1

Docket Number EPA

- HQ

- OPP

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- 0684 www.regulations.gov



## Cyfluthrins Final Work Plan

Registration Review

March 20113 CYFLUTHRINS FINAL WORK PLAN

Introduction

This is the Environmental Protection Agency’s (EPA’s) Final W ork Plan for the registration

review of cyflut hrin. This work plan includes the expected registration review timeline. The work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document , which was posted in the cyfluthrin registration review docket ( EPA

- HQ

- OPP

2010

- 0684 ), and any other comments concerning the initial docket postings. The Summary

Document provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review

decision.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review eac h registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case.

Info rmation on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/

.

Cyfluthrin and beta

- cyfluthrin are pyrethroid insecticides. They are both mixtures of eight

isome rs of the same compound. C yfluthrin is composed of comparable percentages of eight isomers,

whereas beta

- cy fluthrin is an enrichment of the four most efficacious isomers

. Cyfluthrin and beta

cyfluthrin prod ucts are registered for use on agricultural site s, residential indoor/outdoor areas, turf/ornamentals, pets/pet houses, p o ultry processing plant premises, recreational/golf areas, t obacco

, and for use as an o utdoor woo d protection treatment. The first cyfluth rin registration was approved in 1987, while t he first beta

- cyfluthrin registration was approved in 19 95. As a result, Reregistration Eligibility Decisions (REDs) have not been conducted for these compounds.

Comments Received on Preliminary Work Plan :

Multiple comments were received during the 60

- day public comment period on the planned ecological assessment and human health scoping document discussed in the Preliminary Work Plan

. H owever, these comments do not alter the Agency’s work plan outlined in the Preliminary Work

Plan. The representat ive comments and Agency’s responses are summarized in this document. In

the Preliminary Work Plan , EPA also solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were r eceived during the comment period concerning environmental justice or trade irritants, however, the Agency did receive comments on listed and potential impaired water bodies in California (CA) attributed to4

pyrethroids. For further discussion on these co mments please see the Summary of Comments and Agency Response s s ection.

Anticipated Risk Assessment and Data Needs

The Agency anticipates requiring data to conduct a comprehensive ecological risk assessment, including an endangered species risk assessme nt, and to update and revise the human health risk

assessment for all uses of cyfluthrin and beta

- cyfluthrin

. Below is a summary of the issues relevant to the registration review of cyfluthrin and beta

- cyfluthrin and the data the Agency anticipates requir ing.

Ecological Risk:

The most r ecent ecological risk assessments on cyfluthrin and beta

- cyfluthrin were conducted in 2007, 2006 , 2004, and 2001 as a result of several new agricultural uses being added to the product labels.

The Agency has not conducted an ecological risk assessment that supports a complete endangered species determination for cyfluthrin or beta

- cyfluthrin. The ecological risk assessment planned during registration review will allow the Agency to determine whether cyfluthrin and beta

- cy fluthrin ’s use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated

cr itical habitat, the Agency will consult with the U.S. Fish and Wildlife Service ( FWS )

and/or National Marine Fisheries Service (NMFS) (the Services), as appropriate.

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action Network

North America filed a lawsuit in the United States District Court for the Northern District of California, against the Environmental Protection Agency (EPA) for allegedly failing to undergo consultation with the United States Fish and Wildlife Service and the National Marine Fisheries Service regarding the effects of over 350 pesticides, including cyfluthrins

, on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11

- 00293 ( N.D.Cal.).

The Agency anticipates needing the following data in order to conduct a complete ecological risk assessment, including an endangered species assessment for cyfluthrin and beta

cyfluthrin.

The following anticipated studies should be conducted on cyfluthrin:

Environmental fate data gaps

GDLN 835.1230

– Leaching and Adsorption/Desorption (TGAI)

GDLN 835.4100

– Aerobic Soil Metabolism (TGAI, 2 Soils)5 GDLN 835.4200

– An a erobic Soil Metab o lism (TGAI)

GDLN 835.6100

– Environmental Chemistry Method and Independent Laboratory

Validation for soil (Footnote 7)

GDLN 835.6200

– Environmental Chemistry Method and Independent Laboratory

Validation for W ater and S ediment (Footnote 7)

Ecological toxicity data gaps

GDLN 850.2100

– Avian Oral Toxicit y (passerine species ) (TGAI)

GDLN 850.2300

– Avian Reproductive Study

GDLN 850.1025

– Oyster Acute Toxicity (saltwater, cyfluthrin TEP only)

GDLN 850.1035

– Mysid Acute Toxicity (saltwater, cyfluthrin TEP only)

GDLNs 850.4100 & 850.4150

– Seedling Emerge nce & Vegetative Vigor (Tier II)

GDLN 850.4400

– Aquatic Vasular Plant Growth

– Lemna spp

. Tier I I

Non

- GDLN

– Aquatic Invertebrate Acute Toxicity ( Hyalella azteca )

GDLN 850.1790

– Whole sediment: chronic invertebrates freshwater and marine

The following anticipated studies should be conducted on beta

- cyfluthrin :

Environmental fate data gaps

GDLN 835.4100

– Aerobic Soil Metabolism (TGAI, 4 Soils)

GDLN 835.4300

– Aerobic Aquatic Metabolism (TGAI)

GDLN 835.4400

– Anaerobic Aquatic Metabolism (TGAI)

GDLN 8 35.6100

– Environmental Chemistry Method and Independent Laboratory

Validation for soil (Footnote 7)

GDLN 835.6200

– Environmental Chemistry Method and Independent Laboratory

Validation for W ater and S ediment (Footnote 7)

Ecological toxicity dat a gaps
GDLN 850.1350

– Invertebrate Life Cycle , mysid

GDLNs 850.4100 & 850.4150

– Seedling Emergence & Vegetative Vigor (Tier II)

GDLN 850.4400

– Aquatic Vasular Plant Growth

– Lemna spp

. Tier I I

The following data would be used to inform removal perce ntages by waste water treatment, which is an input to the Exposure and Fate Assessment Screening Tool’s ( E

- FAST) down

- the

- drain module. The Office of Pesticide Programs will continue to confer with the Office of Water with the goal of refining our down

- t he

- drain assessment for registration review. These studies can be conducted on either cyfluthrin or beta

- cyfluthrin . The Agency is recommending that these studies be conducted on cyfluthrin

.

o Leachability from Treated Wood

o POTW Effluent Monitoring

o POTW T reatability Study6

Please refer to the “ EFED Registration Review Problem Formulation for Cyfluthrin and Beta

cyfluthrin (July 29, 2010)

, ” for a more detailed discussion of the anticipated ecological risk

assessment and data needs.

Human Health Risk:

The most recent human health risk assessment was conducted in 2007 in association with new uses on grasses, alfalfa, and sugar beets. The mammalian toxicity is very similar for cyfluthrin and beta

- cyfluthrin, and t he combined toxicology database for cyfluthri n and beta

cyfluthrin is considered to be complete except for an immunotoxicity study.

Subsequent to the Agency’s la te st risk assessment, the Agency identified age

- dependent pharmacokinetic factors associated with all pyrethroid insecticides that might lead to uncertainty regarding effects in children. The Agency anticipates re

- evaluating the points of departure (POD) and uncertainty factors used for human health risk assessment during registration review.

The dietary exposure database is adequate to support the existing registrations and tolerances. No new residue chemistry data are expected to be needed . A new drinking water assessment

may be conducted during registration review. Further, a revised dietary risk assessment may be conducted to incl ude updated percent crop treated estimates, updated monitoring data, changes in toxicological endpoints, and revised estimated drinking water concentrations

.

As a result of the revisions to the Agency’s Residential Standard Operating Procedures (SOPs), th e parameters and algorithms for dermal, inhalation, and hand

- to

- mouth exposure

calculations may change. These changes could result in significantly different exposure estimates for indoor and outdoor uses. Therefore, during registration review, a new

res idential exposure assessment is anticipated.

The potential changes mentioned above ( toxicological endpoints, dietary exposure estimates, residential exposure estimates ) have led to a determination that an updated aggregate risk assessment may be needed.

A r evised occupational handler and postapplication assessments may need to be conducted based on updated doses and endpoints for dermal and inhalation risk assessment s

.

During registration review, the tolerance expressions should be revised so that th ey address both coverage and measurement. Please see the human health scoping document for more

details.

Based on the Agency’s review of existing pyrethroid data, EPA has come to the conclusion that the DNT is not a particularly sensitive study for comparing the sensitivity of young and7

adult animals to pyrethroids. EPA has recently determined that, as an alternative to the generation and submission of a new DNT study, pyrethroid registrants may instead choose to cite the six previously submitted DNT studies for pyrethroid pesticides. The Agency is also investigating the need for additional experimentation , specific to the mode of action and pharmacokinetic characteristics of pyrethroids, to evaluate the potential for increased susceptibility of young organisms. Additional information can be found on EPA’s website: http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids

- pyrethrins.html

.

The Agency will make a decision regarding changes to any database uncertainty/safety factors for the cyfluthrins following receipt of the remaining required toxicity data, and following a final determination of the potential for increased susceptibility of infants and children to pyrethroid pesticides based on the results of all available data.

Cyfluthrins are members of the pyrethroid class of insecticides. EPA has developed a draft science policy document on the proposed common mechanism of toxicity for naturally

occurring pyrethrins and synthetic pyrethroids, which was supported by the FIFRA Scientific Advisory Panel (SAP). Upon fin alization of this science policy, the pyrethroids will be subject to a cumulative risk assessment under the FQPA.

The Agency anticipates requiring the following data in order to conduct a complete human health risk assessment for cyfluthrin and beta

- cyf luthrin. The Agency recommends conducting this study with cyfluthrin:

o GDLN 870.7800

– Immunotoxicity Study

Please refer to the “ Cyfluthrin and Beta

- Cyfluthrin Human Health Assessment Scoping Document in Support of Registration Review (July 1

, 2010)

, ” av ailable in the docket, for a detailed discussion of the anticipated human health risk assessment and data needs for cyfluthrin and beta

- cyfluthrin

.

Other Anticipated Data Needs: GLN 830.7050 UV/Visible Light Absorption

– this study is a new data requireme nt under 40 CFR part 158 (Product Chemistry Data Requirements) for registration of a pest icide (food

and non

- food uses). The Agency anticipates requiring this study to obtain basic information about the compound’s identity/composition and the wavelengths at which the compound may be susceptible to photochemical degradation.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence , including effects on endocrine target organ histopathology, organ8

weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment sce narios from the existing hazard database. However, as required by FFDCA section 408(p ), cyfluthrins are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain s ubstances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any

adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients . Cyfluthrins are included on

that list and h ave been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if ne cessary. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http:// www.epa.gov/endo/

.

Other data needs

Agricultural Health Study Cyfluthrins are among several agricultural chemicals included in the Agricultural Health Study (AHS). The AHS began in 1993 and is a collaboration of the National Institute of

Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), the EPA, and the National Institute for Occupational Safety and Health (NIOSH). Designed as a large, long

- term epidemiological study, the AHS collects and analyzes data on the health and work pr actices of nearly 90,000 farmers and their families in Iowa and North Carolina who enrolled in the study before any disease developed. The study focuses particularly on farmers' exposure to 50 chemicals including many of the most widely used pesticides. A s data are collected over a period of years, scientists can compare overall health outcomes for people who differ in whether they have had exposure to various chemicals. While these comparisons cannot conclusively9

demonstrate how exposure affects health, t hey can show some statistical associations. More

information on the AHS can be found at: http://aghealth.nci.nih.gov

.

Timeline

The Agency has created the following estimated timeline for the completion of the cyfluthrin and

beta

- cyfluthrin registratio n review.

Registration Review for Cyfluthrin and Beta

- cyfluthrin

– Projected Registration Review

Timeline

Activities Estimated Date Opening the docket Open Docket and Public Comment Period 2010

– September

Close Public Comment 2010

– November

Case Development

Final Work Plan 2011

– February

Issue DCI 2011

– October

– December

Data Submission 2013

– October

– December Open Public Comment Period for Draft Risk Assessments 2015

– April

- June

Close Public Comment Period 2015

– July

September Registration Review Decision Open Public Comment Period for Proposed Registration Review

D ecision 2015

– October

– December

Close Public C omment P eriod 2016

- Jan.

– Mar. Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2016 Total ( y ears ) 1 6 1. An assessment of the potential cumulative risk from the pyrethroid class of insecticides may impact this

time estimate.

Summary of Comments and Agency Responses:

The cyfluthrin registration review docket was open for a 60

- day comment period beginning on September 22 , 2010. Multiple comments were received from the public and the registrants, however, these comments do not alter the Agency’s work plan outlined in the Preliminary Work

Plan . Below are the Agency’s responses to representative c omments concerning data requirements. For more detailed/complete responses, please see the two Agency document s
, “ Cyfluthrin and Beta

Cyfluthrin. Response to Comments on the Human Health Assessment Scoping Document and Preliminary Work P lan ,” dated 01/27 /2011, and “ Response to Public Comments on the Registration Review Problem Formulation for Ecological Risk, Environmental Fate, Endangered Species, and10

Drinking Water Assessments for Cyfluthrin and Beta

- cyfluthrin ,” dated 02/09/2011, both are

available in the docket EPA

- HQ

- OPP

- 2010

- 0684

.

Comments from Bayer CropScience regarding the Agency’s human health scoping document

1) Bayer CropScience acknowledged that an immunotoxicity study in rats and/or mice is now a requirement. Bayer further stated that it h as submitted guideline toxicology studies in rats and mice that address immunotoxicological properties. Bayer believes that these studies satisfy the requirement for an immunotoxicity study.

Agency’s Response:

Although immunotoxicological information pr ovided in the submitted studies helps to elucidate immunotoxic potential, the information is not adequate to make a complete assessment of immunotoxicity. As a result, the Agency continues to require the submission of an acceptable immunotoxicity study.

2) Bayer CropScience stated that many of the default parameters used in residential exposure assessments do not reflect exposures that would be likely to occur in residential environments and, therefore, the Agency’s assessments overestimate potential ex posure. Bayer plans to conduct a liquid crack and crevice treatment exposure study to quantify and refine the current conservative transferrable residue values used in the EPA human health risk assessment. In addition, Bayer will survey pest control oper ators in order to refine assumptions regarding the quantity of pesticide used in one day. Bayer further stated that, in order to conduct a probabilistic temporal exposure assessment, one must have information concerning how, where, when, and the quantity of each pesticide used. The most recent data are a vailable through the Residential Exposure Joint Venture Survey conducted by the Consumer Specialty Products Association (CSPA) in 2001 and 2002. The CSPA is proposing to conduct a new survey to update pro duct use information. The Agency should support this work and use the data in residential exposure assessments.

Agency’s Response:

During registration review, the Agency will evaluate all chemical

- specific data submitted by the registrants and will inco rporate the data, as appropriate, in order to refine residential and aggregate human health risk assessments. If any of the proposed studies involve potential exposure to human subjects, then protocols for these studies might be subject to review by the A gency’s Human Studies Review Board (HSRB). If this review is necessary, it must occur prior to the initiation of the

studies.

Comments concerning the environment:

1) Comments from Physicians Committee for Responsible Medicine :11

“The Summary Document in dicates that the Agency may request testing for avian acute oral toxicity. We strongly support the use of the newly revised OECD Test Guideline 223 for the acute avian oral toxicity test...”

Agency’s Response:

To date the OECD has adopted the TG 223 guid eline and has issued a validation report. At this time EFED is actively evaluating the results of the OECD validation report to determine if the TG 223 effects endpoints and dose/response information adequately address the purposes of the avian acute

oral data requirement as described in 40 CFR Part 158. Until the Agency’s evaluation of that validation report is completed, EFED will not classify avian toxicity studies performed using the TG 223 protocol and the studies cannot be used to fulfill current da ta requirements.

2) C omments from California Regional Water Quality Control B oard

– central valley region (CRWQCB

- CVR) :

In response to the impairments identified in Weston and Lydy (2010), “... as required by the Clean Water Act, the Central Valley Wate r Board will soon be developing TMDLs to address cyfluthrin and other pyrethroids of concern... The Central Valley Water Board, and the dischargers we regulate, must direct considerable resources to our ongoing efforts to address the water quality impairment s associated with current

- use pesticides that impact water quality such as diazinon, chlorpyrifos, and now pyrethroids... In many ways, pollution prevention through effective regulation of pesticide use would be much more efficient and effective than the reg ulatory options available to water control agencies implementing the Clean Water Act.”

Agency’s Response:

The Agency has been working diligently to ensure that the registrations of pesticides do not cause

unreasonable harms to human health or the environ ment. On going research and method development are being carried out by EPA/OPP to advance models used in the Agency’s risk

assessment for all pesticide use scenarios. In the meantime, the Agency encourages the submissions of reliable monitoring data so t hat our models can be further validated and modified.

3) Comments from California Stormwater Quality Association

“Water quality impacts must be prevented through use restrictions.”

“The registration process must effectively prevent water quality impac ts.”

Agency’s Response:

See Agency’s Response to comments from CRWQCB

- CVR above.12

4) Comments from California Regional Water Quality Control Board

– San Francisco Bay Region

“All data necessary for a scientifically sound environmental risk assessment s hould be requested/reviewed...” including data for sensitive saltwater species ( Americamysis bahia ), chronic sediment toxicity data for salt water species found in the Western U.S., aquatic toxicity data to account for potential increased toxicity in cold water, and data needed for urban exposure

assessments.

“This list should be reviewed in light of available data from the open scientific literature and from studies required by California Department of Pesticide Regulation (DPR), as some of the needed

d ata may already be available or be forthcoming.”

Agency’s Response:

Acceptable toxicity data using A. bahia are available for cyfluthrin and will be used in the cyfluthrin

risk assessment. EFED currently recommends the use of the estuarine/marine amphi pod, Letptocheirus plumulosus , for assessing chronic toxicity of pesticides in sediments because of its long history of development with EPA and by other Agencies (U.S. Army Corps of Engineers). Currently, L. plumulosus is the only estuarine/marine test s pecies for which chronic sediment toxicity testing has been validated for use in the Agency 1 . Although L. plumulosus is distributed along the east coast of the United States, available literature indicates it has similar sensitivity as E.

estuarius

, H. az teca and Ampelisca abdita. 2 Furthermore, the Agency will consider results from other test species provided they are scientifically defensible and appropriate for use in the Agency’s forthcoming risk assessment.

5) Comments from California Regional Wat er Quality Control Board

– San Francisco Bay Region

“Cyfluthrin in POTW effluent can be transferred to biosolids. The Work Plan should evaluate potential impacts from the use of pesticides to biosolids land application in cases where down

- the

drain asses sments indicate that pesticides would partition to biosolids.”

1 USEPA/USACE. 2001. Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- associated Contaminants with the Amphipod Leptocheirus plumulosus . First Edition. EPA EPA 600/R

- 01/020. March 2001

2 DeWitt, T.H., B.L. McGee, R. Alden, H. Phelps, and A. Pinkney. 1992. A multi

- species, multi

- lab comparison of the toxicity of a Chesapeake Bay sediment. Presented at the Thirteenth Annual Meeting of the Society for Environmental Toxicology and Chemistry, Cincinnati, OH, November 8

- 12.

McGee, B.L., C.E. Schlekat, and E. Reinharz. 1993. Assessing sublethal levels of sediment contamination with the estuarine amphipod, Leptocheirus plumulosus

. Environ Toxicol. Chem. 12:577

- 588.

SAIC. 1993a. Draft data report on comparative sensitivity of four amphipod species to sediment associated

contaminants. Submitted to USEPA. EPA contract No. 68

- CO

- 0044. Prepared by Science Applications International Corporation, Narragansett, RI. 15 pp.13

Agency Response:

Discharge of cyfluthrin and/or β

- cyfluthrin into the environment via effluent will be considered to the best degree possible in the risk assessment. The Agency is actively evaluating the extent to which ecological risk from cyfluthrin and β

- cyfluthrin via land application of biosolids should be addressed in its forthcoming environmental fate and ecological risk assessment, and by extension, any additional data that may be re quired. As part of this evaluation, OPP is working closely with the Office of Water which regulates land application of biosolids under the Clean Water Act.

6) Comments from Baye r CropScience regarding Ecological and Environmental Fate Data Requirements

Guideline #835.1230 Mobility Adsorption/Desorption

“Bayer CropScience agrees that a full adsorption/desorption study would provide valuable data to reduce uncertainty concerning the extent of adsorption with concentration as described by the

Freundlich exponent.”

Agency’s Response:

No response is needed.

Guideline #835.4100 Aerobic Soil Metabolism

“Bayer CropScience is submitting the study report “Aerobic Soil Metabolism of β

- Cyflutrhin

phenoxy

- 1,2,3,4,5,6

- 14C6 (cyclopropanecarboxylic acid, 3

- (2,2

- d ichloroethenyl)

- 2,2

- diemthyl

- , cyano(4

- fluoro

- 3

- phenoxyphenyl)methylester) in Sandy Loam from Fresno, California (Bayer Report M

- 079875

- 01

- 1) which was conducted at the request of the California Department of Pesticide Regulation (CDPR). This study will s atisfy one of the β

- cyfluthrin requirements.

Bayer CropScience agrees to submit an aerobic soil metabolism study in two soils with cyfluthrin and at least one of which cyclopropyl

– labels, following issuance of the data call

- in.

Bayer CropScience intends to submit a new study with β

- cyfluthrin on four soils (two European soils and two US soils) with either fluorophenyl

- or cyclopropyl

- labels (at least one with cyclcoprorpyl

label), following issuance of the data call

- in.”

Agency’s Response:

The Agency will review these studies when they are received and will use all relevant scientifically

valid data in the risk assessment.14

Guideline #835.4200 Anaerobic Soil Metabolism

“EPA has requested an anaerobic soil metabolism study conducted with cyfluthrin o n one soil for the evaluation of transformation pathways and three additional soils for rates of transformation

determination.

According to the anaerobic soil metabolism study guideline (#835.4200), the test system will be flooded and changed to anaerob ic condition from aerobic condition at 30 days after treatment (or one

half

- life, whichever comes first). Bayer CropScience has conducted aerobic metabolism studies in two soils with cyfluthrin and one soil with β

- cyfluthrin. The distribution of cyfluthr in, CO 2 , and

bound residues was 60

- 69%, 6

- 17%, and 14

- 17%, respectively, at day 28 after treatment, accounting

for 89

- 94% of the applied material (Wagner et al., 1983). The distribution of β

- cyfluthrin, CO 2 , and bound residues was 66%, 15%, and 14% respec tively, at day 30 after treatment, accounting for 95% of the applied material (Aga, 2002). Only one metabolite (PFB

- acid) was detected at 10% in one soil at day 28, no other metabolites were detected greater than 5% at 28

- 30 days. Thus, at the point

of c onverting the anaerobic soil test system from aerobic to anaerobic conditions by flood ing the systems, the primary residue in the soil will be parent cyfluthrin (or β

- cyfluthrin). Therefore, at that point the test system will be similar to the anaerobic aquatic test system, since in an aquatic system cyfluthrin will partition rapidly into the soil/sediment. Bayer CropScience believes the anaerobic aquatic metabolism study is an appropriate substitution for the anaerobic soil study (see anaerobic aquatic discussion below).”

Agency’s Response:

Anaerobic metabolism studies are requested in both soil and in aquatic systems because degradation rates and pathways can differ in these two environments. Therefore, both studies are needed.

Guideline #835.4300 Aerobic Aquatic Metabolism

“Bayer CropScience agrees to submit an aerobic aquatic metab olism study following issuance of the

data call

- in.”

Agency’s Response:

No response needed.

Guideline # 835.4400 Anaerobic Aquatic Metabolism

“Bayer CropScience agrees to submit an anaerobic metabolism study following issuance of the data

call

- in.”

Ag ency’s Response:15

No response needed.

Guideline #s 835.6100 and 6200 Environmental Chemistry Methods and Independent Laboratory Validations for Soil, Water, and Sediment

“Bayer CropScience agrees to submit modern mass

- spectrometry methods for cyfluthrin in water, sediment, and soil. Bayer CropScience also agrees to conduct ILV on these methods. The methods will separate the four enantiomeric pairs of isomers, I, II, III, and IV. The quantitation of cyfluthrin will be based on the sum of all isomers, an d the quantitation of β

- cyfluthrin will be based on the sum of isomers II and IV. The methods are not intended for data collection in field dissipation studies, thus the inclusion of metabolites (FPB

- acid, FPB

- ald, and DCVA) is not necessary due to their low

to xicity compared to parent.”

Agency’sResponse:

At this time, FPB

- acid ( 4

- fluoro

- 3

- phenoxybenzoic acid ), FPB

- ald ( 4

- fluoro

- 3

- phenoxybenzaldehyde ), and DCVA ( 3

- (2,2

- dichlorovinyl)

- 2,2

- dimethyl

- cyclopropanecarboxylic

acid ) are not considered residues of to xicological concern; therefore, environmental chemistry

methods do not need to include these residues for identification.

Non

- Guideline Study: Wood Leachability Study

“EPA has requested a study to be conducted according to the American Wood Preservers Association Standard Method of Determining the Leachability of Wood Preservatives (E11

- 06).

Bayer CropScience does not understand the justification for this study since we are not aware of any cyfluthrin and β

- cyfluthrin products registered for use as wo od preservative treatments.”

Agency’s Response:

Applications to protect wood from wood

- infesting pests are allowed on some labels such as EPA registration numbers 432

- 1363, 432

- 1377, 432

- 1483, 11556

- 124, and 11556

- 145. Therefore, EPA

still recommends a study conducted according to the American Wood Preservers Association Standard Method of Determining the Leachability of Wood Preservatives (E11

- 06) be requested. The method should be amended so that cyfluthrin is applied as specified on labels instead of impregnated into the woo d. In the absence of data, the Agency would assume that 100% of cyfluthrin applied to wood surfaces is available for washoff.

Guideline # 850.2100 Passerine Avian Oral (Cyfluthrin)

“While Bayer CropScience believes overall tha t the existing studies are sufficient to characterize the toxicity of the cyfluthrins to birds, we recognize that this study is mandatory and will conduct the16

study as requested. It is unlikely that conducting the passerine study will change the risk asses sment for the cyfluthrins.”

Agency’s Response:

No response needed.

Guideline # 850.2300 Avian Reproduction Study (Mallard duck only) (Cyfluthrin)

“In addition to the two cyfluthrin mallard reproduction studies (Carlisle, 1984 and Beavers, 1986)

that t he agency has in their possession, Bayer has identified an additional mallard reproduction study (Beavers et al ., 1990) which will be submitted to meet this data request. It must be noted that Bayer disagrees with the agencies finding of a lack of a NOAEL based on the studies currently in the agencies possession. The three cyfluthrin mallard re production studies consistently support a NOAEL of 250 ppm.”

Agency’s Response:

The Agency looks forward to receiving the data and reviewing them for adequacy and suitability for

use in risk assessment.

Guideline # 850.1025/1035 Oyster and Mysid Acute Toxicity (saltwater; cyfluthrin TEP only) (Cyfluthrin)

“Mollusks are one of the least sensitive taxa to pyrethroids, so additional testing is unlikely to

influence the aquatic risk assessment. Two studies (Barrows, 1984 and Carr, 1986) examining the toxicity of cyfluthrin to the eastern oyster exist. The EC50 values reported by the authors were 5 and 3.42 μg/L; slightly different from the value of 2.69 μg/L cited by agency. Bayer requests clarification from the agency on this discrepancy. Also Table 7.2 (page 75) of EPA problem formulation does not accurately reflect the existence of the two available oyster studies (MRID’s: 00146118 and 00158783), although they are l isted in the bibliography.”

Agency’s Response:

Based on the available data evaluation records (DERs) for these studies, the Barrows and Dillon (1984) oyster study (ACC. No.: 250816; MRID: 00146118) is classified as invalid and is not acceptable for use in risk assessment. The results were based on a static, rather than a flow

- through

system.

Based on the available DER for Carr (1986) (ACC. No.: 262443; MRID 00158783), the results from this study were found to be acceptable for use in risk assessment. The discrepancy between the study reported EC 50 value ( i.e ., 3.42 μg a.i./L) and the one reported in the problem formulation ( i.e

., 2.69 μg a.i./L) is due to the fact that the analysis conducted by EPA(unlike what was done by the study author) did not use the pooled controls (the negative and solvent controls combined).17

Non

- Guideline Study: Aquatic Invertebrate Acute Toxicity ( Hyalel la azteca ) (Cyfluthrin)

“Besides considering additional single species data on non

- standard test organisms, will the agency also consider more complex studies (e.g., mesocosoms and population modeling) that are useful in putting the results of single spec ies studies into an ecological context?”

“Will the agency accept studies with closely related species (e.g., Gammurus spp. ) as meeting this data requirement? Bayer does have a study (Heimbach, 2000) conducted with a non

- USA

formulation for Gammurus pulex which Bayer will submit for review. If the existing data is deemed inadequate to meet the data requirement, Bayer will, upon confirmation that a robust test protocol is available, conduct the study as requested.”

Agency’s Response:

EFED will consider all submitted data for use in the risk assessment conducted for cyfluthrin and β

cyfluthrin. It is unlikely that a mesocosm study would be adequate to fulfill the data requirement for an acute toxicity study with H. azteca . Additionally, unless it can be demonstrated that a related species is at least as sensitive to cyfluthrin as H. azteca , a study with a related species would likely not be adequate to fulfill this data requirement since H. azteca has been demonstrated to be substantially more sensitive to pyrethroids than Daphnia magna . Furthermore, a study using a non

USA formul ation is not adequate for use in risk assessments conducted by the agency unless it can

be demonstrated that the non

- USA formulation is representative of a formulation registered in the

USA.

Non

- Guideline Study: Whole sediment: chronic invertebrates fr eshwater and marine (Cyfluthrin)

“... Bayer would like to work with the agency, industry and experts in the scientific community to ensure that the methods used are robust, reliable, and predictive.

With respect to existing marine 28

- day sediment study ( MRID 46591506) with Leptocheirus plumulosus, reproduction was not included in the initial protocol because amphipod reproduction is not a robust endpoint. However, an analysis of reproduction was performed post study termination on preserved samples. Pleas e see Giddings (2006) for a reporting and analysis of the available data. Bayer believes this existing study, conducted at EPA’s request and with their guidance, should meet the data requirement for a marine chronic sediment study. “

Agency’s Response:

EPA is actively working with the Pyrethroid Work Group ( PWG ) to develop an acceptable methodology for a whole sediment chronic toxicity invertebrate study that would provide results that are adequate for use in risk assessment.18

Regarding the Giddings (2 006) summary ( MRID 46871501 ), the study author made the following

conclusion:

“... (B)oth growth (dry weight at 28 d) and reproduction of L. plumulosus appeared to be subject to unknown sources of variability among and within studies. Until the cause(s) o f this variability have been identified and brought under control, results of the L. plumulosus tests must be interpreted with caution, and the reproduction data are considered unreliable” (p. 27).

Although, EPA will consider the information in this repor t in the risk assessment for the cyfluthrins, based on Giddings’ (2006) own evaluation of the cyfluthrin study, it is unlikely that these data would be adequate to fulfill the data requirement for a marine chronic sediment study

.

Guideline # 850.4100 and 850.4150 Vegetative vigor and Seedling emergence, Tier I/ Tier II (Cyfluthrin)

“The screening study (Lechelt

- Kunze, 2002a) addresses the potential effect of cyfluthrin to non

target plants and should fulfill the regulatory data requirement.... Because c yfluthrin works in insects as a neural toxin, and unlike insects, plants do not have neural networks, it is highly unlikely that cyfluthrin would cause phytotoxicity. Cyfluthrin has been registered for use on a very wide range of plants for many years and while Agency’s review of the available incident data found three phytotox incidents, those incidents are much more likely to be due to other factors (e.g. herbicide contamination resulting from improperly cleaned spray tanks) rather than cyfluthrin... We req uest that considering the properties of cyfluthrin and its long history of safe use on a range of plants, that additional plant testing of cyfluthrin be waived.”

Agency’s Response:

The Agency received this study [Lechelt

- Kunze, C. (2002): Cyfluthrin EC 050: Post

- emergence screening for herbicidal activity. Bayer AG, Monheim, Germany. M

- 056722

- 01

- 2; MRID 48350619] on January 11, 2011; it is being review ed by the Agency. Pending the outcome of the Agency review, this study may or may not fulfill this data requirement.

In addressing this comment, it was determined that a search of EPA/OPP’s Aggregate Incident Database was not included in cyfluthrin problem formulation. Therefore a search of the Aggregate Incident Database was conducted on January 4, 2011, for cyfluthrin in order to gather more information regarding potential plant incidents associated with the use of the chemical. There are currently 132 “minor” plant incidents listed in the Aggregate Incident Database for cyfluthrin that

date from 1999 t o 2004. Since detailed information is not available for the aggregate incidents, it is current EPA policy to assume that these incidents are the result of registered uses unless information19

is provided that indicates otherwise. Therefore, EPA does not re commend waiving the terrestrial plant toxicity data requirement for cyfluthrin at this time.

Guideline # 850.4400 Aquatic Vascular Plant Growth

- Lemna spp. Tiers I/II (Cyfluthrin)

“ Because the cyfluthrin is a pyrethroid and non

- phytotoxic, no study has b een requested by any regulatory authority in the past, and to our knowledge no such study currently exists. Conduct of a study with cyfluthrin is not expected to impact the overall risk assessment. ”

Agency’s Response:

Due to the terrestrial plant incide nts associated with cyfluthrin and a lack of phytotoxicity data for the chemical, there is uncertainty regarding the potential impacts of cyfluthrin on non

- target plants (including aquatic plants). Therefore, the Agency still recommends that these data be requested.

Guideline # 850.1400 or 850.1300/850.1350 Fish Early Life Stage or Invertebrate Life Cycle (β

cyfluthrin)

“ Bay er CropScience understands the A gency’s interest in a Mysidopsis bahia life

- cycle study and will conduct it as requested. ”

Agency’s Response:

No response needed.

Guideline # 850.4100 or 850.4150 Seedling emergence or Vegetative vigor (β

- cyfluthrin)

“ The screening study (Lechelt

- Kunze 2002b), addresses the potential effect of β

- cyfluthrin to non

target plants and fulfills the regul atory data requirement... We request that considering the properties of β

- cyfluthrin and its history of safe use on a range of plants that additional plant testing of β

- cyfluthrin be waived. If, after consid ering the available information , the Agency decid( es) additional plant testing is necessary, we propose that the agency rely on a study with cyfluthrin and hold additional testing with β

- cyfluthrin in reserve. It is highly unlikely that additional toxicity

te sting with plants will generate data that will result in significant impact s to the ecological risk assessment or use pattern.”

Agency’s Response:

The Agency received this study [ Lechelt

- Kunze, C. (2002): Β

- cyfluthrin EC 025: Post

- emergence screening for herbicidal activity. Bayer AG, Monheim, Germ any. M

- 055590

- 02

- 2; MRID 48350620] on January 11, 2011; it is being reviewed by the Agency. Pending the outcome of the Agency review, this study may or may not fulfill this data requirement.20

There are two plant incidents listed for β

- cyfluthrin in the A g gregate Incident Database

. Since detailed information is not available for the aggregate incidents, it is assumed that these incidents are the result of registered uses unless information is provided that indicates otherwise. EPA still

recommends that the se data be requested.

Guideline # 850.4400 Aquatic Vascular Plant Growth

- Lemna gibba (β

- cyfluthrin)

“Because the β

- cyfluthrin is a pyrethroid and non

- phytotoxic, no study has been requested by any regulatory authority in the past, and to our knowledge no such study currently exists. Conduct of a study with β

- cyfluthrin is not expected to impact the overall risk assessment.

If, after considering the available information, the Agency deciding additional plant testing is

necessary, we propose that the A gency rely on a study with cyfluthrin and hold additional testing with β

- cyfluthrin in re serve.”

Agency’s Response:

Due to the terrestrial plant incidents associated with β

- cyfluthrin and a lack of phytotoxicity data for the chemical, there is uncertainty regarding the potential impacts of β

- cyfluthrin on non

- target plants (including aquati c plants). Therefor e, EPA still recommends that these data be requested for both cyfluthrin and β

- cyfluthrin

.

Next Steps:

The A gency plans to issue a DCI for cyfluthrins in 2011 for the data gaps listed under Summary of Data Gaps below. The information received in response to this DCI will be used to conduct the planned human health, ecological risk, and endangered species assessment for cyfluthrins.21

II. Summary of Data Gaps

– Cyfluthrin and B eta

- cyfluthrin

The tables below summarize all outstandi ng data needs for cyfluthrin and beta

- cyfluthrin. These data are anticipated to be included in the data call

- in for registration review.

Anticipated Data R equirement s for Cyfluthrin

Guideline

Number Data Requirement Test

Material Estimated

Timeframe (M onths)

835.1230 Leaching and Adsorption/Desorption TGAI 12

835.4100 Aerobic Soil Metabolism 3 TGAI 24

835.4200 An a erobic Soil Metab o lism 4 TGAI 24

835.6100 (footnote 7 5 ) Environmental Chemistry Method and In dependent

Laboratory Validation

– soil TGAI 24

835.6200 (footnote 7 6 ) Environmental Chemistry Method and In dependent

Laboratory Validation

– water and sediment TGAI 24

850.2100 Avian Oral Toxicity (passerine species) TGAI 12

850.2300 Avian Reproduction Study (Mallard duck only) TGAI 24

850.1025 Oys ter Acute Toxicity, TEP 12

850.1035 Acute Toxicity Estuarine/Marine Organisms

– Mysid TEP 12

850.4100 &

850.4150 Seedling Emergence & Vegetative Vigor (Tier II 7 ) TEP 12

850.4400 Aquatic Plant Growth (aquatic vascular plant toxicity)

(Tier II 8 ) TGAI 12

Non

- GDLN Aquatic Invertebrate Acute Toxicity (Hyalella azteca) TGAI 12

850.1790 Whole sediment: chronic invertebrates freshwater and

marine TGAI 12

Non

- GDLN Leachability from Treated Wood TGAI 12

Non

- GDLN POTW Effluent Monitoring TGAI 12

Non

- GDLN POTW Treatability Study TGAI 12

870.7800 Immunotoxicity Study TGAI 12

3 Two additional soil studies are expected to be required for cyfluthrin.

4 Four additional soi l studies are expected to be required

. 5 40 CFR Part 158 Guideline Study 835.6100 and 835.6200 Footnote 7 states “Environmental chemistry methods used to generate dat a associated with this study must include results of a successful confirmatory method tri al by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement.”

6 40 CFR Part 158 Guideline Study 835.6100 and 835.6200 Footnote 7 states “Environmen tal chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and pr ocedures for independent laboratory validation are available as addenda to the guideline for this test requirement.”

7 Registrants may opt to conduct a Tier I study, with the understanding that any adverse effects (even if <25%) may necessitate a Tier II study. A Tier II study will enable the Agency to conduct an endangered species assessment for nontarget plants.

8 Registrants may opt to conduct a Tier I study, with the understanding that any adverse effects (even if <25%) may necessitate a Tier II study. A Tier II study will enable the Agency to conduct an endangered speci es assessment for nontarget plants.22 Anticipated Data R equirement s for Beta

- cyfluthrin

Guideline

Number Data Requirement Test

Material Estimated

Timeframe (Months)

835.4100 Aerobic Soil Metabolism 1 TGAI 24

835.4300 Aero bic Aquatic Metabolism 2 TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

835.6100 (footnote 7 3 ) Environmental Chemistry Method and Independent

Laboratory Validation

– soil TGAI 24

835.6200 (footnote 7 4 ) Environmental Chemistry Method and In dependen t

Laboratory Validation

– water and sediment TGAI 24

850.1350 Invertebrate Life Cycle, mysid TGAI 12

850.4100 &

850.4150 Seedling Emergence & Vegetative Vigor (Tier II) TEP 12

850.4400 Aquatic Plant Growth

, Lemna gibba TGAI 12

1 One additional s ediment study is expected to be required for beta

- cyfluthrin

2 One additional s ediment study is expected to be required for beta

- cyfluthrin

3 40 CFR Part 158 Guideline Study 835.6100 and 835.6200 Footno te 7 states “Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and pr ocedures for independent laboratory validation a re available as addenda to the guideline for this test requirement.”

4 40 CFR Part 158 Guideline Study 835.6100 and 835.6200 Footnote 7 states “Environmental chemistry methods used to generate dat a associated with this study must include results of a succe ssful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement.”