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The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of chlorinated paraffins in feed and food. The data for experimental animals were reviewed and the CONTAM Panel identified the liver, kidney and thyroid as the target organs for the SCCP and MCCP mixtures tested in repeated dose toxicity studies. Decreased pup survival and subcutaneous haematoma/haemorrhage were also identified as critical effects for an MCCP mixture. For the LCCP mixtures tested, the liver was identified as the target organ. The Panel selected as reference points a BMDL 10 of 2.3 mg/kg bw per day for increased incidence of nephritis in male rats, and of 36 mg/kg bw per day for increased relative kidney weights in male and female rats for SCCPs and MCCPs, respectively. For LCCPs, a reference point relevant for humans could not be identified. Due to the limitations in the toxicokinetic and toxicological database, the Panel concluded that derivation of a health-based guidance value was not appropriate. Only limited data on the occurrence of SCCPs and MCCPs in some fish species were submitted to EFSA. No data were submitted for LCCPs. Thus, a robust exposure assessment and consequently a complete risk characterisation could not be performed. A preliminary risk characterisation based only on the consumption of fish was performed, and the calculated margins of exposure suggested no health concern for this limited scenario. The Panel noted that dietary exposure will be higher due to the contribution of CPs from other foods. The Panel was not able to identify reference points for farm animals, horses and companion animals. No occurrence data for feed were submitted to EFSA. Therefore, no risk characterisation could be performed for any of these animal species., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on hexamethylene tetramine (HMTA) for pigs, poultry, bovines, sheep, goats, rabbits and horses. In 2015, the FEEDAP Panel delivered an opinion on the safety and efficacy of HMTA. In that opinion, the Panel noted that the residues of HMTA in the silage amounted to about 5% of the inclusion level of 600 mg HMTA/kg fresh ensiling material. Since the HMTA residues in silage were analysed as formaldehyde, it was not possible to quantify the contribution of formaldehyde and HMTA to the residues. In the absence of a qualitative and quantitative characterisation of the residues, the Panel could not conclude on the safety of HMTA for the target species. Based on the results of a new study in which HMTA was measured in silage, the concentration of HMTA dropped below the limit of quantification of 6 mg HMTA/kg silage, which corresponds to ~ 1% of the HMTA inclusion level in the fresh ensiling material. However, the formaldehyde concentration was not analysed in the silage. In the absence of a qualitative and quantitative characterisation of the residues, the Panel cannot conclude on the safety of HMTA for the target species., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of lignosulphonate, when used as a technological additive, functional group: binders. In a previous opinion, the FEEDAP Panel could not conclude on the safety of the additive for target species and for the environment. The applicant provided additional information that was assessed in the current opinion. As regards the safety for the target species, the maximum recommended content of lignosulphonate of 10,000 mg/kg complete feed is considered safe in weaned piglet. A safe concentration of lignosulphonate in feed for salmonids and dairy cows could not be identified. The FEEDAP Panel reiterates also its previous conclusions that '10,000 mg lignosulphonate/kg complete feed is safe for chickens for fattening, laying hens and cattle for fattening but a margin of safety cannot be identified. Therefore, this conclusion cannot be extended to all animal species/categories'. Considering the absence of adverse effects confirmed by all the ecotoxicity studies up to very high concentrations, no concerns for the environment are expected from the use of this additive in animal nutrition according the conditions of use. Lignosulphonate is efficacious as pellet binder., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety lactic acid and calcium lactate for all animal species. In 2015 and in 2017, the Panel on Additives and Products or Substances used in Animal Nutrition (FEEDAP) delivered two opinions on the safety of lactic acid and calcium lactate. In that opinion, the panel concluded that the additive is safe for pigs and ruminants at concentrations of 50,000 mg lactic acid/kg complete feed but could not conclude on the safety for poultry and for pre-ruminants. Now the applicant is proposing a new maximum concentration of 20,000 mg lactic acid/kg feed for all other animal species, with the exclusion of pre-ruminants, and provided a new study in chickens for fattening. Based on the results of the new study, the Panel concluded that 20,000 mg lactic acid/kg complete feed is safe for chickens for fattening. The FEEDAP Panel extrapolates the lowest safe level of 20,000 mg lactic acid/kg complete feed observed in chicken for fattening to all animal species other than pigs and ruminants for which 50,000 mg lactic acid/kg is safe, with the exception of pre-ruminants for which a safe dose could not be established. The maximum content of 20,000 mg lactic acid is equivalent to 24,000 mg calcium lactate and 30,000 mg calcium lactate hydrate (hydrate, n = 4-5). The corresponding maximum content in water for drinking would be 8,000 mg lactic acid/L., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of butylated hydroxy anisole (BHA) for all animal species. In 2018, the Panel delivered an Opinion on the safety and efficacy of BHA. The Panel concluded that 'a weight of evidence of the limited data supports that 150 mg BHA/kg complete feed would be a safe dose for all animal species. However, a possible exception could be cat, with its known lower capacity for glucuronidation of phenolic compounds and for which no specific data were available'. The Applicant submitted a review of the metabolism of phenolic compounds in cats and an in vivo study with cats. No specific information on metabolic fate of BHA has been made available for the feline species. The lack of knowledge is of particular relevance considering the additional load of phenolic compounds by dietary BHA for the full lifetime expectancy of cats. Owing the shortcomings in the design and reporting, the in vivo study could not be used to conclude on the safety of BHA for cats. Consequently, the Panel reiterates that no safe concentration of BHA in complete feed for cats could be established., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive sorbitan monolaurate consists of sorbitol (and its anhydrides) esterified with fatty acids derived from coconut oil. It is intended to be used as a technological additive, functional group: emulsifier, in feedingstuffs for all animal species, at a maximum concentration of 85 mg/kg complete feed. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that sorbitan monolaurate is safe for all animal species at the proposed maximum content of 85 mg/kg complete feed and that the use of sorbitan monolaurate in animal nutrition is not expected to pose a risk for the consumer under the proposed conditions of use. Users are unlikely to be exposed to sorbitan monolaurate via inhalation. Sorbitan monolaurate is irritant to skin and eyes and it is not considered a skin sensitiser. Owing the lack of data, the FEEDAP Panel cannot conclude on the safety of the additive for the environment. Sorbitan monolaurate is authorised for use as a food additive with the function of emulsifier. The technological effect underlying its use as a food additive could reasonably be expected to be seen when used in feed., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive cassia gum consists mainly of high-molecular weight polysaccharides composed primarily of a linear chain of 1,4-β-d-mannopyranose units with 1,6-linked α-d-galactopyranose units. In 2014, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of cassia gum in cats and dogs. The Panel concluded, based on positive findings observed in a bacterial reverse mutation test with a semi-refined cassia gum (about 70 mg anthraquinones/kg) but not with purified semi-refined cassia gum that meets the specification as a food additive (< 0.5 mg anthraquinones/kg), that only purified semi-refined cassia gum that meets the specifications of cassia gum as a food additive can be considered safe for cats and dogs, at a maximum content of 1.5% cassia gum (15,000 mg/kg feed) in dry matter, corresponding to 1.32% (13,200 mg/kg feed) in a standardised complete feed with 12% water content. The conclusion was confirmed in an opinion delivered by the Panel in 2017. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information on the safety for cats and dogs. The semi-refined cassia gum under application was mutagenic in a bacterial reverse mutation test in Salmonella Typhimurium strain TA100. Positive results were also observed after heat sterilisation of the test item. Isopropanol purified semi-refined cassia gum did not show mutagenic effect. Examination of various other cassia gum extracts did not identify any source of mutagenicity. The mutagenicity of the semi-refined cassia gum under application cannot be excluded. Therefore, the FEEDAP Panel cannot establish the safety of semi-refined cassia gum for cats and dogs., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive under assessment is pure benzoic acid (> 99.8%), manufactured in the form of flakes. It is intended to be used as a technological feed additive (acidity regulator) in feedingstuffs for weaned piglets and pigs for fattening, with maximum contents of 5,000 and 10,000 mg/kg complete feed, respectively. Benzoic acid is safe for weaned piglets at 5,000 mg/kg complete feed, and at 10,000 mg/kg complete feed for pigs for fattening. The use of benzoic acid in feedingstuffs for piglets and pigs for fattening at the maximum application rate will not affect exposure of consumers to residues or metabolites of concern via food from treated animals. Therefore, the use of benzoic acid as technological additive in feeds for pigs to a maximum inclusion level of 10,000 mg/kg is considered safe for consumers. Benzoic acid is a skin and eye irritant but is not considered to be a skin sensitiser. Exposure via inhalation is unlikely. The use of benzoic acid in feedingstuffs for piglets and pigs for fattening will not pose a risk for the environment. Benzoic acid is efficacious as an acidity regulator in feedingstuffs for weaned piglets and pigs for fattening., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive is a natural mixture mainly composed of illite (~ 53%), montmorillonite (~ 16%) and kaolinite (~ 17%), referred as MIMK. In 2016 and in 2017, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered two opinions on the safety and efficacy of the additive. In these opinions, the Panel concluded that the additive is safe for piglets, pigs for fattening and cattle for fattening and minor growing ruminants at a maximum concentration of 50,000 mg/kg. No conclusions could be drawn on the safety for poultry or any other species/categories. Following these opinions, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species. The applicant submitted a new tolerance study with chickens for fattening showing no adverse effect of the additive MIMK up to 100,000 mg/kg complete feed (twofold the highest recommended use level). The FEEDAP Panel therefore concludes that 50,000 mg MIMK/kg complete feed is safe for chickens for fattening. MIMK was already considered safe, at the same dietary concentration, for cattle for fattening with a margin of safety of two and for piglets but without a margin of safety. Therefore, extrapolation to all animal species is not possible for the concentration of 50,000 mg MIMK/kg complete feed. The Panel notes that the concentration of 20,000 mg MIMK/kg feed was tested in all the tolerance studies assessed and shown to be safe, with a margin of safety of at least 2.5. The Panel concludes that the additive MIMK is safe at 50,000 mg/kg complete feed for chickens for fattening and minor growing poultry species, for cattle for fattening and minor growing ruminant species and growing pigs; and at 20,000 mg/kg complete feed for all other animal species and categories., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the modification of the terms of authorisation of lecithins as a feed additive for all animal species. Lecithins are currently authorised for use in feed for all animal species (Commission Implementing Regulation (EU) 2017/2325). The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion of the additive lecithins in 2016. The Panel concluded that lecithins are safe for the target species, the consumer, the user and the environment, and that they are efficacious as emulsifier. The requested modification refers to the alignment of the specifications of the feed additive to the specifications set for lecithins when used as food additives, and the inclusion in the authorisation of rapeseed among the botanical sources of hydrolysed and de-oiled lecithins and of de-oiled hydrolysed soybean lecithins as an additional form of the additive. Based on the data available, all the lecithins of different botanical origin and their forms under application meet the specifications set for the use of lecithins as a food additive. The Panel therefore recommended applying the specifications set for food additive to the lecithins under application. In its previous opinion, the Panel concluded that lecithins are safe for the target species, the consumer, the user and the environment, and that they are efficacious as an emulsifier. The Panel is not aware of any information related to the use of rapeseed as an additional source of hydrolysed liquid lecithins and de-oiled lecithin powder that would modify the previous conclusions., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive under assessment consists of a natural mixture, mainly composed of dolomite (~ 30%), magnesite (~ 20%) and magnesium-phyllosilicates (talc (~ 35%) and chlorite (~ 15%)). In 2016, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of natural mixture of dolomite plus magnesite and magnesium-phyllosilicates. In this opinion, the Panel concluded that 20,000 mg additive/kg complete feed is considered safe for dairy cows and for piglets (weaned). This conclusion was extended to pigs for fattening while no conclusion could be drawn on the safety for poultry or any other species/categories. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species. The new tolerance studies submitted with cattle for fattening and chickens for fattening showed tolerance of these animal categories to the additive up to approximately fivefold the highest recommended use level. The FEEDAP Panel therefore concluded that 20,000 mg additive/kg complete feed is safe for cattle for fattening and chickens for fattening. The additive at the same dietary concentration was already considered safe in an earlier opinion for piglets and dairy cows. Since the additive at 20,000 mg/kg complete feed is considered safe for four animal categories (three major animal species) with a comparable margin of safety, the conclusion on safety is extrapolated to all animal species. At the safe dietary concentration the additive did not affect the digestibility of the feed (including feed additives)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive consists of single strains of Bacillus subtilis and Aspergillus oryzae , to be used in combination as a technological additive (proposed functional group: Substances for the reduction of anti-nutritional factors) in feed materials for all animal species. An opinion on the two microorganisms was published previously. At this time, the safety of the B. subtilis strain for target animals, consumers, users and the environment was established, but no conclusions could be draw on the safety of the strain of A. oryzae for the target species and consumers or on the efficacy of the additive in reducing anti-nutritional factors. This opinion considers new information intended to address the identified deficiencies in the previous opinion. An extensive analytical search for secondary metabolites was made of the A. oryzae component of the additive and 15 metabolites were detected and quantified. Of the 15 metabolites, 13 occurred in ng/g additive concentrations and were considered not to be of concern. The remaining two compounds, cyclic dipeptides (2,5-diketopiperazines), were detected at concentrations up to 1.5 mg/kg. Both have been identified in a wide range of foods and beverages and there appears to be no reports of adverse reactions to such cyclic dipeptides in processed food. Consequently, none of the metabolites detected were considered likely to cause adverse effects in target animals fed treated feed material or in consumers of products derived from such animals. Data from the analysis of 18 batches of soybean before and after treatment with the two strains were presented in support of the efficacy of the additive. Two classes of anti-nutritional factors were considered; oligosaccharides of the raffinose series and trypsin inhibitor. The microbial strains in combination were able to substantially reduce the concentration of oligosaccharides and trypsin inhibitor naturally present in soybean. Other feed materials were not considered., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Butylated hydroxyanisole (BHA) is a waxy solid consisting for > 98.5% of the active substance, a mixture of 3- tert -butyl-4-hydroxyanisole and 2- tert -butyl-4-hydroxyanisole. It is intended to be used as an antioxidant in feedingstuffs for all animal species and categories. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) considered BHA up to 150 mg/kg complete feed as safe for all animal species except for cats, for which a safe dose could not be established from the tolerance data. BHA is rapidly absorbed from the gastrointestinal tract; it is metabolised rapidly and excreted as such and as metabolites in the urine and faeces. The proportions of the different metabolites vary depending on species and dose. No accumulation of BHA or metabolites was observed in tissues. The Panel concluded that no concern for consumer safety would arise from the use of BHA as a feed additive at the maximum concentration of 150 mg/kg feed. The additive should be considered a skin, eye irritant and a potential skin sensitiser. Exposure of the user via inhalation was considered unlikely; therefore, a risk is not expected. The use of BHA at the maximum concentration proposed is unlikely to pose a risk to the environment. BHA is authorised as an antioxidant for food use at comparable use levels, therefore, no studies were required to demonstrate the efficacy of BHA as an antioxidant in feedingstuffs for all animal species., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive is a natural mixture of talc and chlorite (NTMC) that contains at least 75% of talc and chlorite as main components. The additive is intended for use as a technological additive (functional groups: (i) anticaking agents) in premixtures and feedingstuffs for all animal species at use levels of 1,000-50,000 mg/kg. No safe dietary level of NMTC could be identified for piglets, chickens for fattening and dairy cows. The use of NMTC in animal nutrition is considered not to pose a risk for the consumer of animal tissues and products from animals fed the additive. Talc could cause serious lung disease if repeatedly inhaled in large quantities over a long period. Talc is not irritant to skin and eyes. In the absence of data, no conclusion can be drawn on the skin sensitisation potential of the product. The components of the additive (talc, chlorite, dolomite and magnesite) are ubiquitous in the environment, being natural components of soil. Therefore, it is not expected that its use as a feed additive would adversely affect the environment. The additive NMTC is efficacious as an anticaking agent., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Malachite green (MG) has been widely used in aquaculture to treat a number of microbial and parasitic diseases. It is currently banned in the EU because of the high cytotoxicity and carcinogenic activity, which is also shared by leucomalachite green (LMG), a reduced MG metabolite that can persist in fish tissues for months. There is scant information about the ability of either compound to interact with drug metabolizing enzymes in fish. Therefore we evaluated the in vitro effects of MG and LMG (25, 50 and 100μM) on some DMEs and glutathione (GSH) content in rainbow trout liver subfractions. LMG did not affect any of the examined parameters. In contrast, MG proved to deplete GSH and to depress to a various extent the activities of NAD(P)H cytochrome c reductase, 7-ethoxycoumarin O-deethylase, 1-naphthol uridindiphosphoglucuronyl-transferase and maximally those of 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) accepting 1-chloro2,4-dinitrobenzene (CDNB) as substrate. The inhibition mechanisms of EROD and GST were investigated by means of non-linear Michaelis-Menten kinetics and Lineweaver-Burk plots using 0.175-8μM MG. The calculated IC 50 for EROD was 7.1μM, and the inhibition appeared to be competitive (K i 2.78±0.24μM). In the case of GST, the calculated IC 50 was 0.53μM. The inhibition was best described as competitive toward GSH (Ki 0.39±0.02μM) and of mixed-type toward CDNB (Ki 0.64±0.06μM). Our findings indicate that, contrary to LMG, MG behaves as a relatively strong inhibitor of certain liver DMEs and can reversibly bind GSH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Sodium and potassium alginate are intended to be used as technological additives (functional groups: emulsifiers, stabilisers, thickeners, gelling agents and binders). Sodium alginate is intended to be used in feedingstuffs for pets, other non food-producing animals and fish, with no maximum recommended use level. Potassium alginate is intended to be used in feedingstuffs for cats and dogs at levels up to 40,000 mg/kg feed (on dry matter). Since the functional properties of the additives are determined by the alginate content, sodium and potassium alginate were considered equivalent. The maximum dose considered safe for cats, dogs, other non food-producing animals, salmonids and other fish is 40,000 mg alginates (sodium and potassium salts)/kg complete feed. The use of alginates in feedingstuffs for fish is of no concern for the consumer. Alginates are reported not to be irritant to the skin but mildly irritant to the eyes. They are considered as potential sensitisers to the skin and the respiratory tract. Alginates are high-molecular-weight polymers naturally occurring in brown algae. Their use in feedingstuffs for fish does not pose a risk for the aquatic environment. Alginates are effective as stabilisers, thickeners, gelling agent and binders. No conclusion could be drawn on the efficacy of alginates as emulsifiers., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additives under assessment are lactic acid and calcium lactate. In 2015, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an Opinion on the safety and efficacy of lactic acid and calcium lactate. The FEEDAP Panel could not conclude on the safety of lactic acid in pre-ruminants and poultry. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species. Based on the studies submitted in chickens for fattening and laying hens, no safe concentration of lactic acid and calcium lactate in complete feed for these species could be identified. Owing to the absence of data on tolerated dietary levels of d-lactic acid, no conclusion on the safety of lactic acid in milk replacer for pre-ruminants is possible. Since a safe concentration of lactic acid (and calcium lactate) was established only for pigs and cattle, and not for a third major animal species, no extrapolation to any other species is possible., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive under assessment is a natural mixture mainly composed of illite (~ 53%), montmorillonite (~ 16%) and kaolinite (~ 17%). In 2016, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an Opinion on the safety and efficacy of a natural mixture of illite, montmorillonite and kaolinite (MIMK). The FEEDAP Panel concluded that the additive is safe for piglets and pigs for fattening at a maximum concentration of 20,000 mg/kg, and for cattle for fattening at a maximum concentration of 50,000 mg/kg. However, no conclusion could be drawn for all other species/categories. The Panel also concluded that the additive is efficacious at a minimum concentration of 50,000 mg/kg. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species and on its efficacy at a minimum concentration of 20,000 mg/kg. The applicant submitted a new tolerance study in piglets and an analysis of the previous EFSA opinion regarding poultry and milk-producing animals. The FEEDAP Panel concluded that the additive is safe for piglets and pigs for fattening at 50,000 mg/kg. The Panel concluded that the safe level (50,000 mg/kg) found for cattle for fattening could be extrapolated to minor growing ruminants. The conclusion could be extrapolated to dairy cows and minor ruminant species for milk production. The FEEDAP Panel confirmed that no safe concentration of MIMK in feed for chickens for fattening could be identified. No conclusions could be drawn for all the other animal species/categories. The additive is effective as a pellet binder and an anticaking agent at the lowest level tested of 5,000 mg/kg feed., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive cassia gum consists mainly of high-molecular weight polysaccharides composed primarily of a linear chain of 1,4-β-d-mannopyranose units with 1,6-linked α-d-galactopyranose units. In 2014, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of cassia gum. The FEEDAP Panel concluded, based on positive findings observed in a bacterial reverse mutation test with a semirefined cassia gum (about 70 mg anthraquinones/kg) but not with purified semirefined cassia gum that meets the specification as a food additive (< 0.5 mg anthraquinones/kg), that only purified semirefined cassia gum that meets the specifications of cassia gum as a food additive can be considered safe for cats and dogs, at a maximum content of 1.5% cassia gum (15,000 mg/kg feed) in dry matter, corresponding to 1.32% (13,200 mg/kg feed) in a standardised complete feed with 12% water content. The FEEDAP Panel also concluded that cassia gum should be regarded as a skin and respiratory sensitiser and as a potential irritant to skin and eyes. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information on the safety for all animal species. No new data were submitted to address the potential of the additive to exert mutagenic effects, and therefore, the FEEDAP Panel is not in the position to modify the conclusions reached in the previous opinion., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive cassia gum consists mainly of high-molecular weight polysaccharides composed primarily of a linear chain of 1,4-β-d-mannopyranose units with 1,6-linked α-d-galactopyranose units. In 2014, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of cassia gum. The FEEDAP Panel concluded, based on positive findings observed in a bacterial reverse mutation test with a semirefined cassia gum (about 70 mg anthraquinones/kg) but not with purified semirefined cassia gum that meets the specification as a food additive (< 0.5 mg anthraquinones/kg), that only purified semirefined cassia gum that meets the specifications of cassia gum as a food additive can be considered safe for cats and dogs, at a maximum content of 1.5% cassia gum (15,000 mg/kg feed) in dry matter, corresponding to 1.32% (13,200 mg/kg feed) in a standardised complete feed with 12% water content. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species. The new data submitted, describing a reproduction study in cats, do not address the potential of the additive to exert mutagenic effects, and do not allow conclusions to be drawn on the safety of semirefined cassia gum with an anthraquinone content higher than the one specified for the use as a food additive (< 0.5 mg/kg). The FEEDAP Panel is not in the position to modify the conclusions reached in the previous opinion., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The additive under assessment consists of a natural mixture, mainly composed of dolomite (~ 30%), magnesite (~ 20%) and magnesium-phyllosilicates (talc (~ 35%) and chlorite (~ 15%)). In 2016, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of natural mixture of dolomite plus magnesite and magnesium-phyllosilicates. The FEEDAP Panel concluded that the additive is safe in complete feed for dairy cows, piglets and pigs for fattening at a maximum concentration of 20,000 mg/kg. However, no conclusions could be drawn for all other animal species/categories. Following this opinion, the European Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety for all animal species. The applicant answered with a new submission, an analysis of the previous EFSA opinion, but without new data. The FEEDAP Panel considered the arguments made by the applicant, in relation to the tolerance studies with dairy cows and chickens for fattening. No reason was identified to modify the conclusions reached in the previous opinion., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Dexamethasone is a potent synthetic corticosteroid widely employed as a therapeutic agent in cattle. Besides this legal use, corticosteroids are also administered at low dosages as growth-promoters either alone or in combination with other steroids or with beta-agonists. For this reason, appropriate control plans are established to survey corticosteroid misuse, using liver or urine as biological matrices. Since few data are available about the kinetics of dexamethasone excretion in meat cattle, an experimental study was designed to assess the drug residue levels in urines following either a therapeutic (60 microg of dexamethasone sodium phosphate/kg b.w., for three consecutive days) or a growth-promoting schedule (0.7 or 1.4 mg of dexamethasone sodium phosphate per capita/day for 60 days). The urinary elimination of dexamethasone, which was predominantly excreted in the unmodified form, was determined by high-performance liquid chromatography/tandem mass spectrometry at different time intervals, i.e. during the treatments and after appropriate withdrawal times. Our findings confirm the high and rapid rate of dexamethasone urinary excretion irrespective of the nature of the treatment, and provide useful reference values that can be conveniently employed for forensic purposes.

Malachite green (MG) is still illegally used as a fungicide in aquaculture. In fish it is absorbed and metabolised to its major reduced metabolite, leucomalachite green (LMG). This latter represents the main residue found in fish tissues and may persist for several months. Since MG, suspected to act as a tumour promoter in vitro and in vivo, might be also present as a residue in fish, the present study was undertaken to ascertain the in vitro toxicity of both compounds in two human tumour cell lines (Caco-2 and HEp-2). After 24h incubation with MG, significant decreases of cell viability, measured by neutral red uptake (NRU) or total protein content (TPC) as well as proliferation capability (colony-forming ability, CFA) were noticed in HEp-2 cells; the mean IC(50) value was about 2 microM. As regards the differentiated Caco-2 cells, MG caused a dose-related significant cytotoxicity, measured either by MTT test, the LDH leakage or NRU, with a mean IC(50) value of about 15 microM. By contrast, LMG disclosed, in both cell lines, a lower cytotoxicity compared to MG. These results also show that HEp-2 cells are more sensitive than intestinal cells to the toxic action of both compounds.

Little is known about the effects of aging on the hepatic drug metabolizing capacity of horses despite the relatively long lifespan characterizing this species. A wide array of cytochrome P450 (CYP)-dependent monooxygenases, carboxylesterases and transferases were assayed in liver microsomes from 50 female horses in an age range between less than 1 year to over 12 years. Rather unexpectedly, both the CYP content and the activity of NADPH cytochrome c reductase rose as a function of age. Accordingly, a general increasing trend was recorded in the rate of the in vitro metabolism of the substrates reported to be related to CYP2B-, CYP2E- or CYP3A, although, as detected by Western immunoblotting, only the levels of proteins recognized by anti-rat CYP3A- and CYP2B antibodies appeared to increase consistently. Also the carboxylesterases and uridindiphosphoglucuronyl-transferase (UGT) activity toward 1-naphthol displayed a similar trend, glutathione S-transferase accepting 3,4-dichloronitrobenzene as a substrate being the only enzyme activity showing an age-related decline. A positive correlation was also found between liver cadmium content and CYP amount as well as the activities of most monooxygenases (except for those related to CYP1A), carboxylesterases, and UGT. While confirming that a number of enzyme activities are less expressed in foals, our results contradict the general view that the drug metabolizing capacity drops in elder individuals. Although several other factors can influence the kinetics of foreign compounds in aged animals, data from this study may provide insight in understanding possible age-related differences in drug efficacy and the response to toxic substances in horses.