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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 uncertainties 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 addition, 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 response 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 Requirement 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 Metabolism (835.4300) – No longer required. 

• (T6) Environmental Chemistry Methods and Associated ILVs for Water (835.6200). Still required.

MBC degradate Study Requirement 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 Scenarios: 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 recommendations for the updated status of each of 

these studies.
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Requirements T1 and M1 (835.1230; Batch 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 further data are required. 

Requirements T2 and M2 (835.2130; Hydrolysis)

The registrant proposes that currently available studies (not specified) 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 anticipated 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 use these data. Model inputs for hydrolysis typically include 

hydrolysis rates at three different pHs (4-5, 7, and 9), but do not include hydrolysis rates 

at different temperatures. Since 35°C is not an environmentally relevant temperature, 

particularly for groundwater, the TM/MBC Task Force sees little regulatory 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 assessments can continue for TM and MBC without any 

additional data. However, from the available data EFED can only conclude that TM is 

potentially stable in acidic soils and waters and MBC is generally stable to hydrolysis in the 

environment and, in lieu of any additional data, will make such assumptions in future 

environmental fate modeling. Since groundwater modeling is sensitive to this parameter, the 

registrant should be aware that if studies were to be conducted at higher temperatures and such 

studies revealed that MBC does hydrolyze, the results could be converted to equivalent 

hydrolysis rates for more common environmental conditions. 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 studies are adequate to explain the 

behavior of both TM and MBC in the environment and that no additional studies should be 

required. EFED understands that, for TM, three 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 accepted for quantitative analysis in environmental 

fate studies submitted to the Agency. The soils used in these studies were not fully characterized 
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and there is a potential that TM, while generally rapidly converted to MBC in the environment, is 

somewhat less rapidly converted in some soils and waters, especially under lower pH conditions. 

The TM 835.4100 studies are not critical as long as MBC is the primary exposure concern in risk 

assessments. However, should the need arise to more 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 conservative estimate of TM aerobic soil degradation rates 

in acidic and neutral soils and waters. 

With regards to the 835.4100 studies for MBC, 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. EFED can rely on the other study with benomyl 

applied if this is to be used to support the registrations 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 value by 3x when data from only a single 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 different 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 classified as supplemental and why EFED 

believes this testing on two aerobic aquatic 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 aerobic aquatic metabolism DERs for the 162-4 

studies for thiophanate-methyl and carbendazim. The aerobic aquatic metabolism study 

of thiophanate methyl (MRID 45621401I) is classified as supplemental. 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 demonstrate that the sediment phases were aerobic/anaerobic at the 

time of treatment. Based on the Pesticides Reregistration Rejection Rate Analysis, redox 

potentials of the sediment-water system should be monitored during the study. 

EFED reiterates the above conclusions and stands by the conclusion in the problem formation 

that TM metabolism rates might vary significantly in acidic and alkaline waters. The additional 
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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 studies, EFED remains concerned that MBC may be more stable in 

some waters than the studies with benomyl applied demonstrate. EFED respectfully believes 

these studies should still be required, but is reducing the request to two test sediment water 

systems with technical MBC applied; at least one of these test systems should be significantly 

acidic, but the specific selection of the sediment water systems will be at the registrant’s 

discretion (but they must be fully characterized as required under OCSPP guidelines). 

Requirements T5 and M5 (835.4300; Anaerobic Aquatic Metabolism) 

EFED agrees that the data requirement has been met for TM and that the existing study appears 

to show rapid conversion of TM to MBC (essentially 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 required in the future if a need is identified to 

more fully understand the anaerobic waters transformation 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) which shows a high persistence of MBC in 

anaerobic waters (743 day half-life). 

Requirements T6 and M6 (835.6200; Environmental 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; Treated 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 stain/coatings; treated textiles (non-guidelines): “The sole 

registrant of antimicrobial uses indicates data are available to address the anticipated data need 

for the exterior painted surfaces/wood protective stains/roof coatings. The registrant is currently 

evaluating the market for MBC in the textile industry and the anticipated data need for leaching 

studies in treated textiles should be placed on reserve while the use pattern is clearly defined”. 
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EPA’s Response to Comment: 

The Agency welcomes the submission of leaching data as required for the exterior painted 

surfaces/wood protective stain/coatings. The results of these studies will be used for Risk 

Assessment at the scheduled time for TM/MBC. 

If the registrant intends to keep treated textiles 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 for Thiophanate methyl and the MBC 

degradate 

Thiophanate methyl Seedling Emergence 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) Honey bee Oral and Larval acute Toxicity 

Testing - EFED response 

The registrant has indicated that they have adult 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 have suggested that we hold this requirement in 

reserve pending review of the adult oral test. EFED does not agree that the acute toxicity to 

adults will necessarily be reflective of the chronic toxicity to developing larvae. This has been 

shown to be true for other pesticides that demonstrated relatively low toxicity to adults, but 

higher toxicity to the developing larvae. 

In addition, a recent extensive study on over 200 pesticides found in wax and pollen within hives 

of North America (Mullin, C.A. et al, 2010) has shown that thiabendazole, a closely related 

benzimidazole to thiophanate methyl, was present 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 Carbendazim. This suggests that 

larvae will be exposed this family of chemicals, but does not provide us with the toxicity levels 

at which this type of exposure will prove hazardous to developing larvae. 
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Aquatic Plant Testing with MBC 

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

more sensitive freshwater diatom (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 Thiophanate 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 testing with freshwater and marine diatoms 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 Marine Invertebrate be held in 

reserve pending results of the freshwater invertebrate test based on the fact that estuarine mysid 

chronic test results with MBC show 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 little 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 endpoints 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 plumulosus 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 need 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 patterns of Thiophanate methyl. EFED does not agree 

that there is a true basis for this request and therefore is asking that both the freshwater and 

marine tests be conducted, as requested. EFED 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 Advisor Environmental Risk Branch 5 

Mohammed Ruhman. PhD. Senior Scientist Environmental Risk Branch 5 

Thomas Steeger, PhD Senior Science Advisor Environmental Risk Branch 4 

Scott Glaberman, PhD Biologist Environmental Risk Branch 4 

Laura Parsons, Senior Interdisciplinary Scientist Antimicrobial Division