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一项双中心研究,用于评估和验证一种动物模型,以评估小分子化学物质引起呼吸道过敏的可能性。

A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy.

作者信息

Blaikie L, Morrow T, Wilson A P, Hext P, Hartop P J, Rattray N J, Woodcock D, Botham P A

机构信息

Zeneca Central Toxicological Laboratory, Macclesfield, Cheshire, UK.

出版信息

Toxicology. 1995 Jan 19;96(1):37-50. doi: 10.1016/0300-483x(94)03007-o.

Abstract

This study evaluated a single intradermal injection model in the guinea pig with subsequent inhalation challenge and serological analysis as a method to predict the potential of chemicals to induce respiratory allergy. Four known respiratory allergens (trimellitic anhydride, diphenyl methane diisocyanate, phthalic anhydride and toluene diisocyanate (TDI)) were screened by two industrial research laboratories using this protocol. Dinitrochlorobenzene, a potent contact allergen, was included as a negative control material. In both laboratories, the respiratory allergens, but not the contact allergen, induced high titre antigen-specific antibodies in treated animals. The inhalation challenge results were similar in both laboratories but were less conclusive in that exposure to free TDI failed to induce pulmonary responses, probably because it fails to penetrate to the deep lung in sufficient concentration. Although the assay shows promise as a means of identifying chemical respiratory sensitisers, its use as a routine screen for the prediction of the ability of materials to induce respiratory allergy in man is probably questionable.

摘要

本研究评估了豚鼠皮内单次注射模型,随后进行吸入激发试验和血清学分析,以此作为预测化学物质诱发呼吸道过敏可能性的一种方法。两个工业研究实验室采用该方案对四种已知的呼吸道过敏原(偏苯三酸酐、二苯基甲烷二异氰酸酯、邻苯二甲酸酐和甲苯二异氰酸酯(TDI))进行了筛查。强力接触性过敏原二硝基氯苯作为阴性对照物质。在两个实验室中,呼吸道过敏原而非接触性过敏原在受试动物中诱导产生了高滴度的抗原特异性抗体。两个实验室的吸入激发试验结果相似,但不太具有决定性,因为接触游离TDI未能诱发肺部反应,这可能是由于其未能以足够的浓度渗透到肺深部。尽管该检测方法有望作为识别化学物质呼吸道致敏剂的一种手段,但其作为预测材料诱发人类呼吸道过敏能力的常规筛查方法可能存在疑问。

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