Vol. 23, No. 4
Initiative (LRI) of the American Chemistry Council (cont')
Carol J. Henry and James S. Bus
Development of the Long-Range Research Initiative
Technical Implementation Panels
Selected Examples of Ongoing Projects
Technical Implementation Panels
The Technical Implementation Panels (TIPs) of the American Chemistry
Council are organized to provide technical support and assistance for
each of 10 scientific areas (Table 2). The TIPs
consist of outside experts working in partnership with scientific specialists
from member companies of the American Chemistry Council to support the
Long-Range Research Initiative (LRI). CIIT derives support from the
LRI for research in chemical carcinogenesis; endocrine, reproductive,
and developmental toxicology; neurotoxicology; respiratory toxicology;
and risk assessment methods. Other research organizations are supported
through an extramural, competitive, request-for-proposals process that
addresses scientific issues in endocrine modulation and reproductive
and developmental toxicology, epidemiology, exposure, immunotoxicology,
neurotoxicology, and risk assessment. Requests for proposals are posted
on the American Chemistry Council Web site <http://www.americanchemistry.com>
under the overview information on the LRI.
Table 2 Technical
implementation panels (TIP) of the American Chemistry Council.
Explores the role of chemicals in atmospheric science that will
increase our understanding of the processes affecting formation,
transport, and removal of pollutants in the atmosphere.
Examines the biological mechanisms and dose-response relationships
involving cancers that may be associated with exposure to various
substances. Extrapolation of results from animals to humans,
the role of biomarkers, and gene-related differences in biological
responses are among the issues explored.
Considers the effect that exposure to chemicals might have on
the endocrine, reproductive, and developmental health of human
and wildlife populations.
Addresses research on issues of environmental exposure assessment,
ecological risk assessment and management, and ecosystem dynamics.
Increases scientific understanding of the potential hazards
of chemicals and improves epidemiological methods and their
application in assessing human health risks.
Addresses research designed to characterize human exposure to
chemicals and reduce the uncertainty for quantitative estimates
of exposures associated with the potential human health effects
Sponsors research to develop animal models that predict the
ability of chemicals to induce or exacerbate allergic and other
Examines biologically significant changes in the structure or
function of the nervous system that may result from chemical
Toxicology TIP Sponsors research to improve risk assessment
methods of inhaled reactive gases, understand the pathobiology
and dosimetry of particles and fibers, and improve animal models
of particulate-induced disease.
Assessment Methods TIP
Addresses research to advance human health risk assessment methodologies
for chemicals.describe research supported by the LRI at CIIT
as well as at other research organizations.
The six research principles under which the Long-Range Research Initiative
(LRI) operates reflect the commitment of industry to scientific excellence:
(1) studies will complement existing research by government, academia,
(2) collaborations with key internal stakeholders, academia, and government
(3) experts from academia, government, and industry will participate
in decision-making and provide advice on the quality, direction, and
value of the research conducted;
(4) individual researchers will determine the methods and procedures
to be used in conducting the research;
(5) rigorous scientific principles and laboratory practices will be
used at all times; and
(6) results will be made public regardless of outcome.
The global LRI is coordinated through the Long-Range Research Initiative
Steering Committee of the International Council of Chemical Associations
(ICCA). The United States chemical industry is represented at ICCA through
the American Chemistry Council, the European chemical industry through
the European Chemical Industry Council (CEFIC), and the Japanese chemical
industry through the Japan Chemical Industry Association (JCIA). Each
organization has the responsibility for implementing ICCA principles,
which address scientific excellence, open processes and results, fair
and unbiased conduct, and relevance to the chemical industry.
Selected Examples of Ongoing Projects
An overview of studies being conducted as part
of the Long-Range Research Initiative (LRI) illustrates the depth and
breadth of industry efforts (Table 3).
Some studies involve species extrapolation issues, such as the chloroform
studies conducted at CIIT.
CIIT research on the mechanism of chloroform toxicity was extremely
valuable in assessing the risk to human health from low-level environmental
exposures to chloroform. The examples presented in Table
3 describe research supported by the LRI at CIIT as well as at other
Shortcuts or replacements for long-term bioassays used to determine
the potential hazards of chemicals are being sought throughout the scientific
community. These alternative bioassays are needed to save time and resources
and reduce the number of animals used in toxicity testing. One of these
new technologies, the p53 transgenic animal mouse model, may reduce
the time to detection of tumors following chemical treatment. Before
the p53 model can be used in risk assessments, however, the data from
the model must be understood and interpreted. CIIT is conducting research
to determine the relevance of the p53 model in predicting human health
outcomes. Current CIIT projects involve the investigation of the carcinogenicity
of benzene and the drinking water by-product bromodichloromethane.
Research in the atmospheric sciences sponsored by the LRI is intended
to fill knowledge gaps and aid in the development of future environmental
policies. The priority research themes include atmospheric degradation
pathways, aerosol microphysics and chemistry, and organic compounds
in the global atmosphere. For example, a project on the contribution
of biogenic emissions to urban ozone leverages an existing research
program of the Coordinating Research Council, a nonprofit organization
that directs engineering and environmental studies on the interaction
between automotive equipment and petroleum products.
The chemical industry has historically conducted many epidemiology
studies to determine long-term mortality and cancer incidence in workers
involved in the manufacture of chemical products. The American Chemistry
Council has developed an inventory of mortality and cancer incidence
studies available in the peer-reviewed literature. This worker population
database is a valuable resource for the chemical industry and for the
scientific community at large. The Health Studies Inventory Summary
Report is available on the American Chemistry Council web site <http://www.americanchemistry.com>,
and the database itself can be purchased by both Council members and
nonmembers. The inventory was used for an interpretive review to assess
the overall burden of disease for the population of chemical manufacturing
A critical issue for the chemical industry is in the area of exposure.
As the high-production-volume (HPV) testing program is developed and
implemented and large amounts of chemical, animal, and hazard toxicity
data are generated, exposure data and models to predict patterns of
exposure will be needed to understand better the potential hazards associated
with HPV chemicals. Research is in progress to examine the limitations
of existing models used to predict the occurrence and extent of human
exposure. For example, the Exposure Assessment TIP is sponsoring research
to examine models that predict chemical exposures from oral and dermal
absorption as well as models that focus on an individuals personal
environment, or microenvironment. The Exposure Assessment TIP will also
oversee projects aimed at understanding and developing a framework that
focuses on combinations of exposure pathways and sources and the accumulation
of these exposures over time. Exposure modeling is expected to lead
to better exposure assessment for chemicals. Work on the exposure framework
will help companies understand how a persons exposure is influenced
by activity patterns, age, gender, occupation, and other demographic
The LRI is funding projects that address methods in risk assessment.
One of these projects involved assessment of the human health risks
from formaldehyde using benchmark dose analysis. The significance of
the project was recognized in 1999 when CIIT scientist Dr. Paul Schlosser
received an award from the Risk Assessment Specialty Section of the
Society of Toxicology for his poster presentation on "Formaldehyde Risk
Assessment by Benchmark Dose Analysis Using DNA-Protein Cross-Links
as an Internal Dose Metric." Other research projects address pharmaco-kinetic
modeling, cumulative risks, inter- and intraspecies variability in extrapolation
modeling, and low-dose extrapolation modeling.
The LRI is sponsoring research involving wildlife studies to develop
animal models for detecting endocrine- active materials. Field studies
of songbird reproduction and productivity are under way, and research
is being conducted on fence lizards as a potential reptilian model for
ecological assessment of endocrine-active materials.
Environmental regulation and product stewardship have been very effective
in the last 20 years at reducing exposures to manufactured chemicals.
Through Responsible Care, workers in the chemical industry are 4.5 times
safer than those in all other manufacturing industries (calculated from
tables in the Monthly Labor Review, July 2000). The chemical
industry has also reduced EPA Toxic Release Inventory emissions between
1988 and 1998 by 63% while increasing production over 27% and is talking
with its neighbors through some 300 Community Advisory Panels.
To understand the impact of chemicals on human health and the environment,
the chemical industry and downstream chemical users are engaged in providing
more information to improve understanding of how chemicals are manufactured,
used, distributed, and ultimately disposed of. What are the potential
effects on the environment or on human health associated with low-level
exposures to chemicals? How can the scientific issues associated with
sustainability and life-cycle analysis be identified and developed?
Such questions can only be answered by effectively working with research
communities in academia, government, and industry. In alliance with
CIIT, the Long-Range Research Initiative (LRI) is actively engaged in
improving our understanding about chemicals and finding answers to these