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.
- SourceAvailable from: Carsten Bindslev-Jensen[show abstract] [hide abstract]
ABSTRACT: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed.Journal of Allergy and Clinical Immunology 02/2002; 109(1):24-30. · 12.05 Impact Factor
Article: Fatal food-induced anaphylaxis.Allergy 02/1998; 53(46 Suppl):125-30. · 5.88 Impact Factor
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ABSTRACT: The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 microg to 50 mg, administered in the form of a commercially available peanut flour. One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 microg in two cases. Five subjects did not react to any dose up to 50 mg. Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 microg of peanut protein provokes symptoms in some subjects with peanut allergy.Journal of Allergy and Clinical Immunology 12/1997; 100(5):596-600. · 12.05 Impact Factor