Citation:

COLON, D., E. J. WEBER, J. L. ANDERSON, P. WINGET, AND L. A. SUAREZ. TRANSFORMATION OF NITROSOBENZENES AND HYDROXYLANILINES BY FE (II) SPECIES: ELUCIDATION OF MECHANISM, EFFECT OF FERRIC OXIDES AND PH. Presented at 230th American Chemical Society National Meeting, ENVR 178, Washington, DC, August 28 - September 01, 2005.

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:

The purpose of this work was to (i) study the effect of structure composition on the reactivity of a series of N-hydroxylaniline and nitrosobenzene compounds toward their reduction by Fe(II) species, (ii) evaluate the usefulness of several chemical parameters for predicting the rate of reduction of N-hydroxylaniline compounds in Fe(II) systems, (iii) obtain an insight of the rate determining step for the reduction of N-hydroxylaniline compounds in such systems, (iv) study the effect of pH on the rate of reduction of p-cyano-N-hydroxylaniline (CNHA) and p-cyanonitrosobenzene (CNNO) in the presence of Fe(II) species and (v) determine the reactivity of various ferric oxides and the effect of their surface area loading, toward the reduction of CNHA. CNHA was selected as our model compound for the study of several environmentally relevant variables in the N-hydroxylaniline reduction because its pKa is low enough, i.e., -0.7 to -0.85 (17), to rule out changes in its speciation at the various experimental conditions used in this work.

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