Retrospective Assessment of Mixed Chemical Exposures

描述（由申请人提供）： 暴露的错误分类是流行病学研究中偏倚的一个持久来源。 职业性癌症的研究。出现这种情况的原因如下：（a） 曝光重建通常基于稀疏数据 不确定性;（B）未估计生物相关剂量，例如，为 暴露于吸入性粉尘，工人的累积肺负担不 说明吸入粉尘的滞留和清除情况; 接触多种 化学品没有说明。拟议研究的目的是 制定改进的流行病学暴露和剂量评估方法， 对职业性癌症的研究， 由于数据稀疏，暴露重建，病因学的决定因素 相关剂量和暴露于多种化学品，使用贝叶斯 概率框架将制定和演示该方法 使用来自Falcon bridge的大型职业暴露数据集（1950 - 2000年） 有限公司、萨德伯里，安大略，这是一个世界领先的原镍 生产公司。这里的工人历史上曾接触过几种 镍物质（氧化物、亚硫酸盐和可溶性）、柴油颗粒物，以及 二氧化硅-所有这些都是已证实或怀疑的人类致癌物， 特别是导致肺癌。一种新的贝叶斯方法， 综合专家判断和历史测量，将制定 曝光重建曝光重建将包括 用于估计累积肺剂量的保留和清除模型 氧化物、亚硫酸盐和可溶性镍物质，柴油颗粒物，以及 空气中的二氧化硅然后，曝光重建将可用于 计划在该人群中进行肺癌流行病学病例对照研究。 然而，该方法将适用于其他行业的流行病学 现有数据稀少的研究和接触化学混合物的研究 是常态

DESCRIPTION (provided by applicant): Misclassification of exposure is a persistent source of bias in epidemiologic studies of occupational cancer. This occurs due to the following reasons: (a) exposure reconstructions are typically based on sparse data with significant uncertainty; (b) biologically relevant doses are not estimated, e.g., for exposures to inhaled dusts, the cumulative lung burdens of the worker do not account for retention and clearance of inhaled dusts; exposures to multiple chemicals are not accounted for. The objective of the proposed research is to develop an improved exposure and dose assessment method for epidemiologic research on occupational cancer that accounts for the uncertainties in exposure reconstruction due to sparse data, determinants of etiologically relevant dose, and exposures to multiple chemicals, using a Bayesian probabilistic framework. The methodology will be developed and demonstrated using a large occupational exposure dataset (1950-2000), from Falcon bridge Ltd., Sudbury, Ontario, which is one of the world's leading primary nickel production companies. Workers here have historically been exposed to several nickel species (oxidic, sulfitic, and soluble), diesel particulate matter, and silica - all of which are either proven or suspected human carcinogens, specifically causing lung cancer. A novel Bayesian methodology that synthesizes expert judgment and historical measurements will be developed for exposure reconstruction. The exposure reconstruction will incorporate retention and clearance models for estimating the cumulative lung dose of oxidic, sulfitic, and soluble nickel species, diesel particulate matter, and airborne silica. The exposure reconstruction will then be available for a planned epidemiologic case-control study of lung cancer in this population. However, the methods will be applicable to other industry based epidemiologic studies where the available data are sparse and exposures to chemical mixtures are the norm.