Document ID: EPA-HQ-OPP-2008-0361-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-08T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  1/7/2009

SUBJECT:  Cyhalofop-butyl.  Chronic Dietary (Food and Drinking Water)
Exposure Analysis for the Section 3 Registration Action  

 

PC Code:  082583	DP Number:  358391  

Decision No.:  391343	Registration No.:  62719-356 

Petition No.:  8E7341	Regulatory Action:  Section 3 

Risk Assessment Type:  Single Chemical/Aggregate 	Case No.:  None 

TXR No.:  None	CAS No.:  122008-85-9

MRID No.:   None	40 CFR:  180.576

		              							

	          	

FROM:  	Douglas Dotson, Ph.D., Chemist

	Registration Action Branch II

	Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 		

		

THROUGH:	Thurston Morton, Chemist

		Anant Parmar, Biologist

		HED Dietary Exposure SAC

		Richard Loranger, Ph.D., Senior Scientist

	Registration Action Branch II

Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 	

		

TO:		Sidney Jackson/Dan Rosenblatt, RM Team 05

		RIMUERB

		Registration Division (7505P)

Executive Summary

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 the establishment of a tolerance for wild rice and
re-establishment of the expired tolerance for rice grain.

   

Acute Dietary Exposure Results and Characterization

No toxic effects attributable to a single (i.e., acute) exposure to
cyhalofop-butyl have been identified.  As a result, an acute reference
dose (RfD) was not established for this chemical and an acute dietary
exposure assessment was not conducted.

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

A chronic dietary (food and drinking water) exposure and risk assessment
was conducted for cyhalofop-butyl using tolerance level residues, a
conservative estimate of residues in drinking water, and 100% crop
treated assumptions.  Cyhalofop-butyl exposure from the existing use on
rice and the proposed use on wild rice results in an estimated risk
equivalent to 4.5% of the chronic population adjusted dose (cPAD) for
the U.S. population.  The most highly exposed population subgroup is All
Infants (<1 year old), whose risk utilizes 15% of the cPAD.

Cancer Dietary Exposure Results and Characterization

In accordance with the EPA Final Guidelines for Carcinogen Risk
Assessment (March 29, 2005), cyhalofop-butyl is classified as “not
likely to be carcinogenic to humans.”  As a result, a cancer dietary
exposure assessment was not performed.

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 the point of departure (PoD, NOAEL,
LOAEL, e.g.) divided by the required uncertainty or safety factors.

For acute and non-cancer chronic exposures, HED is concerned when
estimated dietary risk exceeds 100% of the PAD.  HED is generally
concerned when estimated cancer risk exceeds one in one million. 
References that discuss the acute and chronic risk assessments in more
detail are available on the EPA/pesticides web site:  “Available
Information on Assessing Exposure from Pesticides, A User’s Guide,”
21-JUN-2000, web link:      HYPERLINK
"http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf" 
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf  ; or see
SOP 99.6 (20-AUG-1999).

The most recent dietary risk assessment for cyhalofop-butyl was
conducted by M. Doherty (Memo, D282194, 4/9/2002).

II.	Residue Information

Food Residues

For cyhalofop-butyl, the residues of concern for risk assessment
purposes are the combined residues of parent and its acid and diacid
metabolites.  Tolerances for residues of cyhalofop-butyl are established
under 40CFR §180.576.  Tolerances are currently established for
cyhalofop-butyl and its acid and diacid metabolites in/on two
commodities only:  rice grain at 0.03 ppm and rice straw at 8.0 ppm. 
These tolerances were time-limited and expired on 6/1/2007.  IR-4 has
requested that the rice field trial data be translated to wild rice, and
that a tolerance be established for rice, wild, grain, at 0.03 ppm. 
Although rice grain and straw are animal feed items, residues are not
likely to occur in animal commodities.  As a result, tolerances have not
been established for animal commodities and none are included in the
dietary exposure analysis.

Drinking Water Residues

The estimated drinking water concentrations (EDWCs) used in the dietary
risk assessment were provided by the Environmental Fate and Effects
Division (EFED) in the following memorandum: “Drinking Water
Assessment for the Proposed Section 3 Registration of Cyhalofop-butyl
for New Uses on Wild Rice Grown in California” (D357419, K. White,
10/17/2008).  The EDWC was incorporated directly into this dietary
assessment into the food categories “water, direct, all sources” and
“water, indirect, all sources.”

A standard model has been developed to estimate surface water
concentrations from use of pesticides on rice, the Tier I Rice Model. 
The model was modified to account for possible aerobic aquatic
degradation and aquatic dissipation over time, and used to estimate
surface water concentrations in water released from the rice paddy (tail
water).  Estimated drinking water concentrations (EDWCs) in groundwater
were modeled using Tier I SCIGROW (version 2.3, dated July 29, 2003). 
EDWCs represent exposure to total residues of cyhalofop-butyl,
cyhalofop-acid, and cyhalofop-diacid, with the assumption that
cyhalofop-butyl and cyhalofop-acid could be present in the R or S form
or as a mixture of the enantiomers.  Cyhalofop-butyl and its degradates
were not detected in surface water and drinking water monitoring studies
conducted in California where rice is grown.  The chronic groundwater
and surface water EDWCs are 0.152 and 21 ppb, respectively.  As the
surface water value was the higher of the two, it was used in the
chronic dietary exposure analysis.

The residue values (food and drinking water) are included in Attachment
1, Chronic Residue Input File.

III.	Percent Crop Treated Information

The assumption was made that both rice and wild rice would be treated to
a level of 100%.

DEEM-FCID™ Program and Consumption Information

The cyhalofop-butyl 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

HED’s Hazard Identification Assessment Review Committee (HIARC) and
FQPA Safety Factor Committee met to determine the appropriate doses and
endpoints for cyhalofop-butyl for use in human health risk assessments
(HIARC: Doc. No. 014650, 8/10/2001; FQPA: Doc. No. 014655, 8/28/2001). 
The FQPA Safety Factor Committee evaluated the available hazard and
exposure data for cyhalofop-butyl and concluded that the FQPA safety
factor of 10x should be reduced to 1x in assessing the risk posed by
this chemical.  The risk assessment team currently evaluating the
proposed use on wild rice has re-evaluated the toxicity data for
cyhalofop-butyl and is in agreement with the previous conclusions
concerning the toxicity endpoints and FQPA Safety Factor determination. 
HED’s Cancer Assessment Review Committee evaluated mode of action data
for cyhalofop-butyl.  In accordance with the EPA Final Guidelines for
Carcinogen Risk Assessment (March 29, 2005), the Committee classified
cyhalofop-butyl as “not likely to be carcinogenic to humans” (Memo,
TXR No. 0054798, J. Kidwell, 12/20/2007).

The cyhalofop-butyl dietary endpoints are summarized in Table 1, below.

Table 1.  Summary of Toxicological Doses and Endpoints for
Cyhalofop-butyl

for Use in Dietary Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	

RfD/PAD	Study and Toxicological Effects

Acute Dietary

(All Populations)	

No appropriate endpoint attributable to a single dose was available in
the current database.  Therefore, an acute RfD was not established for
the general U.S. population or any population subgroup.

Chronic Dietary

(All Populations)	NOAEL = 1.0 mg/kg/day

	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Chronic RfD =  0.010 mg/kg/day

Chronic PAD = 0.010 mg/kg/day	Carcinogenicity study in mice (MRID
45000418). Kidney effects in females including tubular dilatation,
chronic glomerulonephritis, and hyaline casts at the LOAEL of
10.06/10.28 mg/kg/day, M/F

Cancer

	

Classified as “not likely to be carcinogenic to humans” in
accordance with the EPA Final Guidelines for Carcinogen Risk Assessment
(March 29, 2005).

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.  RfD = reference dose.  

VI.	Results/Discussion 

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 Acute Dietary Exposure Analysis

A toxic effect attributable to a single exposure was not seen in the
available toxicology database for cyhalofop-butyl; therefore, an acute
dietary risk assessment is not required.

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

The chronic dietary exposure and risk estimates for the general U.S.
population and all population subgroups are below 100% of the cPAD.  The
most highly exposed subgroup is All Infants (<1 year old), whose risk
utilizes 15% of the cPAD.  The general U.S. population risk utilizes
4.5% of the cPAD.  The detailed results from the chronic dietary
exposure and risk assessment are summarized in Table 2, below.

Results of Cancer Dietary Exposure Analysis

HED’s Cancer Assessment Review Committee classified cyhalofop-butyl as
“not likely to be carcinogenic to humans” in accordance with the EPA
Final Guidelines for Carcinogen Risk Assessment (March 29, 2005).  As a
result, a cancer dietary exposure analysis was not performed. 

Table 2.  Summary of Dietary Exposure and Risk for Cyhalofop-butyl

(Food and Drinking Water)

Population Subgroup*	

Acute Dietary

(95th Percentile)	

Chronic Dietary	

Cancer

	

Dietary Exposure (mg/kg/day)	

% aPAD	

Dietary Exposure

(mg/kg/day)	

% cPAD	

Dietary Exposure

(mg/kg/day)	

Risk

General U.S. Population	N/A

	N/A

	

0.000451	4.5	

N/A	

N/A

All Infants (< 1 year old)

	

0.001473	15

Children 1-2 years old

	

0.000675	6.7

Children 3-5 years old

	

0.000630	6.3

Children 6-12 years old

	

0.000435	4.4

Youth 13-19 years old

	

0.000328	3.3

Adults 20-49 years old

	

0.000422	4.2

Adults 50+ years old

	

0.000440	4.4

Females 13-49 years old

	

0.000419	4.2

VII.	Characterization of Inputs/Outputs

HED conducted an unrefined dietary risk assessment for cyhalofop-butyl. 
The assessment assumes that all commodities with cyhalofop-butyl
tolerances (i.e., rice and wild rice) contain residues of
cyhalofop-butyl at the tolerance level.  In addition, a conservative
estimate of residues in drinking water was used in the assessment. 
Based on the conservative inputs into the analysis, it is highly
unlikely that the assessment will underestimate chronic dietary exposure
of the general U.S. population or any population subgroup. 

Additional refinements, including the use of percent crop treated
information and monitoring data for rice, could be incorporated into the
assessment.  However, as risk estimates are not of concern, a more
highly refined assessment is not needed at this time.

VIII.	Conclusions

A chronic dietary exposure and risk assessment was conducted for the
proposed and existing food uses of cyhalofop-butyl.  The risk estimates
for the general U.S. population and all population subgroups are below
HED’s level of concern.

List of Attachments

1.  Cyhalofop-butyl  Chronic Residue Input File

2.  Results of Chronic Dietary Exposure Analysis

Attachment 1:  Cyhalofop-butyl Chronic Residue Input File

DEEM/FCID Version 2.03

Chronic NOAEL: 1.0 mg/kg bw/day

Chronic Population Adjusted Dose (cPAD):  0.01 mg/kg bw/day

Filename: C:\Documents and Settings\ddotson\My
Documents\DEEMFCID\Cyhalofop\Cyhalofop.R98

Date created/last modified: 11-19-2008/10:22:07/8

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

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2   

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

15003230 15   Rice, white                        0.030000   1.000  1.000
 

15003231 15   Rice, white-babyfood               0.030000   1.000  1.000
 

15003240 15   Rice, brown                        0.030000   1.000  1.000
 

15003241 15   Rice, brown-babyfood               0.030000   1.000  1.000
 

15003250 15   Rice, flour                        0.030000   1.000  1.000
 

15003251 15   Rice, flour-babyfood               0.030000   1.000  1.000
 

15003260 15   Rice, bran                         0.030000   1.000  1.000
 

15003261 15   Rice, bran-babyfood                0.030000   1.000  1.000
 

15004050 15   Wild rice                          0.030000   1.000  1.000
 

86010000 O    Water, direct, all sources         0.021000   1.000  1.000
 

86020000 O    Water, indirect, all sources       0.021000   1.000  1.000
 

Attachment 2:  Results of Chronic Dietary Exposure Analysis

DEEM-FCID Version 2.03  (1994-98 data)

Chronic NOAEL = 1.0 mg/kg bw/day

Chronic PAD = 0.01 mg/kg bw/day

Residue File name: C:\Documents and Settings\ddotson\MyDocuments

	\DEEMFCID\Cyhalofop\Cyhalofop.R98

Analysis Date 11-19-2008/10:35:41     Residue file dated:
11-19-2008/10:22:07/8

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

                    Total exposure by population subgroup

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

                                                    Total Exposure

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

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

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

U.S. Population (total)                     0.000451                
4.5%

U.S. Population (spring season)             0.000447                
4.5%

U.S. Population (summer season)             0.000484                
4.8%

U.S. Population (autumn season)             0.000436                
4.4%

U.S. Population (winter season)             0.000436                
4.4%

Northeast region                            0.000414                
4.1%

Midwest region                              0.000454                
4.5%

Southern region                             0.000428                
4.3%

Western region                              0.000519                
5.2%

Hispanics                                   0.000518                
5.2%

Non-hispanic whites                         0.000437                
4.4%

Non-hispanic blacks                         0.000429                
4.3%

Non-hisp/non-white/non-black                0.000582                
5.8%

All infants (< 1 year)                      0.001473               
14.7%

Nursing infants                             0.000553                
5.5%

Non-nursing infants                         0.001823               
18.2%

Children 1-6  yrs                           0.000634                
6.3%

Children 7-12 yrs                           0.000412                
4.1%

Females 13-19 (not preg or nursing)         0.000318                
3.2%

Females 20+ (not preg or nursing)           0.000448               
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Males 13-19 yrs                             0.000335                
3.4%

Males 20+ yrs                               0.000405                
4.1%

Seniors 55+                                 0.000439                
4.4%

Children 1-2 yrs                            0.000675                
6.7%

Children 3-5 yrs                            0.000630                
6.3%

Children 6-12 yrs                           0.000435                
4.4%

Youth 13-19 yrs                             0.000328                
3.3%

Adults 20-49 yrs                            0.000422                
4.2%

Adults 50+ yrs                              0.000440                
4.4%

Females 13-49 yrs                           0.000419                
4.2%

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

Cyhalofop-butyl	          Dietary Exposure and Risk Assessment	         
 DP Number: 358391

PC Code:  082583		

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