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CC1-UNEW/ZENE: Molecular Toxicology and Structure Activity Relationships in the Rodent Carcinogenesis of Industrially Important Dienes and the Relevance for Human Cancer

Principal Investigator

Prof. William P Watson
Investigative Toxicology Section
Syngenta Central Toxicology Laboratory (CTL)
Alderley Park
Cheshire, SK10 4TJ
UK
watson@syngenta.com
Tel: +44 1625 514402
Fax: +44 1625 586396

Prof. Bernard Golding
University of Newcastle upon Tyne
Newcastle, NE1 7RU
UK

b.t.golding@ncl.ac.uk
Tel: +44 191 222 6647
Fax: +44 191 222 6929

Description

About one-half of chemicals tested for long-term health effects in laboratory rats and mice have been found to cause cancer. The accuracy of these tests in predicting human cancer risks needs to be fully understood, particularly for chemicals produced and used in large volumes. The key to this is the generation of information about how the rodent cancers are caused, and whether these pathways could also exist in humans. This project will examine molecular mechanisms involved in rodent cancers caused by the industrial chemicals (the dienes butadiene, isoprene and chloroprene), widely used to make rubbers and polymers. Live animals will not be used. Data will be obtained on how the dienes are broken down within cells, and the role of the breakdown products in causing cancer. This will help in setting safe exposure limits for working with these chemicals. It will also be useful in predicting possible toxic effects of chemicals based on their structure.

Related Publications

T Munter, L Cottrell, BT Golding, WP Watson, Detoxication Pathways Involving Glutathione and Epoxide Hydrolase in the in Vitro Metabolism of Chloroprene, Chemical Research in Toxicology 2003, 16, 1287-1297.

T Munter, L Cottrell, S Hill, L Kronberg, WP Watson, BT Golding, Identification of Adducts Derived from Reactions of (1-Chloroethenyl)oxirane with Nucleosides and Calf Thymus DNA, Chemical Research in Toxicology 2002, 15, 1549-1560.

L Cottrell, BT Golding, T Munter, WP Watson, In vitro metabolism of chloroprene: Species differences, epoxide stereochemistry and a dechlorination pathway, Chemical Research in Toxicology 2001, 14, 1552-1562.

Timeline: July 2000 > June 2003

LRI funding: €281,362

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