Threshold dose for peanut: Risk characterization based upon diagnostic oral challenge of a series of 286 peanut-allergic individuals

Abstract

Clinical records of 286 consecutive patients reacting positively with objective symptoms to double-blind, placebo-controlled oral peanut challenges at University Hospital, Nancy, France were examined for individual No Observed Adverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels (LOAELs). After fitting to a log-normal probability distribution model, the ED(10) and ED(05) were 14.4 and 7.3mg (expressed as whole peanut), respectively, with 95% lower confidence intervals of 10.7 and 5.2mg, respectively. Compared to results from a previous study where the ED(10) was based upon individual peanut thresholds gleaned from 12 publications, a statistically significant difference was observed between the ED(50)'s, but not the ED(10)'s of the two probability distribution curves. The Nancy patient group contains more sensitive subjects than the group from the published literature thus contributing to the observed differences. Minimum eliciting dose-distributions for patients with histories of more severe reactions (grade 4 or 5; 40 subjects) did not differ significantly from those of patients with histories of less severe reactions (grades 1-3; 123 subjects). These data and this modeling approach could be used to establish population thresholds for peanut-allergic consumers and thereby provide a sound basis for allergen control measures in the food industry.

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

“…diagnostic series, threshold-finding studies and immunotherapy trials) have reported on MED following challenge studies in adults and children combined (Oppenheimer et al, 1992;Leung et al, 2003;Lewis et al, 2005;Anagnostou et al, 2009), mostly in adults Hourihane et al, 1997;Nelson et al, 1997;Patriarca et al, 2006) (Wensing Marjolein et al, 2002), and mostly in children (Flinterman et al, 2006a;Clark et al, 2008;Clark et al, 2009;Blumchen et al, 2010;Nicolaou et al, 2010;Taylor et al, 2010;Wainstein et al, 2010;Blom et al, 2013). Studies are variable in size, challenge protocol used and type of food tested .…”

“…EDp (expressed as milligrams of peanut and not as milligrams of protein, not included in Appendix A) were calculated by the same authors for peanut using two different datasets (Taylor et al, 2009b;Taylor et al, 2010). In the first study, data were obtained from 185 subjects participating in DBPCFCs for diagnostic purposes, because they were enrolled in immunotherapy trials, or for threshold-finding purposes.…”

“…Using the lognormal probability distribution model, significantly higher ED 10 were estimated from immunotherapy trials (65.5 mg; 95 % CI: 18.7-229 mg) than from diagnostic series (18.0 mg; 95 % CI: 5.8-55.8 mg) or threshold studies (11.9 mg; 95 % CI: 4.8-29.8 mg). In the second study (Taylor et al, 2010), data from diagnostic DBPCFCs of a series of 286 peanut-allergic individuals collected over 14 years in the same clinical setting were used. ED 05 (7.3 mg, 95 % CI: 5.2-10.4 mg) and ED 10 (14.4 mg, 95 % CI: 10.7-19.6 mg) were based on cumulative threshold doses using threshold distributions for objective reactions.…”

Allergenicity attributes of different peanut market types

“…Studies to quantify the risk that undeclared peanut residue poses to peanut allergic consumers who may eat such products rely on population threshold distributions modeled from peanut allergic individuals who have undergone a low-dose peanut challenge using various market types of peanuts (Taylor et al, 2010. It is not known if different peanut market types have different potencies thereby affecting both individual and population-based thresholds for peanut.…”

“May Contain” Allergen Statements: Facilitating or Frustrating Consumers?

“…The minimal eliciting dose (ED) refers to the lowest dose that can trigger an objective reaction in a controlled clinical challenge (Luccioli and Kwegyir-Afful 2014;Taylor et al 2010). The understanding of ED for individuals will improve consumers' quality of life and assist them in making more informed choices whilst purchasing food products (Luccioli and Kwegyir-Afful 2014).…”