General process for the risk assessment of pesticides that interact
with or affect the endocrine system
K. Hamernik
Office of Pesticide Programs, U.S.Environmental Protection
Agency, 1200 Pennsylvania Avenue NW (7509C), Washington, DC 20460-0001,
USA
Abstract: The U.S. Environmental Protection Agency's Office
of Pesticide Programs evaluates human health risk associated with exposure
to pesticide chemicals. Chemical hazard and exposure assessment are
components of the risk assessment process. For the risk assessment of
single chemical conventional-type pesticides, there may be multiple
exposure scenarios depending on the use pattern. Examples include acute
and chronic dietary, and short-, intermediate-, and long-term occupational/residential
exposures. For hazard assessment, available toxicity data and a weight-of
the-evidence approach are used in the process of selecting appropriate
toxicity endpoints for relevant exposure scenarios. The pesticide registration
process requires that certain types of supporting toxicity data be submitted
by the registrant depending in part on the chemical use pattern (e.g.,
food use). Types of toxicity data that might be submitted and used in
hazard assessment include acute, subchronic, chronic, carcinogenicity,
mutagenicity, metabolism, reproduction, developmental, neurotoxicity,
and mechanistic studies. There may be data from multiple exposure routes
(e.g., oral, dermal, inhalation) and from the scientific literature
to consider. Dose-response information is also taken into account. In
endpoint selection for a chemical, endocrine system-related effect(s)
and dose-response relationship(s) are assessed in context of other types
of effects, toxicities, and dose-response relationships noted. Endocrine
system-related endpoints may include frank effects (e.g., endocrine
organ hyperplasia or cancer) or precursor events (blood hormone level
elevations). Endocrine system-related endpoints are generally treated
like other cancer or non-cancer toxicity endpoints (e.g., hepatic cancer,
neurotoxicity) in the risk assessment process. For chemicals with evidence
of endocrine system interaction(s), an endocrine system-related effect
may or may not be the most sensitive or relevant endpoint for a particular
risk assessment exposure scenario. Some chemical examples will be presented.
In the final risk assessment, hazard assessment information is integrated
with exposure information. The assessment may be adjusted, at some point,
for uncertainties in hazard or exposure data. An aggregate risk assessment,
in which multiple sources or routes of exposure are considered, is typically
performed for occupational and residential exposure scenarios. A cumulative
risk assessment may be considered for groups of chemicals with a common
mechanism of toxicity.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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