The projects conducted under the auspices of the multiple chemical exposure research effort have provided important insights into the issue of exposure assessment to multiple chemical agents. We have applied toxicokinetic modeling to study hexane/MEK interactions, ethane/pentane releases as measures of chronic lung disease, and styrene/butadiene interactions. This work has methodologic significance for investigating internal dose and interactive effects when exposure occurs to multiple chemical agents.

The research on the mechanism of arsenic carcinogenicity has produced important results including 1) identification in bladder hyperplasia in C57/bl mice fed methyl-deficient diets and arsenic; 2) determination that persons with skin cancers who have not drunk arsenic containing water for more than 10 years still have differing capacity to metabolize arsenic suggesting that genetic polymorphisms may be involved; 3) studies of global methylation have demonstrated a dose-response relationship between a methyl-deficient diet, arsenic ingestion and DNA methylation status. This finding of hypomethylation of DNA from arsenic has not previously been reported and has important implications for the study of arsenic cancer mechanisms. The current interdisciplinary research underway on arsenic seeks to define the role of DNA methylation in the arsenic derived cancers.

Faculty from the Core are conducting research on exposure assessment, dosimetry, and aerosol characteristics of beryllium in a key defense facility (LANL). This research will use microprocessor-based instrumentation developed in our laboratories to conduct task-based exposure analysis and studies of size distribution to better assess, control and conduct epidemiologic investigations of beryllium exposure in nuclear weapons production facilities. This microprocessor-based sampling equipment represents a major innovation in exposure assessment. The instrument can be used to characterize each task undertaken by a worker during a workday or an individual in a home or other environmental space. The unit also provides a means for studying size distribution of aerosols. This research has significant potential of protecting workers from beryllium-related disease.

The research projects of which Drs. Colome and Winer are collaborators will provide additional information on the relationship between air pollution monitoring and personal exposure. This is a high priority for the NRC in their determination of the most important research priorities for the study of PM. The project on benzene has had highly relevant results. The study employing the REHEX model demonstrated that, on a population basis, exposure to benzene declined substantially in the California South Coast Air Basin between 1989 and 1997, primarily due to reductions in benzene in reformulated gasolines and vehicle exhaust.

EARC members have contributed to understanding the role of allergens in the environment in relation to traffic. The study by Cass and colleagues found that cars and trucks stir up dust laden with allergy-causing plant pollens and molds. Up to 12% of the allergenic particles in air at the tested sites came from road dust. The new data may help explain reports that living near a busy road can exacerbate asthma symptoms. Diesel exhaust has been suggested as one causal factor, but the new study suggests it may also be due to the resuspension of road dust.

EARC members have worked to improve expertise within the Hawaii Department of Health in the design and performance of environmental epidemiology studies. Technical support was provided to establish two ground-based ambient air monitoring stations on the island of Hawaii. The study was based on an assessment of the potential for human respiratory effects of residents on the Big Island living downwind of the Kilauea volcano. The volcano has been undergoing almost-continuous eruption of lava and airborne release of fine particles and gases since 1983, and children have been chronically exposed. A survey was conducted to (a) identify potential ground-based sites to quantify the exposure of residents at ground level, and (b) to develop an experimental protocol for subsequent health assessment; (3) to assess the acute respiratory health of asthmatics living on the island. EARC participation has led to an initial characterization of exposure, and the launching of an acute health effects panel study of asthmatics supported by exposure data to objectively assess the potential public health risk of volcanic emissions exposure on Hawaii.

EARC personnel have developed standardized exposure assessment survey questionnaires for use in several ongoing health investigations. The current version of the survey was based on the Framingham health questionnaire and modified to include a number of additional questions. These modifications included questions about subject health, residential characteristics and history, and physical/temporal/spatial components of activity. EARC personnel also collaborated with investigators from the National Institute of Respiratory Diseases in Mexico City, to transfer the same exposure characterization and documentation approach for application in a longitudinal health study of Mexican school children begun in 1997. EARC personnel provided guidance and led an effort to administer a similar survey instrument in central China, in support of a longitudinal study of smoking, respiratory health, and environmental exposure study being performed by NIEHS Respiratory Effects Research Core members.

In response to a community environmental organization request to the COEP, an EARC investigator helped to develop a sampling plan to assess the potential exposure of community residents in San Diego to airborne toxic chemicals from several large local industrial sites. The impacted neighborhood is an under-served community in the San Diego area. The area is encircled by several heavily-trafficked highways, leading to a significant source of mobile emissions. EARC personnel conducted a neighborhood site visit, identified potential locations for sampling, and worked with the community organization to persuade the State of California and local air pollution regulatory agency to establish a neighborhood-scale specialty air monitoring station in the area. As a result of EARC participation, objective exposure information is being collected to assess anecdotal reports of respiratory health complaints in the community. The State of California has taken an increased interest in the monitoring activities and health concerns of residents in this community, and is considering identifying the community as one site for more intensive exposure and health characterization, as part of a statewide children's health initiative.

The EARC members have been key collaborators in research exchanges with other NIEHS Centers. These include arranging a Center exchange with the UC Berkeley program in 1997; organizing a Center Bioaerosols Workshop in 1997 which attracted 40 investigators from around the country (including Drs. Harriet Burge and Thomas Smith from the Harvard NIEHS Center, and Dr. Jonathan Samet from Johns Hopkins); being a co-investigator with the NIEHS Center at the University of Iowa on the study of endotoxins; and assisting investigators from the NIEHS Center at Columbia on a community-based study they are conducting in Los Angeles. The latter study, directed by Dr. Patrick Kenney of Columbia, involves a comparison of student exposures to air pollutants in New York City and Los Angeles. The field team for this study is spending several months working out of our Center's facilities.