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The joint food and agriculture organization of the United Nations/World Health Organization Expert Committee on Food Additives and its role in the evaluation of the safety of veterinary drug residues in foods.

The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) recommended the evaluation of food additives at the international level through the establishment of an expert committee or committees. These committees evaluated the safety of food additives present as residues resulting from the use of pesticides or veterinary pharmaceuticals. The results of these meetings include international harmonization on acceptable daily intake of these compounds and the maximum residue limit that is permitted to be present within any food of animal or plant origin. The decisions rendered by these committees provide a key element in the elimination of international trade barriers associated with products intended for human consumption.

Agriculture↗

Needs and methods for priority setting for estimating the intake of food additives.

Direct measurement of the intake of food additives is a complex, time-consuming and expensive process. Prioritization of intake surveys is important to focus initial attention on those additives of most concern. Intakes at or below the Acceptable Daily Intake (ADI) are not of concern, by definition, and therefore a high priority should be given to those additives for which simple, but conservative, theoretical estimates of potential intake indicate a probability of exceeding the ADI. Although ADI values for different additives are equivalent, because they are based on No-Observed-Adverse-Effect Levels (NOAELs), the risk associated with intakes above the ADI can only be determined by reference back to the data which are the basis for the ADI estimation. In consequence the nature and severity of toxic effects detected in animal experiments above the NOAEL should be taken into account in the prioritization of intake surveys. A scheme is proposed which incorporates both exposure estimation and toxicology in determining which food additives should be allocated a high priority for inclusion in intake surveys.

Diet Surveys↗

Asthma and anaphylactoid reactions to food additives.

Presumed allergic reactions to hidden food additives are both controversial and important. Clinical manifestations include asthma, urticaria, angioedema, and anaphylactic-anaphylactoid events. Most adverse reactions are caused by just a few additives, such as sulfites and monosodium glutamate. Diagnosis is suspected from the history and confirmed by specific challenge. The treatment is specific avoidance.

Anaphylaxis↗

Evaluation of reactions to food additives: the aspartame experience.

Despite the widespread use of chemical food additives, few criteria exist to evaluate consumer reports of adverse reactions. We analyzed 231 consumer complaints associated with the food additive aspartame. We developed a methodologic approach to evaluate all complaints by adapting general criteria used to investigate adverse reactions to medications. Complaints were ranked according to the effects of cessation and rechallenge. Using this method, we found no clear symptom complex that suggests a widespread public health hazard associated with aspartame use; however, we identified some case reports in which the symptoms may be attributable to aspartame in commonly-consumed amounts. The systematic application of pre-defined review criteria, such as those described here, to monitor consumer complaints related to food additives will help identify products that warrant more focused clinical studies.

Adult↗

Long-term measurement of gastric motility using passive telemetry and effect of guar and cellulose as food additives in dogs.

The suitability of passive telemetry for long-term measurements of gastric motility in two groups of dogs with different body weights, four Beagles and four Labrador Retrievers, was investigated. An intra-abdominal measuring device, with a pressure sensor and electrodes within the gastric wall, allowed the continuous recording of the intensity and frequency of contractions simultaneously with an electromyogram (EMG). In fasting dogs a typical inter-digestive motility cycle was reproducible. Within 15 min of feeding the integral of the pressure curve increased significantly, reaching its maximum 30-45 min post-prandially. The peak frequency also significantly increased immediately after feeding, reaching the maximum of 22 contractions per 5 min. The post-prandial motility patterns of the groups were significantly different. The pressure amplitudes of the Labradors were significantly higher and the peak frequencies significantly lower than the Beagles. The addition of guar to the food (2.5% or 5%) leads to a significant reduction of the intensity of the antral contractions, whereas the frequency was hardly affected. In comparison, the effect of cellulose, as a food additive (2.5% or 5%), was rather modest. The intensity of the post-prandial contractions, influenced by cellulose, was significantly increased in Beagles, but was decreased in Labradors. Passive telemetry has been proven to be a suitable method for the long-term investigation of the physiological gastric motility and the effect of food additives. The measuring device was still functional after removal 8 weeks later.

Animals↗

Effects of alcohols and food additives on glutamate receptors expressed in Xenopus oocytes: specificity in the inhibition of the receptors.

To study the effects of food additives on glutamate receptors, they were expressed in Xenopus oocytes that received an injection of poly(A)+ mRNAs prepared from rat brain. The response of the receptors elicited by kainate (KA) and N-methyl-D-aspartate (NMDA) was measured electrophysiologically in the presence and absence of food additives. Both responses elicited by KA and NMDA were inhibited similarly by addition of additives such as caffeine, vanillin or saccharin. However, inhibition of KA-elicited response by food additives followed a competitive inhibition scheme with two binding sites, while that of NMDA-elicited response followed a simple noncompetitive inhibition scheme. Inhibition constants of food additives for both responses were more than 1 mM. So it is unlikely that food additives taken with processed food interrupt signal transmission under physiological conditions. The specificity of inhibition of both responses was examined by adding various compounds to the bathing solutions containing the agonist. Increase of the number of hydroxyl groups in alcohols with the chain of three carbon atoms decreased the potency of inhibition. Potency of the inhibition depended on the species of functional groups. The order of potency of the inhibition by compounds with a chain of six carbon atoms was alcohol = diamine > aldehyde > carboxylic acid. Hexanol inhibited the receptors more strongly than (3Z)-hexen-1-ol. NMDA-elicited response showed little selectivity in inhibition by structural isomers of pentanol, while KA-elicited response showed some selectivity in inhibition by the structural isomers.

Alcohols↗

Effect on hepatic ornithine decarboxylase of some food additives and synthetic elastomers.

The food additives butylated hydroxytoluene, butylated hydroxyanisole and sodium cyclamate and the precursors for packaging materials acrylamide, acrylic acid, acrylonitrile and vinylpyrrolidone were investigated for their ability to induce hepatic ornithine decarboxylase (ODC) in vivo, in order to obtain indications about their possible tumour-promoting activities. It was shown that butylated hydroxyanisole, acrylonitrile, vinylpyrrolidone and acrylamide have the capacity to increase rat liver ODC activity, while butylated hydroxytoluene, acrylic acid and sodium cyclamate did not affect ODC activity.

Animals↗

Primary mutagenicity screening of food additives currently used in Japan.

Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan. Fourteen out of 200 tested in the Ames assay showed positive effects and 54 out of 242 were positive in the chromosome test. Three additives (erythorbic acid, chlorine dioxide and beet red) were positive only in the Ames test, although their mutagenic potentials were relatively weak, while 43 additives were positive only in the chromosome test. Eleven additives (calcium hypochlorite, cinnamic aldehyde, L-cysteine monohydrochloride, Food Green No. 3 (Fast Green FCF), hydrogen peroxide, potassium bromate, sodium chlorite, sodium hypochlorite, sodium nitrite, cacao pigment and caramel) were positive in both the Ames test and the chromosome test. The usefulness of such primary screening tests combining two different genetic end-points, gene mutation and chromosomal aberration, and some correlation between mutagenicity and carcinogenicity of food additives are discussed.

Animals↗

The identification of Combretum gums which are not permitted food additives, II.

Combretum gums, readily available at low prices in East and West Africa, may be offered for sale as 'gum arabic'. Vigilance is necessary to detect such misrepresentations because Combretum gums differ greatly from gum arabic (Acacia senegal (L.) Willd.) in terms of quality, solution properties and value. Moreover, because there is no toxicological evidence for their safety in use, Combretum gums are not included in any of the international lists of permitted food additives. Food manufacturers and regulatory authorities therefore require data that characterize Combretum gums so that their use in foodstuffs can be prevented. This paper presents such data for the gums from a further six Combretum species. All of these have negative optical rotations similar to that of food grade gum arabic. It is no longer sufficient, therefore, to rely solely on an optical rotation measurement to confirm the identity of gum arabic. The additional analyses necessary to differentiate between Combretum gums and gum arabic are discussed.

Amino Acids↗

[Qualitative and quantitative analysis of the food dyes in complex food additives in the meat industry].

The methodical approach by definition of food dyes in a composition of complex food additives is realized. Research of 98 samples of complex food additives is shown, that realization of research of their composition is necessary for the control of observance of hygienic norms on application of food dyes. In result of qualitative and quantitative research of food dyes in composition, it was revealed, that 3.1% from number of the investigated samples there does not correspond the declaration of a composition, 7.1%--do not correspond to the declared scope, for 2% of products corrective amendments were brought in a recommended dosage in an end-product.

Food Additives↗

Validation analysis of probabilistic models of dietary exposure to food additives.

The validity of a range of simple conceptual models designed specifically for the estimation of food additive intakes using probabilistic analysis was assessed. Modelled intake estimates that fell below traditional conservative point estimates of intake and above 'true' additive intakes (calculated from a reference database at brand level) were considered to be in a valid region. Models were developed for 10 food additives by combining food intake data, the probability of an additive being present in a food group and additive concentration data. Food intake and additive concentration data were entered as raw data or as a lognormal distribution, and the probability of an additive being present was entered based on the per cent brands or the per cent eating occasions within a food group that contained an additive. Since the three model components assumed two possible modes of input, the validity of eight (2(3)) model combinations was assessed. All model inputs were derived from the reference database. An iterative approach was employed in which the validity of individual model components was assessed first, followed by validation of full conceptual models. While the distribution of intake estimates from models fell below conservative intakes, which assume that the additive is present at maximum permitted levels (MPLs) in all foods in which it is permitted, intake estimates were not consistently above 'true' intakes. These analyses indicate the need for more complex models for the estimation of food additive intakes using probabilistic analysis. Such models should incorporate information on market share and/or brand loyalty.

Databases, Factual↗

Antioxidant properties of Mediterranean spices compared with common food additives.

In this study, the antioxidant properties of Mediterranean food spices (annatto, cumin, oregano, sweet and hot paprika, rosemary, and saffron) at 5% concentration and of common food additives (butylated hydroxyanisole [BHA], butylated hydroxytoluene [BHT], and propyl gallate) at 100 microg/g are compared. The ability of these compounds to inhibit lipid peroxidation was, in decreasing order, rosemary > oregano > propyl gallate > annatto > BHA > sweet paprika > cumin > hot paprika > saffron > BHT. Deoxyribose damage is partially inhibited in the presence of cumin extract that exhibits the strongest protective action. The rest of the spices also protect deoxyribose better than the BHA and BHT used in the assay. Finally, the results obtained in the assay point to the prooxidant effect of propyl gallate. Hydrogen peroxide scavenging activity is measured by using peroxidase-based assay systems. In aqueous medium, the spice extracts show lower antioxidant activity than propyl gallate, the decreasing order being cumin > oregano > annatto > rosemary > hot paprika > sweet paprika. BHA and BHT did not scavenge H2O2 Spices are able to scavenge HOCl and protect alpha1-antiproteinase. The results indicate that rosemary and oregano are more effective HOCl scavengers than the other substances analyzed, which, in decreasing order, were propyl gallate, annatto, sweet and hot paprika, saffron, and cumin. The effect of Mediterranean food spices on the oxidative stability of refined olive oil tested by the Rancimat method was compared with common food additives during storage (72 h, 2, 4, and 6 months) at room temperature. The results showed that the spice extracts analyzed have significant stabilizing effects (P < 0.05).

Antioxidants↗

Food additives.

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Enzymes↗

Aspirin-like effects of selected food additives and industrial sensitizing agents.

A number of food additives and industrial chemicals, responsible for inducing symptoms of intolerance in some individuals, have been studied in tests measuring platelet activation by noradrenaline. All the investigated agents inhibited platelet aggregation and this was associated with inhibition of the cyclo-oxygenase-thromboxane pathway. Suboptimal inhibitory concentrations of the agents studied had additive inhibitory effects on platelet aggregation when they were tested in pairs, or when tested with salicylate or aspirin. The results support the theory that some food additives and industrial chemicals induce intolerance because of their aspirin-like properties.

Adolescent↗

Evaluation of certain food additives and contaminants.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives and contaminants, with a view to recommending acceptable daily intakes for humans, and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of principles governing the toxicological evaluation of food additives and contaminants, including flavouring agents, and the establishment and revision of specifications, with comments concerning limits for arsenic, lead and heavy metals. A summary follows of the Committee's evaluations of toxicological data on various specific food additives (including tert-butylhydroquinone, mineral oils, waxes and alitame) and on beta-cyclodextrin, nitrate, nitrite, potassium bromate and the contaminants ochratoxin A and patulin. Annexed to the report are a table summarizing the committee's recommendations for acceptable daily intakes of these substances and changes in the status of specifications, and a list of further toxicological studies required or desired.

Antioxidants↗

Analysis of food additives by ion-pairing electrokinetic chromatography.

A mixture of food additives is separated using ion-pairing electrokinetic chromatography with on-column ultraviolet detection at 190 nm. Tetrabutyl ammonium hydrogen sulfate (TBA) is used as modifier. The effect of the concentration of TBA on the migration behavior of the solutes is investigated. This method is used for the determination of the amount of additives in food samples. The percent relative standard deviation (%RSD) for the migration time is found to be less than 0.9% and that of the peak area is less than 2.5%.

Benzoates↗

Potential carcinogenicity of food additives and contaminants.

The potential role in carcinogenesis of food additives and contaminants presents a complex problem in terms of assessing the risk to the general public. Long-term testing in laboratory animals is still the most feasible method for determining potential carcinogenicity of various chemicals. The disadvantages encountered in the present methods of animal testing are discussed and a review is made of the current status of particular food additives and contaminants under scrutiny as possible carcinogens. It is suggested that, since it may not be possible to remove all carcinogenic materials from the environment, methods to mitigate or neutralize their harmful effects should be sought. Greater cooperation is called for among food technologists, toxicologists, laboratory researchers, and epidemiologists in the decision-making process regarding the role of possibly carcinogenic additives and contaminants.

2-Acetylaminofluorene↗