Zinc and calcium apparent absorption from an infant cereal: a stable isotope study in healthy infants

Fractional apparent absorption of Zn and Ca from a wheat-milk-based infant cereal was studied in six healthy infants (18-30 weeks old). Mineral absorption was measured by a stable-isotope technique based on faecal excretion of the isotopes. Each test meal (40 g cereal) was extrinsically labelled with 70Zn and 42Ca before intake. All faecal material passed during the 21 d following intake of the labelled test meal was collected on trace-element-free nappies. Individual stool samples were analysed for their content of ‘OZn and 42Ca by thermal ionization mass spectrometry. Apparent absorption was calculated as intake minus total faecal excretion of the isotopes over 68-92 h after administration. The fractional apparent absorption values for Zn and Ca were 33.9 (SD 164) % (range 19.2-639 %) and 53.5 (SD 12.6) %) (range 36.7-71.7 %) respectively. Re-excretion of absorbed 70Zn (> 68-92 h to 21 d after intake of the labelled meal) was 044 (SD 038) %] of administered dose while only one infant re-excreted detectable amounts of 42Ca (1.74%) of administered dose). The analysis of individual stool samples confirmed that 72 h is a sufficient time period for complete collections of non-absorbed isotopes in faecal material from infants during the weaning period and that re-excretion of initially absorbed 70Zn and 42Ca (> 68-92 h to 21 d after intake of the labelled meal) is negligibl

Severity scoring of manganese health effects for categorical regression

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data

The use of categorical regression in evidence integration

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report

BACKGROUND: Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs. HEALTH CLAIMS: Codex, EFSA and some national regulatory authorities have established guidelines or regulations that will permit several types of health claims. The scientific basis for claims has been established by the US FDA and EFSA, but not yet by Codex. Evidence-based nutrition differs from evidence-based medicine, but the differences are only recently gaining recognition. Health claims on foods may provide useful information to consumers, but many will interpret the information to mean that they can rely upon the food or nutrient to eliminate a disease risk. NUTRIENT REFERENCE VALUES: NRVs are designed to provide a quantitative basis for comparing the nutritive values of foods, helping to illustrate how specific foods fit into the overall diet. The INL-98 and the mean of adult male and female values provide NRVs that are sufficient when used as targets for individual intakes by most adults. WORLD TRADE ORGANIZATION AGREEMENTS: WTO recognizes Codex as the primary international authority on food issues. Current regulatory schemes based on recommended dietary allowances are trade restrictive. A substantial number of decisions by the EFSA could lead to violation of WTO agreements

Evaluation of four new studies on the potential toxicity of titanium dioxide used as a food additive (E 171)

The European Commission requested EFSA to carry out a scientific evaluation on four studies on the potential toxicity of titanium dioxide (TiO2) used as a food additive (E 171) and to indicate whether they would merit re‐opening the existing opinion of EFSA on the safety of TiO2 (E 171) as a food additive. The results of the Bettini et al. (2017) study did not provide enough justification for a new carcinogenicity study, but, should additional useful mechanistic information become available, this could be reconsidered in future. The new in vitro findings in the Proquin et al. (2017) study did not modify the conclusion on the genotoxicity of TiO2 as stated in the previous EFSA opinion of 2016 on the safety of TiO2 (E 171) as a food additive. The effects of engineered TiO2 nanoparticles reported by the Guo et al. (2017) study were of uncertain biological significance and therefore of limited relevance for the risk assessment of the food additive TiO2 (E 171). There was significant uncertainty in the risk assessment performed by Heringa et al. (2016), which did not include a weight of evidence analysis of the whole database. The Panel considered that the four studies evaluated, highlighted some concerns but with uncertainties, therefore their relevance for the risk assessment was considered limited and further research would be needed to decrease the level of uncertainties. Overall, three of the studies, reporting that TiO2 induced various effects in in vitro and in vivo models, may be useful for hazard identification of TiO2. In the fourth study by Heringa et al. (2016), numerous assumptions were made, which resulted in large uncertainty in their conclusion. Altogether, the Panel concluded that the outcome of the four studies did not merit re‐opening the existing opinion of EFSA related to the safety of TiO2 (E 171) as a food additive

Safety in use of glucosylated steviol glycosides as a food additive in different food categories

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety of glucosylated steviol glycosides proposed for use as a new food additive in different food categories. According to the applicant, glucosylated steviol glycosides preparations consist of not less than 95% (on anhydrous basis) total steviol glycosides, made up of glucosylated steviol glycosides of different molecular weights as well as any remaining steviol glycosides. The applicant proposed that glucosylated steviol glycosides and parent steviol glycosides undergo a common metabolic process in pathway following ingestion and suggested that data from steviol glycosides can be used for read‐across to glucosylated steviol glycosides. The limited evidence provided in the application dossier did not demonstrate the complete hydrolysis of the glucosylated steviol glycosides. No toxicological studies on glucosylated steviol glycoside preparations under evaluation have been provided for its assessment. The Panel concluded that the submitted data are insufficient to assess the safety of the glucosylated steviol glycoside preparations to be used as a new food additive

Refined exposure assessment of polyethylene glycol (E 1521) from its use as a food additive

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the refined exposure assessment of polyethylene glycol (E 1521) when used as a food additive. Polyethylene glycols were evaluated by several international bodies and the AFC Panel previously adopted scientific opinions on the safety polyethylene glycol (E 1521). In 2006, the Panel concluded that based on all the data, consumption of PEG through use as plasticisers in film‐coating formulations for food supplement tablets and/or capsules at the intended use level are not of safety concern. In 2007, in another opinion of the AFC Panel related to d‐alpha‐tocopheryl polyethylene glycol 1000 succinate (TPGS) in use for food for particular nutritional purposes, the Panel noted that TPGS intakes would correspond to intake to PEG 1000 at levels equivalent to 3.3–8.5 mg/kg body wieght (bw) per day which are within the range of group acceptable daily intakes (ADIs) of the SCF (1997) and JECFA (1980). This assessment could only take into account the use of polyethylene glycol (E 1521) in food supplements and thus the food supplements consumers only scenario was performed. It resulted in exposure estimates of polyethylene glycol (E 1521) up to 3.5 mg/kg bw per day at the mean and up to 6.1 mg/kg bw per day at the high level. The current exposure assessment is based on the methodology used in the re‐evaluation of food additives together with reported use levels received following a call for data in 2017. Considering the uncertainties of the exposure assessment, these estimates very likely overestimated the real exposure to polyethylene glycol (E 1521). The Panel also noted that the highest calculated exposure estimate falls within the range of the group ADI previously established by SCF (5 mg/kg bw per day for PEG 300–4000) and of the one set by JECFA (10 mg/kg bw per day for PEG 200–10000)

Evaluation of di‐calcium malate, used as a novel food ingredient and as a source of calcium in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes

The present scientific opinion deals with the evaluation of the safety of di‐calcium malate (DCM) proposed as a novel food ingredient and as a source of calcium for use in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes (FSMP), and with the bioavailability of calcium from this source. The structural formula of the proposed complex is based on expert judgement and not supported by any analytical data. On the basis of the available data, the Panel concluded that there was insufficient scientific evidence of a difference between the proposed novel food ingredient named as di‐calcium malate (DCM) and calcium malate already authorised as a source of calcium included in Annex II to Directive 2002/46/EC. Accordingly, the Panel was unable to assess the safety of DCM as a novel food ingredient. On the basis of the results provided, the Panel considered that DCM does not completely dissociate into calcium and malic acid. The Panel concluded that when DCM dissociates, calcium would be available following ingestion of DCM and the bioavailability would appear similar to values reported for other sources of calcium already permitted. Furthermore, the Panel concluded that on the basis of the information available it was not possible to calculate the exposure to DCM as a source of calcium to foods for the general population, food supplements, total diet replacement for weight control and FSMP

Scientific opinion on the evaluation of authorised ferric sodium EDTA as an ingredient in the context of Regulation (EC) 258/97 on novel foods and Regulation (EU) 609/2013 on food intended for infants and young children, food for special medical purposes and total diet replacement for weight control

The present opinion deals with the evaluation of the proposed increase of the currently authorised maximum amounts of ferric sodium ethylenediaminetetraacetic acid (EDTA) as a novel food ingredient used as a source of iron, and its extension of use in processed cereal‐based foods and baby foods. The applicant also provided information on two forms of ferric sodium EDTA, one previously assessed by EFSA and a new one of finer consistency. To support the proposed changes to the uses of ferric sodium EDTA, the applicant proposed a revision of the current acceptable daily intake (ADI) for EDTA, derived from that set for the food additive calcium disodium EDTA (E 385). The Panel confirmed that ferric sodium EDTA is a source from which iron is bioavailable. In assessing the safety of the proposed revision to the existing specifications for the novel food ingredient ferric sodium EDTA, the Panel noted that this would not discriminate between the previously evaluated substance and the one of finer consistency. In particular, the Panel noted that particle size was not one of the proposed parameters for the revised specifications. The Panel noted that it was not possible to determine whether particles of ferric sodium EDTA in the nano range were present in the product with finer consistency in the solid form. The toxicological data submitted did not add any new relevant information to the database on which the current ADI for EDTA is based. Consequently, the Panel concluded that there was no sound scientific justification to increase the ADI for EDTA and hence increase the use levels of ferric sodium EDTA or introduce additional uses as proposed by the applicant. The Panel recommended that additional toxicological data should be provided to address the shortcomings in the available toxicity database prior to the re‐evaluation of calcium disodium EDTA (E 385)