STUDIES ON PREDICTION AND THRESHOLD LIMIT VALUES OF OCCUPATIONAL SENSITIZERS.

本研究的目的是为建立职业性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：预测致敏性，列出职业致敏物，确定超敏反应的剂量-反应关系，制定职业暴露限值（OELs）。我们在现有报告的基础上修订了列出职业致敏物的表格草案。为了建立它们的OELs，我们首先用动物模型研究了TDI诱导浓度与免疫反应的关系。豚鼠连续5天吸入0.02至1.0 ppm范围内的TDI，每天3小时。三周后，通过吸入tdi -豚鼠白蛋白（TDI-GSA）偶联物对动物进行攻击。评估基于TDI特异性抗体，肺反应…更多es（呼吸频率）和抗原刺激肺肥大细胞释放组胺。结果表明，抗体滴度和肺反应严重程度均符合诱导浓度依赖模式，具有相应的阈值水平。在暴露于0.02 ppm TDI的动物中检测不到抗体和肺反应，但在暴露于0.2 ppm TDI或更高的动物中检测不到。抗体产生和组胺释放的存在与肺反应的引发密切相关，但两者之间不存在相关性。此外，为了模拟职业暴露条件，我们采用0.02 ppm TDI本身作为挑战。类似的肺敏感性的发现被观察到与那些使用缀合物，虽然有弱的程度的肺反应。上述结果表明，目前的模型有助于探索诱导期和激发期肺敏感性的剂量-反应关系，抗体产生和组胺释放可能分别是肺反应暴露和发展的指标。最后，编制了职业致敏剂肺敏感性评价流程图，并建立了职业致敏剂的oel。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