Document ID: EPA-HQ-OPP-2007-0893-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-07-09T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:		June 2, 2008

SUBJECT:	Sethoxydim.  Amended human health risk assessment to support
uses on the Reapeseed Crop Subgroup 20A.

 

PC Code:  121001	DP Barcode: 353276

MRID No.:  None	Registration No.: None

Petition No.: 7E7232	Regulatory Action: None

Assessment Type: Food and Water Exposure	Reregistration Case No.: None

TXR No.: None	CAS No.: 74051-80-2 

FROM:     	David Soderberg, Chemist

		Reregistration Branch 3

		Health Effects Division (7509P)

THROUGH:	Cathy Eiden, Chief 

		RRB3/HED (7509P)

		

TO: 		Barbara Madden/Dan Rosenblatt 

RM05, MUIERB/RD (7505P)

The Interregional Research Project No.4 (IR4) submitted a petition for
translating the existing tolerance on rapeseed/Canola to other members
of the Rapeseed Crop Subgroup 20A.  This document is HED’s amended
human health risk assessment incorporating these proposed new uses. It
contains updated sections of the HED Human Health Risk Assessment of
June 2005 (D312569, W. Donovan, 6/22/2005). The following sections have
been updated to reflect these proposed new uses: residue chemistry,
dietary exposure and risk assessment, and aggregate risk assessment. It
should be emphasized that all the information contained in the June 2005
risk assessment remains unchanged unless specifically noted in this
memorandum. 

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 translating the existing tolerance on rapeseed to other members of a
proposed rapeseed crop subgroup 20A when sethoxydim is applied exactly
as it is to rapeseed.  These additional crops are:  Gold of Pleasure,
Crambe, Cuphea, Echium, Hare’s ear mustard, Lesquerella, Lunaria,
Meadowfoam, Milkweed, Mustard, Oil Radish, Poppy, Sesame, and Sweet
Rocket.  For these crops, multiple applications would be made by ground
and aerial sprays up to a maximum single application rate of 0.47 lb ai
per acre and not to exceed a total seasonal use rate of 0.94 lb ai per
acre as per the existing POAST® Herbicide (18% ai) label. Rapeseed is
the representative crop for this subgroup.  The existing tolerances for
rapeseed, seed (35 ppm) and rapeseed, meal (40 ppm), respectively, will
be applied to all members of crop subgroup 20A, except flax and borage,
which already have independent tolerances.  This new crop subgroup has
been reviewed and approved by HED (ChemSAC, 21 February 2007). However,
the subgroup has not yet been officially established.  Therefore, the
translation is allowable, but individual tolerances are needed for each
crop in this subgroup.  A subgroup tolerance, per se, would not be legal
at this time.  Since individual tolerances apply to individual crops
there is no difficulty with the proposed exceptions for borage and flax
from the crop-group tolerance at this time. Upon official establishment
of the Rapeseed Crop Subgroup 20A, a formal crop group tolerance may
become appropriate, and at that time it may become necessary to address
inclusion of these two crops within the crop subgroup.

 

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 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. No new residue data have been submitted to support this
petition. The available residue data on rapeseed have been generated
using validated analytical methods and are supported by adequate storage
stability data. There are adequate analytical methods to enforce
recommended tolerances. The submitted labels are adequate to support
translation of rapeseed data to the other crops of subgroup 20A.

Residential Exposure and Risk 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.  Postapplication exposures of children may result
from short-term contact with treated turf via dermal and oral routes
(hand-to-mouth activities).  However, since no toxicity was observed as
a result of dermal exposures in the available animal studies, only
exposure from inhalation for adult handlers and incidental ingestion for
children were assessed. The combined exposure of children resulting from
post-application, incidental ingestion of sethoxydim from hand-to-mouth,
turf-to-mouth, soil-to-mouth activities was also estimated. 

The results showed that risk estimates or margins of exposure (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 100 and are not of concern to HED.

The proposed new uses on the Rapeseed Crop Subgroup 20A do not affect
existing residential use patterns and do not impact the current
residential risk assessment reflected in HED’s risk assessment
D318165, W. Donovan, 6/22/2005. No revisions to the current residential
risk assessment are warranted as a result of these new uses.

Dietary Exposure and Risk 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.

In the current assessment, tolerance level residues were used and 100%
crop treated was assumed for all crops, including the crops of crop
subgroup 20A.  Tolerance level residues were also used for livestock,
poultry, eggs and milk.  Thus, both chronic and acute assessments were
Tier 1 assessments.  In accordance with this Tier, the acute assessment
was calculated at the 95th percentile. These assumptions result in a
very conservative dietary exposure and risk assessment. 

The acute dietary risks for combined exposures through food and drinking
water are not of concern to HED for the US general population and all
subgroups.  Based on the 95th percentile of exposure, the general US
population’s exposure is 7.4 % of the aPAD.  The most highly exposed
population subgroup is “children 1-2 years of age” with an estimated
exposure of 17 % of the aPAD.

The chronic dietary risks for combined exposures through food and
drinking water are not of concern to HED. Risk estimates are less than
100% of the chronic population adjusted dose (cPAD) for the US general
population and all subgroups.  The general US population’s exposure
from food plus water is of 34% of the cPAD.  The most highly exposed
population subgroup is “children 1-2 years of age” with an estimated
exposure of 94% of cPAD.

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.

Drinking Water Exposure and Risk 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). 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 used for surface water were:
130 ppb for acute exposure, and 16 ppb for chronic exposures. For ground
water, 1.5 ppb was used to estimate acute and chronic exposures.
(Personal communication with B. Eckels via email 3/24/08).

Aggregate Exposure and Risk Estimates

The proposed new uses of sethoxydim affect exposures through food,
minimally. They do not affect anticipated drinking water
exposures.Although the proposed new uses of sethoxydim do not impact the
residential use directly, the minimal affect on dietary exposures
warranted an update to the aggregate short-term risk assessment.
Consequently, aggregate risk assessments have been conducted for the
following three exposure scenarios: 1) combined exposures through food
and drinking water for acute (1-day) exposures, 2) combined exposures
through food and drinking water for chronic (long-term average)
exposures, and 3) short-term aggregate exposure from food, drinking
water, and residential uses.  A cancer aggregate risk assessment was not
performed because sethoxydim showed no evidence of carcinogenicity.  For
short-term aggregate risk assessments, the inhalation exposures
estimated for adult handlers cannot be combined with dietary (oral)
exposures because there is no common toxic effect across the oral and
inhalation routes of exposure. Intermediate- and long- term residential
exposures were neither expected nor assessed.  As stated previously, no
quantification of dermal exposure is required for any time period.

Estimates of aggregate risk from combined acute (single-day) exposures
to residues of sethoxydim in food and drinking water are the same as
those discussed above under the Dietary Exposure and Risk Estimates
section. Estimates of aggregate risk from combined chronic (average)
exposures to residues of sethoxydim in food and drinking water are the
same as those discussed above under the Dietary Exposure and Risk
Estimates section.

The short-term aggregate risk assessment estimates risk from potential
exposures to sethoxydim, over a 30 day time period, which may result
from residues in food and drinking water, and on home lawns.  High-end
estimates of exposure from lawns, and average estimates of exposure from
food and drinking water are used in the short-term aggregate risk
assessment. A short-term aggregate risk assessment was conducted for
children/toddlers 1-2 years of age. The calculated MOE of 1300 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 currently proposed uses will be added to the label for the
formulated end-use product, Poast® Herbicide (18% ai). It is an
emulsifiable concentrate.  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. The newly proposed uses of sethoxydim on
the Rapeseed Crop Subgroup 20A do not result in any new exposure
scenarios for workers. The existing exposure and risk assessment for
workers reflected in HED’s risk assessment (D318165, W. Donovan,
6/22/05) adequately represents anticipated exposure and risks for
workers as a result of the proposed new uses.

Inhalation exposure and risk were estimated for workers handling
sethoxydim products in 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.

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 conducted a Section 18 risk assessment for an
emergency exemption for the use of sethoxydim on buckwheat (D329545,
D.S. Davis, 7/19/06). HED also conducted a risk assessment to support
new uses on borage, buckwheat, dill, okra, radish, and turnip (D331916,
W. Phang, 10/6/06). Currently, in response to the IR-4 petition for new
uses for the Rapeseed Crop Subgroup 20A, HED has conducted a risk
assessment to support all existing uses and the newly proposed uses.

Under this request, no new data were submitted. There are no new
toxicology studies, occupational, residential, or residue data
associated with this petition. Therefore, the toxicology data are not
repeated here. Instead, the summary of toxicity endpoints selected for
risk assessments is presented in Section 4.0. The relevant information
on the residential and occupational exposure and risk assessments 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, and aggregate risk 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 of approximately 0.3 to 0.5 lbs
ai/A/application, and a maximum seasonal rate not to exceed
approximately 1 lb ai/A (0.94 lb ai/season).  

The registrant is requesting: 

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

Gold of Pleasure, Crambe, Cuphea, Echium, Hare’s ear mustard,
Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard, Oil Radish, Poppy,
Sesame, and Sweet Rocket

Postemergence

Broadcast, band, or spot

Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.47 (0.5) lbs ai/A	2 (with a minimum 14 day retreatment
interval)	0.94 (1.0) lbs ai/A	60	See Footnote1

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 & FQPA Considerations

The sethoxydim toxicology database is sufficient to support establishing
tolerances for the proposed new uses; the database is complete and there
are no data gaps.  The scientific quality of the database for sethoxydim
is relatively high and the toxicity profile can be characterized for all
effects. 

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 database on sethoxydim
indicates that the liver is a major target for this chemical.  In the
chronic toxicity study (dogs), there were significantly increased
absolute and relative liver weights accompanied by supportive clinical
chemistry and histopathology.  Dose-related clinical chemistry
abnormalities were observed in both sexes and  included increased
alkaline phosphatase and ALT and decreased albumin and cholesterol
synthesis.  Dose-related histopathologic lesions were found in the
liver, spleen, and bone marrow.  A mild hepatocellular cytoplasmic
alteration was found in low (1/6), mid (3/6), and high (6/6) doses in
males, and in the mid (1/6) and high (6/6) doses in females.  In
addition,  adverse liver effects were also observed via the oral route
in another species (mice) and via another route of exposure (inhalation)
in rats. 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 Hazard
Identification Assessment Review Committee (HIARC) (Sethoxyydim: HED
Chapter of the RED. D318165, W.H. Donovan, 6/22/2005) and presented in
Table 1a. 

There was no evidence for neurotoxicity in the toxicity database in
either adult or young animals. Clinical signs following sethoxydim
exposure in the developmental toxicity study in the adult rat included
irregular gait, decreased activity, excessive salivation, and anogenital
staining.  These effects were only observed in animals receiving very
high doses of sethoxydim (650 mg/kg/day and 1000 mg/kg/day). All
clinical signs reported for the adult animals were transient, with the
exception of the anogenital staining which did not reverse.  Because the
clinical signs occurred shortly after dosing, only occurred at very high
treatment doses (over one half the limit dose) and were transitory, it
is unlikely that the signs observed are the result of a primary systemic
effect on the nervous system but, rather, are reflective of the general
toxicity at a high dose. Further supporting a lack of neurotoxicity, it
should be noted that clinical signs indicative of nervous system effects
were not observed in any other standard toxicity study for sethoxydim. 
Although none of these other studies dosed up to 650 and 1000 mg/kg/day,
a maximum theoretical dose (MTD) was reached because there was evidence
of other toxicities (e.g., liver effects or body weight reductions). 

There were no effects seen in the young in the rat and rabbit
developmental studies indicative of an effect on the nervous system. 
The main effect seen in the young was an increased incidence of fetal
skeletal variations due to delayed ossification.  In the rat
developmental study, tail abnormalities (filamentous tail or lack of a
tail) were noted.  These abnormalities were observed at a very low
incidence (10 fetuses in 7 litters at 650 mg/kg/day) and at high
treatment doses (650 and 1000 mg/kg/day). In the two-generation
reproduction study in the rat, skeletal malformations (tail anomaly)
were seen in the F1b and F2b offspring in the two-generation rat
reproduction study in 1 out of 244 pups in the F1b generation and 2 out
of 344 pups in the F2b generation. Tail abnormalities may be related to
central nervous system (CNS) malformations; however, in this case, these
tail abnormalities are not likely to be the result of a primary
neurotube effect.  In the rat developmental study, there is no
description of any effect on neural-tube-derived structures.
Furthermore, this class of compounds, the cyclohexones, do not
demonstrate neurotoxicity or developmental malformations of the nervous
system.  

On December 2, 2004, the HED Risk Assessment Review Committee (RARC)
revisited the need for a developmental neurotoxicity study for
sethoxydim.  During that meeting, the RARC concurred with the risk
assessment team that the evidence does not support the need for a
developmental neurotoxicity study; noting that the clinical signs
observed at the high dose are likely to be a high dose phenomena. 
Additionally, the RARC recommended that the “tail abnormalities” be
described as skeletal malformations in the prenatal developmental study
in rats and 2-generation reproductive study in rats, rather than as
indications of neurotoxicity. Given these findings, the RARC recommended
the requirement for a developmental neurotoxicity study be waived.  

Overall, there was some evidence of qualitative susceptibility in the
developmental rat study with the occurrence of more severe effects in
the fetuses (delayed ossification and tail abnormalities) than in the
maternal animals (transient clinical signs including: irregular gait and
decreased activity) at the same dose.  However, these effects were of
low incidence and only observed at a high dose that is considered to be
close to a limit dose.  These effects were seen in the presence of clear
maternal toxicity and clear NOAELs and LOAELs were established for
maternal and developmental toxicities. 

In the reproduction study in rats, pups showed decreases in body weight
(11 to 13%) during lactation at 150 mg/kg/day. Adult female animals
exhibited body weight losses that are considered to be too small to
qualify as a significant adverse effect (8 to 10%) at this same dose.
The body weight changes in the pups are considered minimal and the
consideration of these body weight changes as an adverse effect in the
pups is considered to be conservative. Although technically this
qualifies as some evidence of quantitative susceptibility in the
two-generation reproduction study, the differences observed in body
weight losses between the adult and young animals is marginal and of low
concern. Consequently, there is a low degree of concern for the body
weight and tail effects seen in the rat developmental and rat
reproduction studies.  The developmental toxicity study in rabbits did
not exhibit either quantitative or qualitative susceptibility. Based on
the above information, the HIARC concluded and the RARC upheld that
there were no data gaps and there was low concern for pre- and/or
postnatal toxicity resulting from exposure to sethoxydim. After careful
consideration of the available toxicity data, the FQPA safety factor for
pre- and post-natal sensitivity in the young was reduced to 1X. 

An acute dietary endpoint was selected for the general US 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.  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 

ated 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 - Animals

The nature of the residue in animals is adequately understood. There are
no new significant livestock feed items associated with the proposed new
uses, and the existing livestock tolerances have been used for the
dietary exposure assessment.  The tolerance expression and the residues
of concern in poultry and livestock are the combined residues of
sethoxydim and its metabolites containing the 2-cyclohexen-1-one moiety
(calculated as sethoxydim). [See D318165, W. Donovan, 6/22/05; D327825 &
D327826, D. Soderberg, 8/8/2006.] 

5.2.1	Analytical Methods

Adequate enforcement methodology (gas 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 proposed Rapeseed Crop Subgroup 20A (oilseed)
tolerances. [See D342808, D. Soderberg, 05/07/08.]



5.3	Storage Stability Update

Because no new data were submitted, no new storage stability data are
needed at this time.  

5.4	Magnitude of Residue in Food Update

The data described below for canola (Rapeseed, seed) are from the HED
Chemistry Chapter of the Reregistration Eligibility Decision (RED)
D312567, W. Donovan, 4/22/05.  They are adequate to support the proposed
new uses of sethoxydim on the Rapeseed Crop Subgroup 20A.

 

Eight field trials were conducted in the following six states: ID, MT,
ND, OH, OR, and TN. It was noted that these states represent > 60 % of
the total US canola production (D171714, D171716, D171724, B.A.
Schneider, 6/4/92).  HED concluded that geographical representation for
the submitted field trials for canola is adequate.  Sethoxydim (Poast®
Herbicide) was applied postemergent at two applications at 14-19 day
intervals using the maximum label rate at 0.5 lb ai/A (1X) with PHI's
ranging from 59-61 days.  These treatments were applied as a broadcast
ground application directly to the emerged weeds (4-6 inches tall).  

	

Samples of the forage and seed were stored frozen at < -5°C until
further analysis; samples were analyzed 19 months after initial storage
following harvest. No storage stability data were submitted for this
crop; however, HED concluded that storage stability data developed for
soybean seed were adequate and translatable to canola.  

Slight modifications of the BASF Method 30 and BASF Method 30G were used
for the determination of sethoxydim in canola seeds and forage,
respectively. No samples were analyzed by the Craven Laboratories.  The
limit of quantitation was 0.05 ppm of sethoxydim equivalents for DME or
DME-OH, or 1.0 ppm for the total residue.  Control samples were
fortified with the metabolite MSO and 5-OH-MSO2. The canola forage
samples showed recoveries of MSO ranging from 61 to 115% with an average
of 91± 12%; while for 5-OH-MSO2 ranged from 65 to 114% with an average
of 96± 13%.  The canola seed samples showed recoveries of MSO ranging
from 69 to 115% with an average of 94±14.5%; while for 5-OH-MSO2 ranged
from 59 to 125% with an average of 100±14.7%.

At an application rate of 0.5 lb ai/A and a PHI of 59-61 days, total
sethoxydim residue (calculated as sum of DME plus DME-OH) in canola
forage ranged from <1.0-3.5 ppm while the residues in canola seed ranged
from 3.7-35.0 ppm.  These data are adequate to support the established
sethoxydim tolerance level of 35.0 ppm for canola seed.  

5.5	Processing factors

 

The data described below for canola (Rapeseed, meal) are from the HED
Chemistry Chapter of the Reregistration Eligibility Decision (RED)
D312567, W. Donovan, 4/22/05.  They are adequate to support the proposed
new uses of sethoxydim on the Rapeseed Crop Subgroup 20A.

Sethoxydim was applied at an 4X exaggerated rate (two applications of
0.5 lb ai/A + 1.0 qt/A crop oil concentrate) by a postemergent broadcast
ground application to weeds in canola cultivar 'West Star' located in
North Dakota with a PHI of 61 days.  At harvest, canola seed were stored
frozen within 4 hours and shipped to the Food Protein Research and
Development Center, Texas A&M University for processing.  The processing
study was conducted according to commercial practice.  The canola seed
samples were processed into press cake (meal), soapstock, crude and
refined oil fractions.  The optional oil bleaching and deodorizing steps
were not utilized in the study.  

Processed samples were then stored frozen (-5°C) and shipped to the lab
for analysis.  The canola seed and press cake samples were homogenized
and mixed with dry ice and finely ground and then stored frozen until
analysis.  The residues are quantitated as the sethoxydim dimethyl ester
metabolites, DME or DME-OH by gas chromatography utilizing a capillary
column with a flame photometric detector.  The detection limits for
canola seed, press cake (meal), and soapstock are 0.1 ppm, while the
detection limit for crude and refined oils are 0.04 ppm.  

Samples (press cake, soapstock, and crude and refined oils) were
analyzed 19 months after initial storage following harvest.  No storage
stability data were submitted for this crop; however, HED concluded that
storage stability data developed for soybean seed (non-Craven data) were
adequate and translatable to canola.  

Control samples for each matrix were also fortified at levels ranging
from 0.1 to 500 ppm with 5- OH-MSO2 or with DME.  The recoveries of
5-OH-MSO2 ranged from 73% in the press cake to 116% in canola seed with
an overall average of 86.2 ±13%; whereas the recoveries of DME ranged
from 61% in soapstock to 125% in canola seed with an overall average of
85.1 ±17%.   

       

Residue levels of total sethoxydim equivalents (includes DME and DME-OH)
in crude and refined oil were 76.4 ppm and 3.1 ppm, respectively;
whereas the press cake (meal) fractions contained 131 ppm.  These levels
were compared to a total residue level of 116 ppm in canola seeds. 
Hence, no significant concentration of residues was found in either the
crude or refined oil, but in meal, residues concentrated by a factor of
1.13x.  Multiplying the rapeseed, seed tolerance level of 35 ppm by 1.1x
supports the established tolerance level of 40 ppm for rapeseed, meal.
No new process factors are required for this action.  

5.6	Rotational Crops

No new rotational crop data are required for this action.

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.  

Commodity	Established Tolerance (ppm)	Recommended Tolerance (ppm)

Gold of Pleasure, seed	None	35.0

Gold of Pleasure, meal	None	40.0

Crambe, seed	None	35.0

Crambe, meal	None	40.0

Cuphea, seed	None	35.0

Echium, seed	None	35.0

Hare’s Ear Mustard, seed	None	35.0

Lesquerella, seed	None	35.0

Lunaria, seed	None	35.0

Meadowfoam, seed	None	35.0

Milkweed, seed	None	35.0

Mustard, seed	None	35.0

Oil Radish, seed	None	35.0

Poppy, seed	None	35.0

Sesame, seed	None	35.0

Sweet Rocket, seed	None	35.0

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 the
document:  Acute and Chronic Dietary and Drinking Water Exposure and
Risk Assessments for the Section 3 Registration of Sethoxydim on all
Members of Rapeseed Oilseed Crop Group 20A, Except Borage and Flax. 
(D342808, D. Soderberg, 4/23/08). 

Acute Dietary Exposure Results 

The results of the acute dietary analysis indicate that estimated risks
from exposures to sethoxydim in foods are not of concern to HED. The
risk estimates are less than 100% of the acute population adjusted dose
(aPAD) for the US general population and all subgroups.  At the 95th
percentile of exposure, the general US population’s exposure is
equivalent to 7.2 % of the aPAD.  The most highly exposed subpopulation
is “children 1-2 years of age” with an exposure equivalent to 16% of
the aPAD.

The results of the aggregate acute dietary analysis indicate that acute
aggregate dietary risks from food and drinking water are not of concern
to HED for the US general population and all subgroups.  At the 95th
percentile of exposure, the general US population’s exposure is
equivalent to 7.4 % of the aPAD.  The most highly exposed subpopulation
is “children 1-2 years of age” with an exposure equivalent to 17 %
of the aPAD.

The results of the acute dietary exposure analysis at the 95th, 99th,
and 99.9th percentiles of exposure for food only and food plus water are
reported in D342808, D. Soderberg, 4/23/08.  

Chronic Dietary Exposure Results

The results of the chronic dietary analysis indicate that chronic
dietary exposures from food only are not of concern to HED. Risk
estimates are less than 100% of the chronic population adjusted dose
(cPAD) for the US general population and all subgroups.  The general US
population’s exposure from food is equivalent to 34% of the cPAD.  The
most highly exposed subpopulation is “children 1-2 years of age”
with an exposure equivalent to 94% of cPAD.

The results of the aggregate chronic dietary analysis indicate that
aggregate chronic exposures from food and drinking water are not of
concern to HED. Risk estimates are less than 100% of the chronic
population adjusted dose (cPAD)) for the US general population and all
subgroups.  The general US population’s exposure is equivalent to 34%
of the cPAD.  The most highly exposed subpopulation is “children 1-2
years of age” with an exposure equivalent to 94% of cPAD.

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.

Results of Dietary Exposure and Risk Analysis

The results of the acute and chronic dietary exposure and risk analyses
for food only and food plus water, respectively, are reported in the
tables below.  

Summary of Dietary Exposure and Risk for Sethoxydim  

Food Only

Population Subgroup	Acute Dietary

(95th Percentile)	Chronic Dietary

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

(mg/kg/day)	% cPAD*

General US Population	0.129259	7.2	0.047636	34

All Infants (< 1 year old)	0.190322	11	0.074275	53

Children 1-2 years old	0.293377	16	0.131214	94

Children 3-5 years old	0.253556	14	0.112690	81

Children 6-12 years old	0.167761	9.3	0.072083	52

Youth 13-19 years old	0.103168	5.7	0.043357	31

Adults 20-49 years old	0.086628	4.8	0.036793	26

Adults 50+ years old	0.081074	4.5	0.034655	25

Females 13-49 years old	0.083667	4.7	0.035737	26

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

Summary of Dietary Exposure and Risk for Sethoxydim

Food Plus Water

Population Subgroup	Acute Dietary

(95th Percentile)	Chronic Dietary

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

(mg/kg/day)	% cPAD*

General US Population	0.132821	7.4	0.47974	34

All Infants (< 1 year old)	  0.200810	11	0.75381	54

Children 1-2 years old	0.297125	17	0.131715	94

Children 3-5 years old	0.256073	14	0.113159	81

Children 6-12 years old	0.171893	9.6	0.072406	52

Youth 13-19 years old	0.104972	5.8	0.043600	31

Adults 20-49 years old	0.089478	5.0	0.037108	27

Adults 50+ years old	0.084573	4.7	0.034986	25

Females 13-49 years old	0.087110	4.8	0.036051	26

 *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. Estimates of concentrations of
sethoxydim residues in drinking water were provided by the Environmental
Fate and Effects Division (EFED). The values were derived from modeling
(FIRST Model) performed using the maximum number of applications (4) and
maximum single application rate (0.47 lb ai per acre) for a maximum
seasonal rate of 1.9 lb ai per acre (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).
The table below presents the estimated concentrations of sethoxydim
residues in drinking water.

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 the table below and
are taken directly from the HED Chapter of the Sethoxydim RED. 

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.  The results are
summarized in the tables below. 

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.    

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.    

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.  Intermediate-term and
long-term aggregate exposures are not anticipated.  No quantification of
risk from dermal exposure is 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)

EEM-FCID™, Version 1.3, described in the acute dietary section above. 
The current assessment was an unrefined Tier I assessment that used only
tolerances and no percent crop treated adjustment.  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 US
population and all subgroups.  At the 95th percentile of exposure, the
general US population’s exposure from food and water results in an
exposure equivalent to 7.4% of the aPAD.  The most highly exposed
subpopulation is “children 1-2 years of age” with an exposure
equivalent to 17% of the aPAD.   

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.  This was an unrefined Tier 1
assessment based upon tolerance level residues and no refinement for
percent crop treated.  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 US population and all
subgroups.  The general US population’s average exposure from food
plus water is equivalent to 34% of the cPAD.  The most highly exposed
subpopulation is “children 1-2 years of age” with an exposure
equivalent to 94% of  cPAD.



Summary of Aggregate Exposure and Risks (Food plus water)

Population Subgroup	Acute Dietary

(95th Percentile)	Chronic Dietary

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

(mg/kg/day)	% cPAD*

General US Population	0.132821	7.4	0.47974	34

All Infants (< 1 year old)	  0.200810	11	0.75381	54

Children 1-2 years old	0.297125	17	0.131715	94

Children 3-5 years old	0.256073	14	0.113159	81

Children 6-12 years old	0.171893	9.6	0.072406	52

Youth 13-19 years old	0.104972	5.8	0.043600	31

Adults 20-49 years old	0.089478	5.0	0.037108	27

Adults 50+ years old	0.084573	4.7	0.034986	25

Females 13-49 years old	0.087110	4.8	0.036051	26

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

Short-Term Aggregate Risk Assessments

Short-term aggregate risk assessment estimates potential risks from 1 to
30 day exposures to sethoxydim residues in food and drinking water, and
on home lawns.  High-end estimates of the lawn exposures are combined
with average estimates of exposure from food and drinking water.

Short-term aggregate risk estimates were not calculated for adult
handlers because the toxic effects identified for the oral and
inhalation exposure pathways differ, and no dermal risk assessment is
required. Short-term aggregate risk assessments are required for
children/toddlers, because potential exposures from incidental ingestion
resulting from a child’s contact with turf treated with sethoxydim can
be combined with dietary exposures to sethoxydim in food and drinking
water.  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.  The estimated MOE for
short-term aggregate exposures to sethoxdim is 1300. This MOE is greater
than 100 and not of concern. HED has no concern for short-term aggregate
risk for children/toddlers as a result of the newly proposes uses.



  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	0.131715	0.009	0.14	1300

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 occupational exposure assessment provided in this section has been
excerpted from the HED Chapter of the Reregistration Eligibility
Decision (RED) Document (D318165, W. Donovan, 6/22/05) and Occupational
Exposure/Risk Assessment Document for Sethoxydim (D331918, J. Arthur,
9/25/06).  The occupational risk assessments reflected in these
documents adequately cover the proposed new uses of sethoxydim on the
Rapeseed Crop Subgroup 20A. The proposed new 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.  Occupational
handlers and postapplication workers may be exposed for short- and
intermediate-term durations. 

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

Rapeseed Crop Subgroup 20A	0.47	0.94	60

	

Because of a 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	

Inhalation exposures exposure and risks were estimated for workers for
the following representative 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 provided in the table below provide a range of risk estimates
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 not of concern.  Exposure assumptions and
estimates for occupational handlers are summarized in the table below.

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)

5 MOE = NOAEL/ Daily Inhalation Dose.  Short- and Intermediate-term
Inhalation NOAEL = 81mg/kg/day.

  

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.  

	

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 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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