The ongoing scandal over the Kafkaesque handling of impurity cases with peanut residues in soy lecithin arriving from India provides an opportunity to take stock of allergen risk analysis in food products. An issue unfortunately unknown, as it turns out, to the ‘pass the buck’ clan of Eurocrats and bureaucrats. (1)
The most relevant scientific literature on the subject has already been reported in the previous article to which reference is made. (2) We now turn to the risk analysis approach developed by Allergen Bureau with the Vital® 3.0 system. Validated among others, as will be seen, by FAO, WHO and ILSI.
Vital® 3.0, the reference system for allergen risk analysis in food products
Vital® 3.0(Voluntary Incidental Trace Allergen Labelling) is a system for analyzing allergen risk in food products that is structured as follows:
(i) Identification of Reference Dose, based on Eliciting Dose ED01 and/or ED05. Which are derived from modeling data collected and updated through clinical trials(Oral Food Challenges, OFCs). In order to predict the proportion of the allergic population that might react to increasing doses of individual allergens, (3)
(ii) analysis and/or mathematical simulation of the levels of allergens contained in individual food matrices, based on the levels of incidental contamination of their ingredients. Using mg of total allergen protein in the food intended for consumption as a parameter,
(iii) comparison of Reference Dose with mg of allergenic proteins in the products under investigation, calculation of Margin of Exposure (MoE) of allergic consumers, definition of actions to be taken for risk management(Action Level).
FAO, WHO and ILSI confirm Vital® 3.0 approach.
The scientific consultations organized by FAO and WHO (2021. See footnote 4) and the Guidelines for Practical Allergen Risk Management published in June 2022 by ILSI(International Life Sciences Institute. See footnote 5) converge in confirming the validity of the approach taken by Allergen Bureau in the Vital® 3.0 system.
The Vital® 3.0 system was used in both papers as the first example of a quantitative risk assessment system for major allergens, among several systems considered. In fact, FAO and WHO have declared the best applicability of a system based on the principles of ‘Benchmark Dose‘ (without even needing to apply the MoE) and ‘Probabilistic Hazard Assessment approach‘.
Vital® 3.0, guaranteed protection for allergic consumers
The EDp(population minimal eliciting dose) values identified by Vital® 3.0 (2019) have been found by FAO, WHO and ILSI to be entirely appropriate to prevent underestimation of the likelihood of allergic reactions. Noting that any reactions observed were never severe, only mild or moderate.
FAO and WHO, in particular, have found the ED values of Vital® 3.0 to be amply demonstrated for their ability to protect against the risk of allergic reactions to peanuts. As a result of specific confirmations from expert committees, which include researchers from the Federal Agency for the Safety of the Food Chain (FASFC, Belgium).
Scientific review, zero risk
Scientific reviews conducted by FAO, WHO, and ILSI-after reviewing data on evidence of anaphylactic reactions and data on allergic reactions (to ED01, ED05, ED10)-came to the following conclusions:
(i) All symptoms up to ED05 are mild or moderate,
(ii) Up to 5 percent of the reactions in ED01 and ED05 can be classified as anaphylaxis (according to the World Allergy Organization definition), but none of those found were severe.
Indeed, the FAO/WHO committee noted the extreme rarity of fatal anaphylaxis (1 in 100,000 people/year, in the allergic population). Emphasizing that none of these fatal reactions were associated with exposure to doses at or below the ‘Reference Dose‘ identified by Vital® 3.0.
Food safety goal
The goal of food safety with respect to allergens is defined by FAO, WHO as ”to minimize, to a point where further refinement does not meaningfully reduce health impact, the probability of any clinically relevant objective allergic response, as defined by dose distribution modelling of minimum eliciting doses (MEDs) and supported by data regarding severity of symptoms in the likely range of envisioned Reference Doses (RfD)‘.
This goal can be achieved, FAO, WHO and ILSI, just by following the example of Vital® 3.0:
– starting with an ED05 for the definition of the ‘Reference Dose‘ (indicated as 2 mg of total protein), which corresponds to the rounding without decimals of that identified by Vital® 3.0 (2.0 mg),
– express the analytical results of the evaluation in terms of mg total allergenic food protein/kg food product to ensure a standard in the interpretation of results andAction Level.
Cross-contamination, risk factors
An increased risk has been confirmed in foods where the ingredient with allergen residues is present in a very high proportion-e.g., mustard in pasta, vicenda buried by the Ministry of Health in 2021 (6)-compared to those where the inclusion is instead minimal (e.g., food additives such as soy lecithin, emulsifying additive E 322). After all, arithmetic is an exact science: 10 ppm (part per million) of allergenic protein in an additive used in 0.1 percent share corresponds to 10 ppb (parts per million) in the final food. Zero risk.
Another aspect of possible importance is the distribution of the allergen in the product, distinguished into ‘particulate‘ and ‘non-particulate‘. The former consists of the inclusion in coarse form (e.g., a peanut seed), which is visible to the naked eye, while the latter is neither visible nor separable. The second form (‘non-particulate‘) is considered by VITAL® 3.0 to be ‘readily dispersible‘ and has fewer analytical identification complexities, compared to ‘particulate‘.
Methods of analysis
Both publications, FAO/WHO and ILSI, recommend that the scientific community develop more precise analytical criteria in several aspects:
– Ensuring the performance of analytical methods,
– Increase allergen reference materials,
– Increase understanding of the performance of assays on various food matrices,
– Increase transparency on reagents of specific methods (e.g., ELISA),
– Improve sampling and sample handling from collection to laboratory.
ELISA, analytical uncertainties
Strong potential critical issues have been found by ILSI in the ELISA(Enzyme-Linked Immunosorbent Assay) method, an enzymeimmunoassay technique designed to identify and measure the presence of allergenic proteins). Cross-reaction between similar proteins-just like those in peanuts and soybeans-can in fact lead to false positives.
The use of specific marker proteins in ELISA, on the other hand, can create complexities that today do not seem to guarantee the absolute efficacy of the system in complex food matrices, especially because of the issue of false positives mentioned above.
Cross-reactivity is one of the most serious problems that ILSI suggests should be investigated on a case-by-case basis through in-house validation of the method (subject to accreditation, however). Without neglecting the correct calibration of ELISA, which in turn is important to avoid obtaining nonconforming results.
PCR, more confidence in molecular biology
Polymerase chain reaction (PCR) methods-historically used for the analysis of GMO residues in soybeans-amplify sequences of DNA segments. They are considered specific, sensitive, qualitative and quantitative (in cases of qPCR and Real Time PCR).
The advantage of PCR methods over ELISA is the ability to identify DNA, which-in cases of matrices subjected to technological processes (such as processed foods, e.g., soy lecithin)-tends to resist better than proteins alone (instead identified by ELISA).
Attention, in the PCR method, should be paid to amplification levels (which can lead to false positives when exaggerated. Ex. >50, in soy lecithin) and to the DNA sequence used for amplification, which must be highly specific. (7)
Interim conclusions
Allergen risk analysis on food products is indispensable and required at both stages of self-control – in order to ensure proper information of allergic consumers, including with regard toPrecautionary Allergens Labelling (PAL). See notes 8,9)-and management of possible non-conformities related to impurities and/or cross-contamination.
The culture of food safety cannot be separated from the knowledge of how to analyze, prevent and mitigate risks. The Vital® 3.0 system is now the international standard of reference for the analysis and management of risks related to the possible presence of allergens in food products and should be used by both operators and authorities.
Dario Dongo
Notes
(1) Dario Dongo. greatitalianfoodtrade.co.uk/ideas/false-alerts-scaricabarile-abuse-of-power-and-social-disasters/. GIFT(Great Italian Food Trade). 2.7.22,
(2) Dario Dongo. RASFF, peanuts in soy lecithin from India. Risk analysis. GIFT (Great Italian Food Trade). 3.6.22
(3) The so-called Eliciting Dose (ED, or reaction dose) is the dose of allergen that causes the onset of symptoms in allergic individuals. Oral Food Challenges (OFCs), on the other hand, are food allergy diagnostic tests conducted by controlled administrations of increasing doses of the suspected allergens
(4) FAO/WHO (2021). Summary report of the Ad hoc Joint FAO/WHO Expert Consultation on Risk Assessment of Food Allergens. Part 2: Review and establish threshold levels in foods of the priority allergens. https://bit.ly/3OZjnGj
(5) ILSI (2022). Practical Gudance on the Application of Food Allergen Quantitative Risk Assessment within Food Operations. https://ilsi.eu/wp-content/uploads/sites/3/2022/04/ILSI-Eu_Guidance-on-QRA-final.pdf
(6) The risk of contamination of wheat, pasta and flour products with mustard allergen was reported at the time by the writer (see. Mustard. Allergy prevalence, agricultural uses, contamination risks).
However, the same Office 8 DGISAN of the Ministry of Health that in the case of Indian soy lecithin denied its risk analysis responsibilities (see footnote 1) has decided to approach the case of mustard contamination of pasta in quite another way:
– blanket sampling and analysis was not ordered on the territory of Italy, although the conditions were met, so as not to extend the alert in the RASFF system (see article Mustard alert in wheat. The reminder is dutiful and urgent),
– no recalls or recalls or re-labeling of potentially dangerous foods for allergic consumers have been ordered, as they should have been. And instead, collective ‘shelf‘ information was agreed upon, a measure not provided for in reg. EC 178/02 (Art. 19) nor suitable for informing those who had already purchased food contaminated at levels that health authorities were careful to verify.
The writer, alongside Food Allergy Italy, publicly denounced this shameful handling of a concrete food safety risk that thank goodness did not result in deaths (except that the deaths were attributed to Covid, according to the customs of the time). See the article Mustard allergen alert in wheat, health ministry circular. Analysis,
(7) In both methods of analysis, PCR and ELISA, it is also important to identify an appropriate conversion factor from the allergen to the allergenic protein. To ensure proper application of assessment systems such as Vital® 3.0 or even TNO’s Contamination estimate calculator , promoted in the European iFAAM project,
(8) Dario Dongo. May contain allergens, ABC. GIFT(Great Italian Food Trade). 24.6.18,
(9) Codex Alimentarius. Code of practice on food allergen management for food business operators (CXC 80-2020).
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
