The LLNA is used to test the potential of low molecular weight (LMW) compounds to induce sensitization via the skin. In the present study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose-only during 3 consecutive days for 45, 90, 180 or 360 min/day to various LMW allergens. Ear application (skin LLNA) was used as a positive control. Negative controls were exposed to the vehicle. Three days after the last exposure, proliferation was determined in the draining mandibular lymph nodes and the respiratory tract was examined microscopically. Upon inhalation, the allergens trimellitic anhydride (TMA), phthalic anhydride (PA), hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), dinitrochlorobenzene (DNCB), oxazolone (OXA) were positive and showed stimulation indices (SI) up to 11, whereas trimeric IPDI, formaldehyde and methylsalicyate were negative (viz. SI lower than 3). All compounds, except trimeric IPDI, induced histopathological lesions predominantly in the upper respiratory tract. Exposure by inhalation is a realistic approach to test respiratory allergens. However, based on the local toxicity, the dose that can be applied is (generally) much lower than can be achieved by skin application. It is concluded that strong LMW allergens, regardless their immunological nature, besides the skin can also sensitize the body via the respiratory tract. In addition, the contact allergens were as potent as the respiratory allergens, although the potency ranking differed from that in a skin LLNA.
Arts, J. H., de Jong, W. H., van Triel, J. J., Schijf, M. A., de Klerk, A., van Loveren, H., & Kuper, C. F. (2008). The respiratory local lymph node assay as a tool to study respiratory sensitizers. Toxicological Sciences, 106(2), 423-434. https://doi.org/10.1093/toxsci/kfn199