1 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

August 11, 2015

P C Code: 128819 DP Barcode: 316642, 417353, and 420428

MEMORANDUM

SUBJECT: F orchlorfenuron: Response to Data Waiver Requests for a Terrestrial Field Dissipation Study and an Avian Reproduction Study AND Summary of the Review of an Ecotoxicity Study on the Ecological Effects of Forchlorfenuron

FROM: Christina Wendel, Biologist Greg Orrick, Environmental Scientist ERB2/Environmental Fate and Effects Division (7507P)

THROUGH: Elyssa Arnold, Risk Assessment Process Leader (RAPL) Brian Anderson, Branch Chief ERB2/EFED (7507P)

TO: Marcel Howard, Risk Manager Reviewer Tony Kish, Product Manager PM, Team 22 Fungicide Branch/Registration Division (7505P)

1. Waiver Requests

The Environmental Fate and Effects Division (EFED) has completed its review of the data waiver requests submitted to the Agency in a letter dated July 1, 2013 for a terrestrial field dissipation and an avian reproduction study that we re requested to meet conditional registration requirements for the use on pears, plums, sweet cherries, figs, pistachios and almonds (a single application rate of 0.022 lb a.i./A). A supplementary component of the avian reproduction waiver request was submitted to EFED in March 2014 was a reproduction study with the bobwhite quail. The results of this study are discussed in combination with the review of the waiver request for avian reproduction. EFED’s responses are provided in Table 1 below.

Table 1. Disposition of Waiver Requests for Forchlorfenuron

OCSPP Guideline Study Type DP Barcode Are Additional Data Needed for Risk

Assessment?

835.6100 Terrestrial Field Dissipation 316642 No

850.2300 Avian Reproduction 417353 Yes 2015.08.12 09:53:06 -04'00'2 Submissions:

49165701 Weidenbach, P.C. (E x ponent ® , Inc.). 2013. Forchlorfenuron: Waiver Request for Avian Reproduction, OCSPP Guideline 850.2300. Unpublished report prepared by E x ponent, Inc. for Sponsor KIM-C1, LLC. 9p. (DP barcode 417353).

49165702 Weidenbach, P.C. (E x ponent ® , Inc.). 2013. Forchlorfenuron: Waiver Request for Terrestrial Field Dissapation, OCSPP Guideline 835.6100. Unpublished report prepared by E x ponent, Inc. for Sponsor KIM-C1, LLC. 9p. (DP barcode 316642).

49350901 Frey L.T., Martin K.H., Beavers J.B., and Jaber M. 2014. Forchlorfenuron: A Reproduction Study with the Northern Bobwhite. Unpublished study performed by Wildlife International, Ltd., Easton, Maryland. Laboratory report number 248- 108. Study sponsored by Degussa AG, Product Line Agriculture, D-83308 Trostberg, Germany. Study completed on December 3, 2003 and report amended on March 21, 2014. (DP barcode 420428).

1.1. Request for a Waiver from the Requirement for a Terrestrial Field Dissipation Study for Forchlorfenuron (OCSPP 835.6100)

1.1.1. Basis for Waiver Request

The registrant ’s basis for waiving the required terrestrial field dissipation study was that the maximum application rate is low, making quantitation of residues difficult. Further complications include that fruit and nut orchards will intercept residues, resulting in lower and non-homogeneous soil concentrations, and that soil adsorption and slow microbial degradation will further reduce concentrations over time.

1.1.2. Response to Waiver Request

The Agency currently recommends waiv ing additional environmental fate studies including the terrestrial field dissipation study on the basis of no risk level of concern exceedances from current or proposed uses using conservative assumptions in the absence of data (see DP411314; USEPA, 2013 b ). If a risk level of concern exceedance is identified, the following environmental fate studies of forchlorfenuron may be necessary:

x Soil photolysis study

x Aerobic soil metabolism study (3 additional soils)

x Aerobic aquatic metabolism study

x Anaerobic aquatic metabolism study

x Terrestrial field dissipation study

x Analytical methods in soil and water

Since the Agency has not identified any exceedance of risk thresholds for the currently registered and proposed uses of forchl orfenuron, EFED recommends that RD grant a waiver request for a terrestrial field dissipation study for forchlorfenuron.3 1.2. Request for a Waiver from the Requirement for an Avian Reproduction Study for Forchlorfenuron (OCSPP 850.2300)

1.2.1. Basis for Waiver Request

The registrant’s basis for waiving the required avian reproduction study was that the maximum application rate is low, and deposition on typical avian dietary items would be minimal (estimated to be 5.3 mg/kg on short grass) resulting in low exposure to birds. The registrant estimated for birds ingesting short grass containing forchlorfenuron residues immediately after an application, exposures for different weight classes of birds (20, 100 and 1000 grams) were calculated to be 6.1, 3.5 and 1.5 mg/kg-bw/day, far less than the lowest reproductive NOAEL (144 mg/kg-bw/day) reported in a rat two-generation reproduction toxicity study. Coupled with the fact that forchlorfe nuron is practically non-toxic to birds on an acute basis, the registrant believes an avian reproduction study is not necessary and seeks the concurrence of EPA.

1.2.2. Response to Waiver Request

With the submission of the avian reproduction study with bobwhite quail ( Colinus virginianus ) (MRID 49350901; DP420428), the response to the waiver request became dependent on the review of this study. Based on th e review, there were significant reductions in 14-d survivor body weight at all treatment levels relative to the negative control. These observed effects on 14-d survivor body weight, resulted in a NOAEC of <170 mg a.i./kg-diet (the lowest test concentration tested). Findings of the review are presented in Table 2 below. There were no treatment-related mortalities, abnormal signs of toxicity, or other treatment-related effects on any reproductive parameter analyzed. Therefor e, the bobwhite quail avian reproduction study was determined to be scientifically sound; howev er, the study was classified as supplemental because a valid NOAEC could not be established, due to the effects on the offspring observed in all treatment levels. Without a definitive NOAE C, the study cannot be upgraded to acceptable, and the study does not satisfy the guideline requirement for avian reproduction. To meet guideline requirements additional data on birds (s urrogate for terrestrial-phase amphibians and reptiles) are needed. It is recommended that lower doses be used when conducting the new bobwhite quail reproduction study.

Table 2. Summary of the Submitted Toxicity Data for Forchlorfenuron

MRID Number OCSPP Guideline Study Description Toxicity Endpoint Study Classification Major Issues

49350901 850.2300 Avian Reproduction: Bobwhite quail

(96.95% a.i.; TGAI) NOAEC <170 mg a.i./kg diet LOAEC = 170 mg a.i./kg diet Endpoint affected: reduction in 14

- d survivor body weight Supplemental A definitive NOAEC could not be established, significant effects in 14d survivor body weight were observed at all treatment levels relative to the negative control.

1 TGAI = Technical Grade Active Ingredient4 The exposure estimates associated with the evaluated uses (pears, plums, sweet cherries, figs, pistachios and almonds ) , represent one of the lowest annual application rates for forchlorfenuron, with a single application rate of 0.022 lb a.i./A. Whereas, the maximum use pattern for forchlorfenuron is the use on black and red currants, elderberries, gooseberries, and lingonberries ( i.e., bushberries), and corresponds to an annual application rate of 0.088 lb a.i./A (0.044 lb a.i./A x 2 applications @ a 14d interval). Therefore, the exposure load in theenvironment is greater for these other uses of forchlorfenuron, with maximum estimated dosebased EECs of 21.1, 12.1 and 5.4 mg/kg-bw versus 6.1, 3.5 and 1.5 mg/kg-bw/day for the different weight classes of birds (20, 100 and 1000 grams, respectively).

Reduction in body weight was the most sensitive endpoint seen in both the bobwhite quail study (reduction in 14-d survivor body weight; MRID 49350901), and the rat twogeneration study (reduction in body weight in F1 males & females, and growth retardation in F1 & F2 pups, MRID 44394616). These studies suggest that there may be some consistencies in observed effects across vertebrate species, both birds and mammals. The observed body weight effects cannot be discarded as inessential to fitness or that they are not consistent with other longer term exposure studies in higher vertebrates, as effects were observed across multiple doses in a potentially dose responsive manner in multiple vertebrate species. Therefore, in addition to the bobwhite quail study, in order to fulfil the data requirement for avian reproduction and complete the risk picture for birds on a chronic basis, a mallard duck study is also needed ( Table 3 ).

Table 3. Summary of Toxicity Data Needs for Forchlorfenuron

OCSPP Guideline Data Requirement Submitted Studies (MRID #) Study Classifications Sufficient for risk assessment? Current Additional Data Need

850.2300 Avian Reproduction 49350901 Supplemental

No The bobwhite quail study (MRID 49350901) was classified as supplemental (not upgradable) because a definitive NOAEC could not be established (treatment

- related effects were observed in all test concentrations). T oxicity data are needed for both the bobwhite quail and mallard duck to fulfill the data requirements. None Not applicable5 References:

Nemec, M. 1997. Dietary Two-Generation Re production Study of SKW20010 in Rats: Final Report: Lab Project Number: WIL-171002: WIL-171002B: WIL-171002A. Unpublished study prepared by WIL Research Labs., Inc. 2573 p. MRID 44394616.

USEPA. 2013 a . Wendel, C., G. Orrick, R.D. Jones, J. Holmes, and B. Anderson. Forchlorfenuron: Ecological Risk Assessment for the Section 3 Proposed New Uses on Almonds, Sweet Cherries, Figs, Pears, Pistachios, and Plums Including Prunes. DP barcode 406985. Dated April 24, 2013. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Memorandum to the Registration Division.

USEPA. 2013 b . Wendel, C., G. Orrick, R.D. Jones, J. Holmes, and B. Anderson. Memorandum

“ Forchlorfenuron: Response to Data Waiver Requests for an Avian Reproduction Study and a Soil Dissipation Study with KT-30 (Forchlorfenuron) AND Response to the 75-day Deficiency Letter dated March 14, 2013 .” DP barcode 411314. Dated May 14, 2013. Office of Pesticide Programs, Environmental Fate and Effects Division. Memorandum to the Registration Division.