To date, the epidemiologic literature has been inconclusive regarding the teratogenicity of organic solvents, primarily due to small sample sizes, weak exposure assessment methods, and grouping of solvents and specific malformations. Given that only 3% of infants are born with major malformations, epidemiologic studies of birth defects are often limited to the case-control design and retrospective assessment of exposure. To date many studies have relied upon self-reported occupational exposures or job titles to determine exposure which may have led to exposure misclassification and attenuation or overestimation of risk estimates. A new exposure assessment method has been developed by the National Cancer Institute (NCI method) that uses task and job exposure matrices developed after an extensive literature review. An industrial hygienist uses the matrices as well as his/her own experience to infer exposure for each individual job. The standardized and comprehensive source of exposure information, as well as the identification of exposure determinants (location, quantity, ventilation, temperature, operation and mechanism of release) should provide more reliable, and possibly more valid exposure estimates and less biased effect estimates. ? ? Using this new methodology, we propose to examine the association between exposure to six chlorinated solvents and five specific cardiovascular malformations (CVM) using data previously collected for the Baltimore Washington Infant Study (BWIS) which was carried out between 1981 and 1989. The proposed study will have three specific aims: 1) To determine the association between occupational, chlorinated solvent exposure and cardiovascular malformations among families participating in the Baltimore Washington Infant Study, 1981-1989; 2) to evaluate the inter- and intra-rater reliability of the NCI method in assessing chlorinated solvent exposure; and 3) to assess the impact of potential misclassification of chlorinated solvent exposure on the association between solvents and cardiovascular malformations through statistical methods. The proposed study provides a unique opportunity to use existing data to assess the association between chlorinated solvents and cardiovascular malformations and to further develop retrospective exposure assessment methods, and related statistical methods. ? ? ? ?
