The main emphasis of the project is in the method development for exposure assessment of this potential high risk chemical in human urban environment. This is an essential component of cancer risk assessment approaches related to 1,3-butadiene, both for occupational and for environmental standards.
A method was developed for ambient monitoring of 1,3-butadiene at subparts per million (ppm) level and applied both for urban air sampling and at butadiene production plants in 3 European countries.
It was confirmed that the major primary metabolite of butadiene binds covalently to N-terminal valine of haemoglobin in rats. Although the haemoglobin adduct levels seem to increase linearly with dose in rats, saturation of metabolism is indicated by the nonlinear increase in mice. A specific deoxyribonucleic acid (DNA) adduct analysis method was developed based on N6-alkylated deoxyadenine standard using high performance liquid chromatography (HPLC) 32P postlabelling. This adduct is formed in vitro as well as in vivo, and DNA adducts of butadiene monoepoxide have been detected in lung tissues of mice and rats. The analysis on other tissues and human lymphocyte DNA continues. A method has been developed to detect the depurinated N-7-alkylated guanines excreted in urine, and analysis is ongoing. However, an extensive cytogenetic survey on 3 production units showed no exposure related effects on sister chromatid exchanges, micronuclei or chromosomal aberrations. Studies on ras oncoprotein and transfer growth factors have resulted in neither being detected in human blood samples, the negative results in humans being in accordance with the suggested metabolic differences between mice and humans. New experimental and human biomonitoring approaches are in progress towards a strategic focusing on estimations of human genetic risks.
The project will consist of a comprehensive assessment of 1,3-butadiene, including measurements of ambient levels, individual exposure and uptake, biologically relevant dose, and biological and preclinical effects, leading to a quantitative risk assessment. The main parts of the project are as follows.
Development and validation of methods applicable for human biomonitoring using an experimentally established genotoxic and carcinogenic agent 1,3-butadiene as a model.
Comparison of environmental and biological monitoring methods applicable to low level exposures.
Comparison of the results obtained with different endpoints, particularly between cytogenetic effects and macromolecular binding.
Comparison of abduct levels between environmentally and occupationally exposed humans.
Characterization of individual variation of the target dose as measured by binding to hemoglobin and albumin as a surrogate for critical targets at a given external exposure.
Critical approach to cancer risk estimation of human environmental and occupational exposure to butadiene.
Funding SchemeCSC - Cost-sharing contracts
106 91 Stockholm