Health Hazard Identification Task
Group
Scolarly Products 1995 - 2000
| A
biologically-based dose-response model for developmental
toxicology Author: Leroux, B.G., Other Author(s): W.M. Leisenring, S.H. Moolgavkar, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: Risk Analysis 16(4): 449-458. Abstract: The methods currently used to evaluate the risk of developmental defects in humans from exposure to potential toxic agents do not reflect biological processes in extrapolating estimated risks to low doses and from test species to humans. We develop a mathematical model to describe aspects of the dynamic process of organogenesis, based on branching process models of cell kinetics. The biological information that can be incorporated into the model includes timing and rates of dynamic cell processes such as differentiation, migration, growth, and replication. The dose-response models produced can explain patterns of malformation rates as a function of both dose and time of exposure, resulting in improvements in risk assessment and understanding of the underlying mechanistic processes. To illustrate the use of the model, we apply it to the prediction of the effects of methylinercury on brain development in rats. |
| A flow
cytometric method to screen for beryllium sensitization Author: Jabbour, A.V., Other Author(s): J.A. Hill, R.A. Ponce, K.B. Ertell, T.J. Kavanagh, L.S. Newman, T.K. Takaro, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA. March 14-18. Abstract: |
| A
P53-independent methylmercury-induced g2/M arrest Author: Mendoza, M.C., Other Author(s): Y.C. Ou, S. Hong, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA, March 14-18. Abstract: |
| An index of
harm for exposure to a combination of radiation and
chemical pollutants Author: Curtis, S.B., Other Author(s): S.M. Bartell, E.M. Faustman, and W.C. Griffith. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Radiation Research Society Annual Meeting. Louisville, KY, April. Abstract: |
| An index of
harm for exposure to a combination of radiation and
chemical pollutants Author: Curtis, S.B., Other Author(s): S.M. Bartell, E.M. Faustman and W.C. Griffith. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Risk Analysis Abstract: |
| An index of
harm for exposure to a combination of radiation and
chemical pollutants Author: Curtis, S.B., Other Author(s): S.M. Bartell, E.M. Faustman, and W.C. Griffith. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society for Risk Analysis Annual Meeting, Phoenix, AZ. December 6-9. Abstract: |
| Analysis of
changes in heatshock protein genes in uropithelial cells
as biomarkers of heat stress: applications to DOE
workers. Poster Author: Kirchner, SC., Other Author(s): T.J. Kavanagh, T. Takaro, K.A. Hunt, T.A. Lewandowski, S.W. Hong, C.H. Muller, M. Gold, and E.M. Faustman Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Analysis of
gene expression by laser-induced flourescence as a
biomarker of risk from exposure to toxic and radiological
hazards Author: White, C., Other Author(s): S. Quigley, S. Kirchner, R. Ponce, E. Faustman, and T. Kavanagh. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: University of Washington First Annual Conference on The Health of the Hanford Site: Current Challenges, Richland, WA, December 3-4. Abstract: |
| Analysis of
gene expression changes in uroepithelial cells as
biomarkers of heat stress. Poster Author: Kirchner, S.C., Other Author(s): K.A. Hunt, T.J. Kavangh, T.A. Lewandowski, S.W. Hong, C.H. Muller, M. Gold, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Application
of a biologically-based RFD estimation method to
tetrachlorobibenzo-p-dioxin (TCDD) mediated immune
suppression and enzyme induction Author: McGrath, L.F., Other Author(s): P. Georgopoulos, and M.A. Gallo. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: Risk Analysis 16(4): 439-448. Abstract: The current methods for a reference dose (RfD) determination can be enhanced through the use of biologically-based dose-response analysis. Methods developed here utilizes information from tetrachlorodibenzo-p-dioxin (TCDD) to focus on noncancer endpoints, induction. Dose-response analysis, using the Sigmoid-Emax (EMAX) function, is applied to multiple studies to determine consistency of response. Through the use of multiple studies and statistical comparison of arameter estimates, it was demonstrated that the slope estimates across studies were very consistent. This adds confidence to the subsequent effect dose estimates. This study also compares traditional methods of risk assessment such as the NOAEL/safety factor to a modified benchmark dose approach which is introduced here. Confidence in the estimation of an effect dose (ED10) was improved through the use of multiple datasets. This is key to adding confidence to the benchmark dose estimates. In addition, the Sigrnoid-Emax function when applied to dose-response data using nonlinear regression analysis provides a significantly improved fit to data increasing confidence in parameter estimates which subsequently improve effect dose estimates. |
| Barriers to
respirator use Author: Salazar, M. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Third Annual University of Washington Conference on the Ecological, Community, and Occupational Health Issues at Hanford, November 2-3. Abstract: |
| Beryllium
sensitization at Hanford: Applying the sentinel case
approach to improve exposure assessment Author: Takaro, T. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: Citation: Third Annual University of Washington Conference on the Ecological, Community, and Occupational Health Issues at Hanford, November 2-3. Abstract: |
| Biologically
based dose-response models for developmental toxicants:
Lessons from methylmercury Author: Faustman, E.M., Other Author(s): T.A. Lewandowski, R.A. Ponce, and S.M. Bartell. Document Type: CRESP Published Manuscripts Publication Date: 1999 Citation: Inhalation Toxicology 11: 559-572. Abstract: Risk assessment methods commonly used to evaluate the developmental toxicity of environmental exposures have historically focused on the identification of no adverse effect levels (NOAEL) rather than dose- response modeling. While NOAELS, which are based on identifying the highest level of exposure that does not increase the incidence of an adverse developmental effect, are used to define "acceptably safe" exposure concentrations, they do not allow one to predict response rates across a range of exposures (Faustman & Bartell, 1997). Benchmark dose methods, which use dose-response models fit to the available data, have gained attention because they address several limitations inherent in NOAELS. Along with the increased emphasis on using benchmark-dose models for developmental toxicant risk assessment has come increased attention on establishing and characterizing appropriate dose-response models for developmental toxicants (Allen et al., 1994a, 1994b; Faustman et al., 1994; Faustman & Bartell, 1997; Kavlock et al., 1995). Establishing dose-response models based on underlying biological processes, or biologically based dose-response (BBDR) modeling, has been proposed as a logical basis for establishing these dose-response models. For example, in some cases the use of biologically informed models for benchmark dose calculations has been shown to improve fit of dose-response curves to observed experimental values (Allen et al., 1994b). While toxicological experiments often examine frank disease resulting from relatively high exposures, biological information that is incorporated into BBDR models can provide a basis for defining the dose-response relationship for subtle responses associated with lower, environmentally relevant exposures (e.g., Geacintov & Swenberg, 1991). Of particular interest in our research are the design and application of BBDR models in the assessment of developmental toxicants. Biological research findings have been used to develop BBDR cancer models; however, fewer models have been developed for noncancer end-points. In those cases where experimental data has been used to model developmental toxicity, the resultant models are generally biologically informed, rather than biologically based. For our purposes in this article we define biologically informed as meaning that a model is consistent with biological processes and may consider biological constraints or relationships, though the model may not directly model the biological process. For example, Rai and van Ryzin described a two-stage probability model for developmental toxicity that assumed teratogenicity was contingent upon maternal toxicity (Rai & Van Ryzin, 1985). Faustman et al. broadened the application of this model for developmental toxicity so that adverse birth outcomes were no longer strictly dependent on maternal toxicity; however, no alternative mechanistic pathways for developmental toxicity were proposed (Faustman et al., 1989). Other researchers at that time experimented with alternative statistical approaches to modeling dose-response relationships of the type observed with developmental toxicants and that incorporated basic biological observations (Chen & Kodell, 1989; Gaylor, 1988; Gaylor & Chen, 1993; Gaylor & Razzaghi, 1992; Kimmel & Gaylor, 1988; Kimmel et al., 1989; Williams, 1987). More recent research has ventered on BBDR models in which the model variables, their values, and definition of their interrelationships have been established according to proposed biological processes. The multi-stage model of carcinogenesis stands as one of the first BBDR models that used information derived from experimental observation (Armitage & Doll, 1957). Current BBDR cancer models are generally more sophisticated in their ability to directly model the proposed underlying biology of carcinogenesis than the first cancer models and can directly incorporate information from new animal and human research to improve models. Such models can include knowledge about the number and kinetics of specific mutations and cellular proliferation responses leading to tumor formation (Luebeck & Moolgavkar, 1996; Moolgavkar & Luebeck, 1995; Moolgavkar & Venzon, 1979; Portier et al., 1996; Sherman & Portier, 1.996). For evaluation of developmental toxicity, basic scientific research on understanding the biological relationships of fetal death, malformation, and altered birth weights following environmental exposure has been used to develop biologically informed dose response models (e.g., Catalano et al., 1993, 1994; Krewski & Zhu, 1994; Kupper et al., 1986; Ryan, 1992). BBDR models of developmental toxicity have been developed for specific dys- morphogenic processes, such as palatogenesis (Freni & Zapisek, 1991), and for specific teratogens, such as for 5-fluorouracil (Kavlock & Setzer, 1996; Shuey et al., 1994, 1995). In this article, we describe the development of a biologically based dose-response model for the developmental toxicity of methylmercury (MeHg), which is a well-recognized human and animal neurodevelopmental toxicant. The biological basis for the model lies in the assumption that the developmental toxicity of MeHg can be explained by its ability to alter rates of cell proliferation, differentiation, and cell loss in the developing central nervous system (CNS), and thus reduce the number of properly functioning neurons in the mature brain. For the purposes of this model, we evaluate midbrain development in the fetal rat during the period of gestation days 12-17, as these gestational days are critically important to the establishment of all major nerve foci in the midbrain. We review the rationale for model development, how experimentally derived biological information was used in characterizing model variables, and future directions for improvement and wider application of this BBDR model. |
| Biomarkers:
Mechanistic understanding of the exposure to effect
continuum. Poster Author: McGrath L.F., Other Author(s): R. Ponce, Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Cell cycle
phase-specific expression of cell cycle regulatory genes
in rodent embryonic neuroepithelial cells exposed to
methylmercury Author: McMillan, M.J., Other Author(s): R.A. Ponce, S.C. Kirchner, K.A. Hunt, S. Hong, Y.C. Ou, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1998 Citation: Proceedings of the Teratology Society Annual Meeting 57(4/5):225. Abstract: |
| Cell cycle
phase-specific expression of cell cycle regulatory genes
in rodent embryonic neuroepithelial cells exposed to
methylmercury Author: McMillan, M.J., Other Author(s): R.A. Ponce, S.C. Kirchner, K.A. Hunt, S. Hong, Y.C. Ou, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Teratology Annual Meeting, San Diego, CA, June. Abstract: |
| Changes in
androgen status of solvent-exposed workers Author: Luderer, U. Other Author(s): Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Comments on
“An approach for modeling noncancer dose responses
with an emphasis on uncertainty” and "A
probablistic framework for the reference
dose(probablistic R&D) Author: Bartell, S.M., Other Author(s): and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: Risk Analysis 18(6): 663-664. Abstract: |
| Comments on
proposed rules for USDOE's Chronic Beryllium Disease
Prevention Program, 64 FR 29811, June 3, 1999, Docket
Number EH-RM-98-BRYLM Author: Takaro, T.K., Other Author(s): R. Ponce, A.J. Jabbour, K. Ertell, and J. Abbotts. Document Type: CRESP Reports Publication Date: 1999 Citation: Seattle, WA: University of Washington Abstract: CRESP agrees with USDOE that release of beryllium contaminated buildings or equipment is of paramount concern for the Department. In this document, we clarify our previous recommendations on standards for the release of beryllium contaminated items. We also describe potential health risks from dermal exposure to beryllium, which we recommen that USDOE consider as it develops standards for release of beryllium contaminated materials. |
| Comparative
analyses of exposure estimates based on biomarkers or
predictive models: A case example with dietary
methylmercury intake Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.N. Sanga, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Second Health of the Hanford Site Annual Conference. Richland, WA, November 3-4. Abstract: |
| Comparative
analysis of exposure estimates based on biomarkers of
predictive models: A case example with dietary
methylmercury intake, Presentation Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.N. Sanga, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: International Union of Toxicology VIII Annual Meeting. Paris, France, July 5-9. Abstract: |
| Comparative
analysis of exposure estimates based on biomarkers of
predictive models: A case example with dietary
methylmercury intake. Poster Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.N. Sanga, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: International Union of Toxicology VIII Annual Meeting, Paris, France, July 5-9. Abstract: |
| Comparison of
DOE's recently developed risk prioritization model with
other priority setting tools used for ranking hazardous
waste sites Author: Faustman, E.M., Other Author(s): G. van Belle, T.G. Ewers, J.A. Moore, C. Powers, M. Greenberg, and G.S. Omenn. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1995 Citation: Society for Risk Analysis (SRA) and International Society for Exposure Assessment (ISEA) Joint Meeting. Cambridge, MA. Abstract: |
| Comparisons
between predictive modeling and use of biomarkers in
assessing dietary methylmercury exposure Author: Ponce. R.A., Other Author(s): S.M. Bartell, R.C. Lee, R.U. Sanga, G.S. Omenn, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Platform Health of the Hanford Site Conference: Current Challenges, Richland, WA, December 3-4. Abstract: |
| Comparisons
between predictive modeling and use of biomarkers in
assessing dietary methylmercury exposure Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.C. Lee, W. Griffith, G.S. Omenn, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1998 Citation: Proceedings of the First Annual Health of the Hanford Site Conference: Current Challenges, Round Two Workshops: Community Health, Richland, WA. December 3-4, 1997. Abstract: |
| CRESP at one
year Author: Faustman, E.M. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: Spectrum American Nuclear Society Annual Meeting '96. Seattle, WA. Abstract: |
| CRESP: A new
approach to stakeholder-responsive, cost-effective
research Author: Goldstein, B.D., Other Author(s): C. Powers, J. Moore, E. Faustman, and A. Upton. Document Type: CRESP Reports Publication Date: 1997 Citation: Abstract: |
| Decision
analysis for public health Author: Bartell, S.M. Other Author(s): Document Type: CRESP Educational Courses Given Publication Date: 1997 Citation: University of Washington Risk Assessment graduate course, Seattle, WA, November. Abstract: |
| Decision
analysis for public health Author: Bartell, S.M. Other Author(s): Document Type: CRESP Educational Courses Given Publication Date: 1998 Citation: University of Washington Risk Assessment graduate course, Seattle, WA, October. Abstract: |
| Development
of gene expression analyses as biomarkers of exposure and
effect Author: Kirchner, S.C., Other Author(s): T.J. Kavanagh, J. Woods, T.K. Takaro, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: University of Washington First Annual Conference on The Health of the Hanford Site: Current Challenges, Richland, WA, December 3-4, 1997. Abstract: |
| Development
of gene expression analyses as biomarkers of exposure and
effect Author: Ponce R.A., Other Author(s): S.C. Kirchner, T.J. Kavanagh, J. Woods, T.K. Takaro, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: First Annual Health of the Hanford Site Conference: Current Challenges, Round Two: Occupational Health. Richland, WA, December 3. Abstract: To present efforts underway at the University of Washington Department of Environmental Health to develop techniques that use changes in gene expression in human uroepithelial or UE cells as biomarkers of effect. To describe what is meant by a biomarker, why these tools are useful, and why examining gene expression in uroepithelial cells may be a valid approach for identifying new biomarkers. To present results from experiments investigating gene expression in humans exposed to heat stress as a case application of gene expression in human UE cells. |
| Development
of gene expression analysis as biomarkers of exposure and
effect Author: Ponce, R.A., Other Author(s): S.C. Kirchner, T.J. Kavanagh, J. Woods, T.K. Takaro, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1997 Citation: In Proceedings of the First Annual Health of the Hanford Site Conference: Current Challenges, 274-282. Richland, WA, December 3-4. Abstract: To present efforts underway at the University of Washington, Department of Environmental Health to develop techniques that use changes in gene expression in human uroepithelial or UE cells as biomarkers as effect. To describe what is meant by a biomarker, why these tools are useful, and why examining gene expression in uroepithelial cells may be a valid approach for identifying new biomarkers. Last, to present results from experiments investigating gene expression in humans exposed to heat stress as a case application of gene expression in human UE cells. |
| Development
of public health assessments that consider risks from
methylmercury and nutritional benefits of fish
consumption Author: Ponce, R.A., Other Author(s): S.M. Bartell, C. Carrington, E.M. Faustman, R.C. Lee, and P.M. Bolger. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: 5th International Conference on Mercury as a Global Pollutant, Rio de Janeiro, Brazil, May 23-27, 1999. Abstract: |
| Effect of
tissue binding uncertainty on a PBTK model of
methylmercury in the fetal rat Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Toxicological Letters 95(Suppl. 1), No. P2F148. Abstract: |
| Effects of
uncertainties on exposure estimates to methylmercury: A
Monte Carlo analysis of biomarkers of exposure vs.
predictive dietary estimaiton. Poster Author: Sanga, R.N., Other Author(s): S.M. Bartell, R.A. Ponce, C.H. Pierce, C.R. Joiris, A.A.P. Boischo, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: Best student paper award, Risk assessment specialty section. |
| Effects of
uncertainties on exposure estimates to methylmercury: A
Monte Carlo analysis of biomarkers of exposure vs.
predictive dietary estimation Author: Sanga, R.N., Other Author(s): S.M. Bartell, R.A. Ponce, A.A.P. Boischio, C.R. Joiris, C.H. Pierce, and E.M. Faustman. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Risk Analysis Abstract: We present a general model for differentiating between population heterogeneity and "lack of knowledge" uncertainty in methylmercury (MeHg) exposure assessments using two-dimensional Monte Carlo analysis. Using data from fish-consuming populations in Bangladesh, Brazil, Sweden and the United King, we compared predictive model estimates of dietary methylmercury exposures against those derived from biomarkers (i.e., [Hg]hair, and [Hg]blood). By disaggregating parameter uncertainty into components (i.e., population heterogeneity, measurement error, recall error and sampling error) we obtained estimates of the contribution of each component to the overall uncertainty. Steady-state diet:hair and diet:blood MeHg exposure ratios were estimated for each population and used to develop distributions useful for conducting biomarker-based probabilistic assessments of MeHg exposure. We present 5th and 95th percentile modeled exposure estimates around mean population exposure from each of the four study populations to demonstrate lack of knowledge uncertainty about a true mean. For example, results from a United Kingdon study population showed that a predictive dietary model resulted in an 74% lower lack of knowledge uncertainty about a central mean estimate relative to a hair biomarker model, and also in a 31% lower lack of knowledge uncertainty about a central mean estimate relative to a blood biomarker model. Similar results were obtained for the Brazil and Bangladesh populations. When comparing exposure estimates from the UK population for the predictive model, hair biomarker model, and blood biomarker model to an assumed bias free duplicate diet exposure model from the same population, the blood biomarker was seen to have the least bias amongst all models. Such analyses, used here to evaluate alternative models of dietary MeHg exposure, can be used to refine exposure instruments, to improve information used in site management and remediation decision making, and to identify sources of uncertainty in risk estimates. |
| Effects of
uncertainties on exposure estimates to methylmercury: A
Monte Carlo analysis of biomarkers of exposure vs.
predictive dietary information. Poster Author: Sanga R.N. Other Author(s): S.M. Bartell, R.A. Ponce, A. Boischo, C.R. Joiris, C.H. Pierce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Empirical vs.
mechanistically-based dose-response modeling of
organophosphate pesticide toxicity Author: McGrath, L.F., Other Author(s): and R. Ponce. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA, March 14-18. Abstract: |
| ENVH 577:
Risk assessment 1982 to present Author: Faustman, E.M., Other Author(s): and G.S. Omenn. Document Type: CRESP Educational Courses Given Publication Date: 1997 Citation: University of Washington, Department of Environmental Health. Seattle, WA. Abstract: |
| EOHSI hazard
identification task group overview of projects. Poster Author: McGrath, L.F. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Estimation of
childhood soil ingestion rates with biomonitoring data
from soil remediation studies Author: Bartell, S.M. Other Author(s): Document Type: CRESP Dissertations or Theses Completed Publication Date: 1996 Citation: University of Washington Department of Environmental Health, Seattle, WA. Abstract: |
| Estimation of
soil ingestion rates from observed blood lead loss
following soil remediation Author: Bartell, S.M., Other Author(s): Shirai, J., and J. Kissel. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Evaluating
risk assessment biomarkers using the Value-of-Information
framework Author: Bartell, S.M., Other Author(s): R.A. Ponce, R.C. Lee, T.K. Takaro, G.S. Omenn, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1998 Citation: In proceedings of Spectra ‘98. Denver, CO, September 13-18, 19. Abstract: The development and use of biomarkers in clinical, a rapid occupational and research settings have grown at a rapid pace over the last two decades. In particular, applications of biomarkers to environmental risk assessment have become common. Although biomarkers offer the potential for improving information currently available for risk assessment and risk management, quantitative evaluations of the utility of specific biomarkers are lacking. Such assessments would be valuable for researchers and risk managers in determining whether the costs of developing and applying. biomarkers are justified by the added information they are expected to provide. We present two case examples in which we apply uncertainty analysis and value-of-information analysis to evaluate the utility (defined here as "net benefits") of information derived from biomarkers. In the first case study we examine the uncertainty associated with methylrnercury exposure estimates derived from biomarker-based models and a predictive dietary model, in order to estimate the value of mercury exposure biomarker information. In the second case study, we estimate the disease reduction that is expected to result from alternative genetic susceptibility screening programs for occupational beryllium exposure, and compare the results with the costs of genetic testing. Quantitative ncertainty analysis and value-of-information analysis can be used to estimate the degree to which biomarkers improve risk assessment information and to assess how and when their development and use is justified. |
| Evaluating
risk assessment biomarkers using the value-of-information
framework Author: Bartell, S.M., Other Author(s): R.A. Ponce, R.C. Lee, T.K. Takaro, G.S. Omenn, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: International Conference on Decommissioning and Decontamination and on Nuclear and Hazardous Waste Management, Denver, CO. September 13-18. Abstract: |
| Evaluation of
biomarkers for use in risk assessment and
decision-making: Application of value-of-information
analyses Author: Faustman E.M., Other Author(s): S.M. Bartell, R.C. Lee, T.J. Kavanagh, T.K. Takaro, and R.A. Ponce. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Poster. Conference on Scientific and Engineering Challenges in Remediation of Contaminated Soil and Groundwater, Seattle, WA. May. Abstract: |
| Evaluation of
biomarkers for use in risk assessment and
decision-making: Application of value-of-Information
analyes Author: Faustman, E.M., Other Author(s): S.M. Bartell, R.C. Lee, T.J. Kavanagh, T.K. Takaro, and R.A. Ponce. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Biomarkers, the Genome, and the Individual. U.S. DOE, Charleston, SC., May. Abstract: |
| Evaluation of
biomarkers for use in risk assessment and
decision-making; the value-of- information framework Author: Bartell, S.M., Other Author(s): R.A. Ponce, R.C. Lee, G.S. Ommen and E.M. Faustman. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Evaluation of
potential cancer risks asociated with chemical mixtures
using biologically-based dose-response models:
Sensitivity analyses of models using simulated
experiments Author: Lee, R.C., Other Author(s): E.G. Luebeck, S.B. Curtis, S.M. Bartell, and E.M. Faustman. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Evaluation of
potential cancer risks associated with chemical mixtures
using biologically based dose-response models:
Sensitivity analyses of models using simulated
experiments Author: Lee, R.C., Other Author(s): E.G. Luebeck, S.B. Curtis, S.M. Bartell, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: Society for Risk Analysis (SRA) and International Society for Exposure Assessment (ISEA) Joint Meeting. New Orleans, LA, December 8-11. Abstract: |
| Evaluation of
tissue binding coefficient uncertainty on a PBTK model of
methylmercury in the fetal rat Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: International Union of Toxicology: ICT VIII. INTOX. Paris, France, July 5. Abstract: |
| Experimental
approaches to evaluate mechanisms of developmental
toxicity Author: Faustman, E.M., Other Author(s): R.A. Ponce, M.R. Seeley, and S.G. Whittaker. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1997 Citation: In Handbook of Developmental Toxicology, Chapter 1, edited by R. Hood, 13-41. Boca Raton: C RC Press, Inc. Abstract: |
| Feasability
of uroepithelial cells to identify molecular biomarkers
of heat stress Author: Kirchner, S.C., Other Author(s): S.W. Hong, K.E. Hunt, J.S. Woods, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Field
Measurement of Dermal Soil Loadings in Occupational and
Recreational Activities Author: Holmes, K.K., Other Author(s): J.H. Shirai, K.Y. Richter, J.C. Kissel. Document Type: CRESP Published Manuscripts Publication Date: 1999 Citation: Environmental Research 80(2):148-157. Abstract: Risks associated with dermal exposure to contaminated soil are not well-characterized, but nevertheless must be estimated to define endpoints for remedial strategies. Among the parameters contributing to the uncertainty of these estimates is soil adherence to skin. Pre- and postactivity soil loadings have been obtained from hands, forearms, lower legs, faces, and/or feet of volunteers engaged in various occupational and recreational activities. These data are distinguished from other sources of estimates of soil adherence by the manner of their collection. Soil loads were obtained directly from multiple body parts before and after uncontrived exposure scenarios. Data presented for the first time here supplement prior results and roughly double the available data base. This expanded data base provides a useful perspective on types of behavior likely to lead to soil contact falling within general classes of activity (e.g., background, low, moderate, or high contact). Prior conclusions supported by the additional data include the following: (1) post-activity loadings are typically higher than preactivity levels, demonstrating that exposure is episodic; (2) hand loadings are dependent upon class of activity; (3) hand loadings generally provide conservative estimates of loadings on nonhand body parts within activity classes; and (4) hand loadings do not provide conservative estimates of nonhand loadings across activity classes. Finally quantitative estimates of relative loads on unclothed nonhand body parts are presented. |
| Flow
cytometric determination of metallothionein levels in
human peripheral blood lymphocytes: Utility in
environmental exposure assessment Author: Yurkow, E.J., Other Author(s): and P. R. Makhijani. Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: Journal of Toxicology and Environmental Health 54(6): 445-457. Abstract: Metallothioneins (MT) are ubiquitous, low-molecular-weight proteins that exhibit high binding affinities for heavy metal ions. The expression of these cysteine-rich proteins is induced in response to various types of chemical and physical stresses and therefore can be used to assess human exposure to cytotoxic environmental agents. In the current study, MT levels of human peripheral blood lymphocytes were determined using an MT-specific antibody and flow cytometry. Treatment of human whole blood ex vivo with CdCl2 was found to induce a concentration- and time-dependent increase in lymphocyte MT levels at concentrations as low as 0.3 M and within a 12-h period. Interestingly, differences were observed in the magnitude of cadmium-induced MT levels in the lymphocytes of six human test subjects. Two members of the study population exhibited CdCl2-induced cellular MT levels that were up to twofold greater than the lymphocytes of other human subjects. While the lymphocytes of most test subjects exhibited a symmetric (unimodal) distribution of cadmium-induced MT-specific fluorescence, the cells of two individuals displayed a heterogeneous (nonuniform) distribution of MT levels. Dual-parameter flow cytometric analysis using phenotype-specific antibodies indicated that variations in the responsiveness of subpopulations of lymphocytes to CdCl2 were responsible for the heterogeneous distribution of MT-specific cellular fluorescence. T-helper (CD4-positive) and T-suppressor/cytotoxic (CD8-positive) lymphocytes expressed higher cellular levels of MT than other lymphocyte subpopulations (i.e., B lymphocytes, natural killer cells). Our results suggest that MT protein levels of peripheral blood lymphocytes, as determined by this flow cytometric method, may be used to assess human exposure to toxic metals and to characterize various quantitative/qualitative aspects of the response of individuals to cadmium and possibly to other types of environmental stresses. |
| Flow
cytometric determination of metallothionein levels in
human peripheral blood lymphocytes: Utility in
environmental exposure assessment. Poster Author: Yurkow E.J. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Flow
cytometric method for lymphocyte proliferation test:
Screening for beryllium sensitization at Hanford Author: Jabbour, A.J. Other Author(s): Document Type: CRESP Proceedings Publication Date: 1999 Citation: In proceedings of the Second Annual Health of the Hanford Site Conference, 273-274. Richland, WA:University of Washington. Abstract: Beryllium has been used by DOE and the nuclear industry in reactor cores and rods, tools, and other uses since the 1950s. Human exposure to beryllium can result in chronic beryllium disease (CBD), an immune system-mediated disease resulting in loss of lung function, formation of granulomas, and fibrotic scarring. This disease occurs with a prevalence of 1% among all individuals exposed to beryllium, and can reach higher rates among specific populations. CBD cases have been documented at exposures below the current OSHA 8-hour time weighted average of 1 mg/m3. Medical monitoring currently relies on an assessment of beryllium sensitization based on the lymphocyte proliferation test (LPT), which is used to assess the growth of white blood cells involved in the immune response (i.e., peripheral blood lymphocytes) to beryllium exposure. Sensitization as identified by a positive LPT appears to be highly correlated with later disease. We have investigated factors that could influence the response of peripheral blood lymphocytes to beryllium with the goal of improving the sensitivity and specificity of the currently used LPT. We describe an alternative method based on flow cytometry to the currently used LPT. Our assay allows the evaluation of cell cycle changes during as many as three successive cell division cycles, and can provide cellular and molecular clues to the mechanisms underlying beryllium sensitization. The versatility of this assay should advance our understanding on the causes of CBD, refine currently used clinical assays for identifying beryllium-affected workers at US DOE, and improve the assessment of industrial hygiene and disease prevention programs. |
| Flow
cytometric method for lymphocyte proliferation test:
Screening for beryllium sensitization at Hanford Author: Jabbour, A., Other Author(s): J. Hill, R. Ponce, K. Ertell, T. Kavanagh, L. Newman, T. Takaro, and E. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: University of Washington Second Health of the Hanford Site Annual Conference, Richland, WA, Novermber 3-4. Abstract: |
| Flow
cytometric method for lymphocyte proliferation test:
Screening for Beryllium sensitization at Hanford Author: Jabbour, J., Other Author(s): R. Ponce, M. Rosato, K. Ertell, T. Kavanaugh, L. Newman, T. Takaro and E. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Third Annual University of Washington Conference on the Ecological, Community, and Occupational Health Issues at Hanford, November 2-3. Abstract: |
| Fourth party
to the triparty: Getting involved at Hanford Author: Boiko, P.E., Other Author(s): T.K. Takaro. Document Type: CRESP Published Manuscripts Publication Date: 1995 Citation: llIahee: Journal of the Northwest Environment 11(384): 184-192. Abstract: American taxpayers paid $8 billion over the last eight years to clean up the mixed chemical and nuclear waste at the Hanford Nuclear Reservation, yet this 560-square-mile eastern Washington reserve of complex waste housed in an aged and crumbling infrastructure remains a quagmire of contamination (Zorpette,1996). Assistant Secretary of Energy for Environment, Safety, and Health Tara O'Toole summarized health and safety problems at Hanford by declaring, "The nuclear weapons complex will pose a greater threat in the next 10 years to workers and the public than at its peak of production" (Valenti 1994). |
| Gene
expression analyses in uroepithelial cells from an
arsenate exposed worker population Author: Yager, J.W., Other Author(s): S.C. Kirchner, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA, March 14-18 Abstract: |
| Gene
expression as a biomarker of mercury exposure in raccoons
from the savannah river nuclear weapons facility. Poster Author: Farr, C., Other Author(s): E. Faustman, G. Van Belle, T. Kavanagh, R. Ponce, C. G. Lord, J. Burger, M. Gochfeld, and I. Lehr Brisbin Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Gene
expression as a potential biomarker of inorganic mercury
exposure in terrestrial ecosystems Author: Garry, M.G., Other Author(s): M. Vredevoogd, E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA, March 14-18. Abstract: Biomarkers have shown tremendous benefit in human health risk assessment but their potential has not yet been fully evaluated in ecological settings. Studies with aquatic ecosystems suggest biomarkers can provide benefits in ecological evaluations as well, but few studies have examined terrestrial systems. This research is part of ongoing efforts to investigate the utility of molecular biomarkers in terrestrial ecotoxicology. The present study examines potential changes in gene expression of several stress response related genes (hsp7O, metallothionein [MT], p21) in Tenebrio molitor beetles in response to inorganic mercury (HgCl) exposure. The study design was based on conditions found at Hanford Nuclear Reservations in order to allow laboratory developed biomarkers to be validated in the field, where conditions are more variable. Beetles were exposed to four different levels of HgCl (0, 0.5, 5.0, and 50 ppm in soil) for 12 days. RNA was extracted from each insect and analyzed by a Reverse Northern technique. No dose response patterns in gene expression were noted. Northerns were performed to validate the Reverse Northern findings, but no specific binding was noted, suggesting non-specific binding in the Reverse Northerns. In order to test a more specific probe, oligonucleotides were generated from high species homology regions of hsp7O, MT, and p21 and Northern analyses were performed. In addition, a Northern was performed using a desiccation stress gene (DSP28) cloned from Tenebrio molitor as the probe. Results showed a dose response pattern with HgCl exposure and expression of both DSP28 and the p2l oligonucleotide. Further experiments are underway to investigate alternative hsp7O and MT homology regions. The development of gene expression biomarkers could give subclinical and sensitive data at the both the species and ecosystem level. Supported by USDOE DE-FCO1-95EW55084 and NIEHS T32ESO-7032. |
| Gene
expression changes in individuals exposed to heat stress Author: Kirchner, S.C. Other Author(s): Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Gene
expression patterns as potential biomarkers of heavy
metal exposure in terrestrial ecosystems Author: Vredevoogd, M. Other Author(s): Document Type: CRESP Dissertations or Theses Completed Publication Date: 1998 Citation: University of Washington, Department of Environmental Health, Seattle, WA. Abstract: |
| Gene
expression patterns as potential biomarkers of heavy
metal exposure in terrestrial ecosystems. Poster Author: Vredevoogd, M. Other Author(s): E. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Gene
Expression Patterns as Potential Biomarkers of Heavy
Metal Exposure in Terrestrial Ecosystems. Poster Author: Vredevoogd, M. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: First Annual Health of the Hanford Site Conference: Current Challenges. Richland, WA, December 3-4. Abstract: |
| Human
variability in mercury toxicokinetics and steady state
biomarker ratios Author: Bartell, S.M, Other Author(s): R.A. Ponce, R.N. Sanga, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 2000 Citation: Environmental Research, Section A 84: 127-132. Abstract: |
| Human
variability in steady state blood-to-hair,
blood-to-intake, and hair-to-intake ratios for mercury:
Implications for health risk assessement. Poster Author: Bartell, S.M., Other Author(s): R.A. Ponce, R.N. Sanga, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: 5th International Conference on Mercury as a Global Pollutant. Rio de Janeiro, Brazil, May 23-27. Abstract: |
| Identification
of differentially expressed mitochondrial genes in
methylmercury (MeHg) exposed rat embryonic CNS cells Author: Lu, S., Other Author(s): S.C. Kirchner, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting, Seattle, WA, March 1-5. Abstract: |
| Identifying
mechanisms of developmental toxicity: Application of
tools from molecular biology Author: Kirchner, S.C., Other Author(s): and E.M. Faustman. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1998 Citation: In Molecular Biology in Toxic Response, Chapter 24, edited by A. Puga and K. Wallace, 411-437. Washington, DC: Taylor and Francis. Abstract: |
| Implications
of research for remediation technology design Author: Faustman, E.M. Other Author(s): Document Type: CRESP Published Manuscripts Publication Date: 1999 Citation: Risk Excellence Notes 1(9): 9. Abstract: Research of the CRESP Remediation Technology Task Group aims to identify optimal conditions for cleanup technologies, which can inform policy on environmental remediation. Two projects exemplify this research. At the Department of Energy's (DOE) Hanford 200 West area, Joel Massmann collaborates with contractors at the site to investigate transport and removal of carbon tetrachloride from the vadose zone via soil vapor extraction (SVE), an available technology. A computer model was developed to describe migration of carbon tetrachloride vapors through the vadose zone during SVE remediation. This research at Hanford has identified design changes and timing strategies that can improve SVE efficiency, thereby reducing groundwater contamination. At DOE's Savannah River site, David Kosson and colleagues investigate impacts of soil characteristics on trichloroethylene extraction. Their findings have become driving factors for determining efficient operation and eventual cessation of SVE at the C-Area Burning Rubble Pit. |
| In vivo
determination of cell cycling rates in embryonic rat
neural cells, Poster Author: Lewandowski, T.A., Other Author(s): J.L. Schroeder, R.A. Ponce, S.M. Bartell, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Pacific Northwest Association of Toxicologists Annual Meeting, Leavenworth, WA. September. [Second Place Student Poster Award] Abstract: |
| In vivo
determination of cell cycling rates in embryonic rat
neural cells: Development of a biologically-based
toxicodynamic model for methylmercury risk assessment Author: Lewandowski, T.A., Other Author(s): J.S. Schroeder, R.A. Ponce, S.M. Bartell, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society of Toxicology Annual Meeting, New Orleans, LA, March 14-18. Abstract: |
| Incorporating
scientific information into quantitative risk assessment:
Challenges and options Author: Faustman, E.M., Other Author(s): S.M. Bartell, and T.A. Lewandowski. Document Type: CRESP Educational Courses Given Publication Date: 1998 Citation: National Research Center for Statistics and Environment Seminar, University of Washington, Seattle, WA, April. Abstract: |
| Incorporation
of toxicity information in U.S. Department of Energy
hazardous waste prioritization models Author: Faustman, E.M., Other Author(s): S. Bartell, T.G. Ewers, M . Greenberg, C.W. Powers, and J.A. Moore. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: April, 11. Abstract: |
| Induction of
growth arrest and DNA damage inducible genes Gadd45 and
Gadd153 in primary rodent embryonic cells following
exposure to methylmercury Author: Ying, C.O., Other Author(s): S.A. Thompson, S.C. Kirchner, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1997 Citation: Toxicology and Applied Pharmacology 147: 31-38. Abstract: Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. Studies on the mechanism of MeHg-induced toxicity reveal that inhibition of cell cycle progression may be one way by which MeHg interferes with normal development. In this study, we utilized primary rodent embryonic neuronal cell (CNS) and limb bud (LB) cultures to determine the MRNA expression level of two genes involved in cell cycle arrest, Gadd45 and Gaddl53, both during cellular differentiation and in response to MeHg exposure. A differential expression pattern of Gadd45 and Gaddl53 was observed during CNS and LB differentiation in culture. However, both CNS and LB cells responded to MeHg exposure with a concentration-dependent increase in Gadd45 and Gaddl53 MRNA. Previous studies have shown that McHg exposure (2 ILm) of CNS cells for 24 hr causes a fourfold decrease in the number of cells passing through the cell cycle. The present study shows that at the same exposure concentration, a five- to eightfold increase in Gadd45 MRNA levels and a two- to fourfold increase of Gaddl53 was observed. Induction of Gadd45 was also noted in adult female mice chronically exposed to 10 ppm MeHg, a dose that caused developmental toxicity in vivo. Based on the known involvement of the Gadd genes in cell cycle arrest, activation of these genes could be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms. |
| Induction of
growth arrest and DNA damage-inducible genes Gadd45 and
Gadd153 in primary rodent embryonic cells following
exposure to methylmercury Author: Ou, Y.C., Other Author(s): S.A. Thompson, S.C. Kirchner, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1997 Citation: Toxicology and Applied Pharmacology 147: 31-38. Abstract: Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. Studies on the mechanism of the MeHg-induced toxicity reveal that inhibition of cell cycle progression may be one way by which MeHg interferes with normal development. In this study, we utilized primary rodent embryonic neuronal cells (CNS) and limb bud (LB) cultures to determine the mRNA expression level of two genes involved in cell cycle arrest, Gadd45 and Gadd153, both during cellular differentiation and in response to MeHg exposure. A differential expression pattern of Gadd45 and Gadd 153 was observed during CNS and LB differentiation in culture. However, both CNS and LB cells responded to MeHg exposure with a concentration-dependent increase in Gadd45 and Gadd153 mRNA. Previous studies have shown that MeHg exposure (2mM) of CNS cells for 24 hr causes a fourfold decrease in the number of cells passing through the cell cycle. The present study shows that at the same exposure concentration, a five- to eightfold increase in Gadd45 mRNA levels and a two- to fourfold increase of Gadd153 was observed. Induction of Gadd45 was also noted in adult female mice chronically exposed to 10 ppm MeHg, a dose that caused developmental toxicity in vivo. Based on the known involvement of the Gadd genes in cell cycle arrest, activation of these genes could be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms. |
| Induction of
necrotic and apoptotic cell death following methylmercury
(MeHg) exposure in primary embryonic CNS cells Author: Ou, Y.C., Other Author(s): S. Lu, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting, Seattle, WA, March 1-5. Abstract: |
| Integration
of human health and ecological risk assessment
methodologies with probabilistic risk analysis Author: McGrath, L.F., Other Author(s): and C.W. Powers. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Abstract: |
| Interaction
of blood lead and d-aminolevulinic acid dehydratase
genotype on markers of heme synthesis and sperm
production in lead smelter workers Author: Alexander, B.H., Other Author(s): H. Checkoway, P. Costa-Mallen, E.M. Faustman, J.S. Woods, K.T. Kelsey, C. van Netten, and L.G. Costa. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Investigation
of the temporal correlation between methylmercury-induced
cell cycle arrest and induction of cell cycle specific
genes Author: McMillan, M.J., Other Author(s): Y.C. Ou, R.A. Ponce, S.C. Kirchner, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1996 Citation: Proceedings of the Teratology Society Annual Meeting 55(1): 360. Abstract: |
| Investigation
of the temporal correlation between methylmercury-induced
cell cycle arrest and induction of cell cycle specific
genes Author: McMillan, M.J., Other Author(s): Y.C. Ou, R.A. Ponce, S.C. Kirchner, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: In Proceedings of the Teratology Society Annual Meeting 55(1): 360. Abstract: |
| Linking
ecological risk assessment to human health risk
assessment: Food-chain transfers to humans from
subsistence ecological resources Author: Himmelbauer, L.D., Other Author(s): S.M. Bartell, S. Haness, E. Nobmann, and R.A. Ponce. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Environmental Toxicology and Chemistry Annual Meeting, Charlotte, NC, November. Abstract: |
| Linking
toxicokinetic and toxicodynamic models for methylmercury
developmental toxicity Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: The role of Human Exposure Assessment in the Prevention of Environmental Disease. Rockville, MD, September 22-24. Abstract: |
| Measuring the
reproductive effects of solvents on painters at the
Hanford nuclear reservation Author: Luderer, U., Other Author(s): E.M. Faustman, C. Brodkin, K. Ertell, and T.K. Takaro. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Mechanisms of
methylmercury-induced cell cycle arrest and cell death in
primary embryonic CNS cells Author: Lu, S., Other Author(s): M.J. McMillan, S.C. Kirchner, Y.C. Ou, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: International Union of Toxicology Annual Meeting, Paris, France, July 5-9. Abstract: |
| Methodology
for describing hazards/risks at Hanford site Author: Ponce, R. Other Author(s): Document Type: CRESP Questionnaires and Instruments Under Development Publication Date: 200X Citation: Abstract: |
| Methylmercury
distribution in pregnant rats and their fetuses during
early organogenesis Author: Lewandowski, T.A., Other Author(s): S. Hong, S. Pingree, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Teratology Society Annual Meeting, San Diego, CA, June. Abstract: |
| National
toxicology program studies: Principles of dose selection
and applications to mechanistic based risk assessment Author: Bucher, J.R., Other Author(s): C.J. Portier, J.I. Goodman, E.M. Faustman, and G.W. Lucier. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: Fundamental and Applied Toxicology 31: 1-8. Abstract: A workshop entitled "NTP Studies: Principles of Dose Selection and Applications to Mechanistic Based Risk Assessment" was held at the 34th Annual Meeting of the Society of Toxicology in Baltimore, Maryland. The purpose of the workshop was to provide an overview of factors currently considered important in the selection of doses for NTP studies, to describe some of the confounding factors that can result from the indiscriminate use of bioassay data in quantitative risk assessment, and.to suggest ways in which information from mechanistic studies or studies of biomarkers of exposure or effect might be used to better advantage in risk assessment. |
| New
approaches for human health risk assessment of cancer and
non-cancer endpoints for understanding risks from mixed
wastes Author: Lee, R.C., Other Author(s): and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: Society for Risk Analysis (SRA) and International Society for Exposure Assessment (ISEA) Joint Meeting. New Orleans, LA, December 8-11. Abstract: |
| New
Approaches to Temporal Issues in Human Health Risk
Assessment Author: Faustman, E.M., Other Author(s): S.M. Bartell, R.A.Ponce, G. van Belle and W.C. Griffith Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society for Risk Analysis 1998 Annual Meeting. Phoenix, AZ, December 6-9. Abstract: As a factor affecting both exposure and potency, considerations of time are often some of the most difficult to evaluate in risk assessments. Such considerations include time of life, latency, and duration of exposure. Often, the use of the biomarker data to predict historic exposures relies on assumptions reguarding exposure patterns over time. One asssumption that is commonly made is the assumption of steady-state. To exlpore the impact of time considerations in exposure estimation, we examine how variability in non-steady state exposures may alter the interpretation of biolmarker information using dietary mercury as an example. Blood mercury analysis can be considered to be a pooled sample most highly reflecting recent exposure. Hair Hg analysis, however, can be considered to be intergrator reflecting blood Hg concentration at the time of hair growth . Using a physiologically-baed pharmacokinetic model accounting for variability in model parameters, we demonstrate that considerations of changing dietary patterns have substantial implications for improving the design of sampling strategies for estimating historical exposure. We discuss the role of model variability and dietary pattern in the interpretation of biomarker. |
| Panel on
Public Health Author: Abbotts, J. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Third Annual University of Washington Conference on the Ecological, Community, and Occupational Health Issues at Hanford, November 2-3. Abstract: |
| Paternal
occupational lead exposure and pregnancy outcome Author: Alexander, B.H., Other Author(s): H. Checkoway, C. van Netten, J.D. Kaufman, T.L. Vaughn, B.A. Mueller, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: International Journal of Occupational Environmental Health 2: 280-285. Abstract: Self-reported reproductive histories of male employees of a lead-zinc smelter were related to pre-conception measures of lead exposure to examine associations between paternal occupational lead exposure and adverse pregnancy outcome. The participants reported 2,021 pregnancies which resulted in 1,684 normal live births, 12 stillbirths, 30 birth defects, 203 spontaneous abortions, and 92 "other' outcomes. Birth defects and stillbirths were combined for the analysis. The risk of a stillbirth or birth defect was elevated for pre-conception employment in a high-lead-exposure compared with a low-lead- exposure job (odds ratio = 2.7, 95% confidence interval = 0.7, 9.6). A similar risk was found for pre-conception blood lead levels of 25-39 tLg/dL and - 40 @Lg/dL w hen compared with blood lead levels of <25 @Lg/dL (OR="2.9,95%" CT="0.6," 13.3, and OR="2.5," 95% GI="0.5," 11.6, respectively). No association was found between pre-conception lead exposure and spontaneous abortion. A relatively low response rate to the questionnaire and potentially erroneous reporting of reproductive outcomes by male workers are limitations of the study. |
| PBTK model of
methylmercury toxicity in the fetal rat Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Poster. Society for Risk Analysis Annual Meeting, Phoenix, AZ. December 6-9. Abstract: |
| Physical and
chemical treatment processes Author: Benjamin, M. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: In short course on Hazardous Waste Solvents in Subsurface Environments: Transport, Risks, Remediation. CRESP. Seattle, Washington, September 9-11. Abstract: |
| Policy
analysis and clinical research on occupational beryllium
exposure at DOE sites. Poster Author: Ponce, R.A., Other Author(s): T.K. Takaro, S.M. Bartell, A.J. Jabbour, K. Ertell, J. Abbotts, S. Barnhart, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Responsive science: Forging regulatory resolution at DOE sites, Washington, DC, April 12. Abstract: |
| Proceedings,
an informal collection of papers from the conference Author: Takaro, Tim, Other Author(s): Chairman, Organizing Committee. Document Type: CRESP Proceedings Publication Date: 2000 Citation: Third Annual University of Washington Conference on the Ecological, Community, and Occupational Health Issues at Hanford, November 2-3. Abstract: |
| Quantitaive
analysis of risks and benefits for public health
decisions applied to fish consumption Author: Ponce, R.A., Other Author(s): S.M. Bartell, D. Laflamme, C. Carrington, E.M. Faustman, R.C. Lee, and P.M. Bolger. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Quantitaive
analysis of risks and benefits for public health
decisions applied to fish consumption: Use of QALY
weights with dose-response model Author: Ponce, R.A., Other Author(s): S.M. Bartell, D. LaFlamme, C. Carrington, R.C. Lee, E.M. Faustman, and P.M. Bolger. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Risk Analysis Abstract: |
| Quantitative
analysis of risks and benefits for public health
decisions applied to fish consumption. Poster Author: Ponce, R.A., Other Author(s): S.M. Bartell, D. Laflamme, C. Carrington, E.M. Faustman, R.C. Lee, and P.M. Bolger. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Quantitative
analysis of risks and benefits for public health
decisions applied to fish consumption. Poster Author: Ponce, R.A., Other Author(s): S.M. Bartell, D. LaFlamme, C. Carrington, E.M. Faustman, R.C. Lee, and P.M. Bolger. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Reproductive
and developmental toxicity of metals: Issues for
consideration in human health risk assessment Author: Ponce, R.A., Other Author(s): and E.M. Faustman. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1998 Citation: In Reproductive and Developmental Toxicology, edited by K. Korach. New York: Marcel Dekker Publishers. Abstract: |
| Reproductive
and developmental toxicity of metals: Issues for
consideration in human health risk assessment Author: Faustman, E.M., Other Author(s): and R.A. Ponce. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1998 Citation: In Reproductive and Developmental Toxicity, edited by K. Korach. New York: Marcel Dekker Publishers. Abstract: |
| Review of
noncancer risk assessment: Applications of benchmark dose
methods Author: Faustman, E.M., Other Author(s): and S.M. Bartell. Document Type: CRESP Published Manuscripts Publication Date: 1997 Citation: Human and Ecological Risk Assessment 3(5): 893-920. Abstract: The overall goal of this project is to evaluate and compare risk assessment methods traditionally used for noncancer health risks and to compare them with new approaches. These methods include the no observed adverse effect level (NOAEL), lowest observed adverse effect level (LOAEL), and the more recently proposed benchmark dose (BMD), in whigh a dose is identified using a curve-fitting procedure and a prespecified effect level. Applications of the BMD method are reviewed for developmenw toxicity, reproductive toxicity, neurotoxicity, ecological toxicity, carcinogenicity, and other biological impacts. Evaluations have shown that the benchmark method is generally no more conservative than the NOAEL approach and confers several significant advantages for safety assessment. In addition, traditional safety factor approaches used for RfD calculation based on LOAEL values are overly conservative. Studies show that exposures at NOAELs are not "risk free" but may represent effect levels ranging from 3% Lip to 21%. An important advantage of BMD approaches is that regulatory limits can be consistently set at a given response level rather than being dictated bv studv design. BMD methodology also allows for easy transition to biologically based dose response modeling as such models are developed. V |
| Rising winter
precipitation at the Hanford nuclear reservation,
Washington: Possible implications for surface barrier
performance Author: Yamaguchi D.K., Other Author(s): and S.M. Bartell. Document Type: CRESP Published Manuscripts Publication Date: 1999 Citation: Water Resources Research. Abstract: Water derived from winter (-November-to-March) precipitation carries nuclear and chemical wastes in contaminated soils at the Hanford nuclear site, Washington, downward to the groundwater and adjacent Columbia River. Accordingly, detailed understanding of the nature and variability of winter precipitation at this and site is central to managing groundwater recharge there. Winter precipitation at Hanford has been rising at an average rate of 2.9 mm per decade since November 1912 (P = 0.044). The trend appears to be real because two nearby climate stations show similar (albeit nonsignificant) trends, and a plot of cumulative precipitation at the three stations fails to deflect in the 1940s when the Hanford station was moved. If the trend continues, the precipitation will start to overflow surface barriers intended to limit water infiltration into the soil at acute localities for 1,000 years in 250 to 700 years. This failure rate would compromise plans to halt the migration of contaminants to the groundwater. |
| Rising winter
temperatures upwind and near the Hanford reservation over
the past century: Impact of large-scale human forcing of
rising precipitation Author: Yamaguchi, D.K. Other Author(s): Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: Water Resources Research. September. Abstract: |
| Risk
assessment Author: Faustman, E.M., Other Author(s): and G.S. Omenn. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1995 Citation: In Casarett and Doull's Toxicology: The Basic Science of Poisons, 5th ed., edited by C.D. Klaassen, Chapter 4. New York: McGraw Hill. Abstract: |
| Risk
assessment and screening strategies for beryllium
exposure Author: Bartell, S.M., Other Author(s): T.K. Takaro, R.A. Ponce, J.P. Hill, E.M. Faustman, and G.S. Omenn. Document Type: CRESP Published Manuscripts Publication Date: 2000 Citation: Technology 7: 241-249. Abstract: Respirable beryllium is a potent toxicant that can cause pulmonary granulomous and inflammation in exposed individuals. These effects, known as chronic beryllium disease (CBD), occurred in 1-3% of all beryllium workers and in 4-16% of beryllium machinists in recent investigations. Decades ago, Merril Eisenbud and hius colleagues conducted early epidemiologic research to improve the understanding of CBD risks at low levels of beryllium exposure. Today, CBD continues to pose a challenge to industrial hygienists, toxicologists, and other health professionals and researchers seeking to understand and mitigate this difficult to treat but clearly preventable disease. We discuss current approaches for assessing and managing CBD risk, and highlight current research efforts that may improve our understanding of CBD. Special emphasis is given to the role of genetics in CBD development, the use of immunologically based lymphocyte proliferation testing (LPT) in occupational health surveillance and risk management, and the social, legal and ethical challenges posed by this information in forming appropriate preventative strategies. |
| Risk
assessment, risk communication, and risk management Author: Omenn, G.S., Other Author(s): and E.M. Faustman. Document Type: CRESP Published Books, Chapters, and Sections Publication Date: 1997 Citation: In Oxford Textbook of Public Health: The Scope of Public Health., 3rd ed. Vol. 2., edited by R. Detels, W.W. Holland, J. McEwen, and G.S.Omenn, Chapter 33, 989-986. Boston, MA: Oxford University Press. Abstract: |
| Risk
assessment: An accredited course with workshops on
understanding risk assessment and its role in providing a
framework for making environmental and occupational
health decisions Author: Faustman, E.M. Other Author(s): Document Type: CRESP Educational Courses Given Publication Date: 1996 Citation: University of Washington, Department of Environmental Health. Seattle, WA, February 23. Abstract: |
| Risk
estimation and value-of-information analyses for three
proposed genetic screening programs for chronic beryllium
disease prevention Author: Bartell, S.M., Other Author(s): Ponce, R.A., Takaro, T.K., Zerbe, R.O., Omenn, G.S., and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 2000 Citation: Risk Analysis 20(1): 87-99. Abstract: Genetic differences (polymorphisms) among members of a population are thought to influence susceptibility to various environmental exposures. In practice, however, this information is rarely incorporated into quantitative risk assessment and risk management. We describe an analytic framework for predicting the risk reduction and value-of-information (VOI) resulting from specific risk management applications of genetic biomarkers, and we apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leukocyte Antigen gene variant, HLA-DP1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (approximately 94%) but low specificity (approximately 70%) with respect to CBD among individuals occupationally exposed to respirable beryllium. The expected postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothetical cohort with 1% baseline CBD prevalence. VOI analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed CBD intervention programs based on the genetic susceptibility test. For the example cohort, the expected net VOI per beryllium worker for genetically based testing and intervention is $ 13,000, $ 1,800, and $ 5,100, respectively, based on a health valuation of $ 1.45 million per CBD case avoided. VOI results for alternative CBD valuations are also presented. Despite large parameter uncertainty, probabilistic analysis predicts generally positive utility for each of the three evaluated programs when avoidance of a CBD case is valued at $ 1 million or higher. Although the utility of a proposed risk management program may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consider serious social, legal, and ethical factors. |
| Risk, mercury
levels, and birds: Relating adverse laboratory effects to
field biomonitoring. Poster Author: Burger, J., Other Author(s): and M. Gochfeld. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Risk-influenced
decision making at DOE sites: Time for holistic thinking Author: Faustman, E.M., Other Author(s): and R. Fenske. Document Type: CRESP Symposia, Workshops, and Stakeholder Events Publication Date: 1997 Citation: AMSIE '97 and American Association for the Advancement of Science (AAAS) Annual Meeting. Seattle, WA, February 13-18. Abstract: |
| Semen quality
of men employed at a lead smelter Author: Alexander, B.H., Other Author(s): C. Checkoway, C. van Netten, C.H. Muller, T.G. Ewers, J.D. Kaufman, B.A. Mueller, T.L. Vaughn, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: Occupational and Environmental Medicine 53: 411-416. Abstract: Objective--To evaluate the effects of recent and long term occupational lead exposure on indicators of male reproductive health. |
| Simulation
studies examining possible mechanisms of
trichloroethylene carcinogenicity Author: Lee, R.C., Other Author(s): E.G. Leubeck, S.M. Bartell, and E.M. Faustman. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Human and Ecological Risk Assessment. Abstract: |
| Simulation
studies examining possible mechanisms of
trichloroethylene carcinogenicity Author: Lee, R.C., Other Author(s): E.G. Luebeck, S.M. Bartell, R.A. Ponce and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Poster. Society for Risk Analysis Annual Meeting, Washington, DC. December. Abstract: |
| Spatial
extent of increasing 20th century winter precipitation
upwind of the Hanford nuclear site, Washington Author: Yamaguchi D.K. Other Author(s): Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: Water Resources Research. Abstract: |
| Stakeholder
participation in an Internet forum for communication
about risks at Department of Energy facilities. Poster Author: Griffith, W., Other Author(s): S.B. Curtis, S. M. Bartell, and E. M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Statement of
Rafael A. Ponce, PhD, on behalf of CRESP, University of
Washington, on public hearing on proposed rules: Chronic
Beryllium Disease Prevention Program, Docket
EH-RM-98-BRYLM, Washington, DC, February 11 Author: Ponce, R.A., Other Author(s): J. Abbotts, S. Barnhart, S. Bartell, K. Ertell, E. Faustman, B. Griffith, M. Salazar, and T. Takaro Document Type: CRESP Reports Publication Date: 1999 Citation: Seattle, WA: University of Washington. Abstract: |
| Strontium-90
radiation standards for environmental cleanup. Poster Author: Griffith, W., Other Author(s): S.B. Curtis, S.M. Bartell, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Summary of
meetings between CRESP and Hanford site risk managers Author: McGrath, L.F., Other Author(s): R. Ponce, and J. Abbotts. Document Type: CRESP Symposia, Workshops, and Stakeholder Events Publication Date: 1998 Citation: November. Abstract: |
| Temporal
fallacies in biomarker based exposure inference Author: Bartell, S.M., Other Author(s): R.A. Ponce, W.C. Griffith, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: The role of Human Exposure Assessment in the Prevention of Environmental Disease. Rockville, MD, September 22-24. Abstract: |
| Temporal
fallacies in biomarker based exposure inference. Poster Author: Bartell, S.M., Other Author(s): R.A. Ponce, W.C. Griffith, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1999 Citation: Society for Risk Analysis Annual Meeting, Atlanta, GA, Abstract: |
| Terrestrial
and ecosystem risk methodology that can be used to assess
ecological risk on U.S. Department of Energy sites Author: Bartell, S.M., Other Author(s): C.J. Lewis, K.R. Campbell, and J. Burger. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| The
Department of Energy's Risk Data Sheet: A tool for
evaluating risk across the nuclear weapons complex Author: Faustman, E.M., Other Author(s): and T.G. Ewers. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1996 Citation: Society for Risk Analysis (SRA) and International Society for Exposure Assessment (ISEA) Joint Meeting, session on “Approaches to Performing and Utilizing Risk Assessment at DOE Sites.” New Orleans, LA. Abstract: The Office of Environmental Management (EM) in Department of Energy (DOE) has recently completed the second iteration of a process to evaluate the risks and impacts of the activities ongoing at EM sites. The purpose of this process is to facilitate the prioritization of work and allocation of funds. The key tool of this process is the Risk Data Sheet (RDS). Project managers in the field are responsible for using the RDS for evaluating the activities they are conducting. Each RDS includes a summary describing what activities are being performed, how they are conducted, why they are being performed, what results are expected from the activities. The risks and impacts associated with the conditions and the activities specified are then evaluated by describing three scenarios: 1) before - What are the risks/impacts if this work is not performed?; 2) during - What are the risks/impacts of doing this work?; and, 3) after - What are the residual risks/impacts when this work is complete? For each scenario the following seven categories of impact are evaluated with respect to severity of impact and to the likelihood of the impact occuring: 1) Public Safety and Health, 2) Site Personnel Safety and Health, 3) Environmental Protection 4) Compliance, 5) Mission Impact, 6) Mortgage Reduction, and 7) Social/Cultural/Economic. The evaluations of severity of impact and likelihood occurrance are then summarized into high, medium and low risk levels for each category of impact and each time frame. The data can be used to examine where the high risk currently are, what activities result in the greatest risk reduction, and what activities may cause an increase in risk. |
| The
DOE’s risk data sheet and relative ranking
evaluation framework: Tools for environmental risk
evaluation Author: Faustman, E.M., Other Author(s): S.M. Bartell, T.G. Ewers, R.A. Ponce, M. Greenberg, C.W. Powers, and J.A. Moore. Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| The novel use
of the aRNA technique in uroepithelial cells for looking
at exposures in population studies Author: Kirchner, S.C. Other Author(s): Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| The role of
intracellular glutathione in methylmercury-induced
toxicity in embryonic neuronal cells Author: Ou, Y.C., Other Author(s): C.C. White, C.M. Krejsa, R.A. Ponce, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1999 Citation: Neurotoxicology 20:793-804. Abstract: |
| The use of
scientific research to inform decisions regarding
exposure to contaminants at DOE sites. Poster Author: McGrath L.F., Other Author(s): P. Georgopoulos, and P. Lioy Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| The utility
of decision analysis in evaluating biomarkers Author: Bartell, S.M., Other Author(s): and R.A. Ponce. Document Type: CRESP Educational Courses Given Publication Date: 1997 Citation: Washington State Department of Health Seminar, Olympia, WA, March. Abstract: |
| The utility
of decision analysis in evaluating biomarkers of
susceptibility Author: Bartell, S.M., Other Author(s): and R. Ponce. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Washington State Department of Health (WADOH). Olympia WA, March 27. Abstract: |
| The utility
of mercury exposure biomarkers in risk assessment Author: Ponce, R. Other Author(s): Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Frontier Geosciences, Washington State Department of Health (WADOH). Seattle, WA, March 28. Abstract: |
| The value of
biological information in aflatoxin risk management.
Poster Author: Lee, R.C., Other Author(s): S.M. Bartell, R.A. Ponce, D.L. Eaton, W.C. Griffith, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| The value of
biomarker information in aflatoxin risk management Author: Lee, R.C., Other Author(s): S.M. Bartell, R.A. Ponce, W.C. Griffith, A. C. Cullen, and D.L. Eaton. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society for Risk Analysis 1998 Annual Meeting. Phoenix, AZ, December 6-9. Abstract: |
| The value of
biomarker information in aflatoxin risk management Author: Lee, R.C., Other Author(s): S.M. Bartell, R.A. Ponce, W.C. Griffith, A.C. Cullen, and D.L. Eaton. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Poster. Society for Risk Analysis Annual Meeting, Phoenix, AZ. December 6-9. Abstract: |
| The value of
biomarker information in risk based decisions regarding
atafloxin control Author: Lee, R.C., Other Author(s): S.M. Bartell, R.A. Ponce, A.C. Cullen, D.L. Eaton, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Toxicokinetic
and toxicodynamic modeling of the effects of
methylmercury in the fetal rat Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: The Toxicologist 42(1-S), No. 683. Abstract: |
| Toxicokinetic
and toxicodynamic modeling of the effects of
methylmercury in the fetal rat Author: Lewandowski, T.A., Other Author(s): C.H. Pierce, S.M. Bartell, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Poster. Pacific Northwest Association of Toxicologists Annual Meeting, Ocean Shores, WA. September. Abstract: |
| Toxicokinetic
and toxicodynamic modeling of the effects of
methylmercury on the fetal rat Author: Lewandowski, T.A., Other Author(s): S.M. Bartell, C.H. Pierce, R.A. Ponce, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Tribal
nations and CRESP at Hanford: Opportunities for
collaboration. Workshop to establish a working
relationship between the Yakama, Nez Perce, and the
United Tribes of the Umatilla and CRESP Author: Faustman, E.M., Other Author(s): G.S. Omenn, J.M. Moore, and C. Powers. Document Type: CRESP Symposia, Workshops, and Stakeholder Events Publication Date: 1995 Citation: Seattle, WA, October 27. Abstract: |
| Uncertainty
analysis methods for comparing predictive models and
biomarkers: A case study of dietary methylmercury
exposure Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.C. Lee, T.J. Kavanagh, J.S. Woods, W.C. Griffith, T.K. Takaro, and E.M. Faustman. Document Type: CRESP Published Manuscripts Publication Date: 1998 Citation: Journal of Regulatory Toxicology and Pharmacology 28(2): 96-105. Abstract: Biologically based markers (biomarkers) are currently used to provide information on exposure, health effects, and individual susceptibility to chemical and radiological wastes. However, the development and validation of biomarkers are expensive and time consuming. To determine whether biomarker development and use offer potential improvements to risk models based on predictive relationships or assumed values, we explore the use of uncertainty analysis applied to exposure models for dietary methylmercury intake. We compam exposure estimates based on self-reported fish intake and measured fish mercury concentrations with hiomarker-based expo- sure estimates (i.e., hair or blood mercury concentrations) using a published data set covering I month of exposure. Such a comparison of exposure model predictions allowed estimation of bias and random error associated with each exposure model From these analyses, both bias and random error were found to be important components of uncertainty regarding biomarker based exposure estimates, while the diary based exposure estimate was susceptible to bias. Application of the proposed methods to a simple case study demonstrates their utility in estimating the con tribution of population variability and measurement error in specific applications of biomarkers to envi- ronmental exposure and risk assessment. Such analyses can guide risk analysts and managers in the appropriate validation, use, and interpretation of exposure biomarker information. |
| Understanding
Risk Assessment and Its Role in Providing a Framework for
Making Environmental and Occupational Health Decisions Author: Faustman, E.M. Other Author(s): Document Type: CRESP Upcoming Educational Courses Publication Date: 200X Citation: University of Washington, Department of Environmental Health. Seattle, WA. Abstract: |
| Use of
altered urinary porphyrin expression to measure mercury
burdens: Comparing two occupationally exposed populations
Author: Woods, J. Other Author(s): Document Type: CRESP In Progress Manuscripts Publication Date: 200X Citation: Abstract: |
| Use of
biomarkers in risk assessment and decision making:
Comparisons between predictive modeling and use of
biomarkers in assessing methylmercury exposure Author: Ponce, R.A., Other Author(s): S.M. Bartell, T.J. Kavanagh, J.S. Woods, R.C. Lee, T.K. Takaro, and E.M. Faustman. Document Type: CRESP Submitted Manuscripts Publication Date: 200X Citation: Abstract: |
| Use of
biomarkers in risk assessment and decision-making Author: Ponce, R.A., Other Author(s): S.M. Bartell, R.C. Lee, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Conference on Issues and Applications in Toxicology and Risk Assessment. Dayton, OH, April. Abstract: |
| Use of
children's activity patterns in dermal soil exposure
assessment Author: Wong E.Y. Other Author(s): Document Type: CRESP Dissertations or Theses Completed Publication Date: 1999 Citation: Seattle, WA: University of Washington. Abstract: When performing human health risk assessments, dermail-soil risks frequently need to be calculated. Current regulatory guidance utilizes multiple, non-event specific point estimates of input parameters to produce a single, deterministic estimate of exposure. The Soil Contact Rate (SCR) is proposed as a metric of dermal exposure to soil. The children's SCR utilizes realistic activity pattern data taken from the second Soil Contact Survey (SCS-II), performed in 1998-99. The SCS-II was designed as a nationally representative telephone survey used to gather data regarding the frequency and duration of outdoor play as well as the hand washing and bathing frequency of a randomly chosen child in the household. Respondents reported that their children played outside on grass or dirt surfaces a median of 7 days/wk, 3 hours/day in warm weather and 3 days/wk, 1 hour/day in cold weather months. Respondents reported a median hand wash frequency of 4 times/day and a median bath/shower frequency of 7 times/wk in both warm and cold weather. Washing frequencies were gathered in order to calculate a delay time, the time from the end of an activity leading to soil exposure until soil is removed via washing. Consideration of a delay time can lead to more realistic and increased estimates of total soil exposure time. Based upon survey and empirical data, distributions of activity pattern data, clothing data, and soil adherence were utilized in a two-dimensional Monte Carlo model. Use of two-dimensional Monte Carlo modeling allowed quantification of the contributions of variability and uncertainty to the SCR. Utilizing this methodology, the SCR for player children 5 years or less was calculated to have a median of ~48 g.hr/mo. For comparison, default exposure factor values specified for EPA's reasonably maximally exposed individual scenario can also be used to calculate an SCR. The calculated default equivalent of 406 g.hr/mo corresponds to the 93rd percentile of the median distribution reported here. |
| Use of risk
information in making cleanup decisions at Hanford Author: Ponce, R.A., Other Author(s): and T.K. Takaro. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Second Health of the Hanford Site Annual Conference, Richland, WA, November 3-4. Abstract: |
| Value-of-Information
analyses for biomarkers of susceptibility: Occupational
berylliosis at US DOE sites Author: Bartell, S.M., Other Author(s): R. A. Ponce, T.K. Takaro, G.S. Omenn, T.J. Kavanagh, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: The Health of the Hanford Site: Current Challenges: Occupational Health Session. Richland, WA, December 3-4. Abstract: |
| Value-of-Information
analyses for biomarkers of susceptibiliy: Occupational
berylliosis at US DOE sites Author: Bartell, S.M., Other Author(s): R. A. Ponce, T.K. Takaro, G.S. Omenn, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1997 Citation: Society for Risk Analysis Annual Meeting. Washington, DC, December 7-10. Abstract: |
| Value-of-information
analyses for biomarkers: Susceptibility to chronic
beryllium disease at US DOE sites. In Proceedings of the
Topical Meeting on Risk-based Performance and Decision
Making, Pasco, WA, 205-213 Author: Bartell, S.M., Other Author(s): R.A. Ponce, T.K. Takaro, G.S. Omenn, R.O. Zerbe, and E.M. Faustman. Document Type: CRESP Proceedings Publication Date: 1998 Citation: LaGrange Park, IL: American Nuclear Society, April 5-8. Abstract: We describe a general analytic framework for assessing the utility of specific biomarkers in risk management, and apply it to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease: Differing CBD susceptibility among individuals may be partly attributable to inherited differences in human leukocyte antigen (HLA) genotype. One described HLA-DP gene variant, HLA-DPß1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (83-97%) but low specificity (70%) in assessing the risk of CBD in those occupationally exposed to respirable beryllium. Value-of-information analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed biomarker-based beryllium monitoring and intervention programs. In a population with 10% CBD prevalence, the expected net social value of using the genetic variant (1) as a mandatory screen, (2) as a medical screen for determining lymphocyte proliferation testing &equency, or (3) in a voluntary screening program is estimated to be $130,000, $5500, or $66,000, respectively, per screened individual. Despite large parameter uncertainty, interval analysis indicates generally positive utility for each of the three evaluated programs when CBD prevalence is greater than 1%. Although the utility of a proposed risk management program may be evaluated solely in terms of health and financial costs,. decisions about program implementation must also consider social, legal, and ethical costs and should be determined through open dialogue with all parties. |
| Value-of-information
analyses for biomarkers: Susceptability to chronic
beryllium disease at us DOE sites. Poster Author: Bartell, S., Other Author(s): R. A. Ponce, T. K. Takaro, G. S. Omenn, R. O. Zebe, and E. Fustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: CRESP 1998 Annual Meeting, Dingmans Ferry, Pa, June. Abstract: |
| Value-of-Information
analysis for biomarkers: Susceptibility to chronic
beryllium disease at US DOE sites Author: Bartell, S.M., Other Author(s): R.A. Ponce, T.J. Takaro,G.S. Omenn, and E.M. Faustman. Document Type: CRESP Presentations, Posters, and Abstracts Publication Date: 1998 Citation: Society of Toxicology Annual Meeting. Seattle, WA, March 1-5. Abstract: |
| Weighing the
risks and the benefits: A call for the empirical
assessment of perceived teratogenic risk Author: Polifka, J.E., Other Author(s): E.M. Faustman, and N. Neil. Document Type: CRESP Published Manuscripts Publication Date: 1997 Citation: Reproductive Toxicology 11(4): 633-640. Abstract: Pregnant women are often faced with complex decisions about whether to undergo medical treatment or continue working in an occupational setting that is permeated with hazardous chemicals. The task for these women is to weigh the benefits of these activities against the potential risks that they may have on the developing embryo. Scientific uncertainty with respect to the teratogenicity of drugs and chemicals in humans leaves health care professionals and their pregnant patients with little predictive information. Cognitive research has shown that it is difficult for people to make complex decisions, particularly when the risks are uncertain. Although the problems inherent in counseling pregnant women regarding teratogenic risk are not new, little time has been devoted to the empiric assessment of how people perceive teratogenic risk and how teratogenic risk information can be best communicated. This article explores the variables that have been found, through psychometric research, to influence people's perception of risk and how cognitive models derived from these studies may be applicable to teratogen information counseling. Understanding the variables that shape the perception of teratogenic risk can help health care professionals improve how they communicate these risks to their patients. Improved teratogenic risk communication will result in better management of pregnancies and reduction of costly litigation that ensues when risks are not properly communicated and understood. |
| Who holds the
stakes? A case study of stakeholder identification at two
nuclear weapons production Sites Author: Boiko, P.E., Other Author(s): R.L Morrill, J.M. Flynn, E.M. Faustman, G. van Belle, and G.S. Omenn. Document Type: CRESP Published Manuscripts Publication Date: 1996 Citation: Risk Analysis 16(2): 237-249. Abstract: Traditional risk assessments, including those involving the United States Department of Energy (USDOE), are often criticized for producing useless or noncredible management responses because they did not meaningfully involve the public. The first step to involve the public is to identify appropriate active participants (stakeholders). This study was done to understand the processes used to identify stakeholders to serve on advisory boards established at the two largest remediation sites in the United States: the Hanford Nuclear Reservation in Washington state and the Savannah River Site in South Carolina. The Hanford stakeholder identification process produced an interest-based board whereas the Savannah River Sim strategy produced population-based representation. The basic goals of the stakeholder advisory groups were similar. However, different processes were used to identify the participants for the groups in part because of distinctly different social and cultural conditions in the areas affected by the operations of the two facilities, and in part because of the different level of trust of the USDOE and their contractors at Hanford compared with Savannah River. The discussion analyzes their different needs and potential for successful citizen participation. |