Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 3 No. 1 February 03, 2016 p.27-31
Quantitative analysis of the relationship between the LLNA:DAE method results and the LLNA EC3 values highlights the connection between the elicitation and induction phases during skin sensitization
  • Kunihiko Yamashita (Corporate Research Center, Daicel Corporation / Faculty of Engineering, Dept. of Materials Science and Engineering, Yokohama National University /
Kunihiko Yamashita 1) 3) , Shinsuke Shinoda 2) , Saori Hagiwara 2) , Hiroshi Itagaki 3)
1) Corporate Research Center, Daicel Corporation , 2) Yoshimi Laboratories, Drug Safety Testing Center Co., Ltd. , 3) Faculty of Engineering, Dept. of Materials Science and Engineering, Yokohama National University
Keywords: LLNA, LLNA:DAE, EC3

We previously reported the skin sensitizing potential of 41 different chemicals using a modified local lymph node assay with an elicitation phase (LLNA:DAE). Of these, the measured skin sensitizing potential for 39 was consistent with the reported results from a murine local lymph node assay (LLNA). Furthermore, the increase in the weight of the left ear lymph node per 1% test dose of each chemical (as measured using the LLNA:DAE method) seemed to reflect the class of skin sensitization potency as evaluated by LLNA. However, this relationship has never been quantitatively investigated. In the present study, we sought to determine the connection between the results of the LLNA:DAE method, in terms of lymph node weight, and the skin sensitization potency as indicated by the EC3 value. We evaluated the concentration of each chemical needed to increase the weight of the left ear lymph node by 2 mg, 1 mg, 0.5 mg, and 0.25 mg during the elicitation phase using the LLNA:DAE method. These concentrations were then assessed in terms of how they directly compared to the LLNA EC3 value as well as how they matched the range of the EC3 value (under 1%, 1-10% and over 10%). Finally, clear quantitative relationships between the EC values at 1 mg and the EC3 values were observed using various statistical regression models. These results indicate that results obtained using the LLNA:DAE method can potentially be used to speculate the EC3 range found using LLNA method for these 29 kinds of skin sensitizers.