Page 1 of 46 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



### Cyantraniliprole Response to Public Comments on EP A’s “Proposed Registration of the New Active Ingredient Cyantranilipro le: An Insecticide for Use on Multiple Commodities, Ornamentals, Turfgrass, and in Commercial or Residential BuildingsPage 2 of 46 Table of Contents

1.0 Completeness of database and Coor dination with Intern ational Partners

2.0 Economic impacts

3.0 Health Effects 3.1 Thyroid effects

3.2 Other toxic effects

3.3 Classification of toxic effects

3.4 Mode of action

4.0 Ecological Risk Assessment Methodology

5.0 Environmental Fate and Exposure 5.1 Degradates

5.2 Persistence

5.3 Plant Back Intervals 5.4 Accumulation in plants

5.5 Surface water contamination 5.6 Prophylatic use as a seed treatment 5.7 Water modeling

6.0 Effects on birds and mammals

7.0 Effects on pollinators 7.1 Exposure to dust from treated seed 7.2 Study rates versus label rates 7.3 Exposure from residues in guttation fluid 7.4 Bee dietary exposure assumptions

7.5 Effects on bee larva 7.6 Susceptibility to Varroa mites and Nosema 7.7 Incident reporting system for adverse effects on pollinators 7.8 Effect of timing of application on bee toxicity

8.0 Effects from multiple active ingredients, and/ or multiple formulations used in combination

9.0 Consultation with Fish and Wildlife Service (FWS)

10.0 Labeling 10.1 Labeling to prevent harm to bees and other animals

10.2 Buffers 10.3 Outdoor applications in urban settings 10.4 Enforcement, trainingPage 3 of 46 1.0 Completeness of Database and Coor dination with International Partners

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : There are many uncertainties, which the agency acknowledges, surroundi ng the data used to support a cyantran iliprole registration. Many include long-term impacts on bees. EPA believes that no additiona l studies are required for proposed uses and that the database in complete....In fact, according to EPA, overall acute toxicity for cyantraniliprole remains “uncertain,” and

there is no data for chronic and sublethal effects on devel oping honey bee larvae, no data for potential risks for the proposed application rate, or information on the potential impacts of dust resulting from seed treatment. Many studies used to support registration are inadequate and have methodological short-comings.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) :
2. d. EPA continues to use inadequate t oxicity protocols for assessing the environmental effects on non-target species, particularly species such as social insects; a fact that EPA has acknowledged yet has not corrected. (see Fischer and Moriarty, Pesticide Risk Assessment for Pollinators: Summary of a SETAC Pellston Workshop, SETAC Press, Sept 2011) This is noted throughout the EFED and proposed regi stration for cyantraniliprole. Table 4 (pgs.16-17) of EFED clearly points out that only acute toxicity has been cons idered for terrestrial invertebrates. This is simply unacceptable....

e. Recent and even decades old scientific papers have reviewed the extreme importance of properly conducting toxicity studies, notably for concentra tions or doses orders of magnitude below acute toxicity concentrations or doses, factoring in the relationships between sub-lethal exposure concentrations of toxins with time of exposure. EPA has apparently not incorporated these importa nt considerations into its protocols (Blue Book) and therefore virtually all bioassay toxicity assessments are judged to be inadequate . (see Tennekes and Sanchez-Ba yo, 2013, Toxicology 309, 39-51; Tennekes and Sanchez-Bayo, 2011, J. Environmen tal & Analytic Toxicology S4.001; Druckey H. and Kupfmuller K. 1949 Dosis und Wirkung – Beitrage sur theoretischen Pharmakologie. Edito Cantor GmbH, Friburg im Breisgau, Germany; and others.)

... 3. The Proposed Registration document cont ains totally unfounded and untrue statements. a. On page 5,item II. B it states: the toxicity database for cyantraniliprole is complete. This is simply an gross over statement given that science and certainly not EPA will ever know all there is to know about toxicity of any

substance.

...

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : EPA’s ecological risk assessment of cyantraniliprol e contains a significant number of data gaps, unreliable assumptions, and uncertainties .... EPA admits throughout the agency’s risk assessment of cyantraniliprole

and its various formulations that ther e are numerous data gaps and points of uncertainty regarding the toxicity and environmental effects of cyantraniliprole and its product formulations

.... As the agency acknowledges, there were no acceptable t oxicity data to assess the risks to estuarine/marine invertebrates from chronic exposure to cyantraniliprole. 65

_____ 65 EPA, Amended Risk Assessment, supra note 1, at 7.

S. Von Struensee comment (D ocket # EPA-HQ-OPP-2011-0668-0029) : However, DuPont’s two applications of the novel insecticide cyantraniliprole were all denied for its high toxics to bees. The Committee required the company to study the risks for bees on h oney crops, which should be carried out in China.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : In section IV B. (p. 13), EPA notes it collaborative reviews with other count ries. Glaring omission is any collaboration with the relevant agencies of the European Union. In particular, EPA should be in close coordination and collaboration withPage 4 of 46 the European Food Safety Authority (EFSA). This EU agen cy is actively in process of new procedures for improving toxicity assessment procedures for bees and important rela ted species. As noted elsewhere in these comments, until EPA updates and improves its own procedures for these insects, adding at a minimum chronic, sub-lethal and multiple life stage methodologies, all assessments c onducted under current guidance is tota lly inadequate. It should clearly do so by engaging with the European Union.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : As previously stated, the pesticide is proposed for use as a foliar spray, bark spray, micro sprinkler chemigation, drip chemigation, soil drench, soil treatment , seed treatment, seed piece treatment, or bait. It is unfortunate to see seed treatment on the list of proposed uses. EPA includes potatoes, mustard, and sunflower seeds among the seeds to be treated. This is in contrast to the registration documents we have seen from the European Food Safety Authority, which specifically excl ude pesticide use as a seed treatment.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : 4. The virtually total lack of any independent third party analys is of the effects of this chemical is consistent with past EPA practice, but remains an affront to open public process, is contrary to the scientific method and is in nearly universal deference to applicant data with high potential for interpretive bias, faulty e xperimental design, or even fraud in its representation. The scientific method is fundame ntally based upon independent review absent of conflict of interest concerns, and essential for re petition of experiments or other verifica tion techniques to either confirm or refute findings. That does not happen under the system used by EPA, and EPA has not demonstrated that it acts as an independent party.

a. EPA cited only one independent open literature document (Jacobson and Kenn edy 2011; incomplete bibliographic citation was provided by EPA in Section VI) in the EFED that is explicitly related to cy antraniliprole and then EPA promptly dismissed it as not meeting criteria for considerati on, all for an easily corrected technicality, one that staff could have conducted....namely fa ilure to present application rate data in mass per acre units rather than dose per plant. This is simply a ludicrous non-cred ible excuse. Whether the paper is of subs tantive utility is not the issue. It is indicative of an attitude issue of total deference to appli cant submissions, and has been the track record of previous EPA pesticide reviews as well. This must change for EPA to regain its credibility to the public, and to ensure honest and thorough assessments of environmen tal and public health impacts.

b. The resource list (EFED section VI) is extensive (MRIDs) but as usual is virtually entirely publically inaccessible for any legitimate peer review process. Th at is inexcusable and is an abuse of allowing applicants to invoke the claim of protection of company confidential data. All such documents should be required to be submitted in a form that does

not contain actual confidential info rmation and should be placed for open review in the application docket immediately upon receipt.

c. Furthermore, applicants should be required to fund through application fees legitimate third party independent studies over which they have absolutely no control. Until this is done, all pesticid e applications will remain scientifically suspect.

EPA’s response

The EPA’s evaluation of cyantraniliprole was done as an international collaborat ion with our regulatory partners at the Agency for Food, Environmental and O ccupational Health & Safety of France (ANSES), the

Chemical Review Directorate of th e United Kingdom (CRD), the Pest Management Regulatory Agency of Canada (PMRA) and the Australian Pesticides and Vete rinary Medicines Authority (APVMA). Stage 2 of the joint project required a completeness check of the dossi er as the five regulatory authorities initiated the evaluation. This completeness check is conducted to confirm thatall required studies, in cluding those that may be unique to a single authority ’s statutory requirements, are included in th e dossier. All five parties agreed that the dossier was complete for purposes of commencing th e evaluation. The database for cyantraniliprole isPage 5 of 46 comprised of 839 studies. The applicants submitted all studies required by the EPA for the proposed use patterns. Since this was an international project, EPA also received studies required by other authorities and the partnering countries received studies th at are uniquely EPA requirements. Th e result is a robust and substantial database for cyantraniliprole.

In the evaluation, the primary reviews of the data we re conducted by each authority leading a discipline. The ANSES led the review of the plant/livestock metabolism and core residue studies. The CRD led the review of the environmental fate and ecotoxicolgy. Primary revi ews of product chemistry and efficacy were conducted by

the PMRA. The EPA led the reviews of the acute a nd chronic human toxicology. Each authority then conducted peer reviews of the primary evaluations. Thus, there was broad sc ientific expertise applied to this evaluation; toxicologists, chemists, biologists, environmental scientists, entomologists, and others from every participating regulatory authority evaluated the adequacy of the database and intera cted to develop harmonized conclusions in order to complete the risk assessment process.

To the extent possible, the partne ring countries coordinated and consul ted during their independent risk assessment processes. Differing statut es and regulations dictate how invo lved countries may be in other’s process. For example, other countries do not have th e Food Quality Protection Act and so other countries do not have to meet the statutory requ irements of this Act. The EPA’ s ecological and human health risk assessment processes, however, include meetings of overs ight committees such as the Risk Assessment Review Committee. These meetings were open to EPA’s internat ional partners and they do pa rticipate in the dialog and

contribute to our discussions.

The Agency does not agree that the cyantraniliprole data base is incomplete or insufficient for assessing risk. With our partners, EPA conducted an extensive analysis of cyantraniliprole, encompassing all aspects of the pesticide, and focusing exhaustively on th e pesticide’s potential effects on anim als, plants, soil, and water. An array of chronic studies that were conducted at doses much lower than th e acute studies, allow the Agency to identify sub-lethal effects and incorporate them into th e risk assessment. EPA’s risk assessment processes were developed to include conservative assumptions regarding exposure and pr otective safety factors to reduce uncertainty. Thus, EPA believes its analysis with respect to cyantran iliprole was consistent with the requirements of FIFRA.

Concerns about the existing data for honeybees were specifically raised, in cluding the evaluati on of data from open literature. Open literature data submitted to the Agen cy were inadequate for risk assessment. Guidelines for incorporation of open literature into ecologica l risk assessments are de scribed in USEPA (2004) 1 . Toxicity data from the open literature are identified via the ECOTOX 2 search engine, maintained by the U.S. EPA Office of Research and Development (ORD). To be include d in the ECOTOX database, papers must meet several criteria. Data that pass the ECOTOX screen are evaluate d relative to the data prov ided by the registrant, and may be incorporated qualitatively or qua ntitatively into the risk assessment. No data for chronic or sub-lethal effects on developing honeybee larvae were available; however semi-field studi es and full field studies encompass these endpoints into the outcome of the study. In other words, if adverse effects to hive brood were occurring at a significant magnitude, th ey would have manifested themselves in the total adult population of the hive (a decrease would have been e xpected) or the overwintering success of the hives (a decrease in the number of hives that survived would have been expected). Data were available for several pr oposed application rates. Empirical residue concentra tions from these studies were extrapolat ed out to the highest application rates

1 USEPA. 2004. Overview of the Ecologi cal Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Office of Preven tion, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

2 USEPA 2011. Ecotoxicity database http://cfpub.epa.gov/ecotox/Page 6 of 46 proposed for registration (see the resp onse to comment 7.2 for more detail). The Agency acknowledges that the degree of risk from seed treatment dus t is uncertain, as was stated in the risk assessment. Although many of the honeybee studies had methodological limitations, collectivel y, the Agency and its international partners believe they provided sufficient information to characterize risks to honeybees.

The global evaluation process for cyantraniliprole has been concluded in a number of countries. Cyantraniliprole has received regulato ry approval for use in countries such as Argentina, Canada, Colombia, Guatemala, India, Korea, Malaysia , Mexico, New Zealand, Ukraine and Vietnam. Additionally, sale of cyantraniliprole has been approved in China and the product BeneviaTM is cu rrently being used by growers in that country.

Finally, the European Food Safety Au thority (EFSA) has completed the peer review of the Draft Assessment Report prepared by CRD in the UK. The CRD concluded that cyantraniliprole should be considered of low risk, that no critical areas of concern were identified and that it can be approved under Regulation (EC) No.

1107/2009.Page 7 of 46 2.0 Economic impacts

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : There did not appear to be an economic analysis in the available documents posted to the eDocket for Cyantraniliprole. A comprehensive analysis is essential for assessing the risk-ben efit of this new active ingredient. Consideration of the livelihood of the many small business owners who are commerc ial beekeepers is only a part of the economic analysis. In fact, according to Dr. Sonny Ramaswamy, Director of USDA's National Institute of Food and Agriculture $20-30 billion in agricultural production is dependent on pollination.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : EPA Failed to Consider Adverse Effects on U.S. Ag riculture. - EPA’s risk assessment and the studies and data examined therein strongly suggest that the use of cyantraniliprole would have adverse effects on honey bees and other terrestrial invertebrates, including native bees and other vital pollinator species whose existence is the backbone of the U.S. agricultural economy.

Phil Stansly (University of Fl orida entomology professor) comment (Docket # EPA-HQ-OPP-2011- 0668-0036): Cyantraniliprole is an anxiously awaited addition to the IPM toolbox for many horticultural crops, especially citrus. The US citrus industry is fighting for its survival against a dreaded disease, huanglongbing (HLB) or citrus greening. The vector is a sucking insect, the Asian c itrus psyllid, Diaphorina citri. Cyantraniliprole is effective against this pest as well as the citrus leafminer, damage from which exacerbates another serious disease, citrus canker. An effective product against both pests with a unique mode of action (group 28) will be a most welcome addition key for resistance management. The most criti cal use in this regard will be as a soil applied systemic agent to control both pests in young trees which are most susceptible to both pests and both diseases. Currently, the only options to accomplish this are neonicotinoid insecticides like imidacloprid and thiamethoxam. These are excellent products, but all of one mode of action (group 4A) and therefore need to be rotated with different products to forestall selection for resistance within pest populations. The future of the ci trus industry depends completely on our ability to bring the next generation of trees into profitable production. Registra tion of cyantraniliprole is probably the one thing that would advance us most toward this goal. Therefore, I urge th e agency to facilitate registration of this active ingredient

with all haste.

Henry Yonce (KAC Agricultural Research, Inc.) comment (D ocket # EPA-HQ-OPP-2011-0668-0037): I have conducted research with Cyantraniliprole for four year s in Citrus in Florida. As you know Florida citrus has a serious problem with Asian Citrus Psyl lids. We are limited in active ingredient s for soil applications for ACP control in young trees. The addition of Cyantraniliprole with give the Florida citrus producer a needed rotation active ingredient for resistance management. Cyantraniliprole has excellent control or ACP from soil or foliar applications. It is a much needed active ingredient for ACP control in Florida citrus. Florida citrus growers are anxiously awaiting the registrations of Cyantranilipole.

D. Polk comment (Docket # EPA-HQ-OPP-2011-0668-0038): This active ingredient should be registered as soon as possible. It is effective for a broad range of insects, and is a reduced risk product. Specifically, it is needed to manage a new invasive pest, the spotted wing drosophila (SWD), which has already caused severe damage to the nation's blueberry and other "soft" fruit crops. Without cyantran iliprole, growers will be forces to use higher rates of broad spectrum insecticides that also kill beneficial orga nisms and set integrated pest management (IPM) practices back 30 years. In NJ alone our $80 million blueberry crop is at extremely high risk to SWD, and growers have already

doubled their insecticide use.

Thomas Stopyra (The Packers of Indian Ri ver, Ltd.) comment (Docket # EPA-HQ-OPP-2011-0668- 0039): Chlorantraniliprole or Cyazypyr, which will be marketed as Verimark or Exirel, has the potential to solve a wide array of problems for Florida citrus growers. Currently the new planting are protected by a trunk drench of either imidacloprid or thiamethoxam, both Group 4 chemicals. Th e potential for resistance to these chemistries has been discussed by many entomologists. The introduction of Verima rk would give Florida growers a much needed rotational product without upsetting the delicate ecological balance of beneficial insects. Furthermore, growers are extremely concerned about the recent spread of Huanglongbing (HLB) in the mature plantings. The vector is a piercing-suckingPage 8 of 46 insect known as the Asian citrus psyllid, Diaphorina citri . Foliar applications of Exirel (cyantraniliprole) have been shown to effective against this pest as well as the Citr us Leafminer, which exacerbates Citrus Canker. Cyazypyr, which is an effective product against both pests with a uni que mode of action (Group 28) will be a welcome new tool in the IPM toolbox for pest management. The future of Fl orida’s 9 billion dollar citrus industry depends on our ability to bring the next generation of trees in to profitable production. Registration of Verimark and Exirel (cyantraniliprole) is probably the one thing that would advance us most toward this goal. Therefore, I urge the Agency to expedite the registration of this active ingredient with all haste.

Scott Lambeth (Golden River Fruit Company) comment (Docket # EPA-HQ-OPP-2011-0668-0040): I am a third generation citrus grower in Florida. With the recent spread of the HLB (citrus greening) disease in the state I am concerned that my citrus groves will become non pr oductive and cause our company to go out of business. Our only control against the spread of this disease is to contro l the vector which is the Asian citrus psyllid (ACP). The growers in Florida only have a limited number of chemicals th at we can use to control the ACP, therefore we need to

have new chemicals that offer a different mode of action to he lp us in this fight to control HLB. With the availability of Cyantraniliprole we will be to rotate modes of action whic h is important to us with re gard to being good stewards of the pesticides that we have at our disposal. The tria l work that I have seen indicates that Cyantraniliprole is effecting in controlling the ACP and the citrus leafminer (CLM). The CLM is important to control because it helps in the spread of the citrus canker disease. I urge the agency to expedite the registration of Cy antraniliprole. The future of the Florida citrus grower is at stake without more tools to combat these pests.

John Curtis (Better Crops LLC) comme nt (Docket # EPA-HQ-OPP-2011-0668-0043): Citrus greening (HLB) is a disease vectored by asian citrus psyllid and which is a very serious problem for citrus growers in Florida. This disease is so severe and widespread that the basic challenge is to protect newly-planted trees and ensure that these trees remain healthy and at least reach production (ca. 5 yrs); the citrus industry is basically fighting for survival. At present, neonicotinoid insecticides (e.g. im idacloprid and thiamethoxam) are important tools for managing asian citrus psyllid in newly-planted trees. Th ese neonicotinoid insecticides are all known for systemic and residual insect pest control and which are oftentimes applie d to the soil throughout the growing year. However, overreliance on neonicotinoid insecticides may l ead to potential insect resistance problems and a reliable rotation partner is urgently needed. Cyantraniliprole has a different mode of action, systemic and has similarly effective residual control against many of the same insect pests (includi ng asian citrus psyllid), compared with the existing neonicotinoid insecticides. Cyantraniliprole (both soil and foliar formulations) provides a much-needed opportunity for 'partnering' and 'rotation' with the neonicotinoid's a nd which not only enhances the long-term sustainability of all these chemistries, but also provides citrus growers with both an additional and essentia l tool in getting young trees into production.

EPA’s response

During the evaluation of new pesticides, the EPA uses t oxicity data and conservati ve exposure estimates to determine potential risk to non-target organisms. Mitigation of potentia l risk is achieved through the risk management decision process and may include label and use re strictions. With respect to initial registrations of new pesticides, the relevant subsection of FIFRA, 7 U. S.C. § 136a(c)(5), strongly su ggests that, at least in situations where a new pesticide does not raise signi ficant risk concerns, Congr ess did not intend economic considerations to play much of a role in EPA’s analysis. First, C ongress authorized EPA to waive the requirement that manufacturers submit data on a pestic ide’s efficacy during initial registration — data the agency would undoubtedly need were it to evaluate whether the new pesticid e will be economically beneficial.

See 7 U.S.C. § 136a(c)(5); 40 C.F.R. § 158.400(e)(1) (imple menting this authority); H.R. Rep. No. 95-663, at 27 (1977), reprinted in 1978 U.S.C.C.A.N. 1988, 2000 (“This authority [to waive efficacy data] will be used most commonly with respect to agricu ltural pesticides, due to the high level of knowledge concerning pesticidal efficacy that prevails in the agricultural community . . . .”). Second, FIFRA forbids EPA from refusing to register a pesticide simply because othe r pesticides are equally effective — wh at the statute refers to as a “lack of essentiality,” 7 U.S.C. § 136a(c)(5) (“Where two pestic ides meet the [statutory] requirements . . . , one should not be registered in preference to the other.”) – suggesting that purely economic considerations should notPage 9 of 46 generally be a part of ini tial registration decisions if risk considerations do not support differentiation among pesticides.

As an efficacious insecticide, cyantraniliprole is expected to have biological activity and therefore it may pose a risk to pollinators, as do all insecticides, in general. However, cyantraniliprole wa s granted classification as a Reduced Risk pesticide. This means that compared to existing conventional pesticides such as the organophosphates, carbamates and pyrethr oids, it presents characteristics th at may include lower impact on human health, lower toxicity to non-target organisms, low potential for groundwater contamination, low pest resistance potential and compa tibility with IPM practices.

EPA determined that cyantraniliprole is preferable to almo st all of its registered al ternatives in terms of its environmental and human-health risk profile. Further, ecot oxicity data for cyantranilip role indicates that it is preferable to almost all of its regist ered alternatives. In light of this determination, the Agency considered the potential risks posed by cyantranilip role not to be “unreasonable,” wh en weighed against the benefits it provides. Cyantraniliprole controls lepidoptera, whiteflies, leafminers, psyllids, leaf-f eeding beetles, fruit flies, and sawflies. Cyantraniliprole is effective at contro lling the establishment and population growth of aphids, weevils and thrips. In a comparative qua litative analysis of efficacy, cyantran iliprole is considered to be more efficacious than most of the currently registered alternat ives for citrus psyllid, citrus leafminer, citrus aphid, beet armyworm, cotton bollworm, Silverleaf whitefly, cotton thrips, oriental fruit moth, and obliquebanded

leafroller.

As indicated by commenters 36, 37, 38, 39, 40 and 43, cyantranilip role is expected to be an essential tool to citrus growers and blueberry growers. The citrus industry is under serious threat from citrus greening disease (HLB). Once a tree becomes infected, there is no cure a nd it will die. The only curren t means to protect citrus trees from HLB is through prevention by control of th e Asian Citrus Psyllid. Flor ida and California growers need cyantraniliprole to provide an additional mode of acti on to combat this psyllid. Deaths of trees resulting in serious losses to the citrus industry will also affect beekeepers that rely on citrus for honey production and as a

resource for their bees.

The Agency is also aware of the threat to numerous crops from the invasive fruit fly, the spotted wing Drosophila (SWD). As noted by comment er #38, this pest has already serious ly injured the US blueberry crop. On July 29, 2013, the Washington Post wrote an article a bout the concern that Maine’ s wild blueberry growers have for the threat posed by SWD. There is a zero tolerance standard for SWD in blueberries, a load of harvested blueberries will be rejected no matter the level of infestation. Ex tension agents in blueberry growing states have recommended carbaryl, diazinon, malathion, me thomyl, phosmet, bifenthrin, esfenvalerate and other conventional chemicals, however pre- harvest intervals for these compoun ds are long and SWD infestations occur when fruit is ripe therefore grow ers are in need of tools with short PHIs. Michig an and New Jersey State Lead Agencies have made crisis declarations un der FIFRA Section 18 Emergency Exemption provisions on behalf of blueberry growers for the us e of malathion to combat SWD. Re gistration of cyantraniliprole will provide the growers with a t ool that presents a reduced risk profile compared to the alternative products currently registered or allowed unde r Section 18 authorizatio n. The use of cyantraniliprole can reduce the potential adverse effects from applications of higher rates of these and other pesticides.Page 10 of 46 3.0 Health Effects

3.1 Thyroid effects

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : The agency approved cyantraniliprole as a “reduced risk” candi date for proposed uses based on mammalia n and eco-toxicity profile for this chemical. However, in addition to negative adverse eff ects observed in dogs, which include liver damage, EPA notes that cyantraniliprole alters thyroid homeostasis in laborat ory rats as a result of enhanced metabolism of the thyroid hormones by the liver. Even though the agency states that “cy antraniliprole is not a direct thyroid toxicant,” indirect effects on thyroid function have further implications for e ndocrine disruptive effects. A full evaluation of endocrine disrupting potential should be reviewed further by the ag ency. Given that its current endocrine disruptor screening program (EDSP) is currently still in the process of valida ting tests, selecting chemicals for testing and implementing screening protocols, the agency must use caution when appr oving registration for new active ingredients that show a propensity for endocrine disruption, befo re EPA has finalized its EDSP protocol.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Some of the chronic effects identified included thyr oid weight increase and othe r thyroid abnormalities. Offspring were affected by chronic exposure with d eclines in organ weight and overall pup body weight. These findings suggest that cyantraniliprole may affect a number of mammalian species adversely.

EPA’s response

It is generally known that increases in liver enzyme ac tivities result in increased metabolism of and decreased circulating thyroid hormonal levels in the experimental animals. Th e available data show that the thyroid findings are a consequence of a series of effects that begin with increases in hepatic cytochrome P450 content and UDP-glucuronyltransferase activity leading to decrease s in plasma T4 thyroid ho rmone level and alteration of thyroid hormone homeostasis resulti ng in increases in TSH. Increased plasma TSH then stimulates the thyroid gland resulting in the thyroid follicular epithe lial cell hypertrophy/hyperplasia. These changes followed a classic pattern for a compound that disrupts thyroid homeostasis throug h induction of hepatic metabolizing enzymes including UDP glucuronyltransferase. Cyantranilip role did not inhibit the th yroid peroxidase activity

in an in vitro study supporting the conclusion that cyantraniliprole was not a dir ect thyroid toxicant. Based on the results just descri bed an adverse outcome pathway can be proposed as shown below:

cyantraniliprole dosing → ↑ hepatic cytochrome P-450 and UDP glucoronyltransferase activities

↓

↑ T 4 catabolism → ↓ in T 4 & associated ↓ in T 3

↓

↑ TSH secretion by the Pituitary → thyroid follicular cell hypertrophy/hyperplasia

↑ : Increase ↓ : Decrease

The thyroid effect occurs at substa ntially higher dose levels than the dos e levels which produce liver effects,Page 11 of 46 which are used to establish toxicity endpoints for risk assessment. Therefore, the no observed adverse effect level (NOAEL) selected for the point of departure for risk assessment based on the liver effect will be protective of any thyroid effects seen in th e studies with cyantraniliprole.Page 12 of 46 3.2 Other toxic effects

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : [Comment 2:] p. .... Mention is made by EPA of organ adaptive effects of repeated exposures (e.g. progressively severity of liver weight/enlargement, phosphatase and other enzyme responses, etc.; thyroid alterations; adrenal cortex changes reduced fetal body weight, decrease food utilization efficiency, etc.), yet all are seemingly dismissed as irrelevant and of “no concern” by EPA. These are not trivial health effects, particularly the liver, thyroi d and adrenal organ effects, all key to mammalian detox and meta bolic rate functions. The claim of no concern regarding reproductive or developmental effects is not supported by observed and stat ed facts. Neurotoxic effects are also dismissed however some of same symptoms described as and ascribed to RyR receptor activations are also symptoms of neurotoxicity (impaired regulation of muscle contraction, paralysis) , raising interpretative inadequacies and possible other chemistries and pathways of toxicity.

EPA’s response

In many subchronic toxicity studies in the rats, there were liver effects cons isting of increases in liver weights and hepatocellular hypertrophy without any clinical chemistry or histopathology changes. The liver effects seen in the rat were considered as adaptive (HED Guidan ce Document #G2002.01). Howeve r, in the studies with dogs the liver effects consisted of ch anges in clinical chemistry paramete rs including increases in alkaline phosphatase, alanine aminotransferase and gamma glutamy ltransferase and decreases in total protein, albumin, and cholesterol. Significant increases in absolute and relative liver weights accompanied by microscopic observations (hepatocellular degenera tion and inflammation) were found; th e effects seen in the dog studies were adverse. The liver effects seen in the dogs were c onsidered to be the most sensitive effects and were used in establishing toxicity endpoints and the NOAEL associated with the liver effects wa s employed as the point of departure for risk assessment.

In regards to the developmental and re productive effects, the effects seen in these studies are again seen at dose levels much higher than the point of departure (NOA EL) employed for risk assessment. For example, the lowest adverse effect level seen in the parental an imals of the reproductive study was 14 mg/kg/day, whereas the point of departure used for risk assessment (1 or 3 mg/kg/day) was approximately 5 to 14 times lower than the LOAEL. With the traditional safety factor of 100x, this is protective of any effects seen in the developmental or reproductive studies.

With respect to the potential neurot oxic effects raised by Boulder Innovati ve Technologies, EPA presented the summary results of the acute and subchronic neurotoxicity studies in rats. The acu te neurotoxicity study was tested up to the limit dose (2000 mg/kg), and the subc hronic neurotoxicity was te sted up to 1400 mg/kg/day, which was above the limit dose (1000 mg/kg/day); no neur otoxic effect was found in either study. This was consistent with the literature finding that the mammalia n ryanodine receptors (RyR) were much less sensitive to the effects of anthranilic diamides than insect RyR (ranging from 350 to >2500 times less sensitive) (Lahm, GP et al.,2009; Sattelle, et al., 2008). Cyantraniliprole is a memb er of anthranilic diamides.

_____ HED Guidance Document: He patocellular Hypertrophy: HED Guidan ce Document #G2002.01; October 21, 2002

Lahm G. P., Cordova, D., and Barry J.D. (2009) New and selective ryanodine receptor ac tivators for insect control. Bioorganic & Medicinal Chemistry (2009) .17 (12):

4127-4133.

Sattelle, D.B., Cordova, D., and Cheek, T.R. (2008) Insct rayanodine receptors: molecular targets for novel pest control chemic al. Invert Neurosci (2008) 8:107-119

.Page 13 of 46 3.3 Classification of toxic effects

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : 3. The Proposed Registration document contains tota lly unfounded and untrue statements.... b. On page 5, item II A bottom of paragraph, it states: “T here are no genotoxicity, mu tagenicity, neurotoxicity, or immunotoxicity concerns. There are no developmental or re productive concerns.” These statements are again sweeping scientific arrogance and simply cannot be made honestly, pa rticularly without conditioning them to the very limited testing conducted. Furthermore the following points enumerated in item II B and in C (and elaborated in referenced EPA documents) which do in fact note observed negative effects cont radict the “no concern” claim. EPA must remove this language and clearly acknowledge that ne gative health effects and abnormalities were in fact observed. Furthermore null results from screening tests do not conclusively prove lack of effects, they are only a limited or indicating measure.

EPA Response

The “no concern” phrase is made based upon the data generated by the re quired toxicity studies and in the context of risk assessment of the proposed uses of cyan traniliprole. Comparing the no-observed adverse effect levels (NOAELs), which are used as points of departure for risk assessmen ts, and the lowest-observed adverse effect levels (LOAELs) for immunotoxicity, developmental, or reproductive toxicity, th ere is a large margin of safety ranging from 5 to greater than 1000X difference (5X for offspr ing and maternal LOAEL from the reproduction study and greater than 1 000X from developmental and imm unotoxicity studies). With an additional 100X safety factor to account for inter- a nd intra-species sensitivity, the difference becomes even larger between the value at which cyantraniliprole is regulated and the LOAELs observed in the immunotoxicity, developmental, or repr oductive toxicity studies. Therefore, EPA can state that there is “no concern” for toxicity potentia l raised by the commenter.Page 14 of 46 3.4 Mode of action

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : [Comment 2:]

p. The mode of toxic action (MOA) discussion and data presentati ons of cyantraniliprole is considered inadequate and incomplete. For example the description of MOA as a unre gulated activator of ryanodine (RyR) receptor function does not indicate whether such disruption is irreversible or reversible or cumulative, characteristics with profound influence on longer term chronic or sub-lethal effects that may not display with the toxicity testing performed. Little to no MOA is described for degradates. A thorough docume nted review of MOA chemistry and biochemistry is definitely called for, including parent cyantraniliprole plus all degradates.

EPA’s response

The statement in the risk assessment on the mode of ac tion (MOA) as an unregulated activator of insect RyR channels described the pesticidal mo de of action for killing insects. Since RyRs are found across species, the Agency carefully considered the impact on mammalian Ry Rs by evaluating the toxicity studies submitted to the Agency as well as information in the literature. As stat ed previously, the registrant submitted all of the required toxicity studies as well as some additional special studi es to further characterize cy antraniliprole toxicity to mammals. With respect to the discussion on the effects of cyantraniliprole to human/mammalian RyR receptor function, the Agency reviewed the open literature in addition to evaluatin g the submitted toxicity data. The published literature indicated that insects were much more susceptible to the effects of this class of chemicals. The registrant submitted chronic (long-term) toxicity studies in three different mammalian species, so the potential chronic effects due to any possi ble cumulative effects, as well as sub-lethal effects, with time were assessed. Furthermore, degradates were structurally similar and/or likely to be more readily eliminated from the body. The Agency had conducted a structural activity anal ysis of the degradates to which humans could be exposed to in food and drinking water, which did not demonstrate any stru ctures which would lead to more toxicity than the parent compound. Th erefore, the Agency assumed the pot ential toxic effects produced by degradates were similar to those of the parent chemical, which is a cons ervative assumption, in that at least some of the degradates are likely less potent RyR ligands.Page 15 of 46 4.0 Ecological Risk Assessment Methodology

Center for Biological Diversity comme nt (Docket # EPA- HQ-OPP-2011-0668-0041) : On April 30, 2013 the EPA and the Services received a report from the National Academy of Sciences (NAS) outlining recommendations on specific scientific and technical issues re lated to the development of endangered and threatened species risk assessments for pesticides that are compliant with the both the ESA and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 25 This report provided de tailed recommendations on ways that the Services and the EPA could best incorporate considerations of the sub-lethal, indirect and cumulative effects of pesticide exposure; the effects of chemical mixtures and inert ingredie nts; the ability to use geospatial information, and how to incorporate uncertainty into the risk assessment process. 26 While the report outlines area s for all three agencies to improve, the NAS report made several significant conclusi ons about the current ecol ogical risk assessment process and its use of risk quotients [RQs], including: • The EPA “concentration-ratio approach” for its eco logical risk assessments “is ad hoc (although commonly used) and has unpredictable performance outcomes.” 27
• “RQs are not scientifically defensible for assessing the ri sks to listed species posed by pesticides or indeed for any application in which the desire is to base a decision on the prob abilities of various possible outcomes.” 28
• “The RQ approach does not estimate risk...but rather relies on there being a large margin between a point estimate that is derived to maximize a pesticide’s envir onmental concentration and a point estimate that is derived

to minimize the concentration at which a specified adverse effect is not expected.” 29
• “Adding uncertainty factors to RQs to account for lack of data (on formulation toxicity, synergy, additivity, or any other aspect) is unwarranted because there is no wa y to determine whether the assumptions that are used overestimate or underestimate the probability of adverse effects.” 30

According to the NAS, the EPA concentr ation-ratio approach contrasts sharpl y with a probabilistic approach to assessing risk, which the NAS describes as “technically sound. ” The NAS’s underlying conclusion is that EPA should move towards a probabilistic approach based on population modeling, an ap proach that the NMFS already utilizes. 31
The NAS also recommends that the FWS move towards a pr obabilistic approach in its consultations. Given the significant changes to the EPA’s ecologi cal risk assessment that are likely required to conform with the NAS recommendations, it is arbitrary and capricious for EPA to pr oceed with a registration using a risk assessment process that does not estimate risk without consulting with the Services.

The ecological risk assessment fails to account for the full impacts to listed species and their populations. The FIFRA registration process only addresses toxicity for a single exposure to a single stressor in the lifetime of a standard test organism. 32 This approach is woefully inadequate and fails to assess the overall impacts to the species and the population and address the potential to lead to jeopardy or adverse modification. Th is analysis fails to account for the multiple exposures of pesticides over the life of the indivi dual, including at more sensitive life stages. Multiple exposures can lead to a cumulative effect on species that w ould be more severe than a single exposure, and the single or combined exposure of pesticides at sensitive life stages can have a more acute effect then what is analyzed in EPA’s FIFRA analysis.

The cyantraniliprole ecological risk ass essment also does not account for the “status and trends” of species and critical habitat, the “demographic and ecological status” of species and their population, “the pre-existing stressors in the watersheds where they occur”, or “the specific direct a nd indirect pathways” of pesticide exposures on species and

critical habitat. 33 The type of single exposure analysis employed by EPA fails to address the myriad of impacts that can result from pesticide exposure, and how that exposure would affect the overall popula tion and habitat contributing to the jeopardy of adverse modification.

_____

25 http://www.epa.gov/oppfead1/cb/csb_pa ge/updates/2013/nas-report.html

26 National Academy of Sciences. 2013. Assessing Risks to Endangered and Thre atened Species from Pesticides , Committee on Ecological Risk Assessment under FIFRA and ESA Board on Environmental Studies and Toxicology Di vision on Earth and Life Studies National Research Council (April 30, 2013).

27 Id . at 107.

28 Id . at 11.

29 Id

. 30 Id

.Page 16 of 46 31 Id . at 107.

32 Draft BiOp at 150, lines 5246-47.

33 Draft BiOp at 150, lines 5247-51.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Significantly, the risk assessment uses the seasonal maximum usage amount listed for cyantraniliprole use on agricultural products to be the yearly maximum, desp ite the fact that many of the crops for which the use of cyantraniliprole is proposed have more than one season per year.

EPA’s response

In 2011, the EPA and the Departments of Agriculture, Co mmerce and the Interior re quested that the National Research Council (NRC) of the Natio nal Academy of Science (NAS) convene a committee of independent experts to examine topics pertaini ng to tools and approaches for asse ssing the effects of proposed FIFRA actions on endangered and threatened sp ecies and their critical ha bitats. The Agency is working with the Fish

and Wildlife Service and National Marine Fisheries Servic e to develop a mutually agreeable course of action that incorporates the NAS findings. Additional information and resources regarding the implementation of the NAS recommendations can be found on the Agency’s website ( http://www.epa.gov/espp/2013/nas.html ). Interim approaches for national-level pesticide assessm ents are also provided on the Agency’s Endangered Species Protection Program website ( http://www.epa.gov/espp/2013/interagency.pdf ).

Additionally in respons e to Comment #47, the Agency points to the ecological risk asse ssment where seasonal maximum rates were modeled, although in some instances , multiple crop cycles may take place per year. For “on the field” exposures ( i.e., birds/mammals/terrestrial i nvertebrates consuming trea ted food items directly from the food) it is expected that wi th every new cycle, a new set of plan ts (crops and weed s) or arthropods would be exposed to cyantraniliprole. Therefore, residue carryover from the previous season is not expected to

occur.Page 17 of 46 5.0 Environmental Fate and Exposure

5.1 Degradates

Center for Biological Diversity comme nt (Docket # EPA- HQ-OPP-2011-0668-0041) : The ecological risk assessment also fails to consider the effects of pesticid e degradates on protected species. Degradates, which are the chemicals resulting from pesticides after it has been transf ormed by chemical, photochemical, or biological reactions, also have the ability to impact water quality and wildlife. 21 Pesticides also do not occur in single exposure situations and many different mixtures of pesticides occur in water bodies at the same time. 22 The mixtures of these chemicals combine to have synergistic effects that are substantia lly more dangerous and increase the toxicity to wildlife. 23 The ecological risk assessment completely fails in its oblig ation to analyze the effects of degradates and only states“[g]iven the uncertainty of the behavior and toxic ity of these degradates, their toxicity is assumed to be equivalent to the parent compound, cyantraniliprole.” Such a statement is clearly arbitrary and capricious and cannot be supported by clear evidence before the EPA.

_____ 21 NMFS 2011, Endangered Species Act Section 7 Consultation Draft Biological Opin ion for the Environmental Protection Agency’s Pesticide Gene ral Permit for Discharges from the Application of Pesticides (Draft BiOp) at 4456-4470 lines. Northwest Coalition for Alternativ es to Pesticides, et al., Petition to Require Disclosure of Hazardous Inert Ingred ients on Pesticide Product Labels. 2006. http://www.epa.gov/opprd001 /inerts/petition_ncap.pdf

. 22 Draft BiOp at 118-119, lines 4209-31; Gilliom et al, USGS, Pe sticides in the Nation's Streams and Ground Water, 1992–2001—A Su mmary, available at http://pubs.usgs.gov/fs/2006/3028/

. 23 Draft BiOp at 127-129, lines 4471-4515; Robert J. Gilliom, 2007, Pesticides in the Nation's Streams and Ground Water; Environm ental Science and Technology, v. 41, n.10, pp. 3408–3414, available at http://water.usgs.gov/nawqa/pnsp/pubs /files/051507.ESTfeature_gilliom.pdf

.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Similarly, EPA’s assessment of cyantraniliprole’s biodegradation process and the toxicity of cyantraniliprole and its degradates, are insufficient to support unconditional registrati on under FIFRA. As stated previously, some of the degradates of cyantraniliprole are more persistent and mobile than the parent compound, a concern for ecological effects, as some may be more toxic than the parent and may be able to accumulate over time. 32
The assumption used by EPA that the degradates were equa lly toxic to the parent should not substitute for full assessments of the degradates, especially given that EPA ass erts later that “two of the degradates (IN-HGW87 and INJ9Z38) may be more toxic on an acute oral basis than th e parent, but given that the endpoints were non-definitive, there is uncertainty.” 33 This concern is especially crucial for the degradates that showed more persistence and mobility.

_____ 32 EPA, Amended Risk Assessment, at 22-25

33 Id. at 73.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : The EFED fails to assess or require the conduct of toxicity studies on ev en the known degradates, instead it uses only assumptions about equivalent toxicity of metabolic or abiotic degrad ates and substituents and then inputs these assumptions into

models to estimate the toxicities and health effects. This can only be characterized as guesswork or SWAG. Such data submissions for actual toxicity measurements of all degradat es should be required of the applicant and until provided all registration approval considera tions should be shelved, or the applications totally rejected.

EPA’s response

The Residues of Concern Knowledge-b ased Subcommittee (ROCKS), a co mmittee of EPA toxicologists and

residue chemists that meet to eval uate degradate data and make determ inations on which degradates are of sufficient toxicological concern to be included in human health dietary risk assessments. In the review of the cyantraniliprole degradate profile, the Agency came to the conclusion that none of the degradates were likely to be more toxic than the parent. Considering freshwater in vertebrates as an example, data were available for nine of the ten degradates and indicated that the de gradates were less toxic than the parent for Daphnia magna

. Notably, EPA does not have data for the tenth degradate. When degradate toxicity data are not available, EPA assumes the degradate equally toxic to the parent, unless there is some other information (e.g., chemicalPage 18 of 46 structure) that suggests othe rwise (USEPA, 2012). There is no reason to expect the tenth degradate to be more toxic than the parent.

Regarding the reference to IN-HGW87 and IN-J9Z38, the commenter’s quote was extr acted from the pollinator

section of the risk assessment doc ument. Terrestrial organisms ( i.e., honeybees) and aquatic organisms are assessed separately using different a pproaches. The aquatic analysis us ed the total toxics residue (TTR) approach, which conservatively assumes that all of the de gradates are equally toxic to the parent for aquatic exposures. All existing degradate toxi city data for aquatics support this premise. Concerning environmental exposure, the TTR approach is conservative because the modeling assumes longer half-life and higher mobility constants. Individual degradate modeling would result in less c onservative exposure concentrations.

For the terrestrial analysis, non- definitive toxicity endpoints ( i.e., greater than values ) for some of the degradates leads to some uncertainty about their toxi city. Based on their struct ures, however, the ROCKS did not identify them as potentially being more toxic than the parent. Furthe rmore, the honeybee full field studies did not show overwintering survival di fferences between controls and treatm ent groups. Although toxicity data for each individual degradate were not quantified in th e field study, the study design allows for exposure to cyantraniliprole and all of its degradates in a real-lif e scenario. Thus, EPA believes both the aquatic and the pollinator analyses conservatively represented ri sk and exposure to aquatic organisms and honeybees.

The Agency recognizes that simultaneous exposure to multiple chemicals may have additive or synergistic effects on toxicological responses of non-target organism s. In accordance with th e recent National Academy of Sciences’ recommendations on endangered species assessments, EPA will incorporate chemical mixture data into assessments, when available, on a case-by-case basis. For cyantraniliprole some ecotoxicity data were available for the cyantraniliprole-thiamethoxam formula tion for acute effects to honeybees, parasitic wasp, predatory mite, earthworm, freshwater fish, freshwater invertebrates, and non- vascular plants. These data were incorporated into the Agency’s assessment. If additio nal mixture data with thiamethoxam or other pesticides becomes available, they will be incorporated into future assessments, as appropriate.

____ Literature cited: USEPA. 2012. Guidance for residues of concern in ecological risk assessment. Environmental Fate and Effects Division, Office of Pesticide Programs, United States Environmental Protection Agency, Washington, DC.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : The degradates of cyantraniliprole are described as bot h mobile and persistent. EPA states that “given the uncertainty of the behavior and toxicity of these degradates, their toxicity is assumed to be equivalent to the parent compound, cyantraniliprole.” 60 Yet, the exposure characterization st ated: “Based on degradate aerobic soil metabolism and mobility studies, six of the eight major de gradates had longer dissipation half-life (DT50) values (more persistent) and three of the eight degradates we re more mobile than the parent cyantraniliprole.” 61 Thus, the assumption that the toxicity of the degradates is equiva lent to that of the parent seems a leap of faith.

_____ 60 EPA, Amended Risk Assessment, at 4.

61 Id. at 4.

EPA’s response

It is important to understand toxicity and exposure data are independent of each other. Exposure differences do not have an effect on toxicity. Howeve r, both exposure and toxicity contribute to risk. To illustrate this point, a chemical with high “toxicity” with “low” exposure due to the chemical’s physical and chemical properties may have a limited risk picture. This relationship is accounted for within th e Agency’s risk assessment frameworkPage 19 of 46 which integrates exposure and toxicity endpoints compared against Agency le vels of concern (LOC). For more information on the risk assessment process, please refer to page 46 of the Risk Characterization section of the Agency’s Overview of the Ecological Risk Assessment Process document (USEPA, 2004).

_____ Literature cited:
USEPA. 2004. http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : The EFED fails to consider the potential of reversible reactions of degradates back to prior se quential intermediate compounds or even to the parent pesticide or even to totally different dange rous chemical products. Such chemical reactions have been observed with other pesticides, belatedly after many year s of assuming short half lives in soils (e.g. as reversible reactions in soil have been documented with glyphosate and AMPA, AMPA reverting to glyphosate upon application of phosphorus fertilizers to the soil in subsequent cropping cycles)

EPA’s response

The Agency acknowledges the potentia l for reversible reactions; however , there are no data available to demonstrate that this occurs with cyantraniliprole. The Agency’s risk assessment includes the conservative Total Toxic Residues (TTR) approach, which assumes that all of the degradates are equally as toxic as the parent – cyantraniliprole. Thus, if chemical reactions are occurring that revert cyantraniliprole’s degradates back to the parent, the TTR approa ch accounts for such processes.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : The EFED presents calculated values for the total toxic residues (TTR ) (EFED [Risk Assessment] pa ge 25) based upon half lives in various environmental compartments for parent and degradates. In the second sentence of that paragraph four TTR half lives values are given but only three compartments ar e listed. Something is missing and no correlation of which value assigns to which compartment is possible until clarified/corrected

EPA’s response

Thank you for pointing out an important editorial error. The sentence should read TTR half lives for aqueous photolysis, aerobic soil metabolism, aerobic aquatic metabolism and anaerobic aquatic metabolism studies correspond to 88 days, 1327 days, 589 days and 961 days, respectively.

California Stormwater Quality Association comment (Docket # EP A-HQ-OPP-2011-0668-0035) : We commend EPA for using the Total Toxic Residue approach in the environmental risk assessment. This approach accounts for the contributions of the toxic degradates to the overall aquatic toxicity from cyantraniliprole.

EPA’s response

The Agency agrees that in the absence of data that demonstrates degradates are less toxic than the parent compound, the Total Toxic Residue approach is an appropriately conservativ e course of action.Page 20 of 46 5.2 Persistence

Center for Regulatory Integrity comme nt (Docket # EPA- HQ-OPP-2011-0668-0045) : The environmental fate summary presented in EPA’s decision document focuses on the alkaline hydrolysis of cyantraniliprole at pH 9. There is no mention of data fro m neutral and acidic hydrolysis and soil studies, which show that cyantraniliprole is more persistent under these more commonly found environmental conditions.

EPA’s response

The purpose of the summary was to highlight cyantranilip role’s degradation and dissipation mechanisms. The Agency’s environmental risk assessm ent clearly describes aqueous hydrolys is as a pH dependent depletion

mechanism in the Environmental Fate a nd Transport Characterization (page 28).Page 21 of 46 5.3 Plant Back Intervals

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : The registration recommendation document refers to Directions for Use plant back intervals (PBIs) as a m eans to deal with avoidance of uptake by cyantraniliprole by succession crops of cerea ls, legumes and tuberous and corm vegetables. The PBI time intervals suggested are totally inad equate given the half lives of cyantran iliprole and its numerous degradates, particularly when one acknowledges the soil compartment pe rsistence, and the multiplying half life effects of the numerous degradates for which EPA staff have arbitrarily assigned equivalent toxiciti es to the parent compound cyantraniliprole (without any data to back up that assumption).

EPA’s response The commenter’s suggested method for ascertaining a PBI ( e.g., using the half-life in soil) is not necessary since the Agency has acceptable rotational crop fiel d trial studies (unconfined and confined: OCSPP GLN 860.1900 and 860.1850, respectively) which show actual uptake by plants in succession crops. Rotational crop field trials with representative crop types demonstrated that residues of cyantran iliprole on food commodities are predicted to be <0.01 ppm at a 30-day PBI. Confined rotational fi eld trials (OCSPP GLN 860.1850) with radiolabeled cyantraniliprole show ed that the major portion of the residue on food commodities will be cyantraniliprole at various PBIs. Crops for which cyantran iliprole is not approved may be planted in fields after crops treated with cyantraniliprole provided there is at least a 30-da y interval from application of cyantraniliprole to planting of the new crops. The 30-da y PBI (for crops not listed as primary on the label) is adequate to assure that there will be no quantifiable residues in the follow-on crop.Page 22 of 46 5.4 Accumulation in plants

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : 2i. Another error and flagrant EFED omission is the failure to recognize the potential for accumulation of cyantraniliprole and its degradates in perennial species such as trees, herbs, shrubs, flowers and ornamentals, even in turfgrasses. It is common practice by arborists and landscap e insecticide applying companies to cosmetically or prophylactically apply pesticides such as cyantraniliprole on a seasonal or multip le times per season repeat contract basis, regardless of presence of threshold insect populations. Also plant back intervals do not apply for such plant crops/species. Numerous other systemic pesticides have been documented to bio-accumulate in such perennial plants, even when half lives in other environmental compartments may be relatively short. There is absolutely no data provided in the EFED to address this issue. It is a very real concern that the expression of highly acute toxicity levels of cyantraniliprole and its degrades may appear in nectar, pollen and guttation fluids of such plants (e.g. flowering trees and shrubs, flowering perennials such as roses, etc.)

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044 ) : g. EFED fails to consider or document either the short term , or the cumulative concentration of this pesticide and its degradates from repeated applications in key environmental compartments such as soils, sediments, and there is a total lack of analysis of persistence (half life) and the poten tial for accumulative concentration in plant tissues, both of which have been totally ignored.

l. Also of great concern is the failures in TTR assessments: (1) to not have persistence or t 1/2 data for environmental compartments such as plant tissue and in particular pere nnial plant tissue; and (2) the apparent lack of TTR calculation for repeat applications of the pesticides and th e potential buildup in various environmental compartments with time, within soils and sediments and how that may affect systemically translocated p esticide concentrations into tissue of plants, annuals and particularly perennial plan ts which may be harboring increasing concentrations. Even with the TTR values presented, it is quite clear that accumul ation and build-up can become very serious over multiple seasons, voiding most of the assumptions about safety of allowa ble application rates for crops and other plant species. This of course also affects the assumptions of concentrati ons of the safety of residuals in harvested food and feeds, which may also tend to increase in successive seasons from environmental soil or perennial plant tissue accumulation.

J. Devries comment (Docket # EPA-HQ-OPP-2011-0668-0033) : As a seed treatment, cyantraniliprole will be used prophylactically (as are the neonico tinoids), and hence, their use will be widespread on the landscape. Further, as with neonicotinoids, it is likely that 80-98% of the active ingredient will remain in the soil and be available for transport (Sur and Stork 2003).

_____ Literature cited: Sur, R., and A. Stork. 2003. Uptake, transloca tion and metabolism of imidacloprid in plants. Bulletin of Insectology 56:35–40.

EPA’s response

The Agency acknowledges that cyantran iliprole and its degradates may pers ist in the environment given halflives ranging from 4 to 1800 days, depending on the soi l/environmental scenario. Currently, the Agency does

not have a model that addresses the accumulation of degradates over time; however, a bounding analysis was performed to address this issue. The Agency estimate d the accumulation that could be expected in soils from the use of cyantraniliprole over a 30 -year period using the Pesticide Root Zone Model (PRZM). One factor to

consider is that a number of different degradates form and some are more mobile in the soil than others. For modeling purposes, average Koc values for the degradates ranged from 30 to 14481 mL/g

o.c. Mobile degradates (low Koc) are expected to be susceptible to leachi ng and runoff and may not accu mulate in soils; whereas persistent and immobile degradates (h igh Koc) have the potential to accu mulate over time. Given that no one degradate dominates in a given system , a hypothetical scenario was generated using combined residue half-lives and a Koc value of 1500 mL/g

o.c. This Koc value was higher than cyantraniliprole, but not as high as thePage 23 of 46 degradate with the highest persiste nce (the most immobile degradate is 60 times more stable than cyantraniliprole based on average Koc comparison). Preliminary PRZM results show that when a single application of cyantraniliprole at 0.4 lb ai/A is applied once per year for 30 years assuming mob ility equivalent to or more than cyantraniliprole, that accumulation in th e soil does not occur. Assuming mobility is less than cyantraniliprole, accumulation could be ~0.8 to ~2 lb/A after 30 years.

No data have been submitted that suggest that cyantraniliprole is pe rsistent in plants and thus would bioaccumulate within them over time. Based on plant biology, cyantraniliprole would not be expected to accumulate in deciduous leaves, fruit, flowers, or other pa rts of the plant that are short-lived (i.e., less than one year). Furtherm the Agency is not aware of any additional data that demonstrate bioaccumulation of cyantraniliprole in plants.Page 24 of 46 5.5 Surface water contamination

J. Devries comment (Docket # EPA-HQ-OPP-2011-0668-0033) : The neonicotinoids have contaminated surface waters in many parts of the world at concentrations harmful to aquatic invertebrates (e.g., Van Dijk et al. 2013). It is highly probable that cyantraniliprole (and chlo rantraniliprole) will contaminate surface waters in highly cropped landscapes as the neonicotinoids have done in California (Starner a nd Goh 2012), Texas (Anderson et al. 2013), and prairie Canada (see P. 64 in Mineau and Palmer 2013).

_____ Literature cited: Anderson, T. A., C. J. Salice, R. A. Erickson, S. T. McMurry, S. B. Cox, and L. M. Smith. 2013. Effects of landuse and precipi tation on pesticides and water quality in playa lakes of the southe rn high plains. Chemosphere 92:84-90.

Mineau, P., and C. Palmer. 2013. The impact of the nation’s most widely used insecticides on birds. American Bird Conservancy report, March 2013. 97pp.

Starner, K., and K. S. Goh. 2012. Detections of the neonicotinoid insecticide imidacloprid in

surface waters of thr ee agricultural regions of Califor nia, USA, 2010–2011. Bulletin of

Environmental Contamination and Toxicology: 88:316–321.

EPA’s response

The need to address expected surface water concentrations, and potential e ffects on aquatic invertebrates in the cyantraniliprole ecological risk assessment is appr eciated. The evaluation of highly cropped landscapes is

accounted for within the risk assessment framework wher e the Agency utilizes the point estimate method which integrates exposure and toxicity endp oints against Agency levels of con cern (LOC). In addition, the risk assessment employs numerous regional-specific scenario s to characterize exposure to aquatic organisms in a variety of spatial and agricultural settings.Page 25 of 46 5.6 Prophylatic use as a seed treatment

J. Devries comment (Docket # EPA-HQ-OPP-2011-0668-0033) : As a seed treatment, cyantraniliprole will be used prophylactically (as are the neoni cotinoids), and hence, their use w ill be widespread on the landscape.

... The EPA needs to consider that wetlands, highly productiv e for waterfowl and many wetland-dependent species, very commonly occur embedded within a cropland matrix. The Pr airie Pothole Region of North America is one such example. This area produces an estimated 50-75% of North Am erican waterfowl (Batt et al. 1989), and is one of the most highly cropped landscapes in the world (Siebert et al . 2010). In addition to contamination by runoff, direct deposition of seed treated with cyantraniliprole into wetla nds will occur in this re gion as 30-50% of the wetland basins are impacted by cultivation; many temporary and seas onal wetlands are fully, or partially, cropped in drier years (Stewart and Kantrud 1973; see photos below). Given this extremely high risk to the ecological integrity of important North American wetlands, I urge that the EPA re ject cyantraniliprole as a seed treatment on all field crops.

_____ Literature cited: Batt, B. D. J., M. G. Anderson, C. D. Anderson, and F. D. Caswell. 1989. The use of prairie potholes by North American duc ks. Pages 204-227 in A. van de r Valk (Editor). Northern Prairie Wetlands. Iowa State University Press, Ames, Iowa. USA.

Stewart, R. E., and H. A. Kantrud. 1973. Ecological distribution of breeding waterfowl populations in North Dakota. Journal of Wildlife Management 37:39-50.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : Should approval continue to be considered despite the above noted app lication data and EPA assessment flaws and issues, uses for cosmetic purposes and prophylactic applications, including seed treatments, should not be allowed as these violate the basic principles of integrated pest manageme nt, and prevention of resistance development.

EPA’s response

The prophylactic use of cyantranilipro le as a seed treatment is inte nded to provide protection of young, immature seedlings and roots of potat oes, canola, mustard and sunflowers. All of these crops currently have registered seed treatment products containing other insect icides. Prophylactic seed treatments target pests that include cutworms, flea beetles, Colora do potato beetle and European corn bor er. Soil inhabiting pests such as cutworms may destroy a newly emer ged crop requiring growers the expe nsive and time-consuming burden of purchasing new seed and moving equipment many miles to replant the affected field.

Using treated seeds focuses the pesticide use on a very small and specific site. Alternatives such as ground sprays or in-furrow granular treatments of fields with compounds such as aldicarb (a systemic insecticide registered in 1970) result in greater environmental lo ading than seed treatments. There is less pesticide associated with a seed treatment compared to traditiona l foliar, granular, or in-furrow soil application methods. Less pesticide is available for runoff, and there is great er protection against target pests since the compound is applied where pests are impacting the crop. Additiona lly, seed treatments reduce pesticide exposure to applicators and farm workers compared to traditional field treatments.

Cyantraniliprole is classified as ‘p ractically nontoxic” to birds on an acute oral and sub-acute dietary exposure basis. Avian chronic exposure to cyantraniliprole does not exceed the Level of Con cern. EPA believes that its ecological risk assessment is protecti ve of North American waterfowl.Page 26 of 46 5.7 Water modeling

California Stormwater Quality Association comment (Docket # EP A-HQ-OPP-2011-0668-0035) : The impacts on urban watersheds from the broadcast applicati ons on outdoor urban surfaces ma y be substantially greater

than stated in the risk assessment. Our evaluation of EPA ’s urban runoff modeling suggests that concentrations in urban surface waters may have been substantially underest imated by EPA’s nascent impervious modeling scenario. Based on comparison to the pyrethroids, which have similar outdoor urban and agricultural use patterns, are less water soluble, and appear in urban watersheds at substantially higher concentrati ons than they appear in agricultural watersheds, 8 we strongly question EPA’s estimate that urban surf ace water concentrations would be lower than those occurring in agricultural waters.

While we greatly appreciate EPA’s efforts toward de velopment of modeling capabilities for urban pesticide applications, the current example highlights several areas wh ere the modeling could be impr oved. We believe that one of these areas may be the reason for the unlikely modeli ng conclusion for cyantranilipro le. The model assumes that runoff from pervious surfaces would occur at the same ra te as runoff from impervious surfaces; this runoff is estimated to provide a 6-fold dilution for runoff from impervious surfaces. We strongly question this assumption. For most storms occurring in California and the southwest, th ere is little runoff from pervi ous surfaces—nearly the entire volume of urban runoff is water that originally fell on an impervious surface. We have questions about dry weather flows, pesticide washoff fractions, the relatively low im pervious fraction in the impervious scenario, and other

elements.

_____ 8 See References in: TDC Environmental (2010). Pesticides in Urba n Runoff, Wastewater, and Surface Water: Annual Review of New Sc ientific Findings 2010. Prepared for the UP3 Project. March.

San Francisco Bay Regional Water Quality Co ntrol Board comment (Docket # EPA-HQ-OPP-2011- 0668-0034) : Closely approximating urban runoff characteristics is a critical step in the risk assessment process. We appreciate EPA’s efforts in creating an urban pesticide app lication model for cyantraniliprole. However, we concur that the improvements CASQA recommends are necessary.

EPA’s response

The Agency acknowledges that refine d urban runoff modeling would be bene ficial; however, such modeling is not currently available. Until a refined urban runo ff exposure model is developed and implemented, the Agency’s modeling approach for urban use sites incor porates a number of conserva tive assumptions that are intended to be protective of lower use, lower frequency of use, and reduced exposure. For example, the Agency assumes that all use sites within a pa rticular watershed receive an applica tion at the same time, a conservative assumption considering the spatial a nd temporal variability that exists within even a single residential development. Accounting for these multiple conservative assumptions, there were identified LOC exceedances for freshwater acute and chronic expo sure as well as exceedances for be nthic chronic exposures. Prior to the implementation of an acceptable refine d urban runoff model, the Agency co mpleted a comparative analysis of risk estimates by taxonomic class to ev aluate the potential for the under es timation of exposure from urban use scenarios. This analysis showed that in order to ex ceed the Agency’s acute and chronic LOCs for additional

taxonomic classes the EECs would have to be one to three fold higher than the EECs estimated using the proposed residential/urban area use ra tes (flowerbeds, ground covers, comme rcial and consumer ornamentals, exterior landscapes, trees, turf, residential lawns, park s, athletic fields, nurserie s, grassy/weedy/mulched/bare soil areas, and public health inse ct control). It is unlikely that this one to three fold increase in the EECs would occur in a typical urban exposure scenar io since there is considerable tem poral and spatial va riability in the pattern of application in a reside ntial environment. Therefore, the Agency’s conclusions based on urban exposure scenarios are protective for additional taxonomic classes.Page 27 of 46 6.0 Effects on birds and mammals

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : [Comment 2:] 2q. .... When EPA states that cyantraniliprole is “practica lly nontoxic” to birds and mammals, it does not consider the reality of the toxicity of exposures from eating treated seeds. Anyone who has real field experience can watch birds and rodents follow planting operations to not only pick up uncovered surface seeds but dig out planted seeds, thereby receiving major dosing in a single feeding event. EPA expos ure models and EEC calculations do not model this real behavior. Bottom line is that the EPA simply does not have the knowledge base or the ability to predict with any degree of confidence the consequen ces of adding this new poison.

EPA’s response

The LD 50 for birds is > 2250 mg ai/kg-bw and the LD 50 for mammals is > 5000 mg ai/kg-bw. Based on the Agency’s categories of toxicity (Brooks et al., 1973), a toxicity value above 2000 mg ai/kg-bw is considered “practically non-toxic.”

For rapeseed, the maximum concentration is 1.33 mg ai/seed. Conservatively assuming that the LD 50 for birds is 2250 mg ai/kg-bw and the LD 50 for mammals is 5000 mg ai/kg-bw, 1692 and 3759 seeds would been to be consumed by birds and mammals, respectively, to reach the LD 50

.

For sunflower, the maximum concentration is 0.2 mg a i/seed. Using the same assu mptions for the rapeseed analysis, birds would need to consume 11,250 seeds and mammals would need to consume 25,000 seeds to

reach the LD 50

.

Further, it is unlikely there would be sufficient number of seeds availabl e for consumption to cause a lethal effect using precision planti ng equipment, and labeling language instruct ing growers to incorporate treated seed minimizes availability and non-target exposures. Wher e the typical bird or non-target mammal foraging for seeds, including seeds that were not properly plante d, would reach their caloric intake needs well before consuming the number of seeds needed to reach a leth al effect (USEPA. 1993; B ecker and Ratnayake, 2011).

_____ Brooks, H.L. et al. 1973. Insecticides . Cooperative Extension Service, Kansas State University, Manhattan, Kansas. USEPA. 1993. Wildlife exposure factors handbook. Volume I of II. EPA/600/R-93/187a. Office of Research and Development , Washington, D. C. 20460. Becker, J. and S. Ratnayake. 2011. Acres planted per day and seeding rates of crops grown in the United States. Biological a nd Economic Analysis Division, Office of Pesticide Programs, United States Environmental Protection Agency.Page 28 of 46 7.0 Effects on pollinators

7.1 Exposure to dust from treated seed

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : When it comes to field conditions, the agency is aware that pesticide-tr eated seed, when planted, can produce cont aminated dust plumes which can travel miles exposing bees and other non-target organisms to vari ous residues of pesticide. Studies have documented high bee mortality following seed sowing and exposure to contaminated dust from agricultural fields. 6,7,8 The agency states that cyantraniliprole seed treatment will result in negligible drift. However, under its “Spray Drift Analysis,” there was no discussion on the use of sowing equipment and the sub sequent injection of chemical residues that result in toxic dust plumes that have been documented as a direct threat to foraging bees.

The agency has previously st ated that it intends to encourage new seed coatings and sowing equipment to reduce the emission of pesticide residues into dust. However, while these are short-term measures that may somewhat reduce airborne residues, the implementation of these is several y ears away and would not serve to adequately protect bees from pesticide-treated seed. As cyantrani liprole is being registered for seed treat ment, this opens an atypical exposure pathway (via dust) that the agen cy has not fully accounted for.

_____ 6 Girolami, V. et al. 2011. Fatal powdering of bees in flight with particulates of ne onicotinoids seed coating and humidity impl ication. J. Appl. Entomol . 136:17–

26.

7 Tremolada P, et al. 2010. Field trial for evaluating the effects on honeybees of corn sown using Cruiser and Celest xl treated seeds. Bull Environ Contam

Toxicol .85(3):229-34.

8 Krupke CH, Hunt GJ, Eitzer BD, Andino G, Given K. 2012. Multiple Routes of Pesticide Exposure for Honey Bees Living Near Agric ultural Fields. PLoS ONE 7(1): e29268. doi:10.1371/journal.pone.0029268

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Pollinator exposure to dust from cyantraniliprole-t reated seeds was also not assessed. This has been a major exposure route for honeybees with neonicotinoid-treat ed seeds as dust containing the active ingredients contacts the bees or settles on flowering plants nearby. 58 This route of exposure should be assessed before cyantraniliprole is approved.

EPA’s response

There are many factors associated with the phenomenon of dust-off ( e.g., efficacy of sticking agents, lubricants used to move seed through large pn eumatic planters, planting equipment us ed, weather, and availability of suitable forage in close proximity to the field being plante d). At this time, EPA does not have a suitable tool for modeling dust-off as a route of exposur e from treated seeds. A complexity of factors and the uncertainty for how to parametize the different physics involving dust complicates use of exis ting tools that were calibrated to model vapor phase compounds. The EPA recognizes that pe sticide residues in dust that are generated by the abrasion of treated seed coatings dur ing planting is a potential route of exposure. However, the EPA has been working with registrants, seed treaters, seed equipm ent manufacturers, commodity groups and beekeepers to develop stewardship efforts and best management practices that can reduce the likelihood of dust-off during the planting of treated seeds. Included in these efforts is the development of a lubricant alternative to talc and graphite which are added to planters to facilitate movement of the seed through the planting equipment. The alternative significantly reduces “fugitive dust.” The new l ubricant is expected to be available starting with the 2014 planting season and is not “several years away.”

It is important to note that the bee kill incidents attri buted to fugitive dust from planting are associated with treated corn seed. Corn seed is larg er and dirtier than most seed, it is mo re likely to contain plant particulates (cob, stalk etc) and is planted on far more acreage than any other crop. Cyan traniliprole is not proposed for use

as a corn seed treatment.Page 29 of 46 7.2 Study rates versus label rates

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : In these [semi-field] studies, toxicity to honey bees (adults) was observed at application ra tes lower than those proposed for registration: tests were conducted up to 0.134 lb ai/A, whereas the maximum application rate for some uses is up to 0.69 lb ai/A, and EPA states that “there is uncertainty regarding the effects to honeybee hive health and pollinator services at application

rates above 0.134 lb ai/A.”

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : Adverse Effects [on pollinators] Clearly Shown .... And fr om EPA's own revised assessment it is clear there remain many unknowns for Cyantraniliprole: - Residues from the highest application rates were not available - Field data were not available for higher labeled ra tes of foliar spray applications of Cyantraniliprole.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : All of the studies were also conducted at levels we ll below the proposed application rates, suggesting that higher rates could increase the exposure of pollinators. 51 This is a serious deficiency in the risk assessment because the proposed real-world application rates are entir ely untested. Studies with the lower application rates did suggest negative effects on pollinators that could affect po llination, finding that “the combination of mortality, sublethal effects, and repellence (decr eased foraging) in cyantraniliprole-tr eated plants may affect pollinator

services.” 52 Brood studies intended to assess the effects on the colo nies were also inadequate. While residue testing showed concentrations in pollen and nectar food sources that were below the acute toxicity values for honeybees, these studies were also conducted well below the maximum app lication rates. Risk quotients from this data also suggest potential risks from dietary exposure at the rat es tested, up to 0.134 lb ai/A, still below the maximum proposed rate of 0.68 lb ai/A. Based on the negative imp acts identified at lower rates, and the ongoing pressures on pollinators, cyantraniliprole, both in technical formulati on and end-use product formula tions, should not be approved without further study. In residue studies, higher concentrations of cyantraniliprole were consistently found in pollen, suggesting that bees may be exposed to high concentrations. 53 Without adequate examination, EPA cannot rule out unreasonable adverse effects on these pollinators.

_____ 51 EPA, Amended Risk Assessment, at 69-73.

52 Id. at 139.

53 Id. at 136.

EPA’s response

Cyantraniliprole residues were collect ed from pollen and nectar. The majority of an adult honeybee’s diet is nectar. The scenario that yielded the highest nectar concen tration was a drip application to melons (3 applications at 0.089 lb ai/A with a 7-da y application interval). In total, the melons were exposed to 0.267 lb of cyantraniliprole over a 2-week period. When the nectar residues were converted into a dose, it was found that an adult honeybee would need to consume 6 times the concen tration of cyantraniliprole that was detected in the nectar to exceed the Agency’s Level of Concern. Assuming the increase in cyan traniliprole residues in nectar is linear (a reasonable assumpti on because there is no eviden ce of a biochemically facil itated transport mechanism or barrier to transport beyond that whic h would be expected in a Fick’s Law- base system), this would mean that the application rate would need to be 6 times higher to yield a dose of cyantraniliprole that could cause concern. The maximum cyantraniliprole applicati on rate is 0.69 lb ai/A (potato seed treatment); this is only 3 times higher than the rate in the melon study. Thus, it is unlikel y that adult honeybees would be exposed to oral doses of cyantraniliprole that exceed the Agency’s Level of Concern.Page 30 of 46 In the final labels, both the maximum single applicati on rate and the maximum rate per season were capped at 0.4 lb ai/A (0.175 lb a.i./A/year for cyantraniliprole/thiamethoxam combina tion products), thus making it even more unlikely that adult honeybees w ould be exposed to oral doses exceeding the Agency's Level of Concern.

The Agency acknowledges that field studies were not conducted at the highest cyantraniliprole application rates. Existing studies at the 0.134 lb ai/A showed adverse effects on honeybees, but these were transient effects and hives were able to successfully overwinter. While the residue analysis discussed in the preceding paragraph indicates that cyantranilipro le concentrations are no t likely to cause acute e ffects in adult honeybees at higher application rates, the eff ects to brood at higher application ra tes are uncertain. There is also uncertainty regarding the magnitude of increase for the tr ansient effects that could occur at higher application rates ( i.e., mortality rates could be higher, behavior changes c ould be more intense, duration of effects could be extended). While the Agency recognizes these uncertain ties, the overall weight of evidence concludes we do not expect long-term, chronic effects.Page 31 of 46 7.3 Exposure from residues in guttation fluid

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Even at the lower application rat es, the concentrations of cyantraniliprole in guttation fluid were concerning. Studies have demonstrated that honeybees drink gu ttation fluid and it can be a pathway for exposure to systemic pesticides. 54 The studies cited in EPA’s risk assessment found levels of cyantraniliprole in guttation fluid were also conducted with a 15-day application interval, wh ile some labeled uses would allow for a 7-day interval. This could also contribute to higher levels of cyantraniliprole in guttation fluid in the field. Given that this effect was noticed at a lower rate than proposed, and with less-fre quent applications, more st udies should be conducted to evaluate this exposure pathway.

_____ 54 Girolami, V. et al. 2009. Translocation of Neonicotinoid Insecticides from Coated Seeds to Seedling Guttation Drops: A Novel W ay of Intoxication for Bees. J

Econ Entomol 102(5): 1808-1815.; Hoffman, E & Castle, S. 2012. Imidacloprid in Me lon Guttation Fluid: A Potential Mode of Exposure for Pest and Beneficial Organisms. J Econ Entomol 105(1): 67-71.; Reetz, J. et al. 2011. Neonicotinoid insecticides tr anslocated in guttated droplets of seed-treated maize and w heat: a

threat to honeybees? Apidologie 42: 596-606. [49 Attachment 1]

EPA’s response

The Agency acknowledges that guttation water is a complete exposure pathway for honeybees; however exposure via guttation water is expected to be lowe r than through pollen and n ectar (USEPA 2012; EFSA 2012). Honey bees may obtain water from water bodies, de w on plants, through dietary items (pollen/nectar) as well as guttation fluid. Analyzing risk potential from the consumption of po llen and nectar is expected to be protective of guttation water consumpti on because there is uncerta inty and variability in the extent to which honey bees harvest and use guttation flui d relative to other available sources of water, and relative to the exposures from pollen and nectar, risk pot ential from guttation water is low.

_____ USEPA, 2012. White paper in support of the proposed risk asse ssment process for bees. Office of Chemical Safety and Pollutio n Prevention, United States Environmental Protection Agency, Washington, DC.

EFSA. 2012. Scientific opinion on the scie nce behind the development of a risk asse ssment of plant protection products on bee s ( Apis mellifera, Bombus spp., and solitary bees). EFSA Journa l 2012. 10(5): 2668 (275 p.).Page 32 of 46 7.4 Bee dietary exposure assumptions

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : 2b. Clear statements in the EFED about acute toxicity to honey bees (and by extension other beneficial insects) are made. Proposed Registration doc (p. 12) states “honey bee toxi city data for cyantraniliprole indicated that it is highly

toxic on an acute oral and contact basis..”. EPA al so states the “endpoints are non-definitive” and “toxicity classification is uncertain”. The calculations regarding dose and dietary EEC presented in the EFED (pages 52-53 (Table 19 with EECs), and referenced in the proposed regi stration are questioned by this reviewer. EPA is hereby requested to present full detailed explanations and calculati ons with all assumptions and data sources fully elaborated and with all units of measure clearly included. Notable is the apparent inconsistenci es in the Table 19 values and the** footnote which states that adult bee food consumption rate is 0.292 g/day and the statement in the subsequent paragraph stating that equivale nt [cyantraniliprole] dose rate is also 0.29 2 g/day/adult. These two can clearly not be the same value, so all of the presented data in tables and assessments are called into question.

EPA’s response

Thank you for pointing out this mistake. The adult bee consumption rate should be 0.292 μ g ai/bee (rather than g ai/bee). To calculate a dose, the concentration expected to be found in the pollen/ne ctar must be multiplied by the amount of food that an adult bee consumes per day ( 0.292 μg ai/bee). Table 19 contains doses for the soil application scenarios (based on the Briggs model). The following paragraph contains doses for the seed treatments, which are based on a 1 mg ai/kg pollen prem ise (EPPO 2010). The calculations in Table 19 and the following paragraph are correct.Page 33 of 46 7.5 Effects on bee larva

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : According to the agency, “..honeybee larval toxicity data were not available, only cyantraniliprole doses for adult bees are considered.” 2 EPA then utilized information from field studies to extrapolate the effects of cyantraniliprole on larvae. Acute risks to honey bees are dependent on the life stage and caste of the bee, and it is important to recognize that adult data cannot be accurately used to extrapolate for juveniles.

.... Important questions on cyantraniliprole’s impacts on brood development and long-te rm colony health have not been sufficiently answered. EPA’s conclusion that no long-term effects adverse effects expected for honey bees therefore cannot be made with certainty, even with the help of supplemental studies, and should therefore disqualify cyantraniliprole for registration under FIFRA, as it does not sa tisfy the terms set out in Section 3(c)(7)(A), in that registration will pose “unreasonable adverse effects on the environment.”

_____ 2 USEPA. 2013. Environmental Fate and Ecological Risk Assessment for the Registration of the New Chemical Cyantraniliprole – Ame nded. Office of Pesticide Programs. Washington DC.

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : EFED fails to properly assess the sub-lethal and chronic and immune syst em degradation in non-target species, including many

classes and orders of animals from insects and other invertebra tes, to amphibians, birds, mammals, even humans. This is notably true for key ecologically critical species such as the honey bee in the cyantraniliprole EFED for which only acute toxicity on adult specimens are conducted. Until this is corrected and the substance is proven safe, the application is totally incomplete and should be rejected.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : Larval toxicity was not assessed because experi ments were only performed to evaluate adult honeybees.

EPA’s response

The Agency agrees that honeybee adult to xicity data cannot be used in place of larval toxicity data; larvae may be more or less sensitive to chemicals. Adult toxicity da ta were not used in the risk assessment to estimate risk to larva. While larval toxicity data are not available, the fi eld studies are available. The field studies provide in

situ information about the effects of cyantraniliprole applications at 0.134 lb ai/A to brood development and long-term colony health. If the larv ae in a hive are undergoing adverse t oxicological effects to a significant degree, a decrease in hive population or other colony-level effects will be seen over time – especially during the overwintering period. Three semi-field studies followed the hives that had been e xposed to cyantraniliprole through their overwintering period. Two of the studies showed that hive health and brood development were comparable between the controls and treatment groups at the end of overwintering. The third study showed no differences in hive health/brood development between the control and one trea tment group, but did indicate

some effects between the control and a second treatm ent group. The reasons for the difference are unknown. By weight of evidence, the overwintering semi-field st udies suggest cyantraniliprole at 0.134 lb ai/A does not adversely affect hive health/br ood strength and thus, demonstrate no unreasonable toxicity to larvae.Page 34 of 46 7.6 Susceptibility to Varroa mites and Nosema

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : One study notes that sub-lethal effects of pesticides on young bees, including delayed adu lt emergence, may seem inconsequential but may provide a reproductive advantage for Varroa mites. 3 Combined effects from exposure to p esticide residue in brood comb, such as reduced adult longevity, increased brood mortality, higher fecundity of Varroa mites (due to delayed development and emergence of adult bees) and incr eased susceptibility to pathogens, may c ontribute to reduced honey bee colony health, as affected queens and worker bees are unable to meet the demand for brood production and resources needed to sustain large colony populations. 4

_____ 3 Wu JY, Anelli CM, Sheppard WS (2011) Sub- Lethal Effects of Pesticide Residues in Br ood Comb on Worker Honey Bee (Apis mellifera ) Development and Longevity. PLoS ONE 6(2): e14720. doi:10.1371/journal.pone.0014720

4 Wu JY, Anelli CM, Sheppard WS (2011) Sub- Lethal Effects of Pesticide Residues in Brood Comb on Worker Honey Bee (Apis mellifer a) Development and Longevity. PLoS ONE 6(2): e14720. doi:10.1371/journal.pone.0014720

Center for Regulatory Integrity comme nt (Docket # EPA- HQ-OPP-2011-0668-0045) : Of particular concern is a field study that show ed increased honeybee susceptibility to Varroa mite infestation from exposure to cyantraniliprole. In a recent stakeholder report, USDA and EPA stated that Varroa mites were a major factor in the decline of honeybee populations. If this is true, why would EPA approve the regist ration of a pesticide that has been

shown to increase the Varroa mite population in bees? Even if only one in dustry study shows this negative impact, it should raise a red flag with EPA, and the agency should re quire additional studies before rushing to approve this

insecticide.

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : One very telling section of the EFED report discusses the effects of Cyantr aniliprole with an increase of varroa: "An additional observation was that hives not exposed to cyantraniliprole (cont rols) appeared better able to resist the infestation than those hives that were exposed. This suggests that while cyantraniliprole may have limited effects on honeybees by itself, when combined with other real-world stressors, hive health may be affected."

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : One of the pollinator studies showed th at colonies had increased susceptibility to Varroa mite infestations, which could be mediated by the active ingredient . In this study, it appeared that the hives not exposed to cyantraniliprole were better ab le to resist infestation than those that were exposed. 55 It has been suggested that neonicotinoids may be interfering with the bees’ immune systems and decreasing their ability to fight other similar pathogenic infestations, such as Nosema

. 56 A similar effect may be occurring with cyantraniliprole, but the increase in

Varroa prevalence was not further investigated. Before regist ering cyantraniliprole and its technical and end-use products, EPA must critically assess the indirect effect that exposure to cyantraniliprole may have on bees’ ability to

resist Varroa infestations, since Varroa mites have been identified as one of the major contributing factors in bee declines by the recent EPA/USDA Stakeholder Report. 57

_____ 55 EPA, Amended Risk Assessment, supra note 1, at 73.

56 Pettis, J. et al. 2012. Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema

. Naturwissenschaften 99: 153-158; Alaux et al.

2009. Interactions between Nosema microspores and a neonicotinoid weaken honeybees ( Apis mellifera ). Environmental Microbiology 12(3): 774-782. [49 Attachment 4]

57 United States Department of Agriculture, Report on the National Stakeholders Conference on Honey Bee Health (October 15-17, 2012). available at http://www.usda.gov/documents/R eportHoneyBeeHealth.pdf. [not submitted]

EPA’s response

The Agency evaluated 12 field/semi-fi eld studies on honeybees. Of these, only one suggested that exposure to cyantraniliprole coincided with obser ved increases in susceptibility to Varroa mites. MRID 48688806 also had

hives with Varroa mite infestations during the course of the e xperiment, but none of the observed effects were attributed to a cyantraniliprole- Varroa mite interaction. The Agency’s risk assessment acknowledges that one field study showed a possible incr eased honeybee susceptibility to Varroa mites that coincided withPage 35 of 46 cyantraniliprole exposure. However, given that this was only observed in one st udy out of 12, the study was not designed to definitely test this premise, and Varroa mites were present in other field/semi-field studies without such treatment-related changes in infestation, the preponderance of evid ence does not support a conclusion that

increases in Varroa mite susceptibility is a frequent result in hives exposed to cyantraniliprole.Page 36 of 46 7.7 Incident reporting system fo r adverse effects on pollinators

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : Without a Viable Incident Reporting System, EPA Cannot Track th e Impact of Registration D ecisions - The proposed registration process begs the question of how EPA will de termine if Cyantraniliprole can safely be used in agriculture. At present, there is no viable system for reporting and tr acking pesticide poisonings of honey bees when they occur, making it impossible to document kills caused by problematic pesticides, and restrict their use. It is critical that EPA develop, and impl ement a valid mechanism for tracking poisoning events prior to the registration of Cyantrani liprole, and use this system to gath er data on potential adverse effects.

EPA’s response

Pesticide incidents involving bee kills may be directly reported to beekill@epa.gov . This link is clearly represented on EPA’s Pollinator Protection website with an icon that is very prominent. This link has been advertised in bee journals and pres ented at numerous public meetings. St aff of EPA’s Environmental Fate and Effects Division directly cont act and interview people submitt ing incidents. Incidents are also reported to the

National Pesticide Information Center 3 (NPIC) and these are referred to EPA. Again, EPA staff follow-up on these reports.

Historically, commercial beekeepers in particular have shown gr eat reluctance to report incidents. State Lead Agencies and EPA have been told that beekeepers do not wish to offend growers who either hire their pollination services, or allow them on their land. EPA is also aware that some beekeepers are concerned that residues of pesticides used in thei r hives illegally to control Varroa m ite or other pests may be discovered during the investigation. However, EP A has reached out continuously, both on an individual basis, and publicly to convince beekeepers of the importan ce of incident information and to ur ge beekeepers to report incidents. On August 15, 2013 EPA issued new pollin ator protective labeling for products containing four neonicotinoids. Included in this labeling is text wh ich provides contact information for re porting bee kill incidents which puts the information directly in the hands of the user, which is required on the cyantraniliprole labels. Thus, these pesticide labels will contai n the following statements:

Pesticide incidents (for example, bee kills) should immedi ately be reported to the state/tribal lead agency. For contact information for your state, go to: www.aapco.or g/officials.html. Pesticide incidents should also be reported to the National Pesticide Information Center at: www.npic.orst.edu or directly to EPA at: beekill@epa.gov

Finally, under FIFRA section 6(a)(2), pesticide registrants are legally requ ired to submit factual information regarding unreasonable adverse effects on the environment. For example, incident reports on bee kills have provided useful information on residues (or lack thereof) that were later co rroborated by the state lead agencies. Further, incident reports have been submitted to the Ag ency reporting adverse effects in on-going studies in the European Union. These reports have alerted EPA to eff ects well before the study was completed and are used to

inform risk assessments.

3 http://npic.orst.edu/reportprob.htmlPage 37 of 46 7.8 Effect of timing of aplication on bee toxicity

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044) : [Comment 2:] Further on this point [failure to acknowledge potential fo r accumulation in plants] is the suggestion that avoiding applications of cyantraniliprole during flowering periods can somehow prevent toxicity to non-target species such as honey bees. This is simply unfounded assumption backed up by no data. To propose such an inadequate BMP or Direction for Use is similarly without jus tification or basis in demonstrated fact.

EPA’s response

The Agency reviewed multiple honeybee field studies that demonstrated that adverse effects to honeybees were reduced when applications occurred when bees were not active, suggesting th at direct contact with cyantraniliprole results in toxic eff ects. While this does not directly co rrelate to the conclusion that avoiding applications of cyantraniliprole during flower periods will prevent toxicity to non-target species, it does suggest that risks to honeybees are reduced when the bees are not directly sprayed.

Cyantraniliprole is a systemic compound and it is expected that its residues will be fo und in the pollen/nectar of flowers if applications have been made prior to fl owering, resulting in potential dietary exposure to foraging bees. As discussed earlier, cyantraniliprole residues we re collected from pollen and n ectar. The majority of an adult honeybee’s diet is nectar. Th e scenario that yielded the highest nectar concentration was a drip application to melons (3 applications at 0.089 lb ai/A with a 7-day applicati on interval). In total, the melons were exposed to 0.267 lb of cyantrani liprole over a 2-week pe riod. When the nectar residues were converted into a dose, it was found that an adult honeybee woul d need to consume 6 times the concentration of cyantraniliprole that was detected in the nectar to exceed the Agency’s Level of Concern. Assuming the increase in cyantraniliprole residues in nectar is linear (a reasonable assumption beca use there is no evidence of a biochemically facilitated transport mechanism or barrier to transport be yond that which would be expected in a Fick’s Law-base system), this would mean that the appl ication rate would need to be 6 times higher to yield a dose of cyantraniliprole that could cause concern. Th e maximum cyantraniliprole a pplication rate is 0.69 lb ai/A (potato seed treatment); this is only 3 times higher than the rate in the melon study. Thus, it is unlikely that adult honeybees would be exposed to oral doses of cyan traniliprole that exceed the Agency’s Level of Concern.

In the final labels, both the maximum single applicati on rate and the maximum rate per season were capped at 0.4 lb ai/A, thus making it even more unlikely that adul t honeybees would be exposed to oral doses exceeding the Agency's Level of Concern.Page 38 of 46 8.0 Effects from multiple active ingredients, a nd/or multiple formulations used in combination

Boulder Innovative Technologies co mment (Docket # EPA-HQ-OPP-2011-0668-0044 ) : [Comment 2:] m. The EFED absolutely fails to assess th e effects of multiple pesticides used in combination with cyantraniliprole. This is an ongoing failure of the EPA process of reviewing pesticides. It is even more notable given the intended formula combination with cyantraniliprole with the ac knowledged neonicitinoid honey bee toxin, thiamethoxam, in three of the Syngenta proposed products (see EFED Table 2, page 8-9)

... This EPA review protocol failure to ac knowledge combined pesticide effects must be corrected or all practical reality of the approval process for pesticides must be deemed invalid . It simply does not reflect the real world of pesticide use, notably multiple pesticide applications to the same sites and crops within the same time frames of chemical persistence, and their combined potentially multiplying effects.

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : Field studies for short and long-term effects need to be complete d if combining cyantraniliprole and thiamethoxam.

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : EPA entirely neglected to consider the syne rgistic and cumulative impacts of approving cyantraniliprole and its related products in light of the existing stressors pl aced upon honey bees, vital pollinators, birds, other sensitive species, and the environment. EPA’s ove rsight is significant, in light of similar effects of cyantraniliprole and other neonicotinoid pesticides, as well as proposed co-formulations of cyantraniliprole and

thiamethoxam.

.... EPA also acknowledges that the agency lacked the appropriate field study to verify the risks to honey bees posed by cyantraniliprole-thiamethoxam co-formulations....EPA must separately assess the risks stemming from the use of cyantraniliprole-thiamethoxam co-formulations be fore approving those product registrations.

EPA’s response

The EPA recognizes the importance of exposure to mixtures but assesses the environm ental exposure of a single active ingredient (USEPA, 2004 1 ). There are many types of environmenta l mixtures. First, some pesticides might contain more than one active in gredient, or in the case of formul ated end-use products, they contain additional chemicals that are typica lly designated as inerts which ar e specific to each product. Second, pesticides are often mixed with other chemicals before their application. ( e.g., tank mixes with other pesticides, fertilizers, and adjuvants). Third, non-pesticidal chemi cals from other sources are already in the environment ( e.g., environmental mixtures). Ideally, assessments shoul d be based on exposure to all pesticide components and to other chemicals that are pres ent in the environment. However, qua ntitative estimates of exposure to

environmental mixtures are difficult given the dynamic state of environmen tal mixtures over space and time. In any given location, the amounts of pesticide active ingred ients, inerts, adjuvants, and other environmental chemicals are highly variable and depend on pesticide us es and other sources of environmental exposure. A quantitative assessment of the risk posed by chemical mi xtures requires extensive data, including data on the identity, concentration, and t oxicity of mixture component s. Challenges in assessi ng risk to species posed by pesticide-containing mixtures arise larg ely because of the lack of such data and the lack of understanding of the potential for interactions among mixture components. In the absence of such quant itative data, the possible contribution of specific mixture com ponents to the toxicity of a pes ticide active ingredient cannot be incorporated into a quantitative risk assessment.

However, if evidence from incidents or field observations suggest that ta nk mixed products may be impacting non-target organisms, the EPA can require studies to be conducted. Studies of tank mixes conducted by independent researchers can be and have been used to inform risk assessments.Page 39 of 46 It is important to note that the pollinator assessment does evaluate the risk associated with cyantraniliprole formulated products (including the pr oposed cyantraniliprole-thiamethoxam coformulated product), as these studies are conducted using formulated end- use products as the test substances.

_____ 1 USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Prote ction Agency: Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C. January 23.Page 40 of 46 9.0 Consultation with Fish and Wildlife Service (FWS)

Center for Biological Diversity comme nt (Docket # EPA- HQ-OPP-2011-0668-0041) : Given the results from the ecological risk assessment for cy antraniliprole, the EPA must begin th e informal consultation process with the Services and work towards the pr eparation of a nationwide biologi cal assessment of cyantraniliprole.

.... Section 7(d) of the ESA provides that once a federal ag ency initiates consultation on an action under the ESA, the agency “shall not make any irreversible or irretrievable co mmitment of resources with respect to the agency action which has the effect of foreclosing the formulation or implementation of any reasona ble and prudent alternative measures which would not violate subsection (a)(2) of this section.” 12 The purpose of Section 7(d) is to maintain the environmental status quo pending the completion of consu ltation. Section 7(d) prohibitions remain in effect throughout the consultation period and un til the EPA has satisfied its obligations under Section 7(a)(2) that the action will not result in jeopardy to the species or adverse modifica tion of its critical habitat. An active ingredient cannot be registered for use prior to the completion of the consultati on process. The registration of an active ingredient prior to the completion of consultations would represent an irrevers ible and irretrievable commitment of resources, and would violate the basic requirement of the ESA that each agency of the federal govern ment insure that their actions do not jeopardize listed species or adversely modify critical habitat.

_____ 12 16 U.S.C. § 1536(d)

Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : EPA cannot approve the proposed registrations of cyantraniliprole as a new active ingredient and cyantraniliprole-containing product formulations without firs t consulting with the expert fish and wildlife agencies as required under the ESA. Section 7 of the ESA requires that EPA consult with the expert agencies FWS and/or NMFS to “insure” that actions taken by the agency will not jeopard ize the survival of federally listed species or destroy or adversely modify their designated critical habitats. 69 EPA’s assessment of impacts to federally listed species

concluded that all listed taxa may be indirectly affected and a number may be directly affected by cyantraniliprole application.

_____ 69 See 16 U.S.C. § 1536(a)(2); see also 50 C.F.R. § 402.01(b).

EPA’s response

As stated earlier in section 4, the EPA and the De partments of Agriculture, Commerce and the Interior requested that the National Resear ch Council (NRC) of the National Ac ademy of Science (NAS) convene a committee of independent experts to examine topics pertai ning to tools and approaches for assessing the effects of proposed FIFRA actions on endangered and threatened species and their critical habitats. The Agency is working with the Fish and Wildlife Service and National Marine Fisherie s Service to develop a mutually agreeable course of action that incorporates the NAS findings. Additional information and resources regarding the implementation of the NAS recommendations can be found on the Agency’s website ( http://www.epa.gov/espp/2013/nas.html ). Interim approaches for national-level pesticide assessments are also provided on the Agency’s Endangered Species Protection Program website ( http://www.epa.gov/espp/2013/interagency.pdf ).

It is important to note that the Agency is focusing most of its resources for assessing impacts to listed species on the Agency’s registration review program for currently re gistered pesticides. EPA believes that, as a general matter, currently registered pesticides present a greater degree of risk to list ed species than most new chemistries coming to market, including cyantraniliprole, a nd that it is therefore environmentally preferable in most circumstances for EPA to assess the impacts of ex isting pesticides sooner in the process than newer pesticides that are designed to compete with more risky alternatives. EPA believes that is especially true for cyantraniliprole, where the alternatives include

, organophosphates, carbamates, ne onicotinoids, and pyrethroids. As a result, EPA does not believe the environment or the public would be best served by delaying thePage 41 of 46 registration of cyantraniliprole to co mplete consultation. Focusing EPA’s, FWS’, and NMFS’ limited resources on completing a consultation on the effects of cyantranipro le would by necessity come at the expense of putting more resources into evaluating – and consequently regul ating, where appropriate – what EPA believes to be more toxic compounds, that, among ot her things, pose greater risk, to endangered species than does cyantraniliprole.Page 42 of 46 10.0 Labeling

10.1 Labeling to prevent harm to bees and other animals

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : Inadequate and Unenforceable Labeling Statements - Cyantraniliprole proposed label statements are inadequate and do not go far enough to warn the user of the risks to honey bees. For end use outdoor products, EPA’s propo sed environmental hazard statement is as follows: “Drift and runoff may be hazardous to a quatic organisms in water adjacent to treated areas. This pesticide is toxic to aquatic invertebrates. This product is highly toxic to bees exposed to direct treatment or residues on blooming crops or weeds. Do not apply this product or allow it to drift to blooming crops or weeds if bees are visiting the

treatment area.”

These labels seem to be unrealistic in the real world a nd unenforceable. While spraying before and after bees are active in fields may minimize direct contact exposures, r esidual exposures are still highly toxic and do not solve the problem of minimizing risks.

The agency is also aware that label directions such as th ese are not adhered to in the real-world. Many beekeepers can attest to this. Addressing lack of comp liance has been an area th e agency has not sufficiently addressed throughout the years. These labels are also unenforceable. Moreover, instru ctions to minimize pesticide drift continue to be a challenge especially for aerial applications. It is difficu lt to engineer meaningful hazard statements that can sufficiently mitigate risks and are enfor ceable. Therefore, while the agency cont inues to work with stakeholders in formulating meaningful hazard statemen ts, products toxic to honey bees should not be entered into the marketplace which fosters a lack of compliance and enforcement complications.

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : EFED's own conclusion concerning effects states, "based on available data" that Cyantraniliprole is "highly to very highly toxic to terrestrial insects." The registration of Cyantraniliprole w ould add another highly acutely toxic insecticide that would be applied to blooming crops attractive to honey bees. Th e environmental hazards listed for the "master label" for A17960B ST state Cyantraniliprole is "toxic to wildlife and hi ghly toxic to aquatic invertebrates, oysters and shrimp," for the seed treatment has no mention of EPA's own statement of high acute toxicity to terrestrial insects, i.e. honey bees. As the seed treatment is water soluble, can be mixed w ith fungicides, and/or the coat ed seed planted with talc or fir bark that may affect water runoff, or dust that risks c ontamination by of this highly acutely toxic insecticide, there is no mention on the [seed treatment] label concerning th e toxicity to honey bees and other pollinators.

On the label for Cyantraniliprole for application on turf(A 16901B), it is mixed with Thiamethoxam a known toxin to honey bees. While the environmental hazards section states "This product is highly toxic to bees exposed to direct treatment or residues on blooming crops. Do not apply this product or allow to drift to blooming crops if bees are visiting the treatment area." Additional clarity in this section to protect honey bees and other pollinators, who are working the crop to pollinate it and increase crop output, would be to include language sta ting, for example: "Do not apply to the blooming crop during daylight hours. If applied during the bloom the residue must have at least four hours oftime to dry, prior to honey bees or other pollinato rs returning to the field." However, the EFED analysis states, "One uncertainty is that the residue samples were taken from studies that were far below the maximum application rate; higher application rates may result in highe r residue concentrations in nectar and pollen." So, "no

unreasonable adverse effects" can be determined from the EFED research concerning residues even if there is a dry

time for the insecticide.

The label states an application can be made every seven da ys, yet effects upon the bees exposed to Cyantraniprole can last up to six days ("repellence" --reduced foraging). A pplications should be limited during the pollination period, otherwise the crop will not get pollinate d at all due to Cyantraniliprole exposed pollinators repelled by the treated

crop.Page 43 of 46 Center for Food Safety and American Bird Conservancy comment (Docket # EPA-HQ-OPP-2011- 0668-0047) : The proposed product labels for cyan traniliprole products are insufficien t to ensure protection to human

health and the environment. 79 Many of the studies relied upon by EPA in its risk assessment found adverse effects on honey bees beyond exposure to cyantraniliprole from direct application. For example, one study found “increased mortality [of bees] for two days after treatment and reduced foraging activity for one day after the application [of cyantraniliprole product.]” 80 Another study found that hive populations decreased dramatically after cyantraniliprole application. 81 Yet, the proposed label change for end-use pr oducts containing cyantraniliprole only contains the directive “Do not apply this product or allow it to drift to blooming crops or weeds if bees are visiting the treatment area,” without any directive to mitigate long-term effect s of cyantraniliprole applications on honey bees, other terrestrial invertebrates, or other pollinators. The draft labels also do not contain ad equate warning regarding the adverse effects to aquatic invertebrates or directions of use that would mitigate the risks posed by cyantraniliprole on terrestrial invertebrates, aquatic invertebrates, birds, and/ or mammals, including federally listed species. In short, the current proposed labels fall short of the FIFRA requirement that a pesticide’s labeling “contain directions for use which . . . if complied with . . . are adequa te to protect health and the environment.” 82

_____ 79 7 U.S.C. § 136(q)(1)(F). 80 EPA, Amended Risk Assessment, supra note 1, at 70.

81 Id. at 71. 82 7 U.S.C. § 136(q)(1)(F).

EPA’s response

The draft labels in the public docke t were proposed by the registrants an d the EPA agrees that they do not contain adequate warning rega rding potential adverse effect s to non-target organisms. EPA is requiring various changes before the labels will be acc eptable. In addition to adding buffers, cyantraniliprole product labeling must be revised to include the pollinator protec tive language recently imposed on the nitroguanidine

neonicotinoids 4 . A “Pollinator Protection Box” that clearly informs the applic ator that the product may harm bees, explains how they may be exposed, and provides bee kill reporting contact in formation is required. The use of a “bee icon” is expected to focus the user’s atte ntion on pollinator protective statements. The Directions for Use will impose certain restrictio ns to reduce exposure by limiting appl ications during bloom of target plants when bees are expected to be visiting the site. Th e intent is to more effectiv ely communicate the risk of the pesticide to pollinators. These restrictions are wr itten in mandatory language and must be followed. Deviance from mandatory directions for use would be “use ... in a manner inconsistent with [a registered pesticide’s] labeling” and a violation of FIFRA.

Additionally, labeling for cyantraniliprole seed treatment products will require that seed tags carry statements indicating that pollinators ma y be at risk when exposed to dust during planting.

The Agency is aware that pesticide users, including b eekeepers, misuse pesticides, either deliberately or by failing to read the label. Many state l ead agencies have enhanced their cer tified applicator tr aining programs to emphasize the importance of protecting pollinators while usin g pesticides. States are also sponsoring forums to improve communication between growers and beekeepers.

4 http://www.epa.gov/opp00001/ecosystem/pollinator/index.htmlPage 44 of 46 10.2 Buffers

Center for Biological Diversity comme nt (Docket # EPA- HQ-OPP-2011-0668-0041) : Finally, the proposed product labels make clear how woefully inadequate the EPA review process is for registering pesticide products. The ecological risk assessment concludes that “[f] or freshwater invertebrate exposures, acute listed species buffers range from 0 to 197 ft (TGA I) and 0 to >1000 ft (TEP).” The analysis also determined that the cyantraniliprole-thiamethoxam mixture will require larger bu ffers (over 1000 ft) than cyantraniliprole-only products. Yet, the EPA’s proposed label restrictions for cyantranilipro le states “Do not make ground applications within 25’ or aerial applications within 50’ of lakes, rivers, reservoi rs, permanent streams, marshes, natural ponds, estuaries or coastal areas.” There are no product label restrictions that reference any listed species’ critical habitat, or even

reference to EPA’s Bulletins Live! website which is designed to incorporate site-specific protections for listed species. Simply put, after concluding that the nationwide registrati on of cyantraniliprole could affect listed species nationwide, after concluding that this pesticide is highly toxic to invertebrates, and af ter failing to consult with the Services informally on this registration, the EPA has proposed virt ually no meaningful conservation measures to protect listed species.

Center for Regulatory Integrity comme nt (Docket # EPA- HQ-OPP-2011-0668-0045) : EPA’s solution for reducing risks to aquatic and terrestrial animals is to require spray drift buffers and labeling language on the proposed pesticide products. However, there is no evidence to show that these proposed mitigation measures will be effective, especially for seed treatment, soil injection, soil drench, drip irrigation, and other non-folia r application methods. On the contrary, the proposed labeling language to not apply the products when bees are visiting will not be protective for systemic pesticides that are continuously present in plant tissues. Given the almost non-existent enforcement of bee labeling language by the states, it is unlikely that the proposed labeling language will mitigate risks to bees or other pollinators. Surv eys of consumers have also shown that most people do not read the warning language on pesticide products. Buffers are also a highly co ntroversial mitigation measure, and it is highly unlikely that a 50-foot buffer zone, if used, will prevent mobile pesticides from getting into water bodies. Since the field studies were not conducted at maximum application rates, it is difficult to even calculate the size of an acceptable

buffer zone.

EPA’s response

The spray drift analysis used in th e ecological risk assessment is a c onservative, upper- bound, screening-level analysis using default assumptions fo r both aerial and ground applications, such as large wing or high boom, respectively, and using the upper 90 th percentile of the distribution for very-fine to fine “droplet size distribution” as defined by the American Society of Agricult ural Engineers (ASAE, DSD). While we recognize that drift can/may occur when conditions are met, there is a diminishing amount of residue that is deposited as distance increases from the treated site. The analysis in the ecological risk assessmentrepresents a worst-case scenario. As a risk assessor addresses the layers of conservatism additional refinements of the deposition values are achieved. Further, the assu mption here is that, particularly for non-targ et insects, they will be present in the field at the time of application or that there is suitabl e habitat where they are present where drift is occurring,

which is conservative.

Generically speaking, requiring larger bu ffers is not a scientifically sound, risk-based approach. Also simply adopting buffers that are comparable to what are currently required for alternative pesticides may result in less adoption of cyantraniliprole in th e marketplace and continued use of mo re risky compounds, and again would not be scientifically sound. For exam ple, chlorpyrifos has 25-foot and 150-foot buffers and methomyl has 25- foot and 100-foot buffers for ground and aerial applications , respectively. Given that the cyantraniliprole risk assessment is conservative, a 25-foot buffer for ground appl ications and a 50-foot buffe r for aerial applications

are established to minimize risk and are cons idered appropriate risk mitigation measures.Page 45 of 46 10.3 Outdoor applications in urban settings

San Francisco Bay Regional Water Quality Co ntrol Board comment (Docket # EPA-HQ-OPP-2011- 0668-0034) : We concur fully with the California Stormwat er Quality Association’s (CASQA’s) comments on the proposed decision to register cyantraniliprole.

California Stormwater Quality Association co mment (Docket # EPA- HQ-OPP-2011-0668-0035: To prevent toxicity to aquatic invertebra tes predicted in the environmental risk assessment, we request that EPA not approve the portion of the urban product labels that pr ovide for broadcast applications of cyantraniliprole onto outdoor impervious surfaces in urban areas.

For the suspended concentrate product, we recommend that EPA allow only spot and crack-and crevice treatments. These minimize the quantity of pesticide applied and subject to urban runoff. “Spot” should be clearly defined; we suggest that EPA follow California DPR’s definition that “spot ” is no greater than 2 square feet. If the registrant seeks to include perimeter treatments on the label, we request that the perimeter band be as narrow as feasible to provide pest control (e.g., 1 foot, not 10 feet) and sufficiently narro w to ensure that the quantit y of cyantraniliprole will be sufficiently small that toxicity to aquatic organisms will not occur.

For the fly bait product, we recommend that EPA only allow use of containerized baits outdoors. Containerization of the baits minimizes the exposure to rainwater, thus greatly reducing the quantity in urban runoff. Containerization also prevents off-target exposures to the highly mobile granul es, which when sitting exposed on impervious surfaces may be unintentionally attractive to non-target organisms. If out door broadcast application is allowed, it should be only to pervious surfaces, since granules would be highly susceptible to mobilization in runoff, either from irrigation or precipitation.

EPA’s response

The cyantraniliprole strucural pest product can be applied outdoors as a 10 foot perimeter band, eg. 3 feet up the

exterior wall and out 7 feet horizont ally from the building. Using EPA's current modeling, this perimeter structural application resulted in a lower environmental effect concentration than applications applied to a number of the agricultural crops. The ecological ri sk assessment was conducted using the conservative approach of modeling the ag ricultural crop scen arios. Resulting restrictions include requiring that the product cannot be applied within 25 feet of bodi es of water and there must be a 25 foot uncultivated vegetative filter strip next to the water body.

The cyantraniliprole fly bait product contains 0.5% activ e ingredient and is intended for use by commercial applicators. EPA believes that the product presents a be tter risk profile compared to other fly baits such as methomyl which has been used for years as a scatter bait. Flies are public health pests and cyantraniliprole will provide benefits that outweigh risk associated with runoff fly bait applications to areas around dumpsters, kennels, etc.Page 46 of 46 10.4 Enforcement, training

Beyond Pesticides comment (D ocket # EPA-HQ-OPP-2011-0668-0042) : Inadequate and Unenforceable Labeling Statements - Meanwhile, EPA and state enforc ement capabilities seem to be almost non-existent. Many states do not have the resources or manpower to enforce product labels, collect incident data, or conduct necessary inspections. Given all the challenges that exist with product label compliance, and the declines in bee populations in the U.S., the agency must reconsider granting registration to a product with such high risks to bees without the proper safeguards in place.

National Pollinator Defense Fund co mment (Docket # EPA-HQ-OPP-2011-0668-0046) : The result is readily preventable acute bee kills still happen with regularity, and with impunity for those causing the kills. EPA can solve this problem by clarifying label language, and ensuring states require mandatory training in pollinator protection for applicators, and require state regulators to take thei r enforcement mandate seriously by acting expeditiously to fully investigate each incident, document the incident in a traceable manner, file a comprehensive report of the incident with U.S. E.P.A., and take correctiv e action to avert future poisoning incidents.

EPA’s response

Commenters state that enforcement cap abilities at the state and Federal level are almost nonexistent due to reduced resources and poor labeling. There is some de gree of misuse in all commodities and instances where applicators have willfully i gnored label restrictions or used unauthor ized pesticides. EPA has taken enforcement

action for misuse in numerous situations such as adulte ration of crops and when spra y drift has caused adverse effects. However, EPA believes that most pesticide us ers apply pesticides according to the approved labeling, and the Agency supports continuing education of pe sticide applicators to ma intain certification.