Document ID: EPA-HQ-OPP-2007-0968-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-11-28T05:00Z

SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

							OFFICE OF

							PREVENTION, PESTICIDES AND

							TOXIC SUBSTANCES

MEMORANDUM

DATE:  	07 June 2007  

SUBJECT:	Chlormequat Chloride. Screening-level Acute and Chronic Dietary
(Drinking Water Only) Exposure and Risk Assessment for the
Reregistration Eligibility Decision.

PC Code:	018101		DP Number:	D336716		

REVIEWER:	Donald Wilbur, Chemist

		Reregistration Branch II

Health Effects Division (7509P)

THROUGH:	Sheila Piper, Chemist (CEB)

Dietary Exposure Science Advisory Council (DESAC)

Health Effects Division (7509P)

	And

William J. Hazel, PhD, Branch Chief

Reregistration Branch II

Health Effects Division (7509P)

TO:		Tracy Perry, Chemical Review Manager

Special Review Branch

Special Review and Reregistration Division (7508P)

Executive Summary

A screening-level acute and chronic dietary (drinking water only)
exposure and risk assessment was conducted for chlormequat chloride
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 reregistration eligibility decision.  The assessment included only
the potential for exposure through drinking water, and was conducted to
ensure that there are no serious risk concerns associated with all
registered outdoor uses including bedding plants and containerized
ornamentals in shadehouses and nurseries.  This assessment is an update
to a previous screening-level chronic dietary assessment for chlormequat
chloride (C. Swartz, D332277, 11/20/2006) and incorporates a reduction
in the maximum outdoor use rate from 49.5 to 33.3 lbs a.i./A/year.

   

A Tier I drinking water assessment for acute and chronic dietary
exposure was provided by the Environmental Fate and Effects Division
(EFED) (M. Echeverria, D336717, 03/19/2007).  The highest estimated
drinking water concentrations (EDWC) were found in surface water and
these conservative values were used for the dietary analysis.  

Acute drinking water exposure estimates were generated based on the
deterministic upper bound estimates from EFED’s Tier I (F)IFRA (I)ndex
(R)eservoir (S)creening (T)ool (FIRST) EDWC surface water model. 
Therefore, because of the conservative nature of this model, it is
inappropriate to assess risks based upon exposures at the 99.9th
percentile.  It is more appropriate to consider exposure at the 95th
percentile.  The acute dietary exposure estimates from drinking water
are below HED’s level of concern (< 100% aRfD) for the U.S. population
and all population subgroups at the 95th percentile. The highest exposed
population subgroup was all infants (< 1 year) at 56% of the acute RfD
of 0.9 mg/kg/day.  Based on the screening-level EFED assessment used to
generate the drinking water estimates, HED concludes that there is no
concern for potential acute dietary exposure to chlormequat chloride
from drinking water.

The chronic dietary exposure estimates from drinking water are below
HED’s level of concern      (< 100% cPAD) for the U.S. population and
all population subgroups.  The highest exposed population subgroup was
all infants (< 1 year) at 13% of the chronic RfD of 0.05 mg/kg/day. 
Based on the screening-level EFED assessment used to generate the
drinking water estimates, HED concludes that there is no concern for
potential chronic dietary exposure to chlormequat chloride from drinking
water.

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).  For non-food pesticides, this dose is referred to as the
reference dose (RfD).  The RfD is equivalent to point of departure
(POD), NOAEL, LOAEL, e.g. divided by the required uncertainty or safety
factors (typically interspecies 10x and intraspecies 10x). 

For acute and non-cancer chronic exposures, HED is concerned when
estimated dietary risk exceeds 100% of the aRfD or cRfD. References
which discuss 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 (08/20/1999).

The most recent chronic dietary risk (drinking water only) assessment
for chlormequat chloride was conducted by C. Swartz (D332277,
11/20/2006).

II.	Residue Information

Chlormequat chloride [(2-chloroethyl)trimethylammonium chloride] is a
non-food use plant growth regulator that belongs to the quaternary
ammonium class of chemicals. It is used on ornamental plants grown in
greenhouses, nurseries, and shadehouses.  Chlormequat chloride works
through inhibition of gibberellin biosynthesis in the early stages of
the pathway.  This early blockage prevents the synthesis of numerous
gibberellins needed for normal plant growth and development.

Chlormequat chloride is a non-food use chemical, it has no existing or
proposed uses (and no tolerances) that could result in exposure through
food.  Therefore, the requirements of FQPA do not strictly apply to this
chemical.  Because of this, the standard 10x FQPA uncertainty factor
will not be applied to this assessment.

 Drinking Water Data

The estimated drinking water concentration (EDWC) estimates used in the
dietary risk assessment were provided by the Environmental Fate and
Effects Division (EFED) in the following memorandum: “Tier I Drinking
Water Assessment for Chlormequat Chloride in Support of Reregistration
Eligibility Decision” (M. Echeverria, D336717, 03/19/2007).    EDWCs
were incorporated into DEEM-FCID as the food forms “water, direct, all
sources” and “water, indirect, all sources.”   A summary of the
EDWCs is provided in Table 1.

The highest EDWC was calculated in surface water using the FIRST model
and these upper bound conservative values were used for the drinking
water analysis.  

Tier 1 EDWCs for surface water were generated by EFED from their Tier I
(F)IFRA (I)ndex (R)eservoir (S)creening (T)ool (FIRST) EDWC surface
water model

 FIRST is a screening model designed by the Environmental Fate and
Effects Division (EFED, 2001a) of the Office of Pesticide Programs to
estimate pesticide concentrations found in drinking water from surface
water sources for use in human health risk assessment.  As such, it
provides upper bound values on the concentrations that might be found in
drinking water due to the use of a pesticide.  FIRST is a single-event
model (one runoff event), but can account for spray drift from multiple
applications.  FIRST is hardwired to represent the Index Reservoir, a
standard water body used by the Office of Pesticide Programs to assess
drinking water exposure (Office of Pesticide Programs, 2002).  It is
based on a real reservoir, Shipman City Lake in Illinois, which is known
to be vulnerable to pesticide contamination.

These EDWCs were obtained from modeling using the highest use rate of
all labeled uses with an annual application rate of 33.3 lbs
a.i./A/year.

Since there were unidentified residues in the aquatic and soil
metabolism studies that may be of risk concern, a total toxic residue
approach that assumes all uncharacterized extractable residues are of
equal toxicity to the parent was used to estimate exposure.

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/ .  

Table 1 Tier I EDWC for chlormequat chloride for ground boom spray
applications

Drinking Water Source (Model)	Use rate (lbs a.i./A/year)	EDWC (ppb)

Surface water (FIRST)

 - Acute (peak)

 - Chronic (annual mean)	

33.3

	

2574

91

Groundwater (SCI-GROW)	33.3	24

	Numerous conservative assumptions were used by EFED to generate the
EDWCs.  Based on the following, the resulting EDWCs are deterministic
upper-bound estimates.

Modeled values were used since no monitoring data are available

Assumes 100% of watershed is treated (no percent crop area data is
available, but there is a relatively low amount of chlormequat chloride
applied per year on a nationwide basis, including all indoor uses)

Assumes 100% of the product is absorbed into the ground and/or runs off
(i.e.- no plants on the surface treated, all product makes ground
contact)

Ground boom applications drive the risk even though limited usage is
expected

.	DEEM-FCID™ Program and Consumption Information

Chlormequat chloride acute and chronic dietary exposure assessments were
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 nonconsecutive 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 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 acute hazard value (aRfD or 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.

For chronic dietary exposure assessments, 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 cRfD or cPAD.  This procedure is performed for each
population subgroup.

V.	Toxicological Information

The toxicology database for chlormequat chloride is adequate sufficient
for hazard assessment to support the proposed non-food, non-residential
use.  A summary of the toxicological endpoints for dietary risk
assessment is shown in Table 2.

Table 2.  Summary of Toxicological Doses and Endpoints for Chlormequat
Chloride for Use in Dietary Exposure Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty Factors	RfD 	Study and
Toxicological Effects

Acute Dietary (all populations)	NOAEL=

90 mg/kg/day

	UFA = 10X

UFH = 10X

	aRfD=0.9

mg/kg/day

	Prenatal Developmental-Rat (MRID 42246604)

Single oral LOAEL 180 mg/kg/day, based on overt toxicity signs (tremors,
ataxia) within an hour after a single oral dose in dams(GD6).

Acute Dietary

(Females 13-49 years of age)	N/A	N/A	N/A	The risk assessment is not
appropriate. Also, an acute endpoint was not selected based on the
absence of an appropriate endpoint attributable to a single dose.

Chronic Dietary 

(all populations)	NOAEL =

5 mg/kg/day

	UFA = 10X

UFH = 10X

	cRfD = 0.05 mg/kg/day

	Chronic Toxicity-Dog (MRID 46715201)

LOAEL (mg/kg/day): 10 mg/kg/day, based on salivation (both sexes),
vomiting (females), diarrhea (males), and decreased body weight gain
(males).

Cancer (oral, dermal, inhalation)   	Classification: “Not likely to be
Carcinogenic to Humans” based on the no carcinogenic potential was
noted in the available studies.

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 (intraspecies).  

UFH = potential variation in sensitivity among members of the human
population (interspecies).  

RfD = reference dose.  

N/A = not applicable

FQPA and Uncertainty Factors

As the pesticidal uses of chlormequat chloride do not involve use on
food, no residues in food are expected and tolerances are not required. 
 Therefore, chlormequat chloride uses are not subject to the Food
Quality Protection Act (1996). 

HED notes there is no evidence chlormequat causes increased
susceptibility in infants and children in the submitted data.  The
standard UF of 100X (10X interspecies extrapolation, 10X intraspecies
variability) has been applied to the hazard component of risk.

VI.	Results/Discussion 

.  The DEEM-FCID™ analyses estimate the dietary exposure of the U.S.
population and various population subgroups.  The results reported in
Table 3 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. 

Acute Drinking Water Exposure Results

Acute drinking water exposure estimates were generated based on the
deterministic upper bound estimates from EFED’s Tier I (F)IFRA (I)ndex
(R)eservoir (S)creening (T)ool (FIRST) EDWC surface water model. 
Therefore, because of the conservative nature of this model, it is
inappropriate to assess risks based upon exposures at the 99.9th
percentile.  It is more appropriate to consider exposure at the 95th
percentile.  The acute dietary exposure estimates from drinking water
are below HED’s level of concern (< 100% aRfD) for the U.S. population
and all population subgroups at the 95th percentile.  A summary of the
results from the acute dietary exposure analysis is shown in Table 3.
The highest exposed population subgroup was all infants (< 1 year) at
56% of the acute RfD of 0.9 mg/kg/day.  Based on the screening-level
EFED assessment used to generate the drinking water estimates, HED
concludes that there is no concern for potential acute dietary exposure
to chlormequat chloride from drinking water.

Chronic Drinking Water Exposure Results

The chronic dietary exposure estimates from drinking water are below
HED’s level of concern  (< 100% cPAD) for the U.S. population and all
population subgroups.  The highest exposed population subgroup was all
infants (< 1 year) at 13% of the chronic RfD of 0.05 mg/kg/day.  Based
on the screening-level EFED assessment used to generate the drinking
water estimates, HED concludes that there is no concern for potential
chronic dietary exposure to chlormequat chloride from drinking water.

Table 3. Summary of Acute and Chronic  Dietary (Drinking Water Only)
Exposure and Risk for Chlormequat Chloride

Population Subgroup	Acute Drinking Water

95th  Percentile	Chronic Drinking Water

	aRfD (mg/kg/day)	Dietary Exposure (mg/kg/day)	% aRfD	cRFD (mg/kg/day)
Dietary Exposure

(mg/kg/day)	% cRfD

General U.S. Population	0.9	0.134463    	15   	0.05	0.001918	3.8

All Infants (< 1 year old)

0.506963    	56    

0.006288                	13

Children 1-2 years old

0.210983    	23    

0.002848                 	5.7

Children 3-5 years old

0.192735       	21

0.002666                 	5.3

Children 6-12 years old

0.134174       	15

0.001839                 	3.7

Youth 13-19 years old

0.109085      	12  

0.001386                 	2.8

Adults 20-49 years old

0.124579    	14 

0.001791                 	3.6

Adults 50+ years old

0.112502    	13   

0.001884                 	3.8

Females 13-49 years old 

0.125285      	14

0.001783                 	3.6

VII.	Conclusion

The acute and chronic dietary exposure analyses of conservative surface
water concentrations of chlormequat chloride indicate that all
population subgroups have risk estimates below HED’s level of concern
(< 100% of the hazard value).

VIII.	List of Attachments

Attachment 1  Acute Inputs

Attachment 2  Acute Results

Attachment 3	Chronic Inputs

Attachment 4	Chronic Results

Attachment 1:  Acute Inputs

U.S. Environmental Protection Agency                                
Ver. 2.02

DEEM-FCID Acute analysis for CHLORMEQUAT CHLORIDE

Residue file name: C:\Documents and Settings\dwilbur\My
Documents\DEEM\Chlormequat Chloride\CC acute.R98

Analysis Date 06-04-2007             Residue file dated:
05-17-2007/08:40:38/8

Reference dose (aRfD) = 0.9 mg/kg bw/day

Comment: Chlormequat chloride acute NOAEL=90 mg/kg/day

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

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Food Name                         (ppm)       #1    #2   

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

86010000 O    Water, direct, all sources         2.574000   1.000  1.000

86020000 O    Water, indirect, all sources       2.574000   1.000  1.000

Attachment 2:  Acute Results

U.S. Environmental Protection Agency                                 
Ver. 2.02

DEEM-FCID ACUTE Analysis for CHLORMEQUAT CHLORIDE               
(1994-98 data)

Residue file: CC acute.R98                        Adjustment factor #2
NOT used.

Analysis Date: 06-04-2007/11:57:32    Residue file dated:
05-17-2007/08:40:38/8

Daily totals for food and foodform consumption used.

Run Comment: "Chlormequat chloride acute NOAEL=90 mg/kg/day"

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

Summary calculations (per capita):

                    95th Percentile      99th Percentile      99.9th
Percentile

                   Exposure   % aRfD    Exposure   % aRfD    Exposure  
% aRfD 

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

U.S. Population:

                    0.134463    14.94    0.252560    28.06    0.505316  
 56.15 

All infants:

                    0.506963    56.33    0.726768    80.75    1.301874  
144.65 

Children 1-2 yrs:

                    0.210983    23.44    0.352343    39.15    0.512433  
 56.94 

Children 3-5 yrs:

                    0.192735    21.42    0.302097    33.57    0.493062  
 54.78 

Children 6-12 yrs:

                    0.134174    14.91    0.223095    24.79    0.304673  
 33.85 

Youth 13-19 yrs:

                    0.109085    12.12    0.183531    20.39    0.330092  
 36.68 

Adults 20-49 yrs:

                    0.124579    13.84    0.208625    23.18    0.377378  
 41.93 

Adults 50+ yrs:

                    0.112502    12.50    0.160887    17.88    0.260907  
 28.99 

Females 13-49 yrs:

                    0.125285    13.92    0.201640    22.40    0.357586  
 39.73 

Attachment 3:  Chronic Inputs

U.S. Environmental Protection Agency                                Ver.
2.00

DEEM-FCID Chronic analysis for CHLORMEQUAT CHLORIDE              1994-98
data

Residue file: C:\Documents and Settings\dwilbur\My
Documents\DEEM\Chlormequat Chloride\Chlormequat Chloride.R98

                                                              Adjust. #2
used

Analysis Date 04-17-2007             Residue file dated:
04-17-2007/10:05:37/8

Reference dose (RfD) = 0.05 mg/kg bw/day

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

Food Crop                                       Residue      
Adj.Factors      Comment

EPA Code  Grp  Food Name                          (ppm)       

                                                             #1        
#2 

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

86010000 O    Water, direct, all sources         0.091000   1.000     
1.000   

86020000 O    Water, indirect, all sources       0.091000   1.000     
1.000   

Attachment 4:  Chronic Results

U.S. Environmental Protection Agency                                Ver.
2.00

DEEM-FCID Chronic analysis for CHLORMEQUAT CHLORIDE            (1994-98
data)

Residue file name: C:\Documents and Settings\dwilbur\My
Documents\DEEM\Chlormequat Chloride\Chlormequat Chloride.R98

                                                     Adjustment factor
#2 used.

Analysis Date 04-17-2007/10:06:36     Residue file dated:
04-17-2007/10:05:37/8

Reference dose (RfD, Chronic) = .05 mg/kg bw/day

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

                    Total exposure by population subgroup

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

                                                    Total Exposure

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

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

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

U.S. Population (total)                     0.001918                
3.8%

U.S. Population (spring season)             0.001901                
3.8%

U.S. Population (summer season)             0.002060                
4.1%

U.S. Population (autumn season)             0.001854                
3.7%

U.S. Population (winter season)             0.001854                
3.7%

Northeast region                            0.001750                
3.5%

Midwest region                              0.001939                
3.9%

Southern region                             0.001823                
3.6%

Western region                              0.002198                
4.4%

Hispanics                                   0.002177                
4.4%

Non-hispanic whites                         0.001871                
3.7%

Non-hispanic blacks                         0.001821                
3.6%

Non-hisp/non-white/non-black                0.002351                
4.7%

All infants (< 1 year)                      0.006288               
12.6%

Nursing infants                             0.002332                
4.7%

Non-nursing infants                         0.007790               
15.6%

Children 1-6  yrs                           0.002680                
5.4%

Children 7-12 yrs                           0.001742                
3.5%

Females 13-19 (not preg or nursing)         0.001350                
2.7%

Females 20+ (not preg or nursing)           0.001915                
3.8%

Females 13-50 yrs                           0.001856                
3.7%

Females 13+ (preg/not nursing)              0.001865                
3.7%

Females 13+ (nursing)                       0.002657          
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摧䑶>ᜀChildren 1-2 yrs                            0.002848          
      5.7%

Children 3-5 yrs                            0.002666                
5.3%

Children 6-12 yrs                           0.001839                
3.7%

Youth 13-19 yrs                             0.001386                
2.8%

Adults 20-49 yrs                            0.001791                
3.6%

Adults 50+ yrs                              0.001884                
3.8%

Females 13-49 yrs                           0.001783                
3.6%

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

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