Document ID: EPA-HQ-OPP-2007-0945-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-11-12T05:00Z

SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDES

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

DATE:  		30-SEP-2008  

SUBJECT:		4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB);  Acute and
Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk
Assessments for the Proposed Section 3 Registration Action on Mint.

         	 

PC Code:  019201	DP Barcode:  350511

Decision No.:  383254	Registration No.:  71368-5

Petition No.:  7E7257	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  NA	Case No.:  2365

TXR No.:  NA	CAS No.:  94-81-5

MRID No.:  NA	40 CFR: 180.318

FROM:		Sarah J. Levy, Chemist

Registration Action Branch 1 (RAB1)

Health Effects Division (HED; 7509P)

THROUGH:		Doug Dotson, Ph.D., Chemist

Sheila Piper, Chemist

Dietary Exposure Science Advisory Council (DESAC)

HED (7509P)

and

George F. Kramer, Ph.D., Senior Chemist

RAB1/HED (7509P)

TO:			Sarah J. Levy, Risk Assessor

	RAB1/HED (7509P)

and

			Daniel Rosenblatt, Risk Manager (Team 05) 

Registration Division (RD; 7505P)

Executive Summary

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 analyses were
performed to support a Section 3 use request on mint.  A cancer dietary
assessment was not conducted because MCPB was classified as not likely
to be carcinogenic to humans.

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

Tolerance-level residues and 100 percent crop treated (%CT) data were
used in the acute and chronic dietary assessments.  For both acute and
chronic dietary assessments, all population subgroups have risk
estimates that are below HED's level of concern.  For the acute
assessment, the most highly exposed population subgroup is all infants
(<1 year old; 5.4% of the aPAD (acute population-adjusted dose)).  For
the chronic assessment, the most highly exposed population subgroup is
also all infants (<1 year old; 22% of the cPAD (chronic
population-adjusted dose)).  The use of anticipated residues (ARs),
empirical processing factors, and % crop treated (CT) would refine
further HED’s exposure and risk estimates; however, refinement is not
needed at this time.

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
that 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 which 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 MCPB was conducted by F.
Fort for purposes of the Reregistration Eligibility Decision (RED)
(04-AUG-2005; DP#: 314047).  This document serves as an update to the
last dietary assessment for the RED in which the proposed new use, mint,
is included.

II.	Residue Information

Interregional Research Project No. 4 (IR-4), on behalf of the
Agricultural Experiment Station of Washington, has submitted a petition,
PP#7E7257, proposing the establishment of a permanent tolerance for
residues of the herbicide MCPB in/on mint tops (leaves and stems).  The
residue chemistry data were reviewed in conjunction with this petition
on 30-SEP-2008 (Memo, S. Levy, DP#: 349646).  HED is recommending in
favor for a tolerance of 0.20 ppm (Table 2, below).

MCPB is a selective herbicide used postemergence as a broadcast foliar
application to control broad-leaved annual and perennial weeds (Canada
thistle).  The end-use products are sodium salts; the only registered
food use is on peas (40 CFR §180.318).  There are no livestock
feedstuffs associated with the registered or proposed uses on pea or
mint, respectively.  MCPB is a List B chemical.  HED’s chapter for the
MCPB RED document was issued in 2005 (Memo, E. Méndez, 04-AUG-2005;
DP#: 314047).  

For purposes of this petition, based on the pea foliage metabolism data
and since mint is a minor crop (low-consumption commodity), the nature
of the residue in primary crops is adequately understood based on a
metabolism study conducted with peas.  The HED Metabolism Committee
determined that the residues to be regulated for both tolerance and risk
assessment purposes in plant commodities are the free and conjugated
MCPB and MCPA ((4-chloro-2-methylphenoxy) acetic acid) (08-JUN-1995). 
Note that the current tolerance established under 40 CFR §180.318 is
for residues of MCPB per se in/on peas at 0.1 ppm.  The tolerance
expression should be revised in accordance with HED recommendations (the
HED Metabolism Committee decision and the HED Chapter of the RED) to
include both free and conjugated MCPB and MCPA for plant commodities. 
Also, HED notes that the preferred chemical names for MCPB and MCPA are
4-(4-chloro-2-methylphenoxy)butanoic acid and
(4-chloro-2-methylphenoxy)acetic acid, respectively.  Table 1 is a
summary of the residues of concern.

Table 1.  Residues of Concern in Crops, Livestock, and Drinking Water.

Matrix	Tolerance Expression	Residues for Risk Assessment

Pea and mint	free and conjugated MCPB and MCPA	free and conjugated MCPB
and MCPA

Livestock	NA for purposes of this petition 	NA for purposes of this
petition 

Drinking Water	NA	MCPB and MCPA

Residue Data used for the Acute and Chronic Assessment:

Tolerance-level residues and 100%CT data were used in the acute and
chronic dietary assessments.  The use of ARs, empirical processing
factors, and %CT data would refine further HED’s exposure and risk
estimates.  However, refinements of the dietary exposure estimates are
not needed at this time.  See Table 2 for a summary of the data used in
the acute and chronic assessments.

Table 2.  Data and Residue Estimates Used in the Acute and Chronic
Dietary Analyses.1

RAC	Data Source	Existing Tolerance (ppm)	

HED-Recommended Tolerance Level

(ppm)

Mint	DP#: 349646	--	0.20

		            1  100% CT was assumed for all commodities.

    Drinking Water Data

The drinking water residues used in the dietary risk assessments were
provided by the Environmental Fate and Effects Division (EFED) in a
memorandum by J. Lin (27-FEB-2008; DP#: 343745) and incorporated
directly into this dietary assessment.  Water residues were incorporated
in the DEEM-FCID into the food categories “water, direct, all
sources” and “water, indirect, all sources.”  The estimated
drinking water concentration (EDWC) values for mint were less than the
values calculated for peas; therefore, the EDWC values for peas were
used as the representative drinking water concentrations (Memo, K.
Costello, 03-AUG-2005; DP#: 314053).  Both monitoring analysis and
modeling approach were applied in the pea assessment.  A summary of the
model estimates for drinking water from both surface water and
groundwater sources is shown below.  Surface water estimates were used
in acute and chronic food and water dietary exposure assessments.  For
purposes of this assessment, the highest (i.e., most conservative)
values were used for the acute (54.7 ppb) and chronic (13.5 ppb)
assessments.  The models and their descriptions are available at the EPA
internet site: http://www.epa.gov/oppefed1/ models/water/.

	Surface water (PRZM/EXAMS)

Acute (peak)				54.7 µg/L

Chronic (annual average)		13.5 µg/L

Cancer (30-year average)		7.3 µg/L

Groundwater (SCI-GROW)			2.1 µg/L

IV.	DEEM-FCID™ Program and Consumption Information

MCPB acute and chronic dietary exposure assessments were conducted using
the DEEM-FCID™, Version 2.03 which incorporates consumption data from
USDA’s 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.  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.

For acute exposure assessments, individual one-day food consumption data
are used on an individual-by-individual basis.  The reported consumption
amounts of each food item can be multiplied by a residue point estimate
and summed to obtain a total daily pesticide exposure for a
deterministic exposure assessment, or “matched” in multiple random
pairings with residue values and then summed in a probabilistic
assessment.  The resulting distribution of exposures is expressed as a
percentage of the aPAD on both a user (i.e., only those who reported
eating relevant commodities/food forms) and a per-capita (i.e., those
who reported eating the relevant commodities as well as those who did
not) basis.  In accordance with HED policy, per capita exposure and risk
are reported for all tiers of analysis.  However, for tiers 1 and 2, any
significant differences in user vs. per capita exposure and risk are
specifically identified and noted in the risk assessment.

V.	Toxicological Information

The toxicological endpoints used in this assessment are summarized below
in Table 3 (HED Chapter of the RED Document, E. Méndez, 04-AUG-2005;
DP#: 314047).  The MCPB risk assessment team re-evaluated the endpoints
selected previously.



Table 3.  Summary of Toxicological Doses and Endpoints for MCPB for Use
in Dietary Human 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 females 13-49 years old)
NOAEL = 200 mg/kg/day	UFA = 10x

UFH = 10x

UFDB = 10x

FQPA SF = 10x	Acute RfD = 0.2 mg/kg/day

aPAD = 0.2 mg/kg/day	Acute neurotoxicity (MCPA, rat).  LOAEL = 400
mg/kg/day based on gait impairment in males.

Chronic Dietary (all populations)	

NOAEL = 4.4 mg/kg/day

 	UFA = 10x

UFH = 10x

UFDB = 10x

FQPA SF = 10x	Chronic RfD = 0.0044 mg/kg/day

cPAD = 0.0044 mg/kg/day	Chronic toxicity (MCPA, rat).  LOAEL = 17.6
mg/kg/day based on liver and kidney toxicity.

Cancer (oral)	

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).  UFDB= incomplete database.  FQPA SF = FQPA Safety
Factor.  PAD = population-adjusted dose (a = acute, c = chronic).  RfD =
reference dose.

VI.	Results/Discussion/Conclusions 

The DEEM-FCID™ analysis estimates the dietary exposure of the U.S.
population and various population subgroups.  The results for the acute
and chronic assessments reported in Table 4 are for the U.S. Population,
all infants (<1 year old), children 1-2, children 3-5, children 6-12,
youth 13-19, females 13-49, males 20-49, and adults 50+ years.  A cancer
dietary assessment was not conducted because MCPB was classified as not
likely to be carcinogenic to humans.

The acute and chronic dietary exposure assessments (using tolerance
level residues and 100% CT information for all registered and proposed
uses) were conducted for the general U.S. population and various
population subgroups.  Drinking water values were incorporated directly
into the acute and chronic dietary assessments.  These assessments
conclude that the acute and chronic dietary exposure estimates are not
of concern to HED for the general U.S. population or any population
subgroup.  For the acute assessment, the most highly exposed population
subgroup is all infants (<1 year old; 5.4% of the aPAD).  For the
chronic assessment, the most highly exposed population subgroup is also
all infants (<1 year old; 22% of the cPAD).  The use of ARs, empirical
processing factors, and %CT data would refine further HED’s exposure
and risk estimates; however, refinements are not needed at this time.



Table 4.  Summary of Dietary Exposure and Risk for MCPB.

Population Subgroup	Acute Dietary1

(95th Percentile)	Chronic Dietary1

	Dietary Exposure (mg/kg/day)	%aPAD*	Dietary Exposure (mg/kg/day)	%
cPAD*

U.S. Population (total)	0.002870	1.4	0.000294	6.7

All Infants (< 1 year old)	0.010731   	5.4	0.000977	22

Children 1-2 years old	0.004527   	2.3	0.000455	10

Children 3-5 years old	0.004120   	2.1	0.000415	9.4

Children 6-12 years old	0.002865  	1.4	0.000284	6.5

Youth 13-19 years old	0.002334 	1.2	0.000211	4.8

Adults 20-49 years old	0.002653   	1.3	0.000273	6.2

Adults 50+ years old	0.002408 	1.2	0.000289	6.6

Females 13-49 years old	0.002664 	1.3	0.000271	6.2

1 Acute dietary endpoint of 0.2 mg/kg/day applies to the general U.S.
population and all population subgroups.  Chronic dietary endpoint of
0.0044 mg/kg/day applies to the general U.S. population and all
population subgroups.

*  The highest %aPAD and %cPAD are bolded. 

VII.  List of Attachments

Attachment 1:  DEEM-FCID( Acute Residue Input File.

Attachment 2:  DEEM-FCID( Acute Results File.

Attachment 3:  DEEM-FCID( Chronic Residue Input File.

Attachment 4:  DEEM-FCID( Chronic Results File.

cc:  S. Levy

RDI: DESAC (28-MAR-2008); G. Kramer (30-SEP-2008)

S. Levy:S10953:PY1:(703)305-0783:7590P

Attachment 1:  DEEM-FCID( Acute Residue Input File.

U.S. Environmental Protection Agency                                Ver.
2.02

DEEM-FCID Acute analysis for MCPB

Residue file name: C:\Documents and Settings\slevy\My
Documents\SarahLevy's Files\deem\MCPB\019201a.R98

Analysis Date 03-26-2008            Residue file dated:
03-26-2008/16:57:27/8

Reference dose (aRfD) = 0.2 mg/kg bw/day

Comment: no cancer

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

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Food Name                         (ppm)       #1    #2   

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

06022550 6B   Pea, succulent                     0.100000   1.000  1.000

06022551 6B   Pea, succulent-babyfood            0.100000   1.000  1.000

95002750 O    Peppermint                         0.200000   1.000  1.000

95002760 O    Peppermint, oil                    0.200000   1.000  1.000

95003520 O    Spearmint                          0.200000   1.000  1.000

95003530 O    Spearmint, oil                     0.200000   1.000  1.000

86010000 O    Water, direct, all sources         0.054700   1.000  1.000

86020000 O    Water, indirect, all sources       0.054700   1.000 
1.000Attachment 2:  DEEM-FCID( Acute Results File.

U.S. Environmental Protection Agency                                Ver.
2.02

DEEM-FCID ACUTE Analysis for MCPB                              (1994-98
data)

Residue file: 019201a.R98                         Adjustment factor #2
used.

Analysis Date: 03-26-2008/16:59:21  Residue file dated:
03-26-2008/16:57:27/8

Daily totals for food and foodform consumption used.

Run Comment: "no cancer"

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

Summary calculations (per capita):

                 95th Percentile      99th Percentile      99.9th
Percentile

                Exposure   % aRfD    Exposure   % aRfD    Exposure   %
aRfD 

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

U.S. Population:

                 0.002870     1.44    0.005406     2.70    0.010770    
5.38 

All infants:

                 0.010731     5.37    0.015519     7.76    0.027494   
13.75 

Males 13-19 yrs:

                 0.002348     1.17    0.004376     2.19    0.009979    
4.99 

Males 20+ yrs:

                 0.002473     1.24    0.004033     2.02    0.007580    
3.79 

Seniors 55+:

                 0.002352     1.18    0.003341     1.67    0.005535    
2.77 

Children 1-2 yrs:

                 0.004527     2.26    0.007600     3.80    0.010856    
5.43 

Children 3-5 yrs:

                 0.004120     2.06    0.006413     3.21    0.010465    
5.23 

Children 6-12 yrs:

                 0.002865     1.43    0.004791     2.40    0.006464    
3.23 

Youth 13-19 yrs:

                 0.002334     1.17    0.003886     1.94    0.007059    
3.53 

Adults 20-49 yrs:

                 0.002653     1.33    0.004461     2.23    0.007981    
3.99 

Adults 50+ yrs:

                 0.002408     1.20    0.003430     1.71    0.005587    
2.79 

Females 13-49 yrs:

                 0.002664     1.33    0.004285     2.14    0.007583    
3.79  

Attachment 3:  DEEM-FCID( Chronic Residue Input File.

U.S. Environmental Protection Agency                                Ver.
2.00

DEEM-FCID Chronic analysis for MCPB                              1994-98
data

Residue file: C:\Documents and Settings\slevy\My Documents\SarahLevy's
Files\deem\MCPB\019201c.R98                                             
          Adjust. #2 used

Analysis Date 05-19-2008            Residue file dated:
05-19-2008/14:30:06/8

Reference dose (RfD) = 0.0044 mg/kg bw/day

Comment:no cancer

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

Food Crop                                       Residue      
Adj.Factors      Comment

EPA Code  Grp  Food Name                          (ppm)       

                                                             #1        
#2 

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

06022550 6B   Pea, succulent                     0.100000   1.000     
1.000   

06022551 6B   Pea, succulent-babyfood            0.100000   1.000     
1.000   

95002750 O    Peppermint                         0.200000   1.000     
1.000   

95002760 O    Peppermint, oil                    0.200000   1.000     
1.000   

95003520 O    Spearmint                          0.200000   1.000     
1.000   

95003530 O    Spearmint, oil                     0.200000   1.000     
1.000   

86010000 O    Water, direct, all sources         0.013500   1.000     
1.000   

86020000 O    Water, indirect, all sources       0.013500   1.000     
1.000   

Attachment 4:  DEEM-FCID( Chronic Results File.

U.S. Environmental Protection Agency                                Ver.
2.00

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

Residue file name: C:\Documents and Settings\slevy\My
Documents\SarahLevy's Files\deem\MCPB\019201c.R98                       
                             Adjustment factor #2 used.

Analysis Date 05-19-2008/14:32:31   Residue file dated:
05-19-2008/14:30:06/8

Reference dose (RfD, Chronic) = .0044 mg/kg bw/day

COMMENT 1: no cancer

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

                    Total exposure by population subgroup

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

                                                    Total Exposure

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

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

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

U.S. Population (total)                     0.000294                
6.7%

U.S. Population (spring season)             0.000292                
6.6%

U.S. Population (summer season)             0.000314                
7.1%

U.S. Population (autumn season)             0.000285                
6.5%

U.S. Population (winter season)             0.000286                
6.5%

Northeast region                            0.000271                
6.2%

Midwest region                              0.000297                
6.8%

Southern region                             0.000280                
6.4%

Western region                              0.000335                
7.6%

Hispanics                                   0.000329                
7.5%

Non-hispanic whites                         0.000287                
6.5%

Non-hispanic blacks                         0.000282                
6.4%

Non-hisp/non-white/non-black                0.000360                
8.2%

All infants (< 1 year)                      0.000977               
22.2%

Nursing infants                             0.000371                
8.4%

Non-nursing infants                         0.001206               
27.4%

Children 1-6  yrs                           0.000421                
9.6%

Children 7-12 yrs                           0.000269                
6.1%

Females 13-19 (not preg or nursing)         0.000205                
4.7%

Females 20+ (not preg or nursing)           0.000292                
6.6%

Females 13-50 yrs                           0.000282                
6.4%

Females 13+ (preg/not nursing)              0.000288                
6.5%

Females 13+ (nursing)                       0.000402                
9.1%

Males 13-19 yrs                             0.000216                
4.9%

Males 20+ yrs                               0.000263                
6.0%

Seniors 55+                                 0.000289                
6.6%

Children 1-2 yrs                            0.000455               
10.3%

Children 3-5 yrs                            0.000415                
9.4%

Children 6-12 yrs                           0.000284                
6.5%

Youth 13-19 yrs                             0.000211                
4.8%

Adults 20-49 yrs                            0.000273                
6.2%

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Adults 50+ yrs                              0.000289                
6.6%

Females 13-49 yrs                           0.000271                
6.2%

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

MCPB	               Dietary Exposure and Risk Assessment  	             
            DP#: 350511	

PC Code:  019201

________________________________________________________________________
___________________

Page   PAGE  1  of   NUMPAGES  11 

MCPB                                    	Dietary Exposure and Risk
Assessment  	                              DP#: 350511

PC Code:  019201

________________________________________________________________________
_____________________