2 The Environmental Fate and Effects Division (EFED) and the Antimicrobials Division (AD) have requested additional data or studies for a number of environmental fate and ecological effects data requirements. These data are requested to clarify un certainties regarding risk from current registered uses for Thiophanate methyl and its major degradate MBC, which is also marketed as the active ingredient Carbendazim. The data requests made by EFED for MBC in this Problem Formulation are in conjunction with its formation in the environment after the application of thiophanate methyl for its many crop and commercial uses. The environmental exposure to non-target organisms is expected to be more limited from uses of Carbendazim for tree injections. In addi tion, Carbendazim is registered for use in sealants and coatings and certain data requirements would apply to these antimicrobial uses as well.

Please refer to the following pages for responses to the registrants comments and EFED’s updated decision on each data requirement initially identified in the Problem Formulation (DP Barcodes 413077 and 413078; 3/18/2014).



### Fate and Chemistry Data Needs for Thiophanate methyl and the MBC degradate -EFED response

Environmental fate data requested are summarized below with a letter number code associated with each (requirements with the same number are for the same study type). Although the registrant has commented on the thiophanate methyl (TM) and MBC data requirements separately, we have merged the EFED respons e by study category (because the MBC fate data are primarily for the use of the support of exposure assessments for TM uses.

Thiophanate methyl Study Requirem ent List and Updated Status • (T1).Batch Equilibrium Adsorption/Desorption (835.1230) – No Longer required. • (T2) Hydrolysis (835.2120) – May be required, see below. • (T3) Aerobic Soil Metabolism (835.4100) – May be required, see below. • (T4) Aerobic Aquatic Metabolism (835.4200) – Still recommended but updated. • (T5) Anaerobic Aquatic Metabolis m (835.4300) – No longer required. • (T6) Environmental Chemistry Methods and Asso ciated ILVs for Water (835.6200). Still required.

MBC degradate Study Requiremen t List and Updated Status

• (M1) Batch Equilibrium Adsorption/Desorption {835.1230) – No Longer required. • (M2) Hydrolysis (835.2120) – May be required, see below. • (M3) Aerobic Soil Metabolism (835.4100) – May be required, see below. • (M4) Aerobic Aquatic Metabolism (835.4200)– Still recommended but updated • (M5) Anaerobic Aquatic Metabolism (835.4300) – No longer required. • (M6) Environmental Chemistry Methods and Associated ILVs for Soil and Water (835.6200). Still required. • (M7) Leaching Studies for the Following Use Scenar ios: Exterior Painted Surfaces/Wood Protective Stains/Roof Coatings; Treated Textiles (Non -Guideline) – May be required, see below.

Please read below for detailed comments on the reco mmendations for the updated status of each of

these studies.3 Requirements T1 and M1 (835.1230; Batc h Equilibrium Adsorption/Desorption)

The registrant proposes that previous studies adequately meet this data requirement: MRID 42351001 for thiophanate methyl and for MBC. EFED has re-examined this study and concurs with the registrant, no furt her data are required.

Requirements T2 and M2 (835.2130; Hydrolysis)

The registrant proposes that curr ently available studies (not speci fied) fulfill the hydrolysis data requirement. Additionally, the registrant states:

In addition to conducting a hydrolysis study at a standard temperature of 20 or 25°C, EPA also indicated that it has an anticipat ed data need for a non-guideline hydrolysis study conducted at 35°C. EPA has not provided a rationale for requesting this additional hydrolysis testing, nor, except for a vague reference to the PRZM -GW model, has EPA

indicated how it intends to us e these data. Model inputs for hydrolysis typically include hydrolysis rates at three diffe rent pHs (4-5, 7, and 9), but do not include hydrolysis rates at different temperatures. Si nce 35°C is not an environmen tally relevant temperature, particularly for groundwater, the TM/MBC Task Force sees little re gulatory need for conducting an additional, high temperature hydrolysis study.

A review of existing hydrolysis data (MRID 43129614) does not conclusively confirm that MBC is completely stable at all environmental pH and temperature conditions. Thiophanate methyl also appears to be stable in acidic waters (MRID 40095507).

EFED believes environmental exposure assessment s can continue for TM and MBC without any additional data. However, from the availabl e data EFED can only conclude that TM is potentially stable in acidic so ils and waters and MBC is genera lly stable to hydrolysis in the environment and, in lieu of any additional data, will make such assumptions in future environmental fate modeling. Sinc e groundwater modeling is sensit ive to this parameter, the registrant should be aware that if studies were to be conducted at higher temperatures and such

studies revealed that MBC doe s hydrolyze, the results could be converted to equivalent hydrolysis rates for more common environmental c onditions. If this were to be demonstrated, exposure modeling inputs would be less conservative and might validate a lower exposure

estimate.

Requirements T3 and M3 (835.4100; Aerobic Soil Metabolism)

The registrant has a long response that contends that existing studi es are adequate to explain the

behavior of both TM and MBC in the environmen t and that no additiona l studies should be required. EFED understands that, for TM, th ree soils were tested in a 1976 study (MRID00106085) using thin-layer chromatography ( TLC) for analysis of residues over time, and that, up to the most recent assessment these data were not identified as inadequate to meet current data requirements. TLC is no longer accept ed for quantitative anal ysis in environmental fate studies submitted to the Agency. The soils used in these studies were not fully characterized4 and there is a potential that TM, while generally rapidly converted to MBC in the environment, is somewhat less rapidly converted in some soils an d waters, especially und er lower pH conditions.

The TM 835.4100 studies are not criti cal as long as MBC is the prim ary exposure concern in risk assessments. However, should the need arise to mo re explicitly assess exposure to TM per se in any future Agency risk assessments, EFED reserves the right to assume that results from the TM hydrolysis studies represent the most conservativ e estimate of TM aerobic soil degradation rates

in acidic and neutral soils and waters.

With regards to the 835.4100 studies for M BC, EFED notes that while the MRID 00106085 studies are inadequate by current standards, they do appear to show very high stability of the MBC as a rapidly formed degradate of TM. EF ED can rely on the other study with benomyl applied if this is to be used to support the re gistrations of TM and MBC. However, currently under OCSPP guidelines tests in four soils are required for most pesticides with significant field / outdoor uses. Standard modeling procedure under current EFED guidelines is to multiply the

aerobic soil metabolism halflife valu e by 3x when data from only a si ngle test soil are available. The registrant should be aware of this if they choose to not submit any additional studies. Additionally, the Agency will have to determine the mechanism for reliance of data submitted for the support of the registration of a differe nt active ingredient (benomyl, which is now canceled).

Requirements T4 and M4 (835.4200; Aerobic Aquatic Metabolism)

The registrant’s response for TM reads in part: An acceptable study (classified as "supplemental" ) for two systems (a river water system and a pond water system) is available for TM , so the anticipated need for additional testing is indistinct. The TM/MBC Task Force would benefit from receipt of the DER for the existing study to clarify why it was cl assified as supplemental and why EFED believes this testing on two aerobic aqua tic systems needs to be repeated.

A Memorandum dated 3/3/2003 from EFED to the then Special Review and Reregistration Division states the following:

Attached to this memorandum is the aer obic aquatic metabolism DERs for the 162-4 studies for thiophanate-methyl and carbenda zim. The aerobic aquatic metabolism study of thiophanate methyl (MRID 45621401 I) is classified as supplemen tal. It is scientifically valid, but does not meet the guidelines for an aerobic aquatic metabolism study because the sediment phase was anaerobic at the time of treatment and remained anaerobic throughout the study. The aerobic aquatic study of MBC (MRID 4562001) does not satisfy the guideline requirements for a U.S. EPA Subdivision N, section 162-4, thus it is classified as unacceptable. In the later study, no evidence of redox potential monitoring data was provided to demonstr ate that the sediment phases we re aerobic/anaerobic at the

time of treatment. Based on the Pesticides Re registration Rejection Rate Analysis, redox potentials of the sediment-water system should be monitored during the study.

EFED reiterates the above conclusions and stan ds by the conclusion in the problem formation that TM metabolism rates might vary significantl y in acidic and alkaline waters. The additional5 data are required, but will only be required in two test systems at least one of which is significantly acidic.

With respect to 835.4200 studies for MBC, given the extremely high persistence shown for MBC

in all available aerobic soil stud ies, EFED remains concerned that MBC may be more stable in some waters than the studies with benomyl a pplied demonstrate. EFED respectfully believes

these studies should still be re quired, but is reducing the reques t to two test sediment water systems with technical MBC applie d; at least one of these test systems should be significantly acidic, but the specific selection of the sedime nt water systems will be at the registrant’s discretion (but they must be fully charact erized as required un der OCSPP guidelines).

Requirements T5 and M5 (835.4300; Anaerobic Aquatic Metabolism)

EFED agrees that the data requirement has been met for TM and that th e existing study appears to show rapid conversion of TM to MBC (essentia lly complete within a few days.) No data are required at this time, however, EFED does note that the transformation rate could vary in other

anaerobic waters and additional studies could be re quired in the future if a need is identified to more fully understand the anaerobic waters tran sformation rate under different environmental

conditions.

EFED will also not require additional 835.4300 data for MBC, provided that the Agency can rely on the results of a benomyl study (MRID 41137701) wh ich shows a high persistence of MBC in anaerobic waters (743 day half-life).

Requirements T6 and M6 (835.6200; Environm ental Chemistry Methods and Associated ILVs for Soil and Water)

The registrant has agreed to submit a method for TM in water and for MBC in soil and water. These test methods are still required.

Leaching Studies for the Following Use Scenarios: Exterior Painted Surfaces/Wood

Protective Stains/Roof Coatings; Treate d Textiles (Non-Guideline)

TM/MBC Task Force has sent comments on the Thiophanate-Methyl and Carbendazim Registration Review (Case# 2680). The Task Force has made the following comment on the

antimicrobial uses:

TM/MBC Task Force Comment: Leaching studies for the following use scenarios: Exterior painted surfaces/wood protective stai n/coatings; treated textiles (non-guidelines): “The sole registrant of antimicrobial uses indicates data ar e available to address the anticipated data need for the exterior painted surfaces/w ood protective stains/roof coatings. The registrant is currently evaluating the market for MBC in the textile indu stry and the anticipated data need for leaching

studies in treated textiles shoul d be placed on reserve while the us e pattern is clearly defined”.6 EPA’s Response to Comment:

The Agency welcomes the submission of leachi ng data as required for the exterior painted surfaces/wood protective stain/coatings. The resu lts of these studies will be used for Risk

Assessment at the scheduled time for TM/MBC.

If the registrant intends to keep treated textile s use on the label, the Agency expects submission of leaching data from treated textiles. It is not the policy of the Agency to place any data requirements on the reserve list if the intended use is listed on the label. The Agency expects to receive a cancelation notice from the registrant, if the registrant intends to remove this use from

the label.



### Ecological Effects Data Needs fo r Thiophanate methyl and the MBC degradate

Thiophanate methyl Seedling Emerge nce and Vegetative Vigor testing



### - EFED response Seedling Emergence and Vegetative Vigor testing at higher rates was requested in the original

TM RED based on the labeled rates that exceed the 1.4 lb ai rate that was tested with Topsin M (95% ai test material) (MRID 42123504 Tier I and Tier II test). Onion and soybean emergence were affected at this rate. The vegetative vigor study was considered supplemental due to missing information regarding growth stage of tested plants.

Thiophanate-methyl and MBC (Carbendazim) Hone y bee Oral and Larval acute Toxicity Testing - EFED response

The registrant has indicated that they have a dult oral test results with the honeybee from a 2005 study and that they intend to submit this study. The Agency will make every effort to review this study quickly for determination of acceptability.

The task force has questioned the need for larval toxicity testing based on low toxicity to adult honeybees in the contact toxicity test. They ha ve suggested that we hol d this requirement in reserve pending review of the a dult oral test. EFED does not ag ree that the acute toxicity to adults will necessarily be reflective of the chroni c toxicity to developing larvae. This has been shown to be true for other pesticides that dem onstrated relatively low toxicity to adults, but higher toxicity to th e developing larvae.

In addition, a recent extensive study on over 200 pest icides found in wax and pollen within hives of North America (Mullin, C.A. et al, 2010) ha s shown that thiabendazole, a closely related benzimidazole to thiophanate methyl, was pres ent in concentrations ranging from 1.4 to 5.6 ppb in pollen samples and from 1.4 to 76 ppb in bee wax samples. Carbendazim (MBC) was also detected in pollen and wax at concentrations ranging from 1.5 to 149 ppb in pollen, and from 2.1 to 133 ppb in bee wax. It would seem likely that the presence of MBC was from crop uses of Thiophanate methyl and less likely from tree injection use as Carb endazim. This suggests that larvae will be exposed this family of chemicals, but does not provide us w ith the toxicity levels at which this type of exposure will prove hazardous to developing larvae.7 Aquatic Plant Testing with MBC

The Task Force has proposed that testing with an aquatic vascular plant (Lemna sp) and the

more sensitive freshwater diat om (Navicula pelliculosa) be conducted and hold in reserve all other aquatic plant species testing for MBC as a degradate, until results for these two species can be compared to the results with parent Thi ophanate methyl. EFED does not object to this approach and will determine the need for further species testing pending these results.

However, AD requires testing with both Lemna and green algae. If the EC50 for the green algae is less than 1 ppm, then testi ng with freshwater and marine di atoms and cyanobacteria also is required.

Whole Sediment Chronic Toxicity Testing for Freshwater and Marine Invertebrates

The Task Force has requested that the sediment testing with a Ma rine Invertebrate be held in reserve pending results of the fres hwater invertebrate te st based on the fact that estuarine mysid

chronic test results with MBC s how lower toxicity than that of freshwater organisms. The technical MBC acute 96 hour LC50 for Mysid was 98 ppb and the 48 hour EC50 for technical MBC to Daphnia magna was 110 ppb, so there is li ttle difference between these test species acutely. The MBC degradate data submitted in conjunction with Benomyl registrations (MRID 42723701 flow-through test with mysid and MRID 42529401 static renewal test with Daphnia magna) did show a lower chronic effect endpoin ts for the freshwater crustacean (LOECs = 6.6 ppb for daphnia vs 50.3 ppb for the mysid), but the 2 tests are not completely comparable in their methodology.

As to whether the marine amphipod Leptocheirus pl umulosus will prove more or less chronically

sensitive than the Chironomid insect larvae is a difficult extrapolation to make as they are different taxonomic groups. The registrant has proposed that results from the freshwater insect

larvae sediment test be used to dismiss the n eed for chronic sediment testing with the marine amphipod species. EFED believes that MBC will reach aquatic sediments in both fresh and marine environments based on current use pattern s of Thiophanate methyl. EFED does not agree that there is a true basis for this request and th erefore is asking that both the freshwater and marine tests be conducted, as requested. EF ED and AD recommend that a protocol for the marine test be submitted before commencing the study.

Secondary Review By:

Jim Carleton PhD Senior Scientist Environmental Risk Branch 4 Keith Sappington, PhD Senior Science Advi sor Environmental Risk Branch 5

Mohammed Ruhman. PhD. Senior Scient ist Environmental Risk Branch 5 Thomas Steeger, PhD Senior Science A dvisor Environmental Risk Branch 4 Scott Glaberman, PhD Biologist Environmental Risk Branch 4 Laura Parsons, Senior Interdisciplin ary Scientist Antimicrobial Division