Ritz H L, Evans B L, Bruce R D, Fletcher E R, Fisher G L, Sarlo K
Miami Valley Laboratories, Procter & Gamble Company, Cincinnati, Ohio 45239-8707.
Fundam Appl Toxicol. 1993 Jul;21(1):31-7. doi: 10.1006/faat.1993.1068.
Guinea pigs were exposed once a week for 10 weeks by intratracheal exposure to solutions of 3, 1, 0.3, or 0.1 micrograms of the enzyme protein, Subtilisn Carlsberg (Alcalase), in 250 micrograms of a detergent base. Other groups of guinea pigs were exposed by inhalation (6 hr per day, 4 days a week) to 1 mg/m3 of the aerosolized detergent base containing either 3.5, 1.1, 0.3, or 0.1% Alcalase protein. Evaluations of gross respiratory responses immediately following each intratracheal exposure revealed a significant dose response in respiratory symptoms measurable after the fourth exposure and continuing throughout the study. In the inhalation experiment, during Weeks 4 through 10, animals were observed to have respiratory symptoms which were dependent upon both the dose of enzyme and on total exposure to the enzyme/detergent atmosphere. For both intratracheal and inhalation routes of exposure, the initial appearance of respiratory symptoms coincided with the first appearance of measurable serum allergic antibodies specific to Alcalase. The allergic antibody levels increased with time and dosage by both routes of exposure, and the antibody titers generated by the intratracheal administration of antigen were comparable to those generated by the inhalation route of exposure. These results indicate that the intratracheal technique is appropriate for the evaluation of the respiratory allergic response to a protein.
豚鼠每周经气管内暴露一次,持续10周,暴露于含有3、1、0.3或0.1微克酶蛋白(枯草杆菌蛋白酶卡尔伯格(碱性蛋白酶))的溶液中,该溶液溶解于250微克去污剂基质中。其他豚鼠组通过吸入(每天6小时,每周4天)暴露于含有3.5%、1.1%、0.3%或0.1%碱性蛋白酶蛋白的雾化去污剂基质中,浓度为1毫克/立方米。每次气管内暴露后立即对总体呼吸道反应进行评估,结果显示在第四次暴露后可测量到呼吸道症状出现显著的剂量反应,且在整个研究过程中持续存在。在吸入实验中,在第4周至第10周期间,观察到动物出现呼吸道症状,这些症状既取决于酶的剂量,也取决于酶/去污剂环境的总暴露量。对于气管内和吸入两种暴露途径,呼吸道症状的最初出现与针对碱性蛋白酶的可测量血清过敏抗体的首次出现同时发生。两种暴露途径的过敏抗体水平均随时间和剂量增加,并且气管内给予抗原产生的抗体滴度与吸入途径产生的抗体滴度相当。这些结果表明,气管内技术适用于评估对蛋白质的呼吸道过敏反应。