UNI T ED STATE S ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

. D.C. 20460

April 12, 2013 OFFICE OF CHEMICAL SAFETY AND POLLUTI ON PREVENT I ON

PC Codes: 030001, 030004, 030016, 030019,030025,030035, 030053,030063,030066, 051505 MEMORANDUM DP Barcode: 409900 Subject:
To:

From:

Through: Response to Comments: EFED Regis tration Review Problem Formulation for 2,4-D Garland Waleko , Chemical Review Manager Cathryn Britton, Risk Manager Pesticide Re-evaluation Division (7508P)

# 1/1;(""~**'1/1:2-/13** Meghan Radtke , Ph.D.,**Bi.o logi~** **t** .**-~** ·**~** r...f. 

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# CJ Faruque Khan, Ph.D., Semor Sc1ent1st**~y-** 

## . Environmental Risk Branch 1 Environmental Fa te and Effects Division (7507P) 

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## 4/r)J:> Edward Odenkirchen, Ph.D ., Acting

### Bra~h**Chief~** 

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# 1· Sujatha Sankula, Ph.D., Lead

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# t.J} J Environmental Risk Branch 1 Environmental Fate and Effects Division (7507P)
The Environmental Fate and Effects Division (EFED) received a number of public comments on the Registration Review Problem Formul ation for 2 ,4-D (D402410). Thi s memo documents EFED's responses to the public comments that were received. Where appropriate, the comments have been applied to the Problem Formulation, resulting in a revised document. In addition, an oral larval toxicity test is being requested (per guidance in the Pollinator White Paper) so that a screen ing level risk assessment can be completed for honeybees. The Industry T ask Force II on 2 ,4-D Re search Data submitted study TFII021213

- ; Comments 9

- · 62 p er tain to the EFED Problem Form ulation

. In addition, the Task Force submitted two comments via e·mail, which are addressed at the end ofthis section. Comment 9: Add an additional sentence to the Drinking Water section that expands on the understanding of potential human exposure from the aquatic weed control use.Response: EFED has added the suggested wording. Comments 10-13: Identified corrections to the 2,4-D uses and application rates table (Table 4). Response: EFED has updated the information in Table 4 to include the corrected and additional information. Comment 14: Requested additional information be added to describe the rapid conversion of .2,4

-Dformulations to thefree 2,4-D acid. Response: EFED has added the information tha t was provided by the Task Force. Comment 15: Identified information about the percent formation of C02 in the text that should be added to Table 5. Response: EFED added the additional information to Table 5

. Comment 16: Information regarding the formation of 2,4-DCA under anaerobic aquatic conditions was mislabeled as being for 2,4

-DCP. Response: EFED corrected the error. Comment 17: Identified formatting inconsistencies with several MRID numbers in Table 5. Response: EFED deleted the extra sets of MRID numbers and centered the ones that remained. Comments 18- 20: Requested additional MRID numbers and iriformation be added to the leaching, aquatic field dissipation half-life, andforestjield dissipation half-life rows in Table 5
. Response: EFED added the MRID numbers and additional information that were suggested. Comment 21: Indicated the number of aquatic trials was three rather than two. Response: EFED corrected the sentence. Comment 22 : Requested information be added about the Georgia forestry dissipation study (correctionfrom Table 5). Response: EFED added the information, as suggested

. Comment 23: The duckweed toxicity value is incorrect; the 

### ECso is reported as 0.2992 but should be corrected to 0. 41 mg ae/L (MRID 42712204) (Table 6).

2Response: EFED re-checked MRID 42712204 and found the reported value for duckweed to be ECso = 0.44 mg ai/L (study was performed with DEA). When the toxicity value for DEA is converted to acid equivalents (ae), the EC 5o 

### = 0.2992 mg ae/L. Thus, the reported value in the Problem Formulation appears to be correct and no changes were made. Comment 24: The selected non-vascularplant EC 50 = 3.88 mg ae /L shows up in an earlier EPA document but the EPA DER D157262 concludes that the EC 50 

## = 4.67 mgae/L and the registrant's study MRID 41505903 concludes EC 5

### o = 5.28 mg ae/L (Fable 6). Response: EFED re-checked the DER for MRID 41505903 and found the reported EC 5o 

### = 4.67 mg ai/L (study was performed with DMA). When the toxicity value for DMA is converted to

. acid equivalents (ae), the EC 5o = 3.88 mg ae/L. Thu s, the reported value in the Prob lem

Formulation appears to be correct and no changes were made. Comment 25: For thefreshwater invertebrate chronic endpoint (waterjlea) add the greater than sign (>) before the 16.05 mg ae /L (I' able 6). Response: EFED re-checked the DER for the study (MRID 420 18303) and found that effects were reported at the highest treatment concentration that was tested. Therefore, the NOAEC was set at the second highest treatment concentra tion and is considered definitive. No changes were made to the freshwater invertebrate chronic endpoint. Comment 26: For the estuarine/marinefish acute endpoint (tidewater silverside), add the greater than sign(>) before the 80.24 mg ae/L (Fable 6). Response: EFED re-checked the DER for the study (MRID 42018301) and found that the LCso is reported as >80

.24 mg ae/L

. The entry in Table 6 was updated to reflect this correction. Comment 2 7: Indicated that the use of toxicity datafrom 1P E is non-representative for .freshwater.fish and invertebrates because IPE has an extremely low use rate, low application rate, and selective use only on citrus. It represents less than 0

. 1% of all USA 2,4-D usage. The EHE form should be used instead because 90-95% of all esters applied are of this form. Response: EFED will use the IPE toxicity values for freshwater fish and invertebrates in the analysis of uses for which that ester is regis tered (currently, citrus)

. For other uses , the most sensitive endpoints from other esters w ill be used

. These have been added to Table 7. Comment 28: For the non-vascularplant endpoint (marine diatom), the EC 50 is not correct . The value reported is an EC2 5 and the footnote does not relate to aquaticplants

. Response: EFED re-checked DER20 10866 and verified that the ECso was not reported correctly. The Problem Formulation has been updated accordingly and the footnote has been deleted as it did not relate to aquatic plants (Table 7)

. Comment 29: Footnote 2 in Table 7 refers to a mysid shrimp study, which is not listed in the table.



### 3Response: EFED deleted the footnote. Comment 30: For the avian acute endpoint (northern bobwhite), the 

### LD5o is reported as nondefinitive in Appendix B of the Problem Formulation, but as definitive in Tab le 8. Response: EFED re-checked the DER for MRID 42018301 and determined that the LDs o is definitive. Appendix B was updated to reflect this change. Comment 31: The recent mammal F1 extended genera tion reproduction study should be used instead of the 1985 11986 study that is cited in Table 8. 1) It is not clear that ecological risk endpoints for growth, reproduction or survival apply to wild animal toxicity for risk assessment. 2) There is no 2, 4-D relevant ecological endpoint for wild mammals risk assessment survival. All animals in the reproduction (chronic) study survived at the highest dose tested. 3) Therefore, for wild mammals, the survival endpoint is greater than the highest dose tested in the extended one-gen reproduction study. 4) Accordingly , correct the wild mammal ecotoxicological endpoints. Response: EFED reviewed the more recent mammal F1 extended generation reproduction study and, in conjunction with HED , concluded its endpoints were more refined than the older study. Toxic ity values from the new study were incorporated into Table 8. 1) EFED is unclear about the question/comment. The two -generation rat reproduction study is usually used to characterize chronic/reproductive effects on all mammals. 2) While it is true that all mammals survived at the highest concentration of2,4-D tested, there were other toxicological effects identified. These may affect mammal fitness and the ability to successfully reproduce/s urvive. 3) EFED agrees that the survival endpoint would be greater than the highest dose tested; however, there were other more sensitive endpoints identified in the study (changes to body weight, organ weight, and kidney malformation s)

. 4) EFED updated the endpoints in Table 8 , based on the results of the st udy. The parental NOAEL = 16

.6 mg ae/kg-bw , based on increased kidney weights , and degenerative lesions in the proximal convoluted tubules in Pl rats. The reproductive NOAEL 

### = 45.3 mg/kg bw / day in males, and 40.2 mglkg bw /day in females, based on no reproductive effects observed. The offspring NOAEL 

## = 20.9/ mg/kg bw/day in males and 23.3 mg/kg/day in females based on decreased body weights , increased kidney weights and increased incidence ofdegeneration of the proximal convoluted tubules. Comments 32 and 33: Identified some spelling errors and asked for clarification that the chronic mammal test is a reproduction test. Response: EFED corrected the spelling errors and made the chronic/reproduction clarification

.

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### Comment 34: 1) TEP is considered to be more appropriatefor toxicological endpoints because theformulatedproduct is more representative of actual exposure in the field 2) 

### If acceptable studies are available, then supplemental data should not be used. 3) Fresh weight should not be used as an endpoint because of its greater variability when dry weight from other studies is available

. 4) IPE endpoints should not be used for the assessment because they are only registered on citrus
. In addition, EFED should follow the approach in the RED where esters were considered separately for terrestrialplant exposures because of the difference in solubility. Response: 1) EFED requires TEP testing because of the concern that the other ingredients in a fo rmul ated product may increase its overall toxicity for terrestrial plants. If both TEP and TGAI have been tested and the TGAI toxicity value is more sensitive than the TEP vaiue, EFED will use the most sensitive toxicity value for the assessment. 2) A classification of "supplemental " does not automatically mean that the data are not suitable for quantitative use in risk assessments. EFED has re -checked the supplemental study that was proposed for use (MRID 43982101) and found it to be scientifically sound for the lettuce seedli ng emergence endpoint. 3) EFED agrees that fresh weight is a more variable endpoint than dry weight and the Task Force has correctly pointed out that dry weight is specified as the preferred measurement in 850.4250 and 850.4150. EFED has re-checked these studies and maintains that they are scientifically sound and that this endpoint, as the most sensitive endpoint in some instances, is acceptable for use in risk assessment. These studies were submitted to fulfill requirements by the registrant and did not include dry weight measurements. 4) EFED will only use IPE endpoints to assess thos e registered uses fo r IPE (currently only citrus is registered). The most sensitive endpoints from other esters will be used for the other registered uses. In addition, EFED agrees that the analysis should be conducted as outlined in the RED. Esters and the acid and amine salts will be assessed separately for terrestrial plants. EFED reviewed the suggested toxicity endpoints from the registrant and incorporated them into Tables 6 and 7, as appropriate. 

### Comment 35: Deletefootnote 2from Table 

### 8 because TGAI data is not applicablefor terrestrial plant risk assessment. Response : TGAI is appl icable for terrestrial plant risk assessment, if it is the most sensitive endpoint. The footnote was not deleted. 

### Comments 36 

### and 43: Correct spelling of2-DCP to 2,4-DCP. Response: Corrections were made. 

### Comment 37: MRID 42059601fills the data gap identified for a volatility laboratory study. Response: EFED inadvertently left this study out of the table; it was added, as requested.

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### Comment 38: 835.1410 is an incorrect guideline number; the correct guideline number is 

### 835 .8100. Response: The guideline number was corrected. 

### Comment 39: Correct the study guideline number fo r the aquatic field dissipation stud ies and MRID 43854701 should read 43954701

. Response: The corrections were made. 

### Comment 40: The Task Force will conside r preparing separ ate submissions for the analytical methods for ail of the dissipation studies; however, this information is included in each of the stud y's appendix section. Response: EFED thanks the Task Force for thi s clarification and looks forward to possibly receiving separate submissions for the analytical methods. 

### Comments 41 a11d 42: MRID numbers listed in tables did not match with the species /test chemical description. Response: The MR£0 numbers were corr ected so that they correspond to the correct studies . 

### Comment 44: 2, 4-DCP fate stud ies have beenprovided to EFED
. Response: EFED corrected the Problem Formulation to state that registrant-submitted environmental fate data for 2 ,4-DCP are available. 

### Comments 45 , 47, 48 , 49, 50, 56, 58, 59: Identified a number of typographical errors in the bibliographic entries. Response: EFED made the corrections, as identified by the Task Force . 

### Comments 46 , 51 , 52, 53, 54, 55, 57: Id entified studies that should be added to the bibliography. Response: EFED added the studies , when appropriate (the bluegill sunfish study was not cited in the Problem Formulation and thus , was not added). 

### Comment 60: Indi cated the structures were unreadable in the Table A.1. Response: EFED increased the size of the chemical str uctures in Table A. l. 

### Comment 61: 1) Requested EHE subscript be added for C1di22Ch03 ; 2) correct solubility of EHE to 0.32 mg /

L ; and 3) correct vapor pressures for EHE and IPE.

6Response: 1) The subscript was added. 2) EFED consulted the RED (page 7 and page 145 of the EFED assessment). The value was reported as 0.087 mg/L; thus no changes were made to solubility value for EHE. 3) The vapor pressures for EHE and IPE were corrected to be consistent with the RED. The STIR model res ults were updated with the corrected information and resulted in no risks to birds or mammals. Comment 62: The 

### EHE solubility number should be changed for the SIP model to reflect the correction made in Comment 61. Response: The EHE sol ubility number was not changed; thus, no further changes are needed to the SIP model. Comment EFED Registration Review Problem Formulation, page 19 of 83, Table 8, Taxonomic Group: Mammals, Acute Inhalation: The acute inhalation value listed is LC5o = 0. 78 mg ai /

L, which isfrom a study that has been replaced by a more recent study (MR ID 41957601 LC5o 

### = 5
. 35 mg ai/L). Response: EFED re-visited the inhalation toxicity stu dies and now reports the same value that is reported in the HED Problem Formulation document: LC 50 > 1.79 mg ae!L (MRID 00 161660). Comment EFED Registration Review Problem Formulation, page 19 of 83, Table 8, Taxonomic Group: Mammals, Acute oral: The toxicity value is listed as 441 mg aelkg-bw, based on a TIPA study, but the origin ofthe number is unclear. Given that toxicity values are reported in acid equivalents, why not use the 2,4-D acid acute oral value of699 mg ae/kg-bw? Response: The 441 mg ae/kg-bw number is derived from the TIPA study (MRID 41413501). This study reported the LD so 

### = 1074 mg ai/kg-bw. Converting this to acid equivalents (ae), the LD so is 405 mg ae/kg-bw. The Problem Formulation has been corrected from 441 mg ae/kg-bw to 405 mg ae/kg-bw for the mammal LD 5o. All toxicity data from 2,4-D forms are us eable in risk assessments, but must be converted to acid equivalents so that comparisons can be made. EFED's policy is to choose the most sensitive toxicity value. In this case, TIPA yields a more sensitive value than 2,4-D acid (LD 5o 

### = 699 mg ae/kg-bw). EPA Region 9 (Patti TenBrook) submitted water monitoring datafor 2,4-D. Response: EFED appreciates these data! They will be considered during the risk assessment phase of Registration Review. The National Council for Air and Stream Improvement , Inc
. , submitted general information on 2,4-D application practices inforestry management. Response: EFED appreciates the submission and will consider the refined information on forestry management practices in the risk assessment phase of Registration Review.

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