Safety Evaluation Of Food Additives Research Articles

Exposure to food additive mixtures and type 2 diabetes risk in the NutriNet-Santé cohort

Abstract Background So far, the safety evaluation of food additives has been performed substance by substance, while in real life, millions of individuals are exposed to mixtures of food additives daily. According to preliminary experimental data, some of these chemicals, alone and/or in synergy are suspected to impact metabolic health. The objective of this study was to investigate for the first time the associations between exposure to mixtures of food additives and type 2 diabetes (T2D) risk in a large prospective cohort of French adults. Methods Participants (n = 108,783, 79.2% women, mean age=42.4 years, SD = 14.6) from the NutriNet-Santé cohort (2009-2024) completed repeated 24h-dietary records, detailing industrial product brands. Additive exposure was assessed using composition databases and laboratory assays. Five mixtures of additives were identified through non-negative matrix factorisation (NMF). Associations between these mixtures and the risk of T2D were characterised using multivariable proportional hazards Cox models adjusted for known risk factors. Findings 1115 participants were identified with T2D during follow-up. Two additive mixtures were associated with increased T2D risk. The first mixture included higher exposure to modified starches E14xx, pectins E440, guar gum E412, carrageenan E407, and polyphosphates E452 (HRper 1SD increment=1.11 [1.05-1.18]), p < 0.0001). The second mixture comprised citric acid E330, sodium citrates E331, phosphoric acid E338, sulphite ammonia caramel E150d, acesulfame-K E950, aspartame E951, sucralose E955 and arabic gum E414 (HR1SD=1.13 [1.08-1.18]), p < 0.0001). Interpretation This large prospective cohort study revealed direct associations between T2D risk and exposure to two food additive mixtures. Molecular epidemiology and experimental studies will be necessary to depict underlying mechanisms and potential cocktail effects. Key messages • Consumed together, widely used food additives may contribute to T2D aetiology, shedding light on the detrimental impact of highly processed foods on metabolic health. • This study highlights positives associations between T2D risk and exposure to two food additive mixtures.

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

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.

High Content Analysis technology for evaluating the joint toxicity of sunset yellow and sodium sulfite in vitro

Foods contain various additives that affect our daily lives. At present, food additive safety evaluation standards are based on the toxicity of single additives, but food additives are often used in combination and may have additive, synergistic or antagonistic actions. The current study investigated the toxicity of food additives and mechanisms of damage in HepG2 cells using High Content Analysis (HCA). We used the CCK-8 assay to determine cell viability, providing an experimental basis for determining the safety of food additives. All of the food additives tested were observed to decrease the growth of HepG2 cells in a dose-dependent manner. Sunset yellow and sodium sulfite had IC50 values of 1.06, and 0.30g/L at 24h, respectively. HCA showed that both sunset yellow and sodium sulfite had synergistic effects on cell number, membrane permeability, mitochondrial membrane potential, intracellular calcium level, oxidative stress, and high dose group DNA damage.

Artificial sweeteners

Low-calorie sweeteners are authorised food additives in the European Union (EU). The safety of these sweeteners has been evaluated in accordance with internationally agreed principles for the safety evaluation of food additives. In the EU, the European Commission’s Scientific Committee for Food (SCF) was the scientific guarantor for the safety of food additives until March 2003. Since then this has been taken over by the European Food Safety Authority (EFSA), notably its Scientific Panel on Food Additives and Nutrient Sources Added to Food (ANS Panel). Based on the large number of toxicological studies that are requested for the safety evaluation of food additives, a no observed adverse effect level (NOAEL) is identified for the most sensitive effect in the most sensitive animal species. A safety factor of 100 is normally applied to the NOAEL in order to establish an acceptable daily intake (ADI) for humans. The ADI is the amount of the food additive, expressed on a milligram per kilogram of body weight (bw) basis, that can be ingested daily over a lifetime without any appreciable health risk. The following low-calorie sweeteners have been allocated an ADI by either the SCF or EFSA: acesulfame K, aspartame, cyclamates, neotame, saccharin, steviol glycosides and sucralose.

In Utero Phase Carcinogenicity Testing

Early experimentation with transplacental exposure (1940s) demonstrated that expression of lung tumors in mice was enhanced when urethane was given during development in utero. In 1970, a U. S. Food and Drug Administration (FDA) expert panel on the safety evaluation of food additives and pesticides met and recommended that an in utero exposure phase be added to carcinogenicity testing (U.S. FDA, 1 971). An analysis was conducted of studies in the open scientific literature, in food additive studies available in FDA files and in studies performed by the National Institute of Environmental Health Sciences (NIEHS). While exposure to rodents during only the adult phase provided qualitatively similar results, early neonatal exposure typically provided slightly higher incidences of turnors, and decreased latency to turn or onset in certain scientific studies. In a series of studies recently performed by the NIEHS with three known animal carcinogens, neonatal or adult exposure produced similar tumors in similar tissues. The food additive saccharin, which shows bladder tumors, and eugenol reliably produced tumors only with neonatal exposure. Implieations for carcinogenicity testing of food additives are discussed in light of these experi-mental findings.

A Proposed Model for Safety Assessment of Macronutrient Substitutes

Restriction of fatty foods is an effective means of reducing caloric intake and is consistent with public health goals to reduce the risk of chronic diseases. Compliance with low-fat diets is enhanced by the substitution of foods with the same organoleptic properties as fat, namely flavor, texture, and mouth-feel. Fat substitutes could replace a significant proportion of dietary fat and as such become macronutrient substitutes. The safety of these materials must be established prior to introduction into the food supply. As their use increases so will concerns about their safety. Appropriate methods of safety evaluation must be used. Traditional methods for the safety evaluation of food additives are inappropriate, since concentrations of the test materials high enough to provide a 100-fold safety factor cannot be used. An approach that recognizes the unique nature of macronutrient substitutes and includes the use ofin vitro,whole-animal, and human studies and nutritional, physiological, and toxicological end points is proposed. Evaluations in humans are conducted early in this program but only when the animal data adequately support these studies. Human data will complement the animal data and may eliminate the need for some animal studies. The introduction of postmarketing surveillance will identify consumption patterns, associated adverse reactions, and potentially sensitive segments of the population and will ensure the continued safety of macronutrient substitutes.

Safety evaluation of hydrogenated oils

Processed foods have become an important part of the diet in industrialized countries. Advances in technology have brought about significant changes in the production methods in the food industry and have led to an improvement in texture, colour, shelflife and taste of conventional food products and to the development of novel foods. The safety evaluation of food components has advanced at a rapid pace and is no longer limited to the toxicology of additives and contaminants. The evaluation of the safety of macronutrients is becoming an area of increasing scrutiny, in order to ensure that food processing does not lead to unacceptable changes in the nutritional properties and safety of food products. The evaluation of the biological effects of processed foods distinguishes itself from the safety evaluation of food additives in several aspects. A major problem with respect to toxicological testing of foods in general is that toxicological evaluation of every chemical compound isolated is not tenable. The sensitivity of modern analytical techniques is such that suspect chemicals will be found in any food tested, whether it is as natural as a mother's milk, as simple as water, or as abused as a burned dinner! A more pragmatic approach is therefore required. This comprises the testing of processed foods as prepared or handled under normal factory conditions. In order to illustrate the specific problems that may arise with respect to macronutrient research this paper will focus on fats.

Advances in the safety evaluation of food additives. A conceptual and historical overview of the Acceptable Daily Intake (ADI) and Acceptable Daily Intake 'not specified'.

The Acceptable Daily Intake (ADI) is an internationally recognized quantified expression of the acceptability of food additives. It embraces both a concept and a numerical expression. This paper describes the conceptual origin and progression of this instrument of risk assessment and management in the framework of its history which encompasses three sequential stages: developmental, consolidation and contemporary periods. The review narrates in retrospect how the ADI originated, how it developed, and delineates in prospective its future evolution in the light of advances in the safety evaluation of food additives.

Why was diethylstilbestrol banned in meat production?

Joseph V. Rodricks recently resigned his position as Associate Commissioner for Science at the FDA. His career at FDA spanned 15 years in which he was involved in developing guidelines for the conduct and evaluation of toxicity studies used for the safety evaluation of food additives and contaminants. He is currently Science Director at Clement Associates, a Washington consulting firm specializing in toxic substance hazard evaluation. In the United States, concerns about the safety of food have been embodied in laws that dictate the conditions under which new substances may be deliberately added to foods to achieve des~ired technological goals. These laws recognize that society benefits from the use of additives in food production, but they also place certain demands on manufacturers who wish to introduce such substances into commerce. Specifically, manufacturers are required to provide information about the chemical and toxicological properties of a proposed food additive sufficient to show the safety of the substance under its proposed conditions of use. If a showing of safety (which the law defines as 'reasonable certainty of no harm') cannot be made, then a proposed additive cannot legally be used in food. DES, while not directly added to food, can enter food indirectly because of its use as an animal growth promotant, and it is therefore subject to the food additive requirements of law. In its recent action to prohibit the use of DES as an animal growth promotant, the U.S. Food and Drug Administration (FDA) held that the manufacturers of DES had failed to provide the information necessary to ascertain that animal drug uses of DES are safe. Professor Jukes has thus misinterpreted the basis of FDA's action, the full details of which are set forth in the official document he cites 1.

Food and Drug Administration Advisory Committee on Protocols for Safety Evaluation: Panel on carcinogenesis report on cancer testing in the safety evaluation of food additives and pesticides: August, 1970

Food and Drug Administration Advisory Committee on Protocols for Safety Evaluation: Panel on carcinogenesis report on cancer testing in the safety evaluation of food additives and pesticides: August, 1970

Food and drug administration advisory committee on protocols for safety evaluations: Panel on reproduction report on reproduction studies in the safety evaluation of food additives and pesticide residues

Food and drug administration advisory committee on protocols for safety evaluations: Panel on reproduction report on reproduction studies in the safety evaluation of food additives and pesticide residues

Experimental production of congenital maiformations in mammals by metabolic procedure.

Experimental production of congenital maiformations in mammals by metabolic procedure.