You are here:
DESIGNING PESTICIDE METABOLIC PATHWAY/DEGRADATE DATABASES FOR REGISTRANT SUBMITTED HEALTH EFFECTS/ECOLOGICAL EFFECTS DATA
Citation:
KOLANCZYK, R. C., W. J. JONES, O. MEKENYAN, A. PROTZEL, G. DANNAN, S. ABEL, AND P. K. SCHMIEDER. DESIGNING PESTICIDE METABOLIC PATHWAY/DEGRADATE DATABASES FOR REGISTRANT SUBMITTED HEALTH EFFECTS/ECOLOGICAL EFFECTS DATA. Presented at BOSC SP2 Review, Research Triangle Park, NC, February 07 - 09, 2007.
Impact/Purpose:
This task is divided into four major research areas: (1) Development of computational tools and databases for screening-level modeling of the environmental fate of organic chemicals; (2) Metabolism of xenobiotics: Enhancing the development of a metabolic simulator; (3) Metabonomics: The use of advanced analytical tools to identify toxicity pathways; and (4) Software infrastructure to support development and application of transformation/metabolic simulators.
For many chemicals, multiple transformation/metabolic pathways can exist. Consequently, transformation/metabolic simulators must utilize transformation rate data for prioritization of competing pathways. The prioritization process thus requires the integration of reliable rate data. When this data is absent, it is necessary to generate a database with metabolic and transformation rate constants based on: (1) experimentally measured values, including those requiring the use of advanced analytical techniques for measuring metabolic rate constants in vivo and in vitro; (2) rate constants derived from SPARC and mechanistic-based QSAR models; and (3) data mined from the literature and Program Office CBI. A long-term goal of this project is to build this database. This information will be used to enhance the predictive capabilities of the transformation/metabolic simulators. As indicated previously, exposure genomics, which provide early signs of chemical exposure based on changes in gene expression, will be used to guide chemical fate and metabolism studies. The incorporation of exposure genomics into fate studies will provide information concerning (1) the minimal concentrations at which biological events occur; and (2) the identification of biologically relevant chemicals(s) in mixtures.
The capability of categorizing chemicals and their metabolites based on toxicity pathway is imperative to the success of the CompTox Research Program. Metabonomics, which is the multi-parametric measurement of metabolites in living systems due to physiological stimuli and/or genetic modification, provides such a capability. The application of metabonomics to toxicity testing involves the elucidation of changes in metabolic patterns associated with chemical toxicity based on the measurement of component profiles in biofluids, and enables the generation of spectral profiles for a wide range of endogenous metabolites. Metabolic profiles can provide a measure of the real outcome of potential changes as the result of xenobiotic exposure.
Description:
OPPTS requires information on the toxic effects of pesticide metabolites as well as the parent chemical. Currently, OPP receives metabolic maps with registrant study data submissions, but there is no efficient way to access previously submitted maps on similar chemicals to help with assessment of new chemicals. Information from past studies is used by risk assessors to assess the likelihood that all potentially toxic metabolites have been considered. More efficient use of existing data is needed to meet the challenge of resource limitations and aggressive assessment deadlines. Additionally, without access to this data, it is difficult to identify similarities in chemical metabolism and for researchers to formulate and test hypotheses for the types of chemicals that are of highest concern to EPA.