Document ID: EPA-HQ-OPP-2008-0731-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-07-08T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES,

AND TOXIC SUBSTANCES

MEMORANDUM

Date:		3-June-2009

SUBJECT:	Cyazofamid.  Amendment to D356837, D356878 Human Health Risk
Assessment for Proposed Uses on Fruiting Vegetables and Okra, Grapes
East of the Rocky Mountains, Vegetable Greenhouse Transplants, and
Commercial Application on Residential Turf and Residential Ornamentals.

PC Code:  085651	DP Barcodes:  D366114, D356837, D356878  

Decision Nos.: 399077, 399610	Registration Nos.: 71512-3, 71512-13

Petition No.:  8E7427 	Regulatory Action:  Section 3 Registration 

Risk Assessment Type:  Single Chemical/Aggregate	Case No.: NA

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

MRID No.:  NA	40 CFR: 180.601

FROM:	Nancy J. Tsaur, Risk Assessor

	Amelia Acierto, Chemist

	Barry O’Keefe, Sr. Biologist

	Whang Phang, Toxicologist

	Risk Assessment Branch 3 (RAB3)

	Health Effects Division (7509P)

THROUGH:	Paula Deschamp, Branch Chief 

Risk Assessment Branch 3 (RAB3)

Health Effects Division (7509P)

TO:	Janet Whitehurst/Tony Kish, Risk Management Team 22 

	Fungicide Branch (FB)

	Registration Division (7505P)

		and

	Laura Nollen/Daniel Rosenblatt, Risk Management Team 05

	Fungicide Branch/RIMUERB

	Registration Division (7505P)

This memorandum amends the Cyazofamid Human Health Risk Assessment
(D356836, D356878, Nancy J. Tsaur, 20-May-2009) to reflect the following
changes:

amend proposed use pattern information (Executive Summary)

amend residue chemistry deficiencies (request for a revised Section F)

amend assessed short- and intermediate-term populations in Table 6.2

correct a typographical error in Table 3.2.1

With the exception of these modifications, all the information contained
in the 20-May-2009, 2008 risk assessment document remains unchanged.

Proposed Uses on Turf and Ornamentals

This assessment addresses only the proposed new use of Cyazofamid 400SC
to control: 1) Pythium and Downy mildew diseases on professionally
managed residential turf.  The 400SC formulation is currently registered
for use on professionally managed turf areas such as golf courses and
other non-residential turf areas including sod farms, seed farms,
college and professional sports fields, and commercial lawns.

Recommended Tolerances

The petitioner should submit a revised Section F reflecting the
following recommended tolerances and commodity definitions for the
combined residues of cyazofamid, 4-chloro-2-cyano- N,N
-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide, and its
metabolite CCIM,
4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, expressed as
cyazofamid, in or on the following commodities:

Commodity	Recommended Tolerance (ppm)

Vegetable, Fruiting, Group 8	0.40

Okra	0.40

Short- and Intermediate Term Aggregate Risk Assessment

Incidental oral exposures are not expected for children 6-12 years old;
therefore this population has been removed from the short-term and/or
intermediate-term aggregate risk calculations and Table 6.2 is modified
accordingly.

Table 6.2.  Short-Term and/or Intermediate-Term Aggregate Risk
Calculations 

Population	Short- or Intermediate-Term Scenario

	LOC for Aggregate

Risk1	MOE

food & water2	MOE

oral3	MOE

dermal4	MOE inhalation5	Aggregate MOE

(food and residential)6

General U.S. Population	100	25,100	NA	1,100	NA	1,100

Children 1-2 years old

10,800	1,600	NA	NA	1,400

Summary of Toxicological Endpoints – Typographical correction

The level of concern for adult dermal short-term (1-30 days) and
intermediate-term (1-6 months) exposure is an MOE rather than an Acute
RfD. This correction does not alter calculations used in the risk
assessment.

Table 3.2.1.  Toxicological Doses and Endpoints for Cyazofamid for Use
in Dietary and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	RfD, PAD, Level of Concern for Risk Assessment	Study
and Toxicological Effects

Acute Dietary (General Population, including Infants and Children)	No
adverse effects were observed which could be attributed to a single-dose
exposure for the general population

Acute Dietary

(Females 13-49 years of age)	NOAEL = 100 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Acute RfD = 1.0 mg/kg/day	Rat Prenatal Developmental Toxicity (MRID
45408933)

LOAEL = 1,000 mg/kg/day based on developmental toxicity findings of
increased incidence of bent ribs.

Chronic Dietary (All Populations)	NOAEL= 94.8 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Chronic RfD = 0.948

mg/kg/day

	18-Month Mouse Oral Carcinogenicity (MRID 45408932)

LOAEL = 985 mg/kg/day based on increased skin lesions.

Incidental Oral Short-Term (1-30 days) and Intermediate-Term (1-6
months)	NOAEL= 30 mg/kg/day 	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Residential LOC for MOE = 100	 90-Day oral toxicity study in rats.
LOAEL= 295 mg/kg based on 

Increased number of basophilic tubules of the kidneys, increased urinary
volume, pH, & protein.  This toxicity endpoint is also supported by the
results of a 28-day oral dose- range- finding study in rats. In this
study, at 370 mg/kg/day or above   increased incidence of basophilic
tubules in the kidneys was found.  

Dermal Short-Term (1-30 days) and Intermediate-Term (1-6 months)	For
CHILDREN:

No toxicity was found at 1000 mg/kg in a 28-day dermal toxicity study,
therefore, in the absence of hazard identified for this population, a
risk assessment is not necessary.

	For ADULTS:

NOAEL = 100 mg/kg/day

(Dermal Absorption Rate = 37%)	

UFA= 10x

UFH= 10x

FQPA SF= 1x

	

Residential LOC for MOE = 100	

Rat Prenatal Developmental Toxicity (MRID 45408933)

LOAEL = 1,000 mg/kg/day based on developmental toxicity findings of
increased incidence of bent ribs.

Inhalation Short- Term (1-30 days) and Intermediate-Term (1-6 months)	No
residential exposure is expected via inhalation route.

Cancer (oral, dermal, inhalation)	Classification:  “Not likely to be
Carcinogenic to Humans” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.