Conclusion on the peer review of the pesticide risk assessment of confirmatory data submitted for the active substance dimethoate

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State the United Kingdom, for the pesticide active substance dimethoate are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory mammalian toxicology, residues and ecotoxicology data. The conclusions were reached on the basis of the evaluation of the representative uses of dimethoate as an insecticide on sugar beet and protected lettuce. Concerns are identified

Scientific Opinion on safety and efficacy of coated granulated cobaltous carbonate monohydrate as feed additive for all species

<p>Cobalt(III) is a component of cobalamin. Its essentiality as trace element results from the capacity of certain animal species to synthesise cobalamin by the gastrointestinal microbiota. Feeding cobalt(II) carbonate hydroxide (2:3) monohydrate up to the maximum authorised total cobalt in feed is safe for the target animals. Cobalt is predominantly excreted via the faecal route. Absorbed cobalt follows aqueous excretion routes. About 43 % of body cobalt is stored in muscle; however, kidney and liver are the edible tissues containing the highest cobalt concentrations and are most susceptible to reflect dietary cobalt concentrations. In animals with the capacity to synthesise cobalamin, cobalt is also deposited in tissues as vitamin B<sub>12</sub>. Cobalt(II) cations are genotoxic under <em>in vitro</em> and <em>in vivo</em> conditions. Cobalt(II) carbonate has carcinogen, mutagen and reproduction toxicant (CMR) properties. No data are available on the potential carcinogenicity of cobalt(II) following oral exposure. However, oral exposure may potentially entail adverse threshold-related effects in humans. The estimated population intake of cobalt most likely includes the contribution of foodstuffs from animals fed cobalt-supplemented feedingstuffs. An increase in cobalt exposure by the use of cobalt-containing feed additives is therefore not expected. Considering the population exposure to cobalt, about 4–10 times lower than the health-based guidance value, no safety concern for the consumer is expected for threshold effects of oral cobalt. Cobalt(II) carbonate is a skin and eye irritant, and a dermal and respiratory sensitiser. Its dust is a hazard to persons handling the substance. Exposure by inhalation must be avoided. The use of cobalt from any source at the authorised maximum content in feed does not provide a risk to the environment. The coated granulated cobalt(II) carbonate hydroxide (2:3) monohydrate is available for cobalamin synthesis in the rumen and therefore effective in ruminants; this conclusion is extrapolated to horses and rabbits.</p&gt

Conclusion on the peer review of the pesticide risk assessment of the active substance metobromuron

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State France, for the pesticide active substance metobromuron are reported. The context of the peer review was that required by Commission Regulation (EU) No 188/2011. The conclusions were reached on the basis of the evaluation of the representative use of metobromuron as a herbicide on potatoes. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. The consumer risk assessment should be considered provisional pending the outcome of the requested toxicological information on the metabolites included in the plant residue definitions. A high long-term risk to birds could not be excluded with the available data

Developing and paying for medicines for orphan indications in oncology: utilitarian regulation vs equitable care?

Despite ‘orphan drug' legislation, bringing new medicines for rare diseases to market and securing funding for their provision is sometimes both costly and problematic, even in the case of medicines for very rare ‘ultra orphan' oncological indications. In this paper difficulties surrounding the introduction of a new treatment for osteosarcoma exemplify the challenges that innovators can face. The implications of current policy debate on ‘value-based' medicines pricing in Europe, North America and elsewhere are also explored in the context of sustaining research into and facilitating cancer patient access to medicines for low-prevalence indications. Tensions exist between utilitarian strategies aimed at optimising the welfare of the majority in the society and minority-interest-focused approaches to equitable care provision. Current regulatory and pricing strategies should be revisited with the objective of facilitating fair and timely drug supply to patients without sacrificing safety or overall affordability. Failures effectively to tackle the problems considered here could undermine public interests in developing better therapies for cancer patients

Patient organization involvement and the challenge of securing access to treatments for rare diseases:Report of a policy engagement workshop

Plain English summary Patients with rare diseases often help to develop new treatments for their conditions. But once developed, those treatments are sometimes priced too high for many patients to access them. We became aware that this is a problem in the course of a social science research project that examines the place of rare diseases in health policy. We therefore organized a two-day workshop to try and understand why this problem occurs and what might be done about it. The people who participated in our workshop were: representatives of rare disease patient organizations, experts in matters of drug regulation and assessment of new health technologies, consultants involved with companies producing treatments for rare diseases, and social scientists researching related issues. The main conclusions to emerge from the discussions were as follows: Problems of access to treatments for rare diseases are not just due to high prices; procedures for regulating, assessing and delivering new treatments also need to be better organized. Patients and patient organizations have much to contribute to this process. However, their resources are often very limited. Consequently, more needs to be done to help them use those resources as effectively as possible. In particular, regulators and healthcare providers need to ensure that their procedures are clear and efficiently managed, so as not to waste patient organizations’ time and money. Clearer guidance is needed on what patient organizations can do to provide evidence of the effectiveness of new drugs. Insights gained in tackling rare diseases might also be applicable to common disorders. Finally, the consequences of Brexit for UK policies on rare diseases urgently need to be assessed. Abstract Since the enactment of orphan drug legislation in the USA, Europe and several other countries, an increasing number of treatments for rare diseases have been developed and many of them been approved for marketing. However, such treatments tend to be priced very high, and access to effective treatments remains a major challenge for patients with rare diseases – despite active involvement of patients and their support organizations in various stages of basic and applied research and commercial development. In order to allow patients to benefit from treatments proved effective for their diseases, we need to better understand why this challenge persists, and what steps might be taken to address it. To that end, we organized a policy-engagement workshop, bringing together individuals and organizations with direct experience of trying to secure access to a treatment for a rare disease along with individuals with relevant expertise in regulatory and commissioning processes for new medicines. With additional input from social scientists who offered different perspectives on the value of patient involvement, the workshop aimed to initiate a dialogue among the participants about how to address the challenge in a sustainable manner. Discussions at the workshop stressed that active involvement of patients is as valuable in the regulatory and commissioning processes as in the research and development of new medicines. However, it also highlighted certain risks and costs associated with such involvement. These include the costs of adjusting to abrupt changes in regulatory and commissioning processes, and the risk of being perceived as too close to commercial interests. To optimize use of scarce resources and ensure continuing active involvement, such risks and costs need to be better managed. Participants also noted that, owing to advances in genomic technologies, common diseases are also becoming divided into rare sub-categories, which are equally eligible for orphan drug designation. Consequently, involvement of wider patient communities beyond rare disease communities will be critical for continuing discussions about patients’ involvement in regulatory and commissioning processes, and to consider how patients and their support organizations can best work with other stakeholders – including companies, regulators and policymakers – to ensure access to effective medicines

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on nutrient requirements and dietary intakes of infants and young children in the European Union.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a Scientific Opinion on the nutrient requirements and dietary intakes of infants and young children in the European Union. This Opinion describes the dietary requirements of infants and young children, compares dietary intakes and requirements in infants and young children in Europe and, based on these findings, concludes on the potential role of young-child formulae in the diets of infants and young children, including whether they have any nutritional benefits when compared with other foods that may be included in the normal diet of infants and young children. The Panel concluded on the levels of nutrient and energy intakes that are considered adequate for the majority of infants and young children, and evaluated the risk of inadequate nutrient intakes in infants and young children in living Europe. Dietary intakes of alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), iron, vitamin D and iodine (in some European countries) are low in infants and young children living in Europe, and particular attention should be paid to ensuring an appropriate supply of ALA, DHA, iron, vitamin D and iodine in infants and young children with inadequate or at risk of inadequate status of these nutrients. No unique role of young -child formulae with respect to the provision of critical nutrients in the diet of infants and young children living in Europe can be identified, so that they cannot be considered as a necessity to satisfy the nutritional requirements of young children when compared with other foods that may be included in the normal diet of young children (such as breast milk, infant formulae, follow-on formulae and cow\u2018s milk)

Aquatic food security:insights into challenges and solutions from an analysis of interactions between fisheries, aquaculture, food safety, human health, fish and human welfare, economy and environment

Fisheries and aquaculture production, imports, exports and equitability of distribution determine the supply of aquatic food to people. Aquatic food security is achieved when a food supply is sufficient, safe, sustainable, shockproof and sound: sufficient, to meet needs and preferences of people; safe, to provide nutritional benefit while posing minimal health risks; sustainable, to provide food now and for future generations; shock-proof, to provide resilience to shocks in production systems and supply chains; and sound, to meet legal and ethical standards for welfare of animals, people and environment. Here, we present an integrated assessment of these elements of the aquatic food system in the United Kingdom, a system linked to dynamic global networks of producers, processors and markets. Our assessment addresses sufficiency of supply from aquaculture, fisheries and trade; safety of supply given biological, chemical and radiation hazards; social, economic and environmental sustainability of production systems and supply chains; system resilience to social, economic and environmental shocks; welfare of fish, people and environment; and the authenticity of food. Conventionally, these aspects of the food system are not assessed collectively, so information supporting our assessment is widely dispersed. Our assessment reveals trade-offs and challenges in the food system that are easily overlooked in sectoral analyses of fisheries, aquaculture, health, medicine, human and fish welfare, safety and environment. We highlight potential benefits of an integrated, systematic and ongoing process to assess security of the aquatic food system and to predict impacts of social, economic and environmental change on food supply and demand

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013 . Scientific opinion on Dietary Reference Values for fluoride

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for fluoride, which are provided as Adequate Intake (AI) from all sources, including non-dietary sources. Fluoride is not an essential nutrient. Therefore, no Average Requirement for the performance of essential physiological functions can be defined. Nevertheless, the Panel considered that the setting of an AI is appropriate because of the beneficial effects of dietary fluoride on prevention of dental caries. The AI is based on epidemiological studies (performed before the 1970s) showing an inverse relationship between the fluoride concentration of water and caries prevalence. As the basis for defining the AI, estimates of mean fluoride intakes of children via diet and drinking water with fluoride concentrations at which the caries preventive effect approached its maximum whilst the risk of dental fluorosis approached its minimum were chosen. Except for one confirmatory longitudinal study in US children, more recent studies were not taken into account as they did not provide information on total dietary fluoride intake, were potentially confounded by the use of fluoride-containing dental hygiene products, and did not permit a conclusion to be drawn on a dose-response relationship between fluoride intake and caries risk. The AI of fluoride from all sources (including non-dietary sources) is 0.05 mg/kg body weight per day for both children and adults, including pregnant and lactating women. For pregnant and lactating women, the AI is based on the body weight before pregnancy and lactation. Reliable and representative data on the total fluoride intake of the European population are not available

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion related to the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)

<p>Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver a scientific opinion on the Tolerable Upper Intake Level (UL) of the n-3 LCPUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). Available data are insufficient to establish a UL for n-3 LCPUFA (individually or combined) for any population group. At observed intake levels, consumption of n-3 LCPUFA has not been associated with adverse effects in healthy children or adults. Long-term supplemental intakes of EPA and DHA combined up to about 5 g/day do not appear to increase the risk of spontaneous bleeding episodes or bleeding complications, or affect glucose homeostasis immune function or lipid peroxidation, provided the oxidative stability of the n-3 LCPUFAs is guaranteed. Supplemental intakes of EPA and DHA combined at doses of 2 6 g/day, and of DHA at doses of 2 4 g/day, induce an increase in LDL-cholesterol concentrations of about 3 % which may not have an adverse effect on cardiovascular disease risk, whereas EPA at doses up to 4 g/day has no significant effect on LDL cholesterol. Supplemental intakes of EPA and DHA combined at doses up to 5 g/day, and supplemental intakes of EPA alone up to 1.8 g/day, do not raise safety concerns for adults. Dietary recommendations for EPA and DHA based on cardiovascular risk considerations for European adults are between 250 and 500 mg/day. Supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. No data are available for DPA when consumed alone. In the majority of the human studies considered, fish oils, also containing DPA in generally unknown (but relatively low) amounts, were the source of EPA and DHA.</p&gt