Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel.

Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions.

Acrylamide levels and dietary exposure from foods in the United States, an update based on 2011-2015 data.

Acrylamide is a contaminant that can form in certain plant-based foods during high-temperature cooking. From 2011-2015, the Food and Drug Administration conducted extensive sampling and analyses of acrylamide in foods, as a follow-up to surveys from 2002-2006. We compared acrylamide occurrence data and exposure estimates based on 2011-2015 data with data and exposure estimates from 2002-2006. Acrylamide levels in selected food categories generally did not decrease significantly in 2011-2015 compared with 2002-2006. However, significant decreases in acrylamide concentrations were observed for potato chips and crackers, which may be related to the availability and use of mitigation techniques for reducing acrylamide in foods. Mean dietary intake for those 2 years and older based on 2011-2015 data was 0.36 µg/kg bw/day, comparable to the 0.44 µg/kg bw/day reported by FDA in 2006. French fries and potato products, breakfast cereal, cookies, potato chips, and crackers continue to be the greatest contributors to dietary intake of acrylamide. Infant snack foods were identified as an important contributor to acrylamide intake relative to infant jarred foods. The continued presence of acrylamide in food suggests that manufacturers and governments should continue to pursue efforts to reduce acrylamide in foods that are important contributors to acrylamide intake.

Update of the risk assessment on 3-monochloropropane diol and its fatty acid esters.

The CONTAM Panel updated the assessment of the risks for human health related to the presence of 3-monochloropropane diol (3-MCPD) and its fatty acid esters in food published in 2016 in view of the scientific divergence identified in the establishment of the tolerable daily intake (TDI) in the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (FAO/WHO) report published in 2017. In this update, dose-response analysis was performed following the recent EFSA Scientific Committee guidance on the use of benchmark dose (BMD) approach in risk assessment, and a review of available data on developmental and reproduction toxicity was included. The outcome of this review indicates that in rats short-term exposure to 3-MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity. Decreased sperm count and histopathological changes in the testis and epididymis were observed following longer treatment periods at higher doses. Regarding increased incidence kidney tubular hyperplasia, BMD analysis using model averaging resulted in a BMDL 10 of 0.20 mg/kg bw per day in male rats, which was selected as the new Reference Point (RP) for renal effects. For the effects on male fertility, decreased sperm motility was selected as the most sensitive relevant endpoint and a BMDL 05 of 0.44 mg/kg bw per day was calculated. The RP for renal effects was considered to derive an updated group TDI of 2 µg/kg bw per day for 3-MCPD and its fatty acid esters and was considered protective also for effects on male fertility. The established TDI of 2 µg/kg bw per day is not exceeded in the adult population. A slight exceedance of the TDI was observed in the high consumers of the younger age groups and in particular for the scenarios on infants receiving formula only.

Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL-PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre- and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005-TEQ/g fat in blood sampled at age 9 years based on PCDD/F-TEQs. No association was observed when including DL-PCB-TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F-TEQ only was on average 2.4- and 2.7-fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL-PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half-lives for PFOS and PFOA are about 5 years and 2-4 years, respectively. The derivation of a health-based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.

Assessment of a decontamination process for dioxins and PCBs from fish meal by hexane extraction and replacement of fish oil.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process for fish meal. This process entails solvent (hexane) extraction of fish oil from fish meal to remove dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) as well as dioxin-like (DL-) and non-dioxin-like (NDL-) polychlorinated biphenyls (PCBs) followed by replacement with decontaminated fish oil. All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. The data provided by the feed business operator were assessed with respect to the efficacy of the process, absence of solvent residues, and on information demonstrating that the process does not adversely affect the nature and characteristics of the product. According to data provided, the process was effective in removing PCDD/Fs and DL-PCBs by approximately 70% and NDL-PCBs by about 60%. The data showed that it is possible to meet the current EU requirements with respect to these contaminants, provided that the level of contamination of untreated fish meal is within the range of the tested batches. It is unlikely that hazardous substances (i.e. hexane) remain in the final product. The Panel considered that there is no evidence that fish oil extraction followed by replacement with decontaminated fish oil leads to detrimental changes in the nutritional composition of the fish meal, although some beneficial constituents (e.g. lipophilic vitamins) might be depleted. The feed business operator submitted information to demonstrate safe disposal of the waste material. The CONTAM Panel concluded that the proposed decontamination process to remove dioxins (PCDD/Fs) and PCBs from fish meal by means of solvent extraction and fish oil replacement was assessed to be compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.

Assessment of a decontamination process for dioxins and PCBs from fish meal by replacement of fish oil.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process of fish meal. It consisted of extraction of the fish oil, filtration and adsorption with activated carbon, and replacement with decontaminated fish oil in order to reduce the amount of dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)), and dioxin-like (DL-) and non-dioxin-like (NDL-) polychlorinated biphenyls (PCBs). All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Data provided by the feed business operator were assessed for efficacy of the process and to demonstrate that the process did not adversely affect the characteristics and the nature of the product. The process was effective in removing PCDD/Fs (97%) and DL- and NDL-PCBs (93%). The fish meal produced complied with EU regulations for these contaminants. The Panel considered that the reference to information available in published literature was a pragmatic approach to demonstrate that the replacement of fish oil and the use of activated carbon to adsorb these contaminants does not lead to any detrimental changes in the nature of the fish meal. However, it was noted that the process could deplete some beneficial constituents (e.g. oil-soluble vitamins). Information was provided to demonstrate the safe disposal of the waste material. The CONTAM Panel concluded that on the basis of the information submitted by the feed business operator the proposed decontamination process to remove dioxins (PCDD/Fs) and PCBs from the fish meal by oil extraction followed by replacement with decontaminated fish oil, was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.

Effect on public health of a possible increase of the maximum level for 'aflatoxin total' from 4 to 10 µg/kg in peanuts and processed products thereof, intended for direct human consumption or use as an ingredient in foodstuffs.

EFSA was asked to deliver a scientific opinion regarding the effect on public health of a possible increase of the maximum level (ML) for 'aflatoxin total' (AFT; sum of aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2) from 4 to 10 µg/kg in peanuts and processed products thereof. Aflatoxins are genotoxic and cause hepatocellular carcinomas in humans. The Panel on Contaminants in the Food Chain (CONTAM Panel) evaluated 8,085 samples of peanuts and 472 samples of peanut butter, with > 60% left-censored. The mean concentration of AFT in peanuts was 2.65/3.56 µg/kg (lower bound (LB)/upper bound (UB)) with a maximum of 1,429 µg/kg. The mean concentration in peanut butter was 1.47/1.92 µg/kg (LB/UB) with a maximum of 407 µg/kg. Peanut oil was not included since all data were left-censored and the ML does not apply for oil. Exposure was calculated for a 'Current ML' and 'Increased ML' scenario, and mean chronic exposure estimates for consumers only, amounted to 0.04-2.74 ng/kg body weight (bw) per day and 0.07-4.28 ng/kg bw per day, respectively. The highest exposures were calculated for adolescents and other children. The CONTAM Panel used the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives for the risk characterisation. Under the scenario of the current ML, the cancer risk was estimated to range between 0.001 and 0.213 aflatoxin-induced cancers per 100,000 person years. Under the scenario of the increased ML, it ranged between 0.001 and 0.333 aflatoxin-induced cancers per 100,000 person years. Comparing these data calculated under the current ML scenario with the yearly excess cancer risk of 0.014 shows a higher risk for consumers of peanuts and peanut butter in some surveys. The calculated cancer risks indicate that an increase of the ML would further increase the risk by a factor of 1.6-1.8.

Appropriateness to set a group health-based guidance value for fumonisins and their modified forms.

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for fumonisin B1 (FB 1) of 1.0 µg/kg body weight (bw) per day based on increased incidence of megalocytic hepatocytes found in a chronic study with mice. The CONTAM Panel considered the limited data available on toxicity and mode of action and structural similarities of FB 2-6 and found it appropriate to include FB 2, FB 3 and FB 4 in a group TDI with FB 1. Modified forms of FBs are phase I and phase II metabolites formed in fungi, infested plants or farm animals. Modified forms also arise from food or feed processing, and include covalent adducts with matrix constituents. Non-covalently bound forms are not considered as modified forms. Modified forms of FBs identified are hydrolysed FB 1-4 (HFB 1-4), partially hydrolysed FB 1-2 (pHFB 1-2), N-(carboxymethyl)-FB 1-3 (NCM-FB 1-3), N-(1-deoxy-d-fructos-1-yl)-FB 1 (NDF-FB 1), O-fatty acyl FB 1, N-fatty acyl FB 1 and N-palmitoyl-HFB 1. HFB 1, pHFB 1, NCM-FB 1 and NDF-FB 1 show a similar toxicological profile but are less potent than FB 1. Although in vitro data shows that N-fatty acyl FBs are more toxic in vitro than FB 1, no in vivo data were available for N-fatty acyl FBs and O-fatty acyl FBs. The CONTAM Panel concluded that it was not appropriate to include modified FBs in the group TDI for FB 1-4. The uncertainty associated with the present assessment is high, but could be reduced provided more data are made available on occurrence, toxicokinetics and toxicity of FB 2-6 and modified forms of FB 1-4.

Risks to human and animal health related to the presence of moniliformin in food and feed.

Moniliformin (MON) is a mycotoxin with low molecular weight primarily produced by Fusarium fungi and occurring predominantly in cereal grains. Following a request of the European Commission, the CONTAM Panel assessed the risk of MON to human and animal health related to its presence in food and feed. The limited information available on toxicity and on toxicokinetics in experimental and farm animals indicated haematotoxicity and cardiotoxicity as major adverse health effects of MON. MON causes chromosome aberrations in vitro but no in vivo genotoxicity data and no carcinogenicity data were identified. Due to the limitations in the available toxicity data, human acute or chronic health-based guidance values (HBGV) could not be established. The margin of exposure (MOE) between the no-observed-adverse-effect level (NOAEL) of 6.0 mg/kg body weight (bw) for cardiotoxicity from a subacute study in rats and the acute upper bound (UB) dietary exposure estimates ranged between 4,000 and 73,000. The MOE between the lowest benchmark dose lower confidence limit (for a 5% response - BMDL05) of 0.20 mg MON/kg bw per day for haematological hazards from a 28-day study in pigs and the chronic dietary human exposure estimates ranged between 370 and 5,000,000 for chronic dietary exposures. These MOEs indicate a low risk for human health but were associated with high uncertainty. The toxicity data available for poultry, pigs, and mink indicated a low or even negligible risk for these animals from exposure to MON in feed at the estimated exposure levels under current feeding practices. Assuming similar or lower sensitivity as for pigs, the CONTAM Panel considered a low or even negligible risk for the other animal species for which no toxicity data suitable for hazard characterisation were identified. Additional toxicity studies are needed and depending on their outcome, the collection of more occurrence data on MON in food and feed is recommended to enable a comprehensive human risk assessment.

Risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed.

Fumonisins, mycotoxins primarily produced by Fusarium verticillioides and Fusarium proliferatum, occur predominantly in cereal grains, especially in maize. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to fumonisins and their modified and hidden forms in feed. Fumonisin B1 (FB 1), FB 2 and FB 3 are the most common forms of fumonisins in feedstuffs and thus were included in the assessment. FB 1, FB 2 and FB 3 have the same mode of action and were considered as having similar toxicological profile and potencies. For fumonisins, the EFSA Panel on Contaminants in the Food Chain (CONTAM) identified no-observed-adverse-effect levels (NOAELs) for cattle, pig, poultry (chicken, ducks and turkeys), horse, and lowest-observed-adverse-effect levels (LOAELs) for fish (extrapolated from carp) and rabbits. No reference points could be identified for sheep, goats, dogs, cats and mink. The dietary exposure was estimated on 18,140 feed samples on FB 1-3 representing most of the feed commodities with potential presence of fumonisins. Samples were collected between 2003 and 2016 from 19 different European countries, but most of them from four Member States. To take into account the possible occurrence of hidden forms, an additional factor of 1.6, derived from the literature, was applied to the occurrence data. Modified forms of fumonisins, for which no data were identified concerning both the occurrence and the toxicity, were not included in the assessment. Based on mean exposure estimates, the risk of adverse health effects of feeds containing FB 1-3 was considered very low for ruminants, low for poultry, horse, rabbits, fish and of potential concern for pigs. The same conclusions apply to the sum of FB 1-3 and their hidden forms, except for pigs for which the risk of adverse health effect was considered of concern.

Update of the Scientific Opinion on opium alkaloids in poppy seeds.

Poppy seeds are obtained from the opium poppy (Papaver somniferum L.). They are used as food and to produce edible oil. The opium poppy plant contains narcotic alkaloids such as morphine and codeine. Poppy seeds do not contain the opium alkaloids, but can become contaminated with alkaloids as a result of pest damage and during harvesting. The European Commission asked EFSA to provide an update of the Scientific Opinion on opium alkaloids in poppy seeds. The assessment is based on data on morphine, codeine, thebaine, oripavine, noscapine and papaverine in poppy seed samples. The CONTAM Panel confirms the acute reference dose (ARfD) of 10 µg morphine/kg body weight (bw) and concluded that the concentration of codeine in the poppy seed samples should be taken into account by converting codeine to morphine equivalents, using a factor of 0.2. The ARfD is therefore a group ARfD for morphine and codeine, expressed in morphine equivalents. Mean and high levels of dietary exposure to morphine equivalents from poppy seeds considered to have high levels of opium alkaloids (i.e. poppy seeds from varieties primarily grown for pharmaceutical use) exceed the ARfD in most age groups. For poppy seeds considered to have relatively low concentrations of opium alkaloids (i.e. primarily varieties for food use), some exceedance of the ARfD is also seen at high levels of dietary exposure in most surveys. For noscapine and papaverine, the available data do not allow making a hazard characterisation. However, comparison of the dietary exposure to the recommended therapeutical doses does not suggest a health concern for these alkaloids. For thebaine and oripavine, no risk characterisation was done due to insufficient data. However, for thebaine, limited evidence indicates a higher acute lethality than for morphine and the estimated exposure could present a health risk.

Update: methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin.

EFSA was asked by the European Commission to update the Scientific Opinion on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances in food of animal origin. This guidance document presents a simple and pragmatic approach which takes into account both analytical and toxicological considerations. The RPA shall be based on the reasonably achievable lowest residue concentration that can unequivocally be determined by official control laboratories, i.e. the reasonably achievable lowest decision limit (CCα). The aim is to check whether this concentration is low enough to adequately protect the consumers of food commodities that contain that substance. The proposed step-wise approach applies toxicological screening values (TSVs), based on genotoxic potential, pharmacological activity, as well as other effects of the substance. The highest dietary exposure corresponding to the reasonably achievable lowest CCα for the substance has to be estimated and compared with the TSV. Where equal to or lower than the TSV, the reasonably achievable lowest CCα can be accepted as the RPA. If higher, the sensitivity of the analytical method needs to be improved. In the case where no further analytical improvements are feasible within a short to medium time frame, a substance-specific risk assessment should be considered. This also applies when the potential adverse effects do not allow use of the decision tree, as for high potency carcinogens, inorganic substances or compounds with allergenic effects or causing blood dyscrasias. The CONTAM Panel concluded that RPAs should be food matrix independent. RPAs cannot be applied to non-edible matrices, which are also monitored for non-allowed pharmacologically active substances.

Risk to human and animal health related to the presence of 4,15-diacetoxyscirpenol in food and feed.

4,15-Diacetoxyscirpenol (DAS) is a mycotoxin primarily produced by Fusarium fungi and occurring predominantly in cereal grains. As requested by the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed the risk of DAS to human and animal health related to its presence in food and feed. Very limited information was available on toxicity and on toxicokinetics in experimental and farm animals. Due to the limitations in the available data set, human acute and chronic health-based guidance values (HBGV) were established based on data obtained in clinical trials of DAS as an anticancer agent (anguidine) after intravenous administration to cancer patients. The CONTAM Panel considered these data as informative for the hazard characterisation of DAS after oral exposure. The main adverse effects after acute and repeated exposure were emesis, with a no-observed-adverse-effect level (NOAEL) of 32 µg DAS/kg body weight (bw), and haematotoxicity, with a NOAEL of 65 µg DAS/kg bw, respectively. An acute reference dose (ARfD) of 3.2 µg DAS/kg bw and a tolerable daily intake (TDI) of 0.65 µg DAS/kg bw were established. Based on over 15,000 occurrence data, the highest acute and chronic dietary exposures were estimated to be 0.8 and 0.49 µg DAS/kg bw per day, respectively, and were not of health concern for humans. The limited information for poultry, pigs and dogs indicated a low risk for these animals at the estimated DAS exposure levels under current feeding practices, with the possible exception of fattening chicken. Assuming similar or lower sensitivity than for poultry, the risk was considered overall low for other farm and companion animal species for which no toxicity data were available. In consideration of the similarities of several trichothecenes and the likelihood of co-exposure via food and feed, it could be appropriate to perform a cumulative risk assessment for this group of substances.

Dietary exposures for the safety assessment of seven emulsifiers commonly added to foods in the United States and implications for safety.

Dietary exposure assessment using food-consumption data and ingredient-use level is essential for assessing the safety of food ingredients. Dietary exposure estimates are compared with safe intake levels, such as the acceptable daily intake (ADI). The ADI is estimated by applying a safety factor to an experimentally determined no-observed-adverse-effect level of a test substance. Two food ingredients classified as emulsifiers, carboxymethylcellulose (CMC) and polysorbate 80 (P80), received attention recently due to their putative adverse effects on gut microbiota. Because no published dietary exposure estimates for commonly used emulsifiers exist for the US population, the current investigation focused on the estimation of dietary exposure to seven emulsifiers: CMC, P80, lecithin, mono- and diglycerides (MDGs), stearoyl lactylates, sucrose esters, and polyglycerol polyricinoleate. Using maximum-use levels obtained from publicly available sources, dietary exposures to these emulsifiers were estimated for the US population (aged 2 years and older) for two time periods (1999-2002 and 2003-10) using 1- and 2-day food-consumption data from the National Health and Nutrition Examination Survey, and 10-14-day food-consumption data from NPD Group, Inc.'s National Eating Trends - Nutrient Intake Database. Our analyses indicated that among the emulsifiers assessed, lecithin and MDGs have the highest mean exposures at about 60 and about 80 mg kg-1 bw day-1, respectively, whereas the exposure to CMC is half to one-third that of lecithin or MDGs; and the exposure to P80 is approximately half that of CMC. The review of available safety information such as ADIs established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), in light of our updated dietary exposure estimates for these seven emulsifiers, did not raise safety concerns at the current specified levels of use. Additionally, by examining two time periods (1999-2002, 2003-10), it was concluded that there is no evidence that exposure levels to emulsifiers have substantially increased.

Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms.

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 µg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2 and using a reduction in total leucocyte count as the critical endpoint. An acute reference dose (ARfD) of 0.3 µg for T2 and HT2/kg bw was established based on acute emetic events in mink. Modified forms of T2 and HT2 identified are phase I metabolites mainly formed through hydrolytic cleavage of one or more of the three ester groups of T2. Less prominent hydroxylation reactions occur predominantly at the side chain. Phase II metabolism involves conjugation with glucose, modified glucose, sulfate, feruloyl and acetyl groups. The few data on occurrence of modified forms indicate that grain products are their main source. The CONTAM Panel found it appropriate to establish a group TDI and a group ARfD for T2 and HT2 and its modified forms. Potency factors relative to T2 for the modified forms were used to account for differences in acute and chronic toxic potencies. It was assumed that conjugates (phase II metabolites of T2, HT2 and their phase I metabolites), which are not toxic per se, would be cleaved releasing their aglycones. These metabolites were assigned the relative potency factors (RPFs) of their respective aglycones. The RPFs assigned to the modified forms were all either 1 or less than 1. The uncertainties associated with the present assessment are considered as high. Using the established group, ARfD and TDI would overestimate any risk of modified T2 and HT2.

Scientific opinion on the evaluation of substances as acceptable previous cargoes for edible fats and oils.

Shipping of edible fats and oils into Europe is permitted in bulk tanks, provided that the previous cargo is included in a positive list. The European Commission requested EFSA to evaluate the acceptability as previous cargoes for fats and oils the substances calcium lignosulphonate, methyl acetate, ethyl tert-butyl ether (ETBE) and ammonium sulphate. The evaluation was based on the same criteria as those used for the evaluation of the substances currently on the list in the Annex to Commission Directive 96/3/EC as acceptable previous cargoes for edible fats and oils. Methyl acetate and ETBE meet the criteria for acceptability as previous cargoes. Due to uncertainties, mainly with regard to the composition and toxicity of the low molecular mass fraction, and the fact that the toxicological database is limited to the 40-65 grade and does not cover all grades of calcium lignosulphonate shipped as previous cargoes, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) concluded that calcium lignosulphonate does not meet the criteria for acceptability as a previous cargo. Only food-grade ammonium sulphate meets the criteria for acceptability as a previous cargo due to uncertainties about impurities in other (non-food) grades.

Assessment of a decontamination process for hydrocyanic acid in linseed intended for use in animal feed.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process for the enzymatic treatment and subsequent heating of linseed, in order to reduce the amount of hydrocyanic acid (HCN) present as cyanogenic glycosides. Specifically, it is required that the feed decontamination process is compliant with the acceptability criteria specified in the Commission Regulation (EU) 2015/786 of 19 May 2015. With this aim, the CONTAM Panel assessed the data provided by the feed business operator with respect to the efficacy of the process to remove the contaminant from the linseed batches and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. The data enabled the Panel to conclude that in agreement with the literature the process was able to remove HCN by about 90%, and that it is possible to meet the current EU requirements for quality of linseed with respect to HCN, provided the level of contamination of untreated linseed would be within the range of the tested batches. The Panel noted that the amounts of other products formed during the enzymatic process and remaining in the treated material are not of toxicological concern. The experimental data provided by the feed business operator showed that the characteristics of linseed were not adversely affected by the decontamination process. The CONTAM Panel concluded that, on the basis of the information submitted by the feed business operator, the proposed decontamination process to remove HCN from linseed by means of enzymatic release and subsequent evaporation was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.

Risks for public health related to the presence of furan and methylfurans in food.

The European Commission asked EFSA for a scientific evaluation on the risk to human health of the presence of furan and methylfurans (2-methylfuran, 3-methylfuran and 2,5-dimethylfuran) in food. They are formed in foods during thermal processing and can co-occur. Furans are produced from several precursors such as ascorbic acid, amino acids, carbohydrates, unsaturated fatty acids and carotenoids, and are found in a variety of foods including coffee and canned and jarred foods. Regarding furan occurrence, 17,056 analytical results were used in the evaluation. No occurrence data were received on methylfurans. The highest exposures to furan were estimated for infants, mainly from ready-to-eat meals. Grains and grain-based products contribute most for toddlers, other children and adolescents. In adults, elderly and very elderly, coffee is the main contributor to dietary exposure. Furan is absorbed from the gastrointestinal tract and is found in highest amounts in the liver. It has a short half-life and is metabolised by cytochrome P450 2E1 (CYP2E1) to the reactive metabolite, cis-but-2-ene-1,4-dialdehyde (BDA). BDA can bind covalently to amino acids, proteins and DNA. Furan is hepatotoxic in rats and mice with cholangiofibrosis in rats and hepatocellular adenomas/carcinomas in mice being the most prominent effects. There is limited evidence of chromosomal damage in vivo and a lack of understanding of the underlying mechanism. Clear evidence for indirect mechanisms involved in carcinogenesis include oxidative stress, gene expression alterations, epigenetic changes, inflammation and increased cell proliferation. The CONTAM Panel used a margin of exposure (MOE) approach for the risk characterisation using as a reference point a benchmark dose lower confidence limit for a benchmark response of 10% of 0.064 mg/kg body weight (bw) per day for the incidence of cholangiofibrosis in the rat. The calculated MOEs indicate a health concern. This conclusion was supported by the calculated MOEs for the neoplastic effects.

Assessment of decontamination processes for dioxins and dioxin-like PCBs in fish oil by physical filtration with activated carbon.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of decontamination processes involving the adsorption with activated carbon and physical filtration of fish oil in order to reduce the amount of dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) and dioxin-like polychlorinated biphenyls (DL-PCBs). All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Two feed business operators provided data on their respective decontamination processes, which were assessed in terms of the efficacy of the process and the absence of adverse effects in the nature and characteristics of the product after decontamination. The processes proved to be able to remove PCDD/Fs (82-95%) and DL-PCBs (26-45%) from the fish oil, depending on the process used by the business operator. Given that the level of contamination is within the range of the tested untreated fish oil, it is possible to meet EU requirements for these contaminants after decontamination. The CONTAM Panel considered both the evidence provided by one of the business operators and information in the available literature to conclude that the proposed processes do not lead to any detrimental changes in the nature of the fish oil. However, the process can deplete some beneficial constituents (e.g. vitamins). Information was provided to demonstrate the safe disposal of the waste material. The CONTAM Panel concluded that, on the basis of the information submitted by the feed business operators, the proposed decontamination processes to remove dioxins (PCDD/Fs) and DL-PCBs from the fish oil by means of activated carbon and physical filtration were compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.