title: Threshold dose for peanut: risk characterization based upon published results from challenges of peanut-allergic individuals.
abstract: Population thresholds for peanut are unknown. However, lowest- and no-observed adverse effect levels (LOAELs and NOAELs) are published for an unknown number of peanut-allergic individuals. Publications were screened for LOAELs and NOAELs from blinded, low-dose oral challenges. Data were obtained from 185 peanut-allergic individuals (12 publications). Data were analyzed by interval-censoring survival analysis and three probability distribution models fitted to it (Log-Normal, Log-Logistic, and Weibull) to estimate the ED(10). All three models described the data well and provided ED(10)'s in close agreement: 17.6, 17.0, and 14.6 mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The 95% lower confidence intervals for the ED(10)'s were 9.2, 8.1, and 6.0mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The modeling of individual NOAELs and LOAELs identified from three different types of published studies - diagnostic series, threshold studies, and immunotherapy trials - yielded significantly different whole peanut ED(10)'s of 11.9 mg for threshold studies, 18.0mg for diagnostic series and 65.5mg for immunotherapy trials; patient selection and other biases may have influenced the estimates. These data and risk assessment models provide the type of information that is necessary to establish regulatory thresholds for peanut.
authors.affiliation: Food Allergy Research & Resource Program, Department of Food Science & Technology, University of Nebraska-Lincoln, 255 Food Industry Complex, Lincoln, NE 68583-0919, USA. staylor2@unl.edu
authors.forename: Steve L
authors.initials: SL
authors.lastname: Taylor
authors.forename: Rene W R
authors.initials: RW
authors.lastname: Crevel
authors.forename: David
authors.initials: D
authors.lastname: Sheffield
authors.forename: Jamie
authors.initials: J
authors.lastname: Kabourek
authors.forename: Joseph
authors.initials: J
authors.lastname: Baumert
mesh_terms: D010367:Arachis / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy; D019055:No-Observed-Adverse-Effect Level; D021183:Peanut Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D018570:Risk Assessment
chemical_list: D007073:Immunoglobulin E