Karol M H, Stadler J, Magreni C
Fundam Appl Toxicol. 1985 Jun;5(3):459-72. doi: 10.1016/0272-0590(85)90093-4.
A wide variety of industrial materials is known to cause allergic pulmonary reactions. Respiratory symptoms may occur either immediately upon exposure to the agent (immediate-onset response), or several hours later (delayed-onset reaction). In order to determine both the mechanism of response, and a safe exposure level which would prevent development of pulmonary sensitization, animal models are currently being developed for both types of sensitivity responses. In the models, emphasis is placed on simulating conditions present in the industrial environment. For example, (1) exposure to agents is via the inhalation route, (2) animals are unrestrained and unanesthetized both during exposure and during elicitation of response, and (3) reactive chemicals, as opposed to hapten-protein conjugates, are used for exposure. In the model for immediate-onset sensitivity, concentration-response relationships have been observed between the concentration of agent inhaled and the percentage of animals becoming sensitized. Agents employed were bacterial subtilisin and toluene diisocyanate. Identification of "no observable effect" threshold concentrations implies that exposure levels can be proposed for industrial chemicals which will not result in sensitization of workers. Further development of the animal models, followed by calibration of the models to humans, should allow immunotoxicologic evaluation of chemicals for their respiratory sensitizing ability and recommendation of threshold-limit values (TLVs) which would prevent sensitization.
已知多种工业材料可引起过敏性肺部反应。呼吸道症状可能在接触该物质后立即出现（速发型反应），或在数小时后出现（迟发型反应）。为了确定反应机制以及可预防肺部致敏的安全暴露水平，目前正在针对这两种类型的敏感性反应开发动物模型。在这些模型中，重点是模拟工业环境中存在的条件。例如，（1）通过吸入途径接触物质；（2）在接触和激发反应期间，动物不受限制且未麻醉；（3）使用活性化学物质而非半抗原 - 蛋白质缀合物进行接触。在速发型敏感性模型中，已观察到吸入物质的浓度与致敏动物百分比之间的浓度 - 反应关系。所使用的物质是枯草杆菌蛋白酶和甲苯二异氰酸酯。确定“无明显影响”阈值浓度意味着可以为工业化学品提出不会导致工人致敏的暴露水平。动物模型的进一步开发，随后将模型校准至人类，应能对化学品的呼吸道致敏能力进行免疫毒理学评估，并推荐可预防致敏的阈限值（TLV）。
