Biomedical subjects

T E McKone

Publications and source records attributed to T E McKone.

At least 19 recordsLinked to original sources

PubMed2004

Estimating contaminant dose for intermittent dermal contact: model development, testing, and application.

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure scenarios, skin surface loading and unloading rates, and contaminant movement through the epidermis. In this article we (1) develop and test a finite-difference model of contaminant transport through the epidermis; (2) develop archetypal exposure scenarios based on behavioral data to estimate characteristic loading and unloading rates; and (3) quantify 24-hour accumulation below the epidermis by applying a Monte Carlo simulation of these archetypal exposure scenarios. The numerical model, called Transient Transport through the epiDERMis (TTDERM), allows us to account for variable exposure times and time between exposures, temporal and spatial variations in skin and compound properties, and uncertainty in model parameters. Using TTDERM we investigate the use of a macro-activity parameter (cumulative contact time) for predicting daily (24-hour) integrated uptake of pesticides during complex exposure scenarios. For characteristic child behaviors and hand loading and unloading rates, we find that a power law represents the relationship between cumulative contact time and cumulative mass transport through the skin. With almost no loss of reliability, this simple relationship can be used in place of the more complex micro-activity simulations that require activity data on one- to five-minute intervals. The methods developed in this study can be used to guide dermal exposure model refinements and exposure measurement study design.

Child↗

PubMed2003

Chemical-specific representation of air--soil exchange and soil penetration in regional multimedia models.

In multimedia mass-balance models, the soil compartment is an important sink as well as a conduit for transfers to vegetation and shallow groundwater. Here a novel approach for constructing soil transport algorithms for multimedia fate models is developed and evaluated. The resulting algorithms account for diffusion in gas and liquid components; advection in gas, liquid, or solid phases; and multiple transformation processes. They also provide an explicit quantification of the characteristic soil penetration depth. We construct a compartment model using three and four soil layers to replicate with high reliability the flux and mass distribution obtained from the exact analytical solution describing the transient dispersion, advection, and transformation of chemicals in soil layers with different properties but a fixed boundary condition at the air-soil surface. The soil compartment algorithms can be dynamically linked to other compartments (air, vegetation, groundwater, surface water) in multimedia fate models. We demonstrate and evaluate the performance of the algorithms in a model with applications to benzene, benzo[a]pyrene, MTBE, TCDD, and tritium.

Air Pollutants↗

PubMed2003

Geographical scenario uncertainty in generic fate and exposure factors of toxic pollutants for life-cycle impact assessment.

In environmental life-cycle assessments (LCA), fate and exposure factors account for the general fate and exposure properties of chemicals under generic environmental conditions by means of 'evaluative' multi-media fate and exposure box models. To assess the effect of using different generic environmental conditions, fate and exposure factors of chemicals emitted under typical conditions of (1). Western Europe, (2). Australia and (3). the United States of America were compared with the multi-media fate and exposure box model USES-LCA. Comparing the results of the three evaluative environments, it was found that the uncertainty in fate and exposure factors for ecosystems and humans due to choice of an evaluative environment, as represented by the ratio of the 97.5th and 50th percentile, is between a factor 2 and 10. Particularly, fate and exposure factors of emissions causing effects in fresh water ecosystems and effects on human health have relatively high uncertainty. This uncertainty is mainly caused by the continental difference in the average soil erosion rate, the dimensions of the fresh water and agricultural soil compartment, and the fraction of drinking water coming from ground water.

Australia↗

PubMed2001

Predicting long-range transport: a systematic evaluation of two multimedia transport models.

The United Nations Environment Program has recently developed criteria to identify and restrict chemicals with a potential for persistence and long-range transport (persistent organic pollutants or POPs). There are many stakeholders involved, and the issues are not only scientific but also include social, economic, and political factors. This work focuses on one aspect of the POPs debate, the criteria for determining the potential for long-range transport (LRT). Our goal is to determine if current models are reliable enough to support decisions that classify a chemical based on the LRT potential. We examine the robustness of two multimedia fate models for determining the relative ranking and absolute spatial range of various chemicals in the environment. We also consider the effect of parameter uncertainties and the model uncertainty associated with the selection of an algorithm for gas-particle partitioning on the model results. Given the same chemical properties, both models give virtually the same ranking. However, when chemical parameter uncertainties and model uncertainties such as particle partitioning are considered, the spatial range distributions obtained for the individual chemicals overlap, preventing a distinct rank order. The absolute values obtained for the predicted spatial range or travel distance differ significantly between the two models for the uncertainties evaluated. We find that to evaluate a chemical when large and unresolved uncertainties exist, it is more informative to use two or more models and include multiple types of uncertainty. Model differences and uncertainties must be explicitly confronted to determine how the limitations of scientific knowledge impact predictions in the decision-making process.

Decision Making↗

PubMed2001

Pollutant-specific scale of multimedia models and its implications for the potential dose.

The spatial range is a generic indicator for how far pollutants are likely to travel. It also indicates the appropriate, pollutant-specific area of a multimedia model, which is the square of the spatial range. Formulations of the spatial range can be based on advective or dispersive transport. They differ in whether they take the extent and shape of the earth's surface into account. We suggest the common element of the different approaches is that all account for the persistence and mobility of pollutants. The mobility is the expected travel speed and depends on the partitioning. This paper extends the concept of a pollutant-specific model scale through the introduction of a characteristic atmospheric scale height. It is the height of the atmosphere that would be needed to contain all the pollutant if the entire atmosphere had ground-level concentration, taking into account deposition and degradation. We define the spatial range as the expected advection-driven travel distance of a pollutant molecule released to a specific compartment. This novel analytical formulation is more comprehensive but encompasses all previous advection-based proposals of a spatial range. We evaluate the spatial range and scale height of 288 chemicals for releases to air, surface water, and surface soil. We find a strong correlation between the spatial range for air releases and the scale height because both depend on persistence. We investigate the effect of the spatial scale on calculations of the human toxicity potential, a screening-level risk indicator based on toxicity and potential dose. The product of model area and potential dose is found to be the same for calculations using a fixed model area and those using the pollutant-specific spatial scale. The introduction of the scale height, however, can change the potential dose by more than 1 order of magnitude.

Air Pollutants↗

PubMed2001

Chronic health risks from aggregate exposures to ionizing radiation and chemicals: scientific basis for an assessment framework.

Very little quantitative analysis is currently available on the cumulative effects of exposure to multiple hazardous agents that have either similar or different mechanisms of action. Over the past several years, efforts have been made to develop the methodologies for risk assessment of chemical mixtures, but mixed exposures to two or more dissimilar agents such as radiation and one or more chemical agents have not yet been addressed in any substantive way. This article reviews the current understanding of the health risks arising from mixed exposures to ionizing radiation and specific chemicals. Specifically discussed is how mixed radiation/chemical exposures, when evaluated in aggregation, were linked to chronic health endpoints such as cancer and intermediate health outcomes such as chromosomal aberrations. Also considered is the extent to which the current practices are consistent with the scientific understanding of the health risks associated with mixed-agent exposures. From this the discussion moves to the research needs for assessing the cumulative health risks from aggregate exposures to ionizing radiation and chemicals. The evaluation indicates that essentially no guidance has been provided for conducting risk assessment for two agents with different mechanisms of action (i.e., energy deposition from ionizing radiation versus DNA interactions with chemicals) but similar biological endpoints (i.e., chromosomal aberrations, mutations, and cancer). The literature review also reveals the problems caused by the absence of both the basic science and an appropriate evaluation framework for the combined effects of mixed-agent exposures. This makes it difficult to determine whether there is truly no interaction or somehow the interaction is masked by the scale of effect observation or inappropriate dose-response assumptions.

Animals↗

PubMed2001

Human toxicity potentials for life-cycle assessment and toxics release inventory risk screening.

The human toxicity potential (HTP), a calculated index that reflects the potential harm of a unit of chemical released into the environment, is based on both the inherent toxicity of a compound and its potential dose. It is used to weight emissions inventoried as part of a life-cycle assessment (LCA) or in the toxics release inventory (TRI) and to aggregate emissions in terms of a reference compound. Total emissions can be evaluated in terms of benzene equivalence (carcinogens) and toluene equivalents (noncarcinogens). The potential dose is calculated using a generic fate and exposure model, CalTOX, which determines the distribution of a chemical in a model environment and accounts for a number of exposure routes, including inhalation, ingestion of produce, fish, and meat, and dermal contact with water and soil. Toxicity is represented by the cancer potency q1* for carcinogens and the safe dose (RfD, RfC) for noncarcinogens. This article presents cancer and noncancer HTP values for air and surface-water emissions of 330 compounds. This list covers 258 chemicals listed in U.S. Environmental Protection Agency TRI, or 79 weight-% of the TRI releases to air reported in 1997.

Aging↗

PubMed2000

A systematic uncertainty analysis of an evaluative fate and exposure model.

Multimedia fate and exposure models are widely used to regulate the release of toxic chemicals, to set cleanup standards for contaminated sites, and to evaluate emissions in life-cycle assessment. CalTOX, one of these models, is used to calculate the potential dose, an outcome that is combined with the toxicity of the chemical to determine the Human Toxicity Potential (HTP), used to aggregate and compare emissions. The comprehensive assessment of the uncertainty in the potential dose calculation in this article serves to provide the information necessary to evaluate the reliability of decisions based on the HTP A framework for uncertainty analysis in multimedia risk assessment is proposed and evaluated with four types of uncertainty. Parameter uncertainty is assessed through Monte Carlo analysis. The variability in landscape parameters is assessed through a comparison of potential dose calculations for different regions in the United States. Decision rule uncertainty is explored through a comparison of the HTP values under open and closed system boundaries. Model uncertainty is evaluated through two case studies, one using alternative formulations for calculating the plant concentration and the other testing the steady state assumption for wet deposition. This investigation shows that steady state conditions for the removal of chemicals from the atmosphere are not appropriate and result in an underestimate of the potential dose for 25% of the 336 chemicals evaluated.

Air Pollutants↗

PubMed1999

Parameter uncertainty and variability in evaluative fate and exposure models.

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows us to focus our resources if we want to reduce the uncertainty. The potential dose of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.

Animals↗

PubMed1996

Uncertainties in the link between global climate change and predicted health risks from pollution: hexachlorobenzene (HCB) case study using a fugacity model.

Industrial societies have altered the earth's environment in ways that could have important, longterm ecological, economic, and health implications. In this paper, we examine the extent to which uncertainty about global climate change could impact the precision of predictions of secondary outcomes such as health impacts of pollution. Using a model that links global climate change with predictions of chemical exposure and human health risk in the Western region of the United States of America (U.S.), we define parameter variabilities and uncertainties and we characterize the resulting outcome variance. As a case study, we consider the public health consequences from releases of hexachlorobenzene (HCB), a ubiquitous multimedia pollutant. By constructing a matrix that links global environmental change both directly and indirectly to potential human-health effects attributable to HCB released into air, soil, and water, we define critical parameter variances in the health risk estimation process. We employ a combined uncertainty/sensitivity analysis to investigate how HCB releases are affected by increasing atmospheric temperature and the accompanying climate alterations that are anticipated. We examine how such uncertainty impacts both the expected magnitude and calculational precision of potential human exposures and health effects. This assessment reveals that uncertain temperature increases of up to 5 degrees C have little impact on either the magnitude or precision of the public-health consequences estimated under existing climate variations for HCB released into air and water in the Western region of the U.S.

Biometry↗

PubMed1995

Comparison of multi-media transport and transformation models: regional fugacity model vs. CalTOX.

Two multimedia environmental transport and transformation computer models are summarized and compared. The regional fugacity model published by Mackay and Paterson (1991), termed Fug3ONT, is a four compartment steady-state model designed to simulate the relative distribution of nonionic organic chemicals in a multimedia system. CalTOX is a seven compartment multimedia total exposure model for hazardous waste sites. Both models are based on the principles of fugacity. CalTOX, however, separates the soil into three layers (surface, root, and vadose) and uses a different approach to estimate the diffusive mass transfer rate in soil. These differences result in lower estimates of the steady-state contaminant concentrations of six environmentally relevant chemicals in the root soil of CalTOX as compared to the bulk soil of Fug3ONT. The difference is greatest for compounds with low mobility in soil such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Benzo(a)pyrene where estimates from CalTOX and Fug3ONT differ by more than 3 orders of magnitude. Otherwise, the models provide similar estimates for the distribution of the six chemicals among the air, water, sediment and surface soil.

Air Pollutants↗

PubMed1995

Estimating skin permeation. The validation of five mathematical skin permeation models.

This study provides an analysis of the reliability of five mathematical models, simulating permeation of substances through the skin from aqueous solutions. An extensive database was generated, containing data on 123 measured permeation coefficients of 99 different chemicals and their physicochemical properties. In addition, in this database all relevant experimental conditions are included. The coefficients of the different skin permeation models were estimated by non-linear multiple regression, using the octanol-water partition coefficient and the molecular weight as independent parameters. The reliability of the models was evaluated by testing variation of regression coefficients and of residual variance for subsets of data, randomly selected from the complete database. Three models were considered to provide reliable estimations of the skin permeation coefficient. These are based on the McKone and Howd model, the Guy and Potts model and the Robinson model. The last-mentioned two models were adaptations, because MW0.5 as independent parameter provided a better fit than MW (MW = molecular weight) in the original models. The McKone and Howd model and the Robinson model have the advantage, that they predict more precisely the skin permeation of highly hydrophilic and highly lipophilic chemicals compared to the Guy and Potts model. The revised Robinson model resulted always in the smallest residual variance.

Benzene↗

PubMed1994

Uncertainty and variability in human exposures to soil contaminants through home-grown food: a Monte Carlo assessment.

This paper presents a general model for exposure to homegrown foods that is used with a Monte Carlo analysis to determine the relative contributions of variability (Type A uncertainty) and true uncertainty (Type B uncertainty) to the overall variance in prediction of the dose-to-concentration ratio. Although classification of exposure inputs as uncertain or variable is somewhat subjective, food consumption rates and exposure duration are judged to have a predicted variance that is dominated by variability among individuals by age, income, culture, and geographical region. Whereas, biotransfer factors and partition factors are inputs that, to a large extent, involve uncertainty. Using ingestion of fruits, vegetables, grains, dairy products, and meat and soils assumed to be contaminated by hexachlorobenzene (HCB) and benzo(a)pyrene (BaP) as cases studies, a Monte Carlo analysis is used to explore the relative contribution of uncertainty and variability to overall variance in the estimated distribution of potential dose within the population that consumes home-grown foods. It is found that, when soil concentrations are specified, variances in ratios of dose-to-concentration for HCB are equally attributable to uncertainty and variability, whereas for BaP, variance in these ratios is dominated by true uncertainty.

Algorithms↗

PubMed1993

The value of animal test information in environmental control decisions.

Value of information (VOI) analytic techniques are used to evaluate the benefit of performing animal bioassays to provide information about the cancer potency of specific chemical compounds. These tools allow the identification of the conditions in which the cost of reducing uncertainty about potency, by performing a subchronic or chronic bioassay, is justified by the benefit of having improved information for making control decisions. The decision analytic results are readily scaled to apply to a range of human contact rates (exposures) and a variety of control strategies. The sensitivity of results to uncertainty about animal to human extrapolation and the design of the bioassay is explored. An evaluation of the possible gains in general understanding about the mechanisms of carcinogenicity resulting from chronic bioassays is beyond the scope of this approach.

Animals↗

PubMed1992

Uncertainties in health-risk assessment: an integrated case study based on tetrachloroethylene in California groundwater.

Population risk to an environmental contaminant is represented as the product of a source term; the exposure function, which converts the source into a lifetime-equivalent contact rate in the population; the fraction metabolized; the toxic potency associated with the delivered dose; and the size of the exposed population. Using case studies for contamination of groundwater in California with tetrachloroethylene (PCE), the combined uncertainty in exposure and dose-response models is characterized. Three key issues are addressed: (a) uncertainty in quantifying pathway exposure factors that relate measured environmental concentrations to levels of contact in the exposed population; (b) the uncertainty in the human dose-response models derived from animal data; and (c) an overview of important contributors to the overall uncertainty in population risk estimates.

Administration, Inhalation↗

PubMed1992

Estimating dermal uptake of nonionic organic chemicals from water and soil: I. Unified fugacity-based models for risk assessments.

Contamination of water and soil that might eventually contact human skin makes it imperative to include the dermal uptake route in efforts to assess potential environmental health risks. Direct measurements of dermal uptake from either water or soil are only available for a small number of the thousands of chemicals likely to be found in the environment. We propose here a mass-transfer model for estimating skin permeability and dermal uptake for organic chemicals that contaminate soil and water. Statistical relationships between measured permeabilities and chemical properties reveal that permeability varies primarily with the octanol-water partition coefficient (Kow) and secondarily with the molecular weight. From these results, we derive a fugacity-based model for skin permeability that addresses the inherent permeability of the skin, the interaction of the skin with the environmental medium on skin (water or soil), and retains a relatively simple algebraic form. Model predictions are compared to measured human skin permeabilities for some 50 compounds in water and four compounds in soil. The model is adjusted to account for dermal uptake during both short-term (10-20 min) and long-term (several hour) exposures. This model is recommended for compounds with molecular weight less than or equal to 280 g.

Biological Transport, Active↗

PubMed1991

Estimating human exposure through multiple pathways from air, water, and soil.

This paper describes a set of multipathway, multimedia models for estimating potential human exposure to environmental contaminants. The models link concentrations of an environmental contaminant in air, water, and soil to human exposure through inhalation, ingestion, and dermal-contact routes. The relationship between concentration of a contaminant in an environmental medium and human exposure is determined with pathway exposure factors (PEFs). A PEF is an algebraic expression that incorporates information on human physiology and lifestyle together with models of environmental partitioning and translates a concentration (i.e., mg/m3 in air, mg/liter in water, or mg/kg in soil) into a lifetime-equivalent chronic daily intake (CDI) in mg/kg-day. Human, animal, and environmental data used in calculating PEFs are presented and discussed. Generalized PEFs are derived for air----inhalation, air----ingestion, water----inhalation, water----ingestion, water----dermal uptake, soil----inhalation, soil----ingestion, and soil----dermal uptake pathways. To illustrate the application of the PEF expressions, we apply them to soil-based contamination of multiple environmental media by arsenic, tetrachloroethylene (PCE), and trinitrotoluene (TNT).

Administration, Inhalation↗

PubMed1991

The transfer of trichloroethylene (TCE) from a shower to indoor air: experimental measurements and their implications.

Experiments were performed to measure the transfer of trichloroethylene (TCE), a volatile organic compound (VOC), from tap water in showers to indoor air. In these experiments, the loss of TCE from tap water in the shower is based on the difference between influent and effluent concentrations. We have developed and previously published a three-compartment model, which we use to simulate the 24-h concentration history of VOCs in the shower, bathroom, and remaining household volumes resulting from the use of contaminated tap water. An important input to this model is the transfer efficiency of the VOC from water to air. The experiments reveal that the transfer efficiency of TCE from shower water to air has an arithmetic mean value of 61 percent and an arithmetic standard deviation of 9 percent. Analysis of the results shows that there is no statistically significant difference between the transfer efficiency measured with hot (37 degrees C) or cold (22 degrees C) shower water and that there is no statistically significant change in transfer efficiency with time during a 20-min shower. The implications for exposure assessment are considered.

Air Pollutants↗