Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs

Abstract

There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, safety evaluation reports of food additives listed in Annex II of Regulation (EC) No 1333/2008 of the European Union were screened to qualitatively and quantitatively characterize toxicity induced in laboratory animals. The resulting database was used to identify the critical adverse effects used for risk assessment and to investigate whether food additives share common AOPs. Analysis of the database revealed that often such scrutiny of AOPs was not possible or necessary. For 69% of the food additives, the report did not document any adverse effects in studies based on which the safety evaluation was performed. For the remaining 31% of the 326 investigated food additives, critical adverse effects and related points of departure for establishing health-based guidance values could be identified. These mainly involved effects on the liver, kidney, cardiovascular system, lymphatic system, central nervous system and reproductive system. AOPs are available for many of these apical endpoints, albeit to different degrees of maturity. For other adverse outcomes pertinent to food additives, including gastrointestinal irritation and corrosion, AOPs are lacking. Efforts should focus on developing AOPs for these particular endpoints. Keywords Food additives • Critical adverse effect • Adverse outcome pathway • Acceptable daily intake • 3Rs Abbreviations 3Rs Replacement, refinement, and reduction of animal tests ADI Acceptable daily intake AOP(s) Adverse outcome pathway(s) BMDL Benchmark dose lower confidence limit CAS Chemical abstracts service EDI Estimated daily intake

The use of adverse outcome pathways in the safety evaluation of food additives

“…An AOP to assist in understanding this would be of enormous value to the food industry. As analyzed by Kramer et al (2019) as part of the ILSI Europe expert group activities, the adverse outcomes associated with food additives include a number of non-specific, late-onset and/or local effects, such as body weight changes, for which no AOPs have been developed. Particularly molecular initiating events (MIEs) and early KEs are currently insufficiently identified, and chemicals will likely perturb numerous MIEs simultaneously when point-of-departure values are high.…”

“…There may be several reasons underlying this situation, which may not be easily resolved. First, as shown by the study of Kramer et al (2019), characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs, food additives are not designed to cause biological effects in humans. For only 22% of the food additives currently authorized in the European Union, a specific critical adverse effect has been identified (Kramer et al 2019).…”

“…This workshop was organized on 26-27 February 2019 in Brussels, Belgium and gathered approximately 30 experts with an academic, industrial or regulatory background. The present manuscript describes the major outcomes and recommendations from this workshop, and as such is a follow-up of a study of the ILSI expert group that characterized the coverage of critical effects relevant in the safety evaluation of food additives by AOPs (Kramer et al 2019). The results of the workshop are described followed by some critical considerations and perspectives from the members of the expert group on the use of AOPs in the safety evaluation of food additives.…”

Cancer prevention programmes in Mexico: are we doing enough?

“…In this regard, in several in vitro and in vivo toxicological studies, the carcinogenic and mutagenic effects that produce different additives present in industrially processed foods such as preservatives, dyes, sweeteners, flavourings, etc., have been evaluated. These compounds are present in a very wide range of foods such as drinks, pastries, processed meats, sausages and preserves, to name a few [94,95].…”

“…In Mexico, the Federal Commission for Protection against Health Risks (COFEPRIS in Spanish) as well as the Food and Drug Administration (FDA) in the United States, ensure that substances incorporated as additives in the manufacture of industrialised foods be safe for human consumption [96,97,4,5]. It is important to note that, although it has been shown in studies with cell cultures and in laboratory animals that some food additives and preservatives can be mutagenic and carcinogenic at certain concentrations and at different exposure times, there is no conclusive scientific evidence showing that this effect is seen in human beings exposed daily or occasionally to the concentrations that are present in this type of food [94,95,2,3]. This is probably why they continue to be significantly produced, distributed and consumed in developed and developing countries.…”