STUDIES ON PREDICTION AND CLASSIFICATION OF OCCUPATIONAL RESPIRATORY SENSITIZERS

本研究的目的是为建立职业性过敏性呼吸道过敏的预防措施提供信息。我们开展了这项研究，认识到预防措施的要求如下：过敏性预测、职业致敏剂清单和超敏反应中剂量-反应关系的确认。我们修订了我们先前起草的表格，以展示职业呼吸道敏感剂。修订的主要观点是，分类标准是以信息的可靠性为基础的。为了评估标准，我们调查了选定的几种呼吸道增敏剂是否得到了充分的评估。随后，大体上确认了该标准的性质。流行病学证据的标准需要进一步修订。为了建立评价职业性化学品对小鼠的呼吸道致敏作用的方法，我们分析了小鼠实验…中的细胞因子谱更倾向于使用敏感剂。小鼠通过涂甲苯二异氰酸酯(TDI)致敏，甲苯二异氰酸酯是一种强有力的接触性和呼吸道过敏原。用ELISA法检测PHA刺激的小鼠脾组织中IL-2、IL-4、IL-5和干扰素-γ的表达。染毒后1周和2周，小鼠的总IgE和耳肿胀程度随染毒剂量的增加而显著增加。染毒1周后，1%和5%TDI组小鼠血清IL-2、IL-4和干扰素-γ水平较对照组明显升高。两周后仅IL-4水平下降。在致敏反应与细胞因子的关系上，与即刻型超敏反应相关的IL-4水平与总IgE生成呈正相关。干扰素-γ与接触性超敏反应有关，与耳肿胀相关。因此，细胞因子谱分析可用于评价引起即刻和延迟型超敏反应的致敏剂。为此，我们建立了一系列评价呼吸道致敏作用的方法，增加了职业性致敏剂清单和建立OELs的豚鼠实验模型。较少

The purpose of this study was to provide the information to establish preventive measurements for respiratory allergy from occupational sensitizes. We carried out this study recognizing the requirements of preventive measurements as below : the prediction of allergenicity, listing up of occupational sensitizers and confirmation of dose-response relationship in hypersensitivity reactions. We revised our drafted table, made previously by us, to exhibit occupational respiratory sensitizers. The main revised point was that the criteria of classification was on the basis of reliability of information. To assess the criteria, we investigated whether several respiratory sensitizers selected were given the adequate assessments. Subsequently, the property of the criteria was confirmed generally. The criteria of epidemiological evidences required further revises.To develop methods to evaluate respiratory sensitization of occupational chemicals using mouse, we assayd cytokine profiles in mice exp … More osed to sensitizers. Mice were sensitized by painting of toluene diisocyanate (TDI) , known as a potent contact and respiratory allergen. PHA stimulated IL-2, IL-4, IL-5 and IFN-gamma were detected in spleens by ELISA.After one and two week following the initiation of exposure to TDI,the significant increment of total IgE and ear swelling with depending on exposure dose was found. The levels of IL-2, IL-4 and IFN-gamma in 1 and 5% TDI exposure group increased after one week compared with control group. Only IL-4 level decreased after two weeks. For the relation between sensitization reactions and cytokines, IL-4 level, related to immediate type hypersensitivity, was correlated with total IgE production. IFN-gamma, related to contact hypersensitivity, was correlated with ear swelling. Therefore, the assay of cytokine profiles was suggested to be available for the evaluation of sensitizers causing immediate and delayd type hypersensitivity. Accordingly serial methods to evaluate respiratory sensitization were settled by addition of listing up of occupational sensitizers and guinea-pig experimental model for setting up of OELs which we have developed. Less