Dermal Exposure to Contaminated Soil

Investigators: Annette L. Bunge (PI), Donald L. Macalady (co-PI), and R.H. Guy at University of California, San Francisco

Sponser Organization: National Institute of Environmental Sciences

Duration: 4 year project. Started July 1994. A one-year extension was requested in 1998. Project will be completed in 1999.

Abstract: The objective of this research is to develop and experimentally validate algorithms which predict the absorbed dose following dermal exposure to chemically contaminated soils using known, or easily determined, parameters, such as exposure time, octanol-water partitioning, molecular weight, soil particle chemical which is size distribution, and soil organic and water content. Our rationale is that the systemic human health risk from chemical exposure depends upon the mass of absorbed. Because the skin presents a formidable barrier to many chemicals, the absorbed dose can be considerably less than the exposed dose. Furthermore, the number of different chemicals contaminating soils, and the variety of exposure scenarios, are too numerous to investigate all cases experimentally. It is our contention, therefore, that validated predictive algorithms are needed to estimate dermal absorption following exposure to contaminated soils. Accordingly, this research will systematically investigate dermal absorption from soils by uniquely combining mathematical models with in vitro and in vivo experiments to produce predictive algorithms for the absorbed dose.

Prediction and Assessment of Dermal Exposure

Investigators: R.H. Guy at University of California, San Francisco (PI) and Annette L. Bunge (co-PI)

Sponser Organization: U.S. Air Force Office of Scientific Research (CSM is subcontractor to UCSF)

Duration: 3 year project with one-year extension. Started October 1994. Project will end October 1998.

Abstract: The objective of this research is to develop physicochemically and biologically relevant algorithms with which the rate and extent of absorption of a chemical following dermal contact can be accurately predicted for diverse exposure scenarios. The rationale for the approach described is that manifestation of toxicity (local and/or systemic) following cutaneous exposure requires the transdermal penetration of the chemical. The unique permeation barrier properties of skin dictate that the kinetics of percutaneous absorption will, primarily, determine the severity and time-course of any potential hazard. The long-term objective of meaningful risk assessment following dermal exposure, therefore, requires that the rate of the skin penetration in man be predictable. The specific aims of this project are: (1) to derive algorithms to calculate a chemical's steady-state permeability across the skin, (2) to extend the theoretical calculations to unsteady-state situations, (3) to test the predictions of the unsteady-state modeling in vivo in humans using a novel noninvasive methodology, and (4) to explore applications of the models to the assessment of highly lipophilic chemicals and deposited films.

Structure Activity Relationships for Predicting Pesticide Dermal Absorption from Multimedia

Investigators: Annette L. Bunge (PI), Donald L. Macalady (co-PI), and R.H. Guy at University of California, San Francisco.

Sponser Organization: US. Environmental Protection Agency

Duration: 3 year project. Started May 1995. A one-year extension was requested in 1998. Project will be completed in 1999.

Abstract: The objective of this project is to develop a scientifically accurate procedure for computing realistic estimates of dermal absorption of pesticides from multimedia, including commercial formulations, water, surfaces, soil and air. The computation will ensure protection of human health, consider the full range of media, and yet be simple enough for routine evaluations. These dermal absorption models will be combined with pharmacokinetic models which allow for inhalation and ingestion exposures. We will predict parameters required by the models using structure-activity correlations from the literature, from our previous research, or developed as part of this project. We will demonstrate the models for exposure scenarios typical of organophosphorous insecticide and two herbicides. Other pesticide classes will be investigated as resources and data availability allow.

The Relationships Among Particle-Size, Composition, and Partitioning Phenomena in Aqueous Systems

Investigators: Donald L. Macalady (PI), Annette L. Bunge (co-PI), and James Ranville (co-PI)

Duration: 3 year project. Started December 1996.

Abstract: Understanding partitioning phenomena is crucial to a wide range of environmental processes. In particular, partitioning between aqueous and/or other liquid phases and solid phases such as soils or sediments plays a critical role in determining many characteristics of polluted aqueous systems. Increasing understanding of the fundamental chemistry and physics of these processes has facilitated attempts to mathematically connect characteristics of environmental systems to fundamental molecular properties of anthropogenic chemicals and to estimates of risks associated with intended or incidental environmental exposures. Many of these processes depend on the quantity of particulate organic carbon (POC). Hence, it is important to know if the distribution (both amount and chemical characteristics) of POC varies with particle size in soils, sediments and aquifers.
This research will employ gravitational sedimentation in split-flow thin cells (SPLITT) to obtain gram quantities of samples in individual size fractions within the colloidal and silt size categories. Field-flow fractionation will be used to obtain high resolution sizing and separation within each individual size fraction obtained from SPLITT. These techniques may produce fewer sampling artifacts and will allow more accurate characterization of environmental particles than has been previously possible. The POC associated with these fractions will be characterized using various techniques. These fractions will also be used in partitioning experiments. Correlations will be developed between particle characteristics and observed partitioning.

Dermal Absorption of Chemicals from Evaporating Vehicle Mixtures

Investigators: Annette L. Bunge (PI) and R.H. Guy, Centre Interuniversittaire de Recherche et d'Enseignement, Archamps, France (co-PI)

Sponsor Organization: US Air Force, Office of Scientific Research.

Duration: 3 year project. Started November 1997.

Abstract: The goal of this project is to develop procedures for estimating dermal absorption of organic chemicals from evaporating vehicles using absorption data from occluded (non-evaporating) aqueous solutions. To achieve this goal requires two related but separate studies. First, the relationship between dermal absorption measurements from nonaqueous and aqueous vehicles will be established when evaporation is prevented. Second, the theoretical description of the evaporation process will be experimentally demonstrated. The research approach uses mathematical models of the evaporation and absorption processes to design, and then to analyze data from, dermal absorption experiments, and to address the 5 specific aims of the project, namely: (i) to test if lipophilic vehicles enhance the rate or extent of dermal absorption of other chemicals; (ii) to determine the cause and to assess predictability when vehicles do enhance the rate or extent of dermal absorption of other chemicals; (iii) to test if dermal absorption parameters, namely permeability coefficients and partition coefficients, from occluded nonaqueous vehicles are related predictably to parameters measured (or estimated from measurements made) from occluded aqueous vehicles; (iv) to test if the changes in contact area and concentrations which occur when the vehicle evaporates are predictable and if these changes affect predictably the amount and rate of dermal absorption; and (v) to continue development of skin property databases.

Experimental Validation and Reliability Evaluation of Multimedia Risk Assessment Models

Investigators: Robert Siegrist (PI), Andrew Sheldon (co-PI), and Helen Dawson (co-PI)

Spnsor Organization: US EPA

Duration: December 15, 1996 - December 14, 1998

Abstract: This project will quantitatively evaluate the performance and reliability of multimedia contaminant transport models used for assessing human exposure and health risk from soils contaminated with volatile organic compounds (VOCs). Research methods include large-scale contaminant leaching and volatilization experiments, computer modeling, health risk calculations, and statistical data analysis. Large-scale leaching and volatilization experiments will be performed for in situ soil contamination and for soil treatment residuals (i.e., post-treatment chemical remnants). For typical exposure scenarios, estimated health risk values based on experimentally observed chemical leaching and volatilization behavior will be compared with risk estimates obtained from stochastic contaminant transport model results. Contributions to risk assessment uncertainty from multimedia contaminant transport modeling, versus uncertainty contributions from human chemical intake and toxicological evaluations, will be compared. Statistical error and uncertainty analyses of model-versus experiment-based risk estimates will be used to gauge model performance. The goal is to identity typical model performance for practical risk assessment applications based on input parameters developed from standard site data collection methods, rather than based on model calibrations that cannot be accomplished for most contaminated sites. The information developed during the project will be essential for decision makers who must establish "acceptable" modeling error and uncertainty tolerances for health risk assessments in keeping with the data quality objectives process.