Document ID: EPA-HQ-OPP-2006-0321-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-28T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Oct. 6, 2006

  SEQ CHAPTER \h \r 1 MEMORANDUM

SUBJECT:	Sethoxydim: Amended human health risk assessment to support
uses on borage, buckwheat, dill, okra, radish, and turnip. Petition Nos:
4E6885 & 0E62004

		PC Code:   121001

		DP Barcode:  D 331916

		Registration Action: Section 3 Registration

		Risk Assessment Type: Single Chemical/aggregate

FROM:     	Whang Phang, PhD, Toxicologist

		Reregistration Branch 1

		Health Effects Division (7509P)

THROUGH:	Michael S. Metzger, Chief, RRB1/HED (7509P)

		Paula A. Deschamp, Chief, RAB3/HED (7509P)

To: 		Marcel Howard/Dan Rosenblatt, RM05, MUIERB/RD (7505P)

The Interregional Research Project No.4 (IR4) submitted a petition for
establishing 

tolerances for new uses of sethoxydim on borage, buckwheat, dill, okra,
radish, and turnip.

Based on the newly proposed uses, HED has conducted an amended risk
assessment, and 

this memorandum contains the updated sections of the HED Human Health
Risk

Assessment of June 2005 (D312569, W. Donovan, 6/22/2005), specifically
residue chemistry, 

dietary exposure and risk assessment, aggregate risk assessment,
occupation exposure and risk 

assessment sections. It should be emphasized that all the information
contained in the June 2005 risk assessment remains unchanged unless
specifically noted in this memorandum. Relevant information from the
following documents has been used to support this amended risk
assessment: 

Sethoxydim:	HED Chapter of the Reregistration Eligibility Decision (RED)
Document.  PC Code 121001, DP Barcode D318165. William H. Donovan,
6/22/5005.

Sethoxydim.  	Response to Petition for Tolerance on Borage, buckwheat,
Dill, Okra, 

Radish, and Turnip Greens, Summary of Analytical Chemistry and residue
data. D32785 and 327826, D Soderberg, 8/8/2006.

Sethoxydim.  	Acute and Chronic Aggregate Dietary and Drinking Water
Exposure and Risk Assessments for the Section 3 New Uses on Borage,
Buckwheat, Dill, Okra, Radish and Turnip Greens and to Support the
Establishment of a Crop Group Tolerance for Root and Tuber Vegetables
(Crop Group 1). D332702, D.S. Davis, 9/26/2006

Sethoxydim.	Drinking Water Assessment (Tier 1) for Reregistration
Eligibility Decision.  D312559, William Eckel, 2/7/2005.

  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 

Sethoxydim .	Occupational Exposure/Risk Assessment for the Use of
Sethoxydim on Turnip Greens, Buckwheat, Okra, Borage, Dill and Radish.
D331918, J. Arthur, 9/25/2006.

Sethoxydim. 	ID#06ND08. Section 18 Exemptions for the use of Sethoxydim
on Buckwheat. D329545, D.S. Davis, 7/19/06.

Sethoxydim. 	Data to support Amended Preharvest Intervals for
Cantaloupe, Cucumber, Celery, Mustard Green, and Pepper. Summary of
Analytical Chemistry and Residue Data. D314259 & 322194, N. Dodd,
6/28/2006.

Sethoxydim.	HED Chemistry Chapter of the Registration Eligibility
Decision (RED). Summary of Analytical Chemistry and Residue Data. Case
No. 2600. D312567, W. H. Donovan, 4/22/2005.

1.0 Executive Summary

  SEQ CHAPTER \h \r 1 Sethoxydim is a selective, systemic, post emergent
herbicide used for the control of annual and perennial grass weeds in
broadleaf crops.  Sethoxydim is a member of the cyclohexenone class of
pesticides which include cycloxydim, clethodim, and tralkoxydim.
Tolerances are currently established (40 CFR §180.412) for residues of
sethoxydim and its metabolites on a variety of agricultural commodities
at levels ranging from 0.2 ppm to 75.0 ppm.  Permanent tolerances are
also established in/on the meat and fat of cattle, goats, hogs, horses,
poultry, and sheep at 0.2 ppm; meat byproducts of cattle, goats, hogs,
horses, and sheep at 1.0 ppm (2.0 ppm in meat byproducts of poultry);
eggs at 2.0 ppm, and milk at 0.5 ppm.  The tolerance expression for
plant and livestock commodities includes the combined residues of
sethoxydim and its metabolites containing the 2-cyclohexen-1-one moiety
(calculated as the herbicide) as specified in 40 CFR §180.412.

	

Sethoxydim is currently registered on agricultural crops such as various
fruits, tree nuts, vegetables and herbs, as well as non-agricultural
sites, including ornamentals and flowering plants, recreational areas,
rights-of-way, along fences and hedgerows, and public and commercial
buildings/structures (non-agricultural-outdoors).

The Interregional Research Project No. 4 (IR4) has submitted a petition
for establishing tolerances for new uses of sethoxydim on borage,
buckwheat, dill, okra, radish, and turnip. For these crops multiple
applications would be made by ground or aerial sprays, up to a maximum
single application rate of 0.47 lb ai per acre. 

Hazard Assessment

The toxicity database for sethoxydim is complete, and there are no
datagaps.  The acute toxicity data indicate that sethoxydim is minimally
toxic (Category III) via oral, dermal, and inhalation routes of
exposure.  It is neither irritating to the eye nor the skin (Category
IV).  With repeated dosing, the data show that the liver is a major
target for this chemical. The available carcinogenicity studies found no
increased tumor incidence in either rats or mice. There was no evidence
of neurotoxicity. There were no major developmental and reproductive
effects seen. The toxicity endpoints and the uncertainty factors for
risk assessments are presented in Table 1a (page 9) of this document.

Residue Chemistry

The qualitative nature of the residue in plants is adequately
understood; there are no livestock feed items associated with the
proposed uses. The residue data have been generated using validated
analytical methods and are supported by adequate storage stability data.
There are adequate analytical methods to enforce recommended tolerance.
The available confined rotational crop data are of limited value in
determining the need for rotational crop tolerances. At this time, HED
concluded that no tolerances are required for rotational crops provided
plantback intervals are greater than 30 days. The recommended tolerances
are presented in Table 18 (page 24) of this document.

Residential Exposure Estimates

Homeowners who apply sethoxydim to ornamental gardens and turf may be
exposed for short- term (up to 30 days) durations via the dermal and
inhalation routes.  Short-term postapplication exposures to children may
result from incidental oral contact via hand-to-mouth activities with
treated turf.  No dermal toxicity endpoints were identified, therefore,
only exposure from inhalation (adult handlers) and incidental ingestion
(children) were assessed. The risk for postapplication toddler
short-term incidental ingestion (hand-to-mouth, turf-to-mouth,
soil-to-mouth) was also estimated. 

The results showed that MOEs for residential (non-occupational) handler
range from 1.4x106 to 1.6x106 and for short term post-application
incidental ingestion (children: hand-to-mouth, object-to-mouth, and
ingestion of soil) range from 26,000 to 7.6x106 . These MOEs are above
the target MOE of 100 and are not of concern to HED.

Dietary Exposure Estimates

Acute and chronic dietary exposure assessments for sethoxydim were
conducted using the

 Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database 

(DEEM-FCID(, Version 2.03), which uses food consumption data from the
USDA’s 

Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996
and 1998.

For acute dietary exposure, the assessment was partially refined, using
tolerance level residues for most of the crops with the incorporation of
field trial data and experimental processing factors for some of the
crops expected to be more highly associated with dietary exposure to
sethoxydim. The results of the acute dietary analysis indicate that
acute dietary risks (food only) do not exceed HED’s level of concern
(less than 100% of the acute population adjusted dose (aPAD)) for the
U.S. population and all subgroups .  At the 99.9th percentile, the U.S.
population exposure from food only results in a risk level equivalent to
11% of the aPAD.  The most highly exposed subpopulation is “children
1-2 years of age” with an exposure from food which results in a risk
level equivalent to 19% of the aPAD.

For chronic dietary analysis, tolerance level residues were used and
100% crop treated was assumed.  The results of the chronic dietary
analysis indicate that chronic dietary risks (food only) do not exceed
HED’s level of concern (less than 100% of the chronic population
adjusted dose (cPAD) for the U.S. population and all subgroups.  The
U.S. population exposure from food only results in a risk level which is
equivalent to 6.6% of the cPAD.  The most highly exposed subpopulation
is “children 1-2 years of age” with an exposure equivalent to 16% of
 cPAD.

Drinking Water Exposure Estimates

The sethoxydim residues in drinking water were provided by Environmental
Fate and Effects Division (EFED), the values were derived from modeling
performed using the maximum number of application (4) and maximum
application rates with the Tier 1 model called FIRST, (D312559, W.
Eckel, 2/7/2005). At this time,  EFED confirmed that new water residue
values would not be necessary because the currently proposed uses would
not result in greater exposures relative to those used in the June 2005
assessment. The estimated drinking water concentrations were for surface
water: acute exposure, 130 ppb and chronic exposure, 16 ppb; and for
ground water: acute and chronic exposure, 1.5 ppb.

Aggregate Exposure Scenarios and Risks

Aggregate risk assessments have been conducted for the following
exposure scenarios:  acute and chronic aggregate exposure (food +
drinking water), and short-term aggregate exposure (food + drinking
water + residential).  A cancer aggregate risk assessment was not
performed because sethoxydim showed no evidence of carcinogenicity.  For
short- and intermediate-term aggregate exposure/ risk assessments, the
inhalation exposures estimated for adult handlers cannot be combined
with dietary exposure due to lack of common toxicity via the oral 
(transitory clinical signs: irregular gait at doses of 650 mg/kg & 1000
mg/kg) and inhalation (hepatotoxicity) routes of exposure. Intermediate-
and long- term residential exposure was neither expected nor assessed. 
No quantification of dermal exposure is required for any time period.

Acute aggregate risk assessment (food & drink water)

ing DEEM-FCID™, Version 1.3, The results of the aggregate acute
dietary analysis indicate that acute aggregate dietary risks (food and
water) do not exceed HED’s level of concern for the U.S. population
and all subgroups.  At the 99.9th percentile, the U.S. population
exposure from food and water results in a risk that is equivalent to 11
% of the aPAD.  The most highly exposed subpopulation is “children 1-2
years of age” with an exposure from food and water at 20% of the aPAD

in the chronic dietary risk assessment risk assessment using
DEEM-FCID™, Version 1.3.  The results of the aggregate chronic dietary
analysis indicate that aggregate chronic dietary risks (food plus water)
do not exceed HED’s level of concern (less than 100% of the chronic
population adjusted dose (cPAD)) for the U.S. population and all
subgroups.  The U.S. population exposure from food plus water results in
a risk level which is equivalent to 6.9% of the cPAD.  The most highly
exposed subpopulation is “children 1-2 years of age” with an
exposure equivalent to 16% of  cPAD

Short-Term Aggregate Risk Assessments

The short-term aggregate risk assessments estimate risks likely to
result from 1–30 day exposures to sethoxydim residues from food,
drinking water, and residential pesticide uses.  High-end estimates of
the residential exposure are used in the short-term assessments, and
average values are used for food and drinking water exposures. A
short-term aggregate risk assessment was conducted for children/toddlers
1-2 years of age since this is the child/toddler subpopulation with the
highest estimated food + water exposure. The calculated MOE of 5700 is
substantially greater than the target MOE of 100; therefore, HED has no
concern for short-term aggregate risk for children/toddlers as a result
of the newly proposes uses.

Occupational Exposure Estimates

The currenty proposed uses involved the formulated end-use product, an
emulsifiable concentrate (18% ai), labeled under the tradename, Poast®
Herbicide.  For the proposed crops, multiple ground sprays are made by
ground equipment and aerial application, up to a maximum single
application rate of 0.47 lb ai per acre. Occupational handlers and
postapplication workers may be exposed for short- and intermediate-term
durations. 

Occupational handlers exposure estimates

Handlers inhalation exposure and risk were assessed for the following
scenarios: (1) mixing/loading liquid (open pour) for groundboom
application; (2) mixing/loading liquid (open pour) for aerial
application; (3) mixing/loading/applying with backpack sprayer; (4)
applying with groundboom (open cab); (5) applying with fixed-wing
aircraft (enclosed cockpit); and (6) flagging for aerial application.
The results show that the MOEs range from 8400 for Mixing/Loading Liquid
(open pour) for Aerial Application to 310,000 for mixing, loading and
applying liquid with a backpack sprayer.  These MOEs are above 100, and
therefore, are not of concern.

Occupational Postapplication Exposure and Risks

While the proposed use for sethoxydim is to control grass weeds in
broadleaf crops, accomplishing this purpose can involve limited foliar
application.  Therefore, there is a potential for postapplication
exposure to scouts, harvesters and other field workers.  However,
because no appropriate dermal endpoints were identified for this
exposure potential, and postapplication inhalation exposure is expected
to be negligible, an occupational postapplication risk assessment was
not conducted.  

	

2.0	 Background

In June of 2005, HED completed a human health risk assessment for the
active ingredient, sethoxydim for purposes of a reregistration
eligibility decision (D318165, W.H. Donovan, 6/22/2005). Following that
risk assessment, the registrant submitted data to support amended
preharvest intervals (PHIs) for cantaloupe, cucumber, celery, mustard
green, and pepper. HED evaluated the submission and concluded that the
data were acceptable in support of reduced PHIs and resulted in no
change in tolerances or risks (D314259 & 322194, N. Dodd, 6/28/06).
Subsequently, HED also conducted a Section 18 risk assessment for an
emergency exemption for the use of sethoxydim on buckwheat (D329545,
D.S. Davis, 7/19/06). Currently, HED has been requested to conduct an
updated risk assessment to support the proposed new uses on borage,
buckwheat, dill, okra, radish, and turnip.

Under this request, there are no new toxicology studies or occupational
and residential exposure data. Therefore, the toxicology data are not
repeated here;  the summary of toxicity endpoints selected for risk
assessments is presented in Section 4.0 (pages 8 & 9). The relevant
information on  the residential exposure assessment is excerpted from
June 2005 human health risk assessment (D318165, W.H. Donovan,
6/22/2005).

This memorandum serves to update the residue chemistry, dietary exposure
and risk assessment, aggregate risk assessment, and occupational
exposure assessment sections of the June 2005 human health risk
assessment. All information contained in the 6/22/05 risk assessment
remains unchanged unless specifically noted in this memorandum.

Summary of Proposed Uses

Sethoxydim is generally applied postemergence by ground or aerial
broadcast spray and can also be applied in bands or used as a spot
treatment.  Usually one to three applications are used and in the
current submissions PHIs range from 14 days to 30 days (for turnip
greens) after applications at

 0.3 – 0.5 lbs ai/A/application, usually with a 1 lb ai/A seasonal
rate.  

The registrant is requesting the registration of sethoxydim for uses on
buckwheat, okra, borage, dill, radish, and turnip. Current formulations
of sethoxydim include soluble concentrate (SC) and emulsifiable
concentrate (EC).  The active ingredient (ai) sethoxydim in these
formulations

ranges from 11.15% to 43%.  The directions for the proposed use are
summarized in Table 1.

It should be noted that the submitted crop field trial data are
acceptable to support the proposed PHIs for the individual crops of
borage, buckwheat, dill, okra, radish, and turnip tops.

Table 1.  Summary of Directions for Use of Sethoxydim.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Borage

Postemergence

Broadcast, band, or spot Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.5 lbs ai/A	2	1.0 lbs ai/A	23	See Footnote1

Buckwheat

Postemergence

Broadcast, band, or spot Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.5 lb ai/A	2	1.0 lb ai/A	21	See Footnote1

Dill

Postemergence

Broadcast, band, or spot Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.5 lb ai/A	2	1.0 lb ai/A	14	See Footnote1

Okra

Postemergence

Broadcast, band, or spot Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.3 ai/A, then 0.5 lbs ai/A	3	1.1 lb ai/A	14	See Footnote1

Radish

Postemergence

Broadcast, band, or spot Ground or aerial

	POAST EC 1.5 lbs/gal

7969-58	0.5 lbs ai/A	1	0.5 lb ai/A	14	See Footnote1

Turnip

Postemergence

Broadcast, band, or spot Ground only.	POAST EC 1.5 lbs/gal

7969-58	0.3 lbs ai/A	1	0.3 lbs ai/A	30	Do not use on turnips grown for
roots.  Do not use tops or roots for livestock grazing or feeding.  No
aerial application.

1.  The master label includes the following general use directions:  (1)
use with spray adjuvants, including crop oil concentrate or
modified/methylated seed oil is recommended; and (2) a 30-day plantback
interval is established for any crop for which there is no registered
use of sethoxydim.  

4.0	Hazard Characterization

The sethoxydim toxicology database is sufficient for consideration in
establishing tolerances for the currently requested new uses. The hazard
characterization was presented in the June 22, 2005 HED Chapter of the
RED (W.Donovan, 6/22/2005). The acute toxicity data indicate that
sethoxydim is minimally toxic via oral, dermal and inhalation routes of
exposure.  It is neither irritating to the eye nor the skin.  With
repeated dosing, the primary target organ for this chemical is the
liver. The available carcinogenicity studies found no increased tumor
incidence in either rats or mice. There was no evidence of
neurotoxicity. There were no major developmental and reproductive
effects seen.

Based on the available toxicity data on sethoxydim, the toxicity
endpoints for risk assessment were established by the HIARC
(Sethoxyydim: HED Chapter of the RED. D318165, W.H. Donovan, 6/22/2005)
and presented in Table 1a. The FQPA safety factor for sethoxydim was
reduced to 1X based on completeness of the database and low concern for
pre- and/or postnatal toxicity resulting from exposure to this chemical.
 An acute dietary endpoint was selected for the general U.S. Population,
including infants and children from a rat developmental study.    SEQ
CHAPTER \h \r 1 The acute RfD (aRfD) of 1.8 mg/kg/day is based on a
NOAEL of 180 mg/kg/day with a 100-fold uncertainty factor (10X
interspecies and 10X intraspecies) applied.  At the study LOAEL of 650
mg/kg/day the effect observed included irregular gait.  Since the FQPA
SF was reduced to 1X, the aPAD is equal to the aRfD (1.8 mg/kg/day). 
The chronic dietary endpoint was selected from a   SEQ CHAPTER \h \r 1
mouse combined chronic toxicity/carcinogenicity study.  The chronic RfD
(cRfD) of 0.14 mg/kg/day is based on a NOAEL of 14 mg/kg/day with a
100-fold uncertainty factor (10X interspecies and 10X intraspecies)
applied.  At the study LOAEL of 41.2 mg/kg the effect observed was early
onset of liver effects including hepatocellular hypertrophy and fatty
degeneration.  Since the FQPA SF was reduced to 1X, the cPAD is equal to
the cRfD (0.14 mg/kg/day).    SEQ CHAPTER \h \r 1 Sethoxydim is not a
likely human carcinogen based on lack of evidence of carcinogenicity in
rats and mice.

  SEQ CHAPTER \h \r 1 A rat developmental study was used to select the
dose and endpoint for short-term incidental oral exposure.  The basis
for the endpoint was the maternal NOAEL of 180 mg/kg/day and maternal
LOAEL of 650 mg/kg/day based on irregular gait observed in dams on the
first day of dosing.  The level of concern (LOC) for this endpoint is
for margins of exposure (MOEs) that are less than 100. 
Intermediate-term incidental oral exposure is not anticipated;
therefore, no endpoint was selected.  No dermal toxicity   SEQ CHAPTER
\h \r 1 endpoints have been identified for sethoxydim because no dermal
or systemic toxicity was seen following repeated dermal applications of
sethoxydim at the limit-dose to rabbits.    SEQ CHAPTER \h \r 1 A rat
28-day inhalation study was used for dose and endpoint selection of 0.3
mg/L (81 mg/kg/day) for short-, intermediate- and long-term inhalation
exposure.  At the study LOAEL of 2.4 mg/L (651 mg/kg/day) effects
observed included on liver weight, clinical chemistry (bilirubin) and
histology changes.  The level of concern (LOC) for the short- and
intermediate-term risk assessment for both residential and occupation
exposure is for margins of exposure (MOEs) less than 100.

 

Table 1a.  Summary of T oxicological Doses and Endpoints for
Sethoxydim

Exposure

Scenario	Dose Used in Risk Assessment, UF	FQPA SF*and Level of Concern
for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(Females 13-50 years of age)	NOAEL = 180 mg/kg/day

UF = 100

Acute RfD = 1.8 mg/kg/day	FQPA SF = 1X

aPAD = 

1.8 mg/kg/day	Rat Developmental Toxicity

Developmental LOAEL = 650 mg/kg/day based on decreased fetal body
weight, tail abnormalities, delayed ossification.

Acute Dietary

(General population including infants and children)	NOAEL = 180
mg/kg/day

UF = 100

Acute RfD = 1.8 mg/kg/day	FQPA SF = 1X

aPAD = 

1.8 mg/kg/day	Rat Developmental Toxicity

Maternal LOAEL = 650 mg/kg/day based on irregular gait that was observed
in 12/34 dams on the first day of dosing.

Chronic Dietary

(All populations)	NOAEL= 14 mg/kg/day

UF = 100

Chronic RfD = 

0.14 mg/kg/day	FQPA SF = 1X

cPAD =

 0.14 mg/kg/day	Mouse Carcinogenicity Study

LOAEL = 41 mg/kg/day based on liver hypertrophy and fatty degeneration.

Short-Term Incidental Oral (1-30 days)	NOAEL = 180 mg/kg/day	Residential
LOC for MOE = 100

Occupational = N/A	Rat Developmental Toxicity Study

Maternal LOAEL = 650 mg/kg/day based on irregular gait that was observed
in 12/34 dams on the first day of dosing

Short-, Intermediate-, and Long-Term Dermal	No dose/endpoint selected
Residential LOC for MOE = N/A

Occupational = N/A	Dermal exposure risk assessments are not required
because no dermal or systemic toxicity was seen following repeated
dermal applications of sethoxydim at the limit-dose to rabbits.

Short-Term Inhalation (1 to 30 days)	NOAEL = 81 mg/kg/day	Residential
LOC for MOE = 100

Occupational LOC for MOE = 100	28-day Rat Inhalation Study

LOAEL = 651 mg/kg/day based on increased liver weight, clinical
chemistry (increased total serum bilirubin), and liver histopathology.

Intermediate-Term Inhalation (1 to 6 months)	NOAEL = 81 mg/kg/day
Residential LOC for MOE = 100

Occupational LOC for MOE = 100	28-day Rat Inhalation Study

LOAEL = 651 mg/kg/day based on increased liver weight, clinical
chemistry (increased total serum bilirubin), and liver histopathology

Long-Term Inhalation (>6 months)	NOAEL = 81 mg/kg/day	Residential LOC
for MOE = 300

Occupational LOC for MOE = 300	28-day Rat Inhalation Study

LOAEL = 651 mg/kg/day based on increased liver weight, clinical
chemistry (increased total serum bilirubin), and liver histopathology

Cancer	Not a likely human carcinogen based on the lack of evidence of
carcinogenicity in rats and mice. 

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no
observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic), RfD =
reference dose

5.0	Metabolism Section Update

5.1	Nature of the residue – Plants

		Sethoxydim 

hydroxylated and desethoxylated analogs, and oxazole compounds; very
little (≤0.5%) sethoxydim is left unmetabolized.  The residues of
concern in plants are the combined residues of sethoxydim and its
metabolites containing the 2-cyclohexen-1-one moiety (calculated as
sethoxydim) (D318165, W. Donovan, 6/22/05; D327825 & D327826, D.
Soderberg, 8/8/2006). 

5.2	Nature of the residue

The nature of the residue in plants and animals is adequately
understood.  The residues to be included in the tolerance expression and
in the risk assessment for plant and livestock commodities are the
combined residues of sethoxydim and its metabolites containing the
2-cyclohexen-1-one moiety (calculated as parent sethoxydim) as specified
in 40 CFR § 180.412. However, there are no livestock feed items
associated with the proposed uses; therefore, data requirements for
livestock metabolism data are not relevant to this tolerance petition
(D327825 & D327826, D. Soderberg, 8/8/2006). 

5.2.1	Analytical Methods

Adequate enforcement methodology (gas-liquid chromatography with flame
photometric detection in the sulfur mode) is available [BASF Wyandotte
Corporations’ (BWCs) Method No. 30, 3/15/82; MRID 44864501; Method I,
PAMII] to enforce the tolerance expression for the purpose of this
request.



5.3	Starage Stability Update

With the present submissions concurrent storage stability recoveries
(before and after) were performed with the borage, buckwheat, radish,
and dill field trials D327825 & D327826, D. Soderberg, 8/82006). Table 2
presents the range of frozen storage stability recoveries at the end of
storage for each analyte and crop.  

Table 2. Results of concurrent recoveries at the end of the testing
period after frozen storage for the commodities tested in this
submission   

Crop/Commodity	Analyte	Days of Storage	Range of Recoveries

Radish Tops	MSO	135	76-114%

	5-OH-MSO2	135	84-102%

Radish Roots	MSO	299	48-71%

	5-OH-MSO2	299	20-40%

Borage Seed	MSO	203	60-81%

	5-OH-MSO2	203	67-100%

Okra	MSO	131	Not analyzed

	5-OH-MSO2	131	Not analyzed

Dill/Fresh	MSO	370	82-87%

	5-OH-MSO2	370	89-93%

Dill/Dried	MSO	413	85%

	5-OH-MSO2	413	87-88%

Dill Oil	MSO	387	70-82%

	5-OH-MSO2	287	86-92%

Buckwheat Seed	MSO	174	62-86%

	5-OH-MSO2	174	71-81%

Buckwheat Groats	MSO	75	76-90%

	5-OH-MSO2	75	86-98%

 MSO: sulfoxide;     	 	MSO2: sulfone;  	   	 5-OH-MSO: 5-hydroxysulfone

Except for radish roots, all of these storage stability data were
acceptable.  The radish root stored recoveries were low, did not well
support the residue results found and might have required an adjustment
of residues by three or four fold.  Incorporating radish roots into the
Root and Tuber Crop Group 1, at a tolerance of 4.0 ppm for the crop
group, as recommended below, obviates any potential need for such an
adjustment (D327825 & D327826, D. Soderberg, 8/8/2006). 

5.4	Magnitude of Residue in Food Update

The field trial studies on the proposed crops were found to be adequate
(D327825 & D327826, D. Soderberg, 8/82006). Based upon the results of
the field trial studies, the residues from the proposed crops were
determined and summarized in Table 3. 

Table 3.  Summary of Residues from the Crop Field Trials with
Sethoxydim.

Crop Matrix	

Applic. Rate

(lb ai/A)	

PHI (days)	Residues (ppm)

	Mean	Std. Dev.	HAFT 	Min.	Max.

Buckwheat (proposed use =  1 lb ai/A total application rate, 21-day PHI)

Seed	0.98 – 1.00	19 - 23	8.77	2.77	12.24	3.78	13.74

Okra (proposed use = 1.1 lb ai/A total application rate, 14-day PHI)

Okra Pods	1.09 – 1.14	13-14	0.687	0.337	1.23	0.28	1.32

Borage (proposed use = 1 lb ai/A total application rate, 23-day PHI)

Seed	1.0	27	2.76	0.72	2.9	1.8	3.5

Dillweed (proposed use = 1 lb ai/A total application rate, 14-day PHI)

Leaves and Stems	0.99 - 1.02	13 - 14	5.20  	1.23	6.4	3.4	6.9

Dried Leaves and Stems	0.99 - 1.02	13 - 14	3.08  	1.29	4.15	1.36	4.71

Radish (proposed use = 0.5 lb ai/A total application rate, 14-day PHI)

Top	0.49 - 0.51	13-15	1.35	0.977	3.2	<0.14	3.6

Root	0.49 - 0.51	13-15	0.49	0.200	0.64	<0.09	0.69

5.5	Processing factors

 

The buckwheat field trial studies included studies of the further
processing buckwheat seed into groats; residues were also determined on
fresh dill weed, dried dill weed, and oil. Borage is often grown as
oilseed from which borage oil may be extracted, leading to a borage
press cake, or meal. Although a borage oil processing study was intended
to be performed, heavy rains between cutting and harvest of borage
caused insufficient seed to be collected for conducting the processing
study. It was proposed to translate residues in borage meal and oil from
canola meal. The canola data indicated that there was a lack of
concentration in canola oil, but there was a slight concentration of
canola meal (D327825 & D327826, D. Soderberg, 8/8/2006).  The processing
factors are summarized in Table 4.

 

Table 4.  Processing Factors

Crop	

Commodity	

Residues in RAC (ppm)	Residues in Processed Commodity (ppm) 	

Concentration Factor	

Does the residue concentrate?

Buckwheat	Groats	6.9	8.4	1.22	Yes, slightly

Dillweed	Dried Dillweed	4.30	3.42	0.80	No

	Dill Oil	4.30	0.091	0.02	No

Borage	Borage Oil	2.76	Not determined	Translated from canola, 0.03 for
refined canola, 0.66 for crude canola1	No

	Borage meal	2.76	Not determined	1.13 translated from canola1	Yes,
slightly

1.  Insufficient sample was harvested to determine borage concentration
factors directly.  In lieu of a borage processing study, processing
factors were translated from canola.  

5.6	Rotational Crops

The available confined rotational crop data were determined to be of
limited value in determining the need for rotational crop tolerances
because no data concerning the nature of the residues in rotational
crops were reported.  Based on confined rotational crop study using
soybeans in which the total radioactive residues (TRRs) were generally
less than 10 ppb and an acceptable limited rotational study using the
common moiety method which showed that all residues were below the LOQ
in all rotational crops at all plantback intervals, HED concluded that
no tolerances would be required for rotational crops provided plantback
intervals were greater than 30 days (D312567, W. Donovan, 4/22/2005;
D327825 & D327826, D. Soderberg, 8/8/2006).

5.7	Proposed  and Recommended Tolerances

The tolerance expression for sethoxydim is for the combined residues of
sethoxydim and its metabolites containing the 2-cyclohexen-1-one moiety,
and expressed as sethoxydim.  Current sethoxydim tolerances are listed
in 40 CFR 180.412.  For the individual RACs, the recommended tolerances
were derived with the aid of the Tolerance/MRL Harmonization
Spreadsheet.  The highest tolerance for representative roots and tubers
were used for the Root and Tuber, Crop Group 1 tolerance at 4.0 ppm. 
The turnip green tolerance was translated from the Brassica tolerance,
and tolerances for processed RACs were estimated based upon processing
information.  The borage processed products were estimated from the RAC
tolerance using canola processing information (D327825 & D327826, D.
Soderberg, 8/8/2006). The proposed and recommended tolerances for
presently petitioned crop uses are summarized in Table 5.

Table 5.  Tolerance Summary for Sethoxydim on the currently proposed
uses

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments
(correct commodity definition)

Buckwheat, grain	20	19	From Tolerance Harmonization Spreadsheet

Buckwheat, flour	20	25	From a processing factor of 1.22 applied to the
buckwheat tolerance and raised to 25 ppm because of uncertainties in the
result.  

Okra	4.0	2.5	From Tolerance Harmonization Spreadsheet

Borage, seed	5.0	6.0	From Tolerance Harmonization Spreadsheet

Borage, meal	40	10	From seed, with correction for a small concentration
factor from canola, and uncertainty

Borage, Oil	40	None	No separate tolerance is required because the oil is
covered by the seed tolerance.  

Dillweed, Fresh leaves	10	10	From Tolerance Harmonization Spreadsheet

Dillweed, Dried leaves	10	None	No separate tolerance is required because
the dried dillweed is covered by the fresh dillweed tolerance.  

Radish, Tops	5.0	4.5	From Tolerance Harmonization Spreadsheet

Turnip, Greens	5.0	5.0	Translated from Brassica

Root and Tuber Vegetable, Crop group 1	4.0	4.0	Incorporate both radish
root, and existing tolerances for carrot (currently 1.0 ppm);
horseradish (currently 4.0 ppm); beet, garden (currently 1.0 ppm); beet,
sugar, root (currently 1.0 ppm); and tuberous and corm vegetable
subgroup 1D (currently 4.0 ppm)

6.0	Exposure Characterization/Assessment Section update  

6.1	Dietary Exposure/Pathway

6.1.1	Acute and Chronic Dietary Exposure and Risk Update 

Acute and chronic dietary exposure assessments for sethoxydim were
conducted using the

 Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database 

(DEEM-FCID(, Version 2.03), which uses food consumption data from the
USDA’s 

Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996
and 1998. The acute 

and chronic dietary exposure assessments are excerpted from  Sethoxydim.
 Acute and Chronic

 Aggregate Dietary and Drinking Water Exposure and Risk Assessments for
the Section 3 New Uses on Borage, Buckwheat, Dill, Okra, Radish and
Turnip Greens and to Support the Establishment of a Crop Group Tolerance
for Root and Tuber Vegetables (Crop Group 1) (D332702, D.S. Davis,
9/26/2006). 

	Acute Dietary Exposure Results (Food only)

For all proposed new uses and for commodities in Crop Group 1, the root
and tuber vegetables group, tolerance level residues were incorporated
into the acute dietary assessment and 100% crop treated was assumed. For
those crops with existing uses, available maximum percent crop treated
values provided by the Biological and Economic Analysis Division (BEAD)
were used to refine the acute dietary assessment.  Tolerance level
residues were used for most of the existing uses, but some additional
refinement was obtained through the incorporation of field trial data
for apples, pears and other pome fruits, grapes, oranges, potatoes,
tomatoes, and strawberries. Empirical processing data for apples,
grapes, tomatoes, potatoes and oranges were used, and were sometimes
translated to other members of the crop group.  For livestock
commodities, the available percent crop treated information was
incorporated into the dietary burden calculation and the feeding studies
were used to determine the appropriate residue level, however at least
one food item in each diet was assumed to be 100% crop treated.  

The results of the acute dietary analysis indicate that acute dietary
risks (food only) do not exceed HED’s level of concern (less than 100%
of the acute population adjusted dose (aPAD)) for the U.S. population
and all subgroups (Table 6).  At the 99.9th percentile, the U.S.
population exposure from food only results in a risk level equivalent to
11 % of the aPAD.  The most highly exposed subpopulation is “children
1-2 years of age” with an exposure from food which results in a risk
level equivalent to 19% of the aPAD.

Table 6.  Results of Sethoxydim Acute Dietary Exposure Analysis Using 
DEEM FCID 

Food Only

Population Subgroup	aPAD (mg/kg/day)	95th Percentile	99th Percentile
99.9th Percentile

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

General U.S. Population	0.18	0.062052	3.4	0.107092	6.0	0.197193	11

All Infants (< 1 year old)	0.18	0.092686	5.2	0.148287	8.2	0.242682	13

Children 1-2 years old	0.18	0.137493	7.6	0.211212	12	0.350626	19

Children 3-5 years old	0.18	0.115146	6.4	0.177473	9.9	0.281542	16

Children 6-12 years old	0.18	0.075907	4.2	0.127385	7.1	0.218672	12

Youth 13-19 years old	0.18	0.045950	2.6	0.077993	4.3	0.156306	8.7

Adults 20-49 years old	0.18	0.042777	2.4	0.068711	3.8	0.121839	6.8

Adults 50+ years old	0.18	0.043556	2.4	0.069174	3.8	0.113602	6.3

Females 13-49 years old 	0.18	0.042644	2.4	0.068923	3.8	0.122385	6.8

Table excerpted from D332702 (D.S. Davis, 9/26/2006)

	Chronic Dietary Exposure Results

For the proposed new uses and all commodities in Crop Group 1, the root
and tuber vegetable group, tolerance level residues were used and 100%
crop treated was assumed. For those crops with existing tolerances, the
chronic dietary analysis used tolerance level residues and average
percent crop treated values where available.  Livestock commodity
tolerances were not used; the percent crop treated data for some
livestock feeds were incorporated into the calculations of the
theoretical dietary burdens for livestock, which were then used in
conjunction with the available feeding studies to determine the residues
in livestock commodities.  

The results of the chronic dietary analysis indicate that chronic
dietary risks (food only) do not exceed HED’s level of concern (less
than 100% of the chronic population adjusted dose (cPAD)) for the U.S.
population and all subgroups (Table 7).  The U.S. population exposure
from food only results in a risk level which is equivalent to 6.6% of
the cPAD.  The most highly exposed subpopulation is “children 1-2
years of age” with an exposure equivalent to 16% of  cPAD

Results of Cancer Dietary Exposure Analysis

Sethoxydim is not a likely human carcinogen based on lack of evidence of
carcinogenicity in rats and mice; therefore, a dietary cancer exposure
and risk analysis was not conducted.

Table 7 . Summary of Chronic of Dietary Exposure for Sethoxydim (Food
only)

Population Subgroup	Chronic Dietary	Cancer

	Dietary Exposure

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

(mg/kg/day)	Risk

General U.S. Population	0.009265	6.6	N/A

	N/A

All Infants (< 1 year old)	0.019891	14

Children 1-2 years ld	0.022431	16

Children 3-5 years old	0.019075	14

Children 6-12 years old	0.012982	9.3

Youth 13-19 years old	0.008567	6.1

Adults 20-49 years old	0.007294	5.2

Adults 50+ years old	0.007462	5.3

Females 13-49 years old	0.007137	5.1

 *The values for the highest exposed population for each type of risk
assessment are bolded.

A summary of acute and chronic dietary exposures and risks with food
only is presented in Table 8.

Table 8.  Summary of Dietary Exposure and Risk for Sethoxydim (Food
Only)

Population Subgroup	Acute Dietary

(99.9th 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	0.197193	11	0.009265	6.6	N/A

	N/A

All Infants (< 1 year old)	0.242682	13	0.019891	14

Children 1-2 years old	0.350626	19	0.022431	16

Children 3-5 years old	0.281542	16	0.019075	14

Children 6-12 years old	0.218672	12	0.012982	9.3

Youth 13-19 years old	0.156306	8.7	0.008567	6.1

Adults 20-49 years old	0.121839	6.8	0.007294	5.2

Adults 50+ years old	0.113602	6.3	0.007462	5.3

Females 13-49 years old	0.122385	6.8	0.007137	5.1

 *The values for the highest exposed population for each type of risk
assessment are bolded.

7.0	Water Exposure Risk/Pathway

The Metabolism Assessment Review committee (MARC) determined that the
sulfoxide and sulfone derivates of the sethoxydim (MSO and MSO2) as well
as two other degrades, M1S and M2S were of concern in drinking water
(D246356, R. Loranger, 5/27/98); therefore, for this assessment the
estimated concentrations in drinking water include total residues of
sethoxydim and its metabolites. The sethoxydim residue levels in
drinking water were provided by Environmental Fate and Effects Division
(EFED). The values were derived from modeling (FIRST Model) performed
using the maximum number of application (4) and maximum application
rates (D312559, W. Eckel, 2/7/2005).  The details are presented in the
June 2005 Human Health Risk Assessment on Sethoxydim (D318165, W.
Donovan, 6/22/05).  EFED confirmed that new water residue values would
not be necessary because the currently proposed uses would not result in
greater exposures relative to those used in the June 2005 assessment
(D313456, D314420, W. Eckel, 3/3/2006). Table 9 presents the estimated
concentrations of sethoxydim residues in drinking water.

Table 9.  Estimated Concentrations of Sethoxydim Residues in Drinking
Water.   

Chemical	Surface Water (ppb) 	 Groundwater (ppb)

 	Acute	Chronic	Acute and Chronic

Sethoxydim	130	16	1.5

8.0	Residential Exposure Risk Characterization  				

Non-dietary, non-occupational exposure was addressed in the HED Chapter
of the RED for sethoxydim (D318165, W. Donovan, 6/22/05) and in a
Section 18 Exemptions document (D329545, D.S. Davis, 7/19/06). Following
the completions of these documents, no new information on residential
exposure has been submitted. The currently proposed agricultural uses of
sethoxydim do not impact the prior analyses. Sections of those analyses
are repeated here to allow for transparent calculation of aggregate risk
assessments required to support the proposed new uses. 

Non-Occupational (Residential) Handler Exposure and Risks

Sethoxydim is registered for residential (consumer) use on ornamentals
and flowering plants, recreational areas, and buildings/ structures
(outdoor).  Homeowners who apply sethoxydim to ornamental gardens and
turf may be exposed for short-term durations via the dermal and
inhalation routes.  Dermal endpoints were not selected, so dermal
exposure and risk assessments are not required.  Residential handler
scenarios assessed for sethoxydim are as follows:

Inhalation exposure from mixing/ loading/ applying liquids for low
pressure hand wand application

Inhalation exposure from mixing/ loading/ applying liquids for backpack
sprayers

Inhalation exposure from mixing/ loading/ applying liquids for garden
hose-end sprayers (spot treatment)

Residential (non-occupational) handler MOEs range from 1.4x106 to
1.6x106 and, therefore, do not exceed HED’s level of concern.  Results
from exposure and risk calculations are presented in Table 10, below and
are taken directly from the HED Chapter of the Sethoxydim RED. 

Table 10:  Short-term  Exposures and Risks for Residential
(Non-occupational) Handlers

Exposure Scenario (Scenario #)	

Inhalation Unit Exposure   (Ug/lb ai)1	

Crop2	

Application Rate3	

Daily Area Treated4	

Inhalation Dose (mg/kg/day)5	

Inhalation MOE6

Mixer/Loader/App

Mixing/Loading/Applying Liquids for Low Pressure Handwand application
(1)	

30	

Ornamentals, Flowering Plants, Turf/ Lawn	

0.02 lb ai per gallon	

5 Gallons per day	

0.000049	

1600000

Mixing/Loading/Applying Liquids for Backpack sprayer application (2)	

30	

Ornamentals, Flowering Plants, Turf/ Lawn	

0.02 lb ai per gallon	

5 Gallons per day	

0.000049	

1600000

Mixing/Loading/Applying Liquids for Garden hose-end sprayer(ORETF -
conventional) application (2)	

17	

Ornamentals, Flowering Plants, Turf/ Lawn	

0.47 lb ai per acre	

0.5 Acres per day	

0.000057	

1400000

1Baseline inhalation unit exposures represent no respirator.  Values are
reported in the PHED Surrogate Exposure Guide dated August 1998 or are
from data submitted by the Outdoor Residential Exposure Task Force dated
May 2000.

2Crops and use patterns are from various sources including LUIS and
labels.

3Application rates are based on maximum values found in various sources
including LUIS and various labels.  In most scenarios, a range of
maximum application rates is used to represent the range of rates for
different crops/sites/uses.  Most application rates upon which the
analysis is based are presented as lb ai/A.  In some cases, the
application rate is based on applying a solution at concentrations
specified by the label (i.e., presented as lb ai/gallon).   

4Amount treated is based on the area or gallons that can be reasonably
applied in a single day for each exposure scenario of concern based on
the application method and formulation/packaging type. (Standard
EPA/OPP/HED values).

5Inhalation dose (mg/kg/day) = [unit exposure (ug/lb ai) * 0.001 mg/ g
unit conversion * Inhalation absorption (100%) * Application rate (lb
ai/acre or lb ai/gallon) * Daily area treated (acres or gallons)] / Body
weight (70 kg).

6Inhalation MOE = NOAEL (81 mg/kg/day) / Daily Inhalation Dose. Target
Inhalation MOE is 100.

							

Residential Postapplication Exposure and Risks

Sethoxydim can be used in areas that can be frequented by the general
population including residential areas (i.e. home lawns).  This is
potential for dermal (adults and children) and incidental oral exposure
(children) following application of sethoxydim.  Since there are no
dermal endpoints selected, dermal exposure assessments are not required.
 Incidental oral exposure and risk estimates were derived using the HED
Standard Operating Procedures for Residential Exposure Assessments
(draft December 18, 1997).  Postapplication risk scenarios assessed for
sethoxydim are as follows:

Toddler:  Hand-to-Mouth Activity on Turf

Toddler:  Object-to-Mouth Activity on Turf

Toddler:  Incidental Soil Ingestion.

MOEs for all toddler postapplication risk scenarios (short-term)
exceeded 100 and are therefore not of concern.  Results are summarized
in Tables 11, 12, and 13. 

Table 11 .  Short-term Oral Hand-to-Mouth Exposure and Risk for Children
from Treated Lawns

Exposure Scenario	

Formulation	

Application Rate (lbai/A)	

Percent ai dislodgeable	

TTR1 (µg/cm2)	

Surface Area (cm2)	

Hand to Mouth (events/ hr)	

Extraction  by Saliva	

Exposure Time (hrs/ day)	

Body Weight (kg)	

Daily Dose2 (mg/kg/day)	

MOE3

Hand-to-Mouth (using 5% defalt)	

Spray	

0.47	

5 %	

0.26	

20	

20	

50%	

2	

15	

0.007	

26000

1 Turf Transferrable Residue (ug/cm2) = Application rate (lb ai/A) x
Fraction of ai Available  x  4.54E+8 ug/lb x 2.47E-8 A/cm2

2 Daily Dose = (Turf Transferrable Residue (ug/cm2) x Extraction by
Saliva x Hand Surface Area (cm2/event) x Frequency (events/hr) x 1E-3
mg/ ug  x  ET (hrs/day)] / [Body Weight (kg)]

3 MOE = Short-Term Oral NOAEL (180 mg/kg/day) /Daily Dose.    

Table 12.  Short-term Oral Object-to-Mouth (Turfgrass) Exposure and Risk
for Children from Treated Lawns

Exposure Scenario	

Formulation	

Application Rate (lbai/A)	

Percent ai dislodgeable	

TTR1 (µg/cm2)	

Surface Area Mouthed (cm2/day)	

Body Weight (kg)	

Daily Dose2 (mg/kg/day)	

MOE3

Object-to- Mouth (turf)	

Spray	

0.47	

20 %	

1.05	

25	

15	

0.0018	

100000

1Grass residue (ug/cm2) = [Application Rate (lbs ai/A)  x Fraction of ai
Available x  4.54E+8 ug/lb x 2.47E-8 A/cm2]

2 Daily Dose  = [Grass reside (ug/cm2) x Surface Area Mouthed (cm2/day)
x 1E-3 mg/ug] / [Body Weight (kg)]

3 MOE = Short-Term Oral NOAEL (180 mg/kg/day) /Daily Dose.    

Table 13.   Short-term Exposure and Risk for Children from Ingestion of
Soil

Exposure Scenario	

Formulation	

Application Rate (lbai/A)	

Fraction of ai available	

Soil Residue1 (µg/g)	

Ingestion Rate (mg/day)	

Body Weight (kg)	

Daily Dose2 (mg/kg/day)	

MOE3

Soil Ingestion	

Spray	

0.47	

100%	

3.5	

100	

15	

2.4E-05	

7600000

1 Soil residue (ug/g) = [Application Rate (lbs ai/A)  x Fraction of ai
Available x  4.54E+8 ug/lb x 2.47E-8 A/cm2 x 0.67 cm3/g soil]

2 Daily Dose  = [Soil reside (ug/g) x Ingestion rate (mg/day) x 1E-6
g/ug]  

3 MOE = Short-Term Oral NOAEL (180 mg/kg/day) /Daily Dose.       

Spray Drift

Spray drift is always a potential source of exposure to residents nearby
to spraying operations. However, for sethoxydim exposures resulting from
intentional use in residential settings would pose a worst case
residential risk when compared to any potential exposure from spray
drift.  Because human health risks from existing residential uses of
sethoxydim had previously been assessed and did not result in concerns
for HED, potential spray drift exposures from the currently proposed
agricultural uses would not cause concern to HED.

9.0 	Aggregate Risk Assessment and Risk Characterization updates

As indicated by 1996 FQPA, when there are potential residential
exposures to the pesticide, aggregate risk assessment must consider
exposures from three major sources: oral, dermal and inhalation
exposures.  For short-term aggregate risk assessments, oral and
inhalation exposures can not be aggregated because of a lack of a common
toxic endpoint across the exposure routes.  Long-term aggregate
exposures are not anticipated.  No quantification of dermal risk
assessments are required for any time period because of lack of toxicity
at the limit dose in a 28-day dermal toxicity study. A cancer aggregate
risk assessment was not performed because sethoxydim shows no evidence
of carcinogenicity.

Aggregate exposure/risk assessments were performed for the following
scenarios:

Acute and chronic aggregate exposure (food + drinking water)

Short-term aggregate exposure (residential + food + drinking water)

In the June 22, 2005 human health risk assessment for sethoxydim,
aggregate risk assessment included the residential exposure in the
short-term aggregate risk assessment for children/toddlers because there
was a potential for oral post-application exposure resulting from
residential use of sethoxydim. Aggregate (food and water) risk
assessments were conducted to assess acute and chronic risks using the
Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID(, Version 2.03), which uses food consumption
data from the USDA’s Continuing Surveys of Food Intakes by Individuals
(CSFII) from 1994-1996 and 1998.  Estimated drinking water
concentrations provided by EFED were directly incorporated into the
assessment. 

Acute Aggregate Risk Assessment (Food and Drinking Water)

30 ppb into the dietary risk assessment using DEEM-FCID™, Version 1.3,
described in the acute dietary section above.  The results of the
aggregate acute dietary analysis indicate that acute aggregate dietary
risks (food and water) do not exceed HED’s level of concern for the
U.S. population and all subgroups.  At the 99.9th percentile, the U.S.
population exposure from food and water results in a risk that is
equivalent to 11% of the aPAD.  The most highly exposed subpopulation is
“children 1-2 years of age” with an exposure from food plus water
results in a risk level equivalent to 20% of the aPAD (Table 14). It
should be noted that this acute aggregate risk assessment is a screening
level assessment since a high end water residue value (derived from
FIRST model) has been used. As described in the aggregate exposure
assessment guidance, this situation will rarely, if ever, occur.
However, since risk estimates did not indicate a risk concern, a
refinement of these screening level values were not persued.

Chronic Aggregate Risk Assessment (Food and Drinking Water)

To assess chronic aggregate (food + water) risks, HED incorporated the
chronic surface water EDWC value for total sethoxydim residues of 16 ppb
into the chronic dietary risk assessment described in the chronic
dietary section above.  The results of the aggregate chronic dietary
analysis indicate that aggregate chronic dietary risks (food plus water)
do not exceed HED’s level of concern (less than 100% of the chronic
population adjusted dose (cPAD)) for the U.S. population and all
subgroups.  The U.S. population exposure from food plus water results in
a risk level which is equivalent to 6.9% of the cPAD.  The most highly
exposed subpopulation is “children 1-2 years of age” with an
exposure equivalent to 16% of  cPAD (Table 14 ).



Table 14.  Summary of Aggregate Exposure and Risks (Food plus water)

Population Subgroup	Acute Dietary

(99.9th Percentile)	Chronic Dietary

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

(mg/kg/day)	% cPAD*

General U.S. Population	0.202537	11	0.009603	6.9

All Infants (< 1 year old)	0.243032	14	0.020996	15

Children 1-2 years old	0.355120	20	0.022932	16

Children 3-5 years old	0.283931	16	0.019544	14

Children 6-12 years old	0.221346	12	0.013306	9.5

Youth 13-19 years old	0.165614	9.2	0.008811	6.3

Adults 20-49 years old	0.127659	7.1	0.007608	5.4

Adults 50+ years old	0.114856	6.4	0.007793	5.6

Females 13-49 years old	0.130177	7.2	0.007451	5.3

 *The values for the highest exposed population for each type of risk
assessment are bolded.

Short-Term Aggregate Risk Assessments

The short-term aggregate risk assessments estimate risks likely to
result from 1–30 day exposures to sethoxydim residues from food,
drinking water, and residential pesticide uses.  High-end estimates of
the residential exposure are used in the short-term assessments, and
average values are used for food and drinking water exposures.

Short-term aggregate risk assessments were not calculated for adult
handlers because oral and inhalation endpoints lack a common toxicity
endpoint.  Short-term aggregate risk assessments are required for
children/toddlers, because there is a potential for oral postapplication
exposure resulting from the residential uses of sethoxydim.  A
short-term aggregate risk assessment was conducted for children/toddlers
1-2 years of age since this is the child/toddler subpopulation with the
highest estimated food + water exposure and thus, also protective of
children 3-5 years of age (Table 15).  The calculated MOE of 5700
substantially exceeds the level of concern (LOC) of 100; therefore, HED
has no concern for short-term aggregate risk for children/toddlers as a
result of the newly proposes uses.



Table 15.  Short-Term Aggregate Toddler Risk Assessment

Population Subgroup	NOAEL (mg/kg/day)	Target MOE	Estimated Food + Water
Exposure (mg/kg/day)	Estimated Residential Exposure1 (mg/kg/day)
Estimated Aggregate Exposure (mg/kg/day)	MOE

Short-Term: Children (1 -2 years old)	180	100	0.0229	0.0088	0.0317	5700

1Estimated Residential Exposure is the sum of the incidental oral
hand-to-mouth from treated lawns, incidental oral object-to-mouth from
treated lawns and ingestion of soil.

10.0	Occupational Exposure/Pathway Updates

The occupation exposure assessment is excerpted from Occupational
Exposure/Risk Assessment document for Sethoxydim  (D331918, J. Arthur,
9/25/06).  The currenty proposed uses involved the formulated end-use
product, an emulsifiable concentrate (18% ai), labeled under the
tradename, Poast® Herbicide.  For the proposed crops, multiple ground
sprays are made by ground equipment and aerially, up to a maximum single
application rate of 0.47 lb ai per acre (Table 16).  Occupational
handlers and postapplication workers may be exposed for short- and
intermediate-term durations. 

Table 16.  Summary of Proposed Use Patterns for Sethoxydim.

Crop	Max. Single Application Rate (lb ai/A)	Max. Seasonal Application
Rate (lb ai/A)	PHI (days)	Use Directions and Limitations

Borage	0.47	0.94	23	Applications can be made to actively growing weeds
by aerial, broadcast, band, or spot spraying.

Make postemergence application to weeds when weeds are small.

Buckwheat	0.47	0.94	21

	Dill	0.47	0.94	14

	Okra	0.28	1.03	14

	Radish	0.47	0.47	14

	Turnip	0.47	0.47	14

	

Due to lack of toxicity in the 21-day dermal toxicity at limit dose
(1000 mg/kg) and no developmental toxicity rabbits, no dermal toxicity
endpoint for risk assessment was identified for sethoxydim. 
Occupational assessments were only performed for inhalation exposure,
with the level of concern (LOC) for an MOE < 100.  

 

10.1	Handler Exposure and Risk	

Handlers inhalation exposure and risk were assessed for the following
scenarios: (1) mixing/loading liquid (open pour) for groundboom
application; (2) mixing/loading liquid (open pour) for aerial
application; (3) mixing/loading/applying with backpack sprayer; (4)
applying with groundboom (open cab); (5) applying with fixed-wing
aircraft (enclosed cockpit); and (6) flagging for aerial application. 

The MOEs range from 8400 for Mixing/Loading Liquid (open pour) for
Aerial Application to 310,000 for mixing, loading and applying liquid
with a backpack sprayer.  These MOEs are above 100, and therefore, are
not of concern.  Exposure assumptions and estimates for occupational
handlers are summarized in Table 17.

Table 17.  Inhalation Exposure and Risks for Occupational Handlers

PHED Scenario

Selected from PSEG (8/98)	

PHED Unit Exposure 1

(mg/lb ai) 	

Data Confidence	

Application Rate 2

	

Amount Treated 3

	

Daily 

Dose 4

(mg/kg/day)	

Short/Interm.-Term Inhal.

MOE 5

1. Mixing/Loading  Liquid (open pour) for Groundboom  Application	

0.0012	

High	

0.47 lb ai/A	

200 A/day	

0.0016	

50,000

2. Mixing/Loading Liquid (open pour) for Aerial Application	

0.0012	

High	0.47 lb ai/A	

1200 A/day	

0.0097	

8400

3. Mixing/Loading/Applying with Backpack Sprayer	

0.03	

Low	

0.015 lb ai/Gal.	

40 Gal./day	

0.00026	

310,000

4. Applying Sprays with a Groundboom Sprayer (open cab)	

0.00074	

High	

0.47 lb ai/A	

200 A/day	

0.00099	

82,000

5. Applying with Fixed-Wing Aircraft (enclosed cockpit)	

0.000068	

Medium	

0.47 lb ai/A	

1200 A/day	

0.00055	

150,000

6. Flagging (Sprays) for Aerial Operations	

0.00035	

High	

0.47 lb ai/A	

350 A/day	

0.00082	

99,000

1Unit Exposure values are based on exposure without a respirator.  

2 Maximum application rates were used for screening purposes.

3Standard values for amount treated in a day were used.  Values for
large acreage crops (buckwheat) were used as a worst-case for all other
crops.  Only 350 A/day used for flagger; above this amount would require
GPS or mechanical flagging.

4 Daily Dose = [Unit Exposure (mg/lb ai handled) x Application Rate x
Amount Treated] / Body Weight (70 kg used because endpoint effects were
not considered gender-specific)

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10.2	Occupational Postapplication Exposure and Risks

While the proposed use for sethoxydim is to control grass weeds in
broadleaf crops, accomplishing this purpose can involve limited foliar
application.  Therefore, there is a potential for postapplication
exposure to scouts, harvesters and other field workers.  However,
because no appropriate dermal endpoints were identified for this
exposure potential, and postapplication inhalation exposure is expected
to be negligible, an occupational postapplication risk assessment was
not conducted.  

	

The current label for Poast® has a 12-hour restricted entry interval
(REI).  The sethoxydim technical material has been classified in
Toxicity Category III for acute oral, dermal, and inhalation and
Toxicity Category IV for primary eye irritation and primary skin
irritation.  Per the Worker Protection Standard (WPS), a 12-hour
restricted entry interval (REI) is required for chemicals classified
under Toxicity Category III or IV.  Therefore, the interim REI of 12
hours appearing on the label is in compliance with the WPS.

Sethoxydim:  	Human Health Risk Assessment to Support New Uses          
                   

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