Exposure Assessment Study on Lithium-Ion Battery Fire in Explosion Test Room in Battery Testing Facility.

A lithium-ion battery is a rechargeable battery that uses the reversible reduction of lithium ions to store energy and is the predominant battery type in many industrial and consumer electronics. The lithium-ion batteries are essential to ensure they operate safely. We conducted an exposure assessment five days after a fire in a battery-testing facility. We assessed some of the potentially hazardous materials after a lithium-ion battery fire. We sampled total suspended particles, hydrogen fluoride, and lithium with real-time monitoring of particulate matter (PM) 1, 2.5, and 10 micrometers (µm). The area sampling results indicated that primary potential hazardous materials such as dust, hydrogen fluoride, and lithium were below the recommended limits suggested by the Korean Ministry of Labor and the American Conference of Governmental Industrial Hygienists Threshold Limit Values. Based on our assessment, workers were allowed to return to work.

Mode of silver clearance following 28-day inhalation exposure to silver nanoparticles determined from lung burden assessment including post-exposure observation periods.

Recently revised OECD inhalation toxicity testing guidelines require measurements of lung burden immediately after and for periods following exposure for nanomaterials. Lung burden is a function of pulmonary deposition and retention of nanoparticles. Using lung burden studies as per OECD guidelines, it may be possible to assess clearance mechanisms of nanoparticles. In this study, male rats were exposed to silver nanoparticle (AgNP) aerosols (18.1-19.6 nm) generated from a spark generator. Exposure groups consisted of (1) control (fresh air), (2) low (31.2 ± 8.5 µg/m3), (3) moderate (81.8 ± 11.4 µg/m3), and (4) high concentrations (115.6 ± 30.5 µg/m3). Rats were exposed for 6-h/day, 5-days/week for 4 weeks (28-days) based on the revised OECD test guideline 412. Bronchoalveolar lavage (BAL) fluids were collected on post-exposure observation (PEO)-1 and PEO-7 days and analyzed for inflammatory cells and inflammatory biomarkers. The lung burdens of Ag from AgNPs were measured on PEO-1, PEO-7, and PEO-28 days to obtain quantitative mass concentrations per lung. Differential counting of blood cells and inflammatory biomarkers in BAL fluid and histopathological evaluation of lung tissue indicated that exposure to the high concentrations of AgNP aerosol induced inflammation at PEO-1, slowly resolved at PEO-7 and completely resolved at PEO-28 days. Lung burden measurement suggested that Ag from AgNPs was cleared through two different modes; fast and slow clearance. The fast clearance component was concentration-dependent with half-times ranging from two to four days and clearance rates of 0.35-0.17/day-1 from low to high concentrations. The slow clearance had half-times of 100, 57, and 76 days and clearance rates of 0.009, 0.012, and 0.007/day-1 for the high, moderate and low concentration exposure. The exact mechanism of clearance is not known currently. The fast clearance component which was concentration-dependent could be dependent on the dissolution of AgNPs and the slow clearance would be due to slow clearance of the low dissolution AgNPs secondary particles originating from silver ions reacting with biogenic anions. These secondary AgNPs might be cleared by mechanisms other than dissolution such as mucociliary escalation, translocation to the lymphatic system or other organs.

In vitro to in vivo benchmark dose comparisons to inform risk assessment of quantum dot nanomaterials.

Engineered nanomaterials are currently under review for their potential toxicity; however, their use in consumer/commercial products has continued to outpace risk assessments. In vitro methods may be utilized as tools to improve the efficiency of risk assessment approaches. We propose a framework to compare relationships between previously published in vitro and in vivo toxicity assessments of cadmium-selenium containing quantum dots (QDs) using benchmark dose (BMD) and dosimetric assessment methods. Although data were limited this approach was useful for identifying sensitive assays and strains. In vitro studies assessed effects of QDs in three pulmonary cell types across two mouse strains. Significant dose-response effects were modeled and a standardized method of BMD analysis was performed as a function of both exposure dose and dosimetric dose. In vivo studies assessed pulmonary effects of QD exposure across eight mouse strains. BMD analysis served as a basis for relative comparison with in vitro studies. We found consistent responses in common endpoints between in vitro and in vivo studies. Strain sensitivity was consistent between in vitro and in vivo studies, showing A/J mice more sensitive to QDs. Cell types were found to differentially take up QDs. Dosimetric adjustments identified similar sensitivity among cell types. Thus, BMD analysis can be used as an effective tool to compare the sensitivity of different strains, cell types, and assays to QDs. These methods allow for in vitro assays to be used to predict in vivo responses, improve the efficiency of in vivo studies, and allow for prioritization of nanomaterial assessments. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Neurobehavioral assessment of mice following repeated oral exposures to domoic acid during prenatal development.

Domoic acid (DA) is an algal toxin which has been associated with significant neurotoxicity in humans, non-human primates, rodents, and marine mammals. Developmental exposure to DA is believed to result in neurotoxicity that may persist into adulthood. DA is produced by harmful algal blooms of Pseudo-nitzschia, raising concerns about the consumption of contaminated seafood. We evaluated oral exposures to DA during pregnancy in mice. Doses of 0 (vehicle), 1 or 3mg/kg/d of DA were administered by gavage to C57BL/6J mice on gestational days 10 to 17. The offspring were tested for persistent neurobehavioral consequences during early development, adolescence and adulthood. Neurobehavioral tests revealed both dose- and gender-related differences in several neurobehavioral measures, including motor coordination in the rotarod test, behavior in the elevated plus maze, circadian patterns of activity in Phenotyper cages, gait as assessed in the Catwalk, and exploratory activity in the Morris water maze. This study demonstrated significant gender-specific and persistent neurobehavioral effects of repeated prenatal oral exposures to DA at low-dose levels that did not induce toxicity in dams.

Developing the Regulatory Utility of the Exposome: Mapping Exposures for Risk Assessment through Lifestage Exposome Snapshots (LEnS).

BACKGROUND: Exposome-related efforts aim to document the totality of human exposures across the lifecourse. This field has advanced rapidly in recent years but lacks practical application to risk assessment, particularly for children's health. OBJECTIVES: Our objective was to apply the exposome to children's health risk assessment by introducing the concept of Lifestage Exposome Snapshots (LEnS). Case studies are presented to illustrate the value of the framework. DISCUSSION: The LEnS framework encourages organization of exposome studies based on windows of susceptibility for particular target organ systems. Such analyses will provide information regarding cumulative impacts during specific critical periods of the life course. A logical extension of this framework is that regulatory standards should analyze exposure information by target organ, rather than for a single chemical only or multiple chemicals grouped solely by mechanism of action. CONCLUSIONS: The LEnS concept is a practical refinement to the exposome that accounts for total exposures during particular windows of susceptibility in target organ systems. Application of the LEnS framework in risk assessment and regulation will improve protection of children's health by enhancing protection of sensitive developing organ systems that are critical for lifelong health and well-being. https://doi.org/10.1289/EHP1250.

Seasonal and occupational trends of five organophosphate pesticides in house dust.

Since 1998, the University of Washington's Center for Child Environmental Health Risks Research has followed a community-based participatory research strategy in the Lower Yakima Valley of Washington State to assess pesticide exposure among families of Hispanic farmworkers. As a part of this longitudinal study, house dust samples were collected from both farmworker and non-farmworker households, across three agricultural seasons (thinning, harvest and non-spray). The household dust samples were analyzed for five organophosphate pesticides: azinphos-methyl, phosmet, malathion, diazinon, and chlorpyrifos. Organophosphate pesticide levels in house dust were generally reflective of annual use rates and varied by occupational status and agricultural season. Overall, organophosphate pesticide concentrations were higher in the thinning and harvest seasons than in the non-spray season. Azinphos-methyl was found in the highest concentrations across all seasons and occupations. Farmworker house dust had between 5- and 9-fold higher concentrations of azinphos-methyl than non-farmworker house dust. Phosmet was found in 5-7-fold higher concentrations in farmworker house dust relative to non-farmworker house dust. Malathion and chlorpyriphos concentrations in farmworker house dust ranged between 1.8- and 9.8-fold higher than non-farmworker house dust. Diazinon showed a defined seasonal pattern that peaked in the harvest season and did not significantly differ between farmworker and non-farmworker house dust. The observed occupational differences in four out of five of the pesticide residues measured provides evidence supporting an occupational take home pathway, in which workers may bring pesticides home on their skin or clothing. Further, these results demonstrate the ability of dust samples to inform the episodic nature of organophosphate pesticide exposures and the need to collect multiple samples for complete characterization of exposure potential.

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

BACKGROUND: Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. OBJECTIVES: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. METHODS: Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution. RESULTS: The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 µg/L (95% CI: 0.75, 0.85) and 12.30 µg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. CONCLUSIONS: The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.

Longitudinal mercury monitoring within the Japanese and Korean communities (United States): implications for exposure determination and public health protection.

BACKGROUND: Estimates of exposure to toxicants are predominantly obtained from single time-point data. Fish consumption guidance based on these data may be incomplete, as recommendations are unlikely to consider impact from factors such as intraindividual variability, seasonal differences in consumption behavior, and species consumed. OBJECTIVES/METHODS: We studied populations of Korean (n = 108) and Japanese (n = 106) women living in the Puget Sound area in Washington State to estimate mercury exposure based on fish intake and hair Hg levels at two and three time points, respectively. Our goals were to examine changes in hair Hg levels, fish intake behavior, and Hg body burden over time; and to determine if data from multiple time points could improve guidance. RESULTS/CONCLUSION: More than 50 fish species were consumed, with eight species representing approximately three-fourths of fish consumed by the Japanese and 10 species representing approximately four-fifths of fish intake by the Koreans. Fish species responsible for most Hg intake did not change over time; < 10 species accounted for most of the Hg body burden in each population. Longitudinal variability of hair Hg levels changed slowly across the study period. Japanese with hair Hg levels > 1.2 ppm (mean, 2.2 ppm) consumed approximately 150% more fish than those with levels < or = 1.2 ppm (mean, 0.7 ppm). However, because many participants consumed substantial amounts of fish while having hair-Hg levels < or = 1.2 ppm, the nutritional benefits offered from fish consumption should be obtainable without exceeding the RfD. We observed a 100% difference in fish intake between open-ended and 2-week recall fish consumption surveys. Open-ended survey data better represent Hg intake as determined from hair Hg levels. Single time-point fish intake data appear to be adequate for deriving guidance, but caution is warranted, as study is required to determine the significance of the different outcomes observed using the two survey time frames.

Children's inhalation exposure to methamidophos from sprayed potato fields in Washington State: exploring the use of probabilistic modeling of meteorological data in exposure assessment.

We examined the significance of meteorology and postspray volatilization of methamidophos (an organophosphorus insecticide) in assessing potential inhalation risk to children in an agricultural community. We combined fluxes from sources and dispersion modeling with a range of possible local meteorology to create output to study the variability in potential community exposure as a result of changing temperature, wind speeds and wind directions. This work is based on an aerial spray drift study where air sampling measurements of methamidophos were made before, during and after a spray event were used to examine acute inhalation risk for children living in an Eastern Washington State community in close proximity (between 15 and 200 m) to sprayed potato fields. We compared the measured average air concentrations of methamidophos in the community to a "no observed adverse effect level" for subchronic inhalation to characterize acute and subchronic inhalation risks. The baseline estimates of inhalation exposure were below Environment Protection Agency's (EPA) level of concern based on a target margin of exposure of 300. As meteorological conditions during and after spraying influence the amount of material moving into areas where children reside we used historical meteorological data to drive model simulations that predicted likely air residue concentrations under different wind and temperature conditions. We also added variability to the decay constant and initial emission fluxes to create a 2-D simulation of estimated air concentrations in the community near the fields. This work provides a methodological framework for the assessment of air concentrations of pesticides from agricultural sprays in the absence of extended measurements, although including variability from meteorological conditions. The deterministic as well as the probabilistic risk analyses in this study indicated that postspray volatilization in the specific spray situation analyzed (methamidophos applied on potato fields in Eastern Washington) did not pose acute or subchronic risks as defined by the EPA. However, this study did not consider any pathway of exposure other than inhalation (e.g. diet, dermal, etc.) and the risk assessment should be evaluated in that context.

The application of genetic information for regulatory standard setting under the clean air act: a decision-analytic approach.

In 2002, the U.S. Environmental Protection Agency (EPA) released an "Interim Policy on Genomics," stating a commitment to developing guidance on the inclusion of genetic information in regulatory decision making. This statement was followed in 2004 by a document exploring the potential implications. Genetic information can play a key role in understanding and quantifying human susceptibility, an essential step in many of the risk assessments used to shape policy. For example, the federal Clean Air Act (CAA) requires EPA to set National Ambient Air Quality Standards (NAAQS) for criteria pollutants at levels to protect even sensitive populations from adverse health effects with an adequate margin of safety. Asthmatics are generally regarded as a sensitive population, yet substantial research gaps in understanding genetic susceptibility and disease have hindered quantitative risk analysis. This case study assesses the potential role of genomic information regarding susceptible populations in the NAAQS process for fine particulate matter (PM(2.5)) under the CAA. In this initial assessment, we model the contribution of a single polymorphism to asthma risk and mortality risk; however, multiple polymorphisms and interactions (gene-gene and gene-environment) are known to play key roles in the disease process. We show that the impact of new information about susceptibility on estimates of population risk or average risk derived from large epidemiological studies depends on the circumstances. We also suggest that analysis of a single polymorphism, or other risk factor such as health status, may or may not change estimates of individual risk enough to alter a particular regulatory decision, but this depends on specific characteristics of the decision and risk information. We also show how new information about susceptibility in the context of the NAAQS for PM(2.5) could have a large impact on the estimated distribution of individual risk. This would occur if a group were consequently identified (based on genetic and/or disease status), that accounted for a disproportionate share of observed effects. Our results highlight certain conditions under which genetic information is likely to have an impact on risk estimates and the balance of costs and benefits within groups, and highlight critical research needs. As future studies explore more fully the relationship between exposure, genetic makeup, and disease status, the opportunity for genetic information and disease status to play pivotal roles in regulation can only increase.

Computational models of ethanol-induced neurodevelopmental toxicity across species: Implications for risk assessment.

Computational, systems-based approaches can provide a quantitative construct for evaluating risk in the context of mechanistic data. Previously, we developed computational models for the rat, mouse, rhesus monkey, and human, describing the acquisition of adult neuron number in the neocortex during the key neurodevelopmental processes of neurogenesis and synaptogenesis. Here we apply mechanistic data from the rat describing ethanol-induced toxicity in the developing neocortex to evaluate the utility of these models for analyzing neurodevelopmental toxicity across species. Our model can explain long-term neocortical neuronal loss in the rodent model after in utero exposure to ethanol based on inhibition of proliferation during neurogenesis. Our human model predicts a significant neuronal deficit after daily peak BECs reaching 10-20 mg/dl, which is the approximate BEC reached after drinking one standard drink within one hour. In contrast, peak daily BECs of 100 mg/dl are necessary to predict similar deficits in the rat. Our model prediction of increased sensitivity of primate species to ethanol-induced inhibition of proliferation is based on application of in vivo experimental data from primates showing a prolonged rapid growth period in the primate versus rodent neuronal progenitor population. To place our predictions into a broader context, we evaluate the evidence for functional low-dose effects across rats, monkeys, and humans. Results from this critical evaluation suggest subtle effects are evident at doses causing peak BECs of approximately 20 mg/dl daily, corroborating our model predictions. Our example highlights the utility of a systems-based modeling approach in risk assessment.

A system-based approach to interpret dose- and time-dependent microarray data: quantitative integration of gene ontology analysis for risk assessment.

Although microarray technology has emerged as a powerful tool to explore expression levels of thousands of genes or even complete genomes after exposure to toxicants, the functional interpretation of microarray data sets still represents a time-consuming and challenging task. Gene ontology (GO) and pathway mapping have both been shown to be powerful approaches to generate a global view of biological processes and cellular components impacted by toxicants. However, current methods only allow for comparisons across two experimental settings at one particular time point. In addition, the resulting annotations are presented in extensive gene lists with minimal or limited quantitative information, data that are crucial in the application of toxicogenomic data for risk assessment. To facilitate quantitative interpretation of dose- or time-dependent genomic data, we propose to use combined average raw gene expression values (e.g., intensity or ratio) of genes associated with specific functional categories derived from the GO database. We developed an extended program (GO-Quant) to extract quantitative gene expression values and to calculate the average intensity or ratio for those significantly altered by functional gene category based on MAPPFinder results. To demonstrate its application, we applied this approach to a previously published dose- and time-dependent toxicogenomic data set (J. F. Dillman et al., 2005, Chem. Res. Toxicol. 18, 28-34). Our results indicate that the above systems approach can describe quantitatively the degree to which functional gene systems change across dose or time. Additionally, this approach provides a robust measurement to illustrate results compared to single-gene assessments and enables the user to calculate the corresponding ED(50) for each specific functional GO term, important for risk assessment.

Framing scientific analyses for risk management of environmental hazards by communities: case studies with seafood safety issues.

Risk management provides a context for addressing environmental health hazards. Critical to this approach is the identification of key opportunities for participation. We applied a framework based on the National Research Council's (NRC) analytic-deliberative risk management dialogue model that illustrates two main iterative processes: informing and framing. The informing process involves conveying information from analyses of risk issues, often scientific, to all parties so they can participate in deliberation. In the framing process, ideas and concerns from stakeholder deliberations help determine what and how scientific analyses will be carried out. There are few activities through which affected parties can convey their ideas from deliberative processes for framing scientific analyses. The absence of participation results in one-way communication. The analytic-deliberative dialogue, as envisioned by the NRC and promoted by the National Institute of Environmental Health Sciences (NIEHS), underscores the importance of two-way communication. In this article we present case studies of three groups--an Asian and Pacific Islander community coalition and two Native American Tribes--active in framing scientific analyses of health risks related to contaminated seafood. Contacts with these organizations were established or enhanced through a regional NIEHS town meeting. The reasons for concern, participation, approaches, and funding sources were different for each group. Benefits from their activities include increased community involvement and ownership, better focusing of analytical processes, and improved accuracy and appropriateness of risk management. These examples present a spectrum of options for increasing community involvement in framing analyses and highlight the need for increased support of such activities.

Essential role of extracellular matrix (ECM) overlay in establishing the functional integrity of primary neonatal rat Sertoli cell/gonocyte co-cultures: an improved in vitro model for assessment of male reproductive toxicity.

The development of in vitro models for testicular toxicity may provide important tools for investigating specific mechanisms of toxicity in the testis. Although various systems have been reported, their application in toxicological studies has been limited by the poor ability to replicate the complex biochemical, molecular, and functional interactions observed in the testis. In the present study, we evaluated a significantly improved Sertoli cell/gonocyte co-culture (SGC) system that employs a 3-dimensional extracellular matrix Matrigel (ECM) applied as an overlay instead of a substratum. We explored the dose- and time-dependent effects of the addition of such an ECM overlay on cytoskeletal and morphological changes in the SGC system, and the resulting effects on cellular integrity. Furthermore, we correlated the latter effects with the ECM-dependent modulation of stress and survival signaling pathways and, most critically, the expression levels of the spermatogonia-specific protein, c-Kit. Finally, we applied this co-culture system to investigate the dose- and time-dependent effects on the morphology and induction of apoptosis of cadmium. We observed that the dose-dependent addition of an ECM overlay led to an enhanced attachment of Sertoli cells and facilitated the establishment of SGC communication and cytoskeletal structure, with a dramatic improvement in cell viability. The latter was consistent with the observed dose- and time-dependent modulation of both stress signaling pathways (SAPK/JNK) and survival signaling pathways (ERK and AKT) in the presence of the ECM overlay. Furthermore, the dose-dependent stabilization of c-Kit protein expression confirmed the functional integrity of this co-culture system. We conclude that this modified SGC system will provide investigators with a simple, efficient, and highly reproducible alternative in the screen for testicular cell-specific cytotoxicity and the assessment of molecular mechanisms associated with both normal development and reproductive toxicity induced by environmental toxicants.

Assessing the health benefits of air pollution reduction for children.

Benefit-cost analyses of environmental regulations are increasingly mandated in the United States. Evaluations of criteria air pollutants have focused on benefits and costs associated with adverse health effects. Children are significantly affected by the health benefits of improved air quality, yet key environmental health policy analyses have not previously focused specifically on children's effects. In this article we present a "meta-analysis" approach to child-specific health impacts derived from the U.S. Clean Air Act (CAA). On the basis of data from existing studies, reductions in criteria air pollutants predicted to occur by 2010 because of CAA regulations are estimated to produce the following impacts: 200 fewer expected cases of postneonatal mortality; 10,000 fewer asthma hospitalizations in children 1-16 years old, with estimated benefits ranging from 20 million U.S. dollars to 46 million U.S. dollars (1990 U.S. dollars); 40,000 fewer emergency department visits in children 1-16 years old, with estimated benefits ranging from 1.3 million U.S. dollars to 5.8 million U.S. dollars; 20 million school absences avoided by children 6-11 years old, with estimated benefits of 0.7-1.8 billion U.S. dollars; and 10,000 fewer infants of low birth weight, with estimated benefits of 230 million U.S. dollars. Inclusion of limited child-specific data on hospitalizations, emergency department visits, school absences, and low birth weight could be expected to add 1-2 billion U.S. dollars (1990 U.S. dollars) to the 8 billion U.S. dollars in health benefits currently estimated to result from decreased morbidity, and 600 million U.S. dollars to the 100 billion U.S. dollars estimated to result from decreased mortality. These estimates highlight the need for increased consideration of children's health effects. Key needs for environmental health policy analyses include improved information for children's health effects, additional life-stage-specific information, and improved health economics information specific for children.

A model for optimization of biomarker testing frequency to minimize disease and cost: example of beryllium sensitization testing.

A common problem with medical surveillance programs using biomarkers is determining the optimal frequency of testing to minimize adverse health effects and cost. In the case of beryllium-exposed workers, frequency of testing for beryllium sensitization may be especially important. Recent studies indicate a lack of dose response for beryllium sensitization, but do support a dose response for the development of chronic beryllium disease (CBD). Though unproven, this implies that early identification of sensitization and immediate removal from exposure may reduce development of CBD. A model is proposed to project the optimal frequency of sensitization testing using the current beryllium lymphocyte proliferation test (BeLPT) to minimize disease-related costs, assuming that a positive BeLPT will precede CBD. Conversion rates for cumulative exposure to disease development were adapted from the literature and used with testing costs and cost of disease estimates in the model. The model was run assuming several test frequency regimes. Results support the use of periodic testing in line with the annual schedule proposed in the Final Chronic Beryllium Disease Prevention Program Rule (1999) following initial testing within three months of first beryllium exposure. The financial and health benefits of reducing the time from exposure to detection of early disease was also explored with the model and demonstrated as a highly desirable characteristic for an alternative test or improved BeLPT. Limitations of the approach are discussed as well as options for adapting this biomarker optimization methodology to consider biomarkers of other exposure-associated diseases.