Basketter D A
Unilever Environmental Safety Laboratory, Sharnbrook, Beds. MK44 1LQ, UK.
Toxicol In Vitro. 1994 Aug;8(4):855-9. doi: 10.1016/0887-2333(94)90086-8.
Acute toxicity testing, including testing for irritation and sensitization, traditionally has relied heavily on animal models. While this situation has not yet changed dramatically, new developments and approaches offer opportunities to minimize or ultimately to eliminate altogether the use of animals in specific areas of acute toxicity. The value of a structured approach to toxicological evaluation in skin and eye irritation and contact sensitization is discussed in this report. The general approach is one of undertaking a thorough evaluation of existing knowledge, closely paralleled by consideration of chemical structure-activity relationships, followed by appropriate in vitro testing, or, if there is no alternative, a limited animal study. Then only when absolutely necessary is a standard toxicology assay carried out, often to satisfy regulatory requirements. When ethically acceptable, the strategy may also include studies in humans. If these are done in a thorough manner, they may obviate the need for any animal work and should provide the most relevant toxicological assessment. By use of such a structured approach not only can some or all of the 3Rs be achieved, but data to support alternatives in regulatory toxicology can be generated.
急性毒性测试，包括刺激性和致敏性测试，传统上严重依赖动物模型。虽然这种情况尚未发生显著变化，但新的发展和方法为在急性毒性的特定领域尽量减少或最终完全消除动物的使用提供了机会。本报告讨论了一种结构化方法在皮肤和眼睛刺激性以及接触致敏性毒理学评估中的价值。一般方法是对现有知识进行全面评估，同时密切考虑化学结构 - 活性关系，随后进行适当的体外测试，或者在没有其他选择的情况下，进行有限的动物研究。然后只有在绝对必要时才进行标准毒理学测定，通常是为了满足监管要求。在符合伦理的情况下，该策略还可能包括人体研究。如果以全面的方式进行这些研究，它们可能无需进行任何动物实验，并应提供最相关的毒理学评估。通过使用这种结构化方法，不仅可以实现部分或全部的3R原则，还可以生成支持监管毒理学中替代方法的数据。
