Local lymph node assay as a quantitative risk assessment tool to model biologic skin response of allergic contact dermatitis in the mouse.
Scott-AE; Yucesoy-B; Luster-MI; Kashon-M; Tinkle-SS
Toxicologist 2001 Mar; 60(1):170
The murine local lymph node assay (LLNA) is a method used to screen allergic contact sensitizing chemicals and as such, has been suggested for use as a risk assessment tool to predict the sensitizing and irritant potential of chemicals. Its reproducibility (precision and accuracy) has been validated through an international inter-laboratoty collaborative trial. Because the mathematically derived EC3 parameter predicts the chemical concentration at which skin sensitization occurs, and the LLNA appears to be dose responsive, we asked if the LLNA could be adapted for use as an occupational risk assessment tool. We explored in a mouse model, the relationship between sensitizing and challenge concentrations and the quantitative biological parameters of tritiated thymidine incorporation in auricular lymph node cells and of skin thickness after challenge. Our results indicate that: 1) LLNA data fit highly significant dose response models for the chemicals dinitrochlorobenzene (DNCB) and squaric acid dibutylester (SADBE) (R2=0.884 p<0.0001 and R2=0.855, p<0.0001 respectively). 2) We report a novel EC3 for SADBE equal to 0.1 % in acetone olive oil. 3) Using two different skin sensitization-challenge models, we confirm that DNCB chemical sensitization is dose responsive. In contrast, our data suggest that the quantitative increase in skin thickness following chemical challenge is dependent on a threshold concentration and that the interaction of sensitization and challenge concentration is highly significant (p<0.0001). 4) Finally, we show an empirical association of sensitization dose response in the LLNA with the post-challenge skin thickness. On the basis of these studies, we propose that the LLNA may be adapted in future studies for use in quantitative assessment of occupational exposure to sensitizing chemicals.
Lymph-nodes; Allergies; Irritants; Sensitization; Risk-analysis; Occupational-exposure; Skin-absorption; Skin-exposure
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California