Document ID: EPA-HQ-OPP-2008-0042-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-10-15T04:00Z

SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDES

                                                                        
                   AND TOXIC SUBSTANCES

	

MEMORANDUM 

Date:  6-May-08 

SUBJECT:	Cyprosulfamide: Chronic Aggregate Dietary (Food and Drinking
Water) Exposure and Risk Assessment for the Section 3 Registration
Action (New Active Ingredient) for the proposed uses on field corn, pop
corn, sweet corn and sorghum (seed treatment) 

PC Code:877400  	DP Barcode: D351493  

Decision No.: 378533	Registration No.: None

Petition No.: 7E7206	Regulatory Action: Section 3 Registration,
Tolerance Petitions

Risk Assessment Type: Single chemical aggregate 	Case No.: None

TXR No.: None	CAS No.: 221667-31-8

MRID No.: None	40 CFR: None

FROM:	Seyed Tadayon, Chemist

Reregistration Action Branch 3

Health Effects Division (7509P)

THROUGH:	Thurston Morton, Chemist

David Hrdy, Sr. Scientist

Dietary Exposure Science Advisory Council (DESAC)

Health Effects Division (7509P)

and

William Donovan, Chemist

Reregistration Branch III

Health Effects Division (7509P)

TO:		Karen Angulo, PM

Inert Branch

Registration Division (7505P)

Executive Summary

Acute and cancer dietary assessments were not conducted for
cyprosulfamide.  An acute dietary assessment was not conducted because
an endpoint attributable to a single dose was not identified from the
available data.  A cancer dietary assessment was also not conducted
because cyprosulfamide is not likely to be carcinogenic to humans (CARC
February 29, 2008).

A chronic aggregate dietary (food and drinking water) exposure and risk
assessment was conducted using the Dietary Exposure Evaluation Model
DEEM-FCID™, Version 2.03, which uses food consumption data from the
U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by
Individuals (CSFII) from 1994-1996 and 1998.  The analysis was performed
to support Section 3 requests and permanent tolerances for
cyprosulfamide residues in/on field corn, pop corn and sweet corn. 

  

Chronic Dietary (Food and Drinking Water) Exposure Results and
Characterization

The chronic dietary (food and drinking water) exposure assessment was a
conservative assessment using the recommended tolerance levels and
assuming that 100% of the crop was treated.  Default processing factors
were used in cases where an adequate processing study was not available
for particular matrices in DEEM.  

 

The chronic dietary (food and drinking water) exposure to cyprosulfamide
is below HED’s level of concern for the general U.S. population and
all population subgroups.   

I.	Introduction

Dietary risk assessment incorporates both exposure and toxicity of a
given pesticide.  For acute and chronic assessments, the risk is
expressed as a percentage of a maximum acceptable dose (i.e., the dose
which HED has concluded will result in no unreasonable adverse health
effects).  This dose is referred to as the population adjusted dose
(PAD).  The PAD is equivalent to point of departure (POD, NOAEL, LOAEL,
e.g.) divided by the required uncertainty or safety factors.

This memorandum presents the first dietary risk assessment for
cyprosulafamide,t Therefore

no CFR is yet available.

II.	Residue Information

(See D341999, W.Donovan, 20-May 2008)

Cyrosulfamide applied on field corn, pop corn, sweet corn and sorghum. 

Tolerances have recently been proposed for residues of cyprosulfamide,
[N-[[4-[(cyclopropylamino)
carbonyl]phenyl]sulfonyl]-2-methoxybenzamide], on corn at 0.01 ppm. HED
is presently recommending for the following tolerances for
cyprosulfamide:

Corn, field,
grain……………………………….………….0.01PPM

Corn, pop, grain…………………………………………  
0.01PPM

Corn, sweet, kernel plus cob with husks removed………0.01 PPM

Cattle, meat byproduct……………………………………0.02PPM

Goat, meat byproduct……………………………………..0.02PPM

Horse, meat byproduct……………………………………0.02PPM

Sheep, meat byproduct……………………………………0.02PPM

Residue Data used for the Chronic Assessment:

 

 (See D341999, W.Donovan, XX-May 2008)

The chronic dietary (food and drinking water) exposure assessment for
cyprosulfamide was a conservative assessment using the
recommended/established tolerance levels and assuming that 100% of the
crop was treated.  

   Drinking Water Data

The drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED).  Water
residues were incorporated in the DEEM-FCID into the food categories
“water, direct, all sources” and “water, indirect, all sources.”
  

This drinking water exposure value addresses potential human exposure to
cyprosulfamide residue through ingestion of drinking water from uses on
corn.  No monitoring data of cyprosulfamide were available to the
Environmental Fate and Effects Division (EFED).  Surface water
concentrations were estimated using the Tier I model FIRST.  Ground
water concentrations were estimated using the Tier I SCI-GROW (Screening
Concentration in Ground Water) model.  Cyprosulfamide may be applied by
aerial or ground as per the label for this product.  

Based on modeling result, the estimated chronic surface water (drinking
water) concentration for cyprosulfamide and metabolites M02 and M04 is: 

2.4 ug/L for the 1-in-10 year annual mean concentration (non-cancer
chronic) 

The SCI-GROW estimated ground water (drinking water) concentrations for
cyprosulfamide are not expected to exceed 0.14 μg/L, which was based on
1 application of 0.141 lb ai/acre per application.

This chronic dietary assessment used the value of 2.4 ug/L (ppb) for
drinking water and will represent a conservative estimate for ground
water.

The model and its description are available at the EPA internet site:  
HYPERLINK "http://www.epa.gov/oppefed1/models/water/" 
http://www.epa.gov/oppefed1/models/water/ .  

FCID™ Program and Consumption Information

A cyprosulfamide chronic dietary exposure assessment was conducted using
the Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database DEEM-FCID™, Version 2.03, which incorporates
consumption data from USDA’s Continuing Surveys of Food Intakes by
Individuals (CSFII), 1994-1996 and 1998.  The 1994-96, 98 data are based
on the reported consumption of more than 20,000 individuals over two
non-consecutive survey days.  Foods “as consumed” (e.g., apple pie)
are linked to EPA-defined food commodities (e.g. apples, peeled fruit -
cooked; fresh or N/S; baked; or wheat flour - cooked; fresh or N/S,
baked) using publicly available recipe translation files developed
jointly by USDA/ARS and EPA.  For chronic exposure assessment,
consumption data are averaged for the entire U.S. population and within
population subgroups, but for acute exposure assessment are retained as
individual consumption events.  Based on analysis of the 1994-96, 98
CSFII consumption data, which took into account dietary patterns and
survey respondents, HED concluded that it is most appropriate to report
risk for the following population subgroups: the general U.S.
population, all infants (<1 year old), children 1-2, children 3-5,
children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50+
years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup.

V.	Toxicological Information

The cyprosulfamide Risk Assessment Team selected endpoints for this new
pesticide.  The cyprosulfamide CARC was held on 29-FEB-2008.  An HED
ROCKS meeting was held on 06-MAR-2008 and the RARC was held on
24-APR-2008.

It is recommended that the 10X FQPA safety factor for the protection of
infants and children be removed.  There were two developmental toxicity
studies in rabbits and together these studies demonstrated a NOAEL of
125 mg/kg/day for maternal toxicity and 250 mg/kg/day for developmental
toxicity.  Thus, neither study indicated an increased sensitivity of the
fetuses relative to the doses.  The reproduction study did not
demonstrate increased susceptibility of the offspring to cyprosulfamide.
 Specific neurotoxicity was not identified in the rat, mouse and dog
subchronic or chronic studies or in the rat acute and subchronic
neurotoxicity screen studies.  

 

Table 1.   Summary of Toxicological Doses and Endpoints for
Cyprosulfamide for Use in Dietary Exposure Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	RfD, PAD,
Level of Concern 	Study and Toxicological Effects

Acute Dietary (All Populations)	None	None	None	An endpoint attributable
to a single dose was not identified from the available data.

Chronic Dietary (All Populations)	NOAEL= 39 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Chronic RfD = 

0.39 

mg/kg/day

cPAD = 0.39 mg/kg/day	Chronic feeding/carcinogenicity - rat

LOAEL = 159 mg/kg/day based on nephropathy.

Cancer (oral, dermal, inhalation)	Classification:  “Not Likely to be
Carcinogenic to Humans”

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level. 
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor. 
UFA = extrapolation from animal to human (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  FQPA SF = FQPA Safety Factor.  PAD = population
adjusted dose (a = acute, c = chronic).  RfD = reference dose. 



VI.	Results/Discussion  

As stated above, for the chronic assessment, HED is concerned when
dietary risk exceeds 100% of the PAD.  The DEEM-FCID™ analyses
estimate the dietary exposure of the U.S. population and various
population subgroups.  The results reported in Table 2 are for the
general U.S. Population, all infants (<1 year old), children 1-2,
children 3-5, children 6-12, youth 13-19, females 13-49, adults 20-49,
and adults 50+ years.

Results of Chronic Dietary (Food and Drinking Water) Exposure Analysis

The chronic dietary (food and drinking water) exposure analysis was a
conservative assessment using the recommended tolerance levels and
assuming that 100% of the crop was treated.  Default processing factors
were used in cases where an adequate processing study was not available
for particular matrices in DEEM.  Based on a bovine feeding study with
cyprosulfamide, livestock tolerances are required for cyprosulfamide.  

 

The chronic dietary (food and drinking water) exposure to cyprosulfamide
is below HED’s level of concern for the general U.S. population and
all population subgroups.  

Table 2.  Summary of Dietary (Food and Drinking Water) Exposure and Risk
for Cyprosulfamide

Population Subgroup	Chronic Dietary

	Dietary Exposure (mg/kg/day)	% cPAD

General U.S. Population	0.000072	<1

All Infants (< 1 year old)	0.000194	<1

Children 1-2 years old	0.000119	<1

Children 3-5 years old	0.000121	<1

Children 6-12 years old	0.000087	<1

Youth 13-19 years old	0.000065	<1

Adults 20-49 years old	0.000065	<1

Adults 50+ years old	0.000060	<1

Females 13-49 years old	0.000064	<1

VII.	Characterization of Inputs/Outputs

A conservative chronic dietary (food and drinking water) exposure
assessment was

conducted.  Recommended tolerance level residues of cyprosulfamide
(parent) were used.  The

assessment assumed 100% of the crop was treated.  Default DEEM 7.81
processing factors were

used for corn syrup. 

VIII.	Conclusions

A chronic dietary (food and drinking water) exposure assessment was
conducted for the proposed uses on corn.  A conservative assessment was
conducted using tolerance level residues and assuming 100% of the crop
was treated.  

The chronic dietary (food and drinking water) exposure to cyprosulfamide
is below HED’s level of concern for the general U.S. population and
all population subgroups. The chronic dietary exposure estimates are <1%
cPAD for the general U.S. population and for all other population
subgroup.

IX.		List of Attachments

1.	Chronic Food plus Water Residue Input File

2.	Chronic Food plus Water Results File

Attachment 1:  Chronic Food plus Water Residue Input File

Documents and Settings\stadayon\Desktop\Cyprosulfamid.R98

Chemical: Cyprosulfamide

RfD(Chronic): .39 mg/kg bw/day  NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day  NOEL(Acute):  0 mg/kg bw/day

Date created/last modified: 04-17-2008/08:54:47/8          Program ver.
2.03

Comment: Cyprosulfamid Deem run

------------------------------------------------------------------------
--------

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2   

-------- ---- -------------------------------  ----------  ------ ------
 -------

21000460 M    Beef, meat byproducts             0.020000   1.000  1.000 

21000480 M    Beef, kidney                     	    0.020000   1.000 
1.000  

21000490 M    Beef, liver                                 0.020000  
1.000  1.000  

15001200 15   Corn, field, flour                      0.010000   1.000 
1.000  

15001201 15   Corn, field, flour-babyfood     0.010000   1.000  1.000  

15001210 15   Corn, field, meal                      0.010000   1.000 
1.000  

15001211 15   Corn, field, meal-babyfood     0.010000   1.000  1.000  

15001220 15   Corn, field, bran                      0.010000   1.000 
1.000  

15001230 15   Corn, field, starch                   0.010000   1.000 
1.000  

15001231 15   Corn, field, starch-babyfood  0.010000   1.000  1.000  

15001240 15   Corn, field, syrup                    0.010000   1.500 
1.000  

15001241 15   Corn, field, syrup-babyfood   0.010000   1.500  1.000  

15001250 15   Corn, field, oil                         0.010000   1.000 
1.000  

15001251 15   Corn, field, oil-babyfood        0.010000   1.000  1.000  

15001260 15   Corn, pop                                0.010000   1.000 
1.000  

15001270 15   Corn, sweet                             0.010000   1.000 
1.000  

15001271 15   Corn, sweet-babyfood            0.010000   1.000  1.000  

23001700 M    Goat, meat byproducts         0.020000   1.000  1.000  

23001720 M    Goat, kidney                          0.020000   1.000 
1.000  

23001730 M    Goat, liver                              0.020000   1.000 
1.000  

26003391 M    Sheep, meat-babyfood           0.020000   1.000  1.000  

26003400 M    Sheep, meat byproducts        0.020000   1.000  1.000  

26003420 M    Sheep, kidney                         0.020000   1.000 
1.000  

26003430 M    Sheep, liver                             0.020000   1.000 
1.000  

86010000 O    Water, direct, all sources       0.002400   1.000  1.000  

86020000 O    Water, indirect, all source     0.002400   1.000  1.000  

Attachment 2:  Chronic Food plus Water Results File

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for CYPROSULFAMIDE                   (1994-98
data)

Residue file name: C:\Documents and
Settings\stadayon\Desktop\Cyprosulfamid.R98

                                                 Adjustment factor #2
NOT used.

Analysis Date 04-17-2008/09:19:07     Residue file dated:
04-17-2008/08:54:47/8

Reference dose (RfD, Chronic) =0.39 mg/kg bw/day

COMMENT 1: 

========================================================================
====

                    Total exposure by population subgroup

                                                    		Total Exposure

                                        		
-----------------------------------

          Population                         		mg/kg             		
Percent of   

           Subgroup                      		 body wt/day            		
Rfd       

--------------------------------------   		-------------      			
---------------

U.S. Population (total)                    		 0.000072                		
    0.0%

U.S. Population (spring season)            	 0.000072                	  
                 0.0%

U.S. Population (summer season)                   0.000077              
	                    0.0%

U.S. Population (autumn season)                    0.000069             
 	                    0.0%

U.S. Population (winter season)                      0.000069           
  	                    0.0%

Northeast region                            	               0.000065    
                                          0.0%

Midwest region                              		 0.000075                 
                             0.0%

Southern region                            	               0.000070     
                                         0.0%

Western region                                                0.000079  
                                            0.0%

Hispanics                                 	               0.000082      
                                       0.0%

Non-hispanic whites                                        0.000070     
                                        0.0%

Non-hispanic blacks                                         0.000072    
                                        0.0%

Non-hisp/non-white/non-black                         0.000080           
                                 0.0%

All infants (< 1 year)                                         0.000194 
                                            0.0%

Nursing infants                                                 
0.000070                                              0.0%

Non-nursing infants                                           0.000241  
                                           0.0%

Children 1-6  yrs                                               
0.000118                                              0.0%

Children 7-12 yrs                                               0.000083
                                             0.0%

Females 13-19 (not preg or nursing)                  0.000060           
                                 0.0%

Females 20+ (not preg or nursing)                     0.000064          
                                  0.0%

Females 13-50 yrs                                              0.000068 
                                           0.0%

Females 13+ (preg/not nursing)                          0.000066        
                                    0.0%

Females 13+ (nursing)                                         0.000085  
                                         0.0%

Males 13-19 yrs                                                  
0.000070                                             0.0%

Males 20+ yrs                                                     
0.000062                                             0.0%

Seniors 55+                                                         
0.000059                                             0.0%

됂逃$愂Ĥ摧崥å

	

 

 

-

)

*

+

5

9

:

	

 

*

*

+

:

G

H

I

:

A

B

F

G

H

I

M

N

O

¥

¦

®

¯

¾

À

Ç

È

Ò

Ô

á

 I

f

…

¥

¦

È

â

Þ

ã

ú

#

ó

$

@

&

@

@

&

@

@

&

@

@

@

@

@

12 yrs                                                  0.000087        
                                  0.0%

Youth 13-19 yrs                                                   
0.000065                                           0.0%

Adults 20-49 yrs                                                   
0.000065                                          0.0%

Adults 50+ yrs                              		       0.000060           
                              0.0%

Females 13-49 yrs                          		       0.000064            
 0.0%

Cyprosulfamide	Dietary Exposure and Risk Assessment	DP Number: D351493	

PC Code:  877400		

________________________________________________________________________
______________

 PAGE   

                                                                        
        Page   PAGE  1  of   NUMPAGES  10