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J Allergy Clin Immunol. 2019 Aug 21. pii: S0091-6749(19)31093-0. doi: 10.1016/j.jaci.2019.07.046. [Epub ahead of print]

Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens.

Author information

Netherlands Organisation for Applied Scientific Research (TNO), Zeist, The Netherlands.
Food Allergy Research and Resource Program, Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, United States.
Netherlands Organisation for Applied Scientific Research (TNO), Zeist, The Netherlands. Electronic address:
Murdoch Children's Research Institute and University of Melbourne School of Population and Global Health, Melbourne, Australia.
Allergy Unit, Department of Dermatology, University Hospital, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland; Clinic for Dermatology and Allergology, Kantonsspital St. Gallen, Switzerland.
René Crevel Consulting Ltd, Bedford, United Kingdom.
University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, GRIAC Research Institute, Groningen, the Netherlands.
Allergy Dept, Hospital Clinico San Carlos, Universidad Complutense Madrid, IdISSC, ARADyAL RD16/0006/0009, Madrid, Spain.
Children's Hospital Colorado; School of Medicine, University of Colorado, Boulder, Colorado, United States.
INFANT Centre and Paediatrics and Child Health, University College Cork, Ireland.
Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
Icahn School of Medicine at Mount Sinai, New York, New York, United States.
The Food Allergy Centre and Centre for Immunology and Inflammatory Disease, and Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States.
Section of Paediatrics, Imperial College London, London, United Kingdom; Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia.



Food allergies are a significant public health issue and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility to limit risks to zero, quantitative allergen risk assessment and management strategies are needed.


To develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders, but particularly food allergic individuals.


Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges (DBPCFCs). If DBPCFC data is not available, data from widely used "open" food challenges (OFCs) using pre-defined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research (TNO) and The Food Allergy Research and Resource Program (FARRP) at the University of Nebraska-Lincoln have been collecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens.


In this paper we provide in depth insights into the methodology applied by TNO and FARRP to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. Over 90 examples for determining the individual allergic thresholds are presented.


With the methodology presented in this paper, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption.


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