United States Environmental Protection Agency Environmental Criteria and Assessment Office Cincinnati, OH 45268 Research and Development EPA/600/S9-85/027 Aug. 1986 SERA Project Summary Workshops for the Development of Methodology for Health Risk Assessment Jerry Stara and Linda Erdreich On September 29-30,1982 and July 11-12,1983, fifty environmental scien- tists from industry, academia, and the U.S. Environmental Protection Agency (EPA) met in Cincinnati to explore methods to assess the risks to human health from exposure to multiple chem- ical pollutants. In two workshops spon- sored by EPA's Cincinnati-based Envi- ronmental Criteria and Assessment Office (ECAO), the scientists examined all relevant routes and durations of exposure to update and expand the single-chemical risk assessment meth- ods developed by ECAO. The first workshop investigated a wide range of possible approaches to assessing risks from exposure to multi- ple chemicals. The second workshop was limited to a discussion of five methods to evaluate risks identified in the first workshop as having the most potential for early application, including interspecies conversions, less-than-life- time exposure, and role of pharmaco- kinetic data. This Project Summary was developed by EPA's Environmental Criteria and Assessment Office. Cincinnati, OH, to announce key findings of the research pro/act that is fully documented in three separate reports (see Project Report ordering information at back). Introduction The U.S. EPA's Environmental Criteria and Assessment Office (ECAO) in Cincin- nati sponsored two workshops in 1982 and 1983 to bring together scientists from government, industry, and academia to review and discuss methods for health risk assessment of chemical mixtures. An important secondary purpose of these meetings was to revise and add to the previously published health assessment guidelines (Federal Register, 1980) for assessing the chronic or lifetime health risk of single contaminants so that the more complex questions associated with exposure to chemical mixtures could be addressed. EPA's interest in the development of risk assessment methodology for multiple chemicals stems from recognition of the nature of actual exposures. The Agency has already regulated public exposure to several mixtures including coke-oven emissions and auto and diesel exhaust. Now, with the implementation of Super- fund, the Agency must develop methods for determining the risks posed by thou- sands of unregulated sites in order to set priorities and direct cleanup efforts. In addition, the Agency must respond to imminent hazards posed by chemical spills, and toward that goal, ECAO has developed a rapid response assessment system. Toxicity data are stored in a computer and used to make an assess- ment that can be provided to state or regional officials within 48 hours. Multi- chemical assessments also have a role in other emergency response and remedial action activities such as determining the reduction in risk after a cleanup of a hazardous site. All EPA programs are often dealing with mixtures rather than single pollutants. ------- Approaches to Risk Assessment for Multiple Chemical Exposures Workshop, September 29-30,1982 The developing methodology for assess- ing risks from exposure to multiple chem- icals is based on the current methodology for identifying effects of chronic exposure to a single chemical from a single route. The ECAO in Cincinnati developed original methods for deriving ambient water quality criteria and for conducting risk assessments on a specific group of solvents. The methodology for deriving ambient water quality criteria focused on chronic exposure to a single chemical from a single route of exposure. The solvent methodology expanded this ap- proach to consider the effects of a single chemical by all relevant routes of ex- posure (oral, dermal, and inhalation) and for all exposure durations (acute, short- term, subchronic, and chronic). In both methodologies, risk assessments for car- cinogens associated an exposure level with a particular incidence of cancer using a nonthreshold model that is linear at low doses. Risk assessments for sys- temic toxicants use a threshold model deriving an estimated acceptable daily intake (ADI) by dividing the no-observed- adverse-effect level (NOAEL) by some uncertainty factors. The new methodology examined in the first workshop, when fully developed, will be used to assess risks in specific haz- ardous sites. Ideally, the methodology developed will be used to estimate from the available exposure data, the types of health effects that might be expected, the incidence of these effects, and an est- imate of the relative hazard of each site. Thus, some of the major areas for meth- odology development include a reason- able approach for multiple chemical ex- posures, a system for combining weighing adverse effects, and the selection of a reasonable extrapolation model for toxic effects. These and other relevant issues were addressed during the first workshop held on September 29 and 30,1982. As shown in the listing below, the first day of the workshop focused on the subject of "Sys- temic Toxicants" (noncarcinogenic ef- fects). Presentations were made on seven aspects of this topic. Each presentation was followed by prepared critiques from other attendees and then by a discussion session. Presentations on the second day of the workshop addressed four aspects of the subject of health assessment of exposures to chemical mixtures. Systemic Toxicants (September 29, 1982) 1. Acceptable Daily Intake 2. Interspecies Conversion of Dose and Duration of Exposure 3. Risk Assessment for Less-Than- Lifetime Exposure 4. Incidence and/or Severity of Effects 5. Route-to-Route Extrapolation and the Pharmacokinetic Approach 6. Multiple Route Exposures 7. The Impact of Carcinogens in Risk Assessment of Chemical Mixtures Health Assessment of Exposures to Chemical Mixtures (September 30, 1982) 1. Outline of Issues and Review of Present Approaches 2. Assessment of Exposure 3. Subpopulations at Greater Risk 4. Biological Bases of Toxicant Inter- actions and Mathematical Models Selected Approaches to Risk Assessment for Multiple Chemical Exposures: Progress Report on Guideline Development at ECAO- Cincinnati—Workshop. July 11-12. 1983 The primary objective of this workshop was to encourage discussions of the development and implementation of mul- tiple chemical assessment methodology. To provide structure to these discussions, the meeting was divided into three ses- sions. In Session I, specific selected ap- proaches were proposed for five subjects discussed in the September 1982 work- shop. During Session I of the July 1983 meeting, discussion focused on whether or not the approach was acceptable as stated. If not, an attempt was made to amend the approach to achieve consen- sus or to clearly identify remaining prob- lems or disagreements. The following topics were presented for consensus: interspecies conversion of dose and duration of exposure; calcula- tion of risk for partial-lifetime exposure to carcinogens or toxicants; calculation of ADIs based on quanta), continuous, or graded response data; pharmacokinetic approaches that can be used for conver- sion among various exposure routes; and methods for multichemical assessment. In Session II, several new topics were presented that had not been previously discussed or had been only touched upon in previous meetings. Presentation of brief outlines of the issues was followed by discussion to elicit comments from participants about the direction develop- ment that these issues should follow. New topics included the use of structure-activ- ity relationships, special methods for reproductive endpoints, and use and biological justification of mathematical models. In Session III, issues introduced at previous meetings, but needing further development, were discussed in four workgroups. Invited scientists and the ECAO staff discussed the strengths and limitations of alternative approaches in order to develop guidelines. The objec- tives of this session were eventual de- velopment of scientifically defensible approaches reflecting current knowledge and identification of options that reflected consensus. The following topics were discussed in the three sessions of the July 11-12, 1983 workshop: Consensus Topics (Session I) 1. Interspecies Conversion of Dose and Duration of Exposure—Noncar- cinogenic Toxicants 2. Health Risk Assessment for Less- Than-Lifetime Exposure—Toxi- cants and Carcinogens 3. ADIs Based on Quanta), Contin- uous or Graded Data 4. Pharmacokinetic Approach for Route- to-Route Conversion 5. Multiple Chemical Assessment Presentation of New Topics (Session II) 1. Approaches Using Structure-Activ- ity Relationships 2. Use of Reproductive Effects as Endpoints in Risk Assessment 3. Use and Biological Justification of Mathematical Models Workshops (Session III) 1. Consideration of High Risk (Sensi- tive) Subgroups in Health Risk Assessment 2. Assessment of Multiple Route Ex- posure 3. Ranking the Severity of Effects 4. Use of Exposure Data in Assessing Health Risk ------- The EPA authors Jerry F. Stars and Linda S. Erdnich are with the Environmental Criteria and Assessment Office, Cincinnati. OH 45268. This Project Summary covers three separate reports, entitled: "Approaches to Risk A ssessment for Multiple Chemical Exposures," (Order No. PB 84-182 369; Cost: $22.95, subject to change) "Selected Approaches to Risk Assessment for Multiple Chemical Exposures: Progress Report on Guideline Development at ECAO-Cin," (Order No. PB 84- 226 992; Cost: $16.95, subject to change) "Selected Approaches to Risk Assessment for Multiple Chemical Exposures: Appendix," (Order No. PB 84-227 008; Cost: $ 16.95, subject to change) The above reports will be available only from: National Technical Information Service 5285 Port Royal Road Springfield. VA 22161 Telephone: 703-487-4650 The EPA authors can be contacted at: Environmental Criteria and Assessment Office U.S. Environmental Protection Agency Cincinnati, OH 45268 United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 Official Business Penalty for Private Use $300 EPA/600/S9-85/027 • 0000339 PS ------- |