Detection of respiratory inflammation biomarkers in non-processed exhaled breath condensate samples using reduced graphene oxide.

In this work, we studied several important parameters regarding the standardization of a portable sensor of nitrite, a key biomarker of inflammation in the respiratory tract in untreated EBC samples. The storage of the EBC samples and electrical properties of both EBC samples and the sensor as main standardization parameters were investigated. The sensor performance was performed using differential pulse voltammetry (DPV) in a standard nitrite solution and untreated EBC samples. The storage effect was monitored by comparing sensor data of fresh and stored samples for one month at -80 °C. Results show, on average, a 20 percent reduction of peak current for stored solutions. The sensor's performance was compared with a previous EBC nitrite sensor and chemiluminescence method. The results demonstrate a good correlation between the present sensor and chemiluminescence for low nitrite concentrations in untreated EBC samples. The electrical behavior of the sensor and electrical variation between EBC samples were characterized using methods such as noise analysis, electrochemical impedance spectroscopy (EIS), electrical impedance (EI), and voltage shift. Data show that reduced graphene oxide (rGO) has lower electrical noise and a higher electron transfer rate regarding nitrite detection. Also, a voltage shift can be applied to calibrate the data based on the electrical variation between different EBC samples. This result makes it easy to calibrate the electrical difference between EBC samples and have a more reproducible portable chip design without using bulky EI instruments. This work helps detect nitrite in untreated and pure EBC samples and evaluates critical analytical EBC properties essential for developing portable and on-site point-of-care sensors.

Reactions and Products of Squalene and Ozone: A Review.

This critical review describes the squalene-ozone (SqOz) reaction, or squalene ozonolysis. Ambient ozone penetrates indoors and drives indoor air chemistry. Squalene, a component of human skin oil, contains six carbon-carbon double bonds and is very reactive with ozone. Bioeffluents from people contribute to indoor air chemistry and affect the indoor air quality, resulting in exposures because people spend the majority of their time indoors. The SqOz reaction proceeds through various formation pathways and produces compounds that include aldehydes, ketones, carboxylic acids, and dicarbonyl species, which have a range of volatilities. In this critical review of SqOz chemistry, information on the mechanism of reaction, reaction probability, rate constants, and reaction kinetics are compiled. Characterizations of SqOz reaction products have been done in laboratory experiments and real-world settings. The effect of multiple environmental parameters (ozone concentration, air exchange rate (AER), temperature, and relative humidity (RH)) in indoor settings are summarized. This critical review concludes by identifying the paucity of available exposure, health, and toxicological data for known reaction products. Key knowledge gaps about SqOz reactions leading to indoor exposures and adverse health outcomes are provided as well as an outlook on where the field is headed.

Modeling Effects of Spatial Heterogeneities and Layered Exposure Interventions on the Spread of COVID-19 across New Jersey.

COVID-19 created an unprecedented global public health crisis during 2020-2021. The severity of the fast-spreading infection, combined with uncertainties regarding the physical and biological processes affecting transmission of SARS-CoV-2, posed enormous challenges to healthcare systems. Pandemic dynamics exhibited complex spatial heterogeneities across multiple scales, as local demographic, socioeconomic, behavioral and environmental factors were modulating population exposures and susceptibilities. Before effective pharmacological interventions became available, controlling exposures to SARS-CoV-2 was the only public health option for mitigating the disease; therefore, models quantifying the impacts of heterogeneities and alternative exposure interventions on COVID-19 outcomes became essential tools informing policy development. This study used a stochastic SEIR framework, modeling each of the 21 New Jersey counties, to capture important heterogeneities of COVID-19 outcomes across the State. The models were calibrated using confirmed daily deaths and SQMC optimization and subsequently applied in predictive and exploratory modes. The predictions achieved good agreement between modeled and reported death data; counterfactual analysis was performed to assess the effectiveness of layered interventions on reducing exposures to SARS-CoV-2 and thereby fatality of COVID-19. The modeling analysis of the reduction in exposures to SARS-CoV-2 achieved through concurrent social distancing and face-mask wearing estimated that 357 [IQR (290, 429)] deaths per 100,000 people were averted.

Biomonitoring: A tool to assess PFNA body burdens and evaluate the effectiveness of drinking water intervention for communities in New Jersey.

Elevated perfluorononanoic acid (PFNA) levels, one of many manmade per- and polyfluoroalkyl substances (PFAS), were detected in public water systems/private wells in New Jersey communities. Interventions to end exposure through drinking water were carried out from 2014 to 2016. To evaluate the effectiveness of interventions, a community biomonitoring study was conducted for the communities between 2017 and 2020. A convenience sampling design was used with 120 participants in Year 1 between ages of 20-74 who consumed PFNA-contaminated water. Three blood samples, one year apart, were drawn from each participant and completed for 99 participants. Separated serum samples were measured for 12 PFAS including PFNA. Questionnaires were administered to collect information on demographics and potential sources. Drinking water and house dust collected at the first visit were analyzed for 14 PFAS including PFNA. The PFNA sera levels (Year 1) found 84 out of 120 (70%) participants were higher than the 95th percentile of a nationally representative sample of US adults (NHANES2015-16). Current drinking water and house dust were not significant contributing sources for the study participants. On average, PFNA sera levels were 12 ± 16% (Year 2) and 27 ± 16% (Year 3) lower than the level measured in Year 1 (p < 0.01). The PFNA half-life was estimated around 3.52 years, using a mixed model from 68 high-exposed participants (>95th percentile of NHANES2015-16) with controlling for physiological covariates. The decline in adult serum PFNA levels seen in the years following a community drinking water intervention suggests the intervention effectively reduced PFNA exposure via drinking water.

Exploring the utility of robots in exposure studies.

Obtaining valid, reliable quantitative exposure data can be a significant challenge for industrial hygienists, exposure scientists, and other health science professionals. In this proof-of-concept study, a robotic platform was programmed to perform a simple task as a plausible alternative to human subjects in exposure studies for generating exposure data. The use of robots offers several advantages over the use of humans. Research can be completed more efficiently and there is no need to recruit, screen, or train volunteers. In addition, robots can perform tasks repeatedly without getting tired allowing for collection of an unlimited number of measurements using different chemicals to assess exposure impacts from formulation changes and new product development. The use of robots also eliminates concerns with intentional human exposures while removing health research ethics review requirements which are time consuming. In this study, a humanoid robot was programmed to paint drywall, while volatile organic compounds were measured in air for comparison to model estimates. The measured air concentrations generally agreed with more advanced exposure model estimates. These findings suggest that robots have potential as a methodology for generating exposure measurements relevant to human activities, but without using human subjects.

The Impact of Device Settings, Use Patterns, and Flavorings on Carbonyl Emissions from Electronic Cigarettes.

Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemicals emitted from e-cigarettes such as carbonyls. However, the levels of various carbonyl compounds under real-world vaping conditions have been understudied. This study evaluated the levels of carbonyl compounds (e.g., formaldehyde, acetaldehyde, glyoxal, and diacetyl, etc.) under various device settings (i.e., power output), vaping topographies, and e-liquid compositions (i.e., base liquid, flavor types). The results showed that e-vapor carbonyl levels were the highest under higher power outputs. The propylene glycol (PG)-based e-liquids generated higher formaldehyde and acetaldehyde than vegetable glycerin (VG)-based e-liquids. In addition, fruit flavored e-liquids (i.e., strawberry and dragon fruit) generated higher formaldehyde emissions than mint/menthol and creamy/sweet flavored e-liquids. While single-top coils formed 3.5-fold more formaldehyde per puff than conventional cigarette smoking, bottom coils generated 10-10,000 times less formaldehyde per puff. In general, increases in puff volume and longer puff durations generated significantly higher amounts of formaldehyde. While e-cigarettes emitted much lower levels of carbonyl compounds compared to conventional cigarettes, the presence of several toxic carbonyl compounds in e-cigarette vapor may still pose potential health risks for users without smoking history, including youth. Therefore, the public health administrations need to consider the vaping conditions which generated higher carbonyls, such as higher power output with PG e-liquid, when developing e-cigarette product standards.

Species-level evaluation of the human respiratory microbiome.

BACKGROUND: Changes to human respiratory tract microbiome may contribute significantly to the progression of respiratory diseases. However, there are few studies examining the relative abundance of microbial communities at the species level along the human respiratory tract. FINDINGS: Bronchoalveolar lavage, throat swab, mouth rinse, and nasal swab samples were collected from 5 participants. Bacterial ribosomal operons were sequenced using the Oxford Nanopore MinION to determine the relative abundance of bacterial species in 4 compartments along the respiratory tract. More than 1.8 million raw operon reads were obtained from the participants with ∼600,000 rRNA reads passing quality assurance/quality control (70-95% identify; >1,200 bp alignment) by Discontiguous MegaBLAST against the EZ BioCloud 16S rRNA gene database. Nearly 3,600 bacterial species were detected overall (>750 bacterial species within the 5 dominant phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. The relative abundance of bacterial species along the respiratory tract indicated that most microbes (95%) were being passively transported from outside into the lung. However, a small percentage (<5%) of bacterial species were at higher abundance within the lavage samples. The most abundant lung-enriched bacterial species were Veillonella dispar and Veillonella atypica while the most abundant mouth-associated bacterial species were Streptococcus infantis and Streptococcus mitis. CONCLUSIONS: Most bacteria detected in lower respiratory samples do not seem to colonize the lung. However, >100 bacterial species were found to be enriched in bronchoalveolar lavage samples (compared to mouth/nose) and may play a substantial role in lung health.

Per and polyfluoroalkyl substances (PFAS) blood levels after contamination of a community water supply and comparison with 2013-2014 NHANES.

INTRODUCTION: Per and polyfluoroalkyl substances (PFAS), including perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA), were detected in the community water supply of Paulsboro New Jersey in 2009. METHODS: A cross-sectional study enrolled 192 claimants from a class-action lawsuit, not affiliated with this study, who had been awarded a blood test for 13 PFAS. Study participants provided their blood test results and completed a survey about demographics; 105 participants also completed a health survey. Geometric means, 25th, 50th, 75th, and 95th percentiles of exposure of PFNA blood serum concentrations were compared to that of the 2013-2014 NHANES, adjusted for reporting level. Associations between PFNA, PFOA, PFOS, and PFHxS and self-reported health outcomes were assessed using logistic regression. RESULTS: PFNA serum levels were 285% higher in Paulsboro compared with U.S. residents. PFNA serum levels were higher among older compared with younger, and male compared to female, Paulsboro residents. After adjustment for potential confounding, there was a significant association between increased serum PFNA levels and self-reported high cholesterol (OR: 1.15, 95% CI: 1.02, 1.29). DISCUSSION/CONCLUSION: Further investigation into possible health effects of PFAS exposure in Paulsboro and other community settings is warranted. Since exposure has ceased, toxicokinetics of PFAS elimination should be explored.

Pyrethroid levels in toddlers' breathing zone following a simulated indoor pesticide spray.

Application of pyrethroid insecticides in residential settings may result in children's exposures to these chemicals and possible adverse health effects. Household dust is a recognized reservoir for pyrethroids and a potential medium for multi-route pyrethroid exposure. Young children move and play in a manner that resuspends dust, and since their breathing zone is close to the floor, they will have higher inhalation exposure to pesticide-laden dust than other age groups. Directly measuring a toddler's exposure to household dust presents many logistic challenges. We simulated the dust resuspension induced by a toddler using a robot, which also served as a platform to collect air samples at the toddler's breathing zone height. We performed simulated pyrethroid residential spray and dust resuspension experiments on vinyl and carpeted floors. The mean pyrethroid airborne concentrations in the stationary and mobile samples were 0.065 µg/m3 and 0.143 µg/m3 for the vinyl floor with 1 g/m2 dust loading, and 0.034 µg/m3 and 0.061 µg/m3 for the carpeted floor with 10 g/m2 dust loading, respectively. Pyrethroids concentrations in the settled dust samples were significantly lower than that measured in the stationary and mobile samples in the carpeted floor experiments. Thus, the use of stationary samples and settled dust samples may underestimate a toddler's personal inhalation exposure to pyrethroids in residential houses.

Chronic Exposure to Solvents Among Construction Painters: Reductions in Exposure and Neurobehavioral Health Effects.

OBJECTIVE: The aim of this study was to assess the neurobehavioral effects of lifetime solvent exposure by comparing the performance of painters and demographically comparable controls. METHODS: Performance of exposed painters (N = 133) was compared with unexposed tapers, glaziers, or carpenters (N = 78) on the following domains: motor/perceptual speed, visual contrast, attention, working memory/planning, and visual and verbal memory. Lifetime exposure was estimated with questionnaires, field measurements, and paint composition. RESULTS: After controlling for confounders, lifetime solvent exposure did not predict reduction in performance for overall domains of function. Lifetime solvent exposures predicted subtle alterations for individual tests of verbal learning, motor coordination, and visuospatial accuracy. CONCLUSION: Concentrations of solvents in paints have steadily declined during the working lifetime of subjects in this study. Although reduced performance was observed on individual tests, these alterations were not consistent across tests and unlikely to be of clinical significance.

Evaluation of E-Vapor Nicotine and Nicotyrine Concentrations under Various E-Liquid Compositions, Device Settings, and Vaping Topographies.

Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyrine is a product of nicotine dehydrogenation in e-vapor and is a known inhibitor of human cytochrome P450 enzyme, which mediates nicotine metabolism. However, the emission of nicotine and especially nicotyrine from e-cigarettes has not been studied under real-world vaping patterns. This study examined the impact of e-liquid composition, e-cigarette device power output, and vaping topography on nicotine and nicotyrine concentrations under real-world vaping patterns. The amount of nicotine emitted from e-cigarettes vaped at high e-liquid nicotine levels, high device power, and large puff volumes ranged from 0.365 µg/puff to 236 µg/puff and was comparable to the amount of nicotine emitted from regular cigarettes. E-cigarette coil temperatures (200-300 °C) favored the formation of nicotyrine: E-cigarette vaping generated 2- to 63-fold more nicotyrine per unit nicotine emission than conventional cigarette smoking. High nicotyrine emission from e-cigarettes indicates that nicotine metabolism could be potentially interrupted, which could lead to reduced e-cigarette usage, and result in lower exposures to toxic chemicals (e.g., formaldehyde and acetaldehyde). However, higher serum nicotine levels might increase cancer risks by stimulating nicotinic acetylcholine receptors (nAchRs).

Accuracy and practicality of a portable ozone monitor for personal exposure estimates.

Accurate measurements of personal exposure to atmospheric pollutants such as ozone are important for understanding health risks. We tested a new personal ozone monitor (POM; 2B Technologies) for accuracy, precision, and ease of use. The POM's measurements were compared to simultaneous ozone measurements from a 2B Model 205 monitor and a ThermoScientific 49i monitor, and multiple POMs were placed side-by-side to check precision. Tests were undertaken in a controlled environmental facility, outdoors, and in a private residence. Additionally, ten volunteers wore a POM for five days and answered a questionnaire about its ease of use. The POM measured ozone accurately compared to the 49i ozone monitor, with average relative differences of less than 8%. In the controlled environment tests, the POM's ozone measurements did not change in the presence of additional atmospheric constituents with similar absorption lines to ozone, though there may have been a small decrease in precision and accuracy. Precision between POMs varied by environment (r2 = 0.98 outdoors; r2 = 0.3 to 0.9 in controlled lab conditions). Volunteers reported that the POM was reasonably comfortable to wear, although all reported that they felt that it was too noisy. Overall, the POM is a viable option for personal ozone monitoring.

Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide.

We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate (EBC). We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide. The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract, particularly in asthma. We utilized the unique properties of reduced graphene oxide (rGO); specifically, the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes, thus allowing for highly sensitive electrochemical detection with minimal fouling. Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane (PDMS), which was necessary to analyze small EBC sample volumes. The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode. We characterized the performance of the sensors using standard nitrite/buffer solutions, nitrite spiked into EBC, and clinical EBC samples. The sensor demonstrated a sensitivity of 0.21 µA µM-1 cm-2 in the range of 20-100 µM and of 0.1 µA µM-1 cm-2 in the range of 100-1000 µM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix. To benchmark our platform, we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5 µM. This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.

Estimating infants' and toddlers' inhalation exposure to fragrance ingredients in baby personal care products.

Fragrance ingredients are commonly added to many personal care products to provide a pleasant scent, including those intended for babies. While fragrance chemicals have a long history of safe use, at sufficiently high concentrations some may act as respiratory irritants or sensitizers. Little data have been reported on the inhalation exposures to fragrance compounds to infants and toddlers during bathing and lotion applications. This study demonstrates an in vitro method for measuring breathing zone air concentrations of fragrances from bath products and lotions. It employed simulated infant bathing and lotion application events and a robot to mimic a toddler's movement within a bathroom setting. The air concentrations in an infant's breathing zone were between <1 and 5 µg/m3 for each of seven common fragrance ingredients, while that in the breathing zone of toddlers in the bathroom was ≤ 1µg/m3. The air concentrations from the bathing additive were linearly related to their Henry's law constants and from the lotion inversely related to their octanol-air coefficients. The proposed approach can help refine risk estimates from inhalation exposure to fragrances used in baby products and guide future risk assessments of new products' safety for their use in baby bath products.

Source proximity and meteorological effects on residential outdoor VOCs in urban areas: Results from the Houston and Los Angeles RIOPA studies.

Concentrations of volatile organic compounds (VOCs) measured outside homes in Houston, TX and Los Angeles, CA were characterized by the effects of source proximity and meteorological factors. Benzene, toluene, ethylbenzene, m,p-xylene, o-xylene (BTEX), methyl tert butyl ether (MTBE), tetrachloroethylene (perchloroethylene, PCE), and carbon tetrachloride (CCl4) were examined. Multiple stepwise regression analysis converged the best-fit models with predictors from meteorological conditions and the proximity to specific point, area, and mobile sources on the residential outdoor VOC concentrations. Negative associations of wind speed with concentrations demonstrated the effect of dilution by high wind speed. Atmospheric stability increase was associated with concentration increase. Petrochemical source proximity was a significant predictor for BTEX and MTBE concentrations in Houston. Ethylbenzene and xylene source proximity was a significant predictor in Los Angeles. Close proximity to area sources such as scrap metal recycling or dry cleaning facilities increased the MTBE, PCE, and CCl4 concentrations in Houston and Los Angeles. Models for ethylbenzene, m,p-xylene, and MTBE in Houston, and benzene in Los Angeles explained that for the median values of the meteorological factors, homes closest to influential highways would have concentrations that were 1.7-2.2 fold higher than those furthest from these mobile emission sources. If the median distance to sources were used in the models, the VOC concentrations varied 1.7 to 6.6 fold as the meteorological conditions varied over the observed range. These results highlight that each urban area is unique and localized sources need to be carefully evaluated to understand potential contributions to VOC air concentrations near residences, which influence baseline indoor air concentrations and personal exposures. Results of this study could assist in the appropriate design of monitoring networks for community-level sampling. They may also improve the accuracy of exposure models linking emission sources with estimated pollutant concentrations at the residential level.

Evaluation of Diesel Exhaust Continuous Monitors in Controlled Environmental Conditions.

Diesel exhaust (DE) contains a variety of toxic air pollutants, including diesel particulate matter (DPM) and gaseous contaminants (e.g., carbon monoxide (CO)). DPM is dominated by fine (PM2.5) and ultrafine particles (UFP), and can be representatively determined by its thermal-optical refractory as elemental carbon (EC) or light-absorbing characteristics as black carbon (BC). The currently accepted reference method for sampling and analysis of occupational exposure to DPM is the National Institute for Occupational Safety and Health (NIOSH) Method 5040. However, this method cannot provide in-situ short-term measurements of DPM. Thus, real-time monitors are gaining attention to better examine DE exposures in occupational settings. However, real-time monitors are subject to changing environmental conditions. Field measurements have reported interferences in optical sensors and subsequent real-time readings, under conditions of high humidity and abrupt temperature changes. To begin dealing with these issues, we completed a controlled study to evaluate five real-time monitors: Airtec real-time DPM/EC Monitor, TSI SidePak Personal Aerosol Monitor AM510 (PM2.5), TSI Condensation Particle Counter 3007, microAeth AE51 BC Aethalometer, and Langan T15n CO Measurer. Tests were conducted under different temperatures (55, 70, and 80°F), relative humidity (10, 40, and 80%), and DPM concentrations (50 and 200 µg/m(3)) in a controlled exposure facility. The 2-hr averaged EC measurements from the Airtec instrument showed relatively good agreement with NIOSH Method 5040 (R(2) = 0.84; slope = 1.17±0.06; N = 27) and reported ∼17% higher EC concentrations than the NIOSH reference method. Temperature, relative humidity, and DPM levels did not significantly affect relative differences in 2-hr averaged EC concentrations obtained by the Airtec instrument vs. the NIOSH method (p < 0.05). Multiple linear regression analyses, based on 1-min averaged data, suggested combined effects of up to 5% from relative humidity and temperature on real-time measurements. The overall deviations of these real-time monitors from the NIOSH method results were ≤20%. However, simultaneous monitoring of temperature and relative humidity is recommended in field investigations to understand and correct for environmental impacts on real-time monitoring data.

Feasibility and informative value of environmental sample collection in the National Children's Vanguard Study.

BACKGROUND: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples. METHODS: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children's Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009-September 2010 at up to three home visits: pre-pregnancy (n=306), pregnancy (n=807), and 6-months postnatal (n=117). Collections included air for particulate matter ≤2.5 µm (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalomethanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF). RESULTS: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean=89%); all samples except the air PM2.5 samples had collection times <30 min. Informative value was low for water VOCs (median DF=0%) and pesticide floor wipes (median DF=5%). Informative value was moderate for air samples (median DF=35%) and high for water THMs and HAAs (median DF=91% and 75%, respectively). CONCLUSIONS: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies.

Lessons learned from the application of BEES-C: Systematic assessment of study quality of epidemiologic research on BPA, neurodevelopment, and respiratory health.

Epidemiologic studies evaluating associations between biomarkers of exposure to short-lived chemicals and health endpoints in humans face special challenges. Perhaps the most critical challenges are the need to determine the type and optimal number of samples, and the proper timing of specimen collection. Further, as many short-lived chemicals are ubiquitous in the environment, utmost care is required to avoid sample contamination. A separate set of challenges is associated with appropriate interpretation and reporting of results from multiple simultaneous analyses, which are becoming increasingly feasible. The Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals (BEES-C) instrument is specifically designed to evaluate the quality of epidemiologic studies that measure biomarkers of chemicals with short physiologic half-lives. The instrument provides systematic guidance for evaluating 14 different aspects of study quality divided into three broad categories: 1) biomarker selection and measurement, 2) strategy and execution of exposure assessment, and 3) general considerations of study design and reporting. We evaluated the utility of the BEES-C instrument using epidemiologic studies of exposure to bisphenol A and its association with neurodevelopmental and respiratory health indicators. Each BEES-C element was assessed with respect to needed modifications and concordance among reviewers using professional, scientific judgment. Based on this first use of the BEES-C instrument, we found that most of its elements were effective in comparing the quality of available studies, with reviews generally concordant and justifications consistent. However, we note that certain elements would be improved with slight adjustments and that one of the elements appeared redundant and should be removed.

A proposal for assessing study quality: Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument.

The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals present several challenges, including their presence in analytical laboratories and sampling equipment, difficulty in establishing temporal order in cross-sectional studies, short- and long-term variability in exposures and biomarker concentrations, and a paucity of information on the number of measurements required for proper exposure classification. To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for WOE assessments or for peer review of grants or publications. We describe key issues that affect epidemiology studies using biomonitoring data on short-lived chemicals and propose a systematic instrument--the Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument--for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals. Quality criteria for three areas considered fundamental to the evaluation of epidemiology studies that include biological measurements of short-lived chemicals are described: 1) biomarker selection and measurement, 2) study design and execution, and 3) general epidemiological study design considerations. We recognize that the development of an evaluative tool such as BEES-C is neither simple nor non-controversial. We hope and anticipate that the instrument will initiate further discussion/debate on this topic.