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新型皮肤致敏预测方法中化学呼吸性变应原的行为

Behaviour of chemical respiratory allergens in novel predictive methods for skin sensitisation.

作者信息

Basketter David, Poole Alan, Kimber Ian

机构信息

DABMEB Consultancy Ltd, Sharnbrook, Bedfordshire, UK.

European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 2 Av E Van Nieuwenhuyse, 1160 Brussels, Belgium.

出版信息

Regul Toxicol Pharmacol. 2017 Jun;86:101-106. doi: 10.1016/j.yrtph.2017.03.002. Epub 2017 Mar 6.

Abstract

Asthma resulting from sensitisation of the respiratory tract to chemicals is an important occupational health issue, presenting many toxicological challenges. Most importantly there are no recognised predictive methods for respiratory allergens. Nevertheless, it has been found that all known chemical respiratory allergens elicit positive responses in assays for skin sensitising chemicals. Thus, chemicals failing to induce a positive response in skin sensitisation assays such as the local lymph node assay (LLNA) lack not only skin sensitising activity, but also the potential to cause respiratory sensitisation. However, it is unclear whether it will be possible to regard chemicals that are negative in in vitro skin sensitisation tests also as lacking respiratory sensitising activity. To address this, the behaviour of chemical respiratory allergens in the LLNA and in recently validated non-animal tests for skin sensitisation have been examined. Most chemical respiratory allergens are positive in one or more newly validated non-animal test methods, although the situation varies between individual assays. The use of an integrated testing strategy could provide a basis for recognition of most respiratory sensitising chemicals. However, a more complete picture of the performance characteristics of such tests is required before specific recommendations can be made.

摘要

呼吸道对化学物质致敏引发的哮喘是一个重要的职业健康问题,带来了诸多毒理学挑战。最重要的是,目前尚无公认的呼吸道过敏原预测方法。然而,已经发现所有已知的化学呼吸道过敏原在皮肤致敏化学物质检测中均产生阳性反应。因此,在诸如局部淋巴结检测(LLNA)等皮肤致敏检测中未能诱导出阳性反应的化学物质,不仅缺乏皮肤致敏活性,也缺乏引起呼吸道致敏的可能性。然而,目前尚不清楚体外皮肤致敏试验呈阴性的化学物质是否也可被视为缺乏呼吸道致敏活性。为解决这一问题,已对化学呼吸道过敏原在LLNA以及最近经过验证的非动物皮肤致敏试验中的表现进行了研究。大多数化学呼吸道过敏原在一种或多种新验证的非动物试验方法中呈阳性,尽管不同检测之间情况有所不同。采用综合检测策略可为识别大多数呼吸道致敏化学物质提供依据。然而,在能够提出具体建议之前,需要更全面地了解此类检测的性能特征。

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