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: 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. VKM’s conclusion is as follows: The effects reported in the repeated dose toxicity studies with dogs should be considered as adverse. 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. 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. Risk calculations with both the German model and the UK POEM show low risk if personal protection equipment is used. VKM propose: NOAEL of 0.6 mg/kg bw/day for pymetrozine based on the 1-year study in dogs. 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. 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. 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). VKM supports the classification proposal from Norwegian Food Safety Authority.

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: 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. VKM’s conclusion is as follows: Health: 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. VKM proposes an NOAEL of 1.2 mg/kg bw/day for proquinazid based on the 2 year study with rats. VKM support: The proposed ADI value of 0.01 mg/kg bw/day. • The proposed AOEL value of 0.02 mg/kg bw/day. The proposed ARfD value of 0.2 mg/kg bw/day. • The proposed classification from The Norwegian Food Safety Authority. VKM supports The Norwegian Food and Safety Authority calculations for dermal absorption under Norwegian directions for use (2.6 times higher dilution). Environment: 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. For fish and invertebrates minimal risks are calculated provided that a 3 m buffer zone is used.

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. 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. 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. The assessment was finalized in a meeting on December 13. 2013 by VKM’s Panel on Plant Protection Products. VKM’s conclusions are as follows: Health: It is the opinion of VKM that: The active ingredient fluopyram has low potential for bioaccumulation, and the data do not suggest a sex-specific excretion. An in vivo Comet Assay in rat liver could help to further elucidate the genotoxic potential of fluopyram. It can not be excluded that the reported incidence of “gall bladder absent” is treatment related. 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. The “dumb-bell or incomplete ossification and/or bipartite/normal cartilage” should be considered as a malformation and regarded as treatment related. 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. 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. 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. VKM proposes: NOAEL of 1.2 mg/kg bw/day based on a 2 year feeding study in rats. ADI: 0.012 mg/kg bw/day AOEL: 0.03 mg/kg bw/day ARfD: 0.25 mg/kg bw/day 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. Environment: It is the opinion of VKM that: Worst case degradation rates from laboratory studies should preferably be used to calculate PECsoil values for fluopyram. Both fluopyram and fluopyram-7-hydroxy have a high potential for groundwater contamination. 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. 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. 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. 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.

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). The Norwegian Food Safety Authority would like, in this regard, an assessment of the following: 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. VKM considers both fluopicolide and its main metabolite M-01 (2,6-dichlorobenzamid (BAM)) to be persistent in Norwegian soils and surface waters. Other conclusions from VKM are as follows: Fluopicolide and its main metabolite may have a significant potential for soil accumulation after repeated use under Norwegian conditions.Fluopicolide shows low mobility in both studies and modelling. Metabolite M-01 (BAM) is however highly mobile.There is minimal risk for toxic effects of fluopicolide to terrestrial and aquatic organisms with the proposed application regime.

Risk Assessment of the Pesticide Centium with the Active Substance Clomazone

Centium is a new product in Norway containing the active substance clomazone. The product is applied for use as a herbicide in potato, carrot, cabbage, brussel sprout, swedes, oil seed rape, pea and bean. The Norwegian Institute for Agricultural and Environmental Research recommend approval in potato, carrot, swedes and pea. They do not recommend approval in oil seed rape, cabbage and bean because of lacking documentation on efficacy. The Norwegian Scientific Committee for Food Safety (VKM) was asked by the Norwegian Food Safety Authority to perform a risk assessment on human health and environmental fate of the active substance and the product. The risk assessment of the product was finalized at a meeting May 18, 2011, by VKM’s Scientific Panel on plant protection products (Panel 2). VKM Panel 2’s conclusion is as follows: The active ingredient clomazone is of moderate acute toxicity after oral and inhalation exposure and of low dermal toxicity. The product Centium is of low acute toxicity after oral exposure, by skin contact or by inhalation; however the product may contain a co-formulant, monomeric isocyanate, with sensitizing properties. Due to the lack of documentation on the monomer content, the Panel cannot evaluate the risk of sensitization. UK Poem model estimation of exposure show that exposure to operator is below AOEL and the health risk is therefore minimal. The effects observed in the dog study were considered due to the exposure of clomazone and should therefore be used to determine the NOAEL value. The fertility index used in the two-generation study in rats is not considered relevant as a measure of critical effect. The Panel suggests to use 4000 ppm (354 mg/kg bw/day) which is the highest dose tested in the study. Dose dependent responses were not always evident in the rat teratology study, but significant effects were found at the two highest dose levels (300 and 600 mg/kg bw/day). The observed effects were considered adverse. The proposed NOAEL of 100 mg/kg bw/day was therefore supported. The teratology study with rats is considered relevant for determination of acute reference dose (ARfD) since skeletal malformations can be induced after short exposure periods if the exposure is taking place during a sensitive period of foetal development. The Panel also concludes that based on the results from modeling with MACRO (4.4.2) using the Nordic groundwater scenarios and the input parameters agreed upon in the EU there is a potential for contamination of groundwater exceeding the trigger value of 0.1µg/L for the active ingredient following prescribed usage.

Risk Assessment of the Pesticide Envidor with the Active Substance Spirodiclofen

Envidor is a new product in Norway containing the active substance spirodiclofen. The product is applied for use as an insecticide and acaricide in fruit, berries and ornamentals (field, glasshouses and tunnels). The Norwegian Scientific Committee for Food Safety (VKM) was asked by the Norwegian Food Safety Authority to perform a risk assessment on human health, environmental fate and ecotoxicological effects of the active substance and the product. The risk assessment of the product was finalized at a meeting November 25, 2010, by VKM’s Scientific Panel on plant protection products (Panel 2). VKM Panel 2’s conclusion is as follows: Both Envidor and the active substance spirodiclofen showed low acute oral -, dermal - and inhalation toxicities in animal studies, but showed skin sensitising properties. The estimated risk for operators is assessed as minimal provided adequate use of personal protective equipment. Spirodiclofen may have endocrine disrupting effects, but the in vivo data are not sufficient to make a firm conclusion at this point. Adrenals and other organs of the endocrine system, including the reproductive system, are target organs for chronic toxicity of spriodiclofen. Males seem to be more sensitive than females for adverse reproductive effects of spirodiclofen. Decreased testes and epididymides sizes, testes atrophy and decreased number of sperm were seen both in the parental and subsequent generation of rats. No teratogenic effect of spirodiclofen was seen. The disturbances in the endocrine system may account for the carcinogenic potential of spirodiclofen as evidenced by tumours in testicles, uterus and liver of animals. Spirodiclofen is not considered genotoxic. The Panel regards spirodiclofen to be carcinogenic and toxic to the reproduction in laboratory animals. Both spirodiclofen and its metabolites are rapidly degraded in soil, but while spirodiclofen has a low mobility due to high soil sorption, its metabolites are highly mobile. Use of Envidor with the proposed application regime implies a very high risk for adverse effects on bees and non-target arthropods due to exposure to the active substance spirodiclofen. The risk for adverse effects of spirodiclofen on other terrestrial organisms, and on aquatic organisms provided that a buffer zone of 30 m to surface water is applied, is considered to be minimal.

Risk Assessment of the Insecticide/Acaricide Milbeknock with the Active Substance Milbemectin

Milbeknock is a new insecticide/acaricide containing the new active substance milbemectin, which is a microbial fermentation product of Streptomyces. It is applied for control of mites and leafminers. The intended use is as a foliar spray in fruits (apples/pears), strawberries (only after harvest) and in ornamental plants growing in greenhouse and outdoors. The risk assessment was finalized at a meeting November 24, 2011, by VKM’s Scientific Panel on plant protection products (Panel 2). Panel 2 is in particular asked by the Norwegian Food Safety Authority to look at the following: 1) The human health risk for operators related to the properties of the active substance and the product. 2) The degree of oral absorption. 3) Acute toxicity. 4) The reproduction and developmental toxicity. 5) Establishment of reference values (ADI, AOEL and ARfD). 6) The fate and behaviour in the environment and environmental risk with regard to the properties of Milbeknock and milbemectin. 7) Bioavailability of milbemectin. 8) The microcosm study. VKM Panel 2’s conclusion is as follows: Health: Panel 2 proposes to set the absorption to 50%, which is in agreement with the EU DAR report (propose 47%). For acute toxicicity, Panel 2 concludes that milbemectin probably has a LD50 for dogs between 100 and 200 mg/kg body weight (bw)/day. Dogs seem to be the most sensitive experimental species and should be considered for hazard classification purposes. With respect to reproduction and developmental toxicity, Panel 2 concludes that the documentation of the role of the P-glycoprotein transporter is not convincing, and that the CF1 mice study cannot be used to support the argumentation of no developmental toxicity put forward by the applicant. The following reference values have been estimated: ADI of 0.03 mg/kg bw/day; AOEL of 0.015 mg/kg bw/day and ARfD of 0.067 mg/kg bw/day for milbemectin. Provided that personal protection equipment is used, the AOEL for operators is not exceeded. Environment: With respect to environmental fate, the opinion of the Panel is that the relatively rapid degradation in soil indicates a significant bioavailability in both soil and water-sediment systems. Further it concludes that 0.058µg/L should be regarded as NOECpopulation for the microcosm study. Panel 2 concludes that there is a medium risk of toxic effects on aquatic organisms due to exposure of milbemectin sprayed in fruits with the proposed application regime, provided that a buffer zone of 30 meters to surface water is applied. There are minimal risks of toxic effects on aquatic organisms with sufficient buffer zones in other applied crops. Panel 2 further considers the risk for foliage dwelling non-target predators and parasitoids to be high, and the risk to earthworms to be medium. The strong sorption to soil suggests that the bioavailability in soil may be limited. However, the opinion of the Panel is that the relatively rapid degradation in soil indicates a significant bioavailability. Also, for a substance with such a high log Kow the reported water solubility is relatively high, which will contribute to the availability for biological uptake. The toxicity observed in the microcosm study indicates high bioavailability also in a water/sediment system.

Risk Assessment of the Pesticide Coragen 20 SC with the Active Substance Chlorantraniliprole

Coragen 20 SC is a new product in Norway containing the active substance chlorantraniliprole. It is applied for use in apples against codling moth (Cydia pomonella), apple fruit moth (Argyresthia conjugella) and free leaf living larvae. The Norwegian Scientific Committee for Food Safety (VKM) was asked by the Norwegian Food Safety Authority to perform a risk assessment on human health, environmental fate and ecotoxicological of the active substance and the product. The risk assessment of the product was approved at a meeting 11th of May 2010 by VKMs Scientific Panel on Pesticides (Panel 2). VKMs Panel 2 concludes as following: The product and the active substance have low acute oral, dermal and inhalation toxicities. Both are non-irritating to the skin, and no allergenic potential by skin contact were shown. Coragen was non-irritating to the eyes, while chlorantraniliprole showed a weak irritating potential. Chlorantraniliprole is not shown to have any genotoxic or carcinogenic potential, or to be teratogenic or toxic to the reproduction of female animals. The potential for testicular toxicity of chlorantraniliprole is unclear because the study design and the limited number of young dogs (2/sex/group) do not provide basis for a firm conclusion. No particular target organ for toxicity in any species in the sub-chronic and chronic toxicity studies was seen. The observed dose- and time dependent increased degree of microvesiculation in the zona fasiculata of the adrenal cortex in male rats, is however of uncertain biological significance. All test species (rat, mice, dog) showed physiological adaption to chlorantraniliprole administration (increased liver metabolism with induction of cytochrome P450 enzymes) which was manifested as increased liver weight and hepatocellular hypertrophy. In the chronic toxicity study in mice, the increased liver weight and hepatocellular hypertophy was accompanied with eosinofilic foci, which was assessed as an adverse effect. The no observed effect level (NOAEL) derived from this study serves as basis for calculations of values for acceptable daily intake (ADI) and acceptable operator exposure level (AOEL). In Panel 2‘s opinion a sub-chronic study (90 days) with the technical material (E2Y45-282) including relevant concentration of the impurity IN-G2S78 should be performed. This would bring information on possible influence of the impurity on the toxicological profile of the technical material, and consequently on the assessment of the NOAELs in the various toxic studies. The estimated risk for operator and for bystanders or for workers re-entering treated crops is assessed as minimal. Chlorantraniliprole is persistent in soil with half live of about 1 year. The long half life indicates high potential for accumulation in soil after repeated use, which is confirmed by both model simulations and field studies. The Panel considers field data from the south of Europe not to be relevant for the Nordic conditions based on different climate conditions and soil properties contributing in different directions. The Panel considers that the existing documentation is not sufficient for a firm conclusion on the use of normalised field data for modelling purposes. However, the substance is persistent and expected to accumulate in soil. The Panel concludes that there is minimal risk for toxic effects on mammals, birds, bees, and microorganisms in soil due to chlorantraniliprole exposure with the proposed exposure regime. Panel concludes that there is “very high risk” for effects on in-field non target arthropods from chlorantraniliprole exposure. For soil living invertebrates, earthworms seem rather insensitive to chlorantraniliprole and the Panel considers the toxic effects to be minimal. Panel considers the risk for toxic effects on soil living arthropods to be high. Crustaceans and insects larvae are the aquatic organisms most sensitive to chlorantraniliprole. The Panel concludes that there is a minimal risk of toxic effects on aquatic organisms due to exposure to chlorantraniliprole with the proposed application regime provided that a buffer zone of 30 m to surface water is applied.

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. 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). The Norwegian Food Safety Authority would like, in this regard, an assessment of the following: 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. VKM’s conclusion is as follows: Fate-related issues Isopyrazam is likely to be persistent in Norwegian soils with an associated risk of accumulation after repeated use. 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 g/L in groundwater. 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). Risk to the environment There is minimal risk for toxic effects of isopyrazam to terrestrial organisms. 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.

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: 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. 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). The estimated risk for operator is assessed as minimal both by use of boom spraying (46% of AOEL) and knapsack sprayers (81% of AOEL). 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.

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. 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.