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

Febr uary 4

, 201 6

PC Code s : 147500
MEMORANDUM DP Barcode: D 431158

SUBJECT : EFED Response to Registrant Comments Regarding the Registration Review Problem

Formulation for Pinoxaden

FROM : N.E. Federoff, Wildlife Biologist
Environmental Risk Branch 2
Environmental Fate and Effects Division (7507P)

THRU : Brian Anderson, Chief
Environmental Risk Branch 2
Environmental Fate and Effects Division (7507P )

T O : Neil Anderson , CRM
Pesticide Re

- Evaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the responses to the Registrant (Syngenta Crop Protection, LLC ) comments regarding the preliminary problem

formulation of pinoxaden

.

EPA statement

Additional

Information Requested p. 3 EFED requests that the registrant send copies of three ecotoxicity studies that support the adjuvant Adigor.

Syngenta Comment : Syngenta will provide a courtesy copy of each study report (MRID# 46421506, 46421507, 46421510) in a separate submission.

EPA Response : EFED has received the submission and the studies are currently at the

contractor for review.

EPA statement

5.1 Effects to Aquatic Organisms Table 6. p. 22 Rainbow Trout (Oncorhynchus mykiss) 96 hr LC 50 = 12.3 ppm (407855 100EC) Slightly

toxic 472932

- 02,

2007

Syngenta Comment : The study cited above (MRID 47293202) was conducted using technical pinoxaden (99.1% purity) and not the 100EC formulation. This study was deemed acceptable by the Agency (p. 58) and should fulfill the data gap for acute test with a cold water fish. In order to fulfill the warm water fish requirement (previous study, MR ID 46203036, was classified as supplemental), Syngenta will submit a 96

- hour acute toxicity study with the fathead minnow using technical pinoxaden (conducted in 2008).

EPA Response : EFED will review the data once submitted. EFED agrees that the study (MRID 472932

- 02) used NOA

- 407855 Technical (pinoxaden).Page 2 of 5 EPA statement

5.1 Effects to Aquatic Organisms Table 6. p. 22 Freshwater Acute invertebrates

Water Flea ( Daphnia m agna ) 48 hr EC 50 = 6

ppm (A12127R form + adj) Moderately

toxic 462030

- 31,

2003

Syngenta Comment : The cited study (MRID 46203031) was conducted using the Pinoxaden 100EC formulation (A12303C) plus the ADIGOR (A12127R) adjuvant. However, per the study report, the 48

- hour EC 50 on Daphnia magna was calculated to be 8.5 mg [A12303C+ A12127R]/L rather than 6 mg [formulation + adj]/L cited above.

EPA Response : The study was classified as supplemental and did not fulfill guideline requirements. It was considered invalid by the PMRA. Expressed as Pinoxaden, the EC 50 was reported as 0.132 ppm ai total

. Expressed as A12303C , the EC 50 was reported as 1.93 ppm nominal.

EPA statement

5.1 Effects to Aquatic Organisms Table 6. p. 23 Green Algae ( Pseudokirchneriella subcapitata ) EC 50 = 0.035ppm NOAEL= 0.0037 ppm (10.10 EC) 462031

- 21,

2003

Syngenta Comment : The study cited (MRID 46203121) was conducted using the 100EC formulation (A12303C) plus the ADIGOR (A12127R) adjuvant. The values reported above are

based on calculations of measured A12303C concentrations reported in the study. Syngenta believes that presenting the results in ppm active ingredient (ai) mischaracterizes the toxicity of pinoxaden to green algae as the effects noted in the study are not likely t he result of the presence of pinoxaden. Syngenta has conducted a 96

- hr study with Pseudokirchneriella subcapitata using pinoxaden technical (study to be submitted to the Agency) which resulted in an EC 50 of 3.9 mg
ai/L.

Syngenta will submit two algal toxicity studies on Pseudokirchneriella subcapitata , the first with the technical pinoxaden (NOA407855) and the second with the NOA407854 degradate. Both
studies were conducted for 96

- hours as required by the guideline to fulfill the green algae data

req uirement. The previous green algal studies submitted to the Agency were conducted for 72

hours.

EPA Response : EFED will review the data once submitted.

EPA statement

5.2 Effects to

Terrestrial Organisms p.

24 Tests with the honey bee exposed via oral and contact routes of exposure were conducted with parent pinoxaden, the 10.1% ai formulation, the formulation with adjuvant, and the adjuvant alone. Parent pinoxaden is nontoxic to bees by both oral and contact ro utes of exposure, but the formulated product is moderately toxic via contact exposure. Only the formulation displayed toxicity that might be of concern, but an LD was not established (LD 50 >6.3 μg ai/bee) nor shown to exceed 11 μg ai/bee.Page 3 of 5 Syngenta Comment : The pinoxaden 100EC formulation study cited (MRID 46203110) included both contact and oral routes of exposure. No mortality was observed at the highest treatment level in the contact study (6.4 μg ai/bee). However, the oral exposure resulted in 43% mortality at the highest treatment level (19.1 μg ai/bee). Overall, these results suggest that pinoxaden is practically non

- toxic to honey bees (i.e., LD 50 > 11 μg ai/bee).

EPA Response : EFED agrees that the 100EC formulation of pinoxaden seems to be practically non

- toxic to bees through contact. However, an acceptable oral lethal dose was no t
established for the formulation.

EPA statement

5.2 Effects to

Terrestrial Organisms p.

24 In a 48

- hour acute oral LC 50 test, the honey bee was exposed to

NOA

- 407855 (Pinoxaden 100EC) at nominal concentrations of 0 (negative and solvent controls), 6.3, 13, 25, 50 and 100 μg ai/bee. By 48 hours, there was 0% mortality in the controls and 3, 0, 0, 3 and 3%
in the 6.3, 13, 2 5, 50 and 100 μg ai/bee treatment groups, respectively.

The LC 50 and NOAEC values were >100 and 100 μg ai/bee, respectively. However, the recovery of NOA

- 407855 in the 50% sucrose solution was determined during the definitive acute oral toxicity test. The nominal 6.3, 13, 25, 50 and 100 μg ai/bee treatment levels yielded recoveries of 86, 75, 42, 15 and 6.5% of nominal, respectively. The nominal 6.3 μg ai/bee treatment diet was clear following preparation, the nominal 13 and 25 μg ai/bee diets were

opaque, and the nominal 50 and 100 μg ai/bee diets contained particulate matter and there was residue on the glass of the volumetric flask used for preparation. The particulate matter and residue on the preparation flasks could account for the low recoveries obser ved at the three highest treatment levels (6.5

- 42% of nominal). Syngenta Comment : The study cited (MRID 47293203) used pinoxaden technical (NOA407855) rather than pinoxaden 100EC as cited above. EPA classified this study as invalid
based on the recove ry of pinoxaden in the 50% sucrose solution during the test. However, the nominal doses used in the study of 6.3, 13, 25, 50 and 100 μg ai/bee required nominal concentrations in the test solution of 252, 500, 1000, 2000, and 4000 mg ai/L which were above the water solubility limit for pinoxaden (200 mg/L). Solubility of test material is a significant concern in these studies considering the feeding solution contains 50% sucrose which limits the
amount of water available to dissolve the test material. Eve n with the use of 1% acetone in the study, the practical limit of solubility of the test material is approximately 500 mg ai/L which is equivalent to the acute oral dose of 13 μg ai/bee. Based on these results, the LD 50 can be estimated to be greater than 13 μg ai/bee especially considering only 43% mortality was observed in the 19 μg ai/bee (converted dose) from MRID 46203110. Therefore, technical pinoxaden can be considered practically non

- toxic to honey bees. Repeating the study would likely result in similar difficulties in dissolving the test material and not result in toxicity below the practical limit of solubility.

A previously submitted study (MRID 46203109) using pinoxaden technical (NOA407855)

resulted in an acute oral LD 50 > 100 μg ai /bee. This study was classified as supplemental. BasedPage 4 of 5 on submitted studies, Syngenta believes that the acute oral honey bee Tier 1 requirement has been satisfied and that further testing would not provide additional value to the risk assessment.

EPA Response : EFED agrees that MRID 46203109 resulted in a value >100 ug ai/bee (actually tested as >200 ug ai/bee ) for an acute oral test. Also, in cases where solubility in sucrose solutions is problematic, a suspension can be tested or the conducted study s hould be shown that it was tested with a stable and homologous suspension. In this case, if this can be shown, further testing would likely not be required.

EPA Statement

Section 8. Endangered Species Assessments. p.

28 Consistent with EPA’s res ponsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides. Syngenta Comment: Simple, deterministic screening

- level assessments can facilitate rapid initial screening/exclusion criteria for a pesticide active ingredients’ potential to adversely affect listed (threatened or endangered species) and non

- listed species. Screening

- lev el assessments are conservative by design (to minimize potential type II errors (failure to reject a false null hypothesis of de minimus risk) through incorporation of safety factors and assumptions regarding exposure. If a pesticide exposure results in a risk quotient (RQ) below a predefined level of concern (LOC), then the potential risks are considered de minimus and unlikely to jeopardize the existence of a listed species. If, a RQ is generated that exceeds the LOC, additional higher

- tier scientific inf ormation may be incorporated to refine the risk assessment and more accurately reflect potential exposures and effects to reduce potential type I errors (falsely rejecting the null hypothesis of de minimus risk). This information includes community
level e ffects data, environmental fate, higher tier exposure modelling, monitoring data, geospatial proximity analysis, species biology data, and a variety of refined modelling and assessment procedures. In addition, higher

- tier risk assessments should employ pr obabilistic techniques to more accurately characterize risk. Moreover, where possible and appropriate, risk assessments should consider assemblage

- level effects (populations, communities, and ecosystems) rather than deterministically oriented single specie s approaches. A summary of the types of higher

- tier data and assessment refinements available to more accurately and realistically evaluate potential risks to endangered species is provided in MRID# 49200601 and Brain et al. (2015) (Reference). Syngenta wi ll submit a courtesy copy of this publication concurrently to EPA.

Reference: Brain R, Teed S, Bang J, Thorbek P, Perine J, Peranginangin N, Kim M, Valenti T, Chen W, Breton R, Rodney S, and Moore D. 2015. Risk Assessment Considerations With Regard to the Potential Impacts of Pesticides on Endangered Species. Integrated Environmental Assessment and Management 11: 102

- 117.

EPA Response : In collaboration with the U.S. Fish and Wildlife Service and National Marine Fisheries Service, EPA is continuing to develop and refine the interim scientific methods for evaluation of the potential risk of pesticides to threatened and endangered species, based on the April 2013 National Academy of Science Report recommendations. These methods arePage 5 of 5 currently being developed and vetted in the context of three pilot chemicals (chlorpyrifos, diazinon, and malathion). Once vetted, these new methods will be inco rporated, as appropriate, for other chemicals being evaluated as part of the registration review program.