Description:

Objectives/Hypotheses: Halogenated by-products of drinking water disinfection are of concern because of uncertainty over their health effects, particularly an increased risk of kidney and bladder cancer and widespread consumption. Due to their abundance relative to other halogenated disinfection by-products, haloacetic acids may form macromolecular adducts that could be useful as biomarkers of exposure to disinfectants. Mechanisms of biological activity and disposition of haloacids formed as by-products of water disinfection will be investigated. The major goal of this project is to identify the chemical nature and mechanism of formation of metabolites of the potent bacterial mutagen (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid, more commonly known in its ring-closed form as 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone or MX (for Mutagen "X"), and of macromolecular adducts formed from the low molecular weight haloacetic acids (alkanoic, alkenoic and oxobutenoic acids) chloroacetic acid, dichloroacetic acid, from their brominated analogs bromoacetic and dibromoacetic acid, and from the mixed haloacetic acid bromochloroacetic acid.

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Final Progress Report

1999 Progress Report

Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:01/23/1998

Completion Date:01/22/2001

Record ID: 18628

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Related Organizations:

Role :OWNER

Organization Name :UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

Mailing Address :103 S Bldg Cb 9100

Citation :Chapel Hill

State :NC

Zip Code :27599

Project Information:

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :Drinking Water

Risk Paradigm :EXPOSURE

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :M/DBP (DBP)

Risk Paradigm :RISK ASSESSMENT

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :ARSENIC

Risk Paradigm :RISK ASSESSMENT

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :Drinking Water

Risk Paradigm :RISK ASSESSMENT

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :M/DBP (DBP)

Risk Paradigm :EXPOSURE

Approach :

Two specific approaches will be followed towards elucidating the mechanisms of activity of biologically potent disinfection by-products at the molecular level:

I. Identification and Quantitation of Macromolecular Adducts Formed by Haloacetic Acids: Structural identification and quantitation of DNA adducts will be approached by chromatographic and mass spectrometric techniques. Quantities of adducts sufficient for detailed structural elucidation are often difficult or impossible to obtain by direct modification of DNA, hence direct chemical synthesis will be undertaken to provide standards for investigation of adduct formation in vivo.

II. Investigation of the Metabolism and Disposition of MX: Structural identification of MX metabolites, and their tissue distribution in the rat, will be carried out in order to gain an understanding of the nature of the active species present at potential target organs, and the levels and duration of internal exposure.

Cost :$460,848.00

Research Component :ARSENIC

Risk Paradigm :EXPOSURE

Project IDs:

ID Code :R825957

Project type :EPA Grant