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Research on occupational and environmental agents is undertaken to address several general questions, all needing to be answered as the basis for policies, regulations, and other interventions to mitigate exposures with adverse health impacts:

  • Does the agent cause adverse health effects?

  • How does risk vary with exposure levels?

  • Who is exposed, how are people exposed, and why are people exposed?

  • What groups may be differentially susceptible to the exposure?

  • How can exposures and their related health effects be reduced or eliminated?

The answers to these questions come from research that is based in toxicology, including animal bioassays, in vitro experiments, and brief human exposures for some agents, in epidemiological studies of exposed populations, and in exposure assessments. Intervention studies to reduce exposures are a less frequent approach, but randomized trials have been carried out to assess possibly beneficial interventions and quasiexperimental designs have been used to assess the consequence of policy measures. Mechanistic understanding and evaluation of the impacts of interventions also provide answers to these key questions. In a general framework, we seek to understand the path from sources of exposure to adverse health effects (Fig. 65-1).


General framework for the path from exposure to health outcomes. (Source: Adapted with permission from National Research Council, Committee on Toxicity Testing and Assessment of Environmental Agents, Board on Environmental Studies and Toxicology, Institute for Laboratory Animal Research, Division on Earth and Life Studies. Toxicity testing in the 21st century : a vision and a strategy. Washington, DC: National Academies Press; 20077).

Research is often triggered by concerns about adverse health effects resulting from environmental or occupational exposures. Sentinel events, such as the rare lung disease bronchiolitis obliterans in popcorn workers handling the flavoring diacetyl1 or skin hyperkeratosis following chronic exposure to arsenic in water2 provide a warning by being uncommon and relatively specific. The finding of exposure through biomonitoring may be another trigger, bringing recognition that populations are exposed, as has occurred over the last several decades with the detection in blood samples of per- and polyfluoroalkyl substances that contaminate water and food.3 Research also extends to the mechanisms by which agents cause disease; mechanistic understanding contributes to reducing uncertainties related to interpreting the findings of epidemiological studies and of bioassays, helping to support the extension of toxicological research to humans, gauging the plausibility of associations found in epidemiological studies, and informing the modeling of exposure-response relationships. Ideally, decision-making is based in integration of information from these various lines of research so that the weight of evidence on the key questions above can be determined and the critical uncertainties characterized.

This chapter provides an overview of the research methods used to address environmental and occupational agents. While there are commonalities, worker populations are by nature selected from ...

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