STRUCTURE ACTIVITY HYPOTHESES IN OCCUPATIONAL ASTHMA CAUSED BY LOW-MOLECULAR-WEIGHT SUBSTANCES
STRUCTURE ACTIVITY HYPOTHESES IN OCCUPATIONAL ASTHMA CAUSED BY LOW-MOLECULAR-WEIGHT SUBSTANCES
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DOI：
10.1093/annhyg/35.2.129
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发表时间：
1991-04-01
影响因子：
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通讯作者：
ROBERTSON, A
中科院分区：
文献类型：
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作者：
AGIUS, RM;NEE, J;ROBERTSON, A
许多具有低分子量（小于1000分子量）但不同化学类别的物质被认为是职业性哮喘的病原体。它们的一些主要化学性质突出了它们与人类大分子的相互作用。因此，形成配位络合物的某些过渡金属可以螯合人蛋白质。有几种有机物具有显著的基本性质，这些性质决定了它们的化学反应性。其中一些，如双官能基乙二胺、哌嗪和对苯二胺是已知的哮喘病原体，而它们的单官能对应物，尽管广泛的工业应用，但不是类似公认的原因。这表明，多个反应基团的存在是重要的分子相互作用与人类大分子，最终导致职业性哮喘。还提到了其他物质来解释这些相互作用的假设机制。这种假设的产生是一个前奏定量研究的结构活性关系（QSAR）的假设可以进行测试和修订。孤立的结构活动假说可能不是职业性哮喘风险的充分预测因子。然而，如果将其应用于新的化学实体，它们最终可能证明有助于制定前瞻性健康监测政策和确定流行病学研究的优先事项。
Many substances with a low molecular weight (less than 1000 molecular weight) but of different chemical classes are recognized as causative agents of occupational asthma. Some of their major chemical properties are highlighted in relation to their putative interactions with human macromolecules. Thus, certain transition metals which form co-ordination complexes may chelate human proteins. Several organic substances have marked basic properties which are responsible for their chemical reactivity. Some of these, such as the bifunctional bases ethylene diamine, piperazine and para-phenylene diamine are known causative agents of asthma while their monofunctional counterparts, in spite of wide industrial application, are not similarly recognized causes. This suggests that the presence of multiple reactive groups is of importance in the molecular interactions with human macromolecules that eventually lead to occupational asthma. Reference is also made to other substances to exemplify hypothetical mechanisms of these interactions. Such generation of hypotheses is a prelude to quantitative studies of structure activity relationships (QSARs) where the hypotheses can be tested and revised. Structure activity hypotheses in isolation might not be adequate predictors of the risk of occupational asthma. However, if applied to novel chemical entities they might eventually prove useful in contributing to the development of policies for prospective health surveillance and in establishing priorities for epidemiological research.