In the 1950s, the introduction of organochlorine insecticides containing active ingredients such as lindane, dieldrin, endrin, chlordane, heptachlor, endosulfan and toxaphene was extremely effective in combating a wide variety of crop and livestock pests. In the 1980s, the inhibitory molecular action causing convulsions and neurotoxicity was identified as binding to the pre-synaptic γ-aminobutyric acid-binding receptor A (GABAA)-regulated chloride channel, near to the picrotoxinin-binding site, antagonising membrane hyperpolarisation and inward chloride current. However, it became evident that the properties that made them excellent insecticides might also make them toxic to humans and non-target animal species. Accidental, occupational and suicidal convulsions occurred in humans, and there were marked effects on wildlife, especially in birds, due to accumulation up the food chain. Differential metabolism was an important factor determining the differences between individual insecticides. After a few decades of use, these pesticides were phased out and banned. The now-established multiple aspects of their toxicity in vivo or in vitro continue to be of concern regarding their possible adverse effects on human health through environmental exposure.

Regulation of 5-aminolevulinate synthase 1 (ALAS1) for nonerythroid heme is critical for respiration, cell signaling mechanisms and steroid/drug metabolism. ALAS1 is induced in some genetic disorders but unlike other genes in the heme pathway, a gene variant of ALAS1 associated with inherited disease has not been reported. BALB/c mice carrying a null ALAS1 allele caused by a βGEO insert were developed and used to determine the consequences of heme demand of a semi gene copy number. Homozygous disruption of ALAS1 (−/−) was lethal for embryo development post day 6.5 but expression in heterozygotes (+/−) was sufficient for the number of offspring and survival. In both wild type (WT +/+) and +/− mice expression of ALAS1 RNA was greatest in liver and harderian gland and much lower in kidney, lung, heart, brain and spleen. The effects of one WT ALAS1 allele in +/− mice on mRNA levels in liver and harderian gland were less marked compared to brain and other organs that were examined. Many other genes were up-regulated by heterozygosity in liver and brain but to a minimal extent. Hepatic heme oxygenase 1 (HMOX1) mRNA expression was significantly lower in +/− mice but not in brain. No elevated translation of WT allele ALAS1 mRNA was detected in +/− liver as a compensatory mechanism for the disabled allele. Fasting induced ALAS1 mRNA in both WT and +/− mice but only in +/− was this manifest as increased ALAS1 protein. The hepatic protoporphyria-inducing drug 4-ethyl-DDC caused induction of hepatic ALAS1 mRNA and protein levels in both WT and +/− mice but markedly less in the mice with only one intact allele. The findings illustrate the complex response of ALAS1 expression for heme demand but limited evidence that upregulation of a wild type allele can compensate for a null allele.

The food enzyme xylanase (EC 3.2.1.8) is produced with the genetically modified Trichoderma reesei strain RF5703 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. The food enzyme is intended to be used in brewing processes and grain treatment for the production of starch and gluten fractions. Since residual amounts of the food enzyme are removed during grain treatment, dietary exposure was only calculated for brewing processes. Based on the maximum recommended use levels for brewing processes, dietary exposure to the food enzyme-Total Organic Solids (TOS) was estimated to be up to 0.023 mg TOS/kg body weight (bw) per day. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level at the highest dose tested of 1,000 mg TOS/kg bw per day, resulting in a high margin of exposure of at least 43,000. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended condition of use, the risk of allergic sensitisation and elicitation reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood of such reactions to occur is considered to be low. Based on the data provided and the removal of TOS during the intended food production process, the Panel concluded that this food enzyme does not raise safety concerns under the intended conditions of use. (C) 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

The food enzyme with xylanases (4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) and glucanases active against beta-1,4 linkages is produced with the non-genetically modified fungus Disporotrichum dimorphosporum strain DXL by DSM Food Specialities B.V. The food enzyme is intended to be used in brewing processes. Based on the maximum use level and individual data from the EFSA Comprehensive European Food Database, dietary exposure to the food enzyme-Total Organic Solids (TOS) was estimated to be up to 0.167 mg TOS/kg body weight (bw) per day. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level (NOAEL) at the highest dose of 199 mg TOS/kg bw per day that, compared with the estimated dietary exposure, results in a high Margin of Exposure of at least 1,100. Similarity of amino acid sequences of the identified xylanases and beta-glucanases to those of known allergens was searched. No matches were found for two endo-1,4-beta-glucanases and two endo-1,4-beta-xylanases. However, for a third endo-beta-1,4-glucanase the search resulted in matches with three mite protein sequences. While incidental cases of allergic reactions to endo-1,4-beta-xylanases and beta-glucanases have been reported after inhalation in respiratory sensitised individuals in the workplace, no allergic reactions to xylanases or beta-glucanases have been reported in the literature after oral exposure. The Panel considered that, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use. (C) 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

The food enzyme is a D-xylose aldose-ketose-isomerase (EC 5.3.1.5) produced with the genetically modified Streptomyces rubiginosus strain DP-Pzn37 by Danisco US Inc. Although the production strain contains antibiotic resistance genes, the food enzyme was shown to be free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in an immobilised form for the isomerisation of glucose for the production of high fructose syrups. Residual amounts of total organic solids (TOS) are eliminated by the use of an immobilised food enzyme and further removed by the purification steps applied during the production of high fructose syrups using the immobilised enzyme; consequently, dietary exposure was not calculated. Genotoxicity tests did not raise safety concerns. The systemic toxicity was assessed by a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 85.2 mg TOS/kg body weight (bw) per day, the highest dose tested. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood is considered to be low. Based on the data provided, the immobilisation process and the removal of total organic solids during the production of high fructose syrups, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use. (C) 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Heme Biology, pp. 113-161 (2020) No AccessChapter 6: HEME IN BRAIN FUNCTIONS: POSITIVE AND NEGATIVE ROLESTatyana Chernova and Andrew G. SmithTatyana Chernova and Andrew G. Smithhttps://doi.org/10.1142/9789811211294_0006Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: The following sections are included: Overview Heme synthesis and disturbances pertinent to neuronal cells Contrasting roles of heme as a physiological and toxic molecule Neurotoxic effects of heme Neuroglobin, hemoglobin and their neuroprotective roles Heme oxygenases and neurodegenerative diseases: where does heme come from? Regulatory roles for heme in neurons Neurotrophic effects of heme Heme can act as a gas-sensing regulator of brain functions Heme in circadian pathways Heme and brain aging: role of heme for protection from drug-induced neurotoxicity Does sufficient availability of heme delay aging? Deficiency of heme and Alzheimer's disease Summary References FiguresReferencesRelatedDetails Heme BiologyMetrics History PDF download

The food enzyme is a glucose isomerase (d-xylose aldose-ketose-isomerase; EC 5.3.1.5) produced with a non-genetically modified Streptomycesmurinus strain NZYM-GA by Novozymes A/S. The glucose isomerase is intended only to be used in an immobilised form in glucose isomerisation for the production of high fructose syrups. Residual amounts of total organic solids are removed by the purification steps applied during the production of high fructose syrups using the immobilised enzyme; consequently, dietary exposure was not calculated. Genotoxicity tests did not raise a safety concern. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panelconsidered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood to occur is considered to be low. Based on the data provided, the immobilisation process and the removal of total organic solids during the production of high fructose syrups, the Panelconcluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

The food enzyme lysophospholipase (EC 3.1.1.5) is produced with the genetically modified Trichoderma reesei strain RF7206 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. The lysophospholipase food enzyme is intended to be used in starch processing for the production of glucose syrups. Residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, consequently, dietary exposure was not calculated. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panelidentified a no observed adverse effect level at the highest dose tested of 927mg TOS/kg body weight (bw) per day. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panelconsidered that, under the intended condition of use, the risk of allergic sensitisation and elicitation reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood of such reactions to occur is considered to be low. Based on the data provided and the removal of TOS during the intended food production process, the Panelconcluded that this food enzyme does not raise safety concerns under the intended conditions of use.

The food enzyme considered in this opinion is aquaiysin 1 (EC 3,4.21.111), produced from the genetically modified strain Bacillus subtilis LMGS 25520 by Puratos NV. The production strain was not detected in the food enzyme. Aquaiysin 1 is intended to be used in baking processes. Based on the maximum use level recommended and individual consumption data from the EFSA Comprehensive European Food Consumption Database, dietary exposure to the food enzyme total organic solids (TOS) was estimated to be up to 2.13 mg TOS/kg body weight per day in European populations. Genotoxicity tests indicated no genotoxic concerns. The allergenicity was evaluated by searching for similarity of the amino acid sequence to those of known allergens and 23 matches were found (20 respiratory and 3 dermal allergens). However, the Panel considered that there are no indications for food allergic reactions to the food enzyme. The genetic modifications performed, the manufacturing process, the compositional and biochemical data, the allergenicity and the genotoxicity assessment did not raise safety concerns. The Panel considered the margin of exposure (MOE) calculated from the no observed adverse effect level (INOAEL) determined from the repeated dose 90-day oral toxicity study and the estimated dietary exposure as insufficient to conclude that there is no safety concern for this food enzyme under the intended conditions of use. The Panel noted that recombinant DNA was present in all batches of the food enzyme tested. (C) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Abstract The food enzyme is an endo‐1,4‐β‐xylanase (EC 3.2.1.8) produced with a genetically modified strain of Aspergillus niger (strain XEA), by DSM Food Specialities B.V. The food enzyme is intended to be used in baking and brewing processes. Based on maximum use levels recommended for the food processes and individual consumption data from the EFSA Comprehensive European Food Consumption Database, dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 0.310 mg TOS/kg body weight per day in European populations. Genotoxicity tests with the food enzyme did not indicate a genotoxic concern. A repeated dose 90‐day oral toxicity study in rodents, carried out with this endo‐1,4‐β‐xylanase, showed no concern with respect to systemic toxicity. The allergenicity was evaluated by searching for similarity of the amino acid sequence to those of known allergens; no match was found. The Panel considers that there are no indications for allergic sensitisation and elicitation reactions by dietary exposure to the food enzyme endo‐1,4‐β‐xylanase. Based on the microbial source, the genetic modifications performed, the manufacturing process, the compositional and biochemical data provided, the dietary exposure assessment, the findings in the toxicological studies and the allergenicity assessment, the Panel concludes that this food enzyme does not give rise to safety concerns under the intended conditions of use.

The food enzyme is a glucose oxidase (beta-o-glucose:oxygen 1-oxidoreductase; EC 1.1.3.4) produced with a genetically modified strain of Aspergillus oryzae strain NZYM-KP by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme does not contain the production organism or DNA; therefore, there is no safety concern for the environment. The glucose oxidase is intended to be used in baking processes. Based on the maximum use levels recommended and individual consumption data from the EFSA Comprehensive European Food Consumption Database, dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.156 mg TOS/kg body weight (bw) per day in European populations. The food enzyme did not induce gene mutations in bacteria or chromosome aberrations in human lymphocytes. The subchronic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rodents. A no-observed-adverse-effect level was derived (341 mg TOS/kg bw per day), which compared with the estimated dietary exposure results in a sufficiently high margin of exposure. The allergenicity was evaluated by comparing the amino acid sequence to those of known allergens and one match with a fungal contact allergen was found. The Panel considered that, under the intended condition of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood is considered low. Based on the microbial source, the genetic modifications, the manufacturing process, the compositional and biochemical data, the estimated dietary exposure and the findings in the toxicological studies, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use. (C) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Abstract The food enzyme considered in this opinion is a glucan 1,4‐α‐maltohydrolase (maltogenic α‐amylase; EC 3.2.1.133) produced with the genetically modified Bacillus subtilis strain MAM by the company DSM Food Specialties B. V. The food enzyme contains neither the production microorganism nor recombinant DNA; therefore, no environmental risk assessment is required. However, the Panel emphasises that this conclusion only covers the food enzyme recovered via filter press. The glucan 1,4‐α‐maltohydrolase is intended for use in baking processes. Based on the maximum use levels recommended and individual consumption data from the EFSA Comprehensive European Food Consumption Database, dietary exposure to the food enzyme‐total organic solids (TOS) was estimated to be up to 0.175 mg TOS/kg body weight (bw) per day in European populations. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rodents. A no observed adverse effect level (NOAEL) was derived (986 mg TOS/kg bw per day for both males and females), which, compared with the dietary exposure, results in a sufficiently high margin of exposure. The allergenicity was evaluated by comparing the amino acid sequence to those of known allergens; one match was found. However, the Panel considered that there are no indications for food allergic reactions to this glucan 1,4‐α‐maltohydrolase by dietary exposure. No safety concerns were identified in relation to the genetic modifications, the manufacturing process, the compositional data provided, as well as the exposure, allergenicity and systemic toxicity assessments. However, owing to the incompleteness of the genotoxicity data, the Panel is not able to conclude on the safety of the food enzyme.

Abstract The food enzyme considered in this opinion is an endo‐1,4‐β‐xylanase (EC 3.2.1.8) produced with a genetically modified Bacillus subtilis strain from Puratos N.V. (Belgium). The genetic modifications do not raise safety concerns. The food enzyme contains neither the production organism nor recombinant DNA. The endo‐1,4‐β‐xylanase is intended to be used in baking processes. Based on the maximum use levels recommended for the baking processes, dietary exposure to the food enzyme–total organic solids (TOS) was estimated on the basis of individual data from the EFSA Comprehensive European Food Consumption Database. This exposure estimate is up to 0.008 mg TOS/kg body weight per day in European populations. The food enzyme did not induce gene mutations in bacteria nor clastogenic activity in human lymphocytes. Therefore, there is no concern with respect to genotoxicity. The subchronic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rodents. A no observed adverse effect level was derived, which, compared with the dietary exposure, results in a sufficiently high margin of exposure. The allergenicity was evaluated by searching for similarity of the amino acid sequence to those of known allergens; no matches were found. The Panel considered that there are no indications for food allergic reactions to this xylanase. Based on the microbial source, genetic modifications performed, the manufacturing process, the compositional and biochemical data provided, the findings in the toxicological studies and allergenicity assessment, this food enzyme does not give rise to safety concerns under the intended conditions of use.

The haem biosynthetic pathway is of fundamental importance for cellular metabolism both for the erythroid and nonerythroid tissues. There are several genetic variants of the pathway in the human population that cause dysfunction of one or other of the enzymes resulting in porphyrias of varying severity. Serious chronic hepatic and systemic diseases may result. Some of these can be precipitated by exposure to drugs including hormones, barbiturates and antibiotics, as well as alcohol and particular chlorinated aromatic chemicals. In experimental animals some of the steps of this pathway can also be severely disrupted by a variety of environmental chemicals, potential drugs and pesticides, especially in the liver, leading to the accumulation of uroporphyrins derived from the intermediate uroporphyrinogens or protoporphyrin IX, the immediate precursor of haem. With some of these chemicals this also leads to cholestasis and liver cell injury and eventually hepatic tumours. The review evaluates the available evidence linking hepatic porphyria with carcinogenesis in naturally occurring human genetic conditions and in chemically-induced porphyrias in laboratory animals. The existing data showing gender, strain, and species differences in sensitivity to the chemical-induced porphyrias, liver injury and liver tumours are discussed and the role that transgenically altered mouse models have played in defining the varying mechanisms. Finally, the review proposes a novel, unifying hypothesis linking the hepatotoxicity induced by the accumulation of various porphyrins, with the increased risk of developing hepatic cancer as a long term consequence.

Abstract The food enzyme considered in this opinion is an endo‐1,4‐β‐xylanase (4‐β‐d‐xylan xylanohydrolase; EC 3.2.1.8) produced from the genetically modified Bacillus subtilis strain LMG S‐27588 by the company Puratos N. V. The production strain was not detected in the food enzyme. The endo‐1,4‐β‐xylanase is intended to be used in baking processes. Based on the maximum use levels recommended and individual consumption data from the EFSA Comprehensive European Food Consumption Database, dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 0.325 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests with the food enzyme indicated no genotoxic concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rodents. A no observed adverse effect level (NOAEL) was derived (443 mg TOS/kg bw per day), which, compared with the dietary exposure, results in a sufficiently high margin of exposure. The allergenicity was evaluated by comparing the amino acid sequence to those of known allergens; no match was found. The Panel considered that there are no indications for food allergic reactions to this endo‐1,4‐β‐xylanase by dietary exposure. Based on the genetic modifications, the manufacturing process, the compositional and biochemical data, the dietary exposure assessment, the findings in the toxicological studies and allergenicity assessment, the Panel concludes that this food enzyme does not give rise to safety concerns under the intended conditions of use. The Panel noted that recombinant DNA was present in all batches of the food enzyme tested.

Abstract The food enzyme considered in this opinion is a 4‐α‐d‐glucan maltohydrolase (EC 3.2.1.2) obtained from grain of barley (Hordeum vulgare), by the companies Genencor International B.V. and Senson Oy. This β‐amylase is intended to be used in several food‐manufacturing processes: baking and brewing processes, distilled alcohol production, and starch processing for the production of glucose syrups. The compositional data provided for the food enzyme were considered sufficient. The manufacturing process did not raise safety concerns. Based on the maximum use levels recommended for the respective food processes, dietary exposure to the food enzyme–total organic solids (TOS) was estimated on the basis of individual data from the EFSA Comprehensive European Food Consumption Database. This exposure estimate is similar to or lower than the exposure to a fraction of barley comparable to the food enzyme–TOS, resulting from the consumption of barley‐derived foods. As the food enzyme is derived from edible parts of barley, in line with the requirements of the guidance document on food enzyme assessment, the Panel accepted that there was no need for the provision of toxicological data for this food enzyme and the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use. Considering the potential for allergenicity, the gluten content of the food enzyme was below the detection limit of the analytical method, which is well below the level of 20 mg/kg for ‘gluten‐free’ products. The amino acid sequence of the β‐amylase was compared to those of known allergens and no match was found. The food enzyme β‐amylase from barley is an occupational respiratory allergen and may contain low levels of other allergenic barley proteins that may trigger adverse reactions upon oral challenges in individuals with an oral sensitisation to cereals. The Panel considers that dietary exposure to the food enzyme β‐amylase from barley may result in incidental cases of food allergic reactions.

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to deliver a scientific opinion on the implications for human health of the flavouring rum ether [FL-no: 21.001] in the Flavouring Group Evaluation 500 (FGE.500), according to Regulation (EC) No 1331/2008 and Regulation (EC) No 1334/2008 of the European Parliament and of the Council. Rum ether is a complex mixture of volatile substances obtained by distillation of the reaction products of pyroligneous acid and ethyl alcohol under oxidative conditions in the presence of manganese dioxide and sulfuric acid. A total of 84 volatile constituents have been reported by the applicant. It is a colourless liquid with a rum-like odour and flavour. Its major uses are in the food categories beverages, confectionery and baked goods. The Panel decided to apply a congeneric group-based approach. The 84 reported constituents were allocated to 12 congeneric groups, based on structural and metabolic similarity. For eight of the congeneric groups, the Panel concluded that there is no safety concern at the intended conditions of use. However, the Panel concluded that substances in congeneric group 1 (ethanol and acetaldehyde) and congeneric group 12 (furan) are carcinogenic and genotoxic. The Panel also identified genotoxicity concerns for substances in congeneric group 3 (3-pentene-2-one). The exposure for congeneric group 10 (ethers of various structures) was above the Threshold of Toxicological Concern (TTC) applicable for this group, but a point of departure or health based guidance value that covers all the substances in this group could not be identified. The Panel concluded that according to the overall strategy for the risk assessment of flavouring substances, the presence of genotoxic substances as process-derived constituents of rum ether is of safety concern.

Abstract The food enzyme considered in this opinion is a pullulanase (pullulan 6‐α‐glucanohydrolase; EC 3.2.1.41) produced with a non‐genetically modified Pullulanibacillus naganoensis (strain AE‐PL) by Amano Enzyme Inc. (Japan). The pullulanase food enzyme is intended to be used in starch processing for the production of glucose syrups. Since residual amounts of total organic solid (TOS) in glucose syrups are removed by filtration and purification during starch processing, dietary exposure assessment was not performed. Genotoxicity tests made with the food enzyme indicated no genotoxic potential. A repeated dose 90‐day oral toxicity study in rodents, carried out with the food enzyme, showed minor effects that were considered to be of no biological relevance. The allergenicity was evaluated by comparing the amino acid sequence to those of known allergens and no match was found. The Panel considered that there are no indications for food allergic reactions to dietary intake of this food enzyme. Based on the removal of residual amounts of TOS from glucose syrups, consumer exposure is not expected. In addition, the safety of the manufacturing process, the compositional and biochemical data lead the Panel to conclude that the food enzyme pullulanase from P. naganoensis (strain AE‐PL) does not give rise to safety concerns under the intended conditions of use.

Abstract This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety assessment of the recycling process Märkische Faser (EU register number RECYC0135), which is based on the Next Generation Group (NGR) technology. The input to this process is hot washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post‐consumer PET containers, containing no more than 5% PET from non‐food consumer applications. In this technology, post‐consumer washed and dried PET flakes are melted and degassed in an extruder under vacuum (step 2) and decontaminated during a melt‐state polycondensation under high temperature and vacuum (step 3). In step 4, the melt material is homogenised, extruded under vacuum and subsequently pelletised. Having examined the results of the challenge test provided, the Panel concluded that the steps 2, 3 and 4, are the critical steps for the decontamination efficiency of the process. The operating parameters which control the performance of these steps are well defined and are the temperature and pressure in all steps and the exposed surface area of the melt and its residence time of step 3. It was demonstrated that the recycling process under evaluation is able to ensure that the level of migration of potential unknown contaminants into food is below a conservatively modelled migration of 0.1 μg/kg food. The Panel concluded that recycled PET obtained from the process Märkische Faser is not of safety concern when used up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs for long‐term storage at room temperature. Thermoforming trays are not intended to be used and should not be used in microwave and conventional ovens.

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety assessment of the substance phosphorous acid, mixed 2,4-bis(1,1-dimethylpropyl) phenyl and 4-(1,1-dimethylpropyl) phenyl triesters. The substance was evaluated by the CEF Panel in 2011 and 2,4-di-tert-amylphenol, an impurity and hydrolysis product was re-evaluated by the CEF Panel in 2015. In this application, the applicant requested an increase of the specific migration limit of the substance, currently established at 5 mg/kg food, to 10 mg/kg food, and provided new toxicological studies. Findings from three new in vitro mutagenicity assays on the oxidation products support the conclusion from 2011 that the substance and its oxidation products are not genotoxic. A new toxicokinetic study on the substance supports the consideration from the evaluation in 2011 that the substance does not raise concern for accumulation. The outcome of a new delayed neurotoxicity study on a structurally related substance, phosphorous acid, tris (2,4-di-tert-butylphenyl) ester, which was considered not to cause neurotoxicity in hens, strengthens the conclusion of the Panel in 2011 that the substance does not represent a concern for neurotoxicity. From a new two-generation reproduction toxicity study and a prenatal developmental toxicity study on the substance, a new subchronic toxicity study on its oxidation products that completes the one submitted in 2011 on the substance itself, and a 2-year oral toxicity study on the structurally related substance, the lowest NOAEL was 58-147 mg/kg bw per day (from the 2-year oral toxicity study). Compared to the requested increase of the migration limit, this gives an acceptable margin of safety of 348. Therefore, the CEF Panel concluded that an increase of the specific migration limit of the substance from 5 to 10 mg/kg food is not a safety concern for the consumer. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.