New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver.

Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit ceramide synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue-specific expression pattern, we postulated that the organ-specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5 mg FB1/kg body weight daily for 9 days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides. It also interact with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrate that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2, and CerS1.

New insights into mycotoxin mixtures: the toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic.

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DON

The emerging mycotoxin, enniatin B1, down-modulates the gastrointestinal toxicity of T-2 toxin in vitro on intestinal epithelial cells and ex vivo on intestinal explants.

Enniatins, the most prevalent emerging mycotoxins, represent an emerging food safety issue, because of their common co-occurrence with other fusariotoxins such as trichothecenes co-produced by Fusarium spp on field grains and because of their extensive prevalence in grains. In this study, the intestinal toxicity of enniatin B1 (ENN) alone and mixed with the most toxic trichothecene T-2 toxin (T2) was characterized by using two biological models from pig, the most sensitive species: the intestinal cell line IPEC1 (in vitro exposure) and jejunal explants (ex vivo exposure). Dose-dependent decreases in cell proliferation in IPEC1 and in the histopathological scores of explants were observed for ENN at µM-levels and for T2 at nM-levels, with IC50 values for ENN of 15.8 and 29.7 µM, and for T2 of 9.3 and 15.1 nM in vitro and ex vivo, respectively. Interaction analysis by probabilistic and by determinist approaches showed a less than additive effect both in vitro and ex vivo, at IC50 values, with increasing antagonism with decreasing concentrations of toxins. The results obtained by the determinist median-effect dose analysis and by the nonlinear regression analysis were concordant. All the median-effect doses estimated for IPEC cells were included in the IC50 confidence intervals of the nonlinear regression fitting. Given the occurrence of enniatins, potential synergy following the co-occurrence of enniatins and the major fusariotoxins, especially trichothecene B deoxynivalenol should be investigated.

Infant total diet study in France: Exposure to substances migrating from food contact materials.

A total diet study (TDS) was conducted in France to assess the health risks related to the chemicals in food of non-breastfed children under three years of age (Infant TDS). For the first time, substances coming from food contact materials, such as bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE) and its derivatives, some phthalates, and some ink photoinitiators, were targeted because of growing interest in these substances. Food samples were collected to be representative of the whole diet of non-breastfed children aged 1-36 months, and prepared as consumed prior to analysis. Dietary exposure was assessed for 705 representative children under three years of age. Generally, the substances from food contact materials were detected in few samples: 38% for BPA, 0% for BADGE and its derivatives, 0-35% for phthalates, 1.9% for benzophenone, and 0% for the other ink photoinitiators. Regarding exposure levels, the situation was deemed tolerable for BADGE and its hydrolysis products, di-isodecyl phthalate, dibutyl phthalate, butyl benzyl phthalate, bis(2-ethylhexyl) phthalate, and di-isononyl phthalate, benzophenone, and 4-methylbenzophenone. Only for BPA, the exposure levels of some children exceeded the lowest toxicological value established by the French Agency for Food, Environmental and Occupational Health & Safety at 0.083 µg.kg bw-1.d-1. The temporary tolerable daily intake of the European Food Safety Authority (EFSA), set at 4 µg.kg bw-1.d-1, was never exceeded. However, actual exposure to BPA was probably overestimated, as well as the associated risk, because the foods were sampled prior to the recent regulations banning BPA in food packaging. This study is the first worldwide to provide an estimate of infant food contamination levels and exposures of children under 3 years of age, based on a TDS approach. It therefore provides key data on the exposure of this particularly sensitive population to substances released from food contact materials, and presents useful data for studies evaluating exposure to mixtures or aggregated exposure.

Safety assessment of the substance N,N-bis(2-hydroxyethyl)stearylamine partially esterified with saturated C16/C18 fatty acids, for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of N,N-bis(2-hydroxyethyl)stearylamine partially esterified with saturated C16/C18 fatty acids (SABOFOG F1), FCM No 1081, which is intended to be used as an antistatic and anti-fog agent in all types of polymers at up to 2% w/w. It was requested for use in contact with dry food, acidic foods and alcoholic beverages (represented by simulants E, B and C, respectively) with storage up to 6 months at ambient temperature. The migration data provided did not enable the assessment of the safety of applications intended for contact with foods represented by simulants B and C. In the migrate into simulant E, the non-esterified N,N-bis(2-hydroxyethyl)stearylamine was the main constituent. Its mono- and di-esters migrated to a lower extent. According to the data provided, the Panel concluded that the substance does not raise concern for genotoxicity and accumulation in humans. Based on the results of 28-day oral toxicity study with SABOFOG F1 and on the 90-day oral toxicity study with the read-across substance bis(2-hydroxyethyl)oleylamine, the Panel considered the current SML(T) of 1.2 mg/kg food provided a margin sufficiently large to accommodate the uncertainties related to the read-across approach. Overall, the CEP Panel concluded that N,N-bis(2-hydroxyethyl)stearylamine, of which at least ■■■■■ is partially or fully esterified with saturated C16/C18 fatty acids is not of safety concern for the consumer when used at up to 2% (w/w) in all polymers intended for contact with foods represented by simulant E for up to 6 months at room temperature. Additionally, the migration of the sum of N,N-bis(2-hydroxyethyl)stearylamine and its mono- and di-ester, calculated as N,N-bis(2-hydroxyethyl)stearylamine, should not exceed 1.2 mg/kg, i.e. the SML(T) for FCM substances 19 and 20, in which also the migration of the mono- and di-ester of N,N-bis(2-hydroxyethyl)stearylamine should be included.

The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression.

'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

FELASA accreditation of education and training courses in laboratory animal science according to the Directive 2010/63/EU.

THE FOUR EU FUNCTIONS AND BEYOND: FELASA accredits courses that fulfil the requirements of Functions A, B, C and D as defined by EU Directive, Article 23, as well as for designated veterinarians and specialists in laboratory animal science. MODULARITY AND MOBILITY: Cohesive courses for Functions and for very specific topics are accredited, but flexibility and mobility are possible: a researcher can start his/her training with one FELASA accredited course and complete other modules with another. A course organizer will deliver a FELASA certificate relating to the successfully completed modules. ACCREDITATION PROCESS: The process consists of two major steps: (1) a review of full course documentation provided by the applicant will lead, if successful, to FELASA accreditation. The course is posted on the FELASA website as 'FELASA accredited' and the course provider can deliver FELASA certificates upon successful completion of the course; (2) successful accreditation is followed by an on-site course audit. In the case of a negative outcome of the audit, FELASA accreditation is withdrawn, the course is deleted from the list of FELASA accredited courses and FELASA certificates cannot be issued. To ensure that quality is maintained, continuation of accreditation requires regular revalidation.

Dietary exposure to perfluoroalkyl acids, brominated flame retardants and health risk assessment in the French infant total diet study.

Perfluoroalkyl acids (PFAAs) and brominated flame retardants (BFRs) are widely used and present in human food. Due to the increased susceptibility to pollutants of the young children, we conducted a total diet study focusing on this population. Around 200 baby and common food composite samples, prepared "as consumed", have been analysed for PFAAS, hexabromocyclododecanes, polybrominated biphenyls, polybrominated diphenyl ethers and tetrabromobisphenol A. The dietary exposure of 705 children aged 1-36 months was assessed. PFAAS were detected only in one fish sample. Detection rates varied from 4 to 93% for BFRs, depending on the congeners. Regarding the provisional health-based guidance values set by EFSA in 2018 for PFOA and PFOS at 0.8 and 1.8 ng kg bw-1.d-1, respectively, 20-100% of children exceeded them, depending on the age. Efforts should be made to decrease the PFAAs contamination of common foods. This study also highlighted that for other PFAAs, toxicological studies are needed to set dietary health-based guidance values, to assess their related health risk. Conversely, dietary exposures to BRFs were much lower than the respective health based guidance values or margins of safety were high enough, and consequently not considered at-risk due to very low contamination of the infant specific foods.

Safety assessment of the substance poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBH), CAS No 147398-31-0 and food contact material (FCM) substance No 1059. This biodegradable copolymer is produced by fermentation of palm oil using a genetically modified microorganism (Cupriavidus necator). Overall migration was up to 5.4 mg/kg. Oligomers are hydroxyl-terminated or with crotyl- and hexenyl end-groups from dehydration of hydroxyl end-groups. In the absence of calibration standards, the total oligomer migration was set at the overall migration values. Other degradation products are crotonic acid and (E)-2-hexenoic acid. Crotonic acid is authorised for use in FCMs with a specific migration limit (SML) of 0.05 mg/kg food. For (E)-2-hexenoic acid, no indication for genotoxicity was identified by the EFSA CEF Panel in its group evaluation of flavouring substances in FGE.05Rev2 (EFSA CEF Panel, 2010b). The other migrating substances detected, ■■■■■, are from the authorised substance 'palm oil and/or palm fatty acid distillate' (FCM substance No 9) used as a carbon source for the fermentation and do not give rise to safety concern. A PHBH oligomer mixture was synthesized to simulate that migrating. It did not give rise to concern for genotoxicity. From the repeated dose 90-day oral toxicity study in rats, the Panel identified the no-observed-adverse-effect level (NOAEL) at the highest dose tested in males, 1,364 mg/kg body weight (bw) per day. The Panel concluded that the potential for bioaccumulation of oligomers is low. Overall, the CEP Panel concluded that the substance PHBH is not of safety concern for the consumer if it is used alone or blended with other polymers in contact with all kinds of food during more than 6 months at room temperature or below, including hot-fill or a short heating up phase. The specific migration of all oligomers < 1,000 Da should not exceed 5 mg/kg food. The migration of crotonic acid should not exceed the SML of 0.05 mg/kg food. As the migration of (E)-2-hexenoic acid can be expected to be always lower than that of crotonic acid, no individual restriction is necessary.

Safety assessment of the substance, montmorillonite clay modified with hexadecyltrimethylammonium bromide, for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of montmorillonite clay modified with hexadecyltrimethylammonium bromide (HDTA) when used as an additive at up to ■■■■■ in polylactic acid (PLA) bottles intended for contact with water for long-term storage at ambient temperature or below. The modified clay, which 90% w/w of the particles have a dimension of 33.1 µm or less and the average size is 9 µm, has a layered structure with layers of a thickness below 100 nm. When incorporated in PLA, nanosized layers can be dispersed in the matrix, but are not expected to migrate. Thermal degradation is not expected at the maximum manufacturing temperature. No loss of integrity of the PLA surface due to interaction with bottled water was observed. The overall migration was very low. No migration of HDTA was detected at the limit of detection ■■■■■. Migration of aluminium was below or at the limit of detection ■■■■■, which would conservatively correspond to approximately ■■■■■. Comparative analysis of bottled water with and without the modified clay did not reveal additional peaks corresponding to impurities identified in the modifier and/or in the modified clay. Moreover, ■■■■■, and the modifier HDTA have been evaluated and authorised. Therefore, the CEP Panel concluded that the substance montmorillonite clay modified with HDTA bromide is not of safety concern for the consumer if the substance is used as an additive at up to ■■■■■ in PLA plastic bottles and other containers intended for long-term storage of water at ambient temperature or below, as requested by the applicant.

Safety assessment of the substance trimellitic acid, tris (2-ethylhexyl) ester, for use in food contact materials.

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes and Processing aids (CEP Panel) is on the safety assessment of trimellitic acid, tris(2-ethylhexyl) ester, intended to be used as a plasticiser in the manufacture of soft poly(vinyl chloride) (PVC) materials and articles, such as wrap films (single uses) and tubing (repeated uses) at up to approximately 10% and 40%, respectively. Under the tested conditions, the substance migrated up to 165 µg/kg food from wrap films and was not detected in food simulant in contact with tubing. Based on the three reported in vitro genotoxicity studies, the Panel concluded that the substance does not raise concern for genotoxicity. The lowest no observed adverse effect level (NOAEL), derived from a 90-day oral toxicity study, was 225 mg/kg body weight (bw) per day. Based on data on toxicokinetic and metabolism, the substance does not give rise to concern for accumulation in humans. The substance does not cause developmental effects as induced by phthalic acid, bis(2-ethylhexyl) ester (DEHP). Assuming that impurities migrate pro-rata to a migration of the substance up to 5 mg/kg food, their estimated migration does not raise a safety concern. The Panel concluded that the substance does not raise safety concern for the consumer when used in the manufacture of soft PVC under the conditions requested by the applicant for (i) single use wrap films in contact with food for which simulants A, B and D1 are assigned, as well as (ii) tubing for repeated contacts with food for which simulants A and B are assigned. Overall, the use of the substance does not raise a safety concern if its migration does not exceed 5 mg/kg food. Due to the additional contribution from other sources of exposures, the application of an allocation factor should be considered.

Safety assessment of the substance, titanium dioxide surface treated with fluoride-modified alumina, for use in food contact materials.

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) is a safety assessment of the additive titanium dioxide surface treated with fluoride-modified alumina, a defined mixture of particles of which ■■■■■% in number have a diameter in the range of 1-100 nm. It is intended to be used as filler and colourant up to 25% w/w in potentially all polymer types. Materials and articles containing the additive are intended to be in contact with all food types for any time and temperature conditions. The data provided demonstrate that the additive particles stay embedded even in swollen polar polymers such as polyamide, and do not migrate. Moreover, the additive particles resisted release by abrasion and did not transfer into a simulant for solid/dry foods. Thus, the additive particles do not give rise to exposure via food and to toxicological concern. Migration of solubilised ionic fluoride and aluminium occurs from the surface of the additive particles and particularly from swollen plastic. The Panel concluded that the substance does not raise safety concern for the consumer if used as an additive up to 25% w/w in polymers in contact with all food types for any time and temperature conditions. However, uses in polar polymers swelling in contact with foodstuffs simulated by 3% acetic acid should be limited to conditions simulated by contact up to 4 h at 100°C. This is due to the fact that when used at 25%, and contact was followed by 10 days at 60°C, the migration of aluminium and fluoride largely exceeded the specific migration limit (SML) of 1 and 0.15 mg/kg food, respectively. The Panel emphasises that the existing SMLs for aluminium and fluoride should not be exceeded in any case.

Alteration of mammary gland development by bisphenol a and evidence of a mode of action mediated through endocrine disruption.

The development and function of the mammary gland are endocrine-dependent processes, depending on the stage of development. Foetal and/or postnatal exposure to low doses of BPA alters tissue organisation through epithelial proliferation and stroma-epithelial interactions. BPA also alters the expression of E2-dependent epithelial and stroma transcriptomes. Several signalling pathways are consistent with the observed phenotype: proliferation and apoptosis, a focal adhesion pathway indicating changes in biomechanical properties of the extracellular matrix, and immune function. Some of BPA's effects are reversed by oestrogen and/or GPER inhibitors. BPA also alters the expression of epigenetic marks (EZH2, HOTAIR), which would explain the delayed effect of foetal BPA exposure. In conclusion, experimental evidence shows that pre- or postnatal BPA exposure consistently causes endocrine modifications in the mammary tissue of different animal species, disrupting stromal-epithelial interactions and ultimately increasing its susceptibility to carcinogens. An interspecies comparison highlights why and how these effects apply to humans.

Safety assessment of the active substance selenium nanoparticles, for use in active food contact materials.

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) deals with the safety assessment of selenium nanoparticles, FCM substance No 1070, which is intended to be used as an antioxidant. Selenium nanoparticles are incorporated into the adhesive middle layer of multilayer laminates with an outside polyethylene terephthalate (PET) layer and an inner polyolefin (food contact) layer. The final materials are intended to be used for contact with all food types that are susceptible to oxidation. The specific migration of total selenium was tested using multilayer pouches containing selenium nanoparticles at 0.002 mg/dm2 and filled with 3% acetic acid and 20%, 50% or 95% ethanol for 10 days at 60°C. In all tests, migration of selenium was not detectable. Taking into account current knowledge on the diffusional properties of nanoparticles in polymers, the CEF Panel concluded that there is no safety concern for the consumer if selenium nanoparticles are used in multilayer films and separated from the food by a polyolefin food contact layer for any type of food and under any food contact conditions.

Safety assessment of the substance isobutane, for use in food contact materials.

The substance isobutane is intended to be used as a foaming agent at max 4.5% to produce expanded polystyrene (EPS) to be used for packaging foods, such as fruits, vegetables, meat, fish and cheese, at room temperature or lower. Isobutane is approved in Europe as a food additive (E 943b) to be used quantum satis as a gas propellant only in vegetable oil pan spray (for professional use only) and water-based emulsion spray according to Regulation (EC) No 1333/2008. The purity requirements for the use of isobutane as a food additive are described in Commission Regulation (EU) No 231/2012. The substance is a gas at room temperature. It is a saturated hydrocarbon, obtained with a high level of purity, and is not expected to react under the processing conditions used to make foamed polystyrene materials and articles. Data on migration of isobutane from trays at 20°C for 10 days ranged from 0.2 to 0.4 mg/kg food. Considering the intended applications, estimated exposure is extremely low based on migration data. In the absence of genotoxicity alerts and given the very low toxicity following repeated exposure with no observed adverse effect concentration (NOAEC) of several thousands of mg/m3 by inhalation, it was considered that the use of isobutane as a foaming agent, at the expected exposure from food, does not raise a safety concern.

Safety assessment of the active substance polyacrylic acid, sodium salt, cross-linked, for use in active food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of polyacrylic acid, sodium salt, cross-linked, FCM substance No 1015, which is intended to be used as a liquid absorber in the packaging of fresh or frozen foods such as meat, poultry and seafood as well as fresh fruits and vegetables. Specific migration tests were not performed due to the high absorption of liquids by the substance. The Panel noted that if polyacrylic acid, sodium salt, cross-linked is used not in direct contact with food and placed in a pad under conditions where its absorption capacity is not exceeded, then no migration is to be expected and therefore no exposure from the consumption of the packed food is expected. The Panel also considered that the non-cross-linked polymer and the cross-linkers do not raise a concern for genotoxicity. The CEP Panel concluded that the use of this polyacrylic acid, sodium salt, cross-linked, does not raise a safety concern when used in absorbent pads in the packaging of fresh or frozen foods. The absorbent pads must be used only under conditions in which the absorption capacity of the active substance is not exceeded and direct contact with food is excluded.

Safety assessment of the substance Ln 1,4-benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the additive Ln 1,4-benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) for use in food contact materials. It is a family of mixtures combining the four lanthanides lanthanum (La), europium (Eu), gadolinium (Gd) and/or terbium (Tb) in different proportions as their 1,4-benzene dicarboxylate complexes, used as a taggant in plastics for authentication and traceability purposes. The powdered additive, not in nano form, is intended to be used at up to 100 mg/kg in polyethylene, polypropylene and polybutene. Materials and articles made of these plastics are intended for contact with all foods types at up to 4 h/100°C or for long-term storage at ambient temperature. In tests with food simulants, migration of each Ln was below 5 µg/kg. The Panel considered that irrespective of the composition of the lanthanides, these would dissociate completely from the terephthalic acid salt under aqueous conditions. Evaluation of the genotoxicity studies provided on the individual complexes (La, Eu, Gd and Tb) and on their mixture, taken together with data available in the scientific literature, allows ruling out concern for genotoxicity. Consequently, the CEP Panel concluded that the substance Ln 1,4-benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) does not raise a safety concern for the consumer under the proposed conditions of use and if the migration of the sum of the four lanthanides in ionic form does not exceed 50 µg/kg food.

Safety assessment of the active substances carboxymethylcellulose, acetylated distarch phosphate, bentonite, boric acid and aluminium sulfate, for use in active food contact materials.

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety evaluation of the active substances carboxymethylcellulose, acetylated distarch phosphate (FCM substance No 1071), bentonite, boric acid and aluminium sulfate (FCM substance No 1072). The mixture is intended to be used as a liquid absorber in the packaging of perishable foods to extend their shelf-life. All substances have been evaluated and approved for use as additives in plastic food contact materials and/or as food additives. Migration of boron into foods was up to 0.7 mg/kg food. Migration of aluminium was not detected (limit of detection (LOD) of 0.001 mg/kg). The CEF Panel concludes that the substances carboxymethylcellulose, acetylated distarch phosphate, bentonite, boric acid and aluminium sulfate are not of safety concern for the consumer when used as active components in moisture and liquid absorbers. The absorbent pads must be used under conditions in which direct contact between the active mixture and the food is avoided and the fluid absorption capacity of the absorber is not exceeded.

SUPERSEDED: Safety assessment of the substance poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) for use in food contact materials.

This opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety assessment of poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate), Chemical Abstracts Service (CAS) No 147398-31-0 and food contact material (FCM) substance No 1059, for contact with dry/solid food. This biodegradable (co)polymer is produced by fermentation of palm oil using a genetically modified microorganism (Cupriavidus necator). No migration of oligomers into food simulant E (10 days at 40 and 60°C) was found at a detection limit per single oligomer of 5 µg/kg food. Migration of the degradation product crotonic acid was 8 and 25 µg/kg at the two test temperatures, respectively. The other migrating substances detected, ■■■■■, likely originated from or are related to the authorised substance (FCM No. 9) 'palm oil and/or palm fatty acid distillate' used as carbon source for the fermentation. At the migration levels reported, these migrants do not give rise to safety concern. No genotoxicity data are required for poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) because of its high molecular weight. The fraction below 1,000 Da is 0.5%. The major monomeric unit in the copolymer, 3-hydroxybutyric acid, is an intermediate in fatty acid metabolism. The minor monomeric unit, 3-hydroxyhexanoic acid, tested negative for bacterial gene mutations. Degradation products, which may be present in the (co)polymer, are crotonic acid and (E)-2-hexenoic acid. Crotonic acid is authorised for use in FCM with a specific migration limit (SML) of 0.05 mg/kg food; for (E)-2-hexenoic acid, no indication for genotoxicity was identified by the EFSA CEF Panel in its 2010 group evaluation of flavouring substances in FGE.05Rev2. The CEF Panel concluded that the substance poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) is not of safety concern if used alone or in blends with other polymers for contact with dry/solid food. If the SML of crotonic acid is met, migration of (E)-2-hexenoic acid will also not exceed 0.05 mg/kg food.

Regulatory identification of BPA as an endocrine disruptor: Context and methodology.

BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies. The analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases. From this extensive database, it was considered important to engage in a detailed analysis so as to provide specific and strong evidences of ED while reflecting accurately the complexity of the response as well the multiplicity of adverse effects. An appropriate delineation of the scope of the analysis was therefore critical. Four effects namely, alterations of estrous cyclicity, mammary gland development, brain development and memory function, and metabolism, were considered to provide solid evidence of ED-mediated effects of BPA.