PMID- 18815142 OWN - NLM STAT- MEDLINE DCOM- 20090122 LR - 20100917 IS - 1096-0929 (Electronic) IS - 1096-0929 (Linking) VI - 106 IP - 2 DP - 2008 Dec TI - The respiratory local lymph node assay as a tool to study respiratory sensitizers. PG - 423-34 LID - 10.1093/toxsci/kfn199 [doi] AB - The local lymph node assay (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 three 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, phthalic anhydride, hexamethylene diisocyanate, toluene diisocyanate, isophorone diisocyanate (IPDI), dinitrochlorobenzene, and oxazolone were positive and showed stimulation indices (SIs) up to 11, whereas trimeric IPDI, formaldehyde, and methyl salicylate were negative (viz. SI < 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. FAU - Arts, Josje H E AU - Arts JH AD - TNO Quality of Life, Zeist, the Netherlands. FAU - de Jong, Wim H AU - de Jong WH FAU - van Triel, Jos J AU - van Triel JJ FAU - Schijf, Marcel A AU - Schijf MA FAU - de Klerk, Arja AU - de Klerk A FAU - van Loveren, Henk AU - van Loveren H FAU - Kuper, C Frieke AU - Kuper CF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080923 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 SB - IM MH - Animals MH - Body Weight MH - Chromatography, High Pressure Liquid MH - Dose-Response Relationship, Drug MH - *Local Lymph Node Assay MH - Male MH - Mass Spectrometry MH - Mice MH - Mice, Inbred BALB C MH - Organ Size MH - Particle Size MH - Respiratory System/*drug effects/pathology EDAT- 2008/09/26 09:00 MHDA- 2009/01/23 09:00 CRDT- 2008/09/26 09:00 PHST- 2008/09/26 09:00 [pubmed] PHST- 2009/01/23 09:00 [medline] PHST- 2008/09/26 09:00 [entrez] AID - kfn199 [pii] AID - 10.1093/toxsci/kfn199 [doi] PST - ppublish SO - Toxicol Sci. 2008 Dec;106(2):423-34. doi: 10.1093/toxsci/kfn199. Epub 2008 Sep 23.