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Biomedical subjects

Thomas E McKone

Publications and source records attributed to Thomas E McKone.

17 recordsLinked to original sources

Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA.

In support of planning efforts for the National Children's Study, we conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. We tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. We measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. We also analyzed urine samples for OP pesticide metabolites. Finally, we administered four field-based exposure assessment instruments: a questionnaire; food diary; home inspection; and a self-administered child activity timeline. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples (Spearman's rho=0.18-0.76). Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. The child activity timeline, a novel, low-literacy instrument based on pictures, was successfully used by our participants. Future uses of these data include the development of pesticide exposure models and risk assessment.

Agriculture↗

Confronting workplace exposure to chemicals with LCA: examples of trichloroethylene and perchloroethylene in metal degreasing and dry cleaning.

Life-Cycle Assessment (LCA) aims to assess all environmental impacts "from cradle to grave". Nevertheless, existing methods for Life-Cycle Impact Assessment (LCIA) generally do not consider impacts from chemical exposure at the workplace. This is a severe drawback, because neglecting occupational health effects may result in product or process optimizations at the expense of workers' health. We adapt an existing LCIA method to consider occupational health effects from the use of perchloroethylene (PCE) and trichloroethylene (TCE) in dry cleaning and metal degreasing. The results show that, in applications such as metal degreasing and dry cleaning, long-term (steady-state) concentrations at the workplace are up to 6 orders of magnitude higher than ambient air levels. Legal threshold values may be exceeded, depending on machine technology, size, and surrounding working conditions. The impact from workplace exposure to the total human-toxicity potential of the complete life cycle of PCE and TCE (including use, production, and disposal) is accordingly high. We therefore conclude that occupational health effects need to be considered in LCA to prevent overlooking key environmental-health impacts in LCA.

Air Pollutants, Occupational↗

Assessing the influence of climate variability on atmospheric concentrations of polychlorinated biphenyls using a global-scale mass balance model (BETR-global).

We introduce a new global-scale multimedia contaminant fate model (the Berkeley-Trent Global Model; BETR-Global) that integrates global climate data from the National Centers for Environmental Prediction (NCEP). BETR-Global represents the global environment as a connected set of 288 multimedia regions on a 15 degrees grid. We evaluate the model by simulating the global fate and transport of seven PCB congeners over a 70 year period and find satisfactory agreement between model output and observations of atmospheric PCB concentrations at 11 long-term monitoring stations in the Northern Hemisphere. We demonstrate the use of the model as a tool for understanding global pollutant dynamics by examining the hypothesis that variability in global-scale climate conditions, as reflected bythe North Atlantic Oscillation (NAO), influences atmospheric PCB concentrations in the Northern Hemisphere. We estimate that the maximum variability in atmospheric PCB concentrations attributable to NAO variability is approximately a factor of 2. The influence of variability in the NAO on PCB concentrations in air is most likely to be observed in the winter and spring at monitoring sites in Northern Europe and the Arctic. Analysis of long-term monitoring data from 11 sites shows some statistically significant relationships between NAO indices and atmospheric PCB concentrations during the winter and spring. Giving consideration to competing factors that influence atmospheric PCB concentrations, longer time series of monitoring data are required to fully evaluate the modeling results and to improve our understanding of the role of climate variability on the long-term fate of persistent semivolatile pollutants.

Arctic Regions↗

Mass balance for mercury in the San Francisco Bay area.

We have developed and illustrated a general regional multi-species model that describes the fate and transport of mercury in three forms, elemental, divalent, and methylated, in a generic regional environment including air, soil, vegetation, water, and sediment. The objectives of the model are to describe the fate of the three forms of mercury in the environment and to determine the dominant physical sinks that remove mercury from the system. Chemical transformations between the three groups of mercury species are modeled by assuming constant ratios of species concentrations in individual environmental media. We illustrate and evaluate the model with an application to describe the fate and transport of mercury in the San Francisco Bay Area of California. The model successfully rationalizes the identified sources with observed concentrations of total mercury and methyl mercury in the San Francisco Bay Estuary. The mass balance provided by the model indicates that continental and global background sources control mercury concentrations in the atmosphere but that loadings to water in the San Francisco Bay Estuary are dominated by runoff from the Central Valley catchment and remobilization of contaminated sediments deposited during past mining activities. The model suggests that the response time of mercury concentrations in the San Francisco Bay Estuary to changes in loadings is long, on the order of 50 years.

Atmosphere↗

Organophosphate urinary metabolite levels during pregnancy and after delivery in women living in an agricultural community.

Little information has been published about pesticide exposures experienced by pregnant women. We measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in 600 pregnant, low-income women living in the Salinas Valley, California, an agricultural area. A total of 28% were employed as farm fieldworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Samples were collected twice during pregnancy (mean = 13 and 26 weeks' gestation, respectively) and just after delivery (mean = 9 days). As in other studies, dimethyldithiophosphate levels were higher than those of other urinary OP metabolites. Total DAP metabolite levels in samples collected after delivery were higher than in samples collected during pregnancy. Median metabolite levels at the first and second prenatal sampling points and at the postpartum collection were 102.8, 106.8, and 227.2 nmol/L, respectively. Both prenatal and postpartum metabolite levels were higher in these Salinas Valley women than in a sample of women of childbearing age in the general U.S. population (National Health and Nutrition Examination Survey), although the deviation from U.S. reference levels was most pronounced after delivery. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.

California↗

A comparison between the multimedia fate and exposure models CalTOX and uniform system for evaluation of substances adapted for life-cycle assessment based on the population intake fraction of toxic pollutants.

In life-cycle assessment (LCA) and comparative risk assessment, potential human exposure to toxic pollutants can be expressed as the population intake fraction (iF), which represents the fraction of the quantity emitted that enters the human population. To assess the influence of model differences in the calculation of the population iF ingestion and inhalation iFs of 365 substances emitted to air, freshwater, and soil were calculated with two commonly applied multimedia fate and exposure models, CalTOX and the uniform system for evaluation of substances adapted for life-cycle assessment (USES-LCA). The model comparison showed that differences in the iFs due to model choices were the lowest after emission to air and the highest after emission to soil. Inhalation iFs were more sensitive to model differences compared to ingestion iFs. The choice for a continental seawater compartment, vertical stratification of the soil compartment, rain and no-rain scenarios, and drinking water purification mainly clarify the relevant model differences found in population iFs. Furthermore, pH correction of chemical properties and aerosol-associated deposition on plants appeared to be important for dissociative organics and metals emitted to air, respectively. Finally, it was found that quantitative structure-activity relationship estimates for superhydrophobics may introduce considerable uncertainty in the calculation of population intake fractions.

Animals↗

Applications of contaminant fate and bioaccumulation models in assessing ecological risks of chemicals: a case study for gasoline hydrocarbons.

Mass balance models of chemical fate and transport can be applied in ecological risk assessments for quantitative estimation of concentrations in air, water, soil, and sediment. These concentrations can, in turn, be used to estimate organism exposures and ultimately internal tissue concentrations that can be compared to mode-of-action-based critical body residues that induce toxic effects. From this comparison, risks to the exposed organism can be evaluated. To demonstrate the use of fate models in ecological risk assessment, we combine the EQuilibrium Criterion (EQC) environmental fate model with a simple screening level biouptake model for three representative organisms: a bird, a mammal, and a fish. This effort yields estimates of internal body concentrations that can be compared with levels known to elicit toxic effects. As an illustration, we present an analysis of 24 hydrocarbon components of gasoline that differ in properties but are assumed to elicit toxicity by a common narcotic mode of action. Results demonstrate that differences in chemical properties and mode of entry into the environment lead to profound differences in the efficiency of transport from emission to target biota. We discussthe implications of these results and draw attention to the insights gained about regional fate and ecological risks associated with gasoline. This approach is suitable for assessing single chemicals or mixtures that have similar modes of action. We conclude that the model-based methodologies presented are widely applicable for screening level ecological risk assessments that support effective chemicals management.

Animals↗

Contribution of locally grown foods in cumulative exposure assessments.

Both laboratory and field studies confirm the importance of vegetation for scavenging semivolatile organic chemicals (SVOCs) from the atmosphere and a number of exposure studies have found that the dietary pathway is often a significant contributor to cumulative exposure for these chemicals. However, little information exists on the atmospheric source-to-dietary intake linkage for SVOCs. Because of higher SVOC emissions to urban regions, this linkage is particularly important for foods that are grown, distributed and consumed in or near urban regions. The food pathway can also contribute to dietary exposure for populations that are remote from a pollutant source if the pollutants can migrate to agricultural regions and subsequently to the agricultural commodities distributed to that population. We use available data, the characteristic travel distance, and the CalTOX multimedia model framework to assess the contribution of local sources of food to cumulative SVOC intake. Based on published concentration data for foods, our exposure calculations indicate that the potential intake through ingestion can be up to 1000 times that of inhalation for certain persistent SVOCs. We use the population-based intake fraction (iF) to determine how SVOC intake can vary among food commodities and exposure pathways, and to determine the contribution of airborne emitted SVOCs to the diet in the Northern Hemisphere. We focus on three representative multimedia SVOCs-benzo(a)pyrene, fluoranthene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. The approach presented here provides a useful framework and starting point for source-to-intake assessments for the ambient air-to-dietary exposure pathway.

California↗

Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study.

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups - although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.

Adult↗

Standardized approach for developing probabilistic exposure factor distributions.

The effectiveness of a probabilistic risk assessment (PRA) depends on the quality and relevance of the output from exposure and risk models, which, in turn, depends on the critical inputs to the assessment. These critical inputs are often in the form of probabilistic exposure factor distributions that are derived for the given risk scenario. Deriving probabilistic distributions for model inputs can be time consuming and subjective. The absence of a standard approach for developing these distributions can result in PRAs that are inconsistent and difficult to review by regulatory agencies. We present an approach that reduces subjectivity in the distribution development process without limiting the flexibility needed to prepare relevant PRAs. The approach requires two steps. First, we analyze data pooled at a population scale to (i) identify the most robust demographic descriptors within the population for a given exposure factor, (ii) partition the data into subsets based on these variables, and (iii) construct archetypal distributions for each subpopulation. Second, we sample from these archetypal distributions according to site- or scenario-specific conditions to simulate exposure factor values and use these values to construct the scenario-specific input distribution. The archetypal distributions developed through Step 1 provide a consistent basis for developing scenario-specific distributions so risk assessors will not have to repeatedly collect and analyze raw data for each new assessment. We demonstrate the approach for two commonly used exposure factors--body weight (BW) and exposure duration (ED)--using data that are representative of the U.S. population. For these factors we provide a first set of subpopulation-based archetypal distributions and demonstrate methods for using these distributions to construct relevant scenario-specific probabilistic exposure factor distributions.

Adolescent↗

Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants.

Although intuitively it is apparent that population-level exposure to contaminants dispersed in the environment must be related to the persistence of the contaminant, there has been little effort to quantify this link formally. In this paper we investigate the relationship between overall persistence and/or overall residence time in a multimedia exposure environment and the population-level intake of contaminants as expressed by intake fraction (iF), the cumulative fraction of chemical emitted to the environment that is taken up by members of the population. We demonstrate that for any given contaminant and emission scenario the definition of iF implies that it is directly proportional to the overall multimedia persistence (Pov), or the overall multimedia residence time (Tov). The proportionality constant has dimensions of time and represents the characteristic time for population intake (CTI) of the chemical from the environment. We then apply the CalTOX fate and exposure model to explore how Tov and CTI combine to determine the magnitude of iF We find that CTI has a narrow range of possible values relative to Tov across multiple chemicals and emissions scenarios. We use data from the Canadian Environmental Protection Act Priority Substance List (PSL1) Assessments and multimedia Pov to show that exposure assessments based on empirical observation are consistent with interpretations from the model. Results indicate that Pov derived from screening-level assessments of persistence, bioaccumulation potential, and toxicity (PBT) is a useful indicator of the potential for population-level exposure.

Environmental Exposure↗

Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.

Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures.

Adolescent↗

Exposure chamber measurements of mass transfer and partitioning at the plant/air interface.

Dynamic measures of air and vegetation concentrations in an exposure chamber and a two-box mass balance model are used to quantify factors that control the rate and extent of chemical partitioning between vegetation and the atmosphere. A continuous stirred flow-through exposure chamber was used to investigate the gas-phase transfer of pollutants between air and plants. A probabilistic two-compartment mass balance model of plant/air exchange within the exposure chamber was developed and used with measured concentrations from the chamber to simultaneously evaluate partitioning (Kpa), overall mass transfer across the plant/air interface (Upa), and loss rates in the atmosphere (Ra) and aboveground vegetation (Rp). The approach is demonstrated using mature Capsicum annuum (bell pepper) plants exposed to phenanthrene (PH), anthracene (AN), fluoranthene (FL) and pyrene (PY). Measured values of log Kpa (V[air]/V[fresh plant]) were 5.7, 5.7, 6.0, and 6.2 for PH, AN, FL, and PY, respectively. Values of Upa (m d(-1)) under the conditions of this study ranged from 42 for PH to 119 for FL. After correcting for wall effects, the estimated reaction half-lives in air were 3, 9, and 25 h for AN, FL and PY. Reaction half-lives in the plant compartment were 17, 6, 17, and 5 d for PH, AN, FL, and PY, respectively. The combined use of exposure chamber measurements and models provides a robust tool for simultaneously measuring several different transfer factors that are important for modeling the uptake of pollutants into vegetation.

Atmosphere↗

Indoor particulate matter of outdoor origin: importance of size-dependent removal mechanisms.

Adverse human health effects have been observed to correlate with levels of outdoor particulate matter (PM), even though most human exposure to PM of outdoor origin occurs indoors. In this study, we apply a model and empirical data to explore the indoor PM levels of outdoor origin for two major building types: offices and residences. Typical ventilation rates for each building type are obtained from the literature. Published data are combined with theoretical analyses to develop representative particle penetration coefficients, deposition loss rates, and ventilation-system filter efficiencies for a broad particle size range (i.e., 0.001-10 microm). We apply archetypal outdoor number, surface area, and mass PM size distributions for both urban and rural airsheds. We also use data on mass-weighted size distributions for specific chemical constituents of PM: sulfate and elemental carbon. Predictions of the size-resolved indoor proportion of outdoor particles (IPOP) for various conditions and ambient particle distributions are then computed. The IPOP depends strongly on the ambient particle size distribution, building type and operational parameters, and PM metric. We conclude that an accurate determination of exposure to particles of ambient origin requires explicit consideration of how removal processes in buildings vary with particle size.

Air Movements↗

Intake fraction for multimedia pollutants: a tool for life cycle analysis and comparative risk assessment.

We employ the intake fraction (iF) as an effective tool for expressing the source-to-intake relationship for pollutant emissions in life cycle analysis (LCA) or comparative risk assessment. Intake fraction is the fraction of chemical mass emitted into the environment that eventually passes into a member of the population through inhalation, ingestion, or dermal exposure. To date, this concept has been primarily applied to pollutants whose primary route of exposure is inhalation. Here we extend the use of iF to multimedia pollutants with multiple exposure pathways. We use a level III multimedia model to calculate iF for TCDD and compare the result to one calculated from measured levels of dioxin toxic equivalents in the environment. We calculate iF for emissions to air and surface water for 308 chemicals. We correlate the primary exposure route with the magnitudes of the octanol-water partition coefficient, Kow, and of the air-water partitioning coefficient (dimensionless Henry constant), Kaw. This results in value ranges of Kow and Kaw where the chemical exposure route can be classified with limited input data requirements as primarily inhalation, primarily ingestion, or multipathway. For the inhalation and ingestion dominant pollutants, we also define empirical relationships based on chemical properties for quantifying the intake fraction. The empirical relationships facilitate rapid evaluation of many chemicals in terms of the intake. By defining a theoretical upper limit for iF in a multimedia environment we find that iF calculations provide insight into the multimedia model algorithms and help identify unusual patterns of exposure and questionable exposure model results.

Algorithms↗