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Comprehensive risk analysis of dioxins: development of methodology to assess genetic susceptibility to developmental disturbances and cancer

Objective


The objective is to set a scientifically defendable limit of safe exposure to dioxins, as to developmental effects and cancer. The exceptionally wide inter- and intraspecies differences in sensitivity to dioxins will be scrutinised to diminish this major uncertainty factor in risk assessment. To achieve this general objective, a number of specific objectives are set:
1. To study the molecular mechanisms of dioxin toxicity in a multidisciplinary manner, utilising the mutated receptor causing a remarkable resistance towards dioxin toxicity
2. To resolve in population studies the sensitivity of human being to developmental effects (tooth defect and cleft palate) cancer, and compare these outcomes to results in experimental animals.
3. To perform an up-to-date dioxin risk assessment.

Scientific approach

The work can be divided to five major parts, all of which contain input by several partners.
1. Mechanistic studies aimed at increasing understanding on the mechanism of toxic actions of dioxins. This is necessary, because there are several serious gaps in the information, and a science-based risk assessment is not possible without understanding the basics. This part utilises mutated dioxin receptor genes which the partners have demonstrated in experimental animals, and by means of molecular biology techniques attempt, to pinpoint the critical steps in toxic mechanisms.
2. Human levels in population are established by measuring dioxin-like compounds in fat (breast milk, surgical samples, placentas).
3. The sensitivity of human beings to the developmental effects (especially tooth defects in children) is scrutinised in population studies, and compared with the sensitivity of normal and mutated animals to find out the capability of data to predict human effects.
4. The risk of cancer is studied in human populations by correlating the cancer risk with dioxin concentrations in the body. Especially important is soft tissue sarcoma which is thought to be associated with dioxin exposure.
5. A comprehensive risk assessment exercise is performed on the basis of the whole data set obtained from the proposed studies directed at critical data gaps, and also fully utilising previous information. In an attempt to help decision makers, this continues with a policy-driven risk analysis exercise to illuminate all factors needed in the decision-making process.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

NATIONAL PUBLIC HEALTH INSTITUTE
Address
Mannerheimintie 166
Helsinki
Finland

Participants (5)

AZIENDA OSPEDALIERA "OSPEDALE CIVILE DI VIMERCATE"
Italy
Address
Via Benefattori Ospedale 2
20033 Desio
INSTITUTE OF BIOTECHNOLOGY
Lithuania
Address
8,Graiciuno Street 8
2600 Vilnius
KAROLINSKA INSTITUTE
Sweden
Address
Solnavagen 1
171 77 Stockholm
LINKOEPING UNIVERSITY
Sweden
Address
Hus Origo Campus Valla
581 83 Linkoeping
UNIVERSITY OF HELSINKI
Finland
Address
Yliopistonkatu 4
00014 Helsinki