Humane approches to toxicological evaluations of industrial chemicals — страница 3
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corrosivity. However, the complexity of the immunological system means that contact allergy may not be as readily stadied using in vitro tecniques. The preceding section of this chapter have deal with the areas of ocular toxicity, acute sustemictoxicity, and cutaneous toxicity, and a common theme has emerged. There is, in our opinion, no immediate likelihood of in vitro alternatives replacing laboratory animals in the assessment of acute effects caused by chemical substances. Society demands of the toxicologist a high degree of certainty in determining health hazards, with a minimal tolerance of error. Toxicologists, therefore, need to be cautious that, in their search for alternatives to laboratory animals, they do not reduce the predictive quality of toxicological assessment to the point where people will be put at risk. Selection of a hazard label is particularly dependent on knowing the relative systemic toxicity through the estimation of the median lethal dose (LP50) and the irritant class. The vast majority of chemicals have been classified by data derived from toxicity studies in laboratory animals and, in our experience, with only a small number of chemicals producing adverse acute effects in the acute toxicity tests (Fig. 1). Thus, if there is to be an in vitro alternative to studies in laboratory animals that will have a role in international labeling and classification, it must be very well validated against the animal model. This difficulty should not, however, preclude the use of in vitro tests per se, although it will certainly have a modifying influence on the rate at which they gain acceptance by regulatory authorities. a SYSTEMIC - oral (10%) - dermal (8%) IRRITATION - skin (20%) - eye (21%) SENSITISATION - skin (31%) 22% 3% eye(30%) skin(40%) (2%) (11%) (8%) (6%) c b (75%) FIGURE 1 Acute toxicity studies (outcome of ICI experiments, 1976-1983). (a) Proportion of studies, (b) Proportion of studies with effects, (c) Proportion of all studies. The chemical industry is most concerned for the health and safety of people who may be affected by its products and activities. The toxicologist is pivotal in producing the data that can help reduce risks by improving the knowledge and understanding of the hazardous properties of chemical substances. The use of laboratory animals to investigate these hazards is unavoidable until such time as in vitro alternatives have proven ability to predict the dangers to humans. LITERATURE 1. Jackson S.J., Rhodes C., Oliver G.J.A. Humane approaches to Acute Toxicity Assessment of Industrial Chemicals. // Toxic Substances Journal. 1989. pp.279-299. 2. O Flanerty E.J. Dose Dependens Toxicity. // Commenis Toxicology. 1986. Vol.1. pp. 23-34. 3. Toxicological Evaluations. Potential health hazards of existing chemicals. BG Chemie. Berlin. 1990. 341 p.