Joint Expert Committee On Food Additives Research Articles

Occurrence of ochratoxin A in sweet wines produced in Spain and other countries

A survey for the presence of ochratoxin A (OTA) was undertaken from 2001 to 2005 in 188 samples of sweet wines produced in Spain and in 102 samples originating from other countries: France (n = 49), Austria (9), Chile (9), Portugal (9), Greece (6), Italy (5), Germany (3), Hungary (2), Slovenia (2), Switzerland (2), Canada (1), Japan (1), New Zealand (1), Ukraine (1), South Africa (1) and the USA (1). The analytical method was based on immunoaffinity chromatography clean-up and high-performance liquid chromatography (HPLC) with fluorescence detection. The limit of detection (defined as a signal–noise ratio = 3) was estimated to be 0.01 µg l−1. The limit of quantification (0.02 µg l−1) was checked as being the lowest measurable concentration. OTA was detected in 281 out of 290 samples analysed (96.9% positive) at concentrations ranging from 0.01 to 4.63 µg l−1. The overall mean and median levels were estimated to be 0.50 and 0.14 µg l−1, respectively. In Spanish sweet wines OTA was found in 99% of the samples, with mean and median values of 0.65 and 0.19 µg l−1, respectively. The mean value obtained in this study for OTA in the Spanish sweet wines would result in an intake of about 37.5 and 3.2 ng day−1 of OTA for regular consumers and for the overall population, respectively. These figures represent a minor contribution to the provisional tolerable weekly intake (PTWI) or TWI established by the Joint Expert Committee on Food Additives (JECFA) and the European Food Safety Authority: 3.8 and 3.1% for regular consumers; and 0.4 and 0.3% for the whole adult population, respectively.

Investigation of the causes for the occurrence of residues of the anticoccidial feed additive nicarbazin in commercial poultry

Investigations were undertaken to identify causes for the occurrence of high levels of the zootechnical feed additive nicarbazin in broiler liver at slaughter. The first investigation on 32 commercial broiler flocks involved sampling and analysis for nicarbazin (as dinitrocarbanilide, DNC) in liver from birds during a 3–10-day period after withdrawal of nicarbazin from their feed and before commercial slaughter. DNC residues in liver samples of broilers scheduled as being withdrawn from nicarbazin for ≥6 days ranged from 20 to >1600 µg kg−1 (the specified withdrawal period for nicarbazin is 5 days and the Joint Expert Committee on Food Additives (JECFA) maximum residue limit (MRL) is 200 µg kg−1 liver). Further on-farm investigations on 12 of these flocks, selected on the basis of the feeding system in use and the levels of DNC residues determined in liver, identified issues in feed management contributing to elevated residues in broiler liver. A significant correlation (0.81, p < 0.01, n = 10) between DNC residues in liver samples and in feed samples from the feeding pans was observed. The second investigation on 12 commercial broiler flocks involved sampling and analysis for DNC in liver samples and feed samples from feeding pans and from the feed mill at the three thinnings of birds for commercial slaughter. In the case of one flock, a clear relationship between nicarbazin in feed from the feed mill (10.5 mg kg−1 DNC), in feed from the feeding pans (6.6 mg kg−1 DNC) and in liver (583 µg kg−1 DNC) at first thinning (9 days scheduled withdrawal from nicarbazin) was observed. Such a clear relationship was not observed in other cases, particularly at second and third thinnings, pointing to re-exposure of birds to nicarbazin late in the flock production cycle, probably from the litter. Guidelines outlining best farm practice to eliminate nicarbazin residues in poultry have been published in booklet and poster format for broiler producers and deal with feed system cleaning, feed bin management, feed deliveries, feed usage and records.

Risk assessments of polychlorinated dibenzo‐ p‐dioxins, polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls in food

The polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and dioxin-like polychlorinated biphenyls (dioxin-like PCB) are ubiquitous in food of animal origin and accumulate in fatty tissues of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The toxic responses include dermal toxicity, immunotoxicity, carcinogenicity, and reproductive and developmental toxicity. Toxic equivalency factors have been established for the other PCDD, PCDF and dioxin-like PCB relative to TCDD, and the combined toxicity of a sample can be expressed as toxic equivalent (WHO-TEQ). The EC Scientific Committee for Food evaluated these compounds in 2001. The assessment used the most sensitive adverse toxicological end-points of TCDD in experimental animals. These were developmental and reproductive effects in the male offspring of rats administered TCDD during pregnancy. Because of the large difference between rats and humans in the biological half-life of TCDD, the assessment used a body burden approach to compare across species and derived a tolerable weekly intake of 14 pg TCDD/kg of body weight (bw), which was extended to include all the 2,3,7,8-substituted PCDD and PCDF, and the dioxin-like PCB, and expressed as a group tolerable weekly intake of 14 pg WHO-TEQ/kg bw. The FAO/WHO Joint Expert Committee on Food Additives (JECFA) performed a similar assessment whereas the US Environmental Protection Agency (US EPA) has paid more attention to human data on carcinogenicity.

Justifying the need to prescribe limits for toxic metal contaminants in food-grade silver foils

The use of silver foils in various food preparations is a common practice in Middle Eastern and South East Asian countries. The FAO/WHO Joint Expert Committee on Food Additives (JECFA) has included silver in the list of food additives, but specifications were not prepared. Indian food legislation has included food-grade silver foil and laid down a purity requirement of 99.9%. This leaves an unspecified margin of 0.1% or 1000 µg g−1 for contaminants. Therefore, a study to investigate the levels of metallic contaminants in food-grade silver foil was undertaken. Of 178 foils analysed, 161 (90%) contained silver, whilst 10% were fraudulently made up of aluminium. In the case of silver foils, 46% of the samples adhered to the desired purity requirement of 99.9%, while 54% had a lower silver content. Copper was present in 86.3% of the silver foils, while chromium, nickel and lead contamination was found in over 54% of samples. Cadmium levels were detected in 28% of the silver foils and manganese was present in 6.8% of samples. In silver foils showing metal contaminants, average levels were found for nickel (487 µg g−1), lead (301 µg g−1), copper (324 µg g−1), chromium (83 µg g−1), cadmium (97 µg g−1) and manganese (43 µg g−1), which being appreciable justify the need to prescribe limits for some metals in food-grade silver foil as well as for silver powder used in confectioneries and medicinal preparations. The work reported here should encourage manufacturers to use high-purity raw materials and take suitable precautions to reduce unwarranted exposure of consumers to toxic metal contaminants.

食品のカビ汚染とリスクアセスメント

From the second half of the 1990s, an increased regard has been given to the fungal spoilage of foods as follows: 1) post-harvest diseases and losses of fruits and vegetables, 2) deterioration of low water activity foods by xerophilic fungi, 3) contamination of psychrotolerant or psychrophilic fungi on foodstuffs and processed foods during storage and distribution at low temperature, and 4) spoilage of heat processed foods and soft drinks by heat-resistant fungi. In accordance with an international concern about food safety, mycotoxin contamination of foods has gained much global attention in recent times owing to its potential health hazards. The evaluation of mycotoxin hazards is principally based on the determination of a no-observed effect level (NOEL) in long-term toxicological studies, and the application of a safety factor (usually 100). In addition to hazard assessment, data on the natural occurrence of mycotoxins in various commodities and food intake data are needed to enable exposure assessment. Thus risk assessment of mycotoxins is, in fact, the product of hazard assessment and exposure assessment. In 1997, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) considered estimates of the carcinogenic potency of aflatoxins and the potential risks associated with their intake. Recently the Codex Alimentarius Commission (Codex) has established standards for aflatoxin M1 in milk and for patulin in apple juice. The Codex is an international organization, supported by FAO/WHO, aiming at facilitating world trade and protecting the health of the consumer by developing international standards for food and feeds. Apart from aflatoxins, the JECFA has measured a provisional tolerable daily intake (TDI) for ochratoxin A, patulin, deoxynivalenol, T-2/HT-2 toxins, zearalenone and fumonisins. In 2001, the mycotoxins evaluated or re-evaluated at the JECFA meeting included ochratoxin A, deoxynivalenol, T-2/HT-2 toxins, fumonisins, and aflatoxin M1. In Japan, specific regulations now exist for deoxynivalenol (1.1 ppm) in wheat grains and for patulin (50 ppb) in apple juice and its products.

Safety evaluation of food flavorings.

Food flavorings are an essential element in foods. Flavorings are a unique class of food ingredients and excluded from the legislative definition of a food additive because they are regulated by flavor legislation and not food additive legislation. Flavoring ingredients naturally present in foods, have simple chemical structures, low toxicity, and are used in very low levels in foods and beverages resulting in very low levels of human exposure or consumption. Today, the overwhelming regulatory trend is a positive list of flavoring substances, e.g. substances not listed are prohibited. Flavoring substances are added to the list following a safety evaluation based on the conditions of intended use by qualified experts. The basic principles for assessing the safety of flavoring ingredients will be discussed with emphasis on the safety evaluation of flavoring ingredients by the Food and Agriculture Organization (FAO) and World Health Organization (WHO) Joint Expert Committee on Food Additives (JECFA) and the US Flavor and Extract Manufacturers Expert Panel (FEXPAN). The main components of the JECFA evaluation process include chemical structure, human intake (exposure), metabolism to innocuous or harmless substances, and toxicity concerns consistent with JECFA principles. The Flavor and Extract Manufacturers Association (FEMA) evaluation is very similar to the JECFA procedure. Both the JECFA and FEMA evaluation procedures are widely recognized and the results are accepted by many countries. This implies that there is no need for developing countries to conduct their own toxicological assessment of flavoring ingredients unless it is an unique ingredient in one country, but it is helpful to survey intake or exposure assessment. The global safety program established by the International Organization of Flavor Industry (IOFI) resulting in one worldwide open positive list of flavoring substances will be reviewed.

Toxicology databases and the concept of thresholds of toxicological concern as used by the JECFA for the safety evaluation of flavouring agents

Since 1996 the FAO/WHO Joint Expert Committee on Food Additives (JECFA) has evaluated the safety of 1259 flavouring substances, based on a decision tree that incorporates a series of thresholds of toxicological concern. Safety conclusions are based on the predicted consequences of metabolism and whether the estimated intake is above or below a threshold of toxicological concern that is relevant to that compound. Compounds are allocated to one of three structural classes, and the intake compared with a threshold of toxicological concern derived using data from chronic and sub-chronic toxicity studies on compounds in the same structural class. If the substance is predicted to be metabolised to innocuous products there is no safety concern if the intake is below the threshold, but suitable toxicity data on the compound or structural analogues are required if the intake exceeds the threshold. If the substance is not predicted to be metabolised to innocuous products, and the intake is below the appropriate threshold, safety evaluation is based on data on the compound or structural analogues. An additional threshold of 1.5 μg per day, derived from doses of investigated chemicals giving a calculated cancer risk of one in a million, is applied when appropriate toxicity data are not available.

Surface plasmon resonance biosensor screening of poultry liver and eggs for nicarbazin residues

Nicarbazin is used globally as a feed additive to prevent outbreaks of coccidiosis in broiler chickens. The drug is comprised of a complex of two compounds: 4,4′-dinitrocarbanilide (DNC) and 2-hydroxy–4,6-dimethylpyrimidine (DHP). In 1998, The Joint Expert Committee on Food Additives (JECFA) imposed a maximum residue limit (MRL) of 200 μg kg −1 for DNC, the marker residue, in broiler chickens. Nicarbazin is not licensed for use in egg-laying chickens. An assay was developed for DNC using a Biacore ® surface plasmon resonance (SPR) biosensor. Antiserum was raised in a rabbit to a structural mimic of DNC. Another DNC mimic was immobilised onto a CM5 sensor chip. Binding of the antibody to the chip surface could be detected and was inhibited by the presence of DNC. The chip surface was regenerated using a combination of base and organic solvent and was highly stable over many hundreds of sample injections. A single analytical cycle (sample injection, chip regeneration and system wash) took 7 min to complete. Prior to analysis, nicarbazin was extracted from liver and egg samples using acetonitrile. Liver samples required an additional hexane wash. Limits of detection (3 σ) for liver and eggs were 17 and 19 ng g −1, respectively. A comparison of DNC concentration in livers ( n=8) taken from broilers treated with nicarbazin showed a high correlation ( r 2=0.88) between liquid chromatography (LC) and SPR biosensor results.

Gum Arabic Specifications: Regulatory Revisions and Referrals

A recent Codex Alimentarius decision to refer the Joint Expert Committee on Food Additives (JECFA) 1990 Revised Specification for gum arabic (Acacia senegal) for reconsideration has been made in response to trade interests despite concerned comments by consumer associations. Although the 1990 JECFA Specification remains in force the Codex recognises only the 1978 JECFA Specification, which pre‐dates the introduction of any microbiological requirement to ensure the absence of Salmonellae and Escherichia coli.

Human intake of arsenic and iodine from seaweed-based food supplements and health foods available in the UK.

A number of seaweed-based products were analysed for total and 'reducible' arsenic and total iodine. Maximum potential intakes of the two elements were estimated using the manufacturers' recommended does. The levels of reducible arsenic found were generally low and, with one exception, ingestion of the products is unlikely to lead to the Joint Expert Committee on Food Additives (JECFA) Tolerable Daily Intake being exceeded. Iodine levels varied widely even between different samples of the same product. In a number of these cases the potential iodine intake is very high.

Toxicology of gallates: A review and evaluation

The propyl, octyl and dodecyl esters of gallic acid have been studied extensively in a large number of animal experiments involving oral dosing. Experimental data on general toxicity and studies on reproduction, teratogenicity and mutagenicity are also available. Most of the key toxicity studies, however, date back to the 1950s, do not meet current standards of toxicity testing and do not provide evidence for carcinogenic or mutagenic action of the gallates. Mutagenicity studies with octyl gallate and dodecyl gallate are lacking. The biokinetics of propyl gallate apparently differ from those of octyl and dodecyl gallate, the octyl and dodecyl esters being absorbed and hydrolysed to a lesser degree than the propyl ester. In toxicity studies with propyl gallate, growth retardation, anaemia, kidney and liver changes and hyperplasia of the forestomach were the most prominent effects at dose levels above 10,000 mg/kg feed. At 5000 mg/kg feed, liver enzyme induction was seen. In the available studies with octyl gallate or dodecyl gallate as the test compound, effects were found at 3000 mg/kg feed or higher levels. In studies performed with the various gallates, no effects were observed at a dose level of 1000 mg/kg feed, a level that was adopted as the no-effect level by the FAO/WHO Joint Expert Committee on Food Additives (JECFA) in 1976. This committee established an acceptable daily intake (ADI) for man of 0.2 mg/kg body weight (as a sum of propyl, octyl and dodecyl gallates). A re-evaluation of the toxicity of gallates indicates that a ‘classic’ long-term toxicity study of propyl gallate meeting current standards is required. As yet, the available toxicological evidence indicates that gallates may be used safely as antioxidants.

Regulatory procedures in securing approval for new sweeteners

The introduction of new ingredients into the UK food supply is controlled by various means, largely under the umbrella of the Food & Drugs Act, 1955. Regulations made under the Act cover most categories of food additives by means of positive lists and, in the case of artificial sweeteners, saccharin was until recently the only permitted additive. This situation was changed as a result of recommendations made by the Food Additives & Contaminants Committee (FACC) after a four-year review of sweeteners. In common with other new additives, all sweeteners submitted to the FACC were evaluated first for case of need, and only if this was demonstrated was safety in use considered, all largely on the basis of data submitted by companies or consortia with a commercial interest in the sweeteners. In late 1983, regulations came into operation permitting the use of three new intense sweeteners and three new bulk sweeteners. Companies developing new sweeteners must look to overseas markets in order to help recoup their investment, and this requires a global approval and regulatory strategy, and involvement with international committees such as the FAO/WHO Joint Expert Committee on Food Additives (JECFA) and the EEC Scientific Committee for Food (SCF). Although the legal systems, attitudes to food additives and approval procedures in other countries may be different from those in the UK, the petition data requirements for sweeteners are remarkably similar. However, the interpretation of the data and ideas about the rôle of nonsugar sweeteners may vary widely, leading to a heterogeneous pattern of sweetener approvals throughout the world. We in the UK, consumers and food industry alike, must consider ourselves fortunate that our expert-committee-based approval system is efficient, effective and objective, and generally free from political pressures.