1 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION

AGENCY

PC Code: 120301

DP Barcode : 430590

Date: February 1 1 , 2016

MEMORANDUM

SUBJECT: Thidiazuron

– EFED R esponse s to C omments from Bayer CropScience on the

Draft Environmental Fate and Ecological Risk Assessment in Sup port of Registration Review . Docket ID: EPA

– HQ

– OPP

– 201 5

- 0381

- 0008

FROM: Steve Carey, Biologist William P. Eckel, Ph.D., Senior Science Advisor

Environmental Risk Branch VI Environmental Fate and Effects Division ( 7507P)

REVIEWED

BY: Monica Wait, RAPL

Environmental Risk Branch VI

Environmental Fate and Effects Division (7507P)

THROUGH: Mark Corbin, Branch Chief

Environmental Risk Branch VI Environmental Fate and Effects Division ( 7507P)

TO: Khue Nguyen , Chemical Review Manager

Neil Anderson , Branch Chief Risk Management and Implementation Branch I

Pesticide Re

- Evaluation Division (7508P)

This memorandum transmits the Environmental Fate and Effects Division’s ( EFED ) respo nse to comments submitted by Bayer CropScience (BCS) regarding the Registration Review Joint

Problem Formulation and Draft Risk Assessment of the Environmental Fate and Ecological Risk

of Thidiazuron (DP 424977, 6/16/2015)

. The following pages restate comments made by Bayer CropScience, in summary or verbatim

, with each comment followed by EFED’s response.2 

# Bayer CropScience Comments

Joint Problem Formulation and Draft Risk Assessment of the Environmental Fate and Ecological Risk of Thidiazuron

Docket ID: EPA

- HQ

- OPP

- 201 5

- 0381

- 0008

1. Draft Risk Assessment p. 2; bullet 3 & 4 (also appears in paragraph 1, on p p . 23

- 24, Section

6.4. Excerpt from the Draft Risk Assessment (DRA) : “SIP v. 1.0 indicates drinking water exposure alone.... is a potential pathway of concern for birds foraging in thidiazuron

- treated cotton fields on a chronic exposure basis... these findi ngs also apply to terrestrial

- phase amphibians and reptiles.”

BCS Comment: BCS agrees with the Agency that risk to bird species is unlikely. BCS would also like to point out that chronic avian exposure through drinking water alone is minimal. SIP

v.1.0 is a tier I model that uses overly conservative assumptions.... this scenario is unlikely to

occur.

The mallard, a large bird (1000g) with a NOEC of 298 mg/kg diet was used in the assessment, which was adjusted to a body weight exposure of 14.8 mg/kg bw fo r a 20 g bird. This calculated value represents an inflated exposure ratio as the mallard adjusted to its body weight exposure resulted in a NOEC of 28 mg/kg bw. Using this scenario, SIP results in....”NOT a potential concern for birds”. In addition, the b obwhite quail adjusted to its body weight has a NOEC of 84 mg/kg bw, where SIP indicates... is “NOT a potential concern for birds”.

EFED Response : EFED agrees with BCS that there is not a potential concern for birds through drinking water alone. Thus, in future risk assessment s , EFED will provid e additional characterization of the potential chronic exposure to birds from drinking water alone.

The SIP model is int ended as a conservative screen to determine if the drinking water route of exposure, by itself, might be of potential concern. However, the results of this screen are not meant to provide a definitive analysis about any potential concern. SIP assumes that the chemical is present in the source water at its solubility limit (31 mg/L for thidiazuron), that 100% of drinking water needs are obtained from that source, and that the most sensitive bird, weighing 20 grams, is exposed.

EFED agrees with BCS that the tested birds when adjusted to its dose

- based body weight are 28 and 84 mg/kg

- bw for the mallard and bobwhite quail, respectively. However, to account for all birds, not just the large birds, SIP conservatively uses the 20 g bird (small bird) rather than t he large tested birds in its equation, which resulted in a potential concern because it gives the lowest

dose

- equivalent toxicity value.

Yet, i t is highly unlikely that the chemical would be present at its solubility limit to cause a potential concern fo r small birds

. Relaxing this assumption to half the solubility limit (15 mg/L),

SIP indicates no concern for chronic effects to all birds

. Because even this exposure is very unlikely, EFED does not have any concern for bird chronic effects (including ter restrial

- phase3 amphibians and reptiles) from drinking water alone, given the current toxicity data (NOAEC of 298 mg a.i./kg

- diet).

2. Draft Risk Assessment p. 5; last paragraph Excerpt from the DRA : “ ...it is uncertain whether passerines may be more or less sensitive to this chemical [thidiazuron].... .”

BCS Comment : BCS asks the Agency to consider the need of additional birds tested based on animal welfare and likelihood of effects noted that would impact the risk assessment.

The maximum application rates of thidiazuron were modeled using T

- REX .... the upper bound dietary

- based Kenaga residue estimates on short grass of 69.65 mg a.i./kg diet was less than

1/10 th of the highest concentration tests or near levels where effects on body weight or food consumpti on were observed.... Additionally, thidiazuron has an acute toxicity classification of practically nontoxic to bobwhite quail.

EFED Response: EFED is in need of a study with passerines to address all the uncer tainties in the toxicity profile for all bird s when exposed to thidiazuron

. An acceptable LC 50 has not been established for acute exposure to passerines, which normally results in a presumption of risk for small birds until available data show differently; h owever, in absence of such data, EFED agree s with BCS that the likelihood of effects to small birds would be unlikely and an acute oral study with passerines would not significantly impact the risk assessment for small birds

. Given the potential differences in metabolic rates and pathways which may influence sensitivity compared to other tested birds, toxicity data for passerines are required under 40 CFR Part 158 data requirements. For thidiazuron, no mortality was observed in the acute oral and/or dietary toxicity studies for upland game and wetland species at concentrations of 3,150 mg/kg

- bw or ≥5,000 mg/kg

- diet, respectively. While no clinical signs of toxicity were observed in the bobwhite acute dietary study, effects on bo dy weight and food consumption were reported in the bobwhite acute oral study at 3,150 mg/kg

- bw with no effects observed at 2,150 mg/kg

- bw. The highest dose

- based EEC of 79.32 mg/kg

- bw (for a 20

- g bird) for a thidiazuron application to cotton is approxima tely 27 times lower than where no effects were observed and 40 times lower than the highest dose tested with no mortality in the bobwhite acute oral study. As such, given the relatively low toxicity observed in the available acute avian studies and the di fference between the tested doses and the EECs, and an acute oral study with passerines is not expected to significantly impact the risk assessment for birds. For those reasons, a study with passerines is

not recommended. As a result, an uncertainty is int roduced since the actual toxicity to the passerines is unknown.

3. Draft Risk Assessment p. 10; first paragraph: Excerpt from the DRA : “ .....[drinking water] is a concern for birds foraging in thidiazuron treated cotton fields on a chronic exposure basis ...”

BCS Comment :

- See first comment in section “EPA: page 2; bullet 3 & 4...”

-

EFED Response : See EFED ’s response to #1 above.

4. Draft Risk Assessment p. 10; last bullet: Excerpt from the DRA : “ Thidiazuron is expected to adversely affect the survival and growth of terrestrial plants, mainly dicots ”4 BCS Comment : In the draft risk assessment, lettuce...represent s the sensitive surrogate species for thidiazuron exposure to all non

- target terrestrial plants. ...Lettuce, followed by cucumbers, were the only sensitive species noted in the vegetative vigor study.

All other species tested resulted in NOEC and EC 25 val ues greater than or equal to the highest level tested ( 200 g a.i./ha ). This study (MRID 45921501) reported the lettuce EC 25 value of 1.5 g

a.i./ha , however, the biological No Observed Adverse Effect Concentration (NOAEC) differs

from 0.2 g a.i./ha . MRID 45 921501 repor ts a NOAEC of 1.5 g a.i./ha (0.001 lb a.i./A)

co rresponding to 22% inhibition of shoot dry weight in lettuce. The current Draft Risk Assessment reported a NOAEC at 0.2 g a.i./ha ( 0.0002 lb a.i./A )

, which corresponded to 12%

reduction of shoot d ry weight in lettuce. Evaluation of lettuce shoot dry weight resulted in 12, 27, 12, 22, and 40% inhibition as compared to the controls, corresponding to test levels of 0.20, 0.38, 0.75, 1.5, and 3.0 g a.i./ha. A lack of dose response was observed in this dataset, supported by the only significant inhibition levels spaced at the second lowest (0.38 g a.i./ha) and highest dose levels (3.0 g a.i./ha). The current NOEC selection of 0.2 g a.i./ha by the Agency is a highly conservative representation of the no e ffects level, as the sensitivity was limited to lettuce, and test levels of 0.75 g a.i./ha and 1.5 g a.i./ha were not found significantly differently from controls. Overall, the lack of observed dose response and limited sensitivity (2 out of 10 plant

spec ies tested), should be considered in risk characterization for offsite exposure.

EFED Response: The approach is conservative. The Agency screens whether there are any potential risks to a broader taxonomic group, as for example, terrestrial plants

, by con servatively using lettuce as the sensitive surrogate species. Also, these tested species and the sensitive surrogate species are also surrogates for off

- site non

- target plants and other native species, not just for other crop species.

The Agency agrees t hat lettuce and cucumber were the only sensitive species in the studies; however, EFED’s approach to assess risk concerns for terrestrial plants is to use the most sensitive species in the risk assessment regardless that only two out of ten plant species w ere sensitive to thidiazuron. In addition, the incident reports suggest plant damage from exposure to

thidiazuron

. T ogether, the Agency conservatively assumes risk to the broader group, terrestrial plants, from exposure to thidiazuron. The Agency did note that dicots specifically were at risk.

Additionally, an evalua tion of the statistical models used in the Data Evaluation Records (DER)

for the terrestrial plant studies reviewed by the Agency (MRID 45921501 ) with lettuce indicated

observation differences between the statistical tests, Williams and Dunnett . T he Dunnett’s test

observed statistical ly significant differences in the second lowest and the highest treatment levels when compared to control, while William s ’ t est observed a dose

- dependent response with significant differences in all except the lowest treatment level when compared to control

. Due to

the monotonic trend of the dose

- response r elationship observed in William s ’ test

, it is the correct

choice of test for evaluating this study with lettuce dry weight because the power of a William s test is much larger than the power of the Dunnett test under monotonicity. Thus, EFED is satisfied with its current NOAEC selection for lettuce dry weight.5 5. Draft Risk Assessment p. 14; Section 3.1: Excerpt from the DRA : “ The major degradates of thidiazuron include photoproduct I (photothidazuron, Photoproduct II (phenylurea), and thiazoylurea”.

BCS Comment : The major degradates of thidiazuron include photoproduct I (photothidazuron, Photoproduct II (phenylurea ), and thidiazolurea ”.

EFED Response: The t ypographical error will be corr ected in future risk assessments

.

6. Draft Risk Assessment p p . 14

- 15; Section 4: Excerpt from the DRA: “Aquatic photodegradate AE F132347 (photoproduct I) is moderately toxic and more toxic than the parent compound to freshwater fish... (from page 18, section 6.1)...AE F132347 was used as the stressor for freshwater fish as it was more toxic than the parent compound”.

BCS Comment: In section 4.1, Table 3, the photodegradate AE F132347 is used to represent a more conservative toxicity endpoint than the parent technical grade active ingredient for freshwater fish. Estimated environmental concentrations were generated from the parent compound. These EECs represent a higher concentration than would be present from photodegradate alone. Using the photodegradate endpoint for [freshwater] fish compared to the EECs for the parent to generate a risk quotient should include a discussion of th e conservative assumptions of this approach in the risk assessment.

EFED Response: EFED appreciates BCS’s recommendations for consideration . H owever, t he reason EFED used the parents EECs rather than calculating a lower concentration was to show

that the most conservative scenario did not result in any potential concerns for freshwater fish exposed to the most conservative toxicity value or EEC value. Hence, for brevity, all other scenarios or the conservative approach were not discussed.

7. Draft Risk Assessment p. 15; Section 4.1, Table 3, superscript 3 (also appears on p. 22, Section 6.4, third paragraph) Excerpt from the DRA: “The ACR using rainbow trout acute and fathead minnow chronic data is 5.6, assuming the values are definitive. Empl oying the ACR of 5.6 to the Sheepshead minnow LC 50 of >36 mg a.i./L calculates a chronic toxicity value (NOAEC) of 6.4 mg a.i./L for estuarine/marine fish.

BCS Comment: In the calculation of the ACR for chronic toxicity to estuarine/marine fish, an

ACR of 5.6 was determined. BCS calculated an ACR using endpoints defined in table 3, which resulted in an ACR of 1.2, calculating a chronic toxicity value of 30 mg a.i./L for estuarine/marine fish. BCS agrees with the Agency that there is minimal risk for

estuar ine/marine fish.

EFED Response: The ACR calculations using freshwater fish data were calculated using toxicity data of the parent compound, not from the photodegradate AE F132347 data. The toxicity value (not shown in Table 3) for the parent compound was >32 mg/L (MRID

42069202 ). EFED will clarify the footnote with an insertion in the sentence of ‘(>32 mg/L; parent compound)’ after ‘rainbow trout acute’ in future risk assessments

.6 8. Draft Risk Assessment p. 16; Section 4.2, Table 4: Excerpt from the DRA: “Terrestrial plants, Vegetative Vigor, Lettuce (Dicot) endpoints of EC 25 = 0.001 lb a.i./A and NOAEC = 0.0002 lb a.i./A (MRID 45921501)”

BCS Comment: See comment above “EPA Statement, Page 10; last bullet”

–

EFED Response: See EFED ’s Response # 4 above

.

9. Draft Risk Assessment p. 21; Table 11: Excerpt from the DRA: “Maximum Drift Loadings at Specific Distances for Terrestrial Areas Near Thidiazuron Use Areas Using Default

Conservative Scenario”

BCS Comment: The simulation results in this table are based on default conservative scenario, i.e., high boom height and very fine

- to

- fine droplet size. ...BCS’s label (EPA Reg. No. 264

- 634) specifies a larger drop size (“medium or coarser”) than the default and a boom height (<24 inches) that would be more appropria tely represented in the model by a low boom height. These differences in parameterization have an effect on the results in Table 11, as well as those in Table

17....

EFED Response: Specifications on the label to control spray drift should be consistent acro ss all

thidiazuron end

- use product labels . In absence of consistent language across all product labels,

label language or lack of specific statements on another end

- use product will trigger the use of

the default conservative scenario in EFED’s risk assess ment . Until specifications are consistent across thidiazuron labels, EFED cannot remove the default conservative scenario.

10. Draft Risk Assessment p. 26; Table 16, superscript 3: Excerpt from the DRA: “Corresponding listed toxicity thresholds (NOAEC) were 0.18, 0.004, 0.18 and 0.0002 lb

a.i./A...

BCS Comment: See comment above “EPA Statement, Page 10; last bullet”

—

EFED Response: See EFED ’s Response # 4 above

.

11. Draft Risk Assessment p. 26; Table 16, superscript 4: Excerpt from the DRA: “Values in bold are LOC exceedances (Exceeds the LOC of 1 for potential risk to non

- listed and listed plant species)”

BCS Comment: All values are bolded in this table.

EFED Response: This typographical error will be corrected in future risk assessments

.

12. Draft Risk Ass essment p. 26; Paragraph 2: Excerpt from the DRA: “While likely for one plant species, possible for one species and not likely for the other 8 tested species, it is anticipated that the potential risk to terrestrial plants is limited to susceptible species when exposure to off

- site drift”7 BCS Comment: In addition to the discussion above in comment “EPA Statement, Page 10: last bullet”, it is important to reiterate that no more than two dicot species triggered potential concern

for non

- target plants. ....the Agency should consider multiple factors as well as conservative assumptions in characterizing risk to non

- target terrestrial plant species....the following [list of factors not included]...would be reduced in considering the conservative nature of the current assumptions.

EFED Response: EFED agrees ; however, if Table 18 was revised in the draft risk assessment due to a typographical error as discussed in #14 below, two additional dicot species would potentially be at risk when exposed to off

- site drift . The ex cerpt would be revised to, “While exposure to spray drift only is likely for four out of the ten tested plant species and not likely for

the other six tested species, it is anticipated that the potential risk to terrestrial plants is limited to susceptible species when exposure to off

- site drift”

13. Draft Risk Assessment p. 27; Table 17: Excerpt from the DRA: “Spray Drift (Terrestrial) Assessment for List ed and Non

- listed Terrestrial Plant Species”

BCS Comment: Table 17 presents AgDRIFT simulation results for ground application using both very fine to fine and fine to medium/coarse droplet size categories. The BCS’ label (EPA Reg. No. 264

- 634) instructs t hat the product should be applied with “...medium or coarser spray...” Therefore, the fine to medium/coarse drop size category is the more appropriate size category for AgDRIFT modeling and in fact a very fine

- to

- fine application would be an off

- label

use. The use of the fine to medium/coarse category...[is] overly conservative given the BCS label

restrictions.

The AgDRIFT modeling of ground application...is also based on the assumption of a high boom height. ...The low boom height should be considered for use in the AgDRIFT modeling.

The simulation results for aerial application was based on the AgDRIFT Tier I screening model, higher tier refinement should be considered using AgDRIFT Tier III or AGDISP.

EFED Response: Until specifications in the label to control spray drift are consistent across all

thidiazuron end

- use product labels, EFED cannot remove the default conservative scenario. For

the medium

- coarse droplet size scenario, EFED agrees the low boom height should have been

considered when modeling the scen ario ; however, the input will be considered in future risk assessments. Higher tier refinements can be considered

, but additional specifications are needed

and should be consistent across all thidiazuron labels before AgDRIFT Tier III or AGDISP can

be used

.

14. Draft Risk Assessment p. 28; Table 18: Excerpt from the DRA: “Terrestrial Area EEC”

BCS Comment: The Terrestrial Area EEC at the edge of field given in Table 18 should be 0.1 lb a.i./A, the same value given for that distance in Table 11. The use of 0.1 as an EEC for edge of field does not change any sensitive species, or the outcome of the risk chara cterization, but should be updated for consistency among the modeling results presented in multiple tables.8 EFED Response: EFED agrees with BCS that the EEC in Table 18 should be 0.1 lb a.i./A not
0.01 lb a.i./A

, as was reflected in th e original risk ass essment . Below EFED has recreated Table

18 from the risk assessment (DP 424977

, 6/16/2015 , page 28 ) using the corrected value (0.1 lb a.i./A)

. The revision would indicate two additional plant species are potentially at risk when exposed to s pray drift tha t moves off

- site. The two additional plant species affected are soybean

and tomato.

Table 18. Spray Drift (Terrestrial) Assessment for Remaining Nine Terrestrial Plant Species using Listed Toxicity Endpoint a

Species Dry Area EEC (lb a.i./A) Toxicity (l b a.i./A) Listed Plant RQ Distance from Edge of Field RQ Falls Below

LOC At Edge

of Field 250 feet from Edge of Field At Edge of

Field 250 feet from Edge of Field Terrestrial plants inhabiting dry areas (Default scenario for aerial application)

Corn

0. 1 0.0073 0.178 b 0. 6 0. 0 4 0 feet

Onion 0.18 b 0. 6 0. 0 4 0 feet

Oat 0.18 b 0. 6 0. 0 4 0 feet

Wheat 0.178 b 0. 6 0. 0 4 0 feet Cabbage 0.178 0. 6 0. 0 4 0 feet

Cucumber 0.0056 1 8 1

. 3 328 feet Soybean 0.011 9 0.7 174 feet

Tomato 0.0223 4 0.3 85 feet Turnip 0.178 b 0. 6 0. 0 4 0 feet

a Based on NOAEC.

b Highest test concentration tested. No effects to the species.

*Value in bold indicates the LOC is exceeded.

15. Draft Risk Assessment p. 28: Table 18, superscript “b”: Excerpt from the DRA: “Highest test concentration tested. No effects to the species”

BCS Comment: MRID 45921501 indicates that cabbage should also be marked with superscript

“b”.

EFED Response: EFED agrees. This typographical error will be corrected in future risk

assessments

.

16. Draft Risk Assessment p. 31, Section 7.1; Table 20: No listing is provided for Storage Stability Study (TFD).

BCS Comment: A freezer storage stability study for soil has been submitted previously to the Agency. [MRID 4445070 1; Citation provided]. This Freezer Storage Stability study was carried out in parallel with the TFD study MRID 44454001 by Campbell and Singer (1997).

EFED Response: EFED thanks BCS for providing the citation for the previously submitted storage stabilit y study, and we will review MRID 44450701, as appropriate.9 17. Draft Risk Assessment p. 36; Table 22: Excerpt from the DRA: “Adult Honey Bee Acute Oral Toxicity [data needed for assessment marked

– yes]”

BCS Comment: Adult honey bee acute oral toxicity studies are identified in the draft risk assessment as MRID 46203501 for the TGAI, and MRIDs 46203518 and 46203519 were submitted to the Agency on an SC formulation of Thidiazuron.

EFED Response: EFED agrees that adul t honey bee acute oral toxicity studies were submitted to the Agency and available for the assessment. EFED is not asking for new adult honey bee oral toxicity studies and this error will be corrected in future risk assessments . While adult honey bee

acute contact and oral toxicity studies were submitted, EFED is still in need of the complete set of honey bee toxicity data to conduct a risk assessment for pollinators exposed to thidiazuron

.

18. Draft Risk Assessment p. 40; Appendix II SWCC: Excerpt from the D RA: “Summary of water modeling...”

BCS Comment: Page 40 of the Draft Risk Assessment was inserted into the document as a portrait orientation; however, text is displayed in landscape orientation. Please update.

EFED Response: This error will be corrected in future risk assessment s . However, the full text
of the excerpt

, which was cut

- off on page 40 of the risk assessment is provided below :

“ 

## Summary of Water Modeling of T hi di azuron and the USEPA

Standard Pond

Estimated Environmental Concentrations for thidiazuron are presented in Table 1 for the USEPA
standard pond with the MScottonSTD field scenario. A graphical presentation of the year

- to

year peaks is presented in Figure 1. These values were generated with the Surface Water
Concentration Calculator ( SWCC Version 1.106). Critical input values for the model are

summarized in Tables 2 and 3.

This model estimates that about 4.1% of thidiazuron applied to the field eventually reaches the
water body. The main mechanism of transport from the field to the wat er body is by runoff
(66.1% of the total transport), followed by spray drift (30.6%) and erosion (3.24%).

In the water body, pesticide dissipates with an effective water column half

- life of 725.0 days.
(This value does not include dissipation by transport to the benthic region; it includes only
processes that result in removal of pesticide from the complete system.) The main source of
dissipation in the water column is metabolism (effective average half

- life = 725 days) followed
by volatilization (9.381325E +08 days).

In the benthic region, pesticide dissipates very slowly (300.6 days). The main source of
dissipation in the benthic region is metabolism (effective average half

- life = 300.6 days). The
vast majority of the pesticide in the benthic region (98.77% ) is sorbed to sediment rather than in
the pore water. ”