UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: August 12, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUHJECT: Thiabendazole and Salts: Health Effects Division's Response to Comments on 

the Thiabendazole Preliminary Work Plan (PWP) for Registration Review 

PC Code: 060101 (thiabendazole); 

0601 02 (thiabendazole hypophosphite) 

Decision No.: 492770 

Petition No.: N/ A 

Risk Assessment Type: N/ A 

TXR No.: N/A 

MRID No.: N/ A 

FROM: Jessica Kidwell, Rjsk Assessor 

Sue Hummel, Chemist 

DP Barcode: 421318 

Registration No.: N/A 

Regulatory Action: Registration Review 

Case No.: 2670 

CAS No.: 148-79-8 (thiabendazole); 

28558-32-9 (thiabendazole hypophosphite) 

40 CFR: § 180.242 

}WM--~Lf 

Bonnie Cropp-Koh11igian, Dietary Exposure 

Abdallah Khasawinah, Toxicologist 

RAB IV, Health Effects Division (HED) (7509P) 

THROUGH: Elissa Reaves, Ph.D., Branch Chief 

RAB IV, Health Effects Division (HED) (750 

TO: Ricardo Jones, RM51 

Thomas Moriarty 

RMIB 1, Pesticide Re-Evaluation Division (7508P) 

A second set of public comments was received on the thiabendazole PWP which are pertinent to 

HED concerns. These comments were submitted by Syngenta and were related to the proposed 

developmental thyroid toxicity test, tolerances, additional acute toxicity studies, as well as minor 

errors/omission in the scoping document. (Note: The first set of public comments were addressed 

in a June 14, 2014 memo (0420713) and pertained to tolerances and international 

harmonization.) 

Page 1 ofS 
Summary of Comments from Syngenta: 

• Registrant requests meeting to discuss development thyroid toxicity test 

• The Registrant agrees with EPA's recommendation that tolerances need to be revised 

• Registrant noted that new studies had recently been submitted, acute toxicology studies 

(MRIDs 46556301-46556305, and MRID 47321101- Decision Nos. D318065 and 

0470608). Proposed a revised toxicity profile. 

• Noted an additional dose level was missing in the description of the oral toxicity study 

• Noted errors/misspellings in MRID numbers 

The first two comment below refer specifically to the Thiabendazole Preliminary Work Plan; 

Registration Review: Initial Docket, Case Number 2670; dated March 2014, (EPA-HQ-OPP2014-0175-0008). 

1) Syngenta Comment: Syngenta requests the opportunity to discuss the developmental 

thyroid toxicity study with the Agency. 

PAGE#, Paragraph# EPA statement 

Page 7, Table 1 Developmental thyroid toxicity, rat 

Outstanding Data 

Requirements from 

Conditional Registrations 

HED Response: HED welcomes the opportunity to discuss this outstanding data requirement. 

The Agency will be meeting with Syngenta on August 12, 2014 to discuss the developmental 

thyroid toxicity study design. 

2) Syngenta Comment: Syngenta concurs with the Agency's comment and requests the 

review of the Definition of Residue for Crop Rationale included in this submission. 

PAGE#, Paragraph# EPA statement 

Page 12, Table 4 Tolerances are established under 40 CFR 180.242 for residues of 

Anticipated Risk thiabendazole, however a number of U.S. tolerances are not compatible with 

Assessments for the Canadian or CODEX MRLs. The tolerance residue definition and levels will 

Thiabendazole Registration need to be examined during Registration Review to determine if compatibility 

Review can be achieved. 

HED Response: HED will review the Definition of Residue for Crop Rationale during 

Registration Review. 

Page 2 ofS 
The following comments are specifically related to HED's scoping document ("Thiabendazole 

and Salts: Human Health Risk Scoping Document in Support of Registration 

ReviewH, dated March 12, 2014. (EPA-HQ-OPP-201 4-01 75-0009) 

3) Syngenta Comment: During the RED for thiabendazole, Syngenta conducted and 

submitted new acute toxicology studies (MRIDs 4655630 l-46556305, and MRID 

47321101 ). Please refer to Decision Nos. D318065 and D470608. Syngenta requests the 

acute toxicology results in Table 4 be revised to reflect the new data. 

PAGE#, Paragraph# EPA statement 

Page 5, Paragraph 2 Thiabendazole showed no significant toxicity in a battery of acute toxicity 

tests (Toxicity Category Ill for oral and dermal toxicity, Category Ill for 

inhalation, eye and dermal irritation) and not a sensitizer. 

PAGE#, EPA statement 

Paragraph# 

Page 21 , 

Table 4 Table 4: Tbiabendu.ole Acute t oxidtyi'J"otile: November 2013 

GuJdellne -· Study Type MRID # Results Toxicity 

No. Cateeory 

870. 1100 Acute Oral Toxicity- rat 4 12S8201 ( 198 1) LDso =4735 mg!kg rn 

870.1200 A CU[.c Dennal Toxic ity· 4125 8102 (1989) LD50 = .>2000 III 

rabbit mg/kg -- 870.1300 Acute lnhalation 00 100706 ( 1981) >6.84 mg/L IV 

Toxicity- rat 46454905 >2.63 mg/L Ill 

I {2004)* 

870.2400 Acute Eve Irritation 407&9&06 (1981') Non-irri catll)g IV 

870.2500 Acute De rrnal Irritation 40789807 ( 1981) Non-irritating TV " 870.2600 Skin Sensitiza.tion 40271701 (1986) Non sensitizer - "41. 5% w/w fonnuiation 

New Data to be used· 

Guideline No. Study Type MRID# Results Toxicity Category 

870.1100 Acute Oral Toxicity 46556301 LD50 > 5000mg/kg IV 

- rat 

870.1200 Acute Dermal 46556302 LDso > 5000mg/kg IV 

Toxicity - rabbit 

870.1300 Acute Inhalation 473211 01 LCso > 0.53 mg/L Ill 

Toxicity - rat (both sexes) 

870.2400 Acute eye Irritation 46556303 Reversible within Ill 

48 hrs 

870.2500 Acute Dermal 46556304 Non-irritating IV 

Irritation 

870.2600 Skin Sensitization 46556305 Non sensitizer -

Page 3 of5 
HED Response: HED will revise the toxicity profile to include the new acute toxicity data 

submitted. This revision will be reflected in future thiabendazole actions. 

4) Syngenta Comment: According to TXR 0013986, the NOAEL should be 25 mg/kg/day 

rather than 10 mg/kg/day. This appears to be a typographical error. 

PAGE#, Paragraph# EPA statement 

Page 21, Guideline No. /Study Type 

Table 5 870.3100/3-month oral toxicity study -rats (gavage) 

MRID No. 42942801 (1990) 

Dose Levels: 0, 25, 100, 400 mg/kg/day 

NOAEL = 10 m.g/kg/day 

EPA Response: This typographical error will be corrected and reflected in future thiabendazole 

actions. 

5) Syngenta Comment: There was an additional dose level tested in this study. Please add 

320 mg/kg/day to the dose levels. 

PAGE#, Paragraph# EPA statement 

Page 21, Guideline No. /Study Type 

Table 5 870.31 00/3-month oral toxicity study -rats (gavage) 

MRID No. 42942802 (1990) 

Dose Levels: 0, 10,40,160 mg/kg/day 

NOAEL = 1 0 mg/kg/day 

EPA Response: HED will make this correction and it will be reflected in future thiabendazole 

actions. 

6) Syngenta Comment: Please correct the MRID No. from 48996309 to 

489963 10 for the acute neurotoxicity study. Please correct the MRID No. 

from 48996310 to 48996309 for the subchronic neurotoxicity study. 

PAGE#, Paragraph# EPA statement 

Page 24, Guideline No. /Study Type 

Table 5 870.6200-Acute neurotoxicity in rats 

MRID No. 48996309 (2012) 

Dose Levels: 0, 50, 200, 2000 mg/kg/day 

NOAEL = 50 mQ/kq/day 

PAGE#, Paragraph# EPA statement 

Page 24, Guideline No. /Study Type 

Table 5 870.6200-Subchronic neurotoxicity in rats 

MRID No. 48996310 (2012) 

Dose Levels: 0, 200, 750, 1500 ppm 

Page 4 ofS 
HED Response: HED will make the corrections to the MRIDs as requested. These corrections 

will be reflected in future thiabendazole actions. 

7) Syngenta Comment: Please correct the MRID No. from 48996302 to 48996311 for the 

Immunotoxicity study. 

PAGE#, Paragraph# EPA statement 

Page 27, Guideline No. /Study Type 

Table 5 870. 7800-lmmunotoxicity 

MRID No. 48996302 (2012) 

HED Response: HED will correct the MRID for the Immunotoxicity study for any future 

thiabendazole actions. 

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