Search

In view of the cumulative nature of aluminium in the organism after dietary exposure, the Panel considered it more appropriate to establish a tolerable weekly intake (TWI) for aluminium rather than a tolerable daily intake (TDI). Based on the combined evidence from the abovementioned studies, the Panel established a TWI of 1 mg aluminium/kg bw/week. The estimated daily dietary exposure to aluminium in the general population, assessed in several European countries, varied from 0.2 to 1.5 mg/kg bw/week at the mean and was up to 2.3 mg/kg bw/week in highly exposed consumers. The TWI of 1 mg/kg bw/week is therefore likely to be exceeded in a significant part of the European population. Cereals and cereal products, vegetables, beverages and certain infant formulae appear to be the main contributors to the dietary aluminium exposure. Due to the design of the human dietary studies and the analytical methods used, which only determine the total aluminium content in food, and not the individual aluminium compounds or species present, it is not possible to conclude on the specific sources contributing to the Opinion on safety of aluminium from dietary intake aluminium content of a particular food, such as the amount inherently present, the contributions from use of food additives, and the amounts released to the food during processing and storage from aluminium-containing foils, containers, or utensils. Thus a detailed breakdown by exposure source is not possible.

Although data on use levels and categories of the foods intended for particular nutritional uses have not been provided by the applicant, based on the available information on bioavailability and the conclusions of the NDA Panel, the AFC Panel concludes that safe use of these sources for vanadium added to foods intended for the general population (including food supplements) and foods for particular nutritional uses, cannot be established. The Panel noted the inconsistency and the lack of information on specific elements in the specifications of heavy metals in the different dossiers as well as the high levels of arsenic and lead in the specifications of some vanadium sources in comparison to other sources.

The Panel concludes that the use of copper bisglycinate chelate as a source for copper added for nutritional purposes to food supplements, and of calcium bisglycinate chelate and magnesium bisglycinate chelate as sources for respectively calcium and magnesium added for nutritional purposes to foods for particular nutritional uses and food supplements, and of zinc bisglycinate chelate when used as a source for zinc in foods intended for the general population (including food supplements) and foods for particular nutritional uses, is not of safety concern As regards chromium glycinate nicotinate complex, due to lack of information on the specific identity of its components, the Panel is unable to reach a conclusion on the safety of this source and on the bioavailability of chromium from this source.

The bioavailability of vitamin C from calcium ascorbate with a content of threonate is comparable to that of ascorbic acid. The toxicity studies and mutagenicity tests with calcium ascorbate with a content of threonate, with calcium threonate or L-threonic acid, hemicalcium salt indicate that the compounds are of low toxicity and are not mutagenic. Data on carcinogenicity, long-term studies, reproductive and developmental toxicity of calcium ascorbate with a content of threonate were not presented. Such toxicity studies are not needed in the light of the dissociation of calcium ascorbate with a content of threonate to substances which are physiologically present in the body (ascorbate, threonate, calcium) and considering t at the safety of ascorbic acid (and its calcium and sodium salts), and calcium was previously evaluated. The intended conditions of use of calcium ascorbate with a content of threonate correspond to those of other approved sources of vitamin C. The additional exposure to calcium and threonate through Calcium ascorbate/threonate EFSA Journal (2007) 491, p. 2 of 10 use of supplements with calcium ascorbate with a content of threonate does not represent a cause of safety concern. The Panel noted that threonate is a normal metabolite in the body and concluded that the use of calcium ascorbate containing up to 2% threonate as a source of vitamin C in food supplements is not of safety concern.

According to the available evidence, ethyl lauroyl arginate is devoid of reproductive and developmental toxicity. Long-term carcinogenicity studies are lacking. However, the rapid metabolism of ethyl-Nα-lauroyl-L-arginate to compounds endogenously present in much higher levels, the absence of preneoplastic toxic effects in the in vivo studies performed, together with the absence of genotoxic activity in the mouse lymphoma assay, the human lymphocyte assay and the micronucleus test, does not suggest a carcinogenic potential. Therefore the Panel concludes that there is no need to perform carcinogenicity studies. The Panel notes that effects on white blood cells were seen in different rat strains and in different sexes in two 90-day studies and in the 52-week study and concludes that these effects cannot be disregarded. Therefore the Panel concludes, given the fact that the effects on white blood cell counts at 26 weeks are significant for all dose groups, that the NOAEL for this 52 week study is lower than the lowest dose levels tested, and thus lower than 106 mg/kg bw/day. This is in line with the NOAEL of 47 and 56 mg ethyl lauroyl arginate /kg bw/day for males and females respectively from the 13 week study with the 19.5 % formulation of ethyl lauroyl arginate in propylene glycol. Based on this NOAEL and a safety factor of 100, the Panel established an ADI of 0.5 mg ethyl lauroyl arginate of the proposed specifications /kg bw. The safety factor of 100 is considered sufficient in spite of the fact that the ADI is based on a 90-day study because the effects on white blood cells do not become more severe upon prolonged exposure. Potential dietary exposure to ethyl lauroyl arginate was estimated based on UK food consumption data and on the assumption that it would be present in all food categories for which use levels are proposed. Potential dietary exposure was found to be at or above the ADI in high consumers for both children aged 1.5 to 4.5 (580% of the ADI), children aged 4 to 18 (370% of the ADI) and adults (100% of the ADI). Potential mean dietary exposure to ethyl lauroyl arginate in consumers only was also at or above the ADI for both children aged 1.5 to 4.5 (170% of the ADI) and children aged 4 to 18 (106% of the ADI).

BIT is one of a number of trace impurities which may be present at varying concentrations depending on the synthetic route and the purification processes used to manufacture saccharin. BIT is also a biocide used as an emulsion stabiliser in the preparation of food contact materials. The SCF established a t-TDI for BIT of 0.02 mg/kg bw in 1992. The Panel has estimated the intake of BIT from consumption of saccharin at the Acceptable Daily Intake (ADI) for sodium saccharin of 0-5 mg/kg bw and assuming this saccharin contained BIT at the highest reported concentration (800 mg/kg). Using these assumptions an intake of 0.004 mg BIT/kg bw would result from consumption of saccharin at its ADI. This is around 0.05% of (2000-fold lower than) the no-observed-adverse-effect-level (NOAEL) for BIT in a 90-day oral toxicity study in rats conducted since the SCF established the t-TDI. The Panel accepted that the levels of BIT in commercially available saccharin are usually much lower than 800 mg/kg. The Panel considered that assuming consumption of saccharin at its ADI and containing the highest reported levels of BIT was conservative. The Panel concluded that even the highest levels of BIT detected in these samples do not represent a safety concern.

The estimated dietary exposure to residual formaldehyde in alginates and carrageenan, based on data from the USA on the consumption of ice cream and ready to eat dairy dessert cream, examined by the Panel, is between 400 and 70 times lower than the Tolerable Daily Intake (TDI) value of 150 µg/kg bw set by the World Health Organisation (WHO) for drinking water. No information was available to the Panel on residual formaldehyde in other gelling additives or on their actual use levels. However, the Panel considered an extreme worst case exposure scenario which assumes that an adult could eat 1 kg of food per day containing 2 % of any gelling agent containing 50 mg formaldehyde/kg. This exposure scenario would also include the uses of alginate and carrageenan outlined above. Under these conditions formaldehyde exposure levels would be 1 mg per person per day or for a 60 kg individual approximately 17 µg/kg bw/day, assuming an exposure to 1 kg of food per day containing gelling additives. Formaldehyde in food additives The EFSA Journal (2006) 415, 2 of 10 The estimated dietary exposure levels arising from this worst case exposure scenario would still be approximately 9 times lower than the TDI value of 150 µg/kg b.w. set by the WHO. The Panel examined recent and previous evaluations of formaldehyde and concluded that there is no evidence indicating that formaldehyde is carcinogenic by the oral route. Considering that the potential dietary exposures estimates remain low compared to the toxicological reference values outlined above and that no systemic exposure to formaldehyde is to be expected at the estimated residual levels, the Panel estimates that exposure to gelling additives containing residual formaldehyde at the levels of 50 mg/kg of additive would be of no safety concern.

The Panel concluded that in the absence of genotoxic effects the safety of TPGS can be assessed on the basis of the overall NOAEL equivalent to 1000 mg TPGS/kg body weight per day, established in a subchronic toxicity study in rats. TPGS is only to be used for food for special medical purposes under medical supervision at estimated intakes varying from 5 mg TPGS /kg bw in teenagers to 13 mg TPGS /kg bw in 1 month old infants. Potential intake would be lower in adults. This provides an adequate margin of safety (ratio between the NOAEL and the intake) compared with the NOAEL of 80 to 200 for infants and young children. The Panel also noted that these estimated intakes to TPGS would correspond to intakes to PEG 1000 at levels equivalent to 3.3 – 8.5 mg/kg bw/day. This is within the range of the group Acceptable Daily Intakes established by the EC Scientific Committee on Food (5 mg/kg bw for PEG 300 - 4000) and the Joint FAO/WHO Expert Committee on Food Additives (10 mg/kg bw for PEGs 200 - 10000). The Panel noted that under the current Community legislation foods for special medical purposes should be used under medical supervision. The supervising physician will be in a position to weigh up any risks and benefits to the patient and to ensure that the patient receives an adequate dose of vitamin E. The Panel noted that studies in healthy humans showed that the administration of TPGS, in contrast to fat-soluble vitamin E sources, only slightly elevated the plasma α-tocopherol level. Therefore, TPGS is not a useful source of vitamin E in healthy humans with a normal fat absorption. The Panel therefore concluded that the use of TPGS in foods for special medical purposes is not of safety concern at the anticipated exposure level. However, the Panel noted that it is advised not to apply the TPGS treatment in children with severe impairment of kidney function.

The Panel noted that Red 2G is extensively metabolised to aniline. The Panel noted that the current genotoxicity and carcinogenicity databases on Red 2G and its metabolite, aniline, are limited. However both genotoxic and carcinogenic effects have been observed in rodents treated with aniline. The Panel based its evaluation on the conclusions of the EU Risk Assessment on aniline. This concluded that aniline should be considered as a carcinogen for which a genotoxic mechanism cannot be excluded, based on the following: - aniline was genotoxic in vivo in rats and mice, - there was insufficient mechanistic evidence to discount a genotoxic mechanism for the rodent carcinogenicity, - based on similar metabolism of aniline in animals and humans a carcinogenic risk for man cannot therefore be excluded. Therefore the Panel concluded that it would be prudent to regard Red 2G as being of safety concern since it is extensively metabolised to aniline. Based on these considerations, the Panel withdrew the ADI for Red 2G.

Intake estimates based on the applicant’s proposed use levels of polyethylene glycol as a food additive and on conservative assumptions lead to a calculated intake estimate up to 120 mg/day, amounting to 2 mg/kg bw/day assuming 60 kg bw. Additional exposure to polyethylene glycol may also occur from use of pharmaceutical products both tablets and capsules, for which coating with polyethylene glycol-containing films has been approved. Assuming similar levels of use and intake of pharmaceutical products and food supplements per day the combined intake from food supplements and pharmaceutical products would be about 4 mg/kg bw/day. Limited additional exposure in the EU could occur from the approved use of polyethylene glycol 6000 as a carrier for sweeteners, as well as from the use of the PEG in food contact materials. The estimated daily intakes of the polyethylene glycols from the use as a coating agent for food supplements are below the ADI of 0-10 mg/kg body weight allocated by JECFA and the group TDI of 5 mg/kg body weight established by the SCF for the polyethylene glycols. Therefore, overall the data support the conclusion that consumption of polyethylene glycols (PEG 400, PEG 3000, PEG 3350, PEG 4000, PEG 6000, and PEG 8000) through use as plasticizers in film-coating formulations for food supplement tablets and/or capsules at the intended use level are not of safety concern.

The available studies cover the majority of endpoints considered relevant for assessment of reproductive effects and other toxicities and do not indicate the presence of effects on reproduction or development at doses lower than 50 mg/kg bw/day. The lowest NOAEL of 5 mg/kg bw/day derived in the recent two-generation reproductive toxicity study in mice is based on liver effects. Toxic effects of repeated administration of BPA on the liver in mice have also been observed in previous studies with a LOAEL of 120 mg/kg bw/day, suggesting that liver toxicity is at least as sensitive an endpoint for BPA as reproductive and developmental effects. The NOAEL for liver toxicity in mice is identical to the derived NOAEL for reproductive toxicity of bisphenol A in rats used in the EU RAR, which is based on effects on adult and offspring body weight gain. The Panel’s conclusions are based on the now available, extensive database on repeated-dose toxicity, reproductive and developmental toxicity of BPA in rodents and on the comparison of toxicokinetics in primates, including humans, and rodents. The Panel concluded that the new studies provide a basis for revising the uncertainty factors that were used by the SCF to derive the temporary TDI of 0.01 mg/kg bw in 2002. In particular, the Panel now considers that the database concerning reproduction and development has been considerably strengthened and that the additional uncertainty factor of 5, introduced by the SCF in 2002 for the uncertainties in the database on production and development, is no longer required. The Panel also concluded, in view of the well described species differences in toxicokinetics, howing a low level of free BPA in humans compared with rats, that a default uncertainty factor of 100 applied to the overall NOAEL from the rodent studies can be considered as conservative. The Panel therefore established a full TDI of 0.05 mg BPA/kg bw, derived by applying a 100-fold uncertainty factor to the overall NOAEL of 5 mg/kg bw/day. Dietary exposure assessments on BPA have been made by the Panel for adults, infants and children. The estimates of potential dietary exposure to BPA in infants took account of breast feeding, feeding formula using PC bottles and consumption of commercial foods and beverages. The resulting exposure assessments ranged from 0.2 microg/kg bw/day in 3–month-old breastfed infants up to 13 microg/kg bw/day in 6-12–month-old infants. These estimates were based on conservative migration values of BPA and the 95th percentiles of consumption. The estimates of potential dietary exposure in young children and adults were respectively 5.3 and 1.5 microg/kg bw/day based on conservative migration values of BPA and conservative estimates of consumption of commercial foods and beverages. The Panel noted that the conservative estimates of exposure were less than 30% of the TDI in all population groups considered. These exposure estimates include BPA migration into canned foods and into food in contact with PC table ware or storage receptacles. On the other hand, they do not include either potential migration of BPA from receptacles into food during Bisphenol A for use in food contact materials The EFSA Journal (2006) 428, p. 6 of 75 microwave heating or potential migration of BPA into drinking water due to the use of PC and of epoxy-phenolic resins in water pipes and in water storage tanks. Information on potential migration of BPA from these sources would be useful.

Cassia gum of the old specifications was not mutagenic or clastogenic in mammalian cells. Based on the results of recent genotoxicity studies, cassia gum, prepared by the newly defined production method, did not increase the number revertants in any of the four Ames tester strains (S. typhimurium), nor in the E. coli WP2uvrA test strain both in the presence and absence of S9-metabolic activation. It is concluded that cassia gum complying with the newly defined specifications does not give rise to safety concern with respect to genotoxicity. Long-term carcinogenicity studies on cassia gum were not available. Other related galactomannan gums, including locust (carob) bean, guar gum and tara gum were not carcinogenic when fed to mice and rats. Given that cassia gum is not genotoxic, and that many other related galactomannan gums are not carcinogenic, the Panel does not consider long-term carcinogenicity studies essential for the safety assessment of cassia gum. The toxicological data on cassia gum are insufficient to establish an acceptable daily intake (ADI). On the other hand, the existing data do not give reason for concern. The Panel wishes to stress the importance of inspection of the seeds for cassia gum preparation for the presence of seeds of C. occidentalis which has to be less than 0.1% by selection based on color and shape. Given these results from the toxicological studies, the very low absorption of cassia gum and the fact that, if hydrolysed at all, cassia gum would be degraded to compounds that will enter normal metabolic pathways, the Panel concludes that the use of cassia gum complying with the newly defined specifications as an additive for the proposed food uses is not of safety concern.

This chapter presents a brief review of the history of plant/crop metabolomics and summarizes the instrumental platforms mainly used for unbiased plant profiling investigations, including chromatographic and spectroscopic methods. An overview of metabolomics studies for various plants and crops from different plant families including Asteraceae, Brassicaceae, Fabaceae, Lamiaceae, Poaceae, and Solanaceae is given. Selected examples from the plant families are presented with special emphasis on commercially and nutritionally important staple crops. Plant-specific and non- specific metabolomics databases for plants and crops are briefly outlined.

Im Sommer 1958 wurden in Gros-Lusewitz phanometrische Messungen am Bernburger Fettmais an zwei verschiedenen Stellen des Gelandes durchgefuhrt. Die Abhangigkeit des Wachstums der Blatter und der Geschwindigkeit des Rispenschiebens von Temperatur, Windstarke und Bodenfeuchte wurde ermittelt. Als Optima wurden festgestellt fur die Tagestemperatur 22–25°C, fur die Nachttemperatur 18°C, fur die Bodenfeuchte 20% und fur die Windstarke 0,5 Beaufort.

Es wurde ein neues Kulturgefas beschrieben, das fur die laufende Kontrolle des Knollenwachstums von Kartoffeln geeignet ist.