UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

DATE: July 28, 20 15 

SUBJECT: Cyazofamid. Response to ISK Biosciences Corporation Comments Submitted to 

Cyazofamid Docket (Docket No. EPA-HQ-OPP-2015-01 28). 

PC Code: 085651 

Decision No.: 505936 

Petition No.: NA 

DP Bar code: 0 427776 

Registr ation No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: NA Case No.: 7056 

TXR No.: NA CAS No.: 120116-88-3 

MRJD No.: NA 40 CFR: § 180.60 I 

FROM: Kristin Rury, Biologist ~ ~ /".:) 

Whang Phang, Senior ox c; og ~D Nancy 

Risk Assessment 

Dodd, Chemis

Branch 

t ~~ 

Ill ~B III) 

Health Effects Division (7509P) 

Office of Pesticide Programs 

THROUGH: C.Ju·istine Olinger, Branch Chief ~//~ '-

TO: 

Risk Assessment Branch Ill (RAB3 _,. 

Health Effects Division (7509P) 

Office of Pesticide Programs 

Jose Gayoso, Chemical Review Manager 

Cathryn Britton, Team Leader 

Pesticide Re-Evaluation Division (PRO) (7508P) 

Office of Pesticide Programs 

Executive Summary 

Detailed Response to Comments 

I. Cyazofamid PreliminG1y Work Plan Registration Review: Initial Docket Case Number 

7056 March 2015). 

a. Page -I. Table 1: Anticipated Data Needs for Cyazofamid Registration Review. 

!SK Response: The storage stability data were submitted on November 20, 2006 

(1\1/RID #-16989701). 

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HED Response: The storage stabilty data have been reviewed and the review is now finalized 

(N. Dodd, 0425460, 05/05/20 15). Therefore, the Agency agrees with the Registrant that this 

data gap is resolved. 

b. Page 6, Table 3: Under USE AND USAGE INFORMATION. Formulation Type(s) 

listed is emulsifiable concentrate. /SK Response: The only formulation type 

available is suspension concentrate. 

HED Response: HED agrees with the Registrant that the only registered formulation type 

available is suspension concentrate. 

c. Page 6, Table 3: Under USE AND USAGE NFORMATION. Application 

Method(s) listed include ground, aerial, chemigation, and hand held spray 

equipment. /SK Response: Currently used application methods include only 

broadcast (ground and aerial), chemigation, and soil/growth media drench 

treatment. 

HED Response: The registered cyazofamid labels (EPA Reg. Nos. 071512-2, 07 1512-3, 

071515-13) do not restrict the use of handheld application equipment. It is HED policy to assess 

occupational exposure using handheld equipment for crops HED classifies as '·typical field 

crops" and crops grown in greenhouses. If the Registrant wishes to restrict the use of handheld 

equipment, language should be added to the registered labels restricting these application 

methods. 

2. Cyazofamid. Human Health Assessment Scoping Document in Support of Registration 

Review November 21, 2014 (EPA-HQ-OPP-2015-0128-0006). 

a. Page 2, Executive Summary, second paragraph states that "on .January 8, 2015, 

!-!ED 's Hazard and Science Policy Council (HASPOC), based on a weight of 

evidence approach considering all the available hazard and exposure information 

granted a waiver/or the .rnbchronic neurotoxicity and immunotoxicity studies that 

are required under the 2007 40 CFR toxicology data requirements (TXR No. 

00563-11). !SK Response: We are unsure wily a waiver was considered for tllese 

two studies in 2015 since we llad submitted botll of tllese studies to tile Agency 

011July25, 2015 (MRID Nos. 48891 702 & 48891 701, respectively) in response 

to tile co11ditio11al registration letters of July 29, 2009 (Decision Nos. 469061, 

469062, 469065) and the co11ditio11al registratio11 letters of A ugust 13, 2010 

(Decision Nos. 420978, 420980). Both of these studies were subsequently 

reviewed mulfountl Acceptable/Guideline by the Agency in tlleir DER dated 

July 26, 2013, DP# D405012. Please correct your records. 

HED Response: HED will con-ect the records to reflect that both immunotoxicity and 

subchronic neurotoxicity studies have been submitted and reviewed. These two study 

requirements are met. 

Page 2 or 4 
b. Page 2, Executive Summary. fifth paragraph, and Page 4, Diel01y Exposure, third 

paragraph state "The storage stabilty data are (currently) under review. " /SK 

Response: This data was a condition of registration in 2004. We submitted this 

data 011 November 20, 2006. Since this issue llas not been raised in Agency 

reviews since that time for several new crop registrations, we assumed tile 

Agency llad reviewed tile data am/ found it acceptable. 

HED Response: The storage stabilty data have been reviewed and the review is now finalized 

(N. Dodd, 0 425460, 051051201 5). Therefore, the Agency agrees with the Registrant that this 

data gap is resolved. 

c. Page 3, Introduction, second paragraph, third sentence stales "HomeoHmers may 

apply cyazofamid to residential twf and ornamental plants." (A lso mentioned on 

Page 5). /SK Response: Since we have never intended for this product to be 

sold to tile '10111eow11er, we specifically state 011 our turf label that "Application 

by home-owners to residential turf is prohibited. " As we were instructed by tile 

EPA wlle11 tile turf use was first registered. Please advise if a different 

statement is now required to prevent use 0 11 lawns by tile llomeowner. 

HE D Response: It is now HED policy to conduct a residential assessment for products 

registered on turf and ornamentals unless the use site is restricted on the label. ISK should 

consult with the Registration Division (RO) on the appropri ate label language to delineate the 

intended use sites and specifically restrict application to residential turf. For example: 

.. For use on sod farms, seed farms, go(f courses, professionally managed college and 

professional sports fields, industrial and commercial lawns and other similar 

nonresidential areas. Do not apply to residential twf or twf in residential areas". 

d. Page 3, Hazard Identification/Toxicology, first paragraph, first sentence states 

"The toxicology database for Cyazofamid is adequate for risk assessment, except 

for the immunotoxicity and subchronic neurotoxicity studies." /SK Response: As 

noted in 2a. above, both of these studies were subsequently found acceptable by 

the Agency in their review dated July 26, 2013, DP# D405012. Tile NOAEL 

and LOAEL were determined to be 6000 ppm (1381 mg/kg/day) and >6000 ppm, 

respectively in tile imnwnotoxicity study. Tile NOA EL and LOA EL were 

determined to be 20,000 ppm (1356 mg/kg/day) and >20,000 ppm, respectively 

in tile subchrouic neurotoxicity study. Please correct your records. 

HED Response: HED will correct the record to reflect the immunotoxicity and subchronic 

neurotoxicity studies req uirements are met. In addition, a sentence indicating "the 

toxicology database for cyazofamid is considered complete" will replace the first 

sentence on page 3, Hazard Identificationffoxicology section. 

e. Page 9, Tolerance Assess men/ and fn/ernalional Harmonization, firs! paragraph, 

the discussion on the tolerances, .. . " inc/11cle permanent Section 3 tolerances, a 

Section 18 emergency exemption tolerance, and a tolerance with regional 

Page 3 of 4 
registration. The plant tolerance levels range from 0. 02 ppm lo 1././ ppm. ·· /SK 

Response: Altltouglt the Section 18 tolerance exemption 011 basil (144 ppm) 

didn 't expire until December 31, 2014, it was replaced by Section 3 tolerances 

(30 ppm/or fresh, 90 ppm for dried basil) and registrations for basil that were 

granted 011 September14, 2012. Titus, tlte highest tolerance currently in efect 

is 90 ppm. Please update the document. 

HED Response: The Section 18 tolerance expired on 12/31 /14. The highest tolerance is now 90 

ppm. 

f Page 12, References, Toxicology /SK Response: Please add tltefollowing 

reference: V. Chen; D405012; 7126113; Cyazofamid: Neurotoxicity and 

lmm11110toxicity Data Review. 

HED Response: HED will add the reference. 

g. Page 23, Toxicity Profile Table, second to the last entry, "Study not available''. 

lSK Response: As noted above ill 2a and 2d, a 90-day neurotoxicity and 

immunotoxicity study were submitted and accepted by the Agency, and the table 

should be corrected as follows: 

860.6200b Subchronic neurotoxicity : MRID No. 48891 702 (2012): 

Acceptablelguideli11e; 0, 500, 2000, 20000 ppm (0, 34139, 1341156, & 135611539 

mg/kg/day males/females respectively),· systemic toxicity and 11eurotoxicity NOAEL 

= 20,000 ppm, (1356 mg/kg/day); systemic toxicity and 11eurotoxicity LOA EL > 

20,000 ppm (1356 mg/kg/day) 

870. 7800 28-day Dietary Immunotoxicity Study: MRID No. 48891701 (2012); 

Acceptable/guideline; 0, 600, 3000, 6000 ppm (0, 136, 599, & 1381 mglkg/day); 

Systemic toxicity and im1111111otoxicity NOAEL is 6000 ppm (1381 mg/kg/day) and 

LOAEL is >6000 pprn (1381 mg/kg/day). 

HED Response: HED has corrected this entry. We will correct our records according to the data 

evaluation report (DER). 

HED will correct the hazard and exposure records for cyazofamid during risk assessment phase 

of Registration Review. 

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