Illing H P A, Malmfors T, Rodenburg L
PICS Ltd, Sherwood, Brimstage Road, Heswall, Wirral CH60 1XE, UK.
Regul Toxicol Pharmacol. 2009 Aug;54(3):234-41. doi: 10.1016/j.yrtph.2009.04.006. Epub 2009 May 4.
A series of chemically modified rosin resins have been tested for their potential to cause skin sensitization using the mouse LLNA. Where direct comparative evidence is available, the results of the mouse LLNA are consistent with previously obtained data using the GPMT. Reactions with sufficient fumaric acid or maleic anhydride lead to maleopimaric acid anhydride (an acid anhydride), and give a clear response of a strong sensitizer that definitely requires classification. This sensitization is probably immunologically distinct from that claimed for oxidized rosin. Esterification will deactivate acid anhydrides formed from reacting rosin with maleic anhydride or fumaric acid. However, with maleic anhydride, there remains material capable of inducing a marginal (but classifiable under current criteria) immune response after the rosin had been maleinated and esterified. If proposed potency criteria are used these substances would not be considered 'strong sensitizers'. This response may be a function of a greater solubility in vehicle of the esterified maleinated (or fumarated) rosin over directly esterified material. Solubility limitations in the case of gum rosin directly esterified with pentaerythritol mean that it is not classifiable. Decarboxylated rosin and the glycerol ester of tall oil rosin are adequately soluble, and are not classifiable according to EU criteria. Polymers formed from rosin are also not classifiable as sensitizers. These studies confirm the value of grouping substances for 'read across' and the groupings chosen under the US EPA High Production Volume (HPV) Challenge Program. They also confirm the difficulties involved in dealing scientifically when examining the problem of skin sensitization associated with rosin related substances whilst still meeting current EU regulatory criteria.
已使用小鼠局部淋巴结测定法（LLNA）对一系列化学改性松香树脂引发皮肤致敏的可能性进行了测试。在有直接对比证据的情况下，小鼠LLNA的结果与先前使用豚鼠最大化试验（GPMT）获得的数据一致。与足够的富马酸或马来酸酐反应会生成马来海松酸酐（一种酸酐），并产生明确的强致敏剂反应，这肯定需要进行分类。这种致敏作用可能在免疫学上与氧化松香所声称的致敏作用不同。酯化作用会使松香与马来酸酐或富马酸反应形成的酸酐失活。然而，对于马来酸酐，在松香进行马来酸化和酯化后，仍有物质能够引发轻微的（但根据当前标准可分类）免疫反应。如果使用提议的效力标准，这些物质将不被视为“强致敏剂”。这种反应可能是由于酯化的马来酸化（或富马酸化）松香在载体中的溶解度高于直接酯化的物质。用季戊四醇直接酯化的脂松香存在溶解度限制，这意味着它无法分类。脱羧松香和妥尔油松香的甘油酯具有足够的溶解度，根据欧盟标准无法分类。由松香形成的聚合物也不能归类为致敏剂。这些研究证实了对物质进行“类推”分组的价值以及在美国环保署高产量（HPV）挑战计划下选择的分组。它们还证实了在研究与松香相关物质有关的皮肤致敏问题时，既要科学地处理问题，又要符合当前欧盟监管标准所涉及的困难。
