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The global population is aging rapidly, posing new challenges for the safety evaluation of chemicals. Most toxicity studies use suitably aged animals that resemble healthy adults if they have similar responses. However, this assumption may not be valid because aging affects various physiological functions, such as immunity. The objective of this study was to compare the skin sensitization potential of chemicals in healthy adult mice, aged mice, and an aging mouse model using local lymph node assays (LLNA). Initially, eight-week-old female CBA/Ca, C3H/He (historical control for SAMP1 mice), senescence-accelerated mouse prone 1 (SAMP1), and C57BL6/N mice were compared to verify any differences among these strains. Next, 20-wk-old C3H/He and SAMP1 mice were compared with 80-wk-old C57BL6/N mice. Several concentrations (2.76, 8.3, and 25%) of α-hexyl cinnamaldehyde (HCA) were used as a positive substance for LLNA to determine the skin sensitization potential in each strain. The proliferation of T and B cells and related cytokine production were also measured. A dose-dependent correlation was observed, and a threshold of 1.8 for positive criteria for skin sensitization in LLNA, was surpassed in the CBA/Ca, C3H/He, and C57BL6/N strains, but not in the SAMP1 strain. In 20-wk-old mice, a positive response was observed only in C3H/He mice, whereas no positive response was observed in aged C57BL6 mice and SAMP1 mice. Our findings imply that senescence affects the skin sensitization potential of chemicals as measured using LLNA.

Influence of senescence on the sensitization potential of chemicals detected by local lymph node assays in aged mice