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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

 WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

 

Cyantraniliprole 

 Response to Public Comments on EPA’s “Proposed Registration of the 

New Active Ingredient Cyantraniliprole: An Insecticide for Use on 

Multiple Commodities, Ornamentals, Turfgrass, and in Commercial or 

Residential Buildings 

 
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Table of Contents 

1.0 Completeness of database and Coordination with International 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, training 

 
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1.0 Completeness of Database and Coordination with International Partners

Beyond Pesticides comment (Docket # EPA-HQ-OPP-2011-0668-0042): There are many uncertainties, 

which the agency acknowledges, surrounding the data used to support a cyantraniliprole registration. Many include 

long-term impacts on bees. EPA believes that no additional 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 developing 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 comment (Docket # EPA-HQ-OPP-2011-0668-0044): 

2. 

d. EPA continues to use inadequate toxicity 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 registration for cyantraniliprole. Table 4 (pgs.16-17) of EFED 

clearly points out that only acute toxicity has been considered 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 concentrations 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 important considerations into its protocols (Blue Book) and therefore virtually all 

bioassay toxicity assessments are judged to be inadequate. (see Tennekes and Sanchez-Bayo, 2013, Toxicology 309, 

39-51; Tennekes and Sanchez-Bayo, 2011, J. Environmental & 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 contains 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 cyantraniliprole 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 there 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 toxicity 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 (Docket # 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 honey crops, which should be carried out in China. 

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): In section IV B. 

(p. 13), EPA notes it collaborative reviews with other countries. Glaring omission is any collaboration with the 

relevant agencies of the European Union. In particular, EPA should be in close coordination and collaboration with 
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the European Food Safety Authority (EFSA). This EU agency is actively in process of new procedures for improving 

toxicity assessment procedures for bees and important related 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 conducted under current guidance is totally 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 exclude pesticide use as a seed treatment. 

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): 

4. The virtually total lack of any independent third party analysis 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 experimental design, or even 

fraud in its representation. The scientific method is fundamentally based upon independent review absent of conflict 

of interest concerns, and essential for repetition of experiments or other verification 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 Kennedy 2011; incomplete bibliographic 

citation was provided by EPA in Section VI) in the EFED that is explicitly related to cyantraniliprole and then EPA 

promptly dismissed it as not meeting criteria for consideration, all for an easily corrected technicality, one that staff 

could have conducted....namely failure to present application rate data in mass per acre units rather than dose per 

plant. This is simply a ludicrous non-credible excuse. Whether the paper is of substantive utility is not the issue. It is 

indicative of an attitude issue of total deference to applicant 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 environmental 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. That 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 information 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 pesticide applications will remain 

scientifically suspect. 

EPA’s response

The EPA’s evaluation of cyantraniliprole was done as an international collaboration with our regulatory 

partners at the Agency for Food, Environmental and Occupational Health & Safety of France (ANSES), the 

Chemical Review Directorate of the United Kingdom (CRD), the Pest Management Regulatory Agency of 

Canada (PMRA) and the Australian Pesticides and Veterinary Medicines Authority (APVMA). Stage 2 of the 

joint project required a completeness check of the dossier as the five regulatory authorities initiated the 

evaluation. This completeness check is conducted to confirm that all required studies, including those that may 

be unique to a single authority’s statutory requirements, are included in the dossier. All five parties agreed that 

the dossier was complete for purposes of commencing the evaluation. The database for cyantraniliprole is 
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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 that are uniquely EPA requirements. The result is a robust and substantial 

database for cyantraniliprole. 

In the evaluation, the primary reviews of the data were 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 reviews of product chemistry and efficacy were conducted by 

the PMRA. The EPA led the reviews of the acute and chronic human toxicology. Each authority then 

conducted peer reviews of the primary evaluations. Thus, there was broad scientific 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 interacted to develop harmonized 

conclusions in order to complete the risk assessment process. 

To the extent possible, the partnering countries coordinated and consulted during their independent risk 

assessment processes. Differing statutes and regulations dictate how involved countries may be in other’s 

process. For example, other countries do not have the Food Quality Protection Act and so other countries do 

not have to meet the statutory requirements of this Act. The EPA’s ecological and human health risk 

assessment processes, however, include meetings of oversight committees such as the Risk Assessment Review 

Committee. These meetings were open to EPA’s international partners and they do participate in the dialog and 

contribute to our discussions. 

The Agency does not agree that the cyantraniliprole database 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 the pesticide’s potential effects on animals, plants, soil, and water. An 

array of chronic studies that were conducted at doses much lower than the acute studies, allow the Agency to 

identify sub-lethal effects and incorporate them into the risk assessment. EPA’s risk assessment processes were 

developed to include conservative assumptions regarding exposure and protective safety factors to reduce 

uncertainty. Thus, EPA believes its analysis with respect to cyantraniliprole was consistent with the 

requirements of FIFRA. 

Concerns about the existing data for honeybees were specifically raised, including the evaluation of data from 

open literature. Open literature data submitted to the Agency were inadequate for risk assessment. Guidelines 

for incorporation of open literature into ecological risk assessments are described in USEPA (2004)1. Toxicity 

data from the open literature are identified via the ECOTOX2

 search engine, maintained by the U.S. EPA Office 

of Research and Development (ORD). To be included in the ECOTOX database, papers must meet several 

criteria. Data that pass the ECOTOX screen are evaluated relative to the data provided by the registrant, and 

may be incorporated qualitatively or quantitatively into the risk assessment. No data for chronic or sub-lethal 

effects on developing honeybee larvae were available; however semi-field studies 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, they would have manifested themselves in the total adult population of the 

hive (a decrease would have been expected) 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 proposed application rates. 

Empirical residue concentrations from these studies were extrapolated out to the highest application rates 

 

1

 USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental 

Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. January

23, 2004. 

2

USEPA 2011. Ecotoxicity database http://cfpub.epa.gov/ecotox/ 
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proposed for registration (see the response to comment 7.2 for more detail). The Agency acknowledges that the 

degree of risk from seed treatment dust is uncertain, as was stated in the risk assessment. Although many of the 

honeybee studies had methodological limitations, collectively, 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 regulatory 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 currently being used by growers in 

that country. 

Finally, the European Food Safety Authority (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. 

 
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2.0 Economic impacts

National Pollinator Defense Fund comment (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-benefit of this new active ingredient. Consideration of the 

livelihood of the many small business owners who are commercial 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. Agriculture. - 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 Florida 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 citrus 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 critical 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 citrus industry depends completely on our ability to bring the 

next generation of trees into profitable production. Registration of cyantraniliprole is probably the one thing that 

would advance us most toward this goal. Therefore, I urge the agency to facilitate registration of this active ingredient 

with all haste. 

Henry Yonce (KAC Agricultural Research, Inc.) comment (Docket # EPA-HQ-OPP-2011-0668-0037): 

I have conducted research with Cyantraniliprole for four years in Citrus in Florida. As you know Florida citrus has a 

serious problem with Asian Citrus Psyllids. We are limited in active ingredients 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 cyantraniliprole, growers will be forces to use higher rates of 

broad spectrum insecticides that also kill beneficial organisms 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 River, 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. The potential for resistance to these chemistries has been 

discussed by many entomologists. The introduction of Verimark 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-sucking 
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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 Citrus Leafminer, which exacerbates Citrus Canker. Cyazypyr, 

which is an effective product against both pests with a unique mode of action (Group 28) will be a welcome new tool 

in the IPM toolbox for pest management. The future of Florida’s 9 billion dollar citrus industry depends on our ability 

to bring the next generation of trees into 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 productive and cause our company to go out of business. Our 

only control against the spread of this disease is to control the vector which is the Asian citrus psyllid (ACP). The 

growers in Florida only have a limited number of chemicals that we can use to control the ACP, therefore we need to 

have new chemicals that offer a different mode of action to help us in this fight to control HLB. With the availability 

of Cyantraniliprole we will be to rotate modes of action which is important to us with regard to being good stewards 

of the pesticides that we have at our disposal. The trial 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 Cyantraniliprole. The future of 

the Florida citrus grower is at stake without more tools to combat these pests. 

John Curtis (Better Crops LLC) comment (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. imidacloprid and thiamethoxam) are important tools for 

managing asian citrus psyllid in newly-planted trees. These neonicotinoid insecticides are all known for systemic and 

residual insect pest control and which are oftentimes applied to the soil throughout the growing year. However, overreliance on neonicotinoid insecticides may lead 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 (including 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 and which not only enhances the long-term sustainability of all 

these chemistries, but also provides citrus growers with both an additional and essential tool in getting young trees 

into production. 

EPA’s response 

During the evaluation of new pesticides, the EPA uses toxicity data and conservative exposure estimates to 

determine potential risk to non-target organisms. Mitigation of potential risk is achieved through the risk 

management decision process and may include label and use restrictions. With respect to initial registrations of 

new pesticides, the relevant subsection of FIFRA, 7 U.S.C. § 136a(c)(5), strongly suggests that, at least in 

situations where a new pesticide does not raise significant risk concerns, Congress did not intend economic 

considerations to play much of a role in EPA’s analysis. First, Congress authorized EPA to waive the 

requirement that manufacturers submit data on a pesticide’s efficacy during initial registration — data the 

agency would undoubtedly need were it to evaluate whether the new pesticide will be economically beneficial. 

See 7 U.S.C. § 136a(c)(5); 40 C.F.R. § 158.400(e)(1) (implementing 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 agricultural 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 other pesticides are equally effective — what the statute refers to as a “lack 

of essentiality,” 7 U.S.C. § 136a(c)(5) (“Where two pesticides meet the [statutory] requirements . . . , one should 

not be registered in preference to the other.”) – suggesting that purely economic considerations should not 
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generally be a part of initial 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 was granted classification as a 

Reduced Risk pesticide. This means that compared to existing conventional pesticides such as the 

organophosphates, carbamates and pyrethroids, it presents characteristics that may include lower impact on 

human health, lower toxicity to non-target organisms, low potential for groundwater contamination, low pest 

resistance potential and compatibility with IPM practices. 

EPA determined that cyantraniliprole is preferable to almost all of its registered alternatives in terms of its 

environmental and human-health risk profile. Further, ecotoxicity data for cyantraniliprole indicates that it is 

preferable to almost all of its registered alternatives. In light of this determination, the Agency considered the 

potential risks posed by cyantraniliprole not to be “unreasonable,” when weighed against the benefits it 

provides. Cyantraniliprole controls lepidoptera, whiteflies, leafminers, psyllids, leaf-feeding beetles, fruit flies, 

and sawflies. Cyantraniliprole is effective at controlling the establishment and population growth of aphids, 

weevils and thrips. In a comparative qualitative analysis of efficacy, cyantraniliprole is considered to be more 

efficacious than most of the currently registered alternatives 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, cyantraniliprole 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 and it will die. The only current means to protect citrus 

trees from HLB is through prevention by control of the Asian Citrus Psyllid. Florida and California growers 

need cyantraniliprole to provide an additional mode of action 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 commenter #38, this pest has already seriously injured the US blueberry crop. 

On July 29, 2013, the Washington Post wrote an article about 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. Extension agents in blueberry growing 

states have recommended carbaryl, diazinon, malathion, methomyl, phosmet, bifenthrin, esfenvalerate and other 

conventional chemicals, however pre-harvest intervals for these compounds are long and SWD infestations 

occur when fruit is ripe therefore growers are in need of tools with short PHIs. Michigan and New Jersey State 

Lead Agencies have made crisis declarations under FIFRA Section 18 Emergency Exemption provisions on 

behalf of blueberry growers for the use of malathion to combat SWD. Registration of cyantraniliprole will 

provide the growers with a tool that presents a reduced risk profile compared to the alternative products 

currently registered or allowed under Section 18 authorization. The use of cyantraniliprole can reduce the 

potential adverse effects from applications of higher rates of these and other pesticides. 

 
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3.0 Health Effects 

3.1 Thyroid effects

Beyond Pesticides comment (Docket # EPA-HQ-OPP-2011-0668-0042): The agency approved 

cyantraniliprole as a “reduced risk” candidate for proposed uses based on mammalian and eco-toxicity profile for this 

chemical. However, in addition to negative adverse effects observed in dogs, which include liver damage, EPA notes 

that cyantraniliprole alters thyroid homeostasis in laboratory rats as a result of enhanced metabolism of the thyroid 

hormones by the liver. Even though the agency states that “cyantraniliprole is not a direct thyroid toxicant,” indirect 

effects on thyroid function have further implications for endocrine disruptive effects. A full evaluation of endocrine 

disrupting potential should be reviewed further by the agency. Given that its current endocrine disruptor screening 

program (EDSP) is currently still in the process of validating tests, selecting chemicals for testing and implementing 

screening protocols, the agency must use caution when approving registration for new active ingredients that show a 

propensity for endocrine disruption, before 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 thyroid weight increase and other thyroid abnormalities. 

Offspring were affected by chronic exposure with declines 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 activities result in increased metabolism of and decreased 

circulating thyroid hormonal levels in the experimental animals. The 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 decreases in plasma T4 thyroid hormone level and alteration 

of thyroid hormone homeostasis resulting in increases in TSH. Increased plasma TSH then stimulates the 

thyroid gland resulting in the thyroid follicular epithelial cell hypertrophy/hyperplasia. These changes followed 

a classic pattern for a compound that disrupts thyroid homeostasis through induction of hepatic metabolizing 

enzymes including UDP glucuronyltransferase. Cyantraniliprole did not inhibit the thyroid peroxidase activity 

in an in vitro study supporting the conclusion that cyantraniliprole was not a direct thyroid toxicant. Based on 

the results just described an adverse outcome pathway can be proposed as shown below: 

cyantraniliprole 

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

↓

↑ T4 catabolism → ↓ in T4 & associated

↓ in T3

↓

↑ TSH secretion by the 

Pituitary 

→ thyroid follicular cell 

hypertrophy/hyperplasia 

↑: Increase ↓: Decrease 

The thyroid effect occurs at substantially higher dose levels than the dose levels which produce liver effects, 
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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 the studies with cyantraniliprole. 

 
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3.2 Other toxic effects

Boulder Innovative Technologies comment (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, thyroid and adrenal organ effects, 

all key to mammalian detox and metabolic rate functions. The claim of no concern regarding reproductive or 

developmental effects is not supported by observed and stated 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 consisting 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 Guidance Document #G2002.01). However, in the studies with 

dogs the liver effects consisted of changes in clinical chemistry parameters including increases in alkaline 

phosphatase, alanine aminotransferase and gamma glutamyltransferase and decreases in total protein, albumin, 

and cholesterol. Significant increases in absolute and relative liver weights accompanied by microscopic 

observations (hepatocellular degeneration and inflammation) were found; the effects seen in the dog studies 

were adverse. The liver effects seen in the dogs were considered to be the most sensitive effects and were used 

in establishing toxicity endpoints and the NOAEL associated with the liver effects was employed as the point of 

departure for risk assessment. 

In regards to the developmental and reproductive effects, the effects seen in these studies are again seen at dose 

levels much higher than the point of departure (NOAEL) employed for risk assessment. For example, the 

lowest adverse effect level seen in the parental animals 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 neurotoxic effects raised by Boulder Innovative Technologies, EPA presented the 

summary results of the acute and subchronic neurotoxicity studies in rats. The acute neurotoxicity study was 

tested up to the limit dose (2000 mg/kg), and the subchronic neurotoxicity was tested up to 1400 mg/kg/day, 

which was above the limit dose (1000 mg/kg/day); no neurotoxic effect was found in either study. This was 

consistent with the literature finding that the mammalian 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 member of anthranilic diamides. 

_____ 

HED Guidance Document: Hepatocellular Hypertrophy: HED Guidance Document #G2002.01; October 21, 2002 

Lahm G. P., Cordova, D., and Barry J.D. (2009) New and selective ryanodine receptor activators 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 chemical. Invert Neurosci (2008) 8:107-119. 

 
Page 13 of 46

3.3 Classification of toxic effects

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): 3. The Proposed 

Registration document contains totally unfounded and untrue statements.... 

b. On page 5, item II A bottom of paragraph, it states: “There are no genotoxicity, mutagenicity, neurotoxicity, or 

immunotoxicity concerns. There are no developmental or reproductive concerns.” These statements are again sweeping 

scientific arrogance and simply cannot be made honestly, particularly 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 contradict the “no concern” claim. EPA must remove this 

language and clearly acknowledge that negative 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 required toxicity studies and in the 

context of risk assessment of the proposed uses of cyantraniliprole. Comparing the no-observed adverse effect 

levels (NOAELs), which are used as points of departure for risk assessments, and the lowest-observed adverse 

effect levels (LOAELs) for immunotoxicity, developmental, or reproductive toxicity, there is a large margin of 

safety ranging from 5 to greater than 1000X difference (5X for offspring and maternal LOAEL from the 

reproduction study and greater than 1000X from developmental and immunotoxicity studies). With an 

additional 100X safety factor to account for inter- and 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 reproductive toxicity studies. Therefore, EPA can state that there is “no 

concern” for toxicity potential raised by the commenter. 

 
Page 14 of 46

3.4 Mode of action

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

p. The mode of toxic action (MOA) discussion and data presentations of cyantraniliprole is considered inadequate and 

incomplete. For example the description of MOA as a unregulated 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 documented 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 action (MOA) as an unregulated activator of insect RyR 

channels described the pesticidal mode of action for killing insects. Since RyRs are found across species, the 

Agency carefully considered the impact on mammalian RyRs by evaluating the toxicity studies submitted to the 

Agency as well as information in the literature. As stated previously, the registrant submitted all of the required 

toxicity studies as well as some additional special studies to further characterize cyantraniliprole 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 evaluating 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 possible 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 analysis of the degradates to which humans could be 

exposed to in food and drinking water, which did not demonstrate any structures which would lead to more 

toxicity than the parent compound. Therefore, the Agency assumed the potential toxic effects produced by 

degradates were similar to those of the parent chemical, which is a conservative 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 comment (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 related 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 detailed 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 ingredients; the ability to use geospatial information, and how to 

incorporate uncertainty into the risk assessment process.26 While the report outlines areas for all three agencies to 

improve, the NAS report made several significant conclusions about the current ecological risk assessment process 

and its use of risk quotients [RQs], including: 

• The EPA “concentration-ratio approach” for its ecological risk assessments “is ad hoc (although commonly 

used) and has unpredictable performance outcomes.”27

• “RQs are not scientifically defensible for assessing the risks to listed species posed by pesticides or indeed for 

any application in which the desire is to base a decision on the probabilities 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 environmental 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 way to determine whether the assumptions that are used 

overestimate or underestimate the probability of adverse effects.”30

According to the NAS, the EPA concentration-ratio approach contrasts sharply 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 approach that the NMFS already utilizes.31

The NAS also recommends that the FWS move towards a probabilistic approach in its consultations. Given the 

significant changes to the EPA’s ecological risk assessment that are likely required to conform with the NAS 

recommendations, it is arbitrary and capricious for EPA to proceed 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. This analysis fails to account for the 

multiple exposures of pesticides over the life of the individual, including at more sensitive life stages. Multiple 

exposures can lead to a cumulative effect on species that would 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 assessment 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 and 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 population and habitat contributing 

to the jeopardy of adverse modification. 

_____ 

25 http://www.epa.gov/oppfead1/cb/csb_page/updates/2013/nas-report.html 26 National Academy of Sciences. 2013. Assessing Risks to Endangered and Threatened Species from Pesticides, Committee on Ecological Risk Assessment under 

FIFRA and ESA Board on Environmental Studies and Toxicology Division 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, despite 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, Commerce and the Interior requested that the National 

Research Council (NRC) of the National Academy of Science (NAS) convene a committee of independent 

experts to examine topics pertaining 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 Fisheries 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). 

Additionally in response to Comment #47, the Agency points to the ecological risk assessment 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 invertebrates consuming treated food items directly 

from the food) it is expected that with every new cycle, a new set of plants (crops and weeds) 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 comment (Docket # EPA-HQ-OPP-2011-0668-0041): The ecological risk 

assessment also fails to consider the effects of pesticide degradates on protected species. Degradates, which are the 

chemicals resulting from pesticides after it has been transformed 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 substantially more dangerous and increase the toxicity to wildlife.23 The 

ecological risk assessment completely fails in its obligation to analyze the effects of degradates and only 

states“[g]iven the uncertainty of the behavior and toxicity 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 Opinion for the Environmental Protection Agency’s Pesticide General Permit for 

Discharges from the Application of Pesticides (Draft BiOp) at 4456-4470 lines. Northwest Coalition for Alternatives to Pesticides, et al., Petition to Require 

Disclosure of Hazardous Inert Ingredients 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, Pesticides in the Nation's Streams and Ground Water, 1992–2001—A Summary, 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; Environmental 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 registration 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 equally toxic to the parent should not substitute for full 

assessments of the degradates, especially given that EPA asserts later that “two of the degradates (IN-HGW87 and INJ9Z38) may be more toxic on an acute oral basis than the 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 comment (Docket # EPA-HQ-OPP-2011-0668-0044): The EFED fails 

to assess or require the conduct of toxicity studies on even the known degradates, instead it uses only assumptions 

about equivalent toxicity of metabolic or abiotic degradates 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 degradates should be required of the applicant and until provided 

all registration approval considerations should be shelved, or the applications totally rejected. 

EPA’s response 

The Residues of Concern Knowledge-based Subcommittee (ROCKS), a committee of EPA toxicologists and 

residue chemists that meet to evaluate degradate data and make determinations 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 invertebrates as an example, data were available for nine 

of the ten degradates and indicated that the degradates 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., chemical 
Page 18 of 46

structure) that suggests otherwise (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 extracted from the pollinator 

section of the risk assessment document. Terrestrial organisms (i.e., honeybees) and aquatic organisms are 

assessed separately using different approaches. The aquatic analysis used the total toxics residue (TTR) 

approach, which conservatively assumes that all of the degradates are equally toxic to the parent for aquatic 

exposures. All existing degradate toxicity 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 conservative 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 toxicity. Based on their structures, however, the ROCKS did 

not identify them as potentially being more toxic than the parent. Furthermore, the honeybee full field studies 

did not show overwintering survival differences between controls and treatment groups. Although toxicity data 

for each individual degradate were not quantified in the field study, the study design allows for exposure to 

cyantraniliprole and all of its degradates in a real-life scenario. Thus, EPA believes both the aquatic and the 

pollinator analyses conservatively represented risk 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 organisms. In accordance with the 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 formulation 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 additional 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 both 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 stated: “Based on degradate aerobic soil 

metabolism and mobility studies, six of the eight major degradates had longer dissipation half-life (DT50) values 

(more persistent) and three of the eight degradates were more mobile than the parent cyantraniliprole.”61 Thus, the 

assumption that the toxicity of the degradates is equivalent 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. However, 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 the Agency’s risk assessment framework 
Page 19 of 46

which integrates exposure and toxicity endpoints compared against Agency levels 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 comment (Docket # EPA-HQ-OPP-2011-0668-0044): The EFED fails 

to consider the potential of reversible reactions of degradates back to prior sequential intermediate compounds or even 

to the parent pesticide or even to totally different dangerous chemical products. Such chemical reactions have been 

observed with other pesticides, belatedly after many years 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 potential 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 approach accounts for such processes. 

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): The EFED 

presents calculated values for the total toxic residues (TTR) (EFED [Risk Assessment] page 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 are 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 # EPA-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 conservative course of action. 

 
Page 20 of 46

5.2 Persistence 

Center for Regulatory Integrity comment (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 from 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 cyantraniliprole’s degradation and dissipation mechanisms. The 

Agency’s environmental risk assessment clearly describes aqueous hydrolysis as a pH dependent depletion 

mechanism in the Environmental Fate and Transport Characterization (page 28). 

 
Page 21 of 46

5.3 Plant Back Intervals 

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): The registration 

recommendation document refers to Directions for Use plant back intervals (PBIs) as a means to deal with avoidance 

of uptake by cyantraniliprole by succession crops of cereals, legumes and tuberous and corm vegetables. The PBI 

time intervals suggested are totally inadequate given the half lives of cyantraniliprole and its numerous degradates, 

particularly when one acknowledges the soil compartment persistence, and the multiplying half life effects of the 

numerous degradates for which EPA staff have arbitrarily assigned equivalent toxicities 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 field 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 cyantraniliprole on food commodities 

are predicted to be <0.01 ppm at a 30-day PBI. Confined rotational field trials (OCSPP GLN 860.1850) with 

radiolabeled cyantraniliprole showed that the major portion of the residue on food commodities will be 

cyantraniliprole at various PBIs. Crops for which cyantraniliprole is not approved may be planted in fields after 

crops treated with cyantraniliprole provided there is at least a 30-day interval from application of 

cyantraniliprole to planting of the new crops. The 30-day 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 comment (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 landscape insecticide applying companies to cosmetically or 

prophylactically apply pesticides such as cyantraniliprole on a seasonal or multiple 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 comment (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 potential 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 perennial plant tissue; and (2) the apparent lack of TTR 

calculation for repeat applications of the pesticides and the potential buildup in various environmental compartments 

with time, within soils and sediments and how that may affect systemically translocated pesticide concentrations into 

tissue of plants, annuals and particularly perennial plants which may be harboring increasing concentrations. Even 

with the TTR values presented, it is quite clear that accumulation and build-up can become very serious over multiple 

seasons, voiding most of the assumptions about safety of allowable application rates for crops and other plant species. 

This of course also affects the assumptions of concentrations 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 neonicotinoids), 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, translocation and metabolism of imidacloprid in plants. 

Bulletin of Insectology 56:35–40. 

EPA’s response 

The Agency acknowledges that cyantraniliprole and its degradates may persist in the environment given halflives ranging from 4 to 1800 days, depending on the soil/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 estimated 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 leaching and runoff and may not accumulate in soils; whereas 

persistent and immobile degradates (high Koc) have the potential to accumulate 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 the 
Page 23 of 46

degradate with the highest persistence (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 mobility equivalent 

to or more than cyantraniliprole, that accumulation in the 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 persistent 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 parts 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 chlorantraniliprole) will contaminate surface waters in highly 

cropped landscapes as the neonicotinoids have done in California (Starner and 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 precipitation on pesticides and water 

quality in playa lakes of the southern 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 three agricultural regions of California, 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 effects on aquatic invertebrates in the 

cyantraniliprole ecological risk assessment is appreciated. The evaluation of highly cropped landscapes is 

accounted for within the risk assessment framework where the Agency utilizes the point estimate method which 

integrates exposure and toxicity endpoints against Agency levels of concern (LOC). In addition, the risk 

assessment employs numerous regional-specific scenarios 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 neonicotinoids), and hence, their use will be widespread on the landscape. 

... 

The EPA needs to consider that wetlands, highly productive for waterfowl and many wetland-dependent species, very 

commonly occur embedded within a cropland matrix. The Prairie Pothole Region of North America is one such 

example. This area produces an estimated 50-75% of North American 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 wetlands will occur in this region as 30-50% of the wetland 

basins are impacted by cultivation; many temporary and seasonal 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 reject 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 ducks. Pages 204-227 in A. van der 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 comment (Docket # EPA-HQ-OPP-2011-0668-0044): Should approval 

continue to be considered despite the above noted application 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 management, and prevention of resistance development.

EPA’s response 

The prophylactic use of cyantraniliprole as a seed treatment is intended to provide protection of young, 

immature seedlings and roots of potatoes, canola, mustard and sunflowers. All of these crops currently have 

registered seed treatment products containing other insecticides. Prophylactic seed treatments target pests that 

include cutworms, flea beetles, Colorado potato beetle and European corn borer. Soil inhabiting pests such as 

cutworms may destroy a newly emerged crop requiring growers the expensive 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 loading than seed treatments. There is less pesticide 

associated with a seed treatment compared to traditional foliar, granular, or in-furrow soil application methods. 

Less pesticide is available for runoff, and there is greater protection against target pests since the compound is 

applied where pests are impacting the crop. Additionally, seed treatments reduce pesticide exposure to 

applicators and farm workers compared to traditional field treatments. 

Cyantraniliprole is classified as ‘practically nontoxic” to birds on an acute oral and sub-acute dietary exposure 

basis. Avian chronic exposure to cyantraniliprole does not exceed the Level of Concern. EPA believes that its 

ecological risk assessment is protective of North American waterfowl. 

 
Page 26 of 46

5.7 Water modeling 

California Stormwater Quality Association comment (Docket # EPA-HQ-OPP-2011-0668-0035): The 

impacts on urban watersheds from the broadcast applications on outdoor urban surfaces may 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 underestimated 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 concentrations than they appear in agricultural 

watersheds,8

 we strongly question EPA’s estimate that urban surface water concentrations would be lower than those 

occurring in agricultural waters. 

While we greatly appreciate EPA’s efforts toward development of modeling capabilities for urban pesticide 

applications, the current example highlights several areas where the modeling could be improved. We believe that one 

of these areas may be the reason for the unlikely modeling conclusion for cyantraniliprole. The model assumes that 

runoff from pervious surfaces would occur at the same rate 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, there is little runoff from pervious 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 impervious fraction in the impervious scenario, and other 

elements. 

_____ 

8 See References in: TDC Environmental (2010). Pesticides in Urban Runoff, Wastewater, and Surface Water: Annual Review of New Scientific Findings 2010. 

Prepared for the UP3 Project. March. 

San Francisco Bay Regional Water Quality Control 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 application model for cyantraniliprole. However, we concur 

that the improvements CASQA recommends are necessary. 

EPA’s response 

The Agency acknowledges that refined urban runoff modeling would be beneficial; however, such modeling is 

not currently available. Until a refined urban runoff exposure model is developed and implemented, the 

Agency’s modeling approach for urban use sites incorporates a number of conservative 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 particular watershed receive an application at the same time, a conservative 

assumption considering the spatial and 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 exposure as well as exceedances for benthic chronic exposures. Prior to the 

implementation of an acceptable refined urban runoff model, the Agency completed a comparative analysis of 

risk estimates by taxonomic class to evaluate the potential for the under estimation of exposure from urban use 

scenarios. This analysis showed that in order to exceed 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 rates (flowerbeds, ground covers, commercial and consumer ornamentals, 

exterior landscapes, trees, turf, residential lawns, parks, athletic fields, nurseries, grassy/weedy/mulched/bare 

soil areas, and public health insect control). It is unlikely that this one to three fold increase in the EECs would 

occur in a typical urban exposure scenario since there is considerable temporal and spatial variability in the 

pattern of application in a residential 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 comment (Docket # EPA-HQ-OPP-2011-0668-0044): [Comment 2:] 

2q. .... When EPA states that cyantraniliprole is “practically 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 exposure 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 consequences of adding this new poison. 

EPA’s response 

The LD50 for birds is > 2250 mg ai/kg-bw and the LD50 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 LD50 for birds 

is 2250 mg ai/kg-bw and the LD50 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 LD50. 

For sunflower, the maximum concentration is 0.2 mg ai/seed. Using the same assumptions for the rapeseed 

analysis, birds would need to consume 11,250 seeds and mammals would need to consume 25,000 seeds to 

reach the LD50. 

Further, it is unlikely there would be sufficient number of seeds available for consumption to cause a lethal 

effect using precision planting equipment, and labeling language instructing growers to incorporate treated seed 

minimizes availability and non-target exposures. Where the typical bird or non-target mammal foraging for 

seeds, including seeds that were not properly planted, would reach their caloric intake needs well before 

consuming the number of seeds needed to reach a lethal effect (USEPA. 1993; Becker 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 and 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 (Docket # EPA-HQ-OPP-2011-0668-0042): When it comes to field conditions, 

the agency is aware that pesticide-treated seed, when planted, can produce contaminated dust plumes which can travel 

miles exposing bees and other non-target organisms to various 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 subsequent 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 stated 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 years away and would not serve to adequately protect bees 

from pesticide-treated seed. As cyantraniliprole is being registered for seed treatment, this opens an atypical exposure 

pathway (via dust) that the agency has not fully accounted for. 

_____ 

6 Girolami, V. et al. 2011. Fatal powdering of bees in flight with particulates of neonicotinoids seed coating and humidity implication. 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 Agricultural 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-treated seeds was also not assessed. This has been a 

major exposure route for honeybees with neonicotinoid-treated 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 pneumatic planters, planting equipment used, weather, and availability of 

suitable forage in close proximity to the field being planted). At this time, EPA does not have a suitable tool for 

modeling dust-off as a route of exposure from treated seeds. A complexity of factors and the uncertainty for 

how to parametize the different physics involving dust complicates use of existing tools that were calibrated to 

model vapor phase compounds. The EPA recognizes that pesticide residues in dust that are generated by the 

abrasion of treated seed coatings during planting is a potential route of exposure. However, the EPA has been 

working with registrants, seed treaters, seed equipment 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 lubricant 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 attributed to fugitive dust from planting are associated with 

treated corn seed. Corn seed is larger and dirtier than most seed, it is more likely to contain plant particulates 

(cob, stalk etc) and is planted on far more acreage than any other crop. Cyantraniliprole is not proposed for use 

as a corn seed treatment. 
Page 29 of 46

7.2 Study rates versus label rates 

Beyond Pesticides comment (Docket # EPA-HQ-OPP-2011-0668-0042): In these [semi-field] studies, 

toxicity to honey bees (adults) was observed at application rates 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 comment (Docket # EPA-HQ-OPP-2011-0668-0046): Adverse Effects 

[on pollinators] Clearly Shown .... And from 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 rates 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 well 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 entirely untested. Studies with the lower application rates did 

suggest negative effects on pollinators that could affect pollination, finding that “the combination of mortality, 

sublethal effects, and repellence (decreased foraging) in cyantraniliprole-treated plants may affect pollinator 

services.”52 Brood studies intended to assess the effects on the colonies 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 application rates. Risk quotients from this data also 

suggest potential risks from dietary exposure at the rates tested, up to 0.134 lb ai/A, still below the maximum 

proposed rate of 0.68 lb ai/A. Based on the negative impacts identified at lower rates, and the ongoing pressures on 

pollinators, cyantraniliprole, both in technical formulation and end-use product formulations, 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 collected from pollen and nectar. The majority of an adult honeybee’s diet is 

nectar. The 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 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 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 because there is no evidence of a biochemically facilitated transport mechanism 

or barrier to transport beyond that which 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 application 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 cyantraniliprole that exceed the Agency’s Level of Concern. 
Page 30 of 46

In the final labels, both the maximum single application 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 combination products), thus making it even 

more unlikely that adult honeybees would 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 cyantraniliprole concentrations are not likely to cause acute effects in adult honeybees 

at higher application rates, the effects to brood at higher application rates are uncertain. There is also 

uncertainty regarding the magnitude of increase for the transient effects that could occur at higher application 

rates (i.e., mortality rates could be higher, behavior changes could be more intense, duration of effects could be 

extended). While the Agency recognizes these uncertainties, 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 rates, the concentrations of cyantraniliprole in guttation fluid were 

concerning. Studies have demonstrated that honeybees drink guttation 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, while 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-frequent applications, more studies 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 Way of Intoxication for Bees. J 

Econ Entomol 102(5): 1808-1815.; Hoffman, E & Castle, S. 2012. Imidacloprid in Melon 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 translocated in guttated droplets of seed-treated maize and wheat: 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 lower than through pollen and nectar (USEPA 2012; EFSA 

2012). Honey bees may obtain water from water bodies, dew on plants, through dietary items (pollen/nectar) as 

well as guttation fluid. Analyzing risk potential from the consumption of pollen and nectar is expected to be 

protective of guttation water consumption because there is uncertainty and variability in the extent to which 

honey bees harvest and use guttation fluid relative to other available sources of water, and relative to the 

exposures from pollen and nectar, risk potential from guttation water is low. 

_____

USEPA, 2012. White paper in support of the proposed risk assessment process for bees. Office of Chemical Safety and Pollution Prevention, United States 

Environmental Protection Agency, Washington, DC. 

EFSA. 2012. Scientific opinion on the science behind the development of a risk assessment of plant protection products on bees (Apis mellifera, Bombus spp., and 

solitary bees). EFSA Journal 2012. 10(5): 2668 (275 p.). 

 
Page 32 of 46

7.4 Bee dietary exposure assumptions

Boulder Innovative Technologies comment (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 toxicity data for cyantraniliprole indicated that it is highly 

toxic on an acute oral and contact basis..”. EPA also 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 registration are questioned by this reviewer. EPA is hereby 

requested to present full detailed explanations and calculations with all assumptions and data sources fully elaborated 

and with all units of measure clearly included. Notable is the apparent inconsistencies 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 equivalent [cyantraniliprole] dose rate is also 0.292 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 μg ai/bee (rather than 

g ai/bee). To calculate a dose, the concentration expected to be found in the pollen/nectar 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 premise (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 (Docket # 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-term 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 satisfy 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 – Amended. Office of Pesticide 

Programs. Washington DC. 

Boulder Innovative Technologies comment (Docket # EPA-HQ-OPP-2011-0668-0044): EFED fails to 

properly assess the sub-lethal and chronic and immune system degradation in non-target species, including many 

classes and orders of animals from insects and other invertebrates, 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 experiments were only performed to evaluate adult 

honeybees. 

EPA’s response 

The Agency agrees that honeybee adult toxicity data cannot be used in place of larval toxicity data; larvae may 

be more or less sensitive to chemicals. Adult toxicity data were not used in the risk assessment to estimate risk 

to larva. While larval toxicity data are not available, the field 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 larvae in a hive are undergoing adverse toxicological 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 exposed 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 treatment group, but did indicate 

some effects between the control and a second treatment group. The reasons for the difference are unknown. 

By weight of evidence, the overwintering semi-field studies suggest cyantraniliprole at 0.134 lb ai/A does not 

adversely affect hive health/brood strength and thus, demonstrate no unreasonable toxicity to larvae. 

 
Page 34 of 46

7.6 Susceptibility to Varroa mites and Nosema

Beyond Pesticides comment (Docket # EPA-HQ-OPP-2011-0668-0042): One study notes that sub-lethal 

effects of pesticides on young bees, including delayed adult emergence, may seem inconsequential but may provide a 

reproductive advantage for Varroa mites.3

 Combined effects from exposure to pesticide 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 increased susceptibility to pathogens, may contribute 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 Brood 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 mellifera) Development and 

Longevity. PLoS ONE 6(2): e14720. doi:10.1371/journal.pone.0014720 

Center for Regulatory Integrity comment (Docket # EPA-HQ-OPP-2011-0668-0045): Of particular 

concern is a field study that showed 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 registration of a pesticide that has been 

shown to increase the Varroa mite population in bees? Even if only one industry study shows this negative impact, it 

should raise a red flag with EPA, and the agency should require additional studies before rushing to approve this 

insecticide. 

National Pollinator Defense Fund comment (Docket # EPA-HQ-OPP-2011-0668-0046): One very telling 

section of the EFED report discusses the effects of Cyantraniliprole with an increase of varroa: "An additional 

observation was that hives not exposed to cyantraniliprole (controls) 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 that 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 able 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 registering 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/ReportHoneyBeeHealth.pdf. [not submitted] 

EPA’s response 

The Agency evaluated 12 field/semi-field studies on honeybees. Of these, only one suggested that exposure to 

cyantraniliprole coincided with observed increases in susceptibility to Varroa mites. MRID 48688806 also had 

hives with Varroa mite infestations during the course of the experiment, 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 increased honeybee susceptibility to Varroa mites that coincided with 
Page 35 of 46

cyantraniliprole exposure. However, given that this was only observed in one study 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 evidence 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 for adverse effects on pollinators 

National Pollinator Defense Fund comment (Docket # EPA-HQ-OPP-2011-0668-0046): Without a 

Viable Incident Reporting System, EPA Cannot Track the Impact of Registration Decisions - The proposed 

registration process begs the question of how EPA will determine if Cyantraniliprole can safely be used in 

agriculture. At present, there is no viable system for reporting and tracking 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 implement a valid mechanism for tracking poisoning events 

prior to the registration of Cyantraniliprole, and use this system to gather 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 presented at numerous public meetings. Staff of EPA’s Environmental Fate and 

Effects Division directly contact and interview people submitting incidents. Incidents are also reported to the 

National Pesticide Information Center3 (NPIC) and these are referred to EPA. Again, EPA staff follow-up on 

these reports. 

Historically, commercial beekeepers in particular have shown great 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 their hives illegally to control Varroa mite or other pests may be discovered 

during the investigation. However, EPA has reached out continuously, both on an individual basis, and publicly 

to convince beekeepers of the importance of incident information and to urge beekeepers to report incidents. 

On August 15, 2013 EPA issued new pollinator protective labeling for products containing four neonicotinoids. 

Included in this labeling is text which provides contact information for reporting 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 contain the following statements: 

Pesticide incidents (for example, bee kills) should immediately be reported to the state/tribal lead agency. For 

contact information for your state, go to: www.aapco.org/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 required 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 corroborated by the state lead agencies. 

Further, incident reports have been submitted to the Agency reporting adverse effects in on-going studies in the 

European Union. These reports have alerted EPA to effects well before the study was completed and are used to 

inform risk assessments. 

 

 

3

 http://npic.orst.edu/reportprob.html 
Page 37 of 46

7.8 Effect of timing of aplication on bee toxicity

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

Further on this point [failure to acknowledge potential for 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 justification 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 that direct contact with 

cyantraniliprole results in toxic effects. While this does not directly correlate 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 found in the pollen/nectar of 

flowers if applications have been made prior to flowering, resulting in potential dietary exposure to foraging 

bees. As discussed earlier, cyantraniliprole residues were collected from pollen and nectar. The majority of an 

adult honeybee’s diet is nectar. The 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 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 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 because there is no evidence of 

a biochemically facilitated transport mechanism or barrier to transport beyond that which 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 application 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 cyantraniliprole that exceed the Agency’s Level of Concern. 

In the final labels, both the maximum single application rate and the maximum rate per season were capped at 

0.4 lb ai/A, thus making it even more unlikely that adult 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, and/or multiple formulations used in combination

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

m. The EFED absolutely fails to assess the 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 acknowledged 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 acknowledge 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 comment (Docket # EPA-HQ-OPP-2011-0668-0046): Field studies for 

short and long-term effects need to be completed 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 synergistic and cumulative impacts of approving 

cyantraniliprole and its related products in light of the existing stressors placed upon honey bees, vital pollinators, 

birds, other sensitive species, and the environment. EPA’s oversight 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 before approving those product registrations. 

EPA’s response 

The EPA recognizes the importance of exposure to mixtures but assesses the environmental exposure of a single 

active ingredient (USEPA, 20041

). There are many types of environmental mixtures. First, some pesticides 

might contain more than one active ingredient, or in the case of formulated end-use products, they contain 

additional chemicals that are typically designated as inerts which are 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 chemicals from other sources are already in the environment 

(e.g., environmental mixtures). Ideally, assessments should be based on exposure to all pesticide components 

and to other chemicals that are present in the environment. However, quantitative estimates of exposure to 

environmental mixtures are difficult given the dynamic state of environmental mixtures over space and time. In 

any given location, the amounts of pesticide active ingredients, inerts, adjuvants, and other environmental 

chemicals are highly variable and depend on pesticide uses and other sources of environmental exposure. A 

quantitative assessment of the risk posed by chemical mixtures requires extensive data, including data on the 

identity, concentration, and toxicity of mixture components. Challenges in assessing risk to species posed by 

pesticide-containing mixtures arise largely 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 quantitative data, the possible 

contribution of specific mixture components to the toxicity of a pesticide active ingredient cannot be 

incorporated into a quantitative risk assessment. 

However, if evidence from incidents or field observations suggest that tank 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 proposed 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 Protection 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 comment (Docket # EPA-HQ-OPP-2011-0668-0041): Given the results 

from the ecological risk assessment for cyantraniliprole, the EPA must begin the informal consultation process with 

the Services and work towards the preparation of a nationwide biological assessment of cyantraniliprole. 

.... 

Section 7(d) of the ESA provides that once a federal agency initiates consultation on an action under the ESA, the 

agency “shall not make any irreversible or irretrievable commitment of resources with respect to the agency action 

which has the effect of foreclosing the formulation or implementation of any reasonable 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 consultation. Section 7(d) prohibitions remain in effect 

throughout the consultation period and until the EPA has satisfied its obligations under Section 7(a)(2) that the action 

will not result in jeopardy to the species or adverse modification of its critical habitat. An active ingredient cannot be 

registered for use prior to the completion of the consultation process. The registration of an active ingredient prior to 

the completion of consultations would represent an irreversible and irretrievable commitment of resources, and would 

violate the basic requirement of the ESA that each agency of the federal government 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 first 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 jeopardize 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 Departments of Agriculture, Commerce and the Interior 

requested that the National Research Council (NRC) of the National Academy of Science (NAS) convene a 

committee of independent experts to examine topics pertaining 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 Fisheries 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 registered pesticides. EPA believes that, as a general 

matter, currently registered pesticides present a greater degree of risk to listed species than most new 

chemistries coming to market, including cyantraniliprole, and that it is therefore environmentally preferable in 

most circumstances for EPA to assess the impacts of existing 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, neonicotinoids, and pyrethroids. 

As a result, EPA does not believe the environment or the public would be best served by delaying the 
Page 41 of 46

registration of cyantraniliprole to complete consultation. Focusing EPA’s, FWS’, and NMFS’ limited resources 

on completing a consultation on the effects of cyantraniprole would by necessity come at the expense of putting 

more resources into evaluating – and consequently regulating, where appropriate – what EPA believes to be 

more toxic compounds, that, among other 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 (Docket # 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 proposed environmental hazard statement is as follows: 

“Drift and runoff may be hazardous to aquatic 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 and unenforceable. While spraying before and after bees are 

active in fields may minimize direct contact exposures, residual exposures are still highly toxic and do not solve the 

problem of minimizing risks. 

The agency is also aware that label directions such as these are not adhered to in the real-world. Many beekeepers can 

attest to this. Addressing lack of compliance has been an area the agency has not sufficiently addressed throughout the 

years. These labels are also unenforceable. Moreover, instructions to minimize pesticide drift continue to be a 

challenge especially for aerial applications. It is difficult to engineer meaningful hazard statements that can 

sufficiently mitigate risks and are enforceable. Therefore, while the agency continues to work with stakeholders in 

formulating meaningful hazard statements, 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 comment (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 would add another highly acutely toxic insecticide that would 

be applied to blooming crops attractive to honey bees. The environmental hazards listed for the "master label" for 

A17960B ST state Cyantraniliprole is "toxic to wildlife and highly 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 with fungicides, and/or the coated seed planted with talc or 

fir bark that may affect water runoff, or dust that risks contamination by of this highly acutely toxic insecticide, there 

is no mention on the [seed treatment] label concerning the toxicity to honey bees and other pollinators. 

On the label for Cyantraniliprole for application on turf(A16901B), 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 stating, 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 pollinators 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 higher 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 days, yet effects upon the bees exposed to Cyantraniprole can 

last up to six days ("repellence" --reduced foraging). Applications should be limited during the pollination period, 

otherwise the crop will not get pollinated 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 cyantraniliprole products are insufficient 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 products 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 effects of cyantraniliprole applications on honey bees, other 

terrestrial invertebrates, or other pollinators. The draft labels also do not contain adequate 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 adequate 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 docket were proposed by the registrants and the EPA agrees that they do not 

contain adequate warning regarding potential adverse effects to non-target organisms. EPA is requiring various 

changes before the labels will be acceptable. In addition to adding buffers, cyantraniliprole product labeling 

must be revised to include the pollinator protective language recently imposed on the nitroguanidine 

neonicotinoids4. A “Pollinator Protection Box” that clearly informs the applicator that the product may harm 

bees, explains how they may be exposed, and provides bee kill reporting contact information is required. The 

use of a “bee icon” is expected to focus the user’s attention on pollinator protective statements. The Directions 

for Use will impose certain restrictions to reduce exposure by limiting applications during bloom of target 

plants when bees are expected to be visiting the site. The intent is to more effectively communicate the risk of 

the pesticide to pollinators. These restrictions are written 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 may be at risk when exposed to dust during planting. 

The Agency is aware that pesticide users, including beekeepers, misuse pesticides, either deliberately or by 

failing to read the label. Many state lead agencies have enhanced their certified applicator training programs to 

emphasize the importance of protecting pollinators while using pesticides. States are also sponsoring forums to 

improve communication between growers and beekeepers.

 

 

4

 http://www.epa.gov/opp00001/ecosystem/pollinator/index.html 
Page 44 of 46

10.2 Buffers

Center for Biological Diversity comment (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 (TGAI) and 0 to >1000 ft (TEP).” The analysis also determined that the 

cyantraniliprole-thiamethoxam mixture will require larger buffers (over 1000 ft) than cyantraniliprole-only products. 

Yet, the EPA’s proposed label restrictions for cyantraniliprole states “Do not make ground applications within 25’ or 

aerial applications within 50’ of lakes, rivers, reservoirs, 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 registration of cyantraniliprole could affect listed species nationwide, 

after concluding that this pesticide is highly toxic to invertebrates, and after failing to consult with the Services 

informally on this registration, the EPA has proposed virtually no meaningful conservation measures to protect listed 

species. 

Center for Regulatory Integrity comment (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-foliar 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. Surveys of consumers have also shown that most people do not read the warning 

language on pesticide products. Buffers are also a highly controversial 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 the ecological risk assessment is a conservative, upper-bound, screening-level 

analysis using default assumptions for both aerial and ground applications, such as large wing or high boom, 

respectively, and using the upper 90th percentile of the distribution for very-fine to fine “droplet size 

distribution” as defined by the American Society of Agricultural 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 assessment represents a worst-case 

scenario. As a risk assessor addresses the layers of conservatism additional refinements of the deposition values 

are achieved. Further, the assumption here is that, particularly for non-target insects, they will be present in the 

field at the time of application or that there is suitable habitat where they are present where drift is occurring, 

which is conservative. 

Generically speaking, requiring larger buffers 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 the marketplace and continued use of more risky compounds, and again would 

not be scientifically sound. For example, 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 applications and a 50-foot buffer for aerial applications 

are established to minimize risk and are considered appropriate risk mitigation measures. 

 
Page 45 of 46

10.3 Outdoor applications in urban settings

San Francisco Bay Regional Water Quality Control Board comment (Docket # EPA-HQ-OPP-2011-

0668-0034): We concur fully with the California Stormwater Quality Association’s (CASQA’s) comments on the 

proposed decision to register cyantraniliprole. 

California Stormwater Quality Association comment (Docket # EPA-HQ-OPP-2011-0668-0035: To 

prevent toxicity to aquatic invertebrates predicted in the environmental risk assessment, we request that EPA not 

approve the portion of the urban product labels that provide 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 narrow to ensure that the quantity 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 granules, which when sitting exposed on impervious surfaces may 

be unintentionally attractive to non-target organisms. If outdoor 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 horizontally 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 risk assessment was conducted using the conservative 

approach of modeling the agricultural crop scenarios. Resulting restrictions include requiring that the product 

cannot be applied within 25 feet of bodies 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% active ingredient and is intended for use by commercial 

applicators. EPA believes that the product presents a better 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 (Docket # EPA-HQ-OPP-2011-0668-0042): Inadequate and Unenforceable 

Labeling Statements - Meanwhile, EPA and state enforcement 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 comment (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 their 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 corrective action to avert future poisoning incidents. 

EPA’s response 

Commenters state that enforcement capabilities at the state and Federal level are almost nonexistent due to 

reduced resources and poor labeling. There is some degree of misuse in all commodities and instances where 

applicators have willfully ignored label restrictions or used unauthorized pesticides. EPA has taken enforcement 

action for misuse in numerous situations such as adulteration of crops and when spray drift has caused adverse 

effects. However, EPA believes that most pesticide users apply pesticides according to the approved labeling, 

and the Agency supports continuing education of pesticide applicators to maintain certification.