Guidance on the use of the benchmark dose approach in risk assessment.

The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the no-observed-adverse-effect-level (NOAEL) approach for deriving a Reference Point (RP). The major change compared to the previous Guidance (EFSA SC, 2017) concerns the Section 2.5, in which a change from the frequentist to the Bayesian paradigm is recommended.

Intraspecific variation in metal tolerance modulate competition between two marine diatoms.

Despite widespread metal pollution of coastal ecosystems, little is known of its effect on marine phytoplankton. We designed a co-cultivation experiment to test if toxic dose-response relationships can be used to predict the competitive outcome of two species under metal stress. Specifically, we took into account intraspecific strain variation and selection.

Nitrate and ammonium fluxes to diatoms and dinoflagellates at a single cell level in mixed field communities in the sea.

Growth of large phytoplankton is considered to be diffusion limited at low nutrient concentrations, yet their constraints and contributions to carbon (C) and nitrogen fluxes in field plankton communities are poorly quantified under this condition. Using secondary ion mass spectrometry (SIMS), we quantified cell-specific assimilation rates of C, nitrate, and ammonium in summer communities of large phytoplankton when dissolved inorganic nitrogen concentrations are low in temperate coastal regions. Chain-forming diatoms composed 6% of total particulate organic carbon, but contributed 20% of C assimilation, 54% of nitrate assimilation and 32% of ammonium assimilation within the plankton community.

Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).

Background: The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks.

Purpose: Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU).

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.

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.

Nitrogen uptake potential under different temperature-salinity conditions: Implications for nitrogen cycling under climate change scenarios.

As projected by climate change models, increase in sea surface temperature and precipitation in the future may alter nutrient cycling in the coastal regions due to potential changes in phytoplankton community structure and their ability to assimilate nitrogen (N) and carbon (C). An experiment simulating different temperature and salinity conditions (28C-35 ambient conditions, 28C-31, 31C-35 and 31C-31) in mesocosms containing 1000 L of coastal water from the Arabian Sea was performed and N uptake rates were measured using N tracer technique on 2, 5, 7 and 10 day of the experiment. The results show that, under all conditions, the total N (NO + NH) uptake rates were lower in the beginning and on the final day of the tracer experiment, while it peaked during middle, consistent with chlorophyll a concentrations.

A critical evaluation of health risk assessment of modified mycotoxins with a special focus on zearalenone.

A comprehensive definition introducing the term "modified mycotoxins" to encompass all possible forms in which mycotoxins and their modifications can occur was recently proposed and has rapidly gained wide acceptance within the scientific community. It is becoming increasingly evident that exposure to such modified mycotoxins due to their presence in food and feed has the potential to pose a substantial additional risk to human and animal health. Zearalenone (ZEN) is a well-characterized Fusarium toxin.

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 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.

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.

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

Fumonisins, mycotoxins primarily produced by and , 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 B (FB ), FB and FB are the most common forms of fumonisins in feedstuffs and thus were included in the assessment.

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

Poppy seeds are obtained from the opium poppy L.). They are used as food and to produce edible oil.

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 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.

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 B (FB ) 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 and found it appropriate to include FB , FB and FB in a group TDI with FB .

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--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.

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--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.

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.

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.

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--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.

Chemosensitivity-directed therapy compared to dacarbazine in chemo-naive advanced metastatic melanoma: a multicenter randomized phase-3 DeCOG trial.

Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma.

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.

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.

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed.

Deoxynivalenol (DON) is a mycotoxin primarily produced by fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used.

Assessment of a decontamination process 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 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--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.

Risks for animal health related to the presence of zearalenone and its modified forms in feed.

Zearalenone (ZEN), a mycotoxin primarily produced by Fusarium fungi, occurs predominantly in cereal grains. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to ZEN and its modified forms in feed. Modified forms of ZEN occurring in feed include phase I metabolites α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), zearalanone (ZAN) and phase II conjugates.