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 Respons e 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 Reg istration No.: N/A Regulatory Action: Regi stration Review Case No.: 2670 CAS No.: 148-79-8 (thiabendazole); 28558 -3 2-9 (thiabendazole hypophosphite) 40 CFR : § 180.242

# }WM--~Lf Bonnie Cropp-Koh11igian , Dietary Exposure Abdallah Khasawinah, Toxicologist RAB IV , Health Effects Division (HED) (7509P) THROUGH: E lissa Reave s, 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. T hese comments were submitted by Syngenta and were related to the proposed developmental thyroid toxicity test, tolerances, addit ional acute toxicity studies , as well as minor errors/omission in the scoping document. (Note: The first set ofpublic comments were addre ssed in a June 14 , 2014 memo (0420713) and pertained to tolerance s and international harmonization.)

Page 1 ofSSummary of Comments from Syngenta: • Registrant requests meet ing 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 s ubmitted, acute toxicology studies (MRIDs 46556301-46556 305, and MRID 473211 0 1- Decision Nos. D318065 and 0470608)
. Proposed a revised toxicity profile. • Noted an additional dose level was missing in the description of the oral toxicity s tudy • 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 Deve lopmental 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 reques ts 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 t he 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 ofSThe follow ing comments are specifically related to HED's scoping document ("Thiabendazole and Salts: Human Health Risk Scoping Document in Support ofRegi stration Rev iewH, 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 toxico l ogy 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 tox i city tests (Toxic ity Category Il l for ora l and dermal toxicity, Category Ill for inha l ation, eye and dermal irritation) and not a sensitizer.
PAGE# , EPA statement Paragraph# Page 21 , Table 4 Tab le 4 : Tbiabendu.o le Acute t oxidtyi'J"otile : November 2013 

# -· GuJdellne S tudy Type MRID # Resu lts T oxici ty N o . Cateeory 870. 1 100 Acute Oral Toxicity- rat 4 12S8201 ( 1 98 1 ) LDso =4735 mg!kg 

## rn 870.1200 A C U[.c Dennal Toxic ity · 4125 8102 (1989) LD 50 = .>2000 III rabbit mg/kg



# -- 870.1300 Acute lnhal ation 00 100706 ( 1981) > 6.84 mg/L IV To xicity

- rat 46454905 >2
.63 m g/L Ill 

## I {2004)* 870 .2400 Acute Eve I rri tatio n 4 07& 9&06 (1981') Non -irri catll)g IV 87 0 .25 0 0 Acute De rrn al Irritati o n 40789807 ( 1981) Non-i rrita ting TV " 870.2600 Skin Sensitiza.tion 4027170 1 (1986) Non sensi tiz er 

## -

"41. 5 % w /w fo nnuiation

New Data to be used · Guideline No
. Study Type MRID# Results Toxicity Category 870
. 1100 Acute Oral Toxicity 46556301 LD 50 > 5000mg/kg IV

- rat 870.1200 Acute De r ma l 46556302 LDso > 5000mg/kg IV Toxic ity - rabbit 870
. 1300 Acute Inhalation 4732 11 01 LCso > 0.53 mg/L Ill Tox i ci t y - rat (bot h sexes) 870.2400 Acute eye I rritation 46556303 Reversib l e within I ll 48 hrs 870.2500 Acute Dermal 46556304 Non-irritating IV I rritation 870.2600 Skin Sensitization 46556305 Non sensitizer 

## - Page 

### 3 of5HED 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 fut ure 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 Leve ls: 0, 10,40 , 160 mg/kg/day NOAEL = 1 0 mg/kg/day EPA Response: HED wi ll make this correction and it will be reflected in future thiabendazole actions. 6) Syngenta Comment: P lease 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 ra ts MRID No. 48996310 (2012) Dose Leve ls: 0, 200 , 750 , 1500 ppm Page 4 ofSHED Response: HED will make the corrections to the MRIDs as reques ted
. These corrections wi ll be reflected in future thiabendazole actions. 7) Syngenta Comment: Please correct the MRID No. from 48996302 to 48996311 for the Immunotoxic ity s tudy. PAGE# , Paragraph# EPA statement Page 27, Guideline No. /Study Type Table 5 870. 7800-lmmunotoxicity MRID No
. 48996302 (2012)
HED Response: HED w ill correct the MRID for the Immunotoxicity study for any future thiabendazole actions.

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