PMID- 20933045 OWN - NLM STAT- MEDLINE DCOM- 20110114 LR - 20131121 IS - 1879-3185 (Electronic) IS - 0300-483X (Linking) VI - 279 IP - 1-3 DP - 2011 Jan 11 TI - The respiratory allergen glutaraldehyde in the local lymph node assay: sensitization by skin exposure, but not by inhalation. PG - 115-22 LID - 10.1016/j.tox.2010.09.018 [doi] AB - Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-gamma) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin--besides inhalation-- exposure to aldehydes like GA. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - van Triel, Jos J AU - van Triel JJ AD - TNO Quality of Life, Department of Toxicology and Applied Pharmacology, Zeist, The Netherlands. jos.vantriel@tno.nl FAU - van Bree, Bianca W J AU - van Bree BW FAU - Roberts, David W AU - Roberts DW FAU - Muijser, Hans AU - Muijser H FAU - Duistermaat, Evert AU - Duistermaat E FAU - Woutersen, Ruud A AU - Woutersen RA FAU - Kuper, C Frieke AU - Kuper CF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101007 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Aerosols) RN - 0 (Allergens) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - T3C89M417N (Glutaral) SB - IM MH - Administration, Cutaneous MH - Aerosols MH - Allergens/administration & dosage/*immunology MH - Animals MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Glutaral/administration & dosage/*immunology MH - Inhalation Exposure MH - Interferon-gamma/metabolism MH - Interleukin-4/metabolism MH - Local Lymph Node Assay MH - Lymph Nodes/*drug effects/immunology MH - Lymphocytes/drug effects MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Respiratory Hypersensitivity/*chemically induced/immunology MH - Th2 Cells/immunology EDAT- 2010/10/12 06:00 MHDA- 2011/01/15 06:00 CRDT- 2010/10/12 06:00 PHST- 2010/08/23 00:00 [received] PHST- 2010/09/27 00:00 [revised] PHST- 2010/09/28 00:00 [accepted] PHST- 2010/10/12 06:00 [entrez] PHST- 2010/10/12 06:00 [pubmed] PHST- 2011/01/15 06:00 [medline] AID - S0300-483X(10)00507-X [pii] AID - 10.1016/j.tox.2010.09.018 [doi] PST - ppublish SO - Toxicology. 2011 Jan 11;279(1-3):115-22. doi: 10.1016/j.tox.2010.09.018. Epub 2010 Oct 7.