Conclusion on the peer review of the pesticide risk assessment of confirmatory data submitted for the active substance dimethoate

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State the United Kingdom, for the pesticide active substance dimethoate are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory mammalian toxicology, residues and ecotoxicology data. The conclusions were reached on the basis of the evaluation of the representative uses of dimethoate as an insecticide on sugar beet and protected lettuce. Concerns are identified

Scientific Opinion on the revised exposure assessment of steviol glycosides (E 960) for the proposed uses as a food additive

Following a request from the European Commission, the European Food Safety Authority (EFSA) carried out an exposure assessment of steviol glycosides (E 960) from its use as a food additive, taking into account the proposed extension of uses. In 2010, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) adopted a scientific opinion on the safety of steviol glycosides (E 960) and established an Acceptable Daily Intake (ADI) of 4 mg/kg body weight (bw) per day. Conservative estimates of exposure, both in adults and children, suggested that it is likely that the ADI would be exceeded at the maximum proposed use level. In 2011, EFSA carried out a revised exposure assessment for steviol glycosides based on revised proposed uses and concluded that high level dietary exposure in children may still exceed the ADI. The current refined exposure estimates are based on the currently authorised uses, the proposed extension, and the EFSA Comprehensive Food Consumption Database. The mean dietary exposure to steviol glycosides ranges from 0.1 mg/kg bw/day in adults and the elderly, to 2.4 mg/kg bw/day in toddlers. Estimates at the 95th percentile of exposure range from 0.3 to 4.3 mg/kg bw/day in the elderly and toddlers, respectively. The Panel concluded that dietary exposure to steviol glycosides is considerably lower than that in the previous exposure assessment. Overall, the revised exposure estimates for all age groups remain below the ADI, except for toddlers at the upper range of the high level (95th percentile) estimates, in one country. Moreover, the Panel noted that table top sweeteners may represent an important source of exposure and therefore a MPL with a numerical value, rather than quantum satis, would be preferable, to allow for a more precise estimation of the potential maximum level of exposure from table top sweeteners

EFSA guidance on the submission of applications for authorisation of genetically modified plants under Regulation (EC) No 1829/2003

This document provides guidance to applicants for submitting an application for authorisation of genetically modified (GM) plants for food and feed uses, import and processing, and/or cultivation in the European Union under Regulation (EC) No 1829/2003. The EFSA submission guidance describes the community procedures in the European Union for handling GM plant applications, and provides instructions to applicants on how to prepare and present data in an application. It is supplemented with seven appendices providing templates of data presentation to be followed by applicants, including a completeness checklist. The earlier versions are now updated to account for requirements outlined in Implementing Regulation (EU) No 503/2013. Instructions for submission described in this EFSA guidance are applicable to all GM plant applications submitted under Articles 5, 11, 17 and 23 of Regulation (EC) No 1829/2003

Scientific Opinion on the re-evaluation of hexamethylene tetramine (E 239) as a food additive

Hexamethylene tetramine (HMT) is a food additive, currently only permitted in EU for use in Provolone cheese. The maximum permitted level is 25 mg/kg residual amount, expressed as formaldehyde, the break down product of HMT under acidic conditions. HMT has been previously evaluated by the Joint Expert Committee on Food Additives (JECFA, 1974) who established an ADI of 0.15 mg/kg bw/day based on a reproductive study with a NOEL of 15 mg/kg bw/day. Due to the limitations in the database the Panel could not identify a critical study and therefore to derive an ADI. However, the Panel noted that the exposure to formaldehyde from HMT of high level consumers of Provolone cheese equalled 18 µg formaldehyde/kg bw/day in adults and could be as high as 87 µg formaldehyde/kg bw/day in children according to a theoretical conservative assumption that all ripened cheese consumed was Provolone cheese. Considering the estimated exposure from the very limited permitted use, the toxicological database on HMT, the data from use of HMT therapeutically, the available oral toxicity and toxicokinetic data of formaldehyde and the magnitude of the potential effect on intracellular formaldehyde levels arising from this use of HMT, the Panel concluded that the use of HMT in Provolone cheese at the MPL of 25 mg/kg residual amount, expressed as formaldehyde, would not be of safety concern. However the Panel considered that any increase in the permitted uses of HMT or increases in the MPL of 25 mg /kg residual amount, expressed as formaldehyde would need detailed assessment which might require new toxicity data as well as use levels and/or an evaluation of its impact on formaldehyde levels in vivo

EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2013. Scientific Opinion on Flavouring Group Evaluation 93, Revision 1 (FGE.93Rev1)

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Scientific Opinion on the hazard assessment of endocrine disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment

Upon request of the European Commission, the Scientific Committee (SC) of the European Food Safety Authority reviewed existing information related to the testing and assessment of endocrine active substances (EASs) and endocrine disruptors (EDs). This work was conducted by a working group of experts in endocrinology, risk assessment and toxicology, together with observers from other EU agencies, namely EMA, ECHA and EEA. To distinguish between EDs and other groups of substances with different modes of action, it was concluded that an ED is defined by three criteria: the presence of i) an adverse effect in an intact organism or a (sub)population; ii) an endocrine activity; and iii) a plausible causal relationship between the two. As scientific criteria for adversity have not been generally defined, specific criteria for endocrine disrupting effects could not be identified. Hence, expert judgement is required to assess on a case-by-case basis the (eco)toxicological relevance of changes at the molecular to individual and/or (sub)population level following exposure to an EAS. The SC concluded that a reasonably complete suite of standardised assays for testing the effects of EASs is (or will soon be) available for the oestrogenic, androgenic, thyroid and steroidogenic modalities in mammals and fish, with fewer tests for birds and amphibians. Shortcomings in current tests and for other endocrine modalities and species were reviewed. Critical effect, severity, (ir)reversibility and potency aspects are part of the hazard characterisation of EDs. To inform on risk and level of concern for the purpose of risk management decisions, risk assessment (taking into account hazard and exposure data/predictions) makes best use of available information. Levels of concern are not determined exclusively by risk assessment but also by protection goals set by the risk management

EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on Flavouring Group Evaluation 74, Revision 3 (FGE.74Rev3): Consideration of Simple Aliphatic Sulphides and Thiols evaluated by the JECFA (53rd and 61st meeting) Structurally related to Aliphatic and Alicyclic Mono-, Di-, Tri-, and Polysulphides with or wi thout Additional Oxygenated Functional Groups from Chemical Group 20 evaluated by EFSA in FGE.08Rev5 (2012)

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 19 simple aliphatic sulphides and thiols evaluated by the JECFA at the 53rd meeting in 1999 and the 61st meeting in 2003. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. For nine substances [FL-no: 12.088, 12.179, 12.198, 12.212, 12.238, 12.239, 12.255, 12.257 and 12.291] considered in this FGE, the Panel concluded that they would pose “No safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered for the substances evaluated through the Procedure and for all nine substances, the information is adequate. Thus, the Panel concluded that nine substances [FL-no: 12.088, 12.179, 12.198, 12.212, 12.238, 12.239, 12.255, 12.257 and 12.291] do not give rise to safety concern at their levels of dietary intake, estimated on the basis of the MSDI approach. For 10 candidate substances in FGE.74Rev3 [FL-no: 12.009, 12.013, 12.020, 12.023, 12.045, 12.074, 12.155, 12.169, 12.241 and 12.280] evaluated through the Procedure, the Panel concluded that additional toxicity data are required

EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on Flavouring Group Evaluation 77, Revision 1 (FGE.77Rev1): Consideration of Pyridine, Pyrrole and Quinoline Derivatives evaluated by JECFA (63rd meeting)

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 22 pyridine, pyrrole and quinoline derivatives evaluated by the JECFA (63rd meeting). The revision of this consideration is made since additional toxicity data have become available for isoquinoline [FL-no: 14.001], pyrrole [FL-no: 14.041] and 2-acetylpyrrole [FL-no: 14.047]. The toxicity data on 2-acetylpyrrole should also cover 2-propionylpyrrole [FL-no: 14.068]. Further, additional genotoxicity data on 6-methylquinoline [FL-no: 14.042] have become available. The Panel concluded that for 6-methylquinoline [FL-no: 14.042], the new genotoxicity data did not clear the concern with respect to genotoxicity in vitro and accordingly the substance is not evaluated through the Procedure. For 18 substances [FL-no: 14.001, 14.004, 14.007, 14.030, 14.038, 14.039, 14.041, 14.047, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.068, 14.071, 14.072 and 14.164] considered in this FGE, the Panel agrees with the JECFA conclusion, “No safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach. For three substances [FL-no: 13.134, 14.045 and 14.046], additional toxicological data are still required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been evaluated, and the information is considered adequate for all the substances

EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on Flavouring Group Evaluation 82, Revision 1 (FGE.82Rev1): Consideration of Epoxides evaluated by the JECFA (65 th meeting)

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of five epoxides evaluated by the JECFA at the 65th meeting in 2005. This revision is made due to inclusion of one additional substance, beta-ionone epoxide [FL-no: 07.170], cleared for genotoxicity concern and due to additional toxicity data have become available for beta-caryophyllene epoxide [FL-no: 16.043]. Since publication of FGE.82 one substance epoxy oxophorone [FL-no: 16.051] is no longer supported for use as flavouring substances in Europe by Industry and will therefore not be considered any further. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. For four substances [FL-no: 16.015, 16.018, 16.040 and 16.043] the Panel agreed with the JECFA conclusion, “No safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach. For one substance [FL-no: 07.170] additional toxicity data are required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for four substances, the information is adequate; but for the substance [FL-no: 07.170] further information on stereoisomerism is required

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area