STUDIES ON PREDICTION AND THRESHOLD LIMIT VALUES OF OCCUPATIONAL SENSITIZERS.

本研究的目的是为建立职业致敏剂引起的呼吸道过敏的预防措施提供信息。我们认识到预防措施的要求如下：过敏性预测、职业致敏剂的列出、超敏反应中剂量-反应关系的确认和职业暴露限值(OEL)的设定。我们在现有报告的基础上修订了列出职业敏感剂的草拟表格。为了建立它们的OELs，我们首先利用我们的动物模型研究了TDI的诱导浓度与免疫应答之间的关系。豚鼠吸入0.02~1.0ppm的TDI，每天3h，连续5天。三周后，动物通过吸入TDI-豚鼠白蛋白(TDI-GSA)结合物进行激发。评估是基于TDI特异性抗体，肺反应…更多的ES(如呼吸频率)和抗原刺激肺肥大细胞释放组胺。结果表明，抗体效价和肺部反应的严重程度均呈诱导浓度依赖的方式，并有相应的阈值水平。在暴露于0.02ppm TDI的动物中检测不到抗体和肺部反应，但在暴露于0.2ppm或更高TDI的动物中则检测不到抗体和肺部反应。抗体产生和组胺释放的存在与肺反应的诱发密切相关，但两者之间没有相关性。此外，为了模拟职业暴露条件，我们在挑战时使用了0.02ppm的TDI本身。使用共轭药物的患者也观察到了类似的肺部敏感性结果，尽管肺部反应程度较弱。上述结果表明，本模型可用于探讨诱导和激发时肺敏感性的剂量-反应关系，抗体产生和组胺释放可能分别作为肺反应暴露和发展的指标。最后，给出了评价肺敏感度和建立职业增敏剂OELs的流程图。较少

The purpose of this study was to provide the informations to establish preventive measurements for respiratory allergy from occupational sensitizers. We carried out this study recognizing the requirements of preventive measurements as below : the prediction of allergenicity, listing up of occupational sensitizers, the confirmation of dose-response relationship in hypersensitivity reactions and setting up of occupational exposure limits (OELs). We revised our drafted table exhibiting occupational sensitizers on the bases of current reports. For setting up the OELs of them, first we investigated the relationships between the induction concentration of TDI and immunological responses using our animal model. Guinea pigs were exposed via inhalation to TDI ranging from 0.02 to 1.0 ppm for 3h/day on 5 consecutive days. Three weeks later, animals were challenged via inhalation with TDI-guinea pig albumin (TDI-GSA) conjugates. Evaluations were based on TDI specific antibodies, pulmonary respons … More es (as respiratory rate) and antigen stimulated histamine releases from lung mast cells. The results indicated that both the antibody titer and the severity of pulmonary response followed induction concentration dependent fashions with corresponding threshold levels. Antibodies and pulmonary response were undetectable in animals exposed to 0.02 ppm TDI, but not in those exposure to 0.2 ppm TDI or more. The existences of antibody production and histamine release were associated closely with the elicitation of pulmonary responses, but there was not a relationship between the both. Further, to simulate occupational exposure condition, we employed 0.02 ppm TDI itself at challenge. The similar findings of pulmonary sensitivity were observed with those following the employment of conjugate, though there was weakness in the degree of pulmonary responses. These results above suggested that the current model was useful to explore dose-response relationships in pulmonary sensitivity at induction and challenge phases and that antibody production and histamine release might be indices of the exposure and development of pulmonary responses, respectively. Lastly, the flowchart to evaluate the pulmonary sensitivity and to set up the OELs of occupational sensitizers was made. Less