UNITED STATES ENVIRONMENTAL PROTECTION
AGENCY![](media/image1.png){width="0.9701388888888889in"
height="0.9138888888888889in"}

WASHINGTON, D.C. 20460

MEMORANDUM

DATE: September 6, 2007

SUBJECT: PP#s 6F7040 and #7F7176. Human-Health Risk Assessment for the
Proposed Uses of Acequinocyl on Grapes, the Tree Nut Crop Group, and
Residential Sites (Ornamentals)

PC Code: 006329. DP#s 330281, 337378

Decision#s: 365166, 373834

FROM: Kelly M. Lowe, Environmental Scientist

> PV Shah, Ph.D., Toxicologist
>
> Sarah J. Levy, Chemist
>
> Registration Action Branch 1 (RAB1)
>
> Health Effects Division (HED) (7509P)

THRU: PV Shah, Ph.D., Acting Branch Chief

HED/RAB1 (7509P)

TO: Venus Eagle, Risk Manager RM01

Insecticide Rodenticide Branch

Registration Division (RD) (7505P)

The HED of the Office of Pesticide Programs (OPP) is charged with
estimating the risk to human health from exposure to pesticides. The RD
of OPP has requested that HED evaluate hazard and exposure data and
conduct dietary, occupational, residential and aggregate exposure
assessments, as needed, to estimate the risk to human health that will
result from proposed uses for acequinocyl on the tree nut crop group,
grapes, and residential sites (ornamentals). A summary of the findings
and an assessment of human-health risk resulting from the registered and
proposed uses for acequinocyl are provided in this document. The risk
assessment and occupational/residential exposure assessment was provided
by Kelly Lowe (RAB1), residue chemistry data review, and dietary
exposure assessment were provided by Sarah Levy (RAB1), the hazard
assessment was provided by PV Shah (RAB1), and the drinking water
exposure assessment was provided by Sujatha Sankula of the Environmental
Fate and Effects Division (EFED).

*Recommendation for Tolerances and Registration*

Provided a revised Section F is submitted and a reference standard for
the acequinocyl-OH metabolite is provided to the National Pesticide
Standards Repository, there are no toxicology or residue chemistry data
deficiencies that would preclude establishing permanent tolerances for
acequinocyl residues on grapes and the tree nuts crop group.

Provided that the deficiencies are adequately addressed, HED recommends
establishing the following permanent tolerances for the residues of
acequinocyl and its metabolite, acequinocyl-OH, expressed as parent,
in/on the following raw agricultural commodities (RACs):

> Nut, tree, group 14 0.02 ppm
>
> Grape 1.6 ppm

Registration should be conditional pending resolution of the following
deficiency:

[860.1340 Residue Analytical Method]{.underline}

Revised copies of Morse Methods Meth-133 (revision #3), Meth-135, and
Meth-139 (revision #2), incorporating comments from the Analytical
Chemistry Laboratory should be submitted.

**TABLE OF CONTENTS**

[1.0 EXECUTIVE SUMMARY 4](#__RefHeading___Toc176837742)

[2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION
8](#__RefHeading___Toc176837743)

[2.1 Identification of Active Ingredient
8](#__RefHeading___Toc176837744)

[2.2 Structural Formula of Acequinocyl and Acequinocyl-OH
9](#__RefHeading___Toc176837745)

[2.3 Physical and Chemical Properties of Acequinocyl
9](#__RefHeading___Toc176837746)

[3.0 HAZARD CHARACTERIZATION 9](#__RefHeading___Toc176837747)

[3.1 Hazard Profile 9](#__RefHeading___Toc176837748)

[3.2 FQPA Considerations 12](#__RefHeading___Toc176837749)

[3.3 Dose‑Response Assessment 12](#__RefHeading___Toc176837750)

[3.4 Endocrine Disruption 15](#__RefHeading___Toc176837751)

[4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION
15](#__RefHeading___Toc176837752)

[4.1 Summary of Proposed Uses 16](#__RefHeading___Toc176837753)

[4.2 Dietary Exposure/Risk Pathway 17](#__RefHeading___Toc176837754)

[4.2.1 Residue Profile 17](#__RefHeading___Toc176837755)

[4.3 Water Exposure/Risk Pathway 21](#__RefHeading___Toc176837756)

[4.4 Dietary Exposure Analyses 22](#__RefHeading___Toc176837757)

[4.4.1 Chronic Dietary Exposure Analysis
23](#__RefHeading___Toc176837758)

[4.5 Residential/Non‑Occupational Exposure Pathway
24](#__RefHeading___Toc176837759)

[4.5.1 Residential Handler 24](#__RefHeading___Toc176837760)

[4.5.2 Residential Postapplication 25](#__RefHeading___Toc176837761)

[4.5.3 Other (Spray Drift, etc.) 25](#__RefHeading___Toc176837762)

[5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION
26](#__RefHeading___Toc176837763)

[5.1 Acute Aggregate Risk 26](#__RefHeading___Toc176837764)

[5.2 Short-Term Aggregate Risk 26](#__RefHeading___Toc176837765)

[5.3 Intermediate-Term Aggregate Risk 26](#__RefHeading___Toc176837766)

[5.4 Long-Term Aggregate Risk 27](#__RefHeading___Toc176837767)

[5.5 Cancer Risk 27](#__RefHeading___Toc176837768)

[6.0 CUMULATIVE RISK 27](#__RefHeading___Toc176837769)

[7.0 OCCUPATIONAL EXPOSURE AND RISK ASSESSMENT
27](#__RefHeading___Toc176837770)

[7.1 Occupational Handler 27](#__RefHeading___Toc176837771)

[7.2 Occupational Postapplication 29](#__RefHeading___Toc176837772)

[7.3 Restricted‑Entry Intervals 31](#__RefHeading___Toc176837773)

[8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES
32](#__RefHeading___Toc176837774)

[8.1 Residue Chemistry 32](#__RefHeading___Toc176837775)

[8.2 Toxicology 32](#__RefHeading___Toc176837776)

[8.3 Occupational and Residential Exposure
32](#__RefHeading___Toc176837777)

[]{#__RefHeading___Toc176837742 .anchor}**1.0 EXECUTIVE SUMMARY**

Acequinocyl is a quinoline-type miticide that is currently registered
for use on greenhouse, shadehouse, ornamental, floral, foliage, nursery
crops, pome fruits, citrus fruits, almonds, pistachios, and
strawberries. Acequinocyl is not currently registered for application in
the residential setting. Arysta Corporation has submitted petitions
proposing the use of acequinocyl (Kanemite 15 soluble concentrate (SC),
1.25 lb/gal) on the tree nut crop group, grapes, and residential sites
(ornamentals in landscapes in and around residences, business, public
property, schools, interiorscapes and other non-production areas). In
conjunction with these uses, Arysta is proposing the following permanent
tolerances for acequinocyl and its metabolite acequinocyl-OH, expressed
as acequinocyl:

> Grape Whole fruit 1 ppm
>
> Grape Juice 0.05 ppm
>
> Raisins 0.1 ppm

Arysta is also proposing the following permanent tolerance for
acequinocyl:

> Tree nuts group 0.02 ppm

***Hazard Assessment:*** Acequinocyl has low acute toxicity via the
oral, dermal, and inhalation routes (toxicity categories III and IV). No
ocular or dermal irritation was noted. Acequinocyl is not a dermal
sensitizer. Acequinocyl is a known Vitamin K antagonist; therefore, it
is thought to produce its adverse effects by disrupting the blood
coagulation system as indicated by increased prothrombin time, increased
activated partial thromboplastin time, and internal hemorrhages.

In a subchronic oral toxicity study, a 28‑day dermal toxicity study, and
a chronic feeding/oncogenicity study (all in the rat), acequinocyl
increased prothrombin and activated partial thromboplastin times.
Although clotting factors were not measured in some studies (e.g.,
rat/rabbit developmental toxicity study, mouse subchronic/chronic
toxicity study, and 2‑generation reproduction rat study), internal
hemorrhages were observed. In the combined chronic toxicity/oncogenicity
study in rats, enlarged eyeballs were observed. Hepatotoxicity in the
mouse was evidenced by histopathology and increased liver enzymes.

In both rat and rabbit developmental toxicity studies, acequinocyl
increased the number of resorptions. Developmental effects (i.e.,
resorptions) occurred at a dose that was higher than or the same as the
dose that caused maternal toxicity. In the 2-generation reproduction
toxicity study in the rat, there was no evidence of reproductive
toxicity, nor was there evidence of increased susceptibility of rat or
rabbit fetuses following pre‑ and/or post‑natal exposures.

Acequinocyl was not mutagenic in a *Salmonella typhimurium/Escherichia
coli* assay, *in vitro* mammalian cytogenetics, an *in vitro* mammalian
cell gene mutation assay in L5178Y mouse lymphoma cells, and a
micronucleus assay with mouse erythrocytes. Based on lack of evidence of
carcinogenicity in both rats and mice carcinogenicity studies,
acequinocyl is classified as \"not likely to be carcinogenic to
humans.\"

***Dose-Response Assessment and FQPA Decision:*** The HED Hazard
Identification Assessment Review Committee (HIARC) met on October 14,
2003, to select endpoints for risk assessments and to evaluate the
potential for increased susceptibility of infants and children.

The Committee recommended the Food Quality Protection Act (FQPA) safety
factor for increased susceptibility of infants and children be reduced
to 1X because there are no residual uncertainties for pre‑ and/or
post‑natal toxicity. The endpoints that HIARC considered along with
their values (as applicable) are listed in the following table:

+---------------------+------------------------------------------------+
| **Summary of        |                                                |
| Acequinocyl Risk    |                                                |
| Assessment          |                                                |
| Endpoints**         |                                                |
+---------------------+------------------------------------------------+
| Endpoint            | Value                                          |
+---------------------+------------------------------------------------+
| Acute oral          | Not established because an endpoint of concern |
| reference dose      | attributable to a single dose was not          |
| (aRfD)              | identified                                     |
+---------------------+------------------------------------------------+
| Chronic dietary     | 0.027 mg/kg/day                                |
| population adjusted |                                                |
| dose (cPAD)         | No Observable Adverse Effect Level (NOAEL) =   |
|                     | 2.7 mg/kg/day                                  |
|                     |                                                |
|                     | based on clinical chemistry and microscopic    |
|                     | nonneoplastic lesions in the liver (as seen in |
|                     | the chronic/carcinogenicity study)             |
+---------------------+------------------------------------------------+
| Short‑term          | NOAEL=60 mg/kg/day                             |
| incidental oral and |                                                |
| inhalation          | based on clinical signs and gross necropsy     |
|                     | findings observed in a developmental study in  |
|                     | rabbits                                        |
+---------------------+------------------------------------------------+
| Intermediate‑term   | NOAEL=16 mg/kg/day                             |
| incidental oral and |                                                |
| inhalation          | based on hepatocyte vacuolation seen in a      |
|                     | 90‑day oral study in mice                      |
+---------------------+------------------------------------------------+
| Short‑ and          | NOAEL=200 mg/kg/day                            |
| intermediate‑term   |                                                |
| dermal              | based on increased clotting factor times seen  |
|                     | in a 28‑day dermal study in rats               |
+---------------------+------------------------------------------------+
| Long-term dermal    | NOAEL=2.7 mg/kg/day                            |
| and inhalation      |                                                |
|                     | based on clinical chemistry and microscopic    |
|                     | non‑neoplastic lesions in the liver seen in a  |
|                     | chronic carcinogenicity study in mice          |
+---------------------+------------------------------------------------+
| Dermal penetration  | A dermal penetration factor was not necessary  |
| factor              | for the short- and intermediate-term dermal    |
|                     | assessments because the endpoint was based on  |
|                     | a dermal study. However, because oral studies  |
|                     | were selected for the long-term dermal         |
|                     | exposure assessment, HIARC selected a factor   |
|                     | of 15% based on a dermal penetration study in  |
|                     | rats                                           |
+---------------------+------------------------------------------------+
| Inhalation          | Because oral studies were selected for the     |
| absorption factor   | inhalation exposure assessment, a 100% oral    |
|                     | equivalent inhalation absorption factor is     |
|                     | assumed                                        |
+---------------------+------------------------------------------------+

***Exposure Assessment:***

*Dietary Exposure:* The HED Metabolism Assessment Review Committee
(MARC) determined that the residues of concern in the dietary exposure
and risk assessment are acequinocyl and acequinocyl‑OH (also referred to
as R1) for both tolerance expression and risk assessment purposes. In
addition, for liver and kidney, 2‑hydroxy‑3‑hexanoic acid‑1,4
naphthalenedione (AKM-15) was also included, but for risk assessment
purposes only.

[]{.mark}

A chronic aggregate dietary (food and drinking water) exposure and risk
assessment was conducted for acequinocyl using the Dietary Exposure
Evaluation Model (DEEM-FCID™), Version 2.03, which uses food consumption
data from the U.S. Department of Agriculture's (USDA's) Continuing
Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998.
Tolerance-level residues, DEEM ver. 7.76 default processing factors,
and 100 percent crop treated (%CT) data were used in the chronic dietary
assessment. An acute dietary assessment was not conducted for
acequinocyl because an endpoint of concern attributable to a single dose
was not identified; therefore, an acute RfD was not established. A
cancer dietary assessment was not conducted because acequinocyl was
classified as not likely to be carcinogenic to humans.

For the chronic dietary assessment, the general U.S. population and all
population subgroups have risk estimates which were not of concern to
HED. The chronic dietary exposure estimate for the highest-exposed
population subgroup (children 1-2 years old) is 40% of the cPAD. The use
of anticipated residues (ARs), empirical processing factors, and %CT
would refine further HED's exposure and risk estimates.

[]{.mark}

*Drinking Water Exposure:* For the aquatic exposure modeling, both
parent and metabolite (acequinocyl-OH) concentrations were estimated in
the surface and ground water to address the toxicity concerns associated
with the acequinocyl-OH degradate. The 1-in-10-year peak concentrations
of acequinocyl ranged from 0.18 (CA citrus) to 5.57 (FL nursery plants
except roses) ppb. The 60-day concentrations of acequinocyl ranged from
0.04 to 1.26 ppb.

*Residential Exposure Estimates:* One of the proposed new uses is on
ornamentals in landscapes in and around residences, businesses, public
property, schools, interiorscapes and other non-production areas by
commercial applicators and homeowners. Therefore, there is the potential
for residential handler exposure. Homeowner handlers are expected to
complete all tasks associated with the use of a pesticide product
including mixing and loading (if needed), and application. Based upon
the proposed use pattern, the following residential handler scenarios
have been assessed: (1) mixing/loading/applying liquids with low
pressure handwand, and (2) mixing/loading/applying liquids with hose-end
sprayer.

No chemical-specific data were available with which to assess potential
exposure to pesticide handlers. The estimates of exposure to pesticide
handlers are based upon surrogate study data available from the Outdoor
Residential Exposure Task Force (ORETF) and the Pesticide Handlers
Exposure Database (PHED, August, 1998). Homeowner handler assessments
are based on the assumption that individuals are wearing shorts,
short-sleeved shirts, socks, and shoes. Residential handler exposure
scenarios are considered to be short-term only, due to the infrequent
use patterns associated with homeowner products. There are no risks of
concern for residential handlers (i.e., Margin of Exposure's (MOEs) \>
100).

With respect to residential postapplication exposures, current HED
policy (see the Exposure Science Advisory Council (ExpoSAC) minutes from
8/19/99 and 10/11/01) specifies that no significant postapplication
exposure is anticipated from landscape ornamentals, either by residents
or professional applicators; therefore, no residential postapplication
assessment was conducted.

*Occupational Exposure Estimates:* The proposed use is for application
to tree nut crops, grapes and for homeowner and commercial application
in residential areas (ornamentals). Therefore, there is the potential
for occupational handler and postapplication exposure. Based upon the
proposed use pattern, the following occupational handler scenarios have
been examined: (1) mixing/loading liquids for airblast applications
(PHED); (2) mixing/loading liquids for groundboom applications (PHED);
(3) applying sprays via airblast equipment (PHED); (4) applying sprays
via groundboom equipment (PHED); (5) mixing/loading/applying liquids
with low-pressure handwand (PHED); and (6) mixing/loading/applying
liquids with a hose-end sprayer (ORETF).

The proposed product label involved in this assessment directs
occupational applicators and other handlers to wear long sleeved shirt
and long pants, socks, shoes, and chemical resistant gloves made of
waterproof material. Based on the use pattern, HED believes most
exposure durations will be short-term (1 - 30 days). However, the
ExpoSAC maintains it is possible for commercial applicators to be
exposed to intermediate-term exposure durations (1 - 6 months);
therefore, both short- and intermediate-term exposures have been
assessed. Long-term exposures are not expected, therefore, a long-term
assessment was not conducted. Based on HED's occupational risk
assessment, there are no short- or intermediate-term risks of concern
for occupational handlers (i.e., MOEs \> 100).

Agricultural workers may experience postapplication exposures to
dislodgeable foliar pesticide residues during the course of typical
agricultural activities. There are no chemical-specific data with which
to estimate postapplication exposure of agricultural workers to
dislodgeable residues of acequinocyl. Therefore, postapplication worker
exposure was estimated using the HED ExpoSAC Policy 003.1, Rev. 7 (Aug.
2000, Regarding Agricultural Transfer Coefficients (TCs); Amended
ExpoSAC Meeting notes - 13 Sept 01). For tree nut and grape
applications, risks are not of concern (i.e., MOEs \> 100) on day 0
(Restricted Entry Interval (REI) = 12 hours) for all of the exposure
activities.

Acequinocyl is classified in Toxicity Category III for acute dermal and
acute inhalation. It is classified in Toxicity Category IV for primary
eye irritation and primary skin irritation and it is not a dermal
sensitizer. Therefore, the Worker Protection Standard (WPS) interim
restricted entry interval of 12 hours is adequate to protect
agricultural workers from postapplication exposures to acequinocyl.

*Aggregate Exposure Assessment:* An acute aggregate risk assessment was
not necessary since an appropriate endpoint for the assessment of acute
dietary risk was not identified (no acute hazard is present). An
aggregate risk assessment was performed for short-term aggregate
exposure (food + drinking water + residential exposure) because there
are residential uses. Short-term aggregate exposures and risk estimates
were calculated for adults and the aggregate MOEs are ≥ 100 and are,
therefore, not of concern to HED. Intermediate- and long-term aggregate
assessments were not performed since the use pattern is not expected to
result in residential handler or postapplication exposure of more than
30-day duration. An aggregate cancer risk assessment was not performed
because acequinocyl is not considered to be a carcinogen.

*Recommendation for Tolerances and Registration*

Provided a revised Section F is submitted and a reference standard for
the acequinocyl-OH metabolite is provided to the National Pesticide
Standards Repository, there are no toxicology or residue chemistry data
deficiencies that would preclude establishing permanent tolerances for
acequinocyl residues on grapes and the tree nuts crop group.

Provided that the deficiencies are adequately addressed, HED recommends
establishing the following permanent tolerances for the residues of
acequinocyl and its metabolite, acequinocyl-OH, expressed as parent,
in/on the following RACs:

> Nut, tree, group 14 0.02 ppm
>
> Grape 1.6 ppm

Registration should be conditional pending resolution of the following
deficiency:

[860.1340 Residue Analytical Method]{.underline}

Revised copies of Morse Methods Meth-133 (revision #3), Meth-135, and
Meth-139 (revision #2), incorporating comments from the ACL should be
submitted.

[]{.mark}

[]{.mark}

[]{#__RefHeading___Toc176837743 .anchor}**2.0 PHYSICAL/CHEMICAL
PROPERTIES CHARACTERIZATION**

Provided below are the physical/chemical properties for acequinocyl;
they include product chemistry data. Most of this information was
obtained from the acequinocyl "Pesticide Fact Sheet;" September 26, 2003
(<http://www.epa.gov/opprd001/factsheets/acequinocyl.pdf>).

[]{#__RefHeading___Toc176837744 .anchor}**2.1 Identification of Active
Ingredient**

> Registrant: Arysta Lifescience North America Corporation
>
> Trade Names: Kanemite (EPA Reg. #: 66330-38)
>
> CAS Chemical Name: 2‑(acetyloxy)‑3‑dodecyl‑1,4‑naphthalenedione
>
> CAS Registry No.: 57960-19-7
>
> Common Name: Acequinocyl
>
> PC Code: 006329
>
> Pesticide Type: Miticide
>
> Chemical Family: Quinoline
>
> Target Pests: *Tetranychus, Panonychus* and *Eutetranychus spp* of
> mites
>
> Formulation: Product--Kanemite^TM^ 15 SC; 1.25 lb ai/gal
>
> Types of Formulations: Technical (96.8% ai); End-Use Product (15.8%)
>
> Empirical Formula: C~24~H~32~O~4~
>
> Molecular Weight: 384.5

[]{#__RefHeading___Toc176837745 .anchor}**2.2 Structural Formula of
Acequinocyl and Acequinocyl-OH**

  ---------------------------------------------------- -----------------------------------------
  ![](media/image2.wmf){width="1.8416666666666666in"   ![](media/image3.wmf){width="2.03125in"
  height="1.0833333333333333in"}                       height="1.28125in"}

  Acequinocyl                                          Acequinocyl-OH
  ---------------------------------------------------- -----------------------------------------

[]{#__RefHeading___Toc176837746 .anchor}**2.3 Physical and Chemical
Properties of Acequinocyl**

These physical and chemical properties are for the end-use product
unless otherwise noted.

  ------------------------------------ ----------------------------------
  Appearance:                          Pale yellow

  Physical State:                      Liquid Suspension

  Vapor Pressure:                      1.69 x 10^‑9^ pascals at 25^0^C
                                       (technical)

  Water Solubility:                    6.69 μg/L at 20^0^C (technical)

  Octanol/Water Partition Coefficient  ≥6.2 (technical)
  (Log Kow):                           

  Melting Point:                       59.6°C (technical)

  Density:                             1.13 g/cm^3^
  ------------------------------------ ----------------------------------

Acequinocyl is a liquid at room temperature, thus, any losses due to
volatilization/sublimation are expected to be minimal.

[]{#__RefHeading___Toc176837747 .anchor}**3.0 HAZARD CHARACTERIZATION**

The following documents support the hazard characterization of
acequinocyl:

-   Acequinocyl. 2^nd^ Report of the Hazard Identification Assessment
    Review Committee (HIARC). Meeting Date: October 14, 2003. TXR
    No. 0052234. P. Terse; 13-NOV-2004.

-   Acequinocyl. Report of the Hazard Identification Assessment Review
    Committee. Meeting Date: July 15, 2003. TXR No. 0052075. R. Fricke;
    14-AUG-2003.

The existing toxicological database for acequinocyl is complete and
supports the establishment of permanent tolerances for residues of
acequinocyl in/on the RACs resulting from the proposed uses.

[]{#__RefHeading___Toc176837748 .anchor}**3.1 Hazard Profile**

Acequinocyl binds to the Qo center at Complex III in the mitochondria of
mite cells and, thereby, exerts its miticidal action by inhibiting
electron transfer. Acequinocyl possesses moderate activity against plant
mitochondrial complex III, in contrast to much higher activity against
an insect mitochondrial complex III. There is a lack of information
regarding whether or not acequinocyl inhibits the mammalian
mitochondrial electron transfer system.

Acequinocyl has low acute toxicity via the oral, dermal, and inhalation
routes. No ocular or dermal irritation was noted. Acequinocyl is not a
dermal sensitizer. Acequinocyl is a known Vitamin K antagonist and,
therefore, is thought to disrupt blood coagulation.

In the rat subchronic oral toxicity study, the primary effects included
pallor, swelling of the eyes and limbs, decreased motor activity,
piloerection, reddish urine, increased activated partial thromboplastin
time, increased prothrombin time, and internal hemorrhages. In the mouse
subchronic oral toxicity study, effects included pallor, sunken eyes,
labored/irregular breathing, hunched posture, piloerection, weight loss,
and hepatic vacuolation (blood coagulation profile was not evaluated in
this study). In the dog subchronic oral toxicity study, toxic effects
included reduced body weight gains, reduced food efficiency, decreased
total protein, increased triglyceride levels, elevated platelet counts,
elevated reticulocytes, increased prothrombin time, and decreased liver
and heart weights (absolute). In the rat 28‑day dermal toxicity study,
the primary effects were red‑stained treated skin area, increased
prothrombin time, increased activated partial prothrombin time,
increased fibrinogen levels, and increased heart weights (absolute and
relative to the body weight).

In the rat chronic oral studies, toxic effects included enlarged
eyeballs, increased prothrombin time, and increased activated partial
thromboplastin time. In the mouse chronic oral toxicity study,
hepatotoxicity was indicated by increased liver enzyme levels (alanine
and aspartate aminotransferase), increased liver weight, hepatocyte
vacuolation, and hepatocyte fatty deposition (blood clotting was not
evaluated in this study). In the dog chronic toxicity study, effects
included elevated prothrombin time, increased reticulocyte/platelet
count, reduced body weight gain, and reduced food efficiency.

In the rat, maternal toxicity resulted in pale eyes, piloerection, red
vaginal discharge, and internal hemorrhage at the LOAEL, whereas
developmental toxicity was indicated by increased resorptions and fetal
variations. In the rabbit, maternal toxicity produced body weight loss,
reduced fecal output, reduced food consumption, pale lungs/liver,
internal hemorrhaging, hairloss, and blood-stained urine. The
developmental toxicity study in rabbits identified an increased number
of complete resorptions.

In the rat two-generation reproductive toxicity study, both the maternal
and reproductive toxicity LOAELs were above the high dose tested
(111.2/133.5 mg/kg/day). The offspring systemic LOAEL is 58.9/69.2
mg/kg/day, based on hemorrhagic effects occurring mainly after weaning.

HIARC concluded that exposure to acequinocyl does not pose a
neurotoxicity concern. First, acequinocyl is a known Vitamin K
antagonist; neurotoxic compounds of similar structure were not
identified. Second, although two studies showed effects that could be
indicative of neurotoxicity, HIARC considered these as secondary because
they were observed at very high doses. In the 2‑generation reproduction
study, significant reduction in startle response in F2 pups was observed
in high dose groups (58.9/69.2 mg/kg/day and 111.2/133.5 mg/kg/day).
However, other functional development tests (such as a pupillary reflex
test at 21 days post partum, an open field exploration test at 35‑48
days post partum and a water maze test with a learning phase and a
memory phase at 35‑48 days post partum) that were performed on pups did
not show significant differences as compared to control values even at
the highest dosage level. In the rat subchronic oral toxicity study,
neurotoxicity signs, such as decreased motor activity, piloerection and
hunched posture, were noted at the high dose (252.7/286.0 mg/kg/day).

There was no concern for mutagenic activity as indicated by several
mutagenicity studies, including a bacterial (*Salmonella, E. coli*)
reverse mutation assay, an *in vitro* mammalian chromosomal aberration
assay, an *in vivo* mouse bone marrow micronucleus assay, and a
bacterial DNA damage or repair assay.

There was no evidence of carcinogenic potential in either the rat or
mouse carcinogenicity study, indicating that acequinocyl is \"not
likely\" to be carcinogenic to humans.

Acequinocyl exhibits marginal absorption and relatively rapid and
complete excretion, primarily via the bile and feces in rat. Absorption
appeared to be approaching saturation at high doses. Peak plasma
concentration occurred at 2‑6 hours and the elimination half-life is
about 4.4‑6.5 hours. Acequinocyl undergoes nearly complete metabolism to
hydrolysis products and a glucuronide conjugate.

In feces, three components were identified: (1) parent compound (0.5‑8%
of dose); (2) 2‑hydroxy‑3‑dodecyl‑1, 4‑naphthalenedione (acequinocyl-OH,
12‑36% of dose); and (3) 2‑(1,2‑dioxotetradecyl)‑benzoic acid (AKM-18,
19‑40% of dose).

The major urinary metabolites included: (1) 2‑hydroxy‑3‑hexanoic acid‑1;
4 naphthalenedione (AKM-15); and (2) 2‑hydroxy‑3‑butanoic
acid‑1,4‑naphthalenedions (AKM-14). Neither the parent compound nor the
hydroxy metabolite (acequinocyl-OH) was observed in the urine.

In bile, major metabolites were: (1) parent compound (\<0.1‑0.8% of
dose); (2) acequinocyl-OH (0.2‑4.1% of dose); (3) conjugated
acequinocyl-OH (4‑8%); (4) AKM‑18 (0.5‑2.8% of dose); (5) AKM‑15
(0.5‑4.2% of dose); and (6) AKM‑14 (0.3‑3.1% of dose).

The major components detected in plasma were: (1) parent compound; (2)
acequinocyl-OH; (3) conjugated acequinocyl-OH; (4) AKM‑14; and (5)
AKM‑15.

Excretion via expired air was biologically insignificant. There was no
evidence for selective tissue accumulation or sequestration. The
structures for these metabolites may be found in the Appendix, Table
A-1. Table 3.1 provides the acute toxicity of acequinocyl.

+--------+----------------+----------+-----------------+--------------+
| *      |                |          |                 |              |
| *Table |                |          |                 |              |
| 3.1.   |                |          |                 |              |
| Acute  |                |          |                 |              |
| To     |                |          |                 |              |
| xicity |                |          |                 |              |
| of     |                |          |                 |              |
| Ac     |                |          |                 |              |
| equino |                |          |                 |              |
| cyl.** |                |          |                 |              |
+========+================+==========+=================+==============+
| Gui    | Study Type     | MRID     | Results         | Toxicity     |
| deline |                | #(s)     |                 | Category     |
|        |                |          |                 |              |
| No.    |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute Oral     | 45435011 | LD~50~ \> 5000  | IV           |
| 0.1100 | (rat)          |          | mg/kg           |              |
|        |                |          |                 |              |
| (81-1) |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute Dermal   | 45435012 | LD~50~ \> 2000  | III          |
| 0.1200 |                |          | mg/kg           |              |
|        |                |          |                 |              |
| (81-2) |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute          | 45435013 | LC~50~ \> 0.84  | III          |
| 0.1300 | Inhalation     |          | mg/L            |              |
|        |                |          |                 |              |
| (81-3) |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Primary Eye    | 45435014 | Not an eye      | IV           |
| 0.2400 | Irritation     |          | irritant        |              |
|        |                |          |                 |              |
| (81-4) |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Primary Skin   | 45435015 | Not a dermal    | IV           |
| 0.2500 | Irritation     |          | irritant        |              |
|        |                |          |                 |              |
| (81-5  |                |          |                 |              |
| )      |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 8      | Dermal         | 45435016 | Not a dermal    | N/A          |
| 7.2600 | Sensitization  |          | sensitizer      |              |
|        |                |          |                 |              |
| (81-6) |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+

[]{#__RefHeading___Toc176837749 .anchor}**3.2 FQPA Considerations**

On October 14, 2003, HIARC evaluated the potential for increased
susceptibility of infants and children from exposure to acequinocyl.
Based on the hazard data, HIARC recommended that the FQPA SF be reduced
to 1x. The acequinocyl risk assessment team also evaluated the quality
of the exposure data and recommended for the purposes of these
petitions, and concurred with the previous HIARC conclusion, that the
FQPA SF be reduced to 1x. The recommendation is based on the following:

-   There is no evidence of increased susceptibility of rat or rabbit
    fetuses to *in utero* exposure to acequinocyl. And, there is no
    qualitative and/or quantitative evidence of increased susceptibility
    to acequinocyl following pre/post‑natal exposure in a two‑generation
    reproduction study in rats.

-   There is no concern for developmental neurotoxicity resulting from
    exposure to acequinocyl; a development neurotoxicity study is not
    required.

-   For the purposes of FQPA assessment, the database is complete.

-   The dietary exposure assessment was conducted using Tier 1
    assumptions. This yields conservative exposure estimates which
    overstate actual exposure.

-   The dietary drinking water assessment utilizes model-generated water
    concentration values and associated modeling parameters that are
    designed to provide conservative, health protective, high‑end
    estimates of water concentrations that will not likely be exceeded.

    []{#__RefHeading___Toc176837750 .anchor}**3.3 Dose‑Response
    Assessment**

Table 3.2 provides the HIARC's decisions concerning the toxicity
endpoints needed in this risk assessment.

+----------+---------------+----------------+-------------------------+
| **Table  |               |                |                         |
| 3.2.     |               |                |                         |
| E        |               |                |                         |
| ndpoints |               |                |                         |
| Selected |               |                |                         |
| by HIARC |               |                |                         |
| for      |               |                |                         |
| Ace      |               |                |                         |
| quinocyl |               |                |                         |
| Risk     |               |                |                         |
| Asses    |               |                |                         |
| sment.** |               |                |                         |
+==========+===============+================+=========================+
| Exposure | Dose Used in  | FQPA SF and    | Study and Toxicological |
|          | Risk          | Level of       | Effects                 |
| Scenario | Assessment    | Concern (LOC)  |                         |
|          | (mg/kg/day);  | for Risk       |                         |
|          | UF            | Assessment     |                         |
+----------+---------------+----------------+-------------------------+
| Acute    | Not           | None           | An endpoint of concern  |
| Dietary  | applicable    |                | attributable to a       |
|          |               |                | single dose was not     |
|          |               |                | identified. An aRfD was |
|          |               |                | not established.        |
+----------+---------------+----------------+-------------------------+
| Chronic  | NOAEL=2.7     | FQPA SF=1x     | 18-month                |
| Dietary  |               |                | carcinogenicity study   |
|          | UF=100x       | ^1^cPAD=0.027  | in mice;                |
| (all     |               |                |                         |
| popu     | cRfD=0.027    |                | LOAEL=7.0 mg/kg/day     |
| lations) |               |                | based on clinical       |
|          |               |                | chemistry and           |
|          |               |                | microscopic             |
|          |               |                | nonneoplastic lesions   |
|          |               |                | (brown pigmented cells  |
|          |               |                | and perivascular        |
|          |               |                | inflammatory cells in   |
|          |               |                | liver).                 |
+----------+---------------+----------------+-------------------------+
| Sh       | NOAEL=60      | Residential    | Developmental Study in  |
| ort-Term |               | LOC            | Rabbits;                |
|          |               |                |                         |
| In       |               | (MOE)=100      | maternal LOAEL=120      |
| cidental |               |                | mg/kg/day based on      |
| Oral     |               | Occupational   | clinical signs          |
|          |               | LOC (MOE)=100  | (hematuria, reduced     |
| (1 - 30  |               |                | fecal output, body      |
| days)    |               |                | weight loss, and        |
|          |               |                | reduced food            |
|          |               |                | consumption) and gross  |
|          |               |                | necropsy findings (pale |
|          |               |                | lungs and liver,        |
|          |               |                | hemorrhaging uterus,    |
|          |               |                | fluid in the cecum, fur |
|          |               |                | in the stomach, blood   |
|          |               |                | stained vaginal         |
|          |               |                | opening, blood-stained  |
|          |               |                | urinary bladder         |
|          |               |                | contents/urine).        |
+----------+---------------+----------------+-------------------------+
| I        | NOAEL=16      | Residential    | 90-day oral study in    |
| ntermedi |               | LOC            | mice;                   |
| ate-Term |               |                |                         |
|          |               | (MOE)=100      | LOAEL=81 mg/kg/day      |
| In       |               |                | based on hepatocyte     |
| cidental |               | Occupational   | vacuolation.            |
| Oral     |               | LOC (MOE)=100  |                         |
|          |               |                |                         |
| (1 - 6   |               |                |                         |
| months)  |               |                |                         |
+----------+---------------+----------------+-------------------------+
| Sh       | Dermal        | Residential    | 28-day dermal study in  |
| ort-Term | NOAEL=200     | LOC (MOE)=100  | rats;                   |
| Dermal   |               |                |                         |
|          |               | Occupational   | LOAEL=1000 mg/kg/day    |
| (1 - 30  |               | LOC (MOE)=100  | based on increased      |
| days)    |               |                | clotting factor times.  |
+----------+---------------+----------------+-------------------------+
| I        | Dermal        | Residential    | 28-day dermal study in  |
| ntermedi | NOAEL=200     | LOC (MOE)=100  | rats;                   |
| ate-Term |               |                |                         |
| Dermal   |               | Occupational   | LOAEL=1000 mg/kg/day    |
|          |               | LOC (MOE)=100  | based on increased      |
| (1 - 6   |               |                | clotting factor times.  |
| months)  |               |                |                         |
+----------+---------------+----------------+-------------------------+
| L        | Oral          | Residential    | 18-month                |
| ong-Term | NOAEL=2.7     | LOC (MOE)=100  | carcinogenicity study   |
| Dermal   |               |                | in mice;                |
|          | (dermal       | Occupational   |                         |
| (\>6     | absorption    | LOC (MOE)=100  | LOAEL=7.0 mg/kg/day     |
| months)  | rate=15%)     |                | based on clinical       |
|          |               |                | chemistry and           |
|          |               |                | microscopic             |
|          |               |                | nonneoplastic lesions   |
|          |               |                | (brown pigmented cells  |
|          |               |                | and perivascular        |
|          |               |                | inflammatory cells in   |
|          |               |                | liver).                 |
+----------+---------------+----------------+-------------------------+
| Sh       | Oral NOAEL=60 | Residential    | Developmental toxicity  |
| ort-Term |               | LOC (MOE)=100  | study in rabbits;       |
| In       | (inhalation   |                |                         |
| halation | absorption    | Occupational   | LOAEL=120 mg/kg/day     |
|          | rate=100%)    | LOC (MOE)=100  | based on clinical signs |
| (1 - 30  |               |                | (hematuria, reduced     |
| days)    |               |                | fecal output, body      |
|          |               |                | weight loss, and        |
|          |               |                | reduced food            |
|          |               |                | consumption) and gross  |
|          |               |                | necropsy findings (pale |
|          |               |                | lungs and liver,        |
|          |               |                | hemorrhaging uterus,    |
|          |               |                | fluid in the cecum, fur |
|          |               |                | in the stomach, blood   |
|          |               |                | stained vaginal         |
|          |               |                | opening, blood-stained  |
|          |               |                | urinary bladder         |
|          |               |                | contents/urine).        |
+----------+---------------+----------------+-------------------------+
| I        | Oral NOAEL=16 | Residential    | Subchronic toxicity in  |
| ntermedi |               | LOC (MOE)=100  | mice;                   |
| ate-Term | (inhalation   |                |                         |
| In       | absorption    | Occupational   | LOAEL=81 mg/kg/day      |
| halation | rate=100%)    | LOC (MOE)=100  | based on hepatocyte     |
| (1 - 6   |               |                | vacuolation.            |
| months)  |               |                |                         |
+----------+---------------+----------------+-------------------------+
| L        | Oral          | Residential    | 18-month                |
| ong-Term | NOAEL=2.7     | LOC (MOE)=100  | carcinogenicity study   |
| In       |               |                | in mice                 |
| halation | (inhalation   | Occupational   |                         |
|          | absorption    | LOC (MOE)=100  | LOAEL=7.0 mg/kg/day     |
| (\>6     | rate=100%)    |                | based on clinical       |
| months)  |               |                | chemistry and           |
|          |               |                | microscopic             |
|          |               |                | nonneoplastic lesions   |
|          |               |                | (brown pigmented cells  |
|          |               |                | and perivascular        |
|          |               |                | inflammatory cells in   |
|          |               |                | liver).                 |
+----------+---------------+----------------+-------------------------+
| Cancer   | Not likely to |                |                         |
|          | be            |                |                         |
|          | carcinogenic  |                |                         |
|          | to humans.    |                |                         |
+----------+---------------+----------------+-------------------------+

> NOTE: 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; MOE=margin of exposure; LOC=level of
> concern; NA=Not Applicable.

^1^ cPAD=cRfD / FQPA SF.

*Acute Dietary Endpoint*: The aRfD for the general population, including
infants and children, was not established because an endpoint of concern
attributable to a single dose was not identified. Therefore, this
assessment is not necessary.

*Chronic Dietary Endpoint*: The cRfD of 0.027 mg/kg/day was determined
on the basis of the chronic carcinogenicity study in mice. An UF of 100
(10‑fold for interspecies extrapolation and 10‑fold for intraspecies
variability) was applied to the NOAEL of 2.7 mg/kg/day to derive the
cRfD. The LOAEL of 7.0 mg/kg/day is based on clinical chemistry and
microscopic non‑neoplastic lesions (brown pigmented cells and
perivascular inflammatory cells) in the liver. The FQPA safety factor of
1x is applicable for chronic dietary risk assessment. Therefore, the
cPAD is equal to the RfD and is 0.027 mg/kg/day.

*Short‑ and Intermediate‑Term Incidental Oral and Inhalation Endpoints:*
Short-term incidental oral and inhalation endpoints are based on the
maternal NOAEL of 60 mg/kg/day in the developmental study in rabbits.
The NOAEL of 60 mg/kg/day was based on clinical signs (hematuria,
reduced fecal output, body weight loss, and reduced food consumption)
and gross necropsy findings (pale lungs and liver, hemorrhaging uterus,
fluid in the cecum, fur in the stomach, blood stained vaginal opening,
blood‑stained urinary bladder contents/urine) at the LOAEL of 120
mg/kg/day. Intermediate-term incidental oral and inhalation endpoints
are based on hepatocyte vacuolation seen in the 90-day oral study in
mice (NOAEL=16 mg/kg/day). Because HIARC selected oral NOAELs for the
inhalation exposure assessment, a 100% oral equivalent inhalation
absorption factor is assumed. The level of concern for occupational
exposure is 100.

*Dermal Absorption:* No dermal absorption factor was necessary for the
short- and intermediate-term dermal assessments since the endpoint was
based on a dermal study. However, HIARC selected a dermal absorption
rate of 15% for the long-term dermal assessment. The dermal penetration
study yielded absorptions of 12.23%, 19.75% and 14.77% at 168 hours
(doses were 0.1, 0.01, and 0.001 mg/cm^2^, respectively). Because a
higher dermal absorption value (20%) was observed at the mid‑dose than
observed at the lowest dose (15%), HIARC selected a 15% dermal
absorption value that was based on the average absorption values at the
three doses at 168 hours (7 days).

*Short‑ and Intermediate‑Term Dermal Endpoints:* Short- and
intermediate-term dermal endpoints are based on increased clotting
factor times seen in a rat 28-day dermal toxicity study (NOAEL=200
mg/kg/day). The level of concern for occupational exposure is 100.

*Long-Term Dermal and Inhalation Endpoint:* The long‑term dermal and
inhalation endpoints are based on the NOAEL of 2.7 mg/kg/day in a
chronic carcinogenicity study in mice. The LOAEL of 7.0 mg/kg/day was
based on clinical chemistry and microscopic nonneoplastic lesions (brown
pigmented cells and perivascular inflammatory cells) in the liver.
Because oral studies were selected for dermal exposure assessment, a
dermal penetration factor is required. HIARC selected a dermal
penetration factor of 15% based on a dermal penetration study in rats.
Because HIARC selected an oral NOAEL for the long‑term inhalation
exposure assessment, a 100% oral equivalent inhalation absorption factor
is assumed. The level of concern for occupational exposure is 100.

[]{#__RefHeading___Toc176837751 .anchor}**3.4 Endocrine Disruption**

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate."
Following recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system. EPA also
adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being
considered under the Agency's EDSP have been developed, acequinocyl may
be subjected to further screening and/or testing to better characterize
effects related to endocrine disruption.

[]{#__RefHeading___Toc176837752 .anchor}**4.0 EXPOSURE ASSESSMENT AND
CHARACTERIZATION**

Please refer to the following documents for detailed considerations of
the material summarized in this section:

-   Acequinocyl. PP#s: 6F7040 and 7F7176. Petitions for Uses on Tree
    Nuts and Grapes. Summary of Analytical Chemistry and Residue Data.
    DP# 330439. S. Levy, 9/5/07.

-   Acequinocyl: Chronic Aggregate Dietary (Food and Drinking Water)
    Exposure and Risk Assessment for the Proposed Section 3 Registration
    Action on Grapes and Tree Nuts. DP# 342805. S. Levy, 9/5/07.

-   Ecological Risk Assessment for Use of Acequinocyl (PC 006329) on
    Grapes, Pome Fruits, Citrus, Nuts, and Outdoor Non-Food Uses. DP
    337381, 330467, 330471. August, 2007.

Acequinocyl is a quinoline-type miticide proposed for control of the
two-spotted spider mite (*Tetranychus urticae*), European red mite
(*Panonychus ulmi*), citrus red mite (*Panonychus citric*), and Spruce
spider mite (*Oligonychus ununquis*) on ornamentals and ornamental
nursery plants; the two-spotted spider mite (*Tetranychus urticae*),
Pacific mite (*Tetranychus pacificus*) and the European red mite
(*Panonychus ulmi*) on tree nuts, pistachios, and pome fruit; and the
citrus red mite (*Panonychus citric*), Texas citrus mite (*Eutetranychus
banski*) and strawberry spider mite (*Tetranychus turkestani*) on
strawberries.

Arysta Corporation has submitted petitions proposing the use of
acequinocyl (Kanemite 15 SC, 1.25 lb/gal) on the tree nut crop group,
grapes, and residential sites (ornamentals). In conjunction with these
uses, Arysta has proposed the following permanent tolerances for
acequinocyl and its metabolite acequinocyl-OH, expressed as acequinocyl:

> Grape Whole fruit 1 ppm
>
> Grape Juice 0.05 ppm
>
> Raisins 0.1 ppm

Arysta is also proposing the following permanent tolerance for
acequinocyl:

> Tree nuts group 0.02 ppm

[]{#__RefHeading___Toc176837753 .anchor}**4.1 Summary of Proposed Uses**

Acequinocyl is already registered for use on greenhouse, shadehouse,
ornamental, floral, foliage, nursery crops, pome fruits, citrus fruits,
almonds, pistachios, and strawberries. Acequinocyl is proposed for
application in residential settings. The product, Kanemite™ 15 SC, is
only formulated as a liquid. Provided in Table 4.1 is a summary of
acequinocyl's use directions.

The proposed label directions are adequate and are supported by the
available grape, almond and pecan field trial data.

[]{.mark}

+--------+--------+-----+------+-------+-----+-----------------------+
| *      |        |     |      |       |     |                       |
| *Table |        |     |      |       |     |                       |
| 4.1.   |        |     |      |       |     |                       |
| S      |        |     |      |       |     |                       |
| ummary |        |     |      |       |     |                       |
| of     |        |     |      |       |     |                       |
| Dire   |        |     |      |       |     |                       |
| ctions |        |     |      |       |     |                       |
| for    |        |     |      |       |     |                       |
| Use of |        |     |      |       |     |                       |
| A      |        |     |      |       |     |                       |
| cequin |        |     |      |       |     |                       |
| ocyl** |        |     |      |       |     |                       |
+========+========+=====+======+=======+=====+=======================+
| Trade  | Appli  | A   | Max. | Max.  | PHI | Use Directions and    |
|        | cation | ppl | No.  | Sea   |     | Limitations           |
| Name   | T      | ic. | App  | sonal | (da |                       |
|        | iming, | R   | lic. | Ap    | ys) |                       |
|        |        | ate | per  | plic. |     |                       |
|        | Type,  |     | Se   | Rate  |     |                       |
|        | and    |     | ason |       |     |                       |
|        | Equ    |     |      | (lb   |     |                       |
|        | ipment |     |      | ai/A) |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| **O    |        |     |      |       |     |                       |
| rnamen |        |     |      |       |     |                       |
| tals** |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| Kanemi | Ha     | 0   | Not  | 0.6   | N/A | Do not apply by       |
| te^TM^ | ndheld | .00 | s    |       |     | irrigation system or  |
| 15     | equ    | 125 | peci |       |     | by air. No more than  |
| SC^1^  | ipment | lb  | fied |       |     | 0.25 lb ai/year.      |
|        |        | ai/ |      |       |     | Retreatment interval: |
| 1.25   |        | gal |      |       |     | 14 days.              |
| lb/gal |        |     |      |       |     |                       |
| FlC    |        |     |      |       |     |                       |
|        |        |     |      |       |     |                       |
| \[6633 |        |     |      |       |     |                       |
| 0-38\] |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| **Tree |        |     |      |       |     |                       |
| Nut    |        |     |      |       |     |                       |
| Crop   |        |     |      |       |     |                       |
| G      |        |     |      |       |     |                       |
| roup** |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| Kanemi | Bro    | 0   | 2    | 0.60  | 7   | Do not apply by       |
| te^TM^ | adcast | .30 |      |       |     | irrigation system or  |
| 15 SC  | foliar |     |      |       |     | by air. Retreatment   |
|        | applic |     |      |       |     | interval: 21 days and |
| 1.25   | ation, |     |      |       |     | a minimum application |
| lb/gal |        |     |      |       |     | volume of 100         |
| FlC    | ground |     |      |       |     | gallons/A. REI: 12    |
|        | equ    |     |      |       |     | hours.                |
| \[6633 | ipment |     |      |       |     |                       |
| 0-38\] |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| **Gr   |        |     |      |       |     |                       |
| apes** |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+
| Kanemi | Bro    | 0   | 2    | 0.60  | 7   | Do not apply by       |
| te^TM^ | adcast | .30 |      |       |     | irrigation system or  |
| 15 SC  | foliar |     |      |       |     | by air. Retreatment   |
|        | applic |     |      |       |     | interval: 21 days and |
| 1.25   | ation, |     |      |       |     | a minimum application |
| lb/gal |        |     |      |       |     | volume of 100         |
| FlC    | ground |     |      |       |     | gallons/A. REI: 12    |
|        | equ    |     |      |       |     | hours.                |
| \[6633 | ipment |     |      |       |     |                       |
| 0-38\] |        |     |      |       |     |                       |
+--------+--------+-----+------+-------+-----+-----------------------+

> ^1^ According to master label, alternate brand name is Shuttle™ 15 SC
> Miticide; RD should ensure that the Shuttle™ 15 C Miticide label is
> identical to the Kanemite^TM^ 15 SC label.

[]{#__RefHeading___Toc176837754 .anchor}**4.2 Dietary Exposure/Risk
Pathway**

[]{#__RefHeading___Toc176837755 .anchor}**4.2.1 Residue Profile**

[]{.mark}

***Nature of the Residue--Plants:*** The qualitative nature of
acequinocyl residues in fruit and nut crops is understood based on the
available apple, orange, and eggplant metabolism studies (DP# D284757,
S. Levy, 3/10/04). The data indicate that the metabolism of acequinocyl
in these crops involves the loss of the acetyloxy moiety to form
acequinocyl-OH, opening of the quinone ring to form AKM-18, and
subsequent degradation of the quinone ring to yield polar metabolites
that degrade to phthalic acid. Number range CHAPTERBased on the
structural similarity of acequinocyl-OH to the parent and the presence
of acequinocyl-OH at quantifiable levels in crops, the MARC concluded
that parent and acequinocyl-OH are the residues of concern for risk
assessment and tolerance expression in plant commodities (Memo, S. Levy,
*et al*., 07-JAN-2004; TXR #: 0052294). The acequinocyl risk assessment
team deems the conclusions made by the MARC appropriate for the new uses
as well.

[]{.mark}

***Nature of the Residue--Livestock:*** The qualitative nature of
acequinocyl residues in ruminants is understood based on an adequate
goat metabolism study (Memo, S. Levy, 10-MAR-2004; DP#: 284757). The
metabolism of acequinocyl in goats appears to involve the loss of the
acetyloxyl moiety to form acequinocyl-OH and partial cleavage of the
dodecyl side chain to form AKM-15. Opening and degradation of the
quinone ring was also evidenced by the presence of AKM-18 and phthalic
acid. The MARC concluded that for tolerance expression, the residues of
concern in livestock commodities include parent and acequinocyl-OH. For
risk assessment purposes, the residues of concern in livestock
commodities are parent and acequinocyl-OH (for liver and kidney,
metabolite AKM-15 is to be included as well (Memo, S. Levy, *et al*.,
07-JAN-2004; TXR #: 0052294)).

[]{.mark}

***Magnitude of the Residue--Plants:*** The available pecan, almond, and
grape field trial data are adequate and support the proposed uses. In
five almond field trials (2001) and five pecan field trials (2003),
acequinocyl (1.25 lb/gal SC) was applied to trees during the later
stages of nut development as two broadcast foliar applications at rates
totaling 0.59-0.61 lb ai/A/season (1x rate). At 7 days after the last
application (DAT), combined residues of acequinocyl and acequinocyl-OH
were \<0.02 ppm (\<LOQ) in/on all samples of almond and pecan nutmeats
and 0.43-1.28 ppm in/on almond hulls. Average combined residues were
\<0.02 ppm in/on nutmeats and 0.69 ppm in/on almond hulls. Residue
decline trials on both almonds and pecans indicated that residues
declined at longer post-treatment intervals. The data support the
proposed 0.02-ppm tolerance for tree nuts and the existing 2.0-ppm
tolerance on almond hulls.

[]{.mark}

In the 12 grape field trials conducted in 2005, acequinocyl (SC) was
applied to vines as two broadcast foliar applications during the later
stages of berry development at rates totaling 0.60-0.61 lb ai/A/season
(1x rate). Combined residues of acequinocyl and acequinocyl-OH
(corrected) were \<0.02-0.63 ppm in/on 24 grape samples harvested at 7
DAT, and averaged 0.21 ppm. Data from the grape residue decline trial
indicated that residues of both analytes declined at longer
post-treatment intervals. Using the maximum residue limit (MRL)
calculator, a tolerance level of 1.6 ppm in/on grapes is appropriate.

[]{.mark}

***Magnitude of the Residues--Livestock:*** An adequate cattle feeding
study is available and it is supported by the submitted storage
stability data. In this study, tNumber range CHAPTERhree groups of
lactating dairy cows (4/group) were dosed orally with acequinocyl in
capsules at levels equivalent to 5, 15, and 50 ppm in the feed for up 28
days. These dosing levels are equivalent to 6.9x, 21x and 69x the MDB
(Maximum Dietary Burden) for beef cattle and 11x, 32x, and 103x the MDB
for dairy cattle. Based on the available storage stability data,
residues of both acequinocyl and acequinocyl-OH in milk and tissues were
corrected for potential decline during frozen storage. Combined residues
were \<LOQ (\<0.02 ppm) in all samples of milk and muscle from all dose
groups and in kidney from the 5 and 15 ppm dose groups. However,
quantifiable residues were found in liver and fat from all three dose
groups and in kidneys from the high dose group. As combined residues
were \<LOQ in milk and muscle from cattle dosed at levels equivalent to
103x and 69x the MDB of dairy and beef cattle, respectively, and were
also \<LOQ in kidneys from cattle dosed at 21x the MDB of beef cattle,
quantifiable residues of acequinocyl are unlikely to occur in milk, meat
or kidneys of ruminants. Therefore, tolerances for acequinocyl in these
commodities are not required. Based on the maximum combined residues
observed in liver (0.040 ppm) and fat (0.055 ppm) at the 5 ppm dose
level (6.9x MDB), the maximum expected residues at a 1x feeding level
would be 0.006 ppm in liver and 0.008 ppm in fat. As these levels are
\<LOQ, tolerances set at the LOQ (0.02 ppm) are appropriate for liver
and fat. These data support the existing livestock tolerances.

Exposure of poultry and hog to acequinocyl is not expected, as there are
no existing or proposed tolerances on poultry or hog feedstuffs.

***Magnitude of the Residue in Processed Food and Feed:*** An adequate
grape processing study is available and supports the proposed use on
grapes. The grape processing study demonstrated that the combined
residues of acequinocyl and acequinocyl-OH do not concentrate in either
grape juice (\<0.02x) or raisins (0.15x). Therefore, separate tolerances
are not required for these commodities.

***Residue Analytical Method for Crops and Livestock:*** Once the
petitioner submits revised copies of their analytical methods,
incorporating comments from the ACL, adequate methods will be available
for enforcing tolerances on residues of acequinocyl and acequinocyl-OH
in plant and livestock commodities. These methods include two liquid
chromatography with tandem mass spectrometric detection (LC/MS/MS)
methods for determining residues in/on fruit and nut commodities (Morse
Methods Meth-133 and Meth-135Number range CHAPTER) and another LC/MS/MS
method for determining residues in livestock commodities (Method
Meth-139). For the current petition, samples from the available almond
and pecan field trials were analyzed using Method Meth-135 (revision
#2), samples from the grape field trials and processing study were
analyzed using Method Meth-133 (revision #4), and samples of milk and
cattle tissues from the storage stability study were analyzed using
Method Meth-139 (revision #3). For each of these methods, residues are
extracted with either hexane, acetonitrile (ACN) or aqueous ACN and
cleaned up by solvent partitioning, gel-permeation chromatography, and
silica-gel solid-phase extraction (SPE). Residues of parent and
acequinocyl-OH are then determined by LC/MS/MS using external standards.
A single transition is used for quantitation of each analyte and two
additional transitions are used for confirmation. The limit of
quantitation (LOQ) is 0.01 ppm for each analyte in plant and livestock
commodities, and the reported limit of detection (LOD) was 0.003 ppm of
each analyte in plant commodities.

***Storage Stability in Plants:*** Adequate storage stability data are
available on apple, orange and almond commodities from an earlier
petition (Memo, S. Levy, 10-MAR-2004; DP# D284757). These data indicate
that residues of both acequinocyl and acequinocyl-OH are stable at -20ºC
in apple fruit, juice and wet pomace for up to 5 months. Residues of
parent and acequinocyl-OH were also stable for up to 5 months in whole
oranges stored at ‑20ºC. In citrus processed fractions, both acequinocyl
and acequinocyl-OH were stable in frozen juice and oil for up to 3
months, but declined in dried pulp (32%) at 3 months. In almond nutmeats
and hulls stored at -20ºC, acequinocyl and acequinocyl-OH were stable
for up to 3.5 months.

For the current petitions, a storage stability study was conducted on
grapes in conjunction with the grape field trials. Homogenized samples
of whole grapes were fortified with acequinocyl and acequinocyl-OH, each
at 0.5 ppm, and stored at ‑20°C for up to 177 days (5.8 months).
Residues of acequinocyl were stable in grapes for up to 5.8 months, but
residues of acequinocyl-OH declined by 33%.

[]{.mark}

***Storage Stability in Livestock:*** The data indicate that residues of
acequinocyl are relatively stable at -20ºC for up to \~8.5 months for
milk, liver, kidney, and fat. Residues of acequinocyl were stable in
muscle up to \~3.5 months, but had declined significantly (47%) when
analyzed after 260 days of storage. The data indicate that residues of
acequinocyl-OH are relatively stable at -20ºC for up to \~8.5 months for
milk, liver, and fat. Residues of acequinocyl-OH were stable in muscle
and kidney up to \~3.5 months, but had declined significantly (34% in
muscle and by 36% in kidney) when analyzed after \~260 days of storage.

[]{.mark}

***Confined and Field Accumulation in Rotational Crops:*** Because tree
nuts and grapes are not rotated crops, no data pertaining to rotational
crops are required to support the proposed use.

[]{.mark}

***Submittal of Analytical Reference Standards:*** An analytical
standard for acequinocyl is currently available in the National
Pesticide Standards Repository (electronic communication, T. Cole,
08-JAN-2007); however, a reference standard for acequinocyl-OH has not
yet been submitted. Analytical reference standards must be supplied and
supplies replenished as requested by the Repository. The reference
standard acequinocyl-OH should be sent to the Analytical Chemistry Lab,
which is located at Fort Meade, to the attention of either Theresa Cole
or Frederic Siegelman at the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not
used.)

[]{.mark}

***Proposed and Recommended Tolerances:*** The proposed and recommended
tolerances for the combined residues of acequinocyl are listed below, in
Table 4.2 ([a revised Section F should be submitted]{.underline}). There
are no established or proposed Codex, Canadian, or MRLs for acequinocyl.

In the available almond and pecan field trials conducted at 1x the
proposed rate, the combined residues of acequinocyl and acequinocyl-OH
were each \<LOQ (\<0.01 ppm) in/on all samples of almond and pecan
nutmeats harvested at the proposed 7-day PHI. Therefore, HED recommends
establishing the tolerance for the tree nut crop group at the sum of the
individual LOQs of 0.01 ppm (for a total of 0.02 ppm). The existing
tolerance for residues in/on almond hulls is adequate. Once the
tolerance for the tree nuts crop group has been established, the
separate tolerance on almond should be deleted.

The recommended tolerance level for grapes was determined using Agency
Guidance (*Guidance for Setting Pesticide Tolerances Based on Field
Trial Data* SOP), as all the field trials were conducted at a 1x rate
and quantifiable residues were detected in 23 out of the 24 samples. The
appropriate tolerance for grapes was calculated to be 1.6 ppm.

Although residue data from the ruminant feeding study were corrected for
residue decline during storage, the overall results from the study were
not substantially altered. The feeding study data indicate that
tolerances are not required for residues in milk, meat and kidneys and
tolerances for liver and fat of cattle, goats, horses, and sheep should
be set at the method LOQ (0.02 ppm). Therefore, no changes in the
current livestock tolerances are required.

There are no established or proposed Codex, Canadian or Mexican MRLs for
acequinocyl in on any food/fee crops. Therefore, there is no question
concerning compatibility of the proposed tolerances.

+-----------------+--------------+-------------+-----------------------+
| **Table 4.2.    |              |             |                       |
| Tolerance       |              |             |                       |
| Summary for     |              |             |                       |
| Acequinocyl.**  |              |             |                       |
+-----------------+--------------+-------------+-----------------------+
| Commodity       | Proposed     | HED-        | Comments;             |
|                 | Tolerance    | Recommended |                       |
|                 | (ppm)        | T           | *Correct Commodity    |
|                 |              | olerance^1^ | Definition*           |
|                 |              | (ppm)       |                       |
+-----------------+--------------+-------------+-----------------------+
| Tree Nuts Group | 0.02         | 0.02        | Adequate residue data |
|                 |              |             | are available on      |
|                 |              |             | almonds and pecans.   |
|                 |              |             | Once the tolerance    |
|                 |              |             | for the tree nuts     |
|                 |              |             | crop group has been   |
|                 |              |             | established, the      |
|                 |              |             | separate tolerance on |
|                 |              |             | almond should be      |
|                 |              |             | deleted.              |
|                 |              |             |                       |
|                 |              |             | *Nut, tree, group 14* |
+-----------------+--------------+-------------+-----------------------+
| Grape Whole     | 1            | 1.6         | Adequate residue data |
| Fruit           |              |             | are available, and    |
|                 |              |             | the tolerance was     |
|                 |              |             | calculated using the  |
|                 |              |             | tolerance             |
|                 |              |             | harmonization         |
|                 |              |             | spreadsheet.          |
|                 |              |             |                       |
|                 |              |             | *Grape*               |
+-----------------+--------------+-------------+-----------------------+
| Grape Juice     | 0.05         | None        | As residues were      |
|                 |              |             | reduced in both juice |
|                 |              |             | (\<0.02x) and raisin  |
|                 |              |             | (0.15x), separate     |
|                 |              |             | tolerances are not    |
|                 |              |             | required for these    |
|                 |              |             | commodities.          |
+-----------------+--------------+-------------+-----------------------+
| Raisins         | 0.1          |             |                       |
+-----------------+--------------+-------------+-----------------------+

> ^1^ Acequinocyl tolerances should be set for the combined residues of
> acequinocyl and its metabolite, acequinocyl-OH, expressed as parent.

[]{#__RefHeading___Toc176837756 .anchor}**4.3 Water Exposure/Risk
Pathway**

[]{.mark}

***Environmental Fate Assessment:*** Acequinocyl appears to undergo
fairly rapid transformation in most aquatic and terrestrial
environments. It undergoes hydrolysis with a half-life of a few hours to
less than 2 days under neutral and alkaline pH conditions. However, it
is stable at acidic pH conditions. Photodegradation in water appears to
be the main route of degradation in aquatic environments, with
half-lives occurring in less than 15 minutes in sterile lab and river
water. Acequinocyl also undergoes fast degradation in terrestrial
environments. The half-lives for aerobic biotransformation on soil are
less than 2 days under laboratory conditions and under field conditions,
acequinocyl applied to bare plots dissipated with half-lives ranging
from 2 hrs in California to 14 hours in New York.

Acequinocyl is expected to exhibit low mobility in soil. The soil
adsorption K~d~ for acequinocyl ranges from 678 mL/g in sandy loam soil
to 1,620 mL/g in silty clay loam soil, and in field studies, the parent
was not detected below 0-15 cm soil depth. The bioconcentration factor
for acequinocyl in fish ranged from 307 to 387; therefore, it is
expected to have a moderate tendency to accumulate in fish.

[]{.mark}

***Surface and Ground Water Estimated Drinking Water Concentrations
(EDWCs):*** Acequinocyl is expected to exhibit low mobility in soil and
low potential to leach to ground water due to its high Koc values.
Therefore, exposure estimates from leaching to groundwater were not
evaluated by EFED. For the aquatic exposure modeling, both parent and
metabolite (acequinocyl-OH) concentrations were estimated in the surface
water to address the toxicity concerns associated with acequinocyl-OH
degradate.

EFED's available standard crop scenarios were used to evaluate the
aquatic exposure resulting from acequinocyl applications to grapes,
citrus, tree nuts, pome fruits, and ornamentals. Standard scenarios were
selected for each of these crop groups to assess runoff potential from
vulnerable use sites. The Tier II Pesticide Root Zone/Exposure Analysis
Modeling System (PRZM/EXAMS) model estimated the aquatic concentrations
for acequinocyl resulting from both food and non-food uses using both
model approaches.

The 1-in-10-year peak concentrations of acequinocyl ranged from 0.18 (CA
citrus) to 5.57 (FL nursery plants except roses) ppb. The 60-day
concentrations of acequinocyl ranged from 0.04 to 1.26 ppb.

  ------------------------------------------------------------------------
  **Table 4.3. EDWCs                                    
  Based on                                              
  PRZM-EXAMS.**                                         
  ------------------- --------------- ----------------- ------------------
  Crop Scenario       Peak            21 days           60 days

                      EEC (μg/L or                      
                      ppb)                              

  **Food Uses**                                         

  CA Grapes           0.21            0.07              0.05

  NY Grapes           2.78            1.01              0.53

  FL Citrus           1.99            0.62              0.29

  CA Citrus           0.18            0.06              0.04

  CA Almonds          0.64            0.22              0.10

  GA Pecans           5.05            1.78              0.86

  OR Apples           0.81            0.27              0.15

  PA Apples           3.59            1.36              0.70

  NC Apples           3.03            1.09              0.57

  **Non-Food Uses**                                     

  OR Christmas Trees  0.33            0.11              0.06

  FL Nursery Plants   5.57            2.39              1.26

  FL Nursery Plants   2.79            1.19              0.63
  (Roses)                                               
  ------------------------------------------------------------------------

[]{#__RefHeading___Toc176837757 .anchor}**4.4 Dietary Exposure
Analyses**

[]{.mark}

An acute dietary assessment was not conducted for acequinocyl because an
endpoint of concern attributable to a single dose was not identified;
therefore, an aRfD was not established and an acute dietary assessment
is not necessary. A cancer dietary assessment was not conducted because
acequinocyl was classified as not likely to be carcinogenic to humans.

An acequinocyl chronic dietary exposure assessment was conducted using
the DEEM-FCID™, Version 2.03, which incorporates consumption data from
USDA's CSFII, 1994-1996 and 1998. The 1994-96, 98 data are based on the
reported consumption of more than 20,000 individuals over two
non-consecutive survey days. Foods "as consumed" (e.g., apple pie) are
linked to EPA-defined food commodities (e.g., apples, peeled fruit -
cooked; fresh or N/S; baked; or wheat flour - cooked; fresh or N/S,
baked) using publicly available recipe translation files developed
jointly by USDA/ARS and EPA. For chronic exposure assessment,
consumption data are averaged for the entire U.S. population and within
population subgroups. Based on analysis of the 1994-96, 98 CSFII
consumption data, which took into account dietary patterns and survey
respondents, HED concluded that it is most appropriate to report risk
for the following population subgroups: the general U.S. population, all
infants (\<1 year old), children 1-2, children 3-5, children 6-12, youth
13-19, adults 20-49, females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate. The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure. Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD. This procedure is performed for each
population subgroup.

[]{.mark}

[]{#__RefHeading___Toc176837758 .anchor}**4.4.1 Chronic Dietary Exposure
Analysis**

[]{.mark}

The DEEM-FCID™ analysis estimates the dietary exposure of the U.S.
population and various population subgroups. The chronic dietary
exposure assessment (using tolerance level residues and 100% CT
information for all registered and proposed uses) was conducted for the
general U.S. population and various population subgroups. Drinking water
was incorporated directly into the dietary assessment using the chronic
concentration for surface water generated by the PRZM/EXAMS model. The
highest chronic surface water value (*i.e.*, most conservative) of 1.26
ppb was used for this assessment.

This assessment concludes that the chronic dietary exposure estimates
are not of concern to HED for the general U.S. population (7.3% cPAD)
and all population subgroups. The most highly exposed population
subgroup is children 1-2 years old at 40% of the cPAD. The use of ARs,
empirical processing factors, and %CT data would refine further HED's
exposure and risk estimates; however, refinement is not needed at this
time.

+-----------------------+-----------------------+-----------------------+
| **Table 4.4. Summary  |                       |                       |
| of Dietary Exposure   |                       |                       |
| and Risk for          |                       |                       |
| Acequinocyl.**        |                       |                       |
+=======================+=======================+=======================+
| Population Subgroup   | Chronic Dietary^1^    |                       |
+-----------------------+-----------------------+-----------------------+
|                       | Dietary Exposure      | \% cPAD               |
|                       |                       |                       |
|                       | (mg/kg/day)           |                       |
+-----------------------+-----------------------+-----------------------+
| U.S. Population       | 0.001969              | 7.3                   |
| (total)               |                       |                       |
+-----------------------+-----------------------+-----------------------+
| All Infants (\< 1     | 0.005168              | 19                    |
| year old)             |                       |                       |
+-----------------------+-----------------------+-----------------------+
| **Children 1-2 years  | **0.010892**          | **40**                |
| old**                 |                       |                       |
+-----------------------+-----------------------+-----------------------+
| Children 3-5 years    | 0.006887              | 26                    |
| old                   |                       |                       |
+-----------------------+-----------------------+-----------------------+
| Children 6-12 years   | 0.002837              | 11                    |
| old                   |                       |                       |
+-----------------------+-----------------------+-----------------------+
| Youth 13-19 years old | 0.001246              | 4.6                   |
+-----------------------+-----------------------+-----------------------+
| Adults 20-49 years    | 0.001104              | 4.1                   |
| old                   |                       |                       |
+-----------------------+-----------------------+-----------------------+
| Adults 50+ years old  | 0.001230              | 4.6                   |
+-----------------------+-----------------------+-----------------------+
| Females 13-49 years   | 0.001222              | 4.5                   |
| old                   |                       |                       |
+-----------------------+-----------------------+-----------------------+

^1^ Chronic dietary endpoint of 0.027 mg/kg/day applies to the general
U.S. population and all population subgroups.

[]{#__RefHeading___Toc176837759 .anchor}**4.5
Residential/Non‑Occupational Exposure Pathway**

Please refer to the following documents for detailed considerations of
the material summarized in this section:

-   Acequinocyl: Occupational and Residential Exposure/Risk Assessment
    for the New Use on the Tree Nut Crop Group, Grapes and for Homeowner
    and Commercial Application in Residential Areas. DP#:
    332006, 337473. K. Lowe. 9/6/07.

    []{#__RefHeading___Toc176837760 .anchor}**4.5.1 Residential
    Handler**

One of the proposed new uses for acequinocyl is on ornamentals in
landscapes in and around residences, businesses, public property,
schools, interiorscapes and other non-production areas by commercial
applicators and homeowners. Therefore, there is the potential for
residential handler exposure. Homeowner handlers are expected to
complete all tasks associated with the use of a pesticide product
including mixing and loading (if needed), and application. Based upon
the proposed use pattern, the following residential handler scenarios
have been assessed:

(1) mixing/loading/applying liquids with low pressure handwand
    (ORETF\--fruit trees and ornamentals); and

(2) mixing/loading/applying liquids with hose-end sprayer (ORETF\--
    fruit trees and ornamentals).

No chemical-specific data were available with which to assess potential
exposure to pesticide handlers. The estimates of exposure to pesticide
handlers are based upon surrogate study data available from the ORETF
and the PHED (August, 1998). Homeowner handler assessments are based on
the assumption that individuals are wearing shorts, short-sleeved
shirts, socks, and shoes. Residential handler exposure scenarios are
considered to be short-term only, due to the infrequent use patterns
associated with homeowner products.

Table 4.5 presents the exposure/risks for residential short-term dermal
and inhalation exposures at baseline. Based on HED's residential handler
assessment, there are no risks of concern for residential handlers
(i.e., MOEs \> 100).

+----------------+--------+-------+---------------------+-------------+
| **Table 4.5.   |        |       |                     |             |
| Residential    |        |       |                     |             |
| Handler Dermal |        |       |                     |             |
| and Inhalation |        |       |                     |             |
| Exposures and  |        |       |                     |             |
| Risks.**       |        |       |                     |             |
+================+========+=======+=====================+=============+
| Dermal and     | Appli  | A     | Doses               | MOEs^4^     |
|                | cation | mount | (mg/kg/day)^3^      |             |
| Inhalation     | Rate   | ha    |                     |             |
| Unit Exposures | (lb    | ndled |                     |             |
| (mg/lb ai)     | a      | daily |                     |             |
|                | i/gall | (g    |                     |             |
|                | on)^1^ | allon |                     |             |
|                |        | s)^2^ |                     |             |
+----------------+--------+-------+---------------------+-------------+
| *Mixer/Loa     |        |       |                     |             |
| der/Applicator |        |       |                     |             |
| -- Liquid with |        |       |                     |             |
| Low Pressure   |        |       |                     |             |
| Handwand       |        |       |                     |             |
| (ORETF\--fruit |        |       |                     |             |
| trees and      |        |       |                     |             |
| ornamentals)*  |        |       |                     |             |
+----------------+--------+-------+---------------------+-------------+
| [Derma         | 0      | 5     | [                   | [Dermal]{   |
| l]{.underline} | .00125 |       | Dermal]{.underline} | .underline} |
|                |        |       |                     |             |
| Baseline^5^:   |        |       | Baseline: 0.005     | Baseline:   |
| 56             |        |       |                     | 40,000      |
+----------------+--------+-------+---------------------+-------------+
| [Inhalatio     |        |       | [Inha               | [I          |
| n]{.underline} |        |       | lation]{.underline} | nhalation]{ |
|                |        |       |                     | .underline} |
| Baseline^6^:   |        |       | Baseline: 2.3E-07   |             |
| 0.0026         |        |       |                     | Baseline:   |
|                |        |       |                     | 2.6E+08     |
+----------------+--------+-------+---------------------+-------------+
| *Mixer/Loa     |        |       |                     |             |
| der/Applicator |        |       |                     |             |
| -- Liquid with |        |       |                     |             |
| Hose-End       |        |       |                     |             |
| Sprayer        |        |       |                     |             |
| (ORETF\--      |        |       |                     |             |
| fruit trees    |        |       |                     |             |
| and            |        |       |                     |             |
| ornamentals)*  |        |       |                     |             |
+----------------+--------+-------+---------------------+-------------+
| [Derma         | 0      | 100   | [                   | [Dermal]{   |
| l]{.underline} | .00125 |       | Dermal]{.underline} | .underline} |
|                |        |       |                     |             |
| Baseline: 39   |        |       | Baseline: 0.07      | Baseline:   |
|                |        |       |                     | 2,900       |
+----------------+--------+-------+---------------------+-------------+
| [Inhalatio     |        |       | [Inha               | [I          |
| n]{.underline} |        |       | lation]{.underline} | nhalation]{ |
|                |        |       |                     | .underline} |
| Baseline:      |        |       | Baseline: 2.9E-06   |             |
| 0.0016         |        |       |                     | Baseline:   |
|                |        |       |                     | 2.1E+07     |
+----------------+--------+-------+---------------------+-------------+

^1^ Application rates are the maximum application rates determined from
proposed labels for acequinocyl.

^2^ Amount handled per day values are HED estimates of acres treated per
day based on Exposure SAC SOP #9 "Standard Values for Daily Acres

Treated in Agriculture," industry sources, and HED estimates.

^3^ Dose (mg/kg/day) = Unit exposure(mg/lb ai) x App Rate (lb ai/gal) x
Amount Handled (gal/day) x %Absorption (100% inhalation) /

Body weight (70 kg).

^4^ MOE = NOAEL/Dose; where the short-term dermal NOAEL = 200 mg/kg/day
and short-term inhalation NOAEL = 60 mg/kg/day.

^5^ Baseline Dermal: short-sleeve shirt, short pants, and no gloves.

^6^ Baseline Inhalation: no respirator.

[]{#__RefHeading___Toc176837761 .anchor}**4.5.2 Residential
Postapplication**

With respect to residential postapplication exposures, current HED
policy (see ExpoSAC minutes from 8/19/99 and 10/11/01) specifies that no
significant postapplication exposure is anticipated from landscape
ornamentals, either by residents or professional applicators; therefore,
no residential postapplication assessment was conducted.

[]{#__RefHeading___Toc176837762 .anchor}**4.5.3 Other (Spray Drift,
etc.)**

Spray drift is always a potential source of exposure to residents nearby
to spraying operations. This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for acequinocyl.
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation and
other parties to develop the best spray drift management practices. On a
chemical by chemical basis, the Agency is now requiring interim
mitigation measures for aerial applications that must be placed on
product labels/labeling. The Agency has completed its evaluation of the
new database submitted by the Spray Drift Task Force, a membership of
U.S. pesticide registrants, and is developing a policy on how to
appropriately apply the data and the AgDRIFT^®^ computer model to its
risk assessments for pesticides applied by air, orchard airblast and
ground hydraulic methods. After the policy is in place, the Agency may
impose further refinements in spray drift management practices to reduce
off-target drift with specific products with significant risks
associated with drift.

[]{#__RefHeading___Toc176837763 .anchor}**5.0 AGGREGATE RISK ASSESSMENTS
AND RISK CHARACTERIZATION**

In accordance with the FQPA, HED must consider and aggregate (add)
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures. In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard, or the risks themselves can be aggregated. When
aggregating exposures and risks from various sources, HED considers both
the route and duration of exposure.

[]{#__RefHeading___Toc176837764 .anchor}**5.1 Acute Aggregate Risk**

An endpoint of concern was not identified to quantify acute-dietary risk
to the general population or to any population subgroup. Since an acute
dietary endpoint was not identified, an acute hazard does not exist and
an acute aggregate assessment was not performed.

[]{#__RefHeading___Toc176837765 .anchor}**5.2 Short-Term Aggregate
Risk**

Short-term aggregate risk is made up of dietary and non-dietary sources
of exposure. Since acequinocyl is proposed for use on ornamentals, adult
residential handler exposure is expected. Short-term aggregate risk is
made up of average dietary exposures from food and drinking water
sources, and dermal residential exposures. Inhalation residential
exposures are not included in the aggregate since the inhalation
fraction of exposure to the resident applicator is negligible (see Table
4.5). The adult 50+ years old population is the highest exposed
population and is considered protective of the other adult populations
groups.

Dietary (food and drinking water) exposure is based on a Tier 1 chronic
dietary exposure assessment (see Table 4.3). Residential exposure
estimates are conservative estimates due to the standard assumptions
that were built into the calculations. Residential estimates were taken
from Table 4.5. The short-term aggregate for the adults 50+ years old
population is not of concern to HED.

+----------------------+--------------+---------------+--------------+
| **Table 5.1          |              |               |              |
| Short-Term Aggregate |              |               |              |
| Risk                 |              |               |              |
| Calculations.^1^**   |              |               |              |
+----------------------+--------------+---------------+--------------+
| Population           | Dietary      | Dermal MOE    | Aggregate    |
|                      | MOE^2^       |               |              |
|                      |              |               | MOE^3^       |
+----------------------+--------------+---------------+--------------+
| Adults 50+ years old | 49,000       | 2,900         | 2,700        |
+----------------------+--------------+---------------+--------------+

^1^ Dietary exposure from Table 4.3 and Residential MOE from Table 4.5.

^2^ Dietary MOE = short-term incidental oral NOAEL ÷ chronic dietary
exposure.

^3^ Aggregate MOE (dietary and residential) = 1÷((1÷MOE~dietary~)+
(1÷MOE~dermal~); LOC = 100.

[]{#__RefHeading___Toc176837766 .anchor}**5.3 Intermediate-Term
Aggregate Risk**

Intermediate-term aggregate risk was not calculated since the use
pattern is not expected to result in residential handler or
postapplication exposure of more than 30-day duration.

[]{#__RefHeading___Toc176837767 .anchor}**5.4 Long-Term Aggregate Risk**

Long-term aggregate risk was not calculated because residential handler
or postapplication exposure over the long-term duration (more than 6
months) is not expected based on the use pattern.

[]{#__RefHeading___Toc176837768 .anchor}**5.5 Cancer Risk**

Aggregate cancer risk was not calculated because acequinocyl is not
considered to be a carcinogen.

[]{#__RefHeading___Toc176837769 .anchor}**6.0 CUMULATIVE RISK**

Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a
particular pesticide\'s residues and "other substances that have a
common mechanism of toxicity."

EPA does not have, at this time, available data to determine whether
acequinocyl has a common mechanism of toxicity with other substances.
Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to acequinocyl and any other
substances and acequinocyl does not appear to produce a toxic metabolite
produced by other substances. For the purposes of this tolerance action,
therefore, EPA has not assumed that acequinocyl has a common mechanism
of toxicity with other substances. For information regarding EPA's
efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy
statements released by EPA's Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA's website at
[http://www.epa.gov/pesticides/cumulative/.]{.underline}

[]{#__RefHeading___Toc176837770 .anchor}**7.0 OCCUPATIONAL EXPOSURE AND
RISK ASSESSMENT**

Please refer to the following documents for detailed considerations of
the material summarized in this section:

-   Acequinocyl: Occupational and Residential Exposure/Risk Assessment
    for the New Use on the Tree Nut Crop Group, Grapes and for Homeowner
    and Commercial Application in Residential Areas. DP Barcode:
    332006, 337473. K. Lowe. 9/6/07.

    []{#__RefHeading___Toc176837771 .anchor}**7.1 Occupational Handler**

The proposed use is for application to tree nut crops (almonds, beech
nut, brazil nut, butter nut, cashew, chestnut, chinquapin, filbert,
hickory nut, macadamia nut, pecan, black walnut and English walnut) and
grapes. Therefore, there is the potential for occupational handler and
postapplication exposure.

Based upon the proposed use pattern, the following occupational handler
scenarios have been examined:

> \(1\) mixing/loading liquids for airblast applications (PHED);
>
> \(2\) mixing/loading liquids for groundboom applications (PHED);

\(3\) applying sprays via airblast equipment (PHED);

\(4\) applying sprays via groundboom equipment (PHED);

> \(5\) mixing/loading/applying liquids with low-pressure handwand
> (PHED); and
>
> \(6\) mixing/loading/applying liquids with a hose-end sprayer (ORETF).

No chemical-specific data were available with which to assess potential
exposure to pesticide handlers. The estimates of exposure to pesticide
handlers are based upon surrogate study data available in the PHED
(August, 1998) and from the ORETF. For pesticide handlers, it is HED
standard practice to present estimates of dermal exposure for
"baseline"; that is, for workers wearing a single layer of work clothing
consisting of a long-sleeved shirt, long pants, shoes plus socks and no
protective gloves, as well as for "baseline" and the use of protective
gloves or other Personal Protective Equipment (PPE) as might be
necessary. The proposed product label involved in this assessment
directs applicators and other handlers to wear long-sleeved shirt and
long pants, socks, shoes, and chemical resistant gloves made of
waterproof material.

HED believes most exposure durations will be short-term (1 - 30 days).
However, the ExpoSAC maintains it is possible for commercial applicators
to be exposed to intermediate-term exposure durations (1 - 6 months);
therefore, both short- and intermediate-term exposures have been
assessed. Long-term exposures are not expected, therefore, a long-term
assessment was not conducted.

Table 7.1 presents the estimated risks for workers based on the short
and intermediate-term dermal and inhalation exposures at baseline. There
are no risks of concern for occupational handlers (i.e., MOEs \>100).

+-------+------+-------+---------------+----------+---------+--------+
| **    |      |       |               |          |         |        |
| Table |      |       |               |          |         |        |
| 7.1.  |      |       |               |          |         |        |
| Oc    |      |       |               |          |         |        |
| cupat |      |       |               |          |         |        |
| ional |      |       |               |          |         |        |
| D     |      |       |               |          |         |        |
| ermal |      |       |               |          |         |        |
| and   |      |       |               |          |         |        |
| Inhal |      |       |               |          |         |        |
| ation |      |       |               |          |         |        |
| Expo  |      |       |               |          |         |        |
| sures |      |       |               |          |         |        |
| and   |      |       |               |          |         |        |
| Ris   |      |       |               |          |         |        |
| ks.** |      |       |               |          |         |        |
+=======+======+=======+===============+==========+=========+========+
| Crop  | App  | Area  | Dermal and    | Short-   | MOEs^6^ |        |
| or    | lica | Tr    | Inhalation    | and      |         |        |
| T     | tion | eated | Unit          | I        |         |        |
| arget | Rat  | Daily | Exposures     | ntermedi |         |        |
|       | e^1^ | or    | (mg/lb ai)    | ate-term |         |        |
|       |      | A     |               | Doses    |         |        |
|       |      | mount |               | (mg/kg   |         |        |
|       |      | Handl |               | /day)^5^ |         |        |
|       |      | ed^2^ |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       |               |          | Sho     | Inter  |
|       |      |       |               |          | rt-term | mediat |
|       |      |       |               |          |         | e-term |
+-------+------+-------+---------------+----------+---------+--------+
| *Mixi |      |       |               |          |         |        |
| ng/Lo |      |       |               |          |         |        |
| ading |      |       |               |          |         |        |
| Li    |      |       |               |          |         |        |
| quids |      |       |               |          |         |        |
| Co    |      |       |               |          |         |        |
| ncent |      |       |               |          |         |        |
| rates |      |       |               |          |         |        |
| for   |      |       |               |          |         |        |
| Air   |      |       |               |          |         |        |
| blast |      |       |               |          |         |        |
| Ap    |      |       |               |          |         |        |
| plica |      |       |               |          |         |        |
| tions |      |       |               |          |         |        |
| (P    |      |       |               |          |         |        |
| HED)* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| tree  | 0.3  | 40 A  | [Dermal       | [Der     | [Derma  |        |
| nut   | lb   |       | ]{.underline} | mal]{.un | l]{.und |        |
| crops | ai/A |       |               | derline} | erline} |        |
|       |      |       | Baseline: 2.9 |          |         |        |
|       |      |       |               | B        | Ba      |        |
|       |      |       |               | aseline: | seline: |        |
|       |      |       |               | 0.5      | 400     |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline:     |          | erline} | rline} |
|       |      |       | 0.0012        | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0.00021  | seline: | eline: |
|       |      |       |               |          | 290,000 | 78,000 |
+-------+------+-------+---------------+----------+---------+--------+
| *Mixi |      |       |               |          |         |        |
| ng/Lo |      |       |               |          |         |        |
| ading |      |       |               |          |         |        |
| L     |      |       |               |          |         |        |
| iquid |      |       |               |          |         |        |
| Co    |      |       |               |          |         |        |
| ncent |      |       |               |          |         |        |
| rates |      |       |               |          |         |        |
| for   |      |       |               |          |         |        |
| Groun |      |       |               |          |         |        |
| dboom |      |       |               |          |         |        |
| Ap    |      |       |               |          |         |        |
| plica |      |       |               |          |         |        |
| tions |      |       |               |          |         |        |
| (P    |      |       |               |          |         |        |
| HED)* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| g     | 0.3  | 80 A  | [Dermal       | [Der     | [Derma  |        |
| rapes | lb   |       | ]{.underline} | mal]{.un | l]{.und |        |
|       | ai/A |       |               | derline} | erline} |        |
|       |      |       | Baseline^3^:  |          |         |        |
|       |      |       | 2.9 (HC)      | B        | Ba      |        |
|       |      |       |               | aseline: | seline: |        |
|       |      |       |               | 0.99     | 200     |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline^4^:  |          | erline} | rline} |
|       |      |       | 1.2 (HC)      | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0.00041  | seline: | eline: |
|       |      |       |               |          | 150,000 | 39,000 |
+-------+------+-------+---------------+----------+---------+--------+
| *App  |      |       |               |          |         |        |
| lying |      |       |               |          |         |        |
| S     |      |       |               |          |         |        |
| prays |      |       |               |          |         |        |
| via   |      |       |               |          |         |        |
| Air   |      |       |               |          |         |        |
| blast |      |       |               |          |         |        |
| Equi  |      |       |               |          |         |        |
| pment |      |       |               |          |         |        |
| (P    |      |       |               |          |         |        |
| HED)* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| tree  | 0.3  | 40 A  | [Dermal       | [Der     | [Derma  |        |
| nut   | lb   |       | ]{.underline} | mal]{.un | l]{.und |        |
| crops | ai/A |       |               | derline} | erline} |        |
|       |      |       | Baseline:     |          |         |        |
|       |      |       | 0.36          | B        | Ba      |        |
|       |      |       |               | aseline: | seline: |        |
|       |      |       |               | 0.062    | 3,200   |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline:     |          | erline} | rline} |
|       |      |       | 0.0045        | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0.00077  | seline: | eline: |
|       |      |       |               |          | 78,000  | 21,000 |
+-------+------+-------+---------------+----------+---------+--------+
| *App  |      |       |               |          |         |        |
| lying |      |       |               |          |         |        |
| S     |      |       |               |          |         |        |
| prays |      |       |               |          |         |        |
| via   |      |       |               |          |         |        |
| Groun |      |       |               |          |         |        |
| dboom |      |       |               |          |         |        |
| Equip |      |       |               |          |         |        |
| ment* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| g     | 0.3  | 40 A  | [Dermal       | [Der     | [Derma  |        |
| rapes | lb   |       | ]{.underline} | mal]{.un | l]{.und |        |
|       | ai/A |       |               | derline} | erline} |        |
|       |      |       | Baseline:     |          |         |        |
|       |      |       | 0.014 (HC)    | B        | Ba      |        |
|       |      |       |               | aseline: | seline: |        |
|       |      |       |               | 0.0048   | 42,000  |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline:     |          | erline} | rline} |
|       |      |       | 0.74 (HC)     | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0.00025  | seline: | eline: |
|       |      |       |               |          | 240,000 | 63,000 |
+-------+------+-------+---------------+----------+---------+--------+
| *     |      |       |               |          |         |        |
| Mixin |      |       |               |          |         |        |
| g/Loa |      |       |               |          |         |        |
| ding/ |      |       |               |          |         |        |
| App   |      |       |               |          |         |        |
| lying |      |       |               |          |         |        |
| L     |      |       |               |          |         |        |
| iquid |      |       |               |          |         |        |
| Co    |      |       |               |          |         |        |
| ncent |      |       |               |          |         |        |
| rates |      |       |               |          |         |        |
| with  |      |       |               |          |         |        |
| Low   |      |       |               |          |         |        |
| Pre   |      |       |               |          |         |        |
| ssure |      |       |               |          |         |        |
| Han   |      |       |               |          |         |        |
| dwand |      |       |               |          |         |        |
| (P    |      |       |               |          |         |        |
| HED)* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| r     | 0.0  | 40    | [Dermal       | [Der     | [Derma  |        |
| eside | 0125 | ga    | ]{.underline} | mal]{.un | l]{.und |        |
| ntial | lb   | llons |               | derline} | erline} |        |
| areas | a    |       | Baseline: 100 |          |         |        |
| (or   | i/ga |       |               | B        | Ba      |        |
| namen | llon |       |               | aseline: | seline: |        |
| tals) |      |       |               | 0.071    | 2,800   |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline:     |          | erline} | rline} |
|       |      |       | 0.03          | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0.000021 | seline: | eline: |
|       |      |       |               |          | 21,     | 7      |
|       |      |       |               |          | 100,000 | 50,000 |
+-------+------+-------+---------------+----------+---------+--------+
| *     |      |       |               |          |         |        |
| Mixin |      |       |               |          |         |        |
| g/Loa |      |       |               |          |         |        |
| ding/ |      |       |               |          |         |        |
| App   |      |       |               |          |         |        |
| lying |      |       |               |          |         |        |
| Li    |      |       |               |          |         |        |
| quids |      |       |               |          |         |        |
| with  |      |       |               |          |         |        |
| a     |      |       |               |          |         |        |
| Hos   |      |       |               |          |         |        |
| e-end |      |       |               |          |         |        |
| Sp    |      |       |               |          |         |        |
| rayer |      |       |               |          |         |        |
| (OR   |      |       |               |          |         |        |
| ETF)* |      |       |               |          |         |        |
+-------+------+-------+---------------+----------+---------+--------+
| r     | 0.0  | 100   | [Dermal       | [Der     | [Derma  |        |
| eside | 0125 | ga    | ]{.underline} | mal]{.un | l]{.und |        |
| ntial | lb   | llons |               | derline} | erline} |        |
| areas | a    |       | Baseline: 23  |          |         |        |
| (or   | i/ga |       |               | B        | Ba      |        |
| namen | llon |       |               | aseline: | seline: |        |
| tals) |      |       |               | 0.041    | 4,900   |        |
+-------+------+-------+---------------+----------+---------+--------+
|       |      |       | [Inhalation   | [Inhalat | [In     | [Inhal |
|       |      |       | ]{.underline} | ion]{.un | halatio | ation] |
|       |      |       |               | derline} | n]{.und | {.unde |
|       |      |       | Baseline:     |          | erline} | rline} |
|       |      |       | 0.0016        | B        |         |        |
|       |      |       |               | aseline: | Ba      | Bas    |
|       |      |       |               | 0        | seline: | eline: |
|       |      |       |               | .0000029 | 21,     | 5,6    |
|       |      |       |               |          | 000,000 | 00,000 |
+-------+------+-------+---------------+----------+---------+--------+

^1^ Application rates are the maximum application rates determined from
proposed labels for acequinocyl.

^2^ Amount handled per day values are HED estimates of acres treated per
day based on ExpoSAC SOP #9 "Standard Values for Daily Acres Treated in
Agriculture," industry sources, and HED estimates.

^3^ Baseline Dermal: Long-sleeve shirt, long pants, and no gloves.

^4^ Baseline Inhalation: no respirator.

^5^ Dose (mg/kg/day) = Unit exposure(mg/lb ai) x App Rate (lb ai/acre or
lb ai/gallon) x Area Treated (acres/day) or Amount Handled (gallons) /
Body weight (kg).

^6^ MOE = NOAEL/Dose; where the short- and intermediate-term dermal
NOAEL = 200 mg/kg/day; short-term inhalation NOAEL = 60 mg/kg/day;
intermediate-term inhalation NOAEL = 16 mg/kg/day.

[]{#__RefHeading___Toc176837772 .anchor}**7.2 Occupational
Postapplication**

Agricultural workers may experience postapplication exposures to
dislodgeable foliar pesticide residues during the course of typical
agricultural activities. The ExpoSAC SOP 003.1, Rev. 7 (Aug. 2000,
Regarding Agricultural Transfer Coefficients) lists a number of possible
postapplication agricultural activities related to tree nuts that might
result in pesticide exposure to agricultural workers. TCs expressed as
cm²/hr are identified for each of the postapplication agricultural
activities. The dermal TCs used in this assessment are summarized in
Table 7.2.

  ---------------------------------------------------------------------------------
  **Table 7.2.                                      
  Anticipated                                       
  Postapplication                                   
  Activities and Dermal                             
  Transfer                                          
  Coefficients.**                                   
  --------------------- -------------- ------------ -------------------------------
  Proposed Crops        Policy Crop    TCs          Activities
                        Group Category (cm^2^/hr)   

  Almonds, beech nut,   Tree nut       500          Scouting, Thinning, Irrigation,
  Brazil nut, butter                                Hand Weeding
  nut, cashew,                                      
  chestnut, chinquapin,                             
  filbert, hickory nut,                             
  macadamia nut, pecan,                             
  black walnut and                                  
  English walnut                                    

                                       2,500        Hand Harvest, Hand Pruning,
                                                    Thinning

  Grapes (wine)         Vine/trellis   500          Scouting, Hand Weeding,
                                                    Irrigation, Hedging

                                       1000         Scouting

                                       5000         Thinning, Hand Pruning, Leaf
                                                    Pulling, Hand Harvesting,
                                                    Tying, Training

  Grapes (juice)                       500          Hand Weeding, Scouting and
                                                    Irrigation

                                       1000         Scouting, Training

                                       5000         Tying, Hand Pruning, Hand
                                                    Harvesting, Thinning, Training

  Grapes (tbl/rsn)                     500          Scouting, Hand Weeding

                                       5000         Thinning, Hand Pruning, Hand
                                                    Harvesting

                                       10000        Girdling, Turning (Cane
                                                    Turning), Tying (Cane Turning)
  ---------------------------------------------------------------------------------

The information in the table is based on proprietary and non-proprietary
data.

Since no postapplication data were submitted in support of this
registration action, exposures during postapplication activities were
estimated using dermal TCs from the ExpoSAC Policy Number 3.1:
Agricultural Transfer Coefficients, August 2000, summarized in Table 7.2
above and the following assumptions:

Assumptions:

-   Application Rate = 0.3 lb ai/A

-   Exposure Duration = 8 hours per day

-   Body Weight = 70 kg

-   Dermal Absorption = NA

-   Fraction of a.i. retained on foliage is assumed to be 20% (0.2) on
    day zero (= % dislodgeable foliar residue, DFR, after initial
    treatment). This fraction is assumed to further dissipate at the
    rate of 10% (0.1) per day on following days. These are default
    values established by HED's ExpoSAC.

Daily dermal exposures were calculated on each postapplication day after
application using the following equation:

DE~(t)~ (mg/day) = (TR~(t)~ (µg/cm^2^) x TC (cm^2^/hr) x Hr/Day)/1000
(µg/mg)

Where:

> DE(t) = Daily exposure or amount deposited on the surface of the skin
> at time (t) attributable for activity in a previously treated area,
> also referred to as potential dose (mg ai/day);

TR(t) = Transferable residues that can be dislodgeable foliar residue at
time "t" (µg/cm^2^);

TC = Transfer Coefficient (cm^2^/hour); and

Hr/day = Exposure duration meant to represent a typical workday (hours).

Note that the (TR~(t)~) input may represent levels on the day of
application in the case of short-term risk calculations. Once daily
exposures are calculated, the calculation of daily absorbed dose and the
resulting MOEs use the same algorithms that are described above for the
handler exposures. These calculations are completed for each day or
appropriate block of time after application.

For tree nut and grape applications, risks are not of concern (i.e.,
MOEs \>100) on day 0 (REI = 12 hours) for all of the exposure
activities. Table 7.3 presents a summary of occupational postapplication
risks associated with use of acequinocyl.

+--------+--------+------------------------------+--------+-----------+
| *      |        |                              |        |           |
| *Table |        |                              |        |           |
| 7.3.   |        |                              |        |           |
| S      |        |                              |        |           |
| ummary |        |                              |        |           |
| of     |        |                              |        |           |
| Occupa |        |                              |        |           |
| tional |        |                              |        |           |
| Pos    |        |                              |        |           |
| tappli |        |                              |        |           |
| cation |        |                              |        |           |
| Risks  |        |                              |        |           |
| for    |        |                              |        |           |
| Ac     |        |                              |        |           |
| equino |        |                              |        |           |
| cyl.** |        |                              |        |           |
+========+========+==============================+========+===========+
| Crop   | Appli  | TC (µg/cm^2^)                | Day    | MOE at    |
| Gr     | cation |                              | after  | Day 0^a^  |
| ouping | rate   |                              | Appli  |           |
|        |        |                              | cation | (Level of |
|        | (lb    |                              |        | Concern = |
|        | ai     |                              |        | 100)      |
|        | /acre) |                              |        |           |
+--------+--------+------------------------------+--------+-----------+
| Tree   | 0.3    | 500 (scouting, thinning,     | 0 (12  | 5,200     |
| nut    |        | irrigation, hand weeding)    | hours) |           |
+--------+--------+------------------------------+--------+-----------+
|        |        | 2500 (hand harvest, hand     |        | 1,000     |
|        |        | pruning, thinning)           |        |           |
+--------+--------+------------------------------+--------+-----------+
| Grapes | 0.3    | 500                          | 0 (12  | 5.200     |
|        |        |                              | hours) |           |
|        |        | (Scouting, Hand weeding,     |        |           |
|        |        | Irrigation, Hedging for      |        |           |
|        |        | Grapes (wine); Scouting,     |        |           |
|        |        | Hand weeding for Grapes      |        |           |
|        |        | (tbl/rsn); Hand weeding,     |        |           |
|        |        | Scouting and Irrigation for  |        |           |
|        |        | Grapes (juice))              |        |           |
+--------+--------+------------------------------+--------+-----------+
|        |        | 1000                         |        | 2,600     |
|        |        |                              |        |           |
|        |        | (Scouting for Grapes (wine); |        |           |
|        |        | Scouting, Training for       |        |           |
|        |        | Grapes (juice))              |        |           |
+--------+--------+------------------------------+--------+-----------+
|        |        | 5000                         |        | 520       |
|        |        |                              |        |           |
|        |        | (Thinning, Hand pruning,     |        |           |
|        |        | Leaf pulling, Hand           |        |           |
|        |        | harvesting, Tying, Training  |        |           |
|        |        | for Grapes (wine); Thinning, |        |           |
|        |        | Hand pruning, Hand           |        |           |
|        |        | harvesting for Grapes        |        |           |
|        |        | (tbl/rsn); Tying, Hand       |        |           |
|        |        | pruning, Hand harvesting,    |        |           |
|        |        | Thinning, Training for       |        |           |
|        |        | Grapes (juice))              |        |           |
+--------+--------+------------------------------+--------+-----------+
|        |        | 10000                        |        | 260       |
|        |        |                              |        |           |
|        |        | (Girdling, Turning (Cane     |        |           |
|        |        | turning), Tying (Cane        |        |           |
|        |        | turning) for Grapes          |        |           |
|        |        | (tbl/rsn))                   |        |           |
+--------+--------+------------------------------+--------+-----------+

a MOE = dermal NOAEL (200 mg/kg/day) / dermal dose (mg/kg/day) where the
dermal dose = (dislodgeable foliar residues on day 0, 0.673 µg/cm^2^) \*
(transfer coefficient, cm^2^/hr) \* (exposure time, 8 hr/day) \* (CF1,
0.001 µg/mg) / (Body weight, 70 kg)

[]{#__RefHeading___Toc176837773 .anchor}**7.3 Restricted‑Entry
Intervals**

Acequinocyl is classified in Toxicity Category III for acute dermal and
acute inhalation. It is classified in Toxicity Category IV for primary
eye irritation and primary skin irritation and it is not a dermal
sensitizer. Therefore, the Worker Protection Standard interim restricted
entry interval of 12 hours is adequate to protect agricultural workers
from postapplication exposures to acequinocyl.

[]{#__RefHeading___Toc176837774 .anchor}**8.0 RESIDUE CHEMISTRY AND
TOXICOLOGY DEFICIENCIES**

[]{#__RefHeading___Toc176837775 .anchor}**8.1 Residue Chemistry**

-   Revised Section F.

-   Revised copies of Morse Methods Meth-133 (revision #3), Meth-135,
    and Meth-139 (revision #2), incorporating comments from the ACL
    should be submitted.

-   An analytical reference standard for the metabolite acequinocyl‑OH
    must be submitted to the EPA National Pesticide Standards
    Repository.

[]{.mark}

[]{#__RefHeading___Toc176837776 .anchor}**8.2 Toxicology**

[]{.mark}

None

[]{#__RefHeading___Toc176837777 .anchor}**8.3 Occupational and
Residential Exposure**

None.

Cc: K. Lowe (RAB1); S. Levy (RAB1)

RDI: RAB1 Branch (9/5/07); RAB1 Chemists (9/5/07)

K. Lowe: S10942: PY1:703-347-8989; 7509P:RAB1

**APPENDIX**

+------------+---------------------+-----------------------------------+
| **Table    |                     |                                   |
| A-1.       |                     |                                   |
| Structures |                     |                                   |
| of         |                     |                                   |
| Ace        |                     |                                   |
| quinocyl's |                     |                                   |
| Met        |                     |                                   |
| abolites** |                     |                                   |
+------------+---------------------+-----------------------------------+
| Common     | Chemical Name       | Chemical Structure                |
| Name/Code  |                     |                                   |
+------------+---------------------+-----------------------------------+
| A          | 2-(ace              | ![](media/image4.                 |
| cequinocyl | tyloxy)-3-dodecyl-1 | wmf){width="1.8416666666666666in" |
|            | ,4-naphthalenedione | height="1.0833333333333333in"}    |
+------------+---------------------+-----------------------------------+
| Aceq       | 2-                  | ![](media/image5.                 |
| uinocyl-OH | dodecyl-3-hydroxy-1 | wmf){width="1.8416666666666666in" |
|            | ,4-naphthalenedione | height="1.0833333333333333in"}    |
| (          |                     |                                   |
| Metabolite |                     |                                   |
| R1)        |                     |                                   |
+------------+---------------------+-----------------------------------+
| AKM-18     | 2-(1,2-dioxo        | ![](media/image6.                 |
|            | tetradecyl)-benzoic | wmf){width="1.7006944444444445in" |
|            | acid                | height="1.0833333333333333in"}    |
+------------+---------------------+-----------------------------------+
| AKM-15     | 2                   | ![](me                            |
|            | ‑hydroxy‑3‑hexanoic | dia/image7.wmf){width="2.39375in" |
|            | acid‑1, 4           | height="1.0833333333333333in"}    |
|            | naphthalenedione    |                                   |
+------------+---------------------+-----------------------------------+
| AKM-14     | 2                   | ![](media/image8                  |
|            | ‑hydroxy‑3‑butanoic | .wmf){width="2.296527777777778in" |
|            | acid‑1              | height="1.0722222222222222in"}    |
|            | ,4‑naphthalenedions |                                   |
+------------+---------------------+-----------------------------------+