Norwegian Food Safety Authority Research Articles

Evaluation of novel PCR-based method to assess gill injuries in fish caused by the cnidarian Ectopleura larynx

AbstractGill disease is a major threat to aquaculture of Atlantic salmon, with an unknown and likely underestimated contribution from cnidarians such as jellyfish and biofouling hydroids. To better understand the risk and thus enable mitigation, technology for the certain identification of cnidarian-related gill damage is needed. We used the hydroid Ectopleura larynx in a case study to determine whether the exposure of salmon to nematocyst-bearing hydrozoans can be deducted via non-destructive PCR-based methods. In a field experiment, we evaluated (i) whether swabbing the inside of the gill operculum in farmed Salmo salar and subsequent PCR analysis can provide quantifiable information about the presence of E. larynx material in the gill chamber and, if so, (ii) whether the screening results correlate with histological assessments of gill damage. The developed PCR methods were able to detect the presence of biofouling hydroids in ambient water. However, despite exposure to suspended hydroid particle concentrations that did result in gill damage in some salmon, quantitative PCR results did not correlate with histological gill assessments. For opercular swabs to serve as a diagnostic tool for detecting biofouling-mediated gill damage in live salmon, increased specificity of genetic markers and improved sampling methods are needed.Animal trial permit no. 24252 (granted 06.07.2020, Norwegian Food Safety Authority).

The first case of Echinococcus canadensis found in a moose in Norway: What does it entail?

The first case of Echinococcus canadensis found in a moose in Norway: What does it entail?

The Safety Assessment of Cosmetic Perfumes by Using In Chemico and In Vitro Methods in Combination with GC-MS/MS Analysis.

Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential (in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential (in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption (in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their 'Opinion on Tea tree oil' document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.

PM 3/66 (3) Guidelines for the management of plant health risks of biowaste of plant origin

<scp>PM</scp> 3/66 (3) Guidelines for the management of plant health risks of biowaste of plant origin

Evaluation of the Arguments in the Appeal from Bayer Crop Science of the Decision Made by the Norwegian Food Safety Authority on the Fungicide Infinito with the Active Substances Fluopicolide and Propamocarb

Infinito is a new fungicide containing the two active substances fluopicolide and propamocarb-HCl intended to protect potatoes against the blight pathogen Phytophtora infestans. Fluopicolide is a new active substance in Norway, while propamocarb-HCl is already approved in several products. The risk assessment of Infinito was finalized in a meeting on 29. May 2012 by the Panel on Plant Protection Products of the Norwegian Scientific Committee for Food Safety (VKM).&#x0D; The main conclusions from the risk assessment of Infinito were:&#x0D; &#x0D; VKMs opinion is that both fluopicolide and its main metabolite M-01 (2,6- dichlorobenzamid (BAM)) are persistent in Norwegian soils and surface waters.&#x0D; Fluopicolide and its main metabolite M-01 may accumulate in Norwegian soils.&#x0D; The metabolite M-01 is highly mobile, while fluopicolide shows lower mobility in both studies and modelling.&#x0D; &#x0D; Based on the environmental properties pointed out in the risk assessment, The Norwegian Food Safety Authority (Mattilsynet) turned down the application for use of Infinito in Norway.&#x0D; The decision made by Mattilsynet has been appealed by the applicant, Bayer Crop Science. No new studies have been presented.&#x0D; Mattilsynet has asked VKM to consider the arguments in the appeal from Bayer Crop Science on the risk assessment of Infinito. The appeal and arguments were discussed in a meeting in VKMs Panel on Plant Protection Products on 13. December 2013.&#x0D; The conclusions were as follows:&#x0D; VKM maintains the previous conclusion on the risk assessment on persistence, accumulation and mobility of fluopicolide and one of the metabolites M-01.&#x0D; Our conclusion is further strengthened by additional documentation on:&#x0D; &#x0D; Persistence of M-01 as indicated by data from the National Monitoring program (JOVA) and international studies&#x0D; Accumulation as related to results from 4 year field studies and model calculations using the Finnish PEC calculator&#x0D; Mobility of M-01 as identified by FOCUS PELMO, FOCUS PEARL and MACRO simulations using Swedish and Norwegian scenarios in addition to monitoring results from groundwater in Norway&#x0D; &#x0D; Opinion from EFSA indicating that model simulations and risk of leaching to groundwater from row crops are under-estimated by a factor of six, and should be revised in the new FOCUS scenarios. Half-life calculations based on field studies of mobile substances should be avoided as some of the substances could have escaped to deeper layers and therefore showing artificially high degradation rates.

Risk Assessment of the Biological Control Product «Gulløyelarver» with the Active Organism Chrysoperla Carnea

Gulløyelarver (green lacewing larvae, Chrysoperla carnea) is a product for biological control. The application is for use against aphids in green-houses and tunnels.&#x0D; Gulløyelarver was used in Norway from 1985-1993. An assessment in 2001 concluded however that the use of products with Chrysoperla carnea could represent an environmental risk since it was not known if the species in the products were the same as the ones with natural occurrence in Scandinavia.&#x0D; In this regard, The Norwegian Food Safety Authority would like VKM to perform an assessment of possible risks related to health and environment in light of possible new data.&#x0D; VKM’s conclusions are as follows:&#x0D; Health:&#x0D; The larvae of Chrysoperla carnea have hollow jaws through which they can inject digestive enzymes into their prey. In contact with humans, the larvae are capable of delivering painful bites which may cause local swelling. Such bites are however not considered dangerous, and can be avoided with preventive measures.&#x0D; Allergic asthma and rhino conjunctivitis has been reported in persons working in the production of biological agents with Chrysoperla carnea, but it is the opinion of VKM that such effects are not likely to be relevant for users of the agents.&#x0D; Environment:&#x0D; A previous assessment in 2001 concluded that the use of products with Chrysoperla carnea represented an environmental risk because of the risk of genetic interference with natural populations of the species in Norway.&#x0D; Lacewings belonging to the Chrysoperla carnea complex are considered established and indigenous in Norway, and a recent study by the Norwegian Institute for Agricultural and Environmental Research (Bioforsk) strongly suggests that the lacewings in the commercial products belong to the same cryptic species complex as individuals sampled in Norway. In case the species in the products is different from those present in Norway, any genetic interference with local populations in Norway is prevented by differences in duetting songs.&#x0D; If an invertebrate biological control agent is indigenous and has limited direct or indirect effect on the environment, it is the opinion of VKM that it could be authorized for release in greenhouses or plastic tunnels.&#x0D; Chrysoperla carnea is polyphagous and cannibalistic. They prefer aphids, but may also consume other insects and mites. It is however the opinion of VKM that the environmental risk from this will be minimized in greenhouses and tunnels where the release will be in a contained environment and directed against aphid colonies.&#x0D; Establishment, host range and dispersal ability should be carefully reviewed, even if the species is indigenous. Chrysoperla carnea may establish in the greenhouse and plastic tunnels and may also possess the ability to disperse and survive in the field. However, it is the opinion of VKM that the direct and indirect effects of this are at most moderate, although it cannot be completely excluded that Chrysoperla carnea species in the products might also have properties that have not been reviewed.

Risk Assessment of the Fungicide Infinito with the Active Substances Fluopicolide and Propamocarb HCL

Infinito is a new fungicide containing the two active substances fluopicolide and propamocarb-HCL. Infinito is a new generation fungicide to protect potatoes against the blight pathogen phytophtora infestans. The risk assessment was finalized at a meeting Mai 29, 2012, by the Panel on plant protection products of the Norwegian Scientific Committee for Food Safety (VKM). &#x0D; The Norwegian Food Safety Authority would like, in this regard, an assessment of the following:&#x0D; &#x0D; The fate and behaviour in the environment and the ecotoxicological effects and risks with regard to the properties of Infinito and the active substances. The Panel is particularly asked to look at the following: o The persistence of fluopicolide and its metabolites. o The leaching potential of fluopicolide and its metabolites.&#x0D; &#x0D; VKM considers both fluopicolide and its main metabolite M-01 (2,6-dichlorobenzamid (BAM)) to be persistent in Norwegian soils and surface waters.&#x0D; Other conclusions from VKM are as follows:&#x0D; &#x0D; Fluopicolide and its main metabolite may have a significant potential for soil accumulation after repeated use under Norwegian conditions.&#x0D; &#x0D; &#x0D; &#x0D; Fluopicolide shows low mobility in both studies and modelling. Metabolite M-01 (BAM) is however highly mobile.&#x0D; &#x0D; &#x0D; &#x0D; There is minimal risk for toxic effects of fluopicolide to terrestrial and aquatic organisms with the proposed application regime.&#x0D;

Risk Assessment of the Fungicide Talius with the Active Substances Proquinazid

Talius is a new fungicide containing the new active substance proquinazid. Talius is a fungicide against cereal powdery mildew (Blumeria graminis) in cereals and grass seed. The risk assessment was finalized at a meeting Mai 29, 2012, by VKM’s Scientific Panel on plant protection products (VKM). VKM is in particular asked by the Norwegian Food Safety Authority to look at the following: &#x0D; &#x0D; The human health risk for operators related to the properties of the active substance and the product. o The effects seen in studies on dog and if these effects warrant a classification for chronic toxicity. o The oncogenic effects in liver and thyroid. o The establishment of reference values (ADI, AOEL and ARfD). o Dermal absorption. o The classification and labelling of the active substances and the product. • The fate and behaviour in the environment and the ecotoxical effects and risks with regard to the properties of Talius and proquinazid.&#x0D; &#x0D; VKM’s conclusion is as follows: &#x0D; Health:&#x0D; VKM concluded that a less serious effect (dose-related ocular discharge increase) was seen in dogs in both the 90 days study and 1 year-study. The opinion of the Panel is that cholangiocarcinomas is relevant for the classification of cancer and VKM is concerned about these effects. &#x0D; VKM proposes an NOAEL of 1.2 mg/kg bw/day for proquinazid based on the 2 year study with rats.&#x0D; VKM support:&#x0D; &#x0D; The proposed ADI value of 0.01 mg/kg bw/day. • The proposed AOEL value of 0.02 mg/kg bw/day.&#x0D; &#x0D; &#x0D; &#x0D; The proposed ARfD value of 0.2 mg/kg bw/day. • The proposed classification from The Norwegian Food Safety Authority.&#x0D; &#x0D; VKM supports The Norwegian Food and Safety Authority calculations for dermal absorption under Norwegian directions for use (2.6 times higher dilution).&#x0D; Environment:&#x0D; Proquinazid can be persistent under prevailing conditions in Norway and the Panel considers the results from the Finnish PEC calculator to be relevant for Norwegian conditions and expects that repeated annual applications may cause accumulation in soil up to an equilibrium level under Norwegian conditions.The potential for groundwater contamination from leaching of proquinazid and its metabolites are low. There are minimal risks for toxic effects of proquinazid to terrestrial organisms, sediment dwelling organisms, aquatic plants, and algae with the proposed application regime. &#x0D; For fish and invertebrates minimal risks are calculated provided that a 3 m buffer zone is used.

Risk Assessment of the Insecticide Plenum 50 WG with the Active Substances Pymetrozine

Plenum is a new insecticide containing the new active substance pymetrozine. Plenum is an insecticide against different pests in ornamentals, lettuce, cucumber and tomato in greenhouse and against pollen beetles in oilseed- and turnip rapes. The risk assessment was finalized at a meeting Mai 29, 2012, by VKM’s Scientific Panel on plant protection products (VKM). The Panel is in particular asked by the Norwegian Food Safety Authority to look at the following: &#x0D; &#x0D; The human health risk for operators related to the properties of the active substance and the product. The Panel is in particular asked to look at the following: o The effects seen in studies on dog and if these effects warrant a classification for chronic toxicity. o The oncogenic effects in liver and lungs o The genotoxicity of metabolite CGA 300407. o The effects on reproduction and if the effects seen in teratology studies and developmental neurotoxicity study warrant a classification for developmental toxicity o The establishment of NOAELs and reference values (ADI, AOEL and ARfD). o The classification and labelling of the active substances and the product.&#x0D; &#x0D; VKM’s conclusion is as follows: &#x0D; The effects reported in the repeated dose toxicity studies with dogs should be considered as adverse. &#x0D; The increased incidence of liver and lung tumors should be considered as relevant for humans. It cannot be excluded that a genotoxic mechanism could be involved in the formation of the liver tumors, which would have implications for risk assessment. It should therefore be considered to test pymetrozine in more sensitive in vivo genotoxic endpoints in liver. &#x0D; The effects reported in the teratogenicity studies in rats and rabbits and in the developmental neurotoxicity study in rats should be considered for a classification of pymetrozine for developmental toxicity. &#x0D; Risk calculations with both the German model and the UK POEM show low risk if personal protection equipment is used.&#x0D; VKM propose:&#x0D; &#x0D; NOAEL of 0.6 mg/kg bw/day for pymetrozine based on the 1-year study in dogs.&#x0D; &#x0D; &#x0D; &#x0D; AOEL of 0.006 mg/kg bw/day for pymetrozine based on the NOAEL value at 0.6 mg/kg bw/day from the one year study in dogs and an UF of 100.&#x0D; &#x0D; &#x0D; &#x0D; ADI of 0.006 for pymetrozine based on the NOAEL value at 0.6 mg/kg bw/day from the one year study in dogs and an UF of 100.&#x0D; &#x0D; &#x0D; &#x0D; ARfD of 0.02 mg/kg bw/day for pymetrozine based on the LOAEL value at 8.1 mg/kg bw/day from the developmental neurotoxicity study and an UF of 500 (10 x interspecies difference, 10 x intraspecies difference, 3 x due to the use of a LOAEL value and 2 x due to the adversity of the neurodevelopmental effects).&#x0D; &#x0D; VKM supports the classification proposal from Norwegian Food Safety Authority.

Risk Assessment of the Growth Inhibitor Bonzi with the Active Substance Paclobutrazol

Bonzi is a new plant growth regulator containing the active ingredient paclobutrazol of the triazole chemical class. Bonzi is for use on ornamental plants, such as Chrysanthemum, Perennial Plants, Bedding Plants, Foliage Plants, Geraniums, Hibiscus and Azaleas, in nurseries and greenhouses.&#x0D; &#x0D; VKM was requested by the Norwegian Food Safety Authority to consider the potential of Bonzi and paclobutrazol to induce reproductive effects in humans; in particular the relative sensitivity and relation between maternal effects and the effects on the offspring; and to what extent cleft palate observed in developmental studies in rat can be regarded as a specific teratogenic effect of relevance for humans. The risk assessment was finalized in a meeting in VKM’s Scientific Panel on Plant Protection Products on May 24. 2013.&#x0D; VKM’s conclusions are as follows:&#x0D; &#x0D; No adverse effect on fertility or reproductive performance was seen in rats. VKM concluded that the incidences of twisted snout observed in the F1 and F2 offspring of paclobutrazol treated rats are not likely to represent a developmental alteration, but rather an unspecific toxic effect.&#x0D; &#x0D; Marked maternal toxicity was seen in rats above 250 mg/kg bw/day, while partially ossified 7th cervical transverse processes and supernumerary 14th ribs were found in the offspring at 10 - 40 mg/kg/day. VKM concluded that the latter should be regarded as a direct teratogenic effect of paclobutrazol.&#x0D; &#x0D; Furthermore, VKM concluded that the data from the developmental toxicity studies are inconclusive regarding the effect on cleft palate development in rat foetuses.&#x0D; &#x0D; VKM proposes a NOAEL of 2.5 mg/kg bw/day for paclobutrazol based on a developmental toxicity study in rats.

Risk Assessment of the Fungicide Luna Privilege with the Active Substance Fluopyram

Luna Privilege is a new fungicide for use in apples, pears, outdoor and indoor strawberries, outdoor and indoor lettuces, peas, beans and indoor tomatoes, and contains the new active substance fluopyram.&#x0D; VKM was requested by the Norwegian Food Safety Authority to consider the possible health risk for operators related to the properties of Luna Privilege and fluopyram; in particular to evaluate the potential for bioaccumulation, reproductive and neurotoxic effects, and discuss possible mechanisms involved in liver and thyroid tumor formation observed in rats, and the establishment of NOAELs and reference values.&#x0D; VKM was also asked to evaluate the fate and behaviour of fluopyram in the environment, and the ecotoxicological effects and risks related to its use, in particular the potential for groundwater contamination, safety margins and possible effects on birds and aquatic organisms.&#x0D; The assessment was finalized in a meeting on December 13. 2013 by VKM’s Panel on Plant Protection Products.&#x0D; VKM’s conclusions are as follows:&#x0D; Health:&#x0D; It is the opinion of VKM that:&#x0D; &#x0D; The active ingredient fluopyram has low potential for bioaccumulation, and the data do not suggest a sex-specific excretion.&#x0D; &#x0D; &#x0D; &#x0D; An in vivo Comet Assay in rat liver could help to further elucidate the genotoxic potential of fluopyram.&#x0D; &#x0D; &#x0D; &#x0D; It can not be excluded that the reported incidence of “gall bladder absent” is treatment related.&#x0D; &#x0D; &#x0D; &#x0D; NOAEL for the 90-day feeding study in rats should be set to 3.06 mg/kg bw/day, resulting in an AOEL of 0.03 mg/kg bw/day.&#x0D; &#x0D; &#x0D; &#x0D; The “dumb-bell or incomplete ossification and/or bipartite/normal cartilage” should be considered as a malformation and regarded as treatment related.&#x0D; &#x0D; &#x0D; &#x0D; The time points used for neurotoxic measurements are not optimal to detect neurotoxic effects from acute exposure, since the time window between the first and second measurements is too long.&#x0D; &#x0D; &#x0D; &#x0D; The studies where effects of fluopyram and phenobarbital are compared can not be used to exclude human relevance of the tumor-inducing effect of fluopyram in the liver of female rats.&#x0D; &#x0D; &#x0D; &#x0D; The results from the mechanistic studies are insufficient to support the proposed mode of action for the induction of thyroid follicular cell tumors in male mice, and thus the induction of thyroid tumors in male mice could be relevant for humans.&#x0D; &#x0D; VKM proposes:&#x0D; &#x0D; &#x0D; NOAEL of 1.2 mg/kg bw/day based on a 2 year feeding study in rats.&#x0D; &#x0D; &#x0D; &#x0D; ADI: 0.012 mg/kg bw/day&#x0D; &#x0D; &#x0D; &#x0D; AOEL: 0.03 mg/kg bw/day&#x0D; &#x0D; &#x0D; &#x0D; ARfD: 0.25 mg/kg bw/day&#x0D; &#x0D; &#x0D; Risk calculations for field use of Luna Privilege show minimal risk if personal protective equipment is used. The AOEL of fluopyram for greenhouse use is not exceeded, even without protective equipment. Re-entry and bystander exposure is calculated to be well below the AOEL.&#x0D; Environment:&#x0D; It is the opinion of VKM that:&#x0D; &#x0D; Worst case degradation rates from laboratory studies should preferably be used to calculate PECsoil values for fluopyram.&#x0D; Both fluopyram and fluopyram-7-hydroxy have a high potential for groundwater contamination.&#x0D; &#x0D; &#x0D; &#x0D; The efficacy of buffer zones needs to be considered on a case-by-case basis, and further validation of values for efficacy from the model simulation is necessary.&#x0D; &#x0D; &#x0D; &#x0D; It is further the opinion of VKM that all the refinements used in the risk assessment for birds are relevant. Since the TER values estimated for all crops except for orchards are below the trigger following refinements, it is the view of VKM that the data indicate medium risk for strawberries and pulses, and high risk for lettuce in open field.&#x0D; &#x0D; &#x0D; &#x0D; The use of LC50 values for fluopyram in the TER calculations with a TER trigger value of 100 is overly conservative, and a reduction of the acute trigger for both invertebrates and fish from 100 to 10 for such calculations are suggested.&#x0D; &#x0D; &#x0D; &#x0D; The trigger for acute toxicity is not exceeded for any of the crops. For chronic toxicity, VKM concludes that there is a moderate risk for effects on fish when Luna Privilege is applied to beans/strawberries without the use of a vegetated mitigation buffer-strip.&#x0D;

Risk Assessment of the Fungicide Aviator Xpro EC 225 with the Active Substances Bixafen and Prothioconazole

Aviator Xpro EC 225 is a new fungicide for use in cereals, containing the new active substance bixafen and the already approved active substance prothioconazole. Prothioconazole was assessed by the Norwegian Scientific Committee for Food Safety in 2006, and is therefore not included in this report.&#x0D; VKM was requested by the Norwegian Food Safety Authority to consider the possible health risk for operators related to the properties of bixafen used in Aviator Xpro EC 225; in particular to evaluate the relevance of the effects of bixafen on liver and coagulation parameters observed in rats and mice, thyroid tumours and reproductive effects observed in rats, and the establishment of NOAELs and reference values. VKM was also asked to evaluate the fate and behaviour of bixafen in the environment, and the ecotoxicological effects and risks related to its use. The risk assessment was finalized in a meeting on May 24. 2013 by VKM’s Scientific Panel on Plant Protection Products.&#x0D; VKM’s conclusions are as follows:&#x0D; Health:&#x0D; VKM concluded that the liver effects reported in sub-chronic and chronic studies in rats, dogs and mice exposed to bixafen, as well as the effects on coagulating parameters, should be considered adverse and of relevance to humans.&#x0D; It is the opinion of VKM that the thyroid follicular cell tumours reported in female rats exposed to bixafen is not sufficient to suggest that bixafen has a tumour inducing potential.&#x0D; It is further the opinion of VKM that it cannot be excluded that the reduced pup weight during lactation in the two-generation study is mediated by bixafen via the milk, and that bixafen has a direct effect on the number of stillborn pups in the F1 and F2 generation.&#x0D; Finally, the pup developmental variants and anomalies reported in the teratogenicity study are considered treatment related, and not as secondary effects related to maternal toxicity.&#x0D; VKM proposes a NOAEL of 2.0 mg/kg bw/day based on a 2 year feeding study in rats.&#x0D; VKM support/propose:&#x0D; &#x0D; ADI: 0.02 mg/kg bw/day&#x0D; AOEL: 0.13 mg/kg bw/day&#x0D; ARfD: 0.2 mg/kg bw/day&#x0D; &#x0D; Risk calculations show minimal risk if personal protective equipment is used.&#x0D; Environment:&#x0D; Bixafen is shown to be persistent in soil. VKM considers the results from a field study on a German site and the Finnish PEC calculator to be relevant and concludes that repeated annual applications can cause accumulation in soil under Norwegian conditions. There is also a potential for groundwater contamination from leaching of the metabolite M44.&#x0D; VKM has concluded that the use of bixafen as an ingredient in Aviator Xpro EC 225 with the proposed application regime in Norway will represent a minimal risk for toxic effects to terrestrial organisms.&#x0D; The toxicity of bixafen to aquatic organisms is high, and minimal risk of effects in surface waters can be achieved only if risk mitigation measures with bufferzones of 10 m are applied.

Risk Assessment of the Insecticide Movento 100 SC with the Active Substance Spirotetramat

Movento 100 SC is a new insecticide containing the active substance spirotetramat. The intended use is in stone fruit, pome fruit, vegetables and ornamentals outdoors, and lettuce, tomatoes and cucumbers in greenhouses.&#x0D; VKM was requested by the Norwegian Food Safety Authority to consider possible health risk for operators related to the properties of Movento 100 SC; in particular the relevance of the effects of spirotetramat on thyroid hormones, brain, thymus and body weight observed in dogs, and the reproductive effects of spirotetramat observed in rats. VKM was also asked to consider the fate and behaviour of Movento 100 SC with the active ingredient spirotetramat in the environment, and the ecotoxicological effects and risks related to its use. The risk assessment was finalized in a meeting on May 24. 2013, by VKM’s Scientific Panel on Plant Protection Products.&#x0D; VKM’s conclusions are as follows:&#x0D; Health:&#x0D; VKM concludes that spirotetramat shows toxic effects in dogs and rats that could be relevant for humans. Thyroid and thymus glands are target organs in the oral subchronic toxicity studies of spirotetramat in dogs, and effects are observed from 19 mg/kg bw/day (600 ppm). Decreases in circulating thyroid hormone levels were detected in all three studies carried out with dogs (28-, 90-days and 1-year) and should be considered toxicologically relevant. The opinion of the Panel is that it cannot be excluded that the observed brain dilatation in dogs is treatment-related, and relevant to humans.&#x0D; Furthermore, VKM concludes that the reproductive effect observed in rats could be relevant for humans.&#x0D; VKM proposes a NOAEL of 5 mg/kg bw/day (200 ppm) for spirotetramat based on a 1- year toxicity study in dogs, and a NOAEL of 100 mg/kg bw/day based on the acute neurotoxicity study in rats.&#x0D; VKM supports/proposes:&#x0D; &#x0D; ADI: 0.05 mg/kg bw/day.&#x0D; AOEL: 0.05 mg/kg bw/day.&#x0D; ARfD: 1 mg/kg bw/day.&#x0D; &#x0D; Risk calculations show minimal risk if personal protective equipment is used.&#x0D; Environment:&#x0D; VKM concludes that spirotetramat and its metabolites are not expected to accumulate in soil. It is not expected that spirotetramat or any of its metabolites will reach concentrations in groundwater above the threshold level of 0.1 μg/L when the formulation Movento 100 SC is applied according to the intended use.&#x0D; VKM concludes that use of Movento 100 SC with the active substance spirotetramat according to the proposed application scheme in Norway represents a minimal risk of adverse effects on terrestrial mammals, birds, earthworms, and soil microorganisms. However, in-field effects on sensitive species of predatory mites in the crop cannot be excluded.&#x0D; The risk of adverse effects on bees is minimal providing that spirotetramat is not used on crops during flowering or when bees are actively foraging.&#x0D; For aquatic organisms in surface water, the risk is considered minimal, provided that a 5 m buffer zone to open water is used.

Risk Assessment of the Biological Plant Protection Products Nemasys G and Nemasys H with the Active Organism Heterorhabditis Bacteriophora

Nemasys G and Nemasys H with the nematode Heterorhabditis bacteriophora as the active organism is applied for as a plant protection product in Norway. Nemasys G is intended for use against the garden chafer (Phyllopertha horticola) in lawns and Nemasys H against black vine weevil (Otiorhynchus sulcatus) in strawberries and ornamentals.&#x0D; VKM was requested by the Norwegian Food Safety Authority to consider the possible health and environmental risk related to the properties of Nemasys G and Nemasys H; in particular to evaluate if the nematode is naturally occurring in Norway, the potential for establishing and spreading under Norwegian conditions, possible taxonomic challenges and assessment of the health risk related to its use.&#x0D; The assessment was finalized in October 2014 by VKM’s Panel on Plant Protection Products.&#x0D; VKM’s conclusions are as follows:&#x0D; Natural occurrence of the nematode:&#x0D; The nematode Heterorhabditis bacteriophora has not been observed in Norway, but is widespread world-wide in regions with continental and Mediterranean climates. In Europe it has been isolated in France, Germany, Hungary, Italy, Moldavia, Spain, Switzerland and the UK.&#x0D; Potential for establishing and spreading of the nematode under Norwegian conditions:&#x0D; The thermal preference of H. bacteriophora restricts its establishing. Short term establishment in the growing season is possible in parts of Norway. This nematode has however poor long term survival in soil, especially in the absence of suitable hosts, and the potential for long term establishment in Norway is considered to be low.&#x0D; Taxonomic challenges:&#x0D; There are no taxonomic challenges related to assessment of this nematode.&#x0D; Human health risk for operators:&#x0D; Exposure of user is considered to be low. The use of plant protection products containing Heterorhabditid nematodes against insects has not been associated with health effects on humans. The symbiotic bacteria Photorhabdus luminescens has not been linked to pathogenic effects in humans. It is therefore the view of VKM that the use of the nematode Heterorhabditis bacteriophora with the symbiotic bacteria Photorhabdus luminescens will have minimal health risk for operators.

Opinion on the Safety of BioProtein® by the Scientific Panel on Animal Feed of the Norwegian Scientific Committee for Food Safety

Opinion on the Safety of BioProtein® by the Scientific Panel on Animal Feed of the Norwegian Scientific Committee for Food Safety

Environmental Risk Assessment of the Pesticide Simplex with the Active Substances Aminopyralid and Fluroxypyr

Simplex is a new herbicide in Norway containing the active substances aminopyralid and fluroxypyr. Aminopyralid is a new active substance in Norway, but fluroxypyr is registered in several authorized products. The intended use of the plant protection product is in established grassland for forage, established ley and pasture and in grass at the first year of sowing. &#x0D; During the spring of 2010, the Norwegian Scientific Committee for Food Safety (VKM) performed a human health risk assessment of the active substance aminopyralid and the product on request from the Norwegian Food Safety Authority. On further request from the Norwegian Food Safety Authority, VKM has performed a risk assessment on the fate and the behaviour in the environment and the environmental risk with regard to the properties of the active substance aminopyralid and the product Simplex, which was finalized at a meeting of VKM’s Scientific Panel on plant protection products (Panel 2) on November 25, 2010. VKM Panel 2’s conclusion is as follows: Aminopyralid is highly mobile in soil and the substance is very likely to reach ground water at concentrations above the threshold of 0.1 µg/L. Experimental data (watersediment studies) suggest that aminopyralid is persistent. However, aminopyralid concentrations in surface water are expected to decrease rapidly due to photolytic degradation. The overall risk for adverse effects on terrestrial and aquatic organisms following the proposed application of Simplex is considered to be minimal.

Assessment of the Potential Risks Associated with the Proposed Use of Composted Waste from the Production of Bacitracin as a Soil Additive

Bacitracin is a hexapeptide antibiotic, with a substituted thiazolidine nucleus, produced by some strains of B. licheniformis. It is mainly active against Grampositive bacteria, although many differences in susceptibility exist among the bacterial species.Alpharma A.S. Norway has produced bacitracin for use in human medicine since 1954. Until 1998, the fermentation waste from the production of bacitracin was added to animal feed in some European countries, including Norway, to promote growth of pigs and domestic fowl. In 1998, fermentation waste containing bacitracin as a food additive was banned by the EU to reduce the risk of developing bacitracin-resistant bacteria in animals, and the subsequent possible transfer of such bacteria to humans via the food chain. Use of fermentation waste containing bacitracin as a feed additive has not been officially banned in Norway, but it is no longer used for this purpose. Alpharma is therefore actively seeking alternative uses for their production waste. As the waste material is rich in nutrients, the company proposes that it could be developed as a soil additive by fermenting it with chipped bark and lime. The Norwegian Food Safety Authority (Mattilsynet) commissioned the Panel on Biological Hazards of the Norwegian Scientific Committee for Food Safety (Vitenskapskomitéen for mattrygghet) to develop a risk assessment regarding the use of composted waste material from Alpharma’s production of bacitracin, as a soil additive. In response, an ad hoc Working Group of experts was appointed with the mandate to draft a risk assessment which should include the following elements: assessment of risk to human health and/or the environment in relation to residual content of bacitracin in the finished soil additive product and assessment of the risk in relation to dissemination of the production strain and antimicrobial resistance genes. The Panel on Biological Hazards concludes that the risks to human health and the environment posed by residual bacitracin present in the finished product are minimal. Furthermore, as Bacillus licheniformis is considered essentially non-pathogenic, occurring rarely as an opportunistic pathogen, the risk posed by this bacterium to human health or the environment is very low. It is reasonable to assume that during the early composting process horizontal transfer of bacitracin and erythromycin resistance genes, from the B. licheniformis producer strain to environmental bacteria, will exceed background levels. However, this is considered to represent a low risk to human health and the environment.

Risk Assessment of the Fungicide Bontima with the Active Substances Cyprodinil and Isopyrazam

Bontima is a new fungicide containing the two active substances isopyrazam and cyprodinil. Bontima is a fungicide against the most important diseases in winter and spring barley. Isopyrazam is a new active ingredient with new mechanisms of action that may delay the development of fungicide resistance in treated crops. &#x0D; The risk assessment was finalized at a meeting May 29, 2012, by the Panel on plant protection products of the Norwegian Scientific Committee for Food Safety (VKM). &#x0D; The Norwegian Food Safety Authority would like, in this regard, an assessment of the following: &#x0D; &#x0D; The fate and behaviour in the environment and the ecotoxicological effects and risks with regard to the properties of Bontima and the active substances. The Panel is particularly asked to look at the following: o The persistence of isopyrazam and its metabolites. o The leaching potential of isopyrazam and its metabolites. &#x0D; &#x0D; VKM’s conclusion is as follows: &#x0D; Fate-related issues &#x0D; Isopyrazam is likely to be persistent in Norwegian soils with an associated risk of accumulation after repeated use. &#x0D; Isopyrazam exhibits low mobility in soil and is not expected to reach groundwater, however the two main metabolites are likely to exceed the EUs drinking water limit of 0.1 \(\mu\)g/L in groundwater. &#x0D; Since drainage and runoff, as well as drift, contributes to concentrations in surface water the risk assessment have to consider all these sources. In the EU DAR step 4 calculations, buffer zones of 20 m have been used to reduce runoff levels contributions by 80 %. VKM does not accept the use of these buffer zone modifications for Norwegian topographic conditions (with e.g. steeper agricultural areas). &#x0D; Risk to the environment &#x0D; There is minimal risk for toxic effects of isopyrazam to terrestrial organisms. &#x0D; For the aquatic compartment, there is a high risk for toxic effects of isopyrazam to aquatic organisms with the proposed application regime. This is based on calculations of runoff without buffer zone modifications, from which the resulting TER calculations show high risk of acute effects on fish and a medium risk of acute effects on invertebrates. A minimal risk for toxic effects was calculated for sediment dwelling organisms, aquatic plants, and algae.

Re-Assessment of the Plant Protection Product PROMAN – with the Active Ingredient Metobromuron [Edition 2

Proman is a broad spectrum selective herbicide for potatoes grown outdoors, containing the active substance metobromuron. VKM’s Panel on Plant Protection Products has previously discussed questions concerning Proman raised by The Norwegian Food Safety Authority, and stated its opinion in a report of 21. January 2015 (http://www.vkm.no/dav/3c64afe035.pdf). &#x0D; Following this report, The Norwegian Food Safety Authority turned down the application to register Proman as a plant protection product in Norway. The applicant filed a complaint on this decision, and the VKM Panel has been asked to reassess its previous opinion in light of the information given by the applicant in the complaint. &#x0D; The VKM Panel has discussed the arguments put forward in the complaint. The arguments did not change the Panel’s main conclusions in the original assessment. Some changes in the wording of the conclusions were however done, in order to put more emphasis on areas of uncertainty. &#x0D; These are the standing conclusions of VKM’s Panel on Plant Protection Products:&#x0D; &#x0D; On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males: &#x0D; It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidences of mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the increases in tumours associated with exposure to metobromuron are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study could be relevant for tumour induction in humans. &#x0D; Higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations: &#x0D; VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure should be considered as a whole when assessing for developmental effects. &#x0D; Establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD): &#x0D; VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. The panel suggests an alternative ARfD value of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day for the observations of incomplete ossification in the rat developmental study. &#x0D; The anti-androgenic potential of metobromuron: &#x0D; The rat carcinogenicity study indicates that metobromuron may interact with the endocrine system. The data from the Hershberger in vivo rat study, the in vitro studies, as well as the comparison with demonstrated effects and mechanisms for flutamide and linuron is suggestive of an anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

Human Health Risk Assessment of the Pesticide Simplex with the Active Substances Aminopyralid and Fluroxypyr

Simplex is a new herbicide in Norway containing the active substances aminopyralid and fluroxypyr. Aminopyralid is a new active substance in Norway, but fluroxypyr is found in several authorized products. The application concerns use in established grassland for forage, established ley and pasture and in grass at the first year of sowing. The Norwegian Scientific Committee for Food Safety (VKM) has on a request from the Norwegian Food Safety Authority performed a risk assessment on human health of the active substance and the product. The risk assessment of the product was approved at a meeting May 11 2010 by VKMs Scientific Panel on Pesticides (Panel 2). VKM’s Panel 2 concludes as following: &#x0D; Both Simplex and the active substance aminopyralid are characterized as extremely irritating to the eye based on persistent irritation to the eyes of rabbits. The product Simplex is also found irritating to the rabbit skin. &#x0D; Aminopyralid has low acute toxicity and is not shown to have genotoxic potential, or to be teratogenic or toxic to the reproduction in animals. There may however be a carcinogenic effect of aminopyralid based on an increased number of uterine sarcomas in mice. The main target organs for sub-chronic and chronic toxicity were the caecum (rats), the stomach (dogs, inflammation) and the liver (dogs, hyperthropy). No adverse effects for chronic toxicity were seen in mice. Rabbit was the most sensitive species for toxicity and the no observed effect levels (NOAELs) derived from studies in this species serve as base for calculations of values for acceptable daily intake (ADI) and acceptable operator exposure level (AOEL). &#x0D; The estimated risk for operator is assessed as minimal both by use of boom spraying (46% of AOEL) and knapsack sprayers (81% of AOEL). &#x0D; However, as a result of the hazard classification, a faceshield and gloves are necessary personal protective equipment (PPE) to be worn during mixing and loading operations, due to the risk of serious damage to the eyes and skin irritation.