Tanja Schwerdtle

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.

Assessment of a decontamination process for dioxins and dioxin‐like PCBs in fish oil by physical filtration with activated carbon

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 consisting in 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. The data provided by the feed business operator were assessed with respect to the efficacy of the process and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. As described in scientific literature, the process was effective in removing PCDD/Fs (84%) and DL‐PCBs (55%), and therefore, it is possible to meet the current EU requirements with respect to these contaminants, assuming that the level of contamination of untreated fish oil was within the range of the tested batches. The Panel considered that the reference to information available in published literature was a pragmatic approach to demonstrate that the use of activated carbon adsorption does not lead to any detrimental changes in the nature of the fish oil; however, it was noted that the process could 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 operator the proposed decontamination process to remove dioxins (PCDD/Fs) and DL‐PCBs from the fish oil by means of physical filtration with activated carbon, was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.