Günter Vollmer

Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements

Abstract EFSA was asked by the European Commission to deliver a scientific opinion on the risks for human health related to the presence of pyrrolizidine alkaloids (PAs) in honey, tea, herbal infusions and food supplements and to identify the PAs of relevance in the aforementioned food commodities and in other feed and food. PAs are a large group of toxins produced by different plant species. In 2011, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks related to the presence of PAs in food and feed. Based on occurrence data limited to honey, the CONTAM Panel concluded that there was a possible health concern for those toddlers and children who are high consumers of honey. A new exposure assessment including new occurrence data was published by EFSA in 2016 and was used to update the risk characterisation. The CONTAM Panel established a new Reference Point of 237 μg/kg body weight per day to assess the carcinogenic risks of PAs, and concluded that there is a possible concern for human health related to the exposure to PAs, in particular for frequent and high consumers of tea and herbal infusions. The Panel noted that consumption of food supplements based on PA‐producing plants could result in exposure levels too close (i.e. less than 100 times lower) to the range of doses known to cause severe acute/short term toxicity. From the analysis of the available occurrence data, the CONTAM Panel identified a list of 17 PAs of relevance for monitoring in food and feed. The Panel recommended continuing the efforts to monitor the presence of PAs in food and feed, including the development of more sensitive and specific analytical methods. A recommendation was also issued on the generation of data to identify the toxic and carcinogenic potency of the PAs commonly found in food.

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Abstract Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 μg/kg body weight (bw). However, the uncertainties on the actual exposure in the studies preclude their use for derivation of an acute reference dose (ARfD). Instead, a group ARfD of 0.25 μg/kg bw, applying to TTX and its analogues, was derived based on a TTX dose of 25 μg/kg bw at which no apathy was observed in an acute oral study with mice, applying a standard uncertainty factor of 100. Estimated relative potencies for analogues are lower than that of TTX but are associated with a high degree of uncertainty. Based on the occurrence data submitted to EFSA and reported consumption days only, average and P95 exposures of 0.00–0.09 and 0.00–0.03 μg/kg bw, respectively, were calculated. Using a large portion size of 400 g bivalves and P95 occurrence levels of TTX, with exception of oysters, the exposure was below the group ARfD in all consumer groups. A concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC–MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 1 and 25 μg/kg.

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

Abstract 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.

Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels

Amygdalin is the major cyanogenic glycoside present in apricot kernels and is degraded to cyanide by chewing or grinding. Cyanide is of high acute toxicity in humans. The lethal dose is reported to be 0.5–3.5 mg/kg body weight (bw). An acute reference dose (ARfD) of 20 lg/kg bw was derived from an exposure of 0.105 mg/kg bw associated with a non-toxic blood cyanide level of 20 micro mol (lM), and applying an uncertainty factor of 1.5 to account for toxicokinetic and of 3.16 to account for toxicodynamic inter-individual differences. In the absence of consumption data and thus using highest intakes of kernels promoted (10 and 60 kernels/day for the general population and cancer patients, respectively), exposures exceeded the ARfD 17–413 and 3–71 times in toddlers and adults, respectively. The estimated maximum quantity of apricot kernels (or raw apricot material) that can be consumed without exceeding the ARfD is 0.06 and 0.37 g in toddlers and adults, respectively. Thus the ARfD would be exceeded already by consumption of one small kernel in toddlers, while adults could consume three small kernels. However, consumption of less than half of a large kernel could already exceed the ARfD in adults.

Appropriateness to set a group health based guidance value for nivalenol and its modified forms

Abstract The EFSA Panel on Contaminants in the Food Chain (CONTAM) reviewed new studies on nivalenol since the previous opinion on nivalenol published in 2013, but as no new relevant data were identified the tolerable daily intake (TDI) for nivalenol (NIV) of 1.2 μg/kg body weight (bw) established on bases of immuno‐ and haematotoxicity in rats was retained. An acute reference dose (ARfD) of 14 μg/kg bw was established based on acute emetic events in mink. The only phase I metabolite of NIV identified is de‐epoxy‐nivalenol (DE‐NIV) and the only phase II metabolite is nivalenol‐3‐glucoside (NIV3Glc). DE‐NIV is devoid of toxic activity and was thus not further considered. NIV3Glc can occur in cereals amounting up to about 50% of NIV. There are no toxicity data on NIV3Glc, but as it can be assumed that it is hydrolysed to NIV in the intestinal tract it should be included in a group TDI and in a group ARfD with NIV. The uncertainty associated with the present assessment is considered as high and it would rather overestimate than underestimate any risk.

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

Abstract 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.

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

Abstract 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.

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

Abstract 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.

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

Abstract 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.

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

Abstract 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.