UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. D.C. 20460 

April 12, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

PC Codes: 030001, 030004, 030016, 

030019,030025,030035, 

030053,030063,030066, 

051505 

MEMORANDUM DP Barcode: 409900 

Subject: 

To: 

From: 

Through: 

Response to Comments: EFED Registration 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. (rJ-i CJ 

Faruque Khan, Ph.D., Semor Sc1ent1st ~y- . Environmental Risk Branch 1 

Environmental Fate and Effects Division (7507P) 

t:P11 J ll. t:) // 4/r)J:> Edward Odenkirchen, Ph.D., Acting Bra~h Chief~ C../ V --~ 1· 

Sujatha Sankula, Ph.D., Lead Biologist<'~ ~ f'.S: ~ 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 Formulation for 2,4-D (D402410). This 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 

screening level risk assessment can be completed for honeybees. 

The Industry Task Force II on 2,4-D Research Data submitted study TFII021213-; Comments 9 - · 

62 pertain to the EFED Problem Formulation. In addition, the Task Force submitted two 

comments via e·mail, which are addressed at the end of this 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-D formulations to the free 2,4-D acid. 

Response: EFED has added the information that 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). 

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Response: 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 EC5o = 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-vascular plant EC50 = 3.88 mg ae/L shows up in an earlier EPA 

document but the EPA DER D157262 concludes that the EC50 = 4.67 mgae/L and the 

registrant's study MRID 41505903 concludes EC5o = 5.28 mg ae/L (Fable 6). 

Response: EFED re-checked the DER for MRID 41505903 and found the reported EC5o = 4.67 

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

. acid equivalents (ae), the EC5o = 3.88 mg ae/L. Thus, the reported value in the Problem 

Formulation appears to be correct and no changes were made. 

Comment 25: For the freshwater 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 concentration and is considered definitive. No changes were 

made to the freshwater invertebrate chronic endpoint. 

Comment 26: For the estuarine/marine fish acute endpoint (tidewater silvers ide), 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 data from 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 registered (currently, citrus). For other uses, the most 

sensitive endpoints from other esters will be used. These have been added to Table 7. 

Comment 28: For the non-vascular plant endpoint (marine diatom), the EC50 is not correct. 

The value reported is an EC25 and the footnote does not relate to aquatic plants. 

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. 

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Response: 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 Table 8. 

Response: EFED re-checked the DER for MRID 42018301 and determined that the LDso is 

definitive. Appendix B was updated to reflect this change. 

Comment 31: The recent mammal F1 extended generation reproduction study should be used 

instead of the 198511986 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. 

Toxicity 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/survive. 

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 malformations). 

4) EFED updated the endpoints in Table 8, based on the results of the study. 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 of degeneration 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. 

4 
Comment 34: 1) TEP is considered to be more appropriate for toxicological endpoints because 

the formulated product 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 terrestrial plant exposures because of the difference in solubility. 

Response: 1) EFED requires TEP testing because of the concern that the other ingredients in a 

formulated 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 

seedling 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 those registered uses for 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: Delete footnote 2from Table 8 because TGAI data is not applicable for terrestrial 

plant risk assessment. 

Response: TGAI is applicable 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 42059601 fills the data gap identified for a volatility laboratory study. 

Response: EFED inadvertently left this study out of the table; it was added, as requested. 

5 
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 for the aquatic field dissipation studies and 

MRID 43854701 should read 43954701. 

Response: The corrections were made. 

Comment 40: The Task Force will consider preparing separate submissions for the analytical 

methods for ail of the dissipation studies; however, this information is included in each of the 

study's appendix section. 

Response: EFED thanks the Task Force for this 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 corrected so that they correspond to the correct studies. 

Comment 44: 2, 4-DCP fate studies have been provided 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: Identified 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: Indicated the structures were unreadable in the Table A.1. 

Response: EFED increased the size of the chemical structures 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. 

6 
Response: 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 results 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 solubility 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 is from a study that has been replaced by a more recent study (MRID 

41957601 LC5o = 5.35 mg ai/L). 

Response: EFED re-visited the inhalation toxicity studies and now reports the same value that is 

reported in the HED Problem Formulation document: LC50 > 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 LDso = 1074 mg ai/kg-bw. Converting this to acid equivalents (ae), the 

LDso 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 LD5o. All toxicity data from 2,4-D forms are useable 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 (LD5o = 699 mg ae/kg-bw). 

EPA Region 9 (Patti TenBrook) submitted water monitoring data for 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 in forestry 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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