 2-nitropyrene and 2-nitrofluoranthene, were also measured. Exposures to 1NP were similar in all studied workers, averaging 105±57.9pg/m3 (±standard deviation). Median urinary concentrations of the average of the pre- and post-exposure samples for 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were found to be 3.9 and 2.3pgmetabolite/mg creatinine, respectively in the group of occupationally-exposed subjects (n=17) studied. A direct relationship between workshift exposure to 1NP and urinary 1NP metabolites concentrations was not observed. However, the 1NP exposures and the creatinine-corrected urinary concentrations of the hydroxynitropyrene metabolites in these Peruvian traffic workers were similar to occupationally-exposed taxi drivers in Shenyang, China, and were higher than biomarker levels in office workers from Trujillo without occupational exposure to vehicle exhaust. This study provides further evidence that urinary metabolites of 1NP are associated with exposure to DE and may serve as a useful exposure biomarker.

Evaluating Contaminants of Emerging Concern as tracers of wastewater from septic systems.

Bacterial and nutrient contamination from anthropogenic sources impacts fresh and marine waters, reducing water quality and restricting recreational and commercial activities. In many cases the source of this contamination is ambiguous, and a tracer or set of tracers linking contamination to source would be valuable. In this work, the effectiveness of utilizing a suite of Contaminants of Emerging Concern (CECs) as tracers of bacteria from human septic system effluent is investigated. Field sampling was performed at more than 20 locations over approximately 18 months and analyzed for a suite of CECs and fecal coliform bacteria. The sampling locations included seeps and small freshwater discharges to the shoreline. Sites were selected and grouped according to level of impact by septic systems as determined by previous field sampling programs. A subset of selected locations had been positively identified as being impacted by effluent from failing septic systems through dye testing. The CECs were selected based on their predominant use, their frequency of use, and putative fate and transport properties. In addition, two rounds of focused sampling were performed at selected sites to characterize short-term variations in CEC and fecal coliform concentrations, and to evaluate environmental persistence following source correction activities. The results indicate that a suite of common use compounds are suitable as generalized tracers of bacterial contamination from septic systems and that fate and transport properties are important in tracer selection. Highly recalcitrant or highly labile compounds likely follow different loss profiles in the subsurface compared to fecal bacteria and are not suitable tracers. The use of more than one tracer compound is recommended due to source variability of septic systems and to account for variations in the subsurface condition. In addition, concentrations of some CECs were measured in receiving waters at levels which suggested the potential for environmental harm, indicating that the possible risk presented from these sources warrants further investigation.

Evaluation of urinary metabolites of 1-nitropyrene as biomarkers for exposure to diesel exhaust in taxi drivers of Shenyang, China.

Diesel exhaust (DE) is a significant contributor to the toxicity associated with particulate matter (PM). 1-Nitropyrene (1-NP) has been used as a molecular marker for DE, and the urinary metabolites of 1-NP have been proposed as biomarkers for exposure to DE. In this study, several urinary 1-NP metabolites were evaluated for their utility as markers of short-term exposures to DE. The study population was a cohort of 24 taxi drivers from Shenyang, China, who submitted urine samples collected before, after, and the next morning following their workshifts. The urinary metabolites studied were isomers of hydroxy-1-nitropyrene (3-, 6-, 8- OHNPs) and hydroxy-N-acetyl-1-aminopyrene (3-,6-, 8-OHNAAPs). Exposure to DE was estimated based on exposure to 1-NP in air samples collected during and after the driver's workshift; 6- and 8-OHNP, and 8-OHNAAP were consistently detected in the drivers' urine. Concentrations of the metabolites in the taxi drivers' urine were greater than metabolite levels previously reported in non-occupationally exposed subjects; however no associations were observed between subject-specific exposures to 1-NP and urinary metabolites measured at the end of the workshift or in the next morning void. Significant autocorrelation was observed in metabolite levels in successive urine samples, from which half-lives for urinary elimination of ~10-12 h were estimated. These observations suggest that, in an occupational setting, urinary 1-NP metabolites may be more suitable as markers of ongoing exposure (timescales of several days) rather than indicators of acute exposure associated with single workshifts.

Exposures to particulate air pollution and nitro-polycyclic aromatic hydrocarbons among taxi drivers in Shenyang, China.

Exposures to particulate matter (PM) of both 10-2.5 microm (PM(10-2.5)) and below 2.5 microm (PM(2.5)) were measured for a cohort of taxi drivers in Shenyang, China, during August 2007. PM samples were collected inside and outside the taxi during the drivers' workshifts, and also inside the drivers' homes when they were off-shift. Ambient PM samples were also collected at a stationary location in Shenyang. Elemental carbon (EC) and organic carbon (OC) were also measured in PM collected on quartz filters inside the taxis as well as at the stationary site. Concentrations of three nitro-polycyclic aromatic hydrocarbons (NPAHs), 1-nitropyrene (1NP), 2-nitropyrene (2NP), and 2-nitrofluoranthene (2NFl), were determined in extracts of the PM samples by using a 2D-HPLC-MS/MS method. The 2NP and 2NFl concentrations did not change substantially with sampling location, but the 1NP concentrations were much higher in samples collected inside and outside the taxis as compared with sampling locations that were more removed from traffic. Concentration ratios of specific NPAHs were used to assess the atmospheric conditions in Shenyang during the sampling period. The relatively high ratios of 2NFl/1NP ( approximately 8-50) indicate an important contribution from secondary NPAH formation to ambient NPAH levels, especially for the nontaxi samples. The ratios of 2NFl/2NP (2.5-4.3) indicate that 2NFl is primarily formed via the hydroxyl-initiated reaction.

Analysis of 1-nitropyrene in air particulate matter standard reference materials by using two-dimensional high performance liquid chromatography with online reduction and tandem mass spectrometry detection.

1-Nitropyrene (1-NP) is enriched in diesel exhaust particulate matter (DPM) relative to other sources of particulate matter (PM), and has been proposed as a marker for DPM. However, in ambient air, 1-NP concentrations are typically in the low pg/m(3) range. Therefore, collection of large volume air samples coupled with extensive sample clean-up procedures has been required to achieve adequate detection limits to measure 1-NP in ambient samples. We report here an improved LC-MS/MS method suitable for the detection and quantification of 1-NP in low volume ambient PM samples. The method involves ultrasonic extraction of ambient PM in organic solvent, concentration of the sample under reduced pressure, and two-dimensional HPLC analysis of the extract. 1-NP is isolated on the first HPLC column, then converted to 1-aminopyrene (1-AP) via online reduction in a column packed with a Pt/Rh catalyst. The 1-AP containing fraction from the first column is refocused on a trapping column, then eluted through a second HPLC column prior to MS/MS detection. Deuterated (d(9)) 1-NP (1-dNP) is added to each sample prior to extraction as an internal standard for quantification of 1-NP. The accuracy and precision of the assay, as applied to ambient particulate standard reference materials are 110+/-5.7% for SRM 1650b, 116+/-7.1% for SRM 2975, 108+/-5.8% for SRM 1649a, and 53+/-9.2% for SRM 1648. The analytical limit of detection was 152 fg on column, and analytical limit of quantitation 221 fg on column. To our knowledge, the sensitivity of this method is comparable with GC-NICI-MS methods while having the advantage of considerably less extensive sample preparation. This method is an approximately 10-fold improvement in sensitivity over HPLC methods utilizing fluorescence and/or chemiluminescence detection.