DABMEB Consultancy Ltd, Kingswood, Gloucestershire, GL12 8RN, UK.
Syngenta, Jealott's Hill International Research Centre, Bracknell, UK.
Regul Toxicol Pharmacol. 2024 Mar;148:105584. doi: 10.1016/j.yrtph.2024.105584. Epub 2024 Feb 28.
The increasing drive to understand the likelihood of skin sensitisation from plant protection products (PPPs) in workers and the general public has resulted in recent initiatives to establish a quantitative risk assessment (QRA) methodology applicable to these products and their exposure scenarios. The effective evaluation of skin sensitising substances requires not only the identification of that toxicological hazard, but also determination of relative sensitising potency. Typically, this has been achieved by interpretation of local lymph node assay (LLNA) dose response data, delivering what is known as the EC3 value. This permitted regulatory division of skin sensitisers into defined potency sub-categories, but more importantly enabled derivation of a no expected sensitisation induction level (NESIL) as the point of departure for QRA. However, for many existing substances there is no LLNA data, only older guinea pig results exist. To avoid additional (in vivo) testing, an approach has been outlined to employ guinea pig data and existing regulatory guidelines on the determination of potency sub-categorisation to provide a guinea pig based NESIL. The approach adopts a conservative extrapolation from LLNA NESIL benchmarks to deliver points of departure as the basis for the type of QRA process already in successful use by other industries.
为了深入了解植物保护产品（PPPs）在工人和普通公众中引发皮肤敏感的可能性，最近已经采取了一些措施来建立适用于这些产品及其暴露情况的定量风险评估（QRA）方法。有效评估皮肤致敏物质不仅需要识别这种毒理学危害，还需要确定相对致敏能力。通常，这是通过解释局部淋巴结试验（LLNA）剂量反应数据来实现的，从而提供所谓的 EC3 值。这允许将皮肤敏化剂划分为定义明确的效力亚类，但更重要的是，可以得出无预期致敏诱导水平（NESIL）作为 QRA 的起点。然而，对于许多现有物质，没有 LLNA 数据，只有旧的豚鼠结果。为了避免额外的（体内）测试，已经概述了一种方法，即利用豚鼠数据和现有的关于效力亚类确定的监管指南，提供基于豚鼠的 NESIL。该方法采用从 LLNA NESIL 基准值的保守外推法，提供起点作为其他行业已经成功使用的 QRA 类型的基础。
