UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

DATE: 

SUBJECT: 

TO: 

FROM: 

THROUGH: 

January 28, 2015 

Response to Public Comments on Registration Review Problem Formulation for 

the Ecological Risk Assessment and Drinking Water Exposure Assessment to be 

Conducted for Etoxazole. 

(PC Code No. 107091; DP Barcode 424309) 

Julia Stokes, Chemical Review Manager 

Jill Bloom, Team Leader 

Linda Arrington, Chief 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division (7508W) ' .._~ o/ jl <0 / / ~ 

Justin Housenger, Biologist &J 

Environmental Risk Branch V 

Environmental Fate and Effects Division (7507C) 

· oi/2~/I!JEnvironmental 

Mah T. Shamim, 

Risk 

Ph.D

Branch 

., Chief 

V 

~ 

Environmental Fate and Effects Division (7507C) 

In response to the" Registration Review- Preliminary Problem Formulation for Ecological Risk 

Assessment and Drinking Water Exposure Assessment to be Conducted for Etoxazole" 

(Document ID EPA-HQ-OPP-2014-0133 in www.regulations.gov) (DP Barcode: 0418231 , dated 

July 1, 2014), Valent U.S.A Corporation (hereafter referred to as Valent) provided comments 

during the public comment period. Valent is the sole U.S. registrant of record for etoxazole. The 

purpose of this memorandum is to address those comments. The Environmental Fate and Effects 

Division (EFED) used an outline-type of format to address the comments. The comments were 

often written verbatim while other times they were summarized, as required. EFED's purpose of 

the document is to respond to technical/science-related questions and comments. 

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1. Valent Comment: On the anticipated data need of an Avian Acute Oral Toxicity Test (with 

passerine species, OCSPP 850.2100): 

The comprehensive and state-of-the-art data analyses by the Crop Life America (Poster 

presentation at SETAC North America 35th Annual Meeting is attached in Appendix 1) 

indicate that passerine species have similar sensitivity to mallard duck and bobwhite quail. 

Considering the low acute toxicity of etoxazole to both mallard duck and bobwhite quail (acute 

oral LDso > 2000 mg/kg bw with NOEL = 2000 mg/kg bw for mallard duck, acute 

dietary LCso > 5200 ppm with NOEC = 5200 ppm for both mallard duck and bobwhite 

quail), low toxicity to passerines is also expected. Thus, Valent proposes that the Agency 

remove the acute oral toxicity study with passerine species from the anticipated data needs. 

EFED Response: EFED acknowledges the findings of the SETAC poster. The issue in the 

case of etoxazole, as indicated by the Problem Formulation is that currently only one acute 

avian oral toxicity study is available. The Federal standard for outdoor registrations ( 40 CFR 

Part 158) is two studies with two different species (as is the case with the subacute dietary 

studies). This is to provide any information on the differential toxicity of avian species across 

the acute oral route of exposure. As Valent may be aware, in 2007, the 40 CFR included the 

passerine acute oral study as the new standard in addition to a study with the mallard duck or 

northern bobwhite quail. 

In the case of etoxazole, the case for no impact on risk assessment cannot be made based on 

the following: 

First, as indicated in the PF, the sole passerine acute oral study available for this class of 

chemicals (red winged blackbird study for diflubenzuron) shows increased toxicity over both 

northern bobwhite quail and mallard duck. While this is only one study, this data suggests 

that passerine species may be more sensitive to this class of chemicals including etoxazole. 

Second, as also indicated in the PF, based on current use rates, a passerine study would only 

have to show a two-fold greater sensitivity to the currently available study for mallard duck 

to trigger listed species concerns, twelve-fold greater to trigger non-listed species concerns. 

As indicated by the SET AC poster provided by Valent, for the studies that were completed, a 

passerine endpoint being lower (i.e. more toxic) than the mallard duck occurred 3 3% of the 

time (16/48), certainly within the realm of plausibility and further evidenced by the above 

mentioned study within the same chemical class as etoxazole. 

Based on the rationale provided above and reiterating the fact that only one acute oral toxicity 

study for etoxazole is currently available, EFED recommends retaining the avian acute oral 

toxicity study with a passerine study as part of its anticipated data needs for etoxazole. 

2. Valent Comment: On the anticipated data needs of a Seedling Emergence Study and 

Vegetative Vigor Study OCSPP 850.4100 and OCSPP 850.4150): 

Valent does not consider additional studies are necessary. As mentioned in EFED's 

Preliminary Problem Formulation document, there are currently Tier I Seedling emergence and 

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Tier 1 Vegetative vigor studies available for etoxazole which are both classified as acceptable. 

The NOECs for each study were 0.06lbs a.i/acre. The maximum single application rate for 

etoxazole is 0.18 lbs a.i./acre. Valent has conducted a screening level risk assessment using EPA 

TerrPlant (ver. 1.2.2- attached Appendix 2). There are no LOC exceedances in this screening 

level assessment, and therefore low risk to non-listed and listed (endangered) terrestrial plants is 

expected from the use patterns of etoxazole. Thus, Valent proposes that the Agency removes 

these studies from the anticipated data needs. 

EFED Response: As indicated in Valent's own analysis provided in their response, an 

increase of application rate to the current maximum application rate would yield RQs roughly 

two fold lower than a level of concern exceedance. This analysis however assumed that 

increasing the application rate by three fold would not alter the toxicity already determined 

from previous studies. There are uncertainties in that statement however as Valent's analysis 

assumed the EC2s was the application rate when in fact it was estimated this value was above. 

As stated in the 40 CFR Part 158 and the current terrestrial plant guidelines listed above, 

testing is preferred on the typical end use product (TEP) rather than technical grade active 

ingredient (TGAI) which the available studies for etoxazole used. This is for several reasons 

but primarily because the TEP is more akin to the actual product that will be used in the field 

and EFED would be interested in non-target plant effects from that formulation. Furthermore, 

TEP formulations often have inert ingredients in the formulation that may increase the toxicity 

to terrestrial plants above the level that TGAI does. It is due to this uncertainty as well as the 

maximum application rate increasing three fold over the rate that available studies were 

previously conducted that EFED recommends retaining the seedling emergence and 

vegetative vigor studies as anticipated data needs. EFED reminds Valent these studies should 

be conducted with TEP. 

3. Valent Comment: On the anticipated data needs pollinator data requests (Field Testing for 

Pollinators, honey bee 21-d chronic larval toxicity test, 10-day adult chronic oral toxicity, and 

residues in pollen and nectar studies): 

Etoxazole is also undergoing reregistration under the EU Annex I renewal process according to 

EU regulation EC 11 07/2009. Valent's parent company, Sumitomo Chemical Corporation 

Company, Limited has conducted studies to evaluate the safety to honey bees. Valent will 

submit the available studies and a safety assessment for the use of etoxazole. All data to date 

indicate that etoxazole is of low toxicity to honey bees in both laboratory and semi-field tests. 

EFED Response: EFED looks forward to the submission and receipt of these studies. It is 

not explicitly stated in Valent's response as to which studies of those that were listed as 

anticipated data needs would be part of the reference coming submission. It is worth 

reiterating the fact that EFED is interested particularly in studies that characterize the toxicity 

of etoxazole to honey bee brood as etoxazole is classified as a chitin biosynthesis inhibitor. 

4. Valent Comment: 

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Section 6. b: Receptors- Effects to Terrestrial Organisms 

Valent disagrees with the chronic endpoints for bobwhite quail given in Table 8, Page 20 in the 

Preliminary Problem Formulation (2014). (NOAEC: 286 ppm, LOAEC: 958 ppm). An analysis 

is presented as to how the reviewer's conclusions was based on numerical values per hen 

accompanying a statistical difference but these numbers should be divided by numbers of eggs 

set due to those eggs removed to determine eggshell thickness. Valent concludes by stating that 

both OCSPP 850.2300 and OECD 206 both recommend analyzing recent viable embryos or 

hatchlings of eggs set ,_ 

EFED Response: EFED acknowledges receipt of the rationale provided by Valent and if it 

is determined that a new statistical analysis for this study is needed, it will be completed ahead 

of the time of the Preliminary Risk Assessment as well as any potential changes to the 

endpoint used for risk estimation. 

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