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Our prior work shows that azinphos-methyl pesticide exposure is associated with altered oral microbiomes in exposed farmworkers. Here we extend this analysis to show the same association pattern is also evident in their children. Oral buccal swab samples were analyzed at two time points, the apple thinning season in spring-summer 2005 for 78 children and 101 adults and the non-spray season in winter 2006 for 62 children and 82 adults. The pesticide exposure for the children were defined by the farmworker occupation of the cohabitating household adult and the blood azinphos-methyl detection of the cohabitating adult. Oral buccal swab 16S rRNA sequencing determined taxonomic microbiota proportional composition from concurrent samples from both adults and children. Analysis of the identified bacteria showed significant proportional changes for 12 of 23 common oral microbiome genera in association with azinphos-methyl detection and farmworker occupation. The most common significantly altered genera had reductions in the abundance of Streptococcus, suggesting an anti-microbial effect of the pesticide. Principal component analysis of the microbiome identified two primary clusters, with association of principal component 1 to azinphos-methyl blood detection and farmworker occupational status of the household. The children's buccal microbiota composition clustered with their household adult in ∼95% of the households. Household adult farmworker occupation and household pesticide exposure is associated with significant alterations in their children's oral microbiome composition. This suggests that parental occupational exposure and pesticide take-home exposure pathways elicit alteration of their children's microbiomes.

Silver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. Previous studies have identified AgNP toxicity in airway epithelial cells, but no

The exposome provides a conceptual model for identifying and characterizing lifetime environmental exposures and resultant health effects. In this study, we applied key exposome concepts to look specifically at the neurodevelopmental pesticide exposome, which focuses on exposures to pesticides that have the potential to cause an adverse neurodevelopmental impact. Using household dust samples from a children&rsquo, s agricultural cohort located in the Yakima Valley of Washington state, we identified 87 individual pesticides using liquid chromatography-tandem mass spectrometry. A total of 47 of these have evidence of neurotoxicity included in the Environmental Protection Agency (EPA) (re)registration materials. We used a mixed effects model to model trends in pesticide exposure. Over the two study years (2005 and 2011), we demonstrate a significant decrease in the neurodevelopmental pesticide exposome across the cohort, but particularly among farmworker households. Additional analysis with a non-parametric binomial analysis that weighted the levels of potentially neurotoxic pesticides detected in household dust by their reference doses revealed that the decrease in potentially neurotoxic pesticides was largely a result of decreases in some of the most potent neurotoxicants. Overall, this study provides evidence that the neurodevelopmental pesticide exposome framework is a useful tool in assessing the effectiveness of specific interventions in reducing exposure as well as setting priorities for future targeted actions.

Silver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. Previous studies have identified AgNP toxicity in airway epithelial cells, but no in vitro studies to date have used organotypic cultures as a high-content in vitro model of the conducting airway to characterize the effects of interactions between host genetic and acquired factors, or gene × phenotype interactions (G×P), on AgNP toxicity. In the present study, we derived organotypic cultures from primary murine tracheal epithelial cells (MTEC) to characterize nominal and dosimetric dose-response relationships for AgNP-induced barrier dysfunction, glutathione (GSH) depletion, reactive oxygen species (ROS) production, lipid peroxidation, and cytotoxicity across two genotypes (A/J and C57BL/6J mice), two phenotypes (“Normal” and “Type 2 [T2]-Skewed”), and two exposures (an acute exposure of 24 h and a subacute exposure of 4 hours, every other day, over 5 days [5×4 h]). We characterized the “T2-Skewed” phenotype as an in vitro model of chronic respiratory diseases, which was marked by increased sensitivity to AgNP-induced barrier dysfunction, GSH depletion, ROS production, lipid peroxidation, and cytotoxicity, suggesting that asthmatics are a sensitive population to AgNP exposures in occupational settings. This also suggests that exposure limits, which should be based upon the most sensitive population, should be derived using in vitro and in vivo models of chronic respiratory diseases. This study highlights the importance of considering dosimetry as well as G×P effects when screening and prioritizing potential respiratory toxicants. Such in vitro studies can be used to inform regulatory policy aimed at special protections for all populations.

In vitro micromass culture systems have been proposed as an alternative method for developmental toxicity assessment to reduce the need for resource-intensive in vivo toxicity testing. In this study, a three-dimensional in vitro embryonic mouse midbrain culture system is characterized in two mouse strains to facilitate gene x environment considerations. Gestational day (GD) 11 C57BL/6 or GD 12 A/J mouse midbrain cells were isolated and cultured in high-density micromass format for 22days in vitro (DIV). Hematoxylin intensity and protein content revealed that neuronal differentiation increases linearly over time in both C57BL/6 and A/J cultures. Protein expression showed time-dependent proliferation markers (PCNA) increased significantly between DIV 4-6 compared to DIV 1. Early and late differentiation markers (e.g. β-tubulin III and NMDAɛ1) were expressed between DIV 6-8 and DIV 8-15, respectively. Immunohistochemistry and protein expression results for proliferation and differentiation markers were concordant. Protein expression patterns for the two mouse strain micromass systems were similar. This study characterizes a novel method for investigating early neurogenesis and may be used to characterize neurodevelopmental toxicity in vitro. Our findings show how the use of different mouse strains in neurodevelopmental studies may extend test systems for gene and environment interaction studies.

The take-home pathway is a significant source of organophosphate pesticide exposure for young children (3–5 years old) living with an adult farmworker. This avoidable exposure pathway is an important target for intervention. We selected 24 agricultural communities in the Yakima Valley of Washington State and randomly assigned them to receive an educational intervention (n = 12) to reduce children’s pesticide exposure or usual care (n = 12). We assessed exposure to pesticides in nearly 200 adults and children during the pre and post-intervention periods by measuring metabolites in urine. We compared pre- and post-intervention exposures by expressing the child’s pesticide metabolite concentration as a fraction of the adult’s concentration living in the same household, because the amount of pesticides applied during the collection periods varied. Exposures in our community were consistently higher, sometimes above the 95th percentile of the exposures reported by the National Health and Nutrition Examination Survey (NHANES). While intervention and control communities demonstrated a reduction in the ratio of child to adult exposure, this reduction was more pronounced in intervention communities (2.7-fold, p

CONTEXT: Organophosphorus insecticides (OPs) have been used to control agricultural pests found in Washington state. Farmworkers (FW) have higher exposure to OP pesticides than non-farmworkers (NFW), and FW children may in turn have higher exposure than NFW children. OBJECTIVE: To examine the association between the concentration in house dust of five OPs used commonly in pome fruit orchards and the concentration in urine of dialkylphosphate metabolites (DAP), in a cohort of Hispanic FW and NFW and their children. METHODS: Parents and children participated in three data collection periods over the course of one year. Urine samples were evaluated for the DAPs characteristic of OP exposure, and dust from homes and vehicles was evaluated for intact OP residues. RESULTS: Geometric mean (GM) concentrations of OPs in house and vehicle dust were higher in FW households than NFW households in all agricultural seasons. GM concentration of urinary DAPs was higher for children in FW households than NFW households. DISCUSSION: Regression analysis found a positive association between OP residues in house dust and the children’s urinary DAPs. CONCLUSIONS: To our knowledge this study is the first to report an association between pesticides in house dust and their biological metabolites in urine.

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.

Objective The aim of this study was to examine the impact of a dissemination process to provide individual pesticide results to study participants. Methods After working with community members to disseminate data, 37 participants were recontacted via an interview survey to assess the effectiveness of the dissemination process. Results Almost all participants (97.3%) recalled a home visit from a health promoter; 29 (78.4%) correctly recalled that the health promoter used a thermometer or graphic to explain the results; 26 (70.3%) correctly interpreted graphics showing high and low exposure levels in adults and 75.7% correctly interpreted results for children. Conclusions The study results support the use of a community-based participatory research approach to decide how to best depict and disseminate study results, especially among participants who are often left out of the dissemination process.

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response.

We characterize temporal pathway dynamics of differentiation in an in vitro neurotoxicity model with the aim of informing design and interpretation of toxicological assays. Human neural progenitor cells (hNPCs) were cultured in differentiation conditions up to 21 days. Genes significantly changed through time were identified and grouped according to temporal dynamics. Quantitative pathway analysis identified gene ontology (GO) terms enriched among significantly changed genes and provided a temporal roadmap of pathway trends in vitro. Gene expression in hNPCs was compared with publicly available gene expression data from developing human brain tissue in vivo. Quantitative pathway analysis of significantly changed genes and targeted analysis of specific pathways of interest identified concordance between in vivo and in vitro expression associated with proliferation, migration, differentiation, synapse formation, and neurotransmission. Our analysis anchors gene expression patterns in vitro to sensitive windows of in vivo development, helping to define appropriate applications of the model.

Background Children are especially vulnerable to pesticide exposure and can suffer lasting health effects. Because children of farmworkers are exposed to a variety of pesticides throughout development, it is important to explore temporal patterns of coexposures. Objectives The objectives of this study were to characterize the pesticide co-exposures, determine how they change over time, and assess differences between farmworker and nonfarmworker households. Methods Dust collected from 40 farmworker and 35 nonfarmworker households in the Yakima Valley of the State of Washington in 2005 and then again in 2011 was analyzed for 99 pesticides. Eighty-seven pesticides representing over 28 classes were detected. Pesticides were grouped into classes using U.S. EPA pesticide chemical classifications, and trends in concentrations were analyzed at the class level. Results Levels of organophosphates, pyridazinones, and phenols significantly decreased between 2005 and 2011 in both farmworker and nonfarmworker households. Levels of anilides, 2,6-dinitroanilines, chlorophenols, triclosan, and guanidines significantly increased in both farmworker and nonfarmworker households in 2011 vs. 2005. Among farmworkers alone, there were significantly lower levels of N-methyl carbamates and neonicotinoids in 2011. Conclusions We observed significant reductions in the concentrations of many pesticides over time in both farmworker and nonfarmworker households. Although nonfarmworker households generally had lower concentrations of pesticides, it is important to note that in comparison with NHANES participants, nonfarmworkers and their families still had significantly higher concentrations of urinary pesticide metabolites. This finding highlights the importance of detailed longitudinal exposure monitoring to capture changes in agricultural and residential pesticide use over time. This foundation provides an avenue to track longitudinal pesticide exposures in an intervention or regulatory context. https://doi.org/10.1289/EHP3644.

Understanding the underlying temporal and mechanistic responses to neurotoxicant exposures during sensitive periods of neuronal development are critical for assessing the impact of these exposures on developmental processes. To investigate the importance of timing of neurotoxicant exposure for perturbation of epigenetic regulation, we exposed human neuronal progenitor cells (hNPCs) to chlorpyrifos (CP) and sodium arsenite (As; positive control) during proliferation and differentiation. CP or As treatment effects on hNPCs morphology, cell viability, and changes in protein expression levels of neural differentiation and cell stress markers, and histone H3 modifications were examined. Cell viability, proliferation/differentiation status, and epigenetic results suggest that hNPCs cultures respond to CP and As treatment with different degrees of sensitivity. Histone modifications, as measured by changes in histone H3 phosphorylation, acetylation and methylation, varied for each toxicant and growth condition, suggesting that differentiation status can influence the epigenetic effects of CP and As exposures.

Background Studies suggest that some of the greatest exposure to OPs in children occurs in agricultural communities and various pathways of exposure including the take-home pathway, proximity to orchards, and diet have been explored. However, the importance of the dietary pathway of exposure for children in agricultural communities is not well understood. Objectives Our goal was to ascertain whether there were associations between measures of OP exposure and apple juice, fruit, and vegetable consumption across growing seasons by children of farmworkers and non-farmworkers in a rural agricultural setting. Methods Study participants were children of farmworker (N=100) or non-farmworker (N=100) households from a longitudinal cohort study. Dietary intake of fruits and vegetables was assessed using a “5-A–Day” abbreviated food frequency questionnaire, and exposure to OPs was characterized using three urinary di-methyl and three di-ethyl metabolite measurements per child for each of three growing seasons. We used generalized estimating equations to examine data. Results Consumption frequency of fruits and vegetables was similar between children of farmworkers and non-farmworkers and across seasons. There were a few significant trends between dimethyl metabolites (DMAP) and fruit, vegetable or apple juice consumption; however, no clear pattern held across seasons or occupation. One difference was found in vegetable consumption during the harvest season, where the farmworker families showed a significant relationship between vegetable consumption and dimethyl metabolite levels (p=0.002). We also found a significant difference in this relationship between farmworkers and non-farmworkers (p=0.001). No significant trends between fruit and vegetable consumption and diethyl (DEAP) metabolites were found. Conclusions Our study shows the importance of considering season and parents' occupation in understanding OP exposure routes among children in an agricultural community. The impact of these factors on dietary OP exposure requires a more thorough analysis of the availability and consumption of produce from different sources including farms using pesticides where parents worked.

Reducing residential pesticide exposure requires identification of exposure pathways. mCompared to the agriculture worker ‘take-home’ and residential use pathways, evidence of the ‘drift’ pathway to pesticide exposure has been inconsistent. Questionnaire data from individuals (n=99) and dust samples (n=418) from households across three growing seasons in 2011 were from the For Healthy Kids! study. Summed dimethyl organophosphate pesticide (OP) (Azinphos-Methyl, Phosmet, and Malathion) concentrations were quantified from house dust samples. Spatially-weighted orchard densities surrounding households were calculated based on various distances from homes. Regression models tested associations between orchard density, residential pesticide use, agriculture worker residents, and summed dimethyl OP house dust concentrations. Estimated relationships between orchard density and dimethyl OP in house dust were mixed: a 5% increase in orchard density resulted in 0.3% and 0.5% decreases in dimethyl OP house dust concentrations when considering land-cover 750m or 1250m away from households, respectively, but null associations with land-cover 60m or 200m away. Dimethyl OP house dust concentrations were 400% higher within homes where at least two residents were agriculture workers. Despite inconclusive evidence for the drift pathway due to potential for bias, relationships between number of agriculture workers and dimethyl OP house dust concentration underscores the take-home pathway.

Micromass culture systems have been developed as three-dimensional organotypic in vitro alternatives to test developmental toxicity. We have optimized a murine-based embryonic midbrain micromass system in two genetic strains to evaluate neurodevelopmental effects of gold-cored silver nanoparticles (AgNPs) of differing sizes and coatings—20 nm AgCitrate, 110 nm AgCitrate, and 110 nm AgPVP. AgNPs are increasingly used in consumer, commercial, and medical products for their antimicrobial properties and observations of Ag in adult and fetal brain following in vivo exposures to AgNPs have led to concerns about the potential for AgNPs to elicit adverse effects on neurodevelopment and neurological function. Cytotoxicity was assessed at three time points of development by both nominal dose and by dosimetric dose. Ag dosimetry was assessed in cultures and the gold core component of the AgNPs was used as a tracer for determination of uptake of intact AgNPs and silver dissolution from particles in the culture system. Results by both nominal and dosimetric dose show cell death increased significantly in a dose-dependent manner at later time points (days 15 and 22 in vitro) that coincide with differentiation stages of development in both strains. When assessed by dosimetric dose, cultures were more sensitive to smaller particles, despite less uptake of Ag in smaller particles in both strains.

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.

In a longitudinal agricultural community cohort sampling of 65 adult farmworkers and 52 adult nonfarmworkers, we investigated agricultural pesticide exposure-associated changes in the oral buccal microbiota. We found a seasonally persistent association between the detected blood concentration of the insecticide azinphos-methyl and the taxonomic composition of the buccal swab oral microbiome. Blood and buccal samples were collected concurrently from individual subjects in two seasons, spring/summer 2005 and winter 2006. Mass spectrometry quantified blood concentrations of the organophosphate insecticide azinphos-methyl. Buccal oral microbiome samples were 16S rRNA gene DNA sequenced, assigned to the bacterial taxonomy, and analyzed after “centered-log-ratio” transformation to handle the compositional nature of the proportional abundances of bacteria per sample. Nonparametric analysis of the transformed microbiome data for individuals with and without azinphos-methyl blood detection showed significant perturbations in seven common bacterial taxa (>0.5% of sample mean read depth), including significant reductions in members of the common oral bacterial genus Streptococcus . Diversity in centered-log-ratio composition between individuals' microbiomes was also investigated using principal-component analysis (PCA) to reveal two primary PCA clusters of microbiome types. The spring/summer “exposed” microbiome cluster with significantly less bacterial diversity was enriched for farmworkers and contained 27 of the 30 individuals who also had azinphos-methyl agricultural pesticide exposure detected in the blood. IMPORTANCE In this study, we show in human subjects that organophosphate pesticide exposure is associated with large-scale significant alterations of the oral buccal microbiota composition, with extinctions of whole taxa suggested in some individuals. The persistence of this association from the spring/summer to the winter also suggests that long-lasting effects on the commensal microbiota have occurred. The important health-related outcomes of these agricultural community individuals' pesticide-associated microbiome perturbations are not understood at this time. Future investigations should index medical and dental records for common and chronic diseases that may be interactively caused by this association between pesticide exposure and microbiome alteration.

Exposure to phthalate esters is associated with changes in steroidogenesis, leading to the hypothesis that this is a primary mechanism of phthalate reproductive toxicity. However, some phthalate-induced male reproductive toxicity has been demonstrated in the absence of changes to testosterone production, suggesting additional mechanisms of action. There is evidence that phthalate exposure increases expression of the inflammatory enzyme cyclooxygenase 2 (cox-2). Furthermore, inhibition of cox-2 enhances expression of the steroidogenic acute regulatory protein (StAR), which mediates the rate-limiting step in steroidogenesis. This study hypothesized that phthalate-induced toxicity and testosterone perturbation are mediated in part by cox-2. A 3D in vitro rat testis co-culture to explore the role of cox-2 in phthalate toxicity was employed. Cells were treated with 100 µM dipentyl phthalate (DPP) with and without pre-treatment with the specific cox-2 inhibitor NS-398. Effects were evaluated after 8, 24, and 72 h. DPP exposure significantly increased cox-2 expression at 8 and 24 h (p

Quantum dots (Qdots) are semiconductor nanoparticles with size-tunable fluorescence capabilities with diverse applications. Qdots typically contain cadmium or other heavy metals, hence raising concerns of their potential toxicity, especially in occupational settings where inhalation of nanomaterials may increase the risk of lung disease. Accordingly, we assessed the effects of tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coated CdSe/ZnS Qdots on mouse lung epithelial cells and macrophages. Mouse tracheal epithelial cells (MTEC), grown as organotypic cultures, bone marrow-derived macrophages (BMDM), and primary alveolar macrophages (AM) were derived from C57BL/6J or A/J mice and treated with TOPO-PMAT CdSe/ZnS Qdots (10–160 nM) for up to 24 h. Cadmium analysis showed that Qdots remained in the apical compartment of MTEC cultures, whereas they were avidly internalized by AM and BMDM, which did not differ between strains. In MTEC, Qdots selectively induced expression (mRNA and protein) of neutrophil chemokines CXCL1 and CXCL2 but only low to no detectable levels of other factors assessed. In contrast, 4 h exposure to Qdots markedly increased expression of CXCL1, IL6, IL12, and other pro-inflammatory factors in BMDM. Higher inflammatory response was seen in C57BL/6J than in A/J BMDM. Similar expression responses were observed in AM, although overall levels were less robust than in BMDM. MTEC from A/J mice were more sensitive to Qdot pro-inflammatory effects while macrophages from C57BL/6J mice were more sensitive. These findings suggest that patterns of Qdot-induced pulmonary inflammation are likely to be cell-type specific and genetic background dependent.

MicroRNAs (miRNAs) are small, non-coding RNAs that act as post-transcriptional regulators by silencing messenger RNAs. Because miRNAs do not rapidly degrade, they have the potential to serve as sensitive, predictive, and robust non-invasive biomarkers in bodily fluids. While urinary miRNAs have been used as clinical biomarkers of disease, their roles as potential biomarkers of occupational and environmental exposures has yet to be elucidated. Our study investigated miRNA profiles from archived urinary samples and identified miRNAs associated with occupational exposure to pesticides in farmworkers. Urinary samples were collected from a nested cohort of 27 farmworkers and non-farmworkers (16FW/11 NFW) during two agricultural seasons. MiRNAs were isolated and profiled using PCR arrays. Comparisons were made between occupational and seasonal exposure. Principal components and hierarchical clustering analyses of the ten most frequently expressed miRNAs among groups indicate significant differences in miRNA profiles between farmworker and non-farmworker adults. A seasonal difference in miRNA profiles was observed in farmworkers. Six miRNAs were observed to be associated with farmworker occupation during the post-harvest season. A positive dose-response relationship was observed between five of the farmworker-associated miRNAs and organophosphate pesticide metabolites. Four of the miRNAs associated with farmworker occupation have been associated with target genes involved in neurological functions including neurotransmitter activity and receptor binding. One of the miRNAs associated with farmworker occupation has been associated with acetylcholine binding, acetylcholinesterase activity, and cholinesterase activity which are hallmark pathways affected by organophosphate pesticide exposure. Our findings suggest that miRNA profiles may be novel epigenetic biomarkers of occupational pesticide exposure and early biological response.

With the increased production and widespread commercial use of silver nanoparticles (AgNPs), human and environmental exposures to silver nanoparticles are inevitably increasing. In particular, persons manufacturing and handling silver nanoparticles and silver nanoparticle containing products are at risk of exposure, potentially resulting in health hazards. While silver dusts, consisting of micro-sized particles and soluble compounds have established occupational exposure limits (OELs), silver nanoparticles exhibit different physicochemical properties from bulk materials. Therefore, we assessed silver nanoparticle exposure and related health hazards in order to determine whether an additional OEL may be needed. Dosimetric evaluations in our study identified the liver as the most sensitive target organ following inhalation exposure, and as such serves as the critical target organ for setting an occupational exposure standard for airborne silver nanoparticles. This study proposes an OEL of 0.19 μg/m(3) for silver nanoparticles derived from benchmark concentrations (BMCs) from subchronic rat inhalation toxicity assessments and the human equivalent concentration (HEC) with kinetic considerations and additional uncertainty factors. It is anticipated that this level will protect workers from potential health hazards, including lung, liver, and skin damage.

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.

Organophosphate pesticides are commonly used in the United States, and farmworkers are at risk for chronic exposure. Using data from a community randomized trial to interrupt the take-home pathway of pesticide exposure, we examined the association between floor surface type (smooth floor, thin carpet, and thick carpet) and rooms in which dust samples were collected (living room vs. non-living room) and concentrations of azinphos-methyl residues in home environments. We also examined the association between vehicle type (truck, auto, or other) and footwell floor surfaces (carpeted, smooth surface, or no mat) and concentrations of azinphos-methyl in vehicle dust samples. Dust samples were collected from 203 and 179 households and vehicles, respectively. All households had at least one child aged 2-6. Vehicle dust samples were collected from footwells of the vehicle used for commuting to and from work. A total of 183 samples were collected from living rooms, and 20 were collected from other rooms in the home. Forty-two samples were collected from thick carpets, 130 from thin carpets, and 27 from smooth floor surfaces. Thick and thin carpets had a significantly greater dust mass than smooth floor surfaces (6.0 g/m(2) for thick carpets, 7.8 g/m(2) for thin carpets, and 1.5 g/m(2) for smooth surfaces). Of the 179 vehicle samples, 113 were from cars, 34 from trucks, and 32 from other vehicles. Vehicles with no mats had a significantly higher mass of dust (21.3 g) than those with hard mats (9.3 g) but did not differ from vehicles with plush mats (12.0 g). Further research is needed to characterize the environment in which children may be exposed to pesticides.

Methylmercury (MeHg) is a developmental neurotoxicant and teratogen and is hypothesized to perturb a wide range of biological processes, like other metals including arsenic (As) and cadmium (Cd). Common inbred mouse strains including C57 (sensitive) and SWV (resistant) display differences in sensitivity to metals such as As and Cd when exposed during neurulation. In this study, we investigated the impact of MeHg on neurulation, assessing for potential differences in sensitivity and associated toxicogenomic response in C57 and SWV mouse embryos. Parallel with morphological assessments of neural tube closure, we evaluated quantitative differences in MeHg-induced alterations in expression between strains at the gene level and within gene-enriched biological processes. Specifically, we observed differing sensitivities to MeHg-induced impacts on neural tube closure between C57 and SWV embryos in a time-dependent manner. These observations correlated with greater impact on the expression of genes associated with development and environmental stress-related pathways in the C57 compared to the SWV. Additional developmental parameters (e.g. mortality, growth effects) evaluated showed mixed significant effects across the two strains and did not support observations of differential sensitivity to MeHg. This study provides potential insights into MeHg-induced mechanisms of developmental toxicity, alterations associated with increased MeHg sensitivity and common biological processes affected by metals in embryos undergoing neurulation.

Objective We examined the effectiveness of a community randomized intervention among farmworkers who did and did not work in pome fruit (apples and pears). Methods Urine samples were collected from two cross-sectional groups of farmworkers and analyzed for the presence of dimethylthiophosphate. Results There was no significant time by crop interaction for changes in urinary metabolite concentrations among adult farmworkers (P = 0.79 pome fruit workers; P = 0.83 non-pome fruit workers) or their children (P = 0.25 children of pome fruit workers; P = 0.91 children of non-pome fruit workers). We found greater urinary metabolite concentrations of dimethylthiophosphate among pome fruit workers (compared with non-pome fruit workers) and among workers at final data collection (compared with baseline). Conclusion Further research is needed to identify effective interventions to reduce pesticide exposure in farmworkers and their children.

Common inbred mouse strains, such as the C57BL/6 (C57) and the SWV, display differences in sensitivity to environmental teratogens during gestation. For example, the C57 is more sensitive than the SWV to cadmium (Cd) exposure during neurulation, inducing a higher incidence of neural tube defects (NTDs). Here, we report, using Cd as a model teratogen, the first large scale toxicogenomic study to compare teratogen-induced gene expression alterations in C57 and SWV embryos undergoing neurulation, identifying toxicogenomic responses that associate with developmental toxicity and differential sensitivity. Using a systems-based toxicogenomic approach, comparing Cd-exposed and control C57 and SWV embryos (12- and 24-h postinjection [p.i.] [gestational day 8.0, ip]), we examined differentially expressed genes at multiple levels (biological process, pathway, gene) using Gene Ontology (GO) analysis, pathway mapping and cross-scatter plots. In both C57 and SWV embryos, we observed several gene expression alterations linked with cell cycle–related classifications, however, only in the C57 we observed upregulation of p53-dependent mediators Ccng1 and Pmaip1, previously associated with cell cycle arrest, apoptosis and NTD formation. In addition, we also identified a greater reduction in expression of nervous system development-related genes (e.g., Zic1, En2, Neurog1, Elavl4, Metrn, Nr2f1, Nr2f2) in the C57 compared to the SWV (12-h p.i.). In summary, our results indicate that differences in Cd-induced gene expression profiles between NTD resistant and sensitive strains within enriched biological processes (including developmental and cell cycle–related categories) associate with increased sensitivity to developmental toxicity as determined by observations of increased NTD formation, mortality (resorptions) and reduced fetal growth. Such observations may provide more detailed and useful mechanistic clues for identification of differences in life-stage specific teratogenic response.

Background Exposure to organophosphate (OP) pesticides is an occupational hazard for farmworkers and affects their children through the take-home pathway. Objectives We examined the effectiveness of a randomized community intervention to reduce pesticide exposure among farmworkers and their children. Methods We conducted a baseline survey of a cross-sectional sample of farmworkers (year 1) in 24 participating communities. Communities were randomized to intervention or control. After 2 years of intervention, a new cross-sectional survey of farmworkers was conducted (year 4). Farmworkers with a child 2–6 years of age were asked to participate in a substudy in which urine was collected from the farmworker and child, and dust was collected from the home and the vehicle driven to work. Results The median concentration of urinary metabolites was higher in year 4 than in year 1 for dimethylthiophosphate (DMTP) and dimethyldithiophosphate in adults and for DMTP for children. There were significant increases within both the intervention and control communities between year 1 and year 4 (p < 0.005); however, the differences were not significant between study communities after adjusting for year (p = 0.21). The dust residue data showed azinphos-methyl having the highest percentage of detects in vehicles (86% and 84% in years 1 and 4, respectively) and in house dust (85% and 83% in years 1 and 4, respectively). There were no significant differences between intervention and control communities after adjusting for year (p = 0.49). Conclusions We found no significant decreases in urinary pesticide metabolite concentrations or in pesticide residue concentrations in house and vehicle dust from intervention community households compared with control community households after adjusting for baseline. These negative findings may have implications for future community-wide interventions.

The purpose of this study was to test the hypothesis that glutamate cysteine ligase catalytic subunit (GCLC) promoter polymorphisms are susceptibility factors for type 1 diabetes (T1D), T1D age-at-onset and T1D autoantibodies. T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were genotyped for two GCLC promoter polymorphisms; the GCLC -129 C to T single nucleotide polymorphism (GCLC -129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). Glutamate decarboxylase antibody (GAD65Ab) positive T1D patients with the GCLC -129 SNP C/T genotype have increased GAD65Ab levels (p-value

Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.

Context: Characterization of stress exposure requires understanding seasonal variability in stress biomarkers.Objective: To compare acute and chronic stress biomarkers between two seasons in a cohort of rural, Hispanic mothers.Methods: Stress questionnaires and cortisol measurements (hair, blood and saliva) were collected in the summer and fall.Results: Cortisol biomarkers were significantly different and stress questionnaires were significantly correlated between seasons.Discussion: The variability in cortisol and relative stability of questionnaires between seasons may indicate that cortisol responds to subtle stressors not addressed in questionnaires.Conclusions: There are significant differences in stress biomarkers in our cohort between seasons.

Organophosphate (OP) pesticides are commonly used in the United States, and farmworkers are at risk for chronic exposure. Using a sample of 218 farmworkers in 24 communities and labor camps in eastern Washington State, we examined the association between agricultural crop and OP pesticide metabolite concentrations in urine samples of adult farmworkers and their children and OP pesticide residues in house and vehicle dust samples. Commonly reported crops were apples (71.6%), cherries (59.6%), pears (37.2%), grapes (27.1%), hops (22.9%), and peaches (12.4%). Crops were grouped into two main categories: pome fruits (apples and pears) and non-pome fruits. Farmworkers who worked in the pome fruits had significantly higher concentrations of dimethyl pesticide metabolites in their urine and elevated azinphos-methyl concentrations in their homes and vehicles than workers who did not work in these crops. Among pome-fruit workers, those who worked in both apples and pears had higher urinary metabolites concentrations and pesticide residue concentrations in dust than did those who worked in a single pome fruit. Children living in households with pome-fruit workers were found to have higher concentrations of urinary dimethyl metabolites than did children of non-pome-fruit workers. Adult urinary concentrations showed significant correlations with both the vehicle and house-dust azinphos-methyl concentrations, and child urinary concentrations were correlated significantly with adult urinary concentrations and with the house-dust azinphos-methyl concentration. The results provide support for the take-home pathway of pesticide exposure and show an association between measures of pesticide exposure and the number of pome-fruit crops worked by farmworkers.

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.

Investigations into the potential mechanisms for ethanol-induced developmental toxicity have been ongoing for over 30 years since Fetal Alcohol Syndrome (FAS) was first described. Neurodevelopmental endpoints are particularly sensitive to in utero exposure to alcohol as suggested by the more prevalent alcohol-related neurodevelopmental disorder (ARND). The inhibition of proliferation during neurogenesis and the induction of apoptosis during the period of synaptogenesis have been identified as potentially important mechanisms for ARND. However, it is unclear how these two mechanisms quantitatively relate to the dose and timing of exposure. We have extended our model of neocortical neurogenesis to evaluate apoptosis during synaptogenesis. This model construct allows quantitative evaluation of the relative impacts on neuronal proliferation versus apoptosis during neocortical development. Ethanol-induced lengthening of the cell cycle of neural progenitor cells during rat neocortical neurogenesis (G13-G19) is used to compute the number of neurons lost after exposure during neurogenesis. Ethanol-induced dose-dependent increases in cell death rates are applied to our apoptosis model during rat synaptogenesis (P0-P14), when programmed cell death plays a major role in shaping the future neocortex. At a human blood ethanol concentration that occurs after 3-5 drinks ( approximately 150 mg/dl), our model predicts a 20-30% neuronal deficit due to inhibition of proliferation during neurogenesis, while a similar exposure during synaptogenesis suggests a 7-9% neuronal loss through induction of cell death. Experimental in vitro and in vivo dose-response research and stereological research on long-term neuronal loss after developmental exposure to ethanol is compared to our model predictions. Our computational model allows for quantitative, systems-level comparisons of mechanistic hypotheses for perturbations during specific neurodevelopmental periods.

PurposeTo derive from the environmental risk and knowledge management literatures a model that integrates organizational form, democratic vision and epistemological needs of public agencies responsible for addressing environmental risks. To analyze the knowledge management practices of the United States Department of Energy (USDOE) that is responsible for cleaning up landscapes contaminated by 50 years of plutonium production.Design/methodology/approachThe model was used as a framework for a case study analysis of the USDOE knowledge management practices.FindingsConceptual: a vision of democracy and an understanding of the type of knowledge process can facilitate organizational constancy. Organizational forms should be matched to knowledge process and democratic vision. Empirical: USDOE has behaved erratically in addressing environmental risks viewed through this model of knowledge management.Research limitations/implicationsThe model idealizes democratic visions, epistemological processes and organizational forms. Care should be taken in making predictions for the success or failure of an organizational approach based solely on this model.Practical implicationsPractically, the model aids scholars in making connections between knowledge management and public sector environmental risk management literatures; and provides managers with a systematic framework for relating democratic context knowledge production processes to particular organization forms. Use of this model particularly during agency restructuring may facilitate resolving environmental risks though improving organizational legitimacy, constancy, and knowledge generation capacity.Originality/valueThis is a first attempt at integrating two related but so‐far disconnected literatures (environmental risk management and knowledge management).

Polychlorinated biphenyls (PCB) are the second greatest cause of fish advisories, and are often the greatest contributors to dioxin-like toxic equivalency (TEQ) in fish and seafood. Because fish consumption is associated with both contaminant risks and health benefits, incremental health risks from PCBs in fish should be considered within the context of overall TEQ associated dietary risk to enable consumers to make informed decisions about choosing to eat fish or alternate foodstuffs. In this paper, potential TEQ exposure from PCBs in fish for adults with a variety of consumption patterns and consuming fish from a variety of sources are calculated using recent consumption and fish contaminant data from the literature and compared to total TEQ exposure from all sources. For high-level consumers and individuals eating fish from relatively contaminated sites, PCB TEQ exposure from fish consumption alone may exceed the 1 pg TEQ/kg/day average adult daily intake estimated by EPA, which itself carries an upper bound cancer risk of 1 in 1000. PCB TEQ risk for average consumers of commercial fish is expected to be far less, but is highly uncertain, since there is a dearth of congener specific PCB data for commercial fish and seafood.

To define mechanisms of susceptibility for populations affected by environmental exposures, both exposure and toxicity assessments must be considered. This review examines cultural and lifestyle factors that help define potentially susceptible populations in two groups, Asian and Pacific Islanders (API) and members of Tribal Nations in the Pacific Northwest region of the US and Western Canada. These groups, which may consume 10 times more fish and seafood than average US consumers, have special dietary practices that can lead to significant exposures to persistent pollutants and biotoxins found in fish and shellfish. The mechanism of toxicity of these contaminants is also important. Using the example of dioxin-like polychlorinated biphenyls (PCBs), different risk assessment approaches are presented and the analytical sensitivity needed to assess risk for different consumption groups is evaluated quantitatively. Our studies have also shown that regulatory agencies evaluation of fish consumption for average US populations do not always adequately consider unique consumption and cooking practices of these groups. Partnering with communities is important for appropriate exposure and risk assessments. This also empowers proactive action by communities to evaluate the risks and many benefits of fish and shellfish consumption and develop risk management strategies tailored for their communities.

Biomarker measurements from single time points are often used to make inferences about longer periods of toxicant intake. However, toxicant exposures rarely, if ever, occur under steady-state conditions, and biomarkers are typically most sensitive to recent toxicant exposures. Moreover, toxicant exposures are typically episodic and vary in magnitude over time. While it is often believed that the error introduced by the steady-state assumption is minimal and can safely be ignored, no rationale is typically presented to support this belief. Moreover, no guidelines have been established for determining a de minimus error level or for estimating the degree of error potentially introduced by a fallacious steady-state assumption in biomarker interpretation. We present a statistical framework for evaluating the potential magnitude of the error introduced by the steady-state fallacy and demonstrate applications of the framework to blood mercury and hair mercury exposure biomarkers in human adults. The magnitude of error clearly depends on many factors, including the exposure frequency, exposure magnitude, exposure duration, and exposure inference duration. Graphical presentation of the error as a function of those factors provides insight into the interpretation of mercury exposure biomarkers. We describe a general approach for determining the mean and variance of temporal error, present explicit solutions for several special cases, and demonstrate an example using the framework to evaluate the error resulting from the use of a steady-state model to estimate time-varying exposure from mercury biomarkers.

Little is known about pesticide exposure among farmworkers, and even less is known about the exposure associated with performing specific farm tasks. Using a random sample of 213 farmworkers in 24 communities and labor camps in eastern Washington State, we examined the association between occupational task and organophosphate (OP) pesticide residues in dust and OP metabolite concentrations in urine samples of adult farmworkers and their children. The data are from a larger study that sought to test a culturally appropriate intervention to break the take-home pathway of pesticide exposure. Commonly reported farm tasks were harvesting or picking (79.2%), thinning (64.2%), loading plants or produce (42.2%), planting or transplanting (37.6%), and pruning (37.2%). Mixing, loading, or applying pesticide formulations was reported by 20% of our sample. Workers who thinned were more likely than those who did not to have detectable levels of azinphos-methyl in their house dust (92.1% vs. 72.7%; p = 0.001) and vehicle dust (92.6% vs. 76.5%; p = 0.002). Thinning was associated with higher urinary pesticide metabolite concentrations in children (91.9% detectable vs. 81.3%; p = 0.02) but not in adults. Contrary to expectation, workers who reported mixing, loading, or applying pesticide formulations had lower detectable levels of pesticide residues in their house or vehicle dust, compared with those who did not perform these job tasks, though the differences were not significant. Future research should evaluate workplace protective practices of fieldworkers and the adequacy of reentry intervals for pesticides used during thinning.

A robust approach to defining, understanding, and tracking contaminant levels is crucial to human and ecological risk evaluation and risk management. Whether materials are present in the environment naturally (mercury, radon, nitrogen, phosphorous) and enhanced by human activities or are man-made (DDT and PCBs), the complexity of contaminant distributions and sources requires careful design and implementation of studies to characterize background. Before collection or analyses of data are initiated, an explicit definition of background appropriate to specific risk assessments is needed. Problems associated with determining background levels of contaminants in fish and seafood illustrate some challenges faced by risk assessors. Major differences in estimates of background may result from differences in sampling and analytical methods including selection of sampling locations, approaches to data analysis and synthesis, and tissues selected for analysis. Different approaches may yield background exposure or ...

The U.S. Department of Energy (DOE) is responsible for the cleanup of our nation's nuclear legacy, involving complex decisions about how and where to dispose of nuclear waste and how to transport it to its ultimate disposal site. It is widely recognized that a broad range of stakeholders and tribes should be involved in this kind of decision. All too frequently, however, stakeholders and tribes are only invited to participate by commenting on processes and activities that are near completion; they are not included in the problem formulation stages. Moreover, it is often assumed that high levels of complexity and uncertainty prevent meaningful participation by these groups. Considering the types of information that stakeholders and tribes need to be able to participate in the full life cycle of decision making is critical for improving participation and transparency of decision making. Toward this objective, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP) participated in three public processes relating to nuclear waste transportation and disposal in 1997-1998. First, CRESP organized focus groups to identify concerns about nuclear waste transportation. Second, CRESP conducted exit surveys at regional public workshops held by DOE to get input from stakeholders on intersite waste transfer issues. Third, CRESP developed visual tools to synthesize technical information and allow stakeholders and tribes with varying levels of knowledge about nuclear waste to participate in meaningful discussion. In this article we share the results of the CRESP findings, discuss common themes arising from these interactions, and comment on special considerations needed to facilitate stakeholder and tribal participation in similar decision-making processes.

Congener-specific PCB analysis allows use of toxic equivalency (TEQ) TCDD-based risk assessment approaches when analytical methods are sufficiently sensitive. Many efforts to analyze fish samples for PCB congeners report the majority of samples as non-detects; these data are of little use for human health risk assessment if the limits of analytical detection exceed levels of potential health concern. However, increasing analytical sensitivity is costly and technically difficult. An approach to assess analytical sensitivity needs for risk assessment by defining toxicological endpoints of concern and acceptable risk levels is presented. This framework was applied to assessment of potential PCB TEQ cancer risks to the general United States population and tribal consumers of Columbia River fish, but may be easily adjusted for other situations. A probabilistic model was used to calculate the necessary analytical sensitivity for PCB TEQ cancer risk assessment using the Environmental Protection Agency's new draft cancer risk slope factor for TCDD and fish consumption data. Desired levels of analytical sensitivity were estimated for the congener expected to contribute the most to PCB TEQ, PCB 126, and compared to limits of detection for various analytical methods. The financial and health value of methods with different levels of analytical sensitivity were compared using a value of information approach, which includes analytical cost and cost of potential health outcomes, and a proposed risk assessment utility approach which considers the relative health protectiveness of analytical options non-monetarily. Sensitivity analyses indicate that average consumption rate, cancer risk slope factor choice, and knowledge of existing PCB contamination are important considerations for planning PCB congener analysis.

This article discusses a process for finding insights that will allow federal agencies and environmental professionals to more effectively manage contaminated sites. The process is built around what Etzioni (1968) called mixed-scanning, that is, perpetually doing both comprehensive and detailed analyses and periodically re-scanning for new circumstances that change the decision-making environment. The article offers a checklist of 127 items, which is one part of the multiple-stage scanning process. The checklist includes questions about technology; public, worker, and ecological health; economic cost and benefits; social impacts; and legal issues. While developed for a DOE high-level radioactive waste application, the decision-making framework and specific questions can be used for other large-scale remediation and management projects. © 2002 Wiley Periodicals, Inc.

We have developed a computational model that allows for the evaluation of normal and perturbed neurodevelopmental processes. This mathematical construct is used to test the hypothesis that reduced neuronal production is the critical mechanism behind fetal alcohol syndrome. Model predictions of normal neurodevelopment match independent stereological measures but challenge estimates generated using a previously published model of normal neocortical neuronogenesis. Evaluation of data showing an increased cell cycle length after prenatal exposure to ethanol during neocortical neuronogenesis yields predictions of cellular deficits that can account for the permanent neocortical neuronal loss seen in rodents exposed to ethanol concentrations of public health relevance.

The initial use of composite sampling involved the analysis of many negative samples with relatively high laboratory cost (Dorfman sampling). We propose a method of double compositing and compare its efficiency with Dorfman sampling. The variability of composite measurement samples has environmental interest (hot spots). The precision of these estimates depends on the kurtosis of the distribution; leptokurtic distributions (γ2 > 0) have increased precision as the number of field samples is increased. The opposite effect is obtained for platykurtic distributions. In the lognormal case, coverage probabilities are reasonable for σ < 0.5. The Poisson distribution can be associated with temporal compositing, of particular interest where radioactive measurements are taken. Sample size considerations indicate that the total sampling effort is directly proportional to the length of time sampled. If there is background radiation then increasing levels of this radiation require larger sample sizes to detect the same difference in radiation.