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Interlaboratory evaluation of a cow's milk allergy mouse model to assess the allergenicity of hydrolysed cow's milk based infant formulas

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Author: Esch, B.C.A.M. van · Bilsen, J.H.M. van · Jeurink, P.V. · Garssen, J. · Penninks, A.H. · Smit, J.J. · Pieters, R.H.H. · Knippels, L.M.J.
Source:Toxicology Letters, 1, 220, 95-102
Identifier: 472354
doi: doi:10.1016/j.toxlet.2013.04.008
Keywords: Biology · Allergenicity · Cow's milk allergy · Hydrolysed infant formulas · Mouse model · Safety · Sensitization · Food and Nutrition · Healthy Living · Life Triskelion BV · QS - Quality & Safety RAPID - Risk Analysis for Products in Development · EELS - Earth, Environmental and Life Sciences TNO Bedrijven


This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant. Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge. In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals. Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers. In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups. The cow's milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow's milk protein. The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories. We propose this mouse model as a new strategy for the screening of new hypoallergenic cow's milk formulas. © 2013 Elsevier Ireland Ltd.