STRUCTURE ACTIVITY HYPOTHESES IN OCCUPATIONAL ASTHMA CAUSED BY LOW-MOLECULAR-WEIGHT SUBSTANCES

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.