Department of Product Safety, BASF Schweiz AG, Basel, Switzerland.
BASF SE, Dept. Experimental Toxicology and Ecology, Dept. Material Physics, 67056, Ludwigshafen, Germany.
Regul Toxicol Pharmacol. 2021 Aug;124:104988. doi: 10.1016/j.yrtph.2021.104988. Epub 2021 Jul 2.
Here, we present a non-animal testing battery to identify PSLT (poorly soluble, low toxicity) substances based on their solubility in phagolysosomal lung fluid simulant, surface reactivity and effects on alveolar macrophages in vitro. This is exemplified by eleven organic pigments belonging to five chemical classes that cover a significant share of the European market. Three of the pigments were tested as both, nanoform and non-nanoform. The results obtained in this integrated non-animal testing battery qualified two pigments as non PSLT, one pigment as poorly soluble and eight pigments as poorly soluble and low toxicity in vitro. The low toxic potency of the eight PSLT and the one poorly soluble pigment was corroborated by short-term inhalation studies with rats. These pigments did not elicit apparent toxic effects at 10 mg/m (systemic and in the respiratory tract). One of the pigments, Diarylide Pigment Yellow 83 transparent, however, caused minimal infiltration of neutrophils; hence its low toxicity is ambiguous and needs further verification or falsification. The present test battery provides an opportunity to identify PSLT-properties of test substances to prioritise particles for further development. Thus, it can help to reduce animal testing and steer product development towards safe applications.
在这里，我们提出了一种非动物测试组合，以根据其在吞噬溶酶体肺液模拟物中的溶解度、表面反应性和对体外肺泡巨噬细胞的影响来识别 PSLT（难溶性、低毒性）物质。这由属于五个化学类别的十一种有机颜料组成，涵盖了欧洲市场的很大一部分。其中三种颜料被测试为纳米形式和非纳米形式。该综合非动物测试组合的结果将两种颜料鉴定为非 PSLT，一种颜料鉴定为难溶性，八种颜料鉴定为体外难溶性和低毒性。八种 PSLT 和一种难溶性颜料的低毒性效力通过大鼠短期吸入研究得到证实。这些颜料在 10mg/m（全身和呼吸道）时没有引起明显的毒性作用。然而，有一种颜料，二芳基酰亚胺颜料黄 83 透明，引起了少量中性粒细胞的浸润；因此，其低毒性是不确定的，需要进一步验证或否定。本测试组合为识别测试物质的 PSLT 特性提供了机会，以便为进一步开发将颗粒物质分类，从而有助于减少动物测试并引导产品开发朝着安全应用的方向发展。
