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The respiratory allergen glutaraldehyde in the local lymph node assay: Sensitization by skin exposure, but not by inhalation

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Author: Triel, J.J. van · Bree, B.W.J. van · Roberts, D.W. · Muijser, H. · Duistermaat, E. · Woutersen, R.A. · Kuper, C.F.
Source:Toxicology, 1-3, 279, 115-122
Identifier: 425980
doi: doi:10.1016/j.tox.2010.09.018
Keywords: Nutrition Biology · Toxicology and Applied Pharmacology · Chemical structure · Glutaraldehyde · Inhalation exposure · Local lymph node assay · Respiratory allergy · Sensitization · Healthy Living · Life · QS - Quality & Safety · EELS - Earth, Environmental and Life Sciences


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 18 ppm 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-γ) 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. © 2010 Elsevier Ireland Ltd.