Monsanto Company, member and managing agent of The Acetochlor
Registration Partnership, authorizes the EPA to publish the following
summary of the petition to comply with the Food Quality Protection Act
of 1996. An electronic copy on computer disc is provided with the cover
letter for this submission. 

ENVIRONMENTAL PROTECTION AGENCY

[OPP-XXXX-XXXX; FRL-XXXX-X]

Acetochlor; Notice of Filing a Pesticide Petition to Establish
Tolerances for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA)

ACTION: Notice

SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by docket identification (ID) number
OPP-XXXX-XXXX, must be received on or before XXXX.

ADDRESS: Comments may be submitted electronically, by mail, or by hand
delivery/courier.  Follow the detailed instructions as provided in Unit
I, of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: James A. Tompkins (PM 25), Registration
Division (750C), Office of pesticide programs, Environmental Protection
Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20450-0001; telephone
number: (703) 308-9364; e-mail address:   HYPERLINK
"mailto:Tompkins.Jim@epa.gov"  Tompkins.Jim@epa.gov .

* * * * * * * * * * * * * *

Summary of Petition

	A summary of the pesticide petition is printed below as required by
section 408(d)(3) of the FFDCA.  The petition summary was prepared by
the Petitioner and represents the views of the Petitioner. The petition
summary announces the availability of a description of the analytical
methods available to EPA for the detection and measurement of the
pesticide chemical residues or an explanation of why no such method is
needed.

Monsanto Company

Pesticide Petition (PP) xxxxxx

EPA has received a pesticide petition PPxxxxxx from Monsanto Company,
1300 I Street NW, Suite 450 East, Washington DC 2005, (a member of the
Acetochlor Registration Partnership, ARP) proposing pursuant to section
408(d) of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C.
346a(d), to amend 40 CFR Part 180.470 by revising tolerances for the
residues of acetochlor
(2-chloro-2'-methyl-6'-ethyl-N-ethoxymethylacetanilide) and its
metabolites containing either the 2-ethyl-6-methylaniline (EMA) or the
2-(1-hydroxyethyl)-6- methyl-aniline (HEMA) moiety, to be expressed as
acetochlor equivalents, in or on the following raw agricultural
commodities when present therein as a result of the application of
acetochlor to soil or growing crops: corn, field, forage at 4.5 ppm;
corn, field, stover at 3.0 ppm. 

EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports granting of the petition.
 Additional data may be needed before EPA rules on the petition.

A.	Residue Chemistry

1. Plant Metabolism. The metabolism of acetochlor has been studied in
corn, soybeans and sorghum. Acetochlor metabolizes extensively to yield
a complex array of polar metabolites. The major metabolic pathways are:
(i) uptake of soil metabolites and subsequent metabolism, (ii) uptake of
acetochlor followed by oxidative metabolism and conjugation, and (iii)
uptake of acetochlor, conjugation with glutathione and subsequent
catabolism. EPA has determined that the tolerance expression contain
parent and metabolites hydrolyzed to EMA and HEMA.  

2.  Analytical method. An adequate enforcement method for residues of
acetochlor in crops has been approved.  Acetochlor and its metabolites
are hydrolyzed to either EMA or HEMA, which are determined by HPLC-OCED
and expressed as acetochlor equivalents. 

3.  Magnitude of the residues.  Residue trials with field corn show that
the proposed tolerances will not be exceeded when acetochlor is used as
directed.  The maximum tolerable application rate made to corn in
residue studies demonstrated that acetochlor does not concentrate in the
processed commodities.

B.	Toxicological Profile

1.  Acute toxicity.  The EPA has classified technical acetochlor as
toxicity category III for acute oral, dermal and inhalation toxicity,
and eye irritation.  Two dermal irritation studies are available. 
Severe irritation resulting in a classification of Toxicity Category II
was observed in a study conducted with an obsolete source of technical
acetochlor while only minimal irritation resulting in a Toxicity
Category IV classification was noted with a higher purity test material
that is more representative of current technical material.  Acetochlor
is known to be a skin sensitizer.

2.  Genotoxicity.  Acetochlor has been evaluated in an extensive battery
of in vitro and in vivo genotoxicity studies.  Acetochlor was not
mutagenic in the Ames Salmonella assay but exhibited a weakly positive
response in a mouse lymphoma gene mutation assay.  Acetochlor also
exhibited a weakly positive response in the first of two Chinese hamster
ovary hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) gene
mutation assays but was clearly negative in a subsequent CHO/HGPRT
assay.  Acetochlor was clastogenic at cytotoxic dose levels in an in
vitro cytogenetics assay in human lymphocytes.  However, no evidence of
clastogenicity or other genotoxic effect was observed in a number of in
vivo assays, including a rat bone marrow chromosomal aberration assay,
two mouse micronucleus assays and dominant lethal mutation assays in
rats and mice.  No evidence of DNA damage was noted in an in vitro
unscheduled DNA synthesis (UDS) assay in rat hepatocytes.  A weakly
positive response was noted in an in vivo rat hepatocyte UDS assay, but
only at an excessively high dose level associated with marked
hepatotoxicity and mortality.  Furthermore, no evidence of DNA damage
was observed in rat nasal olfactory cells (the primary oncogenic target
site for acetochlor) using gel electrophoresis following 1 or 18 weeks
of dietary exposure to acetochlor.

	The clastogenic effect observed with acetochlor in vitro has been shown
to be a result of the reactive chloroacetyl moiety and is most evident
under test conditions where glutathione concentrations are low.  This
effect has not been observed under in vivo conditions where higher
glutathione levels result in the protective binding of acetochlor to
glutathione instead of the SH-groups of chromatin and other critical
cellular proteins.  Thus, the overall weight of evidence indicates that
the positive responses observed with acetochlor in some in vitro studies
are not relevant in vivo and that acetochlor would not pose a
significant risk of genotoxicity to humans under anticipated conditions
of exposure. 

3.  Subchronic toxicity.  Two 90-day rat feeding studies have been
conducted, at dietary concentrations ranging from 20 to 6000 ppm.  The
primary effects observed in these studies were decreased weight gain and
food consumption.  Minor changes were noted in several clinical
pathology parameters and in liver and kidney weights but these were not
associated with any histopathological changes.  The overall No
Observable Adverse Effect Level (NOAEL) for both studies combined was
200 ppm (approximately 18 mg/kg/day).

Two subchronic dog studies were conducted in which acetochlor was
administered via capsule at dose levels ranging from 2 to 200 mg/kg/day.
 In a 119-day study, excessive toxicity, including emaciation, decreased
body weight and a high rate of mortality, was noted at 200 mg/kg/day. 
Changes in several clinical pathology parameters, increased organ
weights and histopathological lesions of the liver, kidney and bone
marrow were observed at 200 and 75 mg/kg/day.  Slightly increased serum
ALT activity in males and slightly increased relative liver weights in
females were also noted at 25 mg/kg/day, the lowest dose tested. 
However, due to lack of corroborative clinical pathology and/or
histopathological findings, these were not considered to be indicative
of a treatment-related adverse effect.  In a 90-day study, decreased
body weight gain, clinical signs of toxicity, clinical pathology changes
and increases in relative liver weight were noted at 60 mg/kg/day, the
highest dose tested (HDT).  No effects were observed at 10 mg/kg/day,
the next lowest dose level.  Thus, based on the results of both studies
combined, 25 mg/kg/day is considered to be the overall NOAEL for
subchronic toxicity of acetochlor in dogs.

	Subchronic (21-day) dermal toxicity studies have been conducted with
both rats and rabbits.  The NOAEL for systemic effects in rabbits was
400 mg/kg/day based on mortality and decreased body weight at 1,200
mg/kg/day. No signs of systemic toxicity were noted in rats at dose
levels up to 100 mg/kg/day (HDT).   

4.  Chronic toxicity and oncogenicity.  Two one-year dog studies have
been conducted with acetochlor.  In the first study, dogs were
administered acetochlor via capsule at dose levels of 0, 4, 12, and 40
mg/kg/day.  Slightly decreased food consumption, markedly decreased body
weight gain, testicular atrophy and some indications of liver toxicity
were observed at 40 mg/kg/day.  A possible indication of liver toxicity
was also noted in one animal at 12 mg/kg/day but no effects on any
parameter were noted at 4 mg/kg/day.  In a second study, dogs were
administered acetochlor via capsule at dose levels of 0, 2, 10, and 50
mg/kg/day.  Excessive toxicity (including weight loss, emaciation,
clinical signs of toxicity, alterations in a number of clinical
pathology parameters, macroscopic lesions in a number of organs, and
histopathological changes in the brain, kidneys and testes) was evident
at 50 mg/kg/day and resulted in the premature sacrifice (post week 39)
of a number of high-dose animals for humane reasons.  Histopathological
changes in the kidneys were also observed at 10 mg/kg/day.  No
treatment-related effects were noted at 2 mg/kg/day. Thus, based on both
studies, the overall NOAEL for chronic toxicity of acetochlor in dogs is
considered to be 4 mg/kg/day.

Three chronic rat feeding studies have been conducted with acetochlor,
at dietary concentrations ranging from 18 to 5000 ppm (approximately 0.8
to 297 mg/kg/day for both sexes combined).  The overall results from the
three studies indicate that the Maximum Tolerated Dose (MTD) for
acetochlor in rats is approximately 1000 ppm (54 mg/kg/day).  The
primary indications of toxicity at this level were decreased body
weights, mild liver effects (as evidenced by increased liver weights and
clinical pathology changes) and kidney lesions.  Increased incidences of
nasal olfactory and thyroid follicular tumors were observed at dose
levels greater than or equal to 1000 ppm.  The EPA also considered a
single nasal tumor at 500 ppm in one study to be treatment related,
although a single nasal tumor was also observed in a control animal from
a subsequent acetochlor study.  An increased incidence of liver tumors
occurred only at 5000 ppm, a dose level which greatly exceeded the MTD,
and is thus not considered relevant for human risk assessment.  Based on
all 3 studies, the overall NOAEL for chronic toxicity in the rat was
considered to be 200 ppm (approximately 10 mg/kg/day).  This dose level
was also considered to be the unequivocal NOEL for oncogenicity.

A number of mechanistic studies have been conducted to determine the
mode of action for the thyroid and nasal tumors observed in the chronic
rat feeding studies with acetochlor.  These studies have demonstrated
that both tumors are produced non-genotoxic, threshold-mediated
mechanisms to which the rat is especially sensitive.  The thyroid tumors
are caused by induction of a liver enzyme, UDP-glucuronyltransferase
(UDPGT), that results in decreased levels of thyroid hormone and a
compensatory increase in thyroid stimulating hormone (TSH), which acts
upon the rat thyroid to induce hyperplasia and ultimately neoplasia. 
This is a well-known mechanism in rats that is widely believed to have
little or no relevance to humans.  The nasal tumors result from the
formation of reactive iminoquinone metabolites by the rat olfactory
tissue.  These metabolites bind to the cysteine residues in nasal
proteins and cause oxidative stress.  The resulting cytotoxicity and
regenerative cell proliferation, if sustained, eventually results in
formation of olfactory tumors.  However, large species differences at
several steps in the production of the reactive quinoneimine metabolites
indicate that this mode of action would be unlikely to occur in humans,
particularly at anticipated levels of exposure.  

 Two mouse oncogenicity studies have been conducted with acetochlor, at
dietary concentrations ranging from 10 to 5000 ppm (approximately 1.2 to
973 mg/kg/day).  Increased mortality, decreased weight gain, anemia and
signs of kidney and liver toxicity were noted at 1500 and 5000 ppm. 
Renal toxicity and anemia were also noted at 1000 ppm (approximately 126
mg/kg/day), which was considered to be the MTD.  Some minor differences
from controls were noted at 100 ppm but were not considered to be
toxicologically significant.  Thus, the ARP concluded that 100 ppm
(approximately 12 mg/kg/day) was the NOAEL for mice.  The EPA, however,
considered the slight differences at 100 ppm to be indicative of a
treatment-related adverse effect and concluded that 10 ppm
(approximately 1.1 mg/kg/day) was the NOAEL.  A treatment-related
increased incidence of liver tumors was noted in male mice at 5000 ppm. 
However, these tumors were not considered relevant for human risk
assessment since they occurred only at a dose level that greatly
exceeded the MTD.  Slightly increased incidences of lung tumors and
histiocytic sarcomas were also noted.  However, these tumors  were
considered unrelated to treatment by panels of independent expert
pathologists and of only equivocal relationship to treatment by the EPA.
  

5.  Reproductive and developmental toxicity.  Studies in rats and
rabbits indicate that acetochlor has only minimal potential to induce
reproductive or developmental toxicity, and that such effects occur only
in the presence of significant maternal toxicity.  No evidence of
increased sensitivity to offspring was noted in either species.

Two rat developmental toxicity studies have been conducted, at dose
levels ranging from 40 to 600 mg/kg/day.  In the first study, rats were
administered acetochlor by gavage at dose levels of 0, 50, 200, and 400
mg/kg/day.  Decreased maternal weight gain and clinical signs of
toxicity were observed at 400 mg/kg/day.  A slight decrease in mean
fetal weights was also noted at 400 mg/kg/day.  However, this was not
considered to be treatment-related because the difference was not
statistically significant and the mean value was well within the
historical control range.  EPA, however, disagreed and has concluded
that this was evidence of developmental toxicity.  In a second study,
rats were administered acetochlor at dose levels of 0, 40, 150, and 600
mg/kg/day.  Both maternal and fetal toxicity were observed at 600
mg/kg/day, as evidenced by animals sacrificed moribund, clinical
observations, decreased maternal weight gain, increased
post-implantation loss and decreased fetal weight.  No maternal or
developmental effects were noted at 150 mg/kg/day.  Thus, based on the
results from both studies combined, the ARP considers 200 mg/kg/day to
be the overall NOAEL for maternal toxicity and 400 mg/kg/day to be the
overall NOAEL for developmental toxicity.

Two rabbit developmental toxicity studies have been conducted, at dose
levels ranging from 15 to 300 mg/kg/day.  No developmental toxicity was
noted at any dose level.  The overall NOAEL for maternal toxicity was
100 mg/kg/day based on decreased weight gain at 190 mg/kg/day, and
decreased weight gain and mortality at 300 mg/kg/day. 

Three multigeneration rat reproduction studies have been completed, at
dietary concentrations ranging from 18 to 5000 ppm.  In the first study,
acetochlor was administered at dietary concentrations of 0, 500, 1500
and 5000 ppm.  Decreased numbers of live pups at birth and decreased pup
weights (particularly during the latter portion of lactation) were
observed at 5000 ppm.  However, this level also induced excessive
parental toxicity as indicated by substantially decreased body weights
(up to 33% in females) and kidney lesions.  Decreased parental body
weights and a slight decrease in pup weights were also noted at 1500
ppm.  Based on these results, 500 ppm (approximately 30 to 46 mg/kg/day)
was considered to be the NOAEL for both parental and offspring toxicity.
 In a second study, acetochlor was administered at dose levels of 0, 18,
175 and 1750 ppm.  No effect on reproductive performance was noted at
any dose level.  Decreased body weights, slightly reduced food
consumption and increased relative organ weights in parents, and
decreased pup weight gain during lactation, were noted at 1750 ppm. 
Thus, 175 ppm (approximately 13 to 18 mg/kg/day) was considered to be
the NOAEL for both parental and offspring toxicity.  In the most recent
study, acetochlor was administered to rats at dietary concentrations of
0, 200, 600 and 1750 ppm.  Effects observed in adult animals at 1750 and
600 ppm included decreased body weights; increased liver, kidney and/or
thyroid weights; and histopathological changes (including benign tumors)
of the nasal olfactory epithelium.  Decreased pup weights were noted at
both 600 and 1750 ppm.  Decreased numbers of uterine implantations and a
delay in vaginal opening in F1 pups were also noted at 1750 ppm. 
However, the delayed vaginal opening was attributed to the delay in
reaching critical body weight, and not a specific developmental effect,
since the body weight of the 1750 ppm pups at time of vaginal opening
was comparable to that of controls.  Based on these results, 600 ppm
(approximately 57 to 71 mg/kg/day) was considered to be the NOAEL for
reproductive effects while 200 ppm (approximately 19 to 22 mg/kg/day)
was the NOAEL for overall toxicity.  

	6.  Neurotoxicity.  No evidence of a direct or specific effect on the
nervous system was observed in acute and subchronic neurotoxicity
studies conducted in the rat.  In the acute study, acetochlor produced
general signs of toxicity, including mortality and transient changes in
motor activity, following a single oral dose of 1500 mg/kg.  A
statistically significant decrease in motor activity was also noted one
day after dosing in females at 500 mg/kg.  However, this was not
considered to be treatment related because the activity level of these
animals was higher than prior to dosing and there was no change in
habituation.  Therefore, 500 mg/kg/day was considered by the ARP to be
the NOAEL.  EPA, however, has concluded that the NOAEL for this study
was 150 mg/kg/day.

	In the subchronic study, acetochlor was administered to rats for 13
weeks at dietary concentrations of 0, 200, 600 and 1750 ppm.  Decreased
weight gain and food consumption were observed at 1750 ppm but no
evidence of neurotoxicity was observed at any dose level.  The NOAEL for
this study was 600 ppm (approximately 52 mg/kg/day).  

7.  Animal metabolism.  Numerous in vivo studies have been conducted to
evaluate the absorption, distribution, metabolism and/or excretion of
acetochlor in rats, mice, monkeys, goats and hens.  In addition, the
metabolism of acetochlor has also been evaluated in vitro using liver
and nasal tissues from rats, mice and monkeys, and nasal tissues in
humans.  These studies have shown that acetochlor is well absorbed
following oral administration and is extensively metabolized and rapidly
excreted.  No major sex differences were noted.  However, significant
species differences were observed, particularly with respect to the
formation and distribution of the metabolite(s) believed responsible for
the occurrence of nasal tumors in the rat.  

8.  Metabolite toxicology.  A number of studies have been conducted to
evaluate the potential effects that may be associated with the t-ethane
sulfonic (ESA) and t-oxanilic (OXA) acid metabolites of acetochlor. 
These are environmental degradates that are formed by soil microbes and
have been detected in ground and surface water. These metabolites are
highly polar and water soluble, and lack the reactive chlorine of parent
acetochlor.  The results from the toxicology studies indicate that
acetochlor ESA and OXA are more poorly absorbed, more rapidly excreted
and exhibit a lower degree of toxicity than parent acetochlor. 
Furthermore, they do not produce the preneoplastic changes responsible
for the rat nasal and thyroid tumors that occur with parent acetochlor,
and thus are unlikely to be carcinogenic.  Consequently, the EPA has
concluded that the ESA and OXA metabolites should not be included in the
acute, chronic or cancer risk assessments for acetochlor.

	9.  Endocrine disruption.  No evidence of a direct effect of acetochlor
on the endocrine system has been observed.  As previously noted,
acetochlor did produce a secondary effect on thyroid hormone homeostasis
at high dose levels in rats as a result of induction of the hepatic
enzyme UDPGT.  However, this is a relatively common finding in rats that
is generally thought to have little to no relevance to human risk
assessment, particularly at the low doses to which humans are likely to
be exposed.  Similarly, the observation of delayed vaginal opening at
the high-dose level in the most recent reproduction study is also
considered to be a secondary effect resulting from decreased body weight
gain in the pups.  Neither of these findings is considered to pose a
significant concern for human risk assessment.

C.	Aggregate Exposure

1.  Dietary exposure - Food.  Acetochlor is currently registered for use
on field corn, sweet corn, pop corn and sorghum.  Tolerances for
acetochlor and/or its metabolites containing the EMA or HEMA moieties
have been established for field corn, sweet corn, pop corn and sorghum,
and tolerances for indirect or inadvertent residues have been
established for the rotational crops soybean; wheat; cereal grains,
group 16 (except corn, grain sorghum, rice and wheat); sugar beet; pea
and bean, dried shelled, subgroup 6C (except soybean); potato; sunflower
seed; and animal feed, nongrass, group 18.  No tolerances have been
established for livestock commodities because there is no reasonable
expectation of finite residues based on the results of exaggerated rate
feeding studies.

Potential acute and chronic dietary exposures were estimated by EPA (in
the Human Health Risk Assessment associated with the petition for
tolerances on sorghum and sweet corn, and on new rotational crops (PC
Code: 121601, DP Barcode:  D335367, D.S. Davis and W. Drew) using the
Dietary Exposure Evaluation Model-Food Consumption Intake Database
(DEEM-FCID™, version 2.03, Exponent, Inc).  Food consumption was based
on data from the 1994-1996 USDA Continuing Surveys of Individual Intakes
(CSFII) and the 1998 Supplemental Children’s Survey.  The acute
dietary analysis was based on tolerance level residues and 100% crop
treated assumptions for all commodities.  Experimentally derived
processing factors were used for cereal grain commodities.  Default
values were used for all other processed commodities.   The chronic
dietary analysis included anticipated residues from field trial data and
100% crop treated assumptions for all commodities.  Experimentally
derived processing factors were used for cereal grain commodities. 
Default values were used for all other processed commodities.  

2.  Dietary exposure - Water.  The ARP has conducted extensive
monitoring of surface and ground water for residues of acetochlor and
has included the results of these studies in the overall dietary
exposure assessment using the DEEM-FCID software.  These monitoring data
were collected in corn-growing areas during a period of high use of
acetochlor.  Therefore, these monitoring data are appropriate for
characterizing potential ground and surface water residues from the
proposed use of acetochlor as described in this petition.  The drinking
water values used in the dietary risk assessment were based on
information provided by the ARP water monitoring program.  Exposure to
acetochlor parent was significantly higher in the surface water
monitoring sites than in the ground water monitoring sites; therefore,
the concentration used in the acute dietary assessment was from a
surface water monitoring sites that produced the highest concentration
of 0.01821 ppm.  The concentration used in the chronic dietary
assessment was from a surface water monitoring sites that produced the
highest time-weighted annualized mean (TWAM) concentration for a single
year of 0.00143 ppm.  Water residues were incorporated in the
DEEM-FCID™ analysis into the food categories “water, direct, all
sources” and “water, indirect, all sources”.

3.  Non-Dietary Exposure.  There are no residential or non-agricultural
uses of acetochlor.  Therefore, non-dietary, non-occupational exposure
to acetochlor is expected to be negligible.  In addition, 21-day dermal
toxicity studies with acetochlor indicate a very low potential for
systemic toxicity, even after repeated dermal exposures.  Thus,
potential risks from non-occupational, non-dietary exposure to
acetochlor are considered to be negligible and were not included within
the aggregate risk assessment.

D.	Cumulative Effects

	Acetochlor is a close structural analog of alachlor, another member of
the chloroacetanilide family of herbicides that also produces nasal
olfactory and thyroid follicular tumors in rats.   Mechanistic studies
indicate that these two chemicals share common modes of action for both
the nasal and thyroid tumors.  However, the EPA and FIFRA Scientific
Advisory Panel have concluded that the thyroid tumors are not an
appropriate endpoint for cumulative risk assessment for acetanilides
because increased incidences of these tumors were marginal and/or
occurred only at high dose levels, and were produced via a well-known,
non-genotoxic mechanism to which the rat is especially sensitive. 
Therefore, a cumulative risk assessment for combined residues of
alachlor and acetochlor should be based only on the potential for
formation of nasal olfactory tumors. 

E.	Safety Determination

	

	1. Endpoint Selection.    Potential acute and chronic risks from
exposure to acetochlor were determined using the toxicology endpoints
utilized by EPA in the March 2006 Tolerance Reassessment Eligibility
Decision (TRED) document.  Acute risks for all population subgroups were
assessed using an acute RfD of 0.15 mg/kg.  This was based on a NOAEL of
150 mg/kg from the acute rat neurotoxicity study and a 1000-fold
uncertainty factor.  Although no evidence of increased sensitivity to
offspring was noted in rats or rabbits following in utero and/or
postnatal exposure, the EPA applied an additional 10X database
uncertainty factor due to the lack of a developmental neurotoxicity
(DNT) study.  Chronic (non-cancer) risks were assessed using a chronic
RfD of 0.02 mg/kg/day which was derived from a NOAEL of 2.0 mg/kg/day
from the second one-year dog study and a 100-fold uncertainty factor. 
No additional database or FQPA uncertainty factor was utilized for the
chronic risk assessment since the Agency concluded that the NOAEL from a
DNT study would be greater than the NOAEL from the one-year dog study
and would thus not impact the risk assessment.  

	In January 2007, the EPA revised the cancer classification of
acetochlor to “Suggestive Evidence of Carcinogenic Potential” and
concluded that the potential carcinogenic risks should be evaluated
using a non-linear, margin-of-exposure (MOE) approach.  A point of
departure of 10 mg/kg/day, based on the unequivocal NOEL for rat nasal
tumors, was identified as the most sensitive point of departure for
evaluating cancer risk.  However, the Agency did not conduct a specific
aggregate cancer risk assessment for acetochlor since the chronic RfD,
which is based on a NOAEL of 2 mg/kg/day, would be protective against
both non-cancer and cancer effects.  Nevertheless, a specific aggregate
cancer risk assessment for acetochlor based on the 10 mg/kg/day point of
departure is presented here.  In addition, a cumulative risk assessment
was also conducted to assess the potential risks for nasal tumors from
combined exposures to alachlor and acetochlor.  For the cumulative risk
assessment, acetochlor was assumed to have 1/20th the relative potency
of alachlor based on unequivocal oncogenic NOELs of 10 and 0.5
mg/kg/day, respectively.   

 

2.  Acute Exposure and Risk.  Based on the above assumptions, the
current and proposed uses of acetochlor would result in estimated 95th
percentile acute dietary (food and water) exposures of 1.30 x 10-3
mg/kg/day for the overall US population and 3.97 x 10-3 mg/kg/day for
all infants, the most highly exposed population subgroup.   These
exposures represent approximately <1% and 2.6% of the aPAD,
respectively.  In general, exposures utilizing less than 100% of the
aPAD are not of concern.  Therefore, there is a reasonable certainty
that acute dietary exposure to acetochlor will not pose a significant
risk to human health, including infants and children.

3.  Chronic Exposure and Risk.  Based on the above assumptions, chronic
dietary (food and water) exposure of the overall US population to
acetochlor is estimated to be 1.2 x 10-4 mg/kg/day.  This represents <1%
of the cPAD.  Chronic dietary exposure to all infants (<1 year old), the
most highly exposed population subgroup, is estimated to be 2.2 x 10-4
mg/kg/day, which represents about 1.1% of the cPAD.  Both of these
values are well below 100% of the cPAD.  Therefore, there is a
reasonable certainty that dietary (food and water) exposure to
acetochlor will not pose a significant risk of chronic toxicity to the
US population, including infants and children.

4.  Cancer Risk.  (i) Acetochlor: HED has determined that it is no
longer appropriate to regulate cancer risk for acetochlor using a Q1*;
however, nasal tumors in the rat, for which a mode of action has been
identified, remain as a tumor of concern for human exposure.  The
chronic RfD, which is based on a NOAEL of 2 mg/kg/day, is considered to
be protective of the nasal tumors, for which a point of departure of 10
mg/kg/day was identified.  Therefore, a separate quantitative cancer
risk assessment is not required.  

(ii) Cumulative:  The current cumulative risk assessment for the
chloroacetanilides (Protzel et al., March 8, 2006, EPA Memorandum) notes
that alachlor is the index chemical and acetochlor is included in the
assessment with a relative potency 1/20th of alachlor.  Acceptable MOEs
in that analysis, and the lack of any increase in exposure based on this
petition result in a reasonable certainty that dietary exposures to the
combined residues of alachlor and acetochlor will not pose a significant
risk of cancer.  

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Overall Conclusion of Safety.  Based on the data summarized herein,
there is a reasonable certainty that no harm will result to the US
population, including infants and children, from the current and
proposed uses of acetochlor.  

F.	International Tolerance

There are no Codex Maximum Residue Levels established for residues of
acetochlor on agricultural commodities.

