UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

DATE: 8/22/2014 

SUBJECT: Thiophanate-Methyl (TM)/Carbendazim (MBC). Response to Registrants' 

Comments on Registration Review Preliminary Workplan (Docket ID No. EPAOPP-2014-0004) 

PC Code: 10200 l (Thiophanate-Methyl) DP Barcode: D420917, 420919 

128872 (Carbendazim) 

Decision No.: 492147,492148 

Petition No.: N/A 

Registration No.: N/ A 

Regulatory Action: Registration Review 

Risk Assessment Type: N/ A Case No.: 2680 

TXR No.: N/A CAS No.: 23564-05-8 (Thiophanate-Methyl) 

10605-21-7 (Carbendazirn) 

MRID No.: N/A 40 C.FR: 180.371 (Thiophanate-Methyl) 

FROM: 

\ . --- ( \ \ ..... - -\· ..... -

Linnea J. Hansen, Ph.D., Biologist l ·~.>. · .. -:;; j ..._ · '' 

Margarita Collantes, M.S., Biologis{ ~.~. "-> --,/ \--.. ,,--· ' ,} -,· 

Douglas Dotson, Ph.D., Chemist ,lJ. }/&t::...c?..t 

Risk Assessment Branch II 

Health Effects Division (7509P)/Office of Pesticide Programs 

Nathan Mottl, Biologist /1/:lfk.-·r-.'1 l/l(,;:(;rJ' 1 • 

J Ch Ph D ·r . 1 . 1 . v.[,{.,;,"( c 1<..>-·'-''-- onathan en, .. , oxtco og1st·· ..,A(...-'l.\ "' · - •• 

Risk Assessment Science Support Branch · 

Antimicrobials Division (751 OP)/Oftice of'Pesticide Programs 

THROUGH: Christina Swartz, Branch Chief (~~~-~~- /!:__"' Risk Assessment Branch li ..:,:/ 

Health Effects Division (7509P)/Office of Pesticide Programs 

TO: Carissa Cyran, Chemical Review Manager, PM Team 51 

Thomas Moriarty, RM Team 51 

Pesticide Re-Evaluation Division (7508P)/Oftice of Pesticide Programs 
BACKGROUND 

The Agency recently prepared a human health risk assessment seeping document for registration 

review ofthiophanate-methyl (TM) and its metabolite carbendazim (MBC)(D413079, M. 

Collantes, et al., 3/20/20 14). The Thiophanate-Methyl and Carbendazim Task Force submitted 

comments on the Agency's preliminary workplan and anticipated data requirements for TM and 

MBC (Docket ID No. EPA-HQ-OPP-2014-0004). These comments related to several toxicity 

study requirements requested by the Health Effects Division (HED) and exposure study 

requirements requested by the Antimicrobials Division (AD). In this memorandum, the Agency 

is responding to the comments from the TMIMBC Task Force regarding these data requirements, 

as well as a number of exposure-related data requirements identified by AD. 

CONCLUSIONS 

In preparation of the seeping document, the Agency identified the following as data requirements 

to support registration review of TM and MBC: ( 1) a rat subchronic inhalation toxicity study 

(OPPTS 870.3265) on TM, (2) a rat developmental thyroid toxicity study on TM (no guideline 

number) and (3) an immunotoxicity study (OPPTS 870.7800) on MBC. The following 

comments from the TM/MBC Task Force on these requirements are addressed by HED and AD: 

( 1) Submission of a 28-day inhalation toxicitv studv on TM instead of a 90-day study: The 

Task Force noted that EPA would accept a rat 28-day inhalation toxicity study on TM in 

lieu of a 90-day inhalation toxicity study. The Agency requested inclusion of thyroid 

measures in this study and review of the study protocol prior to initiation of the study. 

EPA Response: EPA concurs that a rat 28-day inhalation toxicity study with assessment 

of thyroid parameters will satisfy the guideline requirement for a subchronic inhalation 

toxicity study, and that the study protocol should be submitted for review. A 90-day 

inhalation study is not required at this time. 

(2) Need for the rat developmental thyroid toxicity studv for TM: The Task Force requested 

that the Agency reserve the requirement for a developmental thyroid study on TM 

pending review of the rat extended one-generation reproductive toxicity study on MBC. 

This request is based on the following rationale: the extended one-generation study will 

assess both neurological parameters and thyroid weight, pathology, and parental and pup 

thyroid hormone levels. As TM is rapidly metabolized to MBC, the Task Force proposes 

that the MBC study will adequately assess potential thyroid toxicity from TM, and that 

the requirement for a developmental thyroid study on TM should be held in reserve 

pending its review. 

EPA Response: Although TM is metabolized to MBC, it has been shown to affect the 

liver and thyroid. Effects on the thyroid are observed in several species exposed to TM, 

but the available studies on MBC do not show toxicity to the thyroid. There remain 

uncertainties regarding the relative sensitivity to effects from TM during early 

development, for example, due to differences in metabolic capacity in the liver. 

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Examination of the thyroid in offspring in the rat two-generation reproductive toxicity 

study (MRIDs 42899101-05 and 43624401) was not performed until postnatal week 8, 

which does not address the developmental window of concern. Because thyroid effects 

can result in permanent developmental effects, this study is required to support 

registration review of TM. 

(3) Need for an immunotoxicitv studv on MBC: The Task Force requested that the Agency 

reserve the requirement for an immunotoxicity study on MBC pending review of the rat 

extended one-generation reproductive toxicity study on MBC, which includes evaluation 

of several parameters relevant to immunotoxicity (white blood cell count, spleen and 

thymus weight, and histopathology). 

EPA Response: The Agency will reserve the requirement for an immunotoxicity study 

pending review of the extended one-generation reproductive toxicity study. Upon 

consideration of that data, the requirement for an immunotoxicity study will be 

determined. 

(4) Need for exposure data for MBC: The Agency has required exposure data to assess 

occupational and residential handler exposures (dermal and inhalation) associated with 

the use of an airless sprayer, low pressure hand wand, and brush/roller; various 

pouring/mixing activities for liquid and solid materials (paints/stains and slurries); and 

indoor surface residue dissipation data for plastic toys and textiles. The Task Force has 

indicated the exposure data requirement will be satisfied through its membership in the 

American Chemistry Council's (ACC) Antimicrobial Exposure Assessment Task Force II 

(AEATF Il). For the textiles and toys, the Task Force is reassessing the role ofMBC in 

the textile market, and intends to limit the use of MBC in plastics to articles that are not 

toys. Pending a final decision with respect to MBC in textiles and plastics, the Task 

Force has requested the Agency hold the residue dissipation requirement in reserve. 

EPA Response: The Agency considers the proposed use of the AEA TF II data to be an 

acceptable approach to providing the additional occupational and residential exposure 

information for MBC. With respect to the impregnated toys, no data would be required if 

these products are removed from the market. Likewise, no data would be required if 

textiles containing MBC are no longer marketed. 

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