UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF

	PREVENTION, PESTICIDES

	AND TOXIC SUBSTANCES

MEMORANDUM

Date:		17-January-2008

Subject:	Buprofezin - Human-Health Risk Assessment for Application to
Low-Growing Berries, Olives, Leafy Vegetables (except Brassica), and
Fruiting Vegetables.

Petition #s:	7E7207; 7E7253	DP #s:	339827; 343065

Decision #s:	378399; 382454	PC Code	275100

From:		Tom Bloem, Chemist

		P.V. Shah, Ph.D., Toxicologist

		Registration Action Branch 1 (RAB1)/Health Effects Division (HED)
(7509P)

		Mark Dow, Ph.D., Biologist

		Risk Integration, Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (RD; 7505P)

Thru:		Dana Vogel, Branch Chief

		RAB1/HED (7509P)

To:		Daniel Rosenblatt/Susan Stanton (RM 05)

		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 all registered/proposed buprofezin uses.

A summary of the findings and an assessment of human risk resulting from
the registered/proposed buprofezin uses are provided in this document.
The risk assessment, residue chemistry review, and dietary risk
assessment were provided by Tom Bloem (RAB1), the hazard
characterization by P.V. Shah (RAB1), the occupational/residential
exposure (ORE) assessment by Mark Dow (RIMUERB), and the drinking water
assessment by Keara Moore of the Environmental Fate and Effects Division
(EFED).

Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc188838883"  1.0  EXECUTIVE
SUMMARY	  PAGEREF _Toc188838883 \h  3

  HYPERLINK \l "_Toc188838884"  2.0  PHYSICAL/CHEMICAL PROPERTIES
CHARACTERIZATION	  PAGEREF _Toc188838884 \h  7

  HYPERLINK \l "_Toc188838885"  3.0  HAZARD CHARACTERIZATION	  PAGEREF
_Toc188838885 \h  7

  HYPERLINK \l "_Toc188838886"  3.1  Hazard Profile	  PAGEREF
_Toc188838886 \h  8

  HYPERLINK \l "_Toc188838887"  3.2  FQPA Considerations	  PAGEREF
_Toc188838887 \h  8

  HYPERLINK \l "_Toc188838888"  3.3  Dose-Response Assessment	  PAGEREF
_Toc188838888 \h  10

  HYPERLINK \l "_Toc188838889"  3.4  Endocrine Disruption	  PAGEREF
_Toc188838889 \h  12

  HYPERLINK \l "_Toc188838890"  4.0  EXPOSURE ASSESSMENT	  PAGEREF
_Toc188838890 \h  12

  HYPERLINK \l "_Toc188838891"  4.1  Summary of Registered Uses
PAGEREF _Toc188838891 \h  12

  HYPERLINK \l "_Toc188838892"  4.2  Summary of Proposed Uses	  PAGEREF
_Toc188838892 \h  13

  HYPERLINK \l "_Toc188838893"  4.3  Dietary Exposure/Risk Pathway
PAGEREF _Toc188838893 \h  14

  HYPERLINK \l "_Toc188838894"  4.3.1  Food Residue Profile	  PAGEREF
_Toc188838894 \h  14

  HYPERLINK \l "_Toc188838895"  4.3.2  Water Residue Profile
Exposure/Risk Pathway	  PAGEREF _Toc188838895 \h  18

  HYPERLINK \l "_Toc188838896"  4.4  Dietary Exposure Analyses	  PAGEREF
_Toc188838896 \h  19

  HYPERLINK \l "_Toc188838897"  4.5  Residential Exposure/Risk Pathway
PAGEREF _Toc188838897 \h  20

  HYPERLINK \l "_Toc188838898"  5.0  AGGREGATE RISK ASSESSMENTS AND RISK
CHARACTERIZATION	  PAGEREF _Toc188838898 \h  20

  HYPERLINK \l "_Toc188838899"  6.0  CUMULATIVE RISK	  PAGEREF
_Toc188838899 \h  20

  HYPERLINK \l "_Toc188838900"  7.0  OCCUPATIONAL EXPOSURE	  PAGEREF
_Toc188838900 \h  21

  HYPERLINK \l "_Toc188838901"  7.1  Occupational Handler Exposure and
Risk	  PAGEREF _Toc188838901 \h  21

  HYPERLINK \l "_Toc188838902"  7.2  Post-application Exposure and Risk
 PAGEREF _Toc188838902 \h  22

  HYPERLINK \l "_Toc188838903"  7.3  REI	  PAGEREF _Toc188838903 \h  23

  HYPERLINK \l "_Toc188838904"  8.0  DATA NEEDS/LABEL REQUIREMENTS
PAGEREF _Toc188838904 \h  24

  HYPERLINK \l "_Toc188838905"  8.1  Toxicology	  PAGEREF _Toc188838905
\h  24

  HYPERLINK \l "_Toc188838906"  8.2  Residue Chemistry	  PAGEREF
_Toc188838906 \h  24

  HYPERLINK \l "_Toc188838907"  8.3  Occupational/Residential	  PAGEREF
_Toc188838907 \h  24

 1.0  EXECUTIVE SUMMARY

Background/Proposed Use:  Buprofezin is a chitin biosynthesis inhibitor
that controls a variety of Homoptera spp. (planthoppers, leafhoppers,
whiteflies, and scales) through disruption of molting, suppression of
oviposition, and reduction in egg viability.  Buprofezin is registered
to Nichino America, Inc.; the 70% wettable-powder (WP), 70% dry-flowable
(DF), and/or 40% suspension concentrate (3.6 lb/gal SC) formulations are
currently registered for repeated foliar applications to several fruit
and vegetable commodities with tolerances for residues of buprofezin per
se ranging from 0.02 - 80 ppm (40 CFR 180.511).  Tolerances have also
been established for residues of buprofezin per se, as a result of
secondary residues, in milk (0.01 ppm) and ruminant and hog fat (0.05
ppm), liver (0.05 ppm), meat (0.05 ppm) and meat byproducts (0.05 ppm).
The registered buprofezin uses are not expected result in residential
exposure.

The Interregional Research Project No. 4 (IR-4) is proposing new uses
for buprofezin on olives and members of the low-growing berry subgroup
(13G), expanding the existing use on lettuce to include all leafy
vegetables (except Brassica), and reducing the preharvest interval (PHI)
for tomato from 7 days to 1 day and expanding this use to all fruiting
vegetables.  The following tolerances for residues of buprofezin per se
were also proposed:

Strawberry	2.5 ppm

Bearberry	2.5 ppm

Bilberry	2.5 ppm

Blueberry, lowbush	2.5 ppm

Cloudberry	2.5 ppm

Cranberry	2.5 ppm

Lingonberry	2.5 ppm

Muntries	2.5 ppm

Patrtidgeberry	2.5 ppm

Olive	3.0 ppm

Olive oil 	9.0 ppm

Vegetable, leafy, except Brassica, group 4	25 ppm

Vegetable, fruiting, group 8 	1.8 ppm

Okra	1.8 ppm

Hazard Characterization and Dose Response:  Buprofezin falls into
Toxicity Category III for acute oral toxicity and Toxicity Category IV
for acute dermal toxicity, acute inhalation toxicity, eye irritation,
and dermal irritation.  It is not a dermal sensitizer.

In subchronic toxicity studies, the primary effects of concern in the
rat were increased microscopic lesions in male and female liver and
thyroid, increased liver weights in males and females, and increased
thyroid weight in males.  In chronic studies in the rat, an increased
incidence of follicular cell hyperplasia and hypertrophy in the thyroid
of males were reported.  Increased relative liver weights were reported
in female dogs.  Buprofezin was not carcinogenic to male and female
rats.  In the mouse, increased absolute liver weights in males and
females, along with an increased incidence of hepatocellular adenomas
and hepatocellular adenomas plus carcinomas in females were reported.
Based on the increased incidence of liver tumors in female mice only, no
evidence of carcinogenicity in rats, and no evidence of genotoxicity in
submitted guideline studies using in vitro and in vivo genotoxicity
assays, the HED Cancer Assessment Review Committee (CARC) classified
buprofezin as having “Suggestive Evidence of Carcinogenicity, but not
sufficient to assess human carcinogenic potential."  No quantification
of cancer risk is required.  The CARC noted that although buprofezin was
negative in in vitro and in vivo genotoxicity assays, the findings from
the published literature indicate that it causes cell transformation and
induces micronuclei in vitro; however, in the absence of a positive
response in an in vivo micronucleus assay, it was concluded that
buprofezin may have aneugenic potential which is not expressed in vivo.

Developmental and reproductive toxicity studies do not raise concern for
increased susceptibility in offspring since toxicity in the offspring
was found at dose levels that were also toxic to the parent(s) and the
effects observed in the offspring were not more severe, qualitatively,
than the effects observed in the parent(s).

Dose-Response and Food Quality Protection Act Safety Factor (FQPA SF)
Decision:  The HED Hazard Identification Assessment and Review Committee
(HIARC) selected points of departure (PODs) for acute dietary (females
13-50 years old only; no acute endpoint identified for the remaining
population subgroups); chronic dietary; short- and intermediate-term
incidental oral; and short-, intermediate- and long-term dermal and
inhalation risk assessments.  The CARC classified buprofezin as
“Suggestive Evidence of Carcinogenicity, but not sufficient to assess
human carcinogenic potential;” therefore, a cancer exposure analysis
was not performed.

Table 1 summarizes the PODs chosen for the exposure scenarios assessed
as part of the current document.  Due to the lack of a comparative
28-day thyroid assay in rats (young -vs- old), a 10x database
uncertainty factor (UF) was applied to all exposure assessments based on
thyroid effects (this is a FQPA database UF for dietary and residential
assessments).  However, since the thyroid effects were seen in rats and
since it has been established that rats are more susceptible to thyroid
effects than humans, HED concluded that the interspecies UF may be
reduced to 3x for these assessments.  Based on the conservative residue
assumptions used in the dietary risk assessment (there are currently no
residential uses), the completeness of the residue chemistry and
environmental fate databases, and since there are no residual
uncertainties regarding pre- or post-natal toxicity and a developmental
neurotoxicity (DNT) study is not required, FQPA safety factors related
to these issues were reduced to 1x.  Therefore, the total UF for chronic
dietary and inhalation risk assessments is 300x (10x database
uncertainty, 3x interspecies variation, and 10x intraspecies variation;
these endpoints are based on thyroid effects) and the total UF for acute
dietary and dermal assessments is 100x (10x interspecies variation and
10x intraspecies variation; these endpoints are not based on thyroid
effects).

Table 1:  Summary of the Endpoints Chosen for the Exposure Scenarios
Assessed as part of the Current Document.

Risk Assessment Scenario	Dose Used in Risk Assessment	Level of Concern
(LOC) for Risk Assessment	Study and Endpoint

Acute Dietary:  females 13-50 yrs old	aPAD1=

2.0 mg/kg/day	(100% of aPAD	developmental toxicity study/rats:  based on
reduced ossification & decreased body weight in offspring.

Chronic Dietary:  general population	cPAD=

0.0033 mg/kg/day	(100% of cPAD	2-yr chronic feeding study/rats:
increased incidence of follicular cell hyperplasia and hypertrophy in
the thyroid in males.

Short-term and Intermediate-term Dermal	dermal NOAEL = 300 mg/kg/day
MOEs2≤100	24-day dermal toxicity study in rats: inflammatory
infiltrate of the liver in females and an increase in acanthosis and
hyperkeratosis in the skin of females.

Short-term and Intermediate-term Inhalation 	oral NOAEL =

13 mg/kg/day

100% inhalation absorption	MOEs≤300	90-day oral toxicity in rats:
organ weight changes and microscopic findings in the liver and thyroid
of males and females and in the kidney of males (enlarged hepatocytes,
hepatocellular nuclei, and nucleoli in the liver; thickening and
hyperplasia of follicular epithelial cells in the thyroid, hyaline
droplets and basophilic bodies in the kidneys).

1  aPAD = acute population-adjusted dose = NOAEL ÷ (FQPA SF x
interspecies/intraspecies variation.

2  MOE = margin of exposure = NOAEL (no-observable-adverse-effect-level)
÷ exposure.

Dietary Exposure Estimates:  The acute and chronic dietary exposure and
risk assessments were conducted using the Dietary Exposure Evaluation
Model - Food Consumption Intake Database (DEEM-FCID(, ver. 2.03).
DEEM-FCID( incorporates food consumption data from the United States
Department of Agriculture (USDA) Continuing Surveys of Food Intakes by
Individuals (CSFII; 1994-1996 and 1998).

The acute analysis assumed DEEM™ (ver. 7.81) default processing
factors and 100% crop treated for all commodities.  Tolerance-level
residues were assumed for all commodities excluding meat and milk.
Since meat and milk (limit of quantitation (LOQ) tolerances) residues
were only detected in the feeding study at 6.8-9.3x the maximum
theoretical dietary burden (MTDB), residues in these commodities were
normalized to 1x the MTDB.  The acute analysis also incorporated the
acute Pesticide Root Zone Model 3 (PRZM3; Carsel,1997)/Exposure Analysis
Modeling System (EXAMS; Bums, 2002; Tier 2) surface drinking water
estimate resulting from application of buprofezin to citrus (highest
acute estimate; 2 x 2.0 lb ai/acre; retreatment interval (RTI) = 60
days).    SEQ CHAPTER \h \r 1 The resulting acute exposure estimate for
females 13-49 years old is not of concern to HED (7% acute
population-adjusted dose (aPAD)).  No acute dietary endpoint was
identified for the remaining population subgroups.

 of concern to HED (≤91% cPAD; children 1-2 years old were the most
highly exposed population).

Aggregate Risk Estimates:  The proposed/registered buprofezin uses are
not expected to result in residential exposure.  Therefore, the acute
and chronic exposure estimates provided in the Dietary Exposure Section
represent aggregate exposure.

Occupational Exposure Estimates:  Based on the proposed use patterns,
pesticide handlers are anticipated to have short- and intermediate-term
dermal and inhalation exposure and agricultural workers are anticipated
to have short- and intermediate-term post-application dermal exposure.
No chemical-specific data are available to assess potential exposures to
pesticide handlers or to estimate post-application exposure to
agricultural workers.  Therefore, for handlers, the exposure assessment
was conducted using data available in the Pesticide Handlers Exposure
Database (PHED; ver. 1.1; 1998) and the post-application exposure
assessment was conducted using the Standard Operating Procedures (SOPs)
for Residential Exposure Assessment (18-Dec-1997) with revisions by
HED’s Exposure Science Advisory Council (ExpoSAC).  In addition,
transfer coefficients (TCs) used to calculate post-application exposure
are taken from the interim TC policy developed by ExpoSAC using
propriety data from the Agricultural Re-entry Task Force (ARTF) database
(SOP 003.1).

Since short-term dermal and inhalation exposure share a common target
organ (liver), HED concluded that these routes of exposure should be
aggregated (aggregate risk index (ARI) approach due to different LOCs).
Provided mixer/loaders wear protective gloves as directed on the labels,
all ARIs are >1 and are not of concern to HED.  Based on the interim
Worker Protection Standard (WPS) and the acute toxicity data, the
proposed 12-hour restricted-entry interval (REI) is acceptable.

Recommendations:  Provided the petitioner submits revised Sections B and
F, HED concludes that the toxicological, residue chemistry, and ORE
databases support an unconditional registration for the proposed crops
and establishment of the tolerances listed in Table 2 for residues of
buprofezin per se.  HED notes that the currently established lettuce
(head and leaf) and tomato tolerances may be deleted.

Table 2:  HED-Recommended Tolerances for Residues of Buprofezin per se.

Commodity	Recommended Tolerance (ppm)

Bearberry 	2.5

Bilberry	2.5

Blueberry, lowbush	2.5

Cloudberry	2.5

Cranberry	2.5

Lingonberry	2.5

Muntries	2.5

Partridgeberry	2.5

Strawberry	2.5

Olive	3.5

Olive, oil	4.8

Vegetable, leafy, except Brassica, group 4 (except head lettuce and
radicchio)	35

Lettuce, head	6.0

Radicchio	6.0

Vegetable, fruiting, group 8 (except non-bell pepper)	1.3

Pepper, non-bell	4.0

Okra	4.0

Summary of Deficiencies:

●Revised Section B

●Revised Section F

2.0  PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

Table 3:  Nomenclature of Buprofezin.

Compound

Common name	Buprofezin

Company experimental names	BF1

IUPAC name
2-tert-butylimino-3-isopropyl-5-phenyl-3,4,5,6-tetrahydro-3H-1,3,5-thiad
iazin-4-one

CAS name
2-[(1,1-dimethylethyl)imino]tetrahydro-3(1-methylethyl)-5-phenyl-4H-1,3,
5-thiadiazin-4-one

CAS #	69327-76-0

End-use products/EP	Courier™ 70WP (EPA Reg. No. 71711-15) and
Courier™ 40%SC (EPA Reg. No. 71711-20)

Table 4:  Physicochemical Properties of the Technical Grade Test
Compound.

Melting point/range	104-106 °C

pH	7.8

Density	1.18 g/cm3

Water solubility	0.382 g/liter at 25 °C

Solvent solubility	520 g/liter - chloroform; 320 g/liter - toluene; 240
g/liter acetone

20 g/liter hexane

Vapor pressure	9.4 x 10-6 mm Hg at 20 °C

Dissociation constant (pKa)	not available

Octanol/water partition coefficient Log(KOW)	4.31 at 20 °C

UV/visible absorption spectrum	not available

3.0  HAZARD CHARACTERIZATION

HIARC:  HED Doc. Nos. 014093, 014221, and 051342; FQPA SFC:  HED Doc.
No. 014138; CARC:  HED Doc. No. 014045; Risk Assessment Documents:
D284767, T. Bloem et al., 20-Nov-2001; D327268, T. Bloem et al.,
21-Feb-2007

HED has reviewed the toxicological database and presented this
information in full in the 20-November-2001 human-health risk assessment
(D284767, T. Bloem et al.).  Since this assessment, HED has reevaluated
the UFs and toxicological data gaps (human-health risk assessment,
D327268, T. Bloem et al., 21-Feb-2007).  The following is a summary of
the information provided in these documents (Attachment 2 is a summary
of the Toxicological Profile).

The HIARC requested a 28-day inhalation toxicity study as a condition of
registration.  However, based on the low volatility and low inhalation
toxicity (Category IV) of buprofezin and inhalation MOEs >1000 for the
proposed uses, the 28-day inhalation toxicity study is waived for the
proposed uses (see HED SOP 2002.01: Guidance: Waiver Criteria for
Multiple-Exposure Inhalation Toxicity Studies, 08/15/02).  If in the
future, requests for new uses or formulations are submitted that may
result in a significant change in either the toxicity profile or
exposure scenarios, HED will reconsider this data requirement.  In
addition, the HIARC requested a comparative thyroid assay (28-day
thyroid assay; young -vs- old); HED has subsequently determined that
provided a 10x database UF is applied to all exposure scenarios based
upon thyroid effects, the submission of the comparative thyroid assay is
at the discretion of the petitioner (see D327268, T. Bloem et al.,
21-Feb-2007).

3.1  Hazard Profile

Buprofezin falls into Toxicity Category III for acute oral toxicity and
Toxicity Category IV for acute dermal toxicity, acute inhalation
toxicity, eye irritation, and dermal irritation.  It is not a dermal
sensitizer.

In subchronic toxicity studies, the primary effects of concern in the
rat were increased microscopic lesions in male and female liver and
thyroid, increased liver weights in males and females, and increased
thyroid weight in males.  In chronic studies in the rat, an increased
incidence of follicular cell hyperplasia and hypertrophy in the thyroid
of males were reported.  Increased relative liver weights were reported
in female dogs.  Buprofezin was not carcinogenic to male and female
rats.  In the mouse, increased absolute liver weights in males and
females, along with an increased incidence of hepatocellular adenomas
and hepatocellular adenomas plus carcinomas in females were reported.
Based on the increased incidence of liver tumors in female mice only, no
evidence of carcinogenicity in rats, and no evidence of genotoxicity in
submitted guideline studies using in vitro and in vivo genotoxicity
assays, the CARC (HED Doc. No. 014045) classified buprofezin as having
“Suggestive Evidence of Carcinogenicity, but not sufficient to assess
human carcinogenic potential."  No quantification of cancer risk is
required.  The CARC noted that although buprofezin was negative in in
vitro and in vivo genotoxicity assays, the findings from the published
literature indicate that it causes cell transformation and induces
micronuclei in vitro; however, in the absence of a positive response in
an in vivo micronucleus assay, the was concluded that buprofezin may
have aneugenic potential which is not expressed in vivo.

The developmental toxicity study in the rat produced reduced
ossification and reduced pup weight at maternally toxic doses (death,
decreased pregnancy rates, increased resorption rates).  No
developmental toxicity was observed in the rabbit at or below maternally
toxic dose levels.  The reproductive toxicity study showed decreased pup
body weights at dose levels where liver effects (increased relative
and/or absolute liver weights) and decreased body weight gains were
observed in the parental generations.  These studies do not raise
concern for increased susceptibility in offspring since toxicity in the
offspring was found at dose levels that were also toxic to the parent(s)
and the effects observed in the offspring were not more severe,
qualitatively, than the effects observed in the parent(s).  These data
do not indicate a basis for concern for neurotoxicity.  The rat
metabolism study indicated that 95% of the administered dose was
excreted in urine and feces within 72 hours (feces - 79.1%; urine -
12.9%).  In the feces, about 45% of the radioactivity was recovered as
parent compound, with the remainder as several metabolites.  Buprofezin
does not appear to bioaccumulate.

Recommendation for Aggregate Exposure Risk Assessments:  Currently there
are no residential exposures; therefore, a discussion concerning
aggregating chronic dietary with incidental oral, dermal, and/or
inhalation exposures is unnecessary.  However, agricultural workers are
anticipated to have short- and intermediate-term dermal and inhalation
exposure (long-term dermal and inhalation exposures are not
anticipated).  Since short- and intermediate-term dermal and inhalation
exposure share a common target organ (liver), HED concluded that these
routes of exposure should be aggregated.

3.2  FQPA Considerations

At a meeting held on 22-Oct-2002, the HIARC concluded that the
toxicology database for buprofezin is complete for FQPA assessment.  It
was concluded that developmental toxicity studies in rats and rabbits
and the 2-generation reproduction study in rats provided no indication
of increased susceptibility of rats or rabbits following in utero
exposure or of rats following pre/postnatal exposure to buprofezin (see
previous page).  HED notes that there is evidence of thyroid toxicity
following subchronic and chronic exposures to rats as well as chronic
exposures to dogs characterized as decreases in serum thyroxine levels
and increased thyroid weights in dogs and histopathological lesions in
the subchronic and chronic toxicity studies in rats.  However, HED
concludes that a DNT study is not required since this study would not
address thyroid toxicity concerns. Instead, a comparative thyroid assay
(28-day; young -vs- adult) animals conducted with buprofezin would be
more appropriate as this study would determine if the thyroid effects
occur at a lower dose in young -vs- adult animals.  HED notes that
although rats are very susceptible to thyroid hormone disruption and
thyroid follicular cell carcinogenesis, no thyroid tumors were observed
in chronic and carcinogenicity studies in mice and rats.  Given the
marginal thyroid toxicity found, it is anticipated that any effects of
buprofezin on thyroid hormones may also be marginal.  Thus, the
requested comparative thyroid assay study in rats is viewed as a
confirmatory test to evaluate its effect on thyroid homeostasis.  Since
the petitioner has not submitted the requested comparative thyroid
assay, HED concludes that a database UF of 10x should be applied to all
exposure assessments whose endpoint is based on thyroid effects.  The
database UF is not applicable to the acute endpoint since a single dose
of a chemical would not be expected to perturb thyroid  homeostasis in
the adult or the young due to the buffering of thyroid hormone
concentrations by homeostatic mechanisms for compounds with short half
lives, like buprofezin (half-life = 1 to 2 days).  This database UF was
not applied to dermal exposure assessments because no thyroid effects
were seen in a dermal toxicity study (thyroid effects were monitored).
In addition, since it has been established that rats are more
susceptible to thyroid effects than humans, HED concluded that the
interspecies UF may be reduced to 3x for all exposure assessments whose
endpoint is based on thyroid effects seen in rats. Based on the
conservative residue assumptions used in the dietary risk assessment
(there are currently no residential exposures), the completeness of the
residue chemistry and environmental fate databases, and since there are
no residual uncertainties regarding pre- or post-natal toxicity, FQPA
safety factors related to these issues were reduced to 1x.  Table 5 is a
summary of the UFs applicable to the current risk assessment.

Table 5:  Summary of UFs for Buprofezin.

Safety Factors	Factor	Rationale for the Factor	Endpoints the Factor is
Applied

LOAEL to NOAEL

(FQPA UFL and UFL)	1x	all PODs are based on a NOAEL	all

Subchronic to Chronic

(FQPA UFS and UFS)	1x	subchronic studies not used for chronic exposure
assessments	all

Incomplete Database

(FQPA UFDB and UFDB)	10x1	comparative thyroid assay in rats (thyroid
hormone measurements; adult versus young animals)1	all exposure
assessment whose endpoint is based on rat thyroid effects

Uncertainties related to exposure and residual uncertainties regarding
pre- or post-natal toxicity (SFFQPA)	1x	based on the res. chem. and
environmental fate databases, conservative residue assumptions used in
the dietary exposure analyses (currently no residential exposures), and
no residual uncertainties regarding pre- or post-natal toxicity	all
assessments conducted as part of the current review

Inter-/Intra-species variation (UFA/H)	100x	default (10x/10x
intra-/inter-species variation)	all exposure assessments whose endpoint
is not based on rat thyroid effects

Inter-/Intra-species variation (UFA/H)	30x	default 10x intraspecies
variation factor and reduction in the interspecies variation factor from
10x to 3x as it has been demonstrated that rats are more susceptible to
thyroid effects than humans 	all exposure assessments whose endpoint is
based on rat thyroid effects

1  Provided a 10x database UF is applied to all exposure scenarios based
upon thyroid effects, the submission of the comparative thyroid assay is
at the discretion of the petitioner (see D327268, T. Bloem et al.,
21-Feb-2007).

3.3  Dose-Response Assessment

A summary of buprofezin PODs for occupational assessments are provided
in Table 6.  A summary of buprofezin PODs for dietary and residential
assessments are provided in Table 7.  Residential dermal, inhalation,
and incidental oral assessments are not required as part of this
assessment and the LOCs given in Table 7 assumes a SFFQPA  of 1x.

Table 6:  Summary of Toxicological Dose and Endpoints for Occupational
Buprofezin Exposure Assessments.

Exposure

Scenario	POD	UFs and LOC for Risk Assessment	Study and Toxicological
Effects

Short-Term Dermal

≤ 100	24-day Dermal Toxicity Study - Rat; LOAEL = 1000 mg/kg/day based
on inflammatory infiltrate of the liver in females and an increase in
acanthosis and hyperkeratosis of the skin in females.

Intermediate-Term Dermal

(1-6 Months)	Dermal NOAEL=300 mg/kg/day	UF1 = 1x; UFA/H2= 100x

LOC MOEs ≤ 100	24-day Dermal Toxicity Study - Rat; LOAEL = 1000
mg/kg/day based on inflammatory infiltrate of the liver in females and
an increase in acanthosis and hyperkeratosis of the skin in females.

Long-Term Dermal

(>6 Months)	Oral NOAEL= 1.0 mg/kg/day

10% dermal penetration	UF1 = 10x; UFA/H2= 30x

LOC MOEs ≤ 300	Two-Year Chronic/Feeding Study - Rat; LOAEL = 8.7
mg/kg/day based on increased incidence of follicular cell hyperplasia
and hypertrophy in the thyroid in males.

Short-Term Inhalation

(1-30 days)	Oral NOAEL= 13.0 mg/kg/day

100% inhalation absorption	UF1=10x; UFA/H2= 30x

LOC MOEs ≤ 300	90-day Oral Toxicity Study - Rat; LOAEL = 68.6
mg/kg/day based on organ weight changes and microscopic findings in the
liver and thyroid of both males and females and in the kidney of males.

Intermediate-Term Inhalation

(1-6 Months)	Oral NOAEL= 13.0 mg/kg/day

100% inhalation absorption	UF1=10x; UFA/H2= 30x

LOC MOEs ≤ 300	90-day Oral Toxicity Study - Rat; LOAEL = 68.6
mg/kg/day based on organ weight changes and microscopic findings in the
liver and thyroid of both males and females and in the kidney of males.

Long-Term Inhalation

(>6 Months)	Oral NOAEL= 1.0 mg/kg/day

100% inhalation absorption	UF1=10x; UFA/H2= 30x

LOC MOEs ≤ 300	Two-Year Chronic/Feeding Study - Rat; LOAEL = 8.7
mg/kg/day based on increased incidence of follicular cell hyperplasia
and hypertrophy in the thyroid in males.

Cancer 	Classification: “Suggestive Evidence of Carcinogenicity, but
not sufficient to assess human carcinogenic potential.”

1  UF = total of UFL, UFS, and UFDB (see Table 5).

2  UFA/H = intraspecies and interspecies UFs (see Table 5).

Table 7:  Summary of Toxicological Dose and Endpoints for Dietary and
Residential Buprofezin Exposure Assessments.

Exposure

Scenario	POD	FQPA SFs and LOC for Risk Assessment	Study and
Toxicological Effects

Acute Dietary

(females 13 - 50 yrs old)	Oral NOAEL = 200  mg/kg/day	FQPA SF1=1x;
UFA/H2=100x

aPAD = NOAEL÷(UFA/H x FQPA SF) = 2.0 mg/kg/day	Developmental Toxicity
Study - Rat; LOAEL = 800 mg/kg/day based on reduced ossification &
decreased body weight in offspring.

Acute Dietary

(general population including infants and children)	No appropriate
endpoint was identified for the general population which might occur
following a single dose or exposure, including maternal toxicity in
developmental studies.

Chronic Dietary

(all populations)	Oral NOAEL = 1.0 mg/kg/day	FQPA SF1=10x; UFA/H2=30x

cPAD = NOAEL÷(UFA/H x FQPA SF) = 0.0033 mg/kg/day	Two-year chronic
toxicity/ carcinogenicity Study - Rat; LOAEL = 8.7 mg/kg/day based on
increased incidence of follicular cell hyperplasia and hypertrophy in
the thyroid of males.

Short-Term Incidental oral

(1-30 Days)	Oral NOAEL= 13.0 mg/kg/day	FQPA SF1=10x; UFA/H2=30x

Residential LOC MOEs ≤ 3003	90-day Oral Toxicity Study - Rat; LOAEL =
68.6 mg/kg/day based on organ weight changes and microscopic findings in
the liver and thyroid of both males and females and in the kidney of
males.

Intermediate-Term Incidental oral

(1-6 Months)	Oral NOAEL= 13.0 mg/kg/day	FQPA SF1=10x; UFA/H2=30x

Residential LOC MOEs ≤ 3003	90-day Oral Toxicity Study - Rat; LOAEL =
68.6 mg/kg/day based on organ weight changes and microscopic findings in
the liver and thyroid of both males and females and in the kidney of
males.

Short-Term Dermal

(1-30 days)	Dermal NOAEL=300 mg/kg/day	FQPA SF1 = 1x; UFA/H2=100x

Residential LOC MOEs ≤ 1003	24-day Dermal Toxicity Study - Rat; LOAEL
= 1000 mg/kg/day based on inflammatory infiltrate of the liver in
females and an increase in acanthosis and hyperkeratosis of the skin in
females.

Intermediate-Term Dermal

(1-6 Months)	Dermal NOAEL=300 mg/kg/day	FQPA SF1 = 1x; UFA/H2=100x

Residential LOC MOEs ≤ 1003	24-day Dermal Toxicity Study - Rat; LOAEL
= 1000 mg/kg/day based on inflammatory infiltrate of the liver in
females and an increase in acanthosis and hyperkeratosis of the skin in
females.

Long-Term Dermal

(>6 Months)	Oral NOAEL= 1.0 mg/kg/day

10% dermal penetration	FQPA SF1 = 10x; UFA/H2=30x

≤ 3003	Two-Year Chronic/Feeding Study - Rat; LOAEL = 8.7 mg/kg/day
based on increased incidence of follicular cell hyperplasia and
hypertrophy in the thyroid in males.

Short-Term Inhalation

(1-30 days)	Oral NOAEL= 13.0 mg/kg/day

100% inhalation absorption	FQPA SF1=10x; UFA/H2=30x

Residential LOC MOEs ≤ 3003	90-day Oral Toxicity Study - Rat; LOAEL =
68.6 mg/kg/day based on organ weight changes and microscopic findings in
the liver and thyroid of both males and females and in the kidney of
males.

Intermediate-Term Inhalation

(1-6 Months)	Oral NOAEL= 13.0 mg/kg/day

100% inhalation absorption	FQPA SF1=10x; UFA/H2=30x

Residential LOC MOEs ≤ 3003	90-day Oral Toxicity Study - Rat; LOAEL =
68.6 mg/kg/day based on organ weight changes and microscopic findings in
the liver and thyroid of both males and females and in the kidney of
males.

Long-Term Inhalation

(>6 Months)	Oral NOAEL= 1.0 mg/kg/day

100% inhalation absorption	FQPA SF1=10x; UFA/H2=30x

Residential LOC MOEs ≤ 3003	Two-Year Chronic/Feeding Study - Rat;
LOAEL = 8.7 mg/kg/day based on increased incidence of follicular cell
hyperplasia and hypertrophy in the thyroid in males.

Cancer 	Classification: “Suggestive Evidence of Carcinogenicity, but
not sufficient to assess human carcinogenic potential.”

1  FQPA SF = total of FQPA UFL, FQPA UFS, FQPA UFDB, and/or SFFQPA (see
Table 5).

2  UFA/H = intraspecies and interspecies UFs (see Table 5).

3  LOC for residential incidental-oral, inhalation, and dermal exposure
assessments assumes a 1x SFFQPA.

 3.4  Endocrine Disruption

EPA is required under the Federal Food Drug and Cosmetic Act (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, buprofezin may be subjected to
further screening and/or testing to better characterize effects related
to endocrine disruption.

4.0  EXPOSURE ASSESSMENT

-D340284, T. Bloem, 16-Jan-2008 (residue chemistry review)

-D346965, T. Bloem, 16-Jan-2008 (dietary exposure review)

-D339828, K. Moore, 7-Jan-2008 (EFED water estimates)

4.1  Summary of Registered Uses

There are currently three end-use products for buprofezin registered to
Nichino America, Inc. for use on food/feed crops, including a 70% WP
(APPLAUD( 70WP, EPA Reg. No. 71711-15), a 70% DF (APPLAUD( 70DF, EPA
Reg. No. 71711-21), and a 3.6 lb/gal SC (Courier 40SC, EPA Reg. No.
71711-20).  The 70% WP and/or 70% DF formulations are registered for
uses on almonds, pistachios, bananas, pome fruits, stone fruit, citrus
fruits, grapes, and various tropical fruits, and the 3.6 lb/gal SC
formulation is registered for uses on cotton, cucurbit vegetables,
lettuce, snap beans, and tomatoes.  Applications may be made using
ground or aerial equipment, and rates range from 0.25-0.38 lb ai/A for
field and vegetable crops and 0.39-2.0 lb ai/A for perennial fruit crops
(0.70 - 3.16 lbs ai/acre/season).  Buprofezin is not currently
registered for application in the residential setting.

Tolerances for residues of buprofezin per se in/on plant commodities
ranging from 0.02 - 80 ppm (40 CFR 180.511) are currently established.
Tolerances have also been established for residues of buprofezin per se,
as a result of secondary residues, in milk (0.01 ppm) and ruminant and
hog fat (0.05 ppm), liver (0.05 ppm), meat (0.05 ppm) and meat
byproducts (0.05 ppm).

4.2  Summary of Proposed Uses

IR-4 is proposing the following:  a new use for the 70% DF on olives to
control scales; a new use for the 3.6 lb/gal SC on low-growing berries
subgroup 13G to control whiteflies; expanding the existing use for the
3.6 lb/gal SC on lettuce to include all leafy vegetables (except
Brassica); and reduction in the tomato PHI from 7 days to 1 day for the
3.6 lb/gal SC and expanding this use to all fruiting vegetables.

Proposed 70% DF and 3.6 lb/gal SC labels were provided.  The labels
indicate that application through irrigation equipment is prohibited and
indicate the following rotational crop restrictions:  crop listed on the
label may be planted at any time, small grain crops and leafy vegetable
may be planted 30 days after application, and all other crops may be
planted 60 days following application. Both labels include a REI of 12
hours and indicated that occupational pesticide handlers must wear
personal-protective equipment (PPE) composed of a long-sleeved shirt,
long pants, shoes plus socks, chemical-resistant gloves (EC label only),
water-resistant gloves (DF label only), and protective eyewear (EC label
only).  Table 8 is a summary of the proposed use directions.

The label directions are adequate to allow evaluation of the residue
data relative to the proposed use.  Based on the available residue
chemistry data, a revised Section B which incorporates the following
changes should be submitted:  (1) a minimum RTI of 7 days should be
specified for all leafy vegetable crops; (2) the reference to grapes
should be removed from the use directions for olives; (3) the 3.6 lb/gal
SC label should be revised to prohibit the application to all greenhouse
grown crops except tomatoes (Chemistry Science Advisory Council
(ChemSAC) minutes the 9-Oct-2002 and 28-Nov-2007 meetings); and (4) the
following rotational crop intervals should be specified:  0 days for all
labeled crops, 30 days for leafy vegetables, 60 days for root and tuber
vegetables, and 365 days for all other crops.

Table 8:  Summary of Directions for Use of Buprofezin.

Applic. Timing, Type,

and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate  (lb ai/A)	Max. No. App. per Season	Max.
Seasonal App. Rate (lb ai/A)	PHI

(days)	Use Directions and Limitations

Bearberry, Bilberry, Lowbush Blueberry, Cloudberry, Cranberry,

Lingonberry, Muntries, Partridgeberry, and Strawberry

Broadcast foliar, during fruiting.  Ground equipment.	3.6 lb/gal SC

uipment  in 80-120/≥5 GPA1; a minimum RTI of 10 days is specified

Leafy Vegetables (except Brassica)

Broadcast foliar, during vegetative development.  Ground or air
equipment.	3.6 lb/gal SC

[71711-20]	0.25-0.38	2/crop cycle

4/year	0.76/crop

1.53/year	7	Apply by ground/air equipment in ≥20/≥5 GPA; a minimum
7-day RTI is specified for lettuce.

Olive

Broadcast foliar, during fruit development.

Ground equipment	70% DF

[71711-21]	1.51- 2.01	2	4.11	21	Apply by ground/air equipment in
111-150/≥5 GPA; a minimum 50-day RTI is specified.

Fruiting Vegetables (eggplant, groundcherry, okra, pepino, pepper
(including bell pepper, chili pepper, cooking pepper, pimento, and sweet
pepper) and tomato)

Broadcast foliar; Ground or air equipment.	3.6 lb/gal SC

Apply by ground/air equipment in  ≥20/≥5 GPA; for greenhouse-grown
tomatoes apply in a minimum of 20 GPA; a minimum 5-day RTI is specified.

1  GPA = gallons per acre.

4.3  Dietary Exposure/Risk Pathway

4.3.1  Food Residue Profile

or the BF4 conjugates, reduction of the DEEM™ (ver. 7.81) default
processing factors for fruit crops and in crops with an extended
interval from initial application to harvest is inappropriate.

Table 9:  Summary of MARC decisions for Buprofezin.

Matrix	Residues of Concern

	For Risk Assessment	For Tolerance Expression

plants	buprofezin1,2	buprofezin

rotational crops	buprofezin, BF9, and BF12	buprofezin

ruminant tissue	buprofezin and  BF2	buprofezin

milk	buprofezin and BF23	buprofezin

poultry and eggs	Due to the limited residues in egg and tissue samples
collected from the poultry metabolism study, the MARC determined that a
conclusion pertaining to the residues of concern in egg and poultry was
not possible.

water	buprofezin	not applicable

1  The residues of concern in fruit crops and crops with an interval
greater than ~50 days from initial application to harvest are buprofezin
and BF4 conjugates.

2  Residues of concern in grape juice are buprofezin, BF4 conjugates,
and BF12; BF12 is a residue of concern in grape juice because the BF12
grape juice processing factor (0.75x) is much greater than the
buprofezin grape juice processing factor (0.14x) and residues of BF12
may be significant in grape juice.

Plants:  Buprofezin was the major residue identified in the lettuce,
cotton, and tomato metabolism studies (all other identified residues
were at <10% total radioactive residue (TRR)).  The lemon metabolism
study provided data for fruit treated 75 and 14 days prior to harvest
and treated only 75 days prior to harvest.  Buprofezin (66% TRR,
preharvest interval (PHI) = 14 days; 18% TRR, PHI = 75 days) and BF 4
conjugates (6% TRR, PHI = 14 days; 34% TRR, PHI = 75 days) were the
major identified residues (all other identified residues were <10% TRR).
 Based on the results of these studies, the MARC made the conclusions
summarized in Table 9.

The MARC also requested that the petitioner submit orange, apple, and
grape processing studies conducted using the labeled retreatment and
preharvest intervals but at 5x the labeled rate.  The processing studies
should employ an analytical method which includes a hydrolysis step and
monitor for residues of BF9, BF12, and BF26 (BF9, BF12, and BF26 are
hydrolysis products of BF4 conjugates).  These data will enable HED to
determine the potential magnitude of BF4 conjugates in the RACs
(normalized to 1x) and determine if the BF4 conjugates, if present,
possess different processing factors than parent.  The need for
additional BF4 conjugate magnitude of the residue data will be
determined upon submission and review of these data.

Ruminants:  BF2 was the major residue identified in liver and kidney
(residue in fat and muscle were (0.020 ppm) and BF23 was the major
residue identified in milk from the ruminant metabolism study (all other
residue were <10% TRR; 3.5x MTDB).  The petitioner also submitted a
poultry metabolism study (131x the MTDB).  Based on these data the MARC
concluded the following:  (1) due to the low TRRs in egg and tissue
samples collected from the poultry metabolism study, the nature of the
residue in poultry could not be determined; (2) the tolerance expression
for milk and ruminant tissues will include only buprofezin; (3) for
purposes of risk assessment, the residues of concern in milk are
buprofezin and BF23; (4) for purposes of risk assessment, the residues
of concern in ruminant tissues are buprofezin and BF2.

Rotational Crops:  Buprofezin, BF9, and BF12 were the major residues
identified in the confined rotational crop study.  However, the field
rotational crop studies resulted in the identification of only
buprofezin.  Provided the petitioner validated the storage intervals
used in the field rotational study (validation of buprofezin, BF 9 and
BF 12 is necessary), the MARC concluded that buprofezin was the only
residue of concern in rotated crops.

The petitioner validated the storage interval for all commodities from
the field rotational crop study excluding BF9 and BF12 in/on wheat grain
and wheat straw (46804701.der.wpd).  The wheat grain and wheat straw
storage stability data resulted in recovers of <70% for the intervals
employed in the field rotational crop study; therefore, the <LOQ BF9 and
BF12 residues measured in wheat grain and wheat straw are not validated
and HED can not exclude BF9 and BF12 as residues of concern in
rotational crops.

Magnitude of the Residue - Plants:  The petitioner submitted adequate
field trial and processing studies to support the application of the
proposed formulations to the proposed crops; the number and locations of
the field trials are sufficient and the samples were analyzed using an
adequately validated method (storage intervals were also validated;
Table 10 is a summary of the field trial data).  Based on these data and
the tolerance maximum residue limit (MRL) calculator, HED concludes that
the tolerances listed in Table 11 for residues of buprofezin per se are
appropriate.  A revised Section F is requested.

Table 10:  Summary of Residue Data from Crop Field Trials with
Buprofezin.

Crop matrix	Total App. Rate  (lb ai/A)	Analyte	PHI (days)	Residue Levels
(ppm)1,2

n	Min.	Max.	HAFT3	Median	Mean	Std. Dev.

Strawberry (proposed use = 2 x 0.38 lb ai/A; 2-day PHI)

Strawberry	0.676-0.707	Buprofezin	2-4	18	0.10	1.20	1.15	0.44	0.58	0.31

Olive (proposed use = 2 x 2.01 lb ai/A; 21-day PHI)

Olives	4.23-4.33	Buprofezin	21-23	8	0.41	1.66	1.60	1.10	1.07	0.43

Leafy Vegetables (except Brassica; proposed use = 2 x 0.38 lb ai/A;
7-day PHI)

Spinach	0.758-0.778	Buprofezin	7	12	0.71	18.10	16.70	6.74	7.18	5.05

BF9

12	<0.01	<0.01	<0.01	<0.01	<0.01	--

BF12

12	<0.01	<0.01	<0.01	<0.01	<0.01	--

Celery	0.746-0.794	Buprofezin	7	12	0.35	12.00	11.25	2.97	4.10	3.59

BF9

12	<0.01	0.04	0.04	0.01	0.01	0.01

BF12

12	<0.01	<0.01	<0.01	<0.01	<0.01	--

Lettuce, leaf4	1.525	Buprofezin	7	9	1.18	11.49	11.49	6.08	6.12	4.00

	10	9	0.67	7.81	7.81	4.02	4.07	2.87

	14	9	0.13	5.49	5.49	2.23	2.37	2.07

BF9	7, 10,  and 14	24	<0.01	<0.01	<0.01	<0.01	<0.01	--

BF12

24	<0.01	<0.01	<0.01	<0.01	<0.01	--

Lettuce, head

(with wrapper leaves)4	1.525	Buprofezin	7	11	0.27	4.41	4.41	2.02	1.99
1.12

	10	11	0.14	4.30	4.30	0.48	0.95	1.16

	14	11	0.02	4.56	4.56	0.50	0.82	1.29

BF9	7, 10,  and 14	30	<0.01	<0.01	<0.01	<0.01	<0.01	--

BF12

30	<0.01	<0.01	<0.01	<0.01	<0.01	--

Lettuce, head

(without wrapper leaves)4	1.525	Buprofezin	7	9	0.03	1.33	1.33	0.17	0.33
0.43

	10	9	0.01	0.46	0.46	0.03	0.10	0.15

	14	9	0.01	0.29	0.29	0.03	0.07	0.09

BF9	7, 10,  and 14	30	<0.01	<0.01	<0.01	<0.01	<0.01	--

BF12

30	<0.01	<0.01	<0.01	<0.01	<0.01	--

Fruiting Vegetables (proposed use = 2 x 0.38 lb ai/A; 1 day PHI)

Bell pepper	0.746-0.787	Buprofezin	1	16	0.10	0.96	0.86	0.31	0.34	0.24

Non-bell pepper	0.761-0.785	Buprofezin	1	6	0.10	1.10	1.05	0.48	0.56	0.42

Tomato6	0.747-0.826	Buprofezin	1	56	0.016	0.539	0.471	0.098	0.129	0.102

	0.752-0.763	BF9	1	8	<0.01	<0.01	<0.01	<0.01	<0.01	--

	0.752-0.763	BF12	1	8	<0.01	<0.01	<0.01	<0.01	<0.01	--

	0.747-0.788	BF26	1	6	<0.01	<0.01	<0.01	<0.01	<0.01	--

1  Residues are expressed in terms of each analyte.

2  The validated LOQ is 0.01 ppm for each analyte in leafy vegetable
crops;  the validated LOQ for BF9, BF12, and BF26 in tomato is 0.01 ppm;
 the LLMV for the remaining crop/analyte combinations is 0.05 ppm.  For
calculation of median, mean and standard deviation, the method LOQ was
assumed for residue values <LOQ.

3  HAFT = Highest-Average Field Trial.

4  Residue values for lettuce were obtained from an earlier HED review
(D261869, 4/24/00, T. Bloem).

5  Although the lettuce field trials were conducted at 2x the maximum
seasonal rate, the single application rates used in the field trials
(~0.38 lb ai/A) were equivalent to 1x maximum single rate, and HED has
concluded that the two earliest applications would not contribute
substantially to overall residue levels (D296493, 12/17/03, T. Bloem).
Therefore, the available lettuce data are acceptable for supporting the
maximum labeled rate 0.77 lb ai/A/crop.

6  This summary includes tomato field trials submitted as part of the
current petition as well as tomato field trials submitted and reviewed
as part of an earlier petition (D340901, 9/7/2007, T. Bloem).

Magnitude of the Residue - Rotational Crops/Livestock:  Since there are
not feed commodities associated with the proposed crops (see OPPTS
860.1000 Table 1) and provided revised labels are submitted, issues
concerning the magnitude of the residue in livestock and rotational
crops are not relevant to this petition.

Enforcement Methods - Plants:  The methods used in the field trial
studies were adequately validated and are similar to the method
validated by the Analytical Chemistry Branch (ACB) and forwarded to the
Food and Drug Administration (FDA) for publication in the Pesticide
Analytical Manual I (PAM I; D278950, T. Bloem, 8- Nov-2001; D278952, T.
Bloem, 8-Nov-2001; D324423, T. Bloem, 14-Dec-2005).  Since adequate
method validation and concurrent recoveries were attained in the field
trial studies, HED concludes that the method validated by ACB is
appropriate for enforcement of the tolerances associated with these
petitions.

FDA Multiresidue Methods:  The petitioner submitted data concerning the
behavior of buprofezin through FDA multiresidue testing Protocols C –
F.  Acceptable results were attained for buprofezin under the GC
conditions specified in Protocol C.  Acceptable recoveries of buprofezin
were attained from tomatoes using Protocol D Method 302 E1 without the
optional Florisil column and Protocol E Method 303 E1 with Florisil
cleanup C1 or C2.  Acceptable recoveries of buprofezin were attained
from cottonseed using Protocol F Method 304 E5 with Florisil cleanup C1
or C2.  This information has been forwarded to FDA (D262532, T. Bloem,
4-Feb-2000).

Proposed and Recommended Tolerances:  Table 11 is a summary of the
HED-recommended tolerances for residues of buprofezin per se.  Except
for tomato, there are currently no established Codex, Canadian, or
Mexican MRLs for residues of buprofezin per se in/on the proposed
commodities.  For tomato, there are Codex and Mexican MRLs for residues
of buprofezin per se of 1 ppm and 0.5 ppm, respectively.  HED notes that
the MRL harmonization tolerance calculator recommended for 0.45 ppm
tomato tolerance; however, this tolerance is based on residue data which
employed a ~28-day RTI rather than the proposed 5-day RTI.  Therefore,
the recommended 0.45 ppm tolerance may be to low and HED concluded that
it would be more appropriate to set the tomato tolerance based on the
bell pepper residue data (see D340284 (T. Bloem, 16-Jan-2008) for
further information).  Since the international tomato MRLs are less than
the HED recommended tolerance, harmonization is not possible.  A revised
Section F is requested

Table 11:  HED-recommended Tolerances.

Commodity	HED-Recommended Tolerance (ppm)	Comments (requested revisions
to the submitted Section F)

Bearberry 	2.5	--

Bilberry	2.5

	Blueberry, lowbush	2.5

	Cloudberry	2.5

	Cranberry	2.5

	Lingonberry	2.5

	Muntries	2.5

	Partridgeberry	2.5

	Strawberry	2.5

	Olive	3.5	Increase tolerance to 3.5 ppm.

Olive, oil	4.8	Decrease tolerance to 4.8 ppm.

Vegetable, leafy, except Brassica, group 4 (except head lettuce and
radicchio)	35	Increase proposed tolerance to 35 ppm and change commodity
definition.

Lettuce, head	6.0	Propose a tolerance.

Radicchio	6.0	Propose a tolerance.

Vegetable, fruiting, group 8 (except non-bell pepper)	1.3	Decrease
tolerance to 1.3 ppm and change commodity definition.

Pepper, non-bell	4.0	Propose a tolerance.

Okra	4.0	Increase tolerance to 4.0 ppm.

4.3.2  Water Residue Profile Exposure/Risk Pathway

The MARC determined that only the parent compound, buprofezin, is of
concern in drinking water (see Table 9).

Drinking Water Fate Assessment:  Buprofezin may get into surface water
via spray drift, in solution in runoff water, or attached to soil
particles eroded during runoff events.  If it reaches acidic water
(pH(5), buprofezin is expected to slowly hydrolyze.  In neutral or
alkaline water (pH(7), buprofezin will likely remain bound to sediment
or suspended particles (due to its high soil/water partitioning
coefficients), and could persist for several months if the water is
deep, static, and/or cloudy.  However, buprofezin persistence may be
reduced significantly by photolysis if the water is shallow and clear.
Based on the Henry's Law constant, buprofezin loss to air is expected to
be minor.  Although moderately persistent in soils, the use rates and
the mobility/leaching data indicated that buprofezin will have low
propensity to leach into ground water.

Modeled Drinking Water Estimates:  EFED generated the surface water and
ground water estimates using the   SEQ CHAPTER \h \r 1 PRZM3 (ver.
3.12.2; 2-May-2005)/EXAMS (ver. <IP_ADDRESS>; 25-Apr-2005) and Screening
Concentration in Ground Water (SCIGROW; Tier 1) models, respectively.
EFED also provided estimates for the concentration of buprofezin in
flooded cranberry fields using a modification of the Tier 1 Rice Model
(ver. 1.0).  The Rice Model (ver. 1.0) takes the total annual
application and calculates partitioning of the pesticide between the
water and the sediment according to a linear Kd partitioning model
(assumes an 18 inch water depth).  Concentrations are assumed to be
immediately and evenly distributed throughout the water.  Dissipation
processes such as degradation, volatilization, and dilution with
untreated water upon release are not considered by the Rice Model (ver.
1.0).  Based on the proposed cranberry application scenario (2 x 0.38 lb
ai/acre) and since the Rice Model (ver. 1.0) does not consider
degradation and dilution, HED concludes that the resulting estimate
represents a highly conservative acute concentration and is not
appropriate for chronic exposure analyses.  Table 12 is a summary of the
resulting water concentrations.

Table 12:  Estimated Drinking Water Concentrations for Buprofezin (ppb).

	Acute	Chronic	Long-term average

Surface1	57.4	12.5	9.1

Ground2	0.09	0.09	0.09

Flooded Craneberry Field3	47.9	--	--

1  PRZM/EXAMS surface water estimate based on the citrus application
scenario (2 x 2.0 lb ai/acre; RTI = 60 days); assumed the default 87% of
the basin is planted with the target crop and 100% of the target crop
treated.

2  SCI-GROW estimate assuming the citrus application scenario (2 x 2.0
lb ai/acre; RTI = 60 days).

3  Tier 1 Rice Model SCI-GROW estimate assuming the caneberry
application scenario (2 x 0.38 lb ai/acre; RTI = 10 days; 18 inch water
depth).

4.4  Dietary Exposure Analyses

The acute and chronic dietary exposure and risk assessments were
conducted using the DEEM-FCID( (ver. 2.03).  DEEM-FCID( incorporates
food consumption data from the USDA CSFII (1994-1996 and 1998).  The
current assessment is being conducted in support of a new use on olives
and the low-growing berry subgroup 13G, expanding the existing use on
lettuce to include all leafy vegetables (except Brassica), and reduction
in the tomato PHI from 7 days to 1 day and expanding this use to all
fruiting vegetables.

The acute analysis assumed DEEM™ (ver. 7.81) default processing
factors and 100% crop treated for all commodities.  Tolerance-level
residues were assumed for all commodities excluding meat and milk.
Since meat and milk (LOQ tolerances) residues were only detected in the
feeding study at 6.8-9.3x the MTDB, residues in these commodities were
normalized to 1x the MTDB.  The acute analysis also incorporated the
acute PRZM3/EXAMS (Tier 2) surface drinking water estimate resulting
from application of buprofezin to citrus (highest acute estimate; 2 x
2.0 lb ai/acre; RTI = 60 days).    SEQ CHAPTER \h \r 1 The resulting
acute exposure estimate for females 13-49 years old is not of concern to
HED (7% aPAD; see Table 13).  No acute endpoint was identified for the
remaining population subgroups.

(≤91% cPAD; children 1-2 years old were the most highly exposed
population; see Table 14).

Table 13:  Summary of Acute Dietary Exposure and Risk for Buprofezin.

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

Exposure (mg/kg/day)	%aPAD

Females 13-49 years old	0.67	0.134232	7

Table 14:  Summary of Chronic Dietary Exposure and Risk for Buprofezin.

Population Subgroup	cPAD (mg/kg/day)	Chronic

Exposure (mg/kg/day)	%cPAD

General U.S. Population	0.0033	0.001626	49

All Infants (< 1 year old)

0.002769	84

Children 1-2 years old

0.002999	91

Children 3-5 years old

0.002483	75

Children 6-12 years old

0.001715	52

Youth 13-19 years old

0.001155	35

Adults 20-49 years old

0.001524	46

Adults 50+ years old

0.001562	47

Females 13-49 years old

0.001531	46

4.5  Residential Exposure/Risk Pathway

There are no registered or proposed residential uses for buprofezin.
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 groundboom application methods.  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.  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 data base 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 and risks associated with aerial as well as other
application types where appropriate.

5.0  AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION

In accordance with the FQPA, when there are potential residential
exposures to a pesticide, aggregate risk assessment must consider
exposures from three major routes: oral, dermal, and inhalation.  There
are three sources for these types of exposures:  food, drinking water,
and residential uses.  In an aggregate assessment, exposures from
relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated.  When aggregating exposures and risks from various
sources, HED considers both the route and duration of exposure.

The proposed/registered buprofezin uses are not expected to result in
residential exposure.  Therefore, the acute and chronic exposure
estimates provided in the Dietary Exposure Section represent aggregate
exposure.

6.0  CUMULATIVE RISK

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 buprofezin and any other
substance and buprofezin does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA has  assumed that buprofezin does not have 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   HYPERLINK
http://www.epa.gov/pesticides/cumulative/.
http://www.epa.gov/pesticides/cumulative/.

7.0  OCCUPATIONAL EXPOSURE

-D346746, M. Dow, 5-Dec-2007

The techniques used to assess occupational risk have been developed and
refined by the HED ExpoSAC and reflect HED SOPs.  A summary of the
proposed application scenario can be found in Section 4.2.

7.1  Occupational Handler Exposure and Risk

Based upon the proposed new use patterns, HED believes the most highly
exposed occupational pesticide handlers (mixers/loaders/applicators)
will be:  (1) mixer/loader using open pour loading of liquids; (2)
mixer/loader using open-pour loading of dry flowables; (3) aerial
applicator; (4) applicator using open-cab ground-boom sprayer; and (5)
applicator using open-cab airblast sprayer.

Commercial and private/grower applicators are expected to have
short-term duration (1-30 days) exposures.  The areas planted in most of
these crops are relatively small in comparison to many monocultured
field crops such as corn, soybeans, cotton or wheat.   For all but
olive, 2 applications per season are permitted and retreatment intervals
vary from 5 – 10 days.  Although 4 applications may be made to olive,
the retreatment interval is 50 days.  In addition, HED believes that
such things as climatic factors and mechanical failures make it unlikely
that even commercial pesticide handlers would be exposed for more than
30 consecutive days.  However in this case, since the short-term
duration exposure and intermediate-term duration exposure toxicological
endpoints are the same, the risks calculated for short-term exposures
are adequate to assess intermediate-term exposures should they occur.

No chemical-specific data are available with which to assess potential
exposure to pesticide handlers (i.e., mixer/loaders and applicators).
The estimates of exposure in this document are based upon study data
available in the PHED (v. 1.1, 1998).  HED is aware that some private
(i.e., grower/applicators) pesticide handlers may conduct all
functions, that is, mix/load and apply the material.  The available
exposure data for combined mixer/loader/applicator scenarios are limited
in comparison to the monitoring of these two activities separately.
These exposure scenarios are outlined in the PHED Surrogate Exposure
Guide (August 1998).   HED has adopted a methodology to present the
exposure and risk estimates separately for the job functions in some
scenarios and to present them as combined in other cases.  Most exposure
scenarios for hand-held equipment (such as hand wands, backpack
sprayers, and push-type granular spreaders) are assessed as a combined
job function.  With these types of hand-held operations, all handling
activities are assumed to be conducted by the same individual.  The
available monitoring data support this and HED presents them in this
way.  Conversely, for equipment types such as fixed-wing aircraft,
groundboom tractors, or air-blast sprayers, the applicator exposures are
assessed and presented separately from those of the mixers and loaders.
By separating the two job functions, HED determines the most appropriate
levels of PPE for each aspect of the job without requiring an
applicator to wear unnecessary PPE that may be required for a
mixer/loader (e.g., chemical-resistant gloves may only be necessary
during the pouring of a liquid formulation).

A MOE of 100 is adequate to protect occupational pesticide handlers from
dermal exposures.  Provided mixer/loaders wear protective gloves as
directed on the labels, all dermal MOEs are > 100 and the dermal risks
and are not of concern to HED.  A MOE of 300 is adequate to protect
occupational pesticide handlers from inhalation exposure.  Since all
inhalation MOEs are > 300, the inhalation risks are not of concern to
HED.  Since short-term dermal and inhalation exposure share a common
target organ (liver), HED concluded that these routes of exposure should
be aggregated (ARI approach due to different LOCs).  Provided
mixer/loaders wear protective gloves as directed on the labels, all ARIs
are >1 and are not of concern to HED.  Table 15 is a summary of
occupational exposures and risks.

Table 15:  Summary of Short- and Intermediate-Term Exposure & Risk for
Occupational Handlers.

Unit Exposure1

mg ai/lb handled	Applic. Rate

lb ai/unit	Units Treated2	Avg. Daily Exposure3

mg/kg/day	MOE4	ARI5

Mixer/Loader Open Pour Loading Liquid

Dermal:

SLNG	2.9

SLWG	0.023

Inhal.:	0.0012	0.38 lb ai/A	350 A/day	Dermal:

SLNG6 	5.51

SLWG6 	0.044

Inhal.:	0.0023	Dermal:

SLNG	54

SLWG	6,800

Inhal.:	5,700	SLNG	0.52

SLWG	15

Mixer/Loader Open Pour Loading Dry Flowable

Dermal:

SLNG	0.0084

SLWG	0.0069

Inhal.:	0.0017	2.0 lb ai/A	40 A/day	Dermal:

SLNG	0.0096

SLWG	0.0079

Inhal.:	0.0019	Dermal:

SLNG	31,000

SLWG	38,000

Inhal.:	6,800	SLNG	21

SLWG	21

Aerial Applicator7

Dermal:

SLNG	0.0050

Inhal.:	0.000068	0.38 lb ai/A	350 A/day	Dermal:

SLNG	0.0095

Inhal.:	0.00013	Dermal:

SLNG	32,000

Inhal.:	100,000	SLNG	160

Applicator – Open Cab Groundboom

Dermal:

SLNG	0.014

SLWG	0.014

Inhal.:	0.00074	0.38 lb ai/A	200 A/day	Dermal:

SLNG	0.015

SLWG	0.015

Inhal.:	0.0008	Dermal:

SLNG	20,000

SLWG	20,000

Inhal.:	16,000	SLNG	43

SLWG	43

Applicator – Open Cab Airblast

Dermal:

SLNG	0.36

SLWG	0.24

Inhal.:	0.0045	2.0 lb ai/A	40 A/day	Dermal:

SLNG	0.41

SLWG	0.27

Inhal.:	0.0051	Dermal:

SLNG	700

SLWG	1,100

Inhal.:	2,500	SLNG	3.8

SLWG	4.7

1  Unit Exposures are taken from PHED (Ver. 1.1, 1998).   Inhal. =
Inhalation.  Units = mg a.i./pound of active ingredient handled. 2
Units Treated are taken from “Standard Values for Daily Acres Treated
in Agriculture”; SOP  No. 9.1.  ExpoSAC  (Revised 5- Jul-2000).

3  Average Daily Dose (ADD) = Unit Exposure x Applic. Rate x Units
Treated ( Body Weight (70 kg).

4  MOE = NOAEL ( ADD.  NOAEL = 300 mg/kg/day for short- and
intermediate-term dermal and 13.0 mg/kg/day for short- and
intermediate-term inhalation.

5  ARI = 1 ÷ ((1÷MOEdermal ÷ MOELOC dermal)+(1÷MOEinhalation ÷
MOELOC inhalation)

6  SLNG = long-sleeved short, long pants, socks, and shoes (no gloves);
SLWG = long-sleeved short, long pants, socks,  shoes, and gloves.

7  Pilots not required to wear protective gloves.

7.2  Post-application Exposure and Risk

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@

 “SOPs for Residential Exposure Assessments (18-Dec-1997)" with
revisions by the ExpoSAC.

The ExpoSAC  SOP Number 003.1 (Revised 7-Aug-2000) and amended by
“ExpoSAC meeting Notes - 13-Sep-2001") lists a number of possible
post-application agricultural activities relative to the proposed crop
uses that might result in post-application, “re-entry” exposure.
Hand harvesting results in the highest TC for all the proposed new crop
uses.  For fruiting vegetables, the TC is 1,000 cm2/hr; for leaf petiole
vegetables and for olive, the TC is 2,500 cm2/hr; and for high-bush
blueberries, the TC is 5,000 cm2/hr.  Although hand harvesting high-bush
blueberries results in the highest TC, in this case it does not result
in the greatest exposure due to the difference in application rate (2.0
lb ai/acre for olives and 0.38 lb ai/acre for berries).  Therefore, hand
harvesting of olives was assessed below and constitutes the greater
exposure and risk (of the proposed new uses).

The TCs discussed in this assessment are from an interim TC SOP
developed by HED’s ExpoSAC using proprietary data from the ARTF
database (SOP # 003.1).  It is the intention of the ExpoSAC that this
SOP will be periodically updated to incorporate additional information
about agricultural practices in crops and new data on TCs.  Much of this
information will originate from exposure studies currently being
conducted by the ARTF, from further analysis of studies already
submitted to the Agency, and from studies in the published scientific
literature.  Post-application reentry exposure may be estimated using
the following convention.

PDRt	= DFRt x CF1 x TC x ET

PDRt	= potential dose rate on day “t” (mg/day)

DFRt	= dislodgeable foliar residue on day “t” (ug/cm2; see below for
equation)

CF1	= weighted unit conversion factor changing µg to mg (0.001 mg/µg)

TC  	=  transfer coefficient (cm2/hr) (2,500 cm²/hr)

ET	= Exposure Time (hr/day)

	DFRt	= (AR * F) * (1 - D)t * CF2 * CF3 where:

	AR	= application rate (lb a.i./ft2 or lb a.i./Acre) (2.0 lb ai/A for
berries)

	F	= fraction of a.i. retained on foliage (unitless =  20%)

	D	= fraction of residue that dissipates daily (unitless) (10%)

	t	= post-application day on which exposure is being assessed

	CF2	= conversion factor lb a.i. to µg for DFR (4.54 x 108 µg/lb)

	CF3	= conversion factor to convert surface area units (ft2) in
application rate to cm2 for DFR value (1.08 x 10-3 	ft2/cm2 or 2.47 x
10-8 acre/cm2 if rate is per acre).

The PDRt is then normalized to the body weight of a worker.  The result
is expressed as mg/kg/day.  The body weight used is determined by the
toxicological endpoint identified for use in the assessment.  For this
assessment, the toxicological endpoints are identified from a dermal
exposure study; therefore, 70-kg body weight is used to calculate the
MOE.

DFRt	= 2.0 lb ai/acre x 0.2 x (1 - D)0 x 4.54 x 108 µg/lb x 2.47 x
10-8A/cm2 = 4.48 µg a.i./cm2

PDRt	= 4.48 µg a.i./cm2 x 0.001 mg/µg x 2,500 cm2/hr x 8 hr/day  =
89.6 mg/day

Dose	= 89.6 mg/day ( 70 kg body weight = 1.28 mg/kg/day.

MOE	= NOAEL ( Dose = 300 mg/kg/day ÷ 1.28 mg/kg/day = 234

A MOE >100 is sufficient to protect agricultural workers.  The estimated
MOE, based on conservative assumptions, is >100 and, therefore, is not
of concern to HED.  Since there is a 12-hour restricted entry interval
during which sprays will have dried and since volatilization is expected
to be negligible, HED assumes post-application inhalation exposures are
negligible.

7.3  REI

The proposed labels indicate a REI of 12 hours.  Buprofezin is
classified as Toxicity Category IV for acute dermal, acute inhalation,
eye irritation and dermal irritation.  It is not a dermal sensitizer.
Therefore, the interim WPS REI of 12 hours is sufficient to protect
agricultural workers.

8.0  DATA NEEDS/LABEL REQUIREMENTS഍⸸‱吠硯捩汯杯൹

●The HIARC has required a 28-day inhalation toxicity study in rats
with thyroid hormone measurements (T3, T4, and Thyroxin) because of the
concern for exposure via this route.  However, per HED SOP 2002.01, this
study is not required for the currently proposed uses.

8.2  Residue Chemistry

●Revised Section B

●Revised Section F

8.3  Occupational/Residential

●None

Attachment 1:  Chemical Structures

Attachment 2:  Toxicological Profile

RDI: RAB1 review (16-Jan-2008)

T. Bloem:S10945:PY1:(703)-605-0217(7509P)

Attachment 1: Attachment 1: Chemical Structures

Compound Name	Structure

buprofezin;

BF2

BF4

BF9

BF12

BF23

Attachment 2:  Toxicological Profile

Guideline No.

Study Type

MRID No. (year) Classification

Dose Levels

Results

870.3100; 90-day oral toxicity in rat

42935201 (1986)

Acceptable/Guideline

NOAEL:13.0 mg/kg/day Males or M); 16.3 mg/kg/day (Females or F)

LOAEL:68.6 mg/kg/day (M); 81.8 mg/kg/day females based on incr. rel.
thyroid wt–males, increased liver weights–M/F, incr. microscopic
lesions in liver & thyroid–M/F

870.3200; 24-day dermal toxicity in rat

44394024 (1995)

Acceptable/non-guideline

Systemic NOAEL: 300 mg/kg/day; Dermal NOAEL: 300 mg/kg/day

Systemic LOAEL: 1000 mg/kg/day based on increased focal necrosis with an
inflammatory infiltrate in liver(F)

Dermal LOAEL: 1000 mg/kg/day based on increased acanthosis and
hyperkeratosis in skin (F)

870.3700a; Developmental Toxicity in rat

42873813 (1987)

Acceptable/guideline

Maternal NOAEL 200 mg/kg/day; Developmental NOAEL 200 mg/kg/day

Maternal LOAEL 800 mg/kg/day based on mortality, decreased pregnancy
rates, increased resorption rates

Developmental LOAEL 800 mg/kg/day based on reduced ossification, reduced
pup weight, fetal edema.

870.3700b; Developmental Toxicity in rabbit

42873812 (1986)

Acceptable/guideline

Maternal NOAEL 50 mg/kg/day; Developmental NOAEL 250 mg/kg/day

Maternal LOAEL 250 mg/kg/day based on decreased food consumption,
decreased body weights.

Developmental LOAEL, not established (> 250 mg/kg/day)

870.3800; Reproduction and fertility effects in rats

42873814, 44394027 (1997)

Acceptable/guideline

Parental NOAEL 7.89 mg/kg/day

Reproductive/Developmental NOAEL 7.89 mg/kg/day

Parental LOAEL 81.47 mg/kg/day based on decreased body weight gain and
on organ weight changes

Reproductive/Developmental LOAEL 81.47 mg/kg/day based on decreased pup
weight.

870.4100; Chronic toxicity in dogs

42873810 (1994)

Acceptable/guideline

NOAEL 2 mg/kg/day; LOAEL 20 mg/kg/day based on increased bile duct
hyperplasia M/F, increased serum alkaline phosphatase activity M/F,
increased relative & absolute liver wts and decreased liver function in
females.

870.4300; Chronic toxicity/ carcinogenicity in rat

42935202, 44394025 (1997)

Acceptable/guideline

NOAEL 1.0 mg/kg/day; LOAEL 8.7 mg/kg/day based on increased incidence of
follicular cell hyperplasia and hypertrophy in thyroid in males.  No
evidence of carcinogenicity

870.4200; Carcinogenicity study in mice

42873811 (1992)

Acceptable/guideline

NOAEL 1.82 / 17.9 mg/kg/d (M/F); LOAEL 17.40 / 191.0 mg/kg/d (M/F) based
on increased absolute liver weights in males & females, increased
hepatocellular adenomas in females, increased hepatocellular adenomas +
carcinomas in females

870.5100; Mutagenicity: gene mutation in Salmonella

42873815 (1988)

Acceptable/guideline

not mutagenic, with or without activation tested up to cytotoxic levels

870-5300; Mutagenicity: gene mutation in mouse lymphoma

42873816 (1988)

Acceptable/guideline

not mutagenic, with or without activation tested up to cytotoxic levels

870.5300; Mutagenicity: in vitro human cytogenetic assay

42873818 (1988)

Acceptable/guideline

摧巾Ë

or chromosomal aberrations tested up to cytotoxic levels

870.5300; Mutagenicity: mouse micronucleus assay

42873817 (1983)

Acceptable/guideline

negative for micronucleus induction in bone marrow cells of males and
females tested up to cytotoxic levels

870.5300; Mutagenicity: Unscheduled DNA synthesis

42873819 (1988)

Acceptable/guideline

negative for DNA repair tested up to cytotoxic levels

870.7485; Metabolism

42873820, 44394029 (1999)

Acceptable/guideline

79.1% recovered from feces, 12.9% from urine within 72 hr.

45.4% recovered as parent cpd, several metabolites identified.

Buprofezin (275100)	Human-Health Risk Assessment	D339827

page   PAGE  1  of   NUMPAGES  26


[Federal Register Volume 80, Number 212 (Tuesday, November 3, 2015)]
[Rules and Regulations]
[Pages 67642-67645]
[FR Doc No: 2015-27900]

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R01-OAR-2015-0546; A-1-FRL-9933-89-Region 1]

Approval and Promulgation of Air Quality Implementation Plans;
Connecticut; Volatile Organic Compound Emissions From Large Aboveground
Storage Tanks

AGENCY: Environmental Protection Agency (EPA).

ACTION: Direct final rule.

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

SUMMARY: The Environmental Protection Agency (EPA) is approving a State
Implementation Plan (SIP) revision submitted by the State of
Connecticut. The revision amends Regulations of Connecticut State
Agencies (RCSA) section 22a-174-20 to update the requirements for
controlling volatile organic compound (VOC) emissions from large
aboveground storage tanks. The intended effect of this action is to
approve these regulations into the Connecticut SIP. This action is
being taken in accordance with the Clean Air Act (CAA).

DATES: This direct final rule will be effective January 4, 2016, unless
EPA receives adverse comments by December 3, 2015. If adverse comments
are received, EPA will publish a timely withdrawal of the direct final
rule in the Federal Register informing the public that the rule will
not take effect.

ADDRESSES: Submit your comments identified by Docket ID Number EPA-R01-
OAR-2015-0546, by one of the following methods:
    1. www.regulations.gov: Follow the on-line instructions for
submitting comments.
    2. Email<EMAIL_ADDRESS>    3. Fax:<PHONE_NUMBER>.
    4. Mail: ``Docket Identification Number EPA-R01-OAR-2015-0546,''
David Mackintosh, Air Quality Planning Unit, Office of Ecosystem
Protection, U.S. Environmental Protection Agency, EPA New England
Regional Office, 5 Post Office Square--Suite 100, (Mail code OEP05-2),
Boston, MA 02109-3912.
    5. Hand Delivery or Courier. Deliver your comments to: Anne Arnold,
Manager, Air Quality Planning Unit, Office of Ecosystem Protection,
U.S. Environmental Protection Agency, EPA New England Regional Office,
5 Post Office Square--Suite 100, (Mail code OEP05-2), Boston, MA 02109-
3912. Such deliveries are only accepted during the Regional Office's
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business are Monday through Friday, 8:30 a.m. to 4:30 p.m., excluding
legal holidays.
    Instructions: Direct your comments to Docket ID Number EPA-R01-OAR-
2015-0546. EPA's policy is that all comments received will be included
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unless the comment includes information claimed to be Confidential
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email, information that you consider to be CBI or otherwise protected.
The www.regulations.gov Web site is an ``anonymous access'' system,
which means EPA will not know your identity or contact information
unless you provide it in the body of your comment. If you send an email
comment directly to EPA without going through www.regulations.gov your
email address will be automatically captured and included as part of
the comment that is placed in the public docket and made available on
the Internet. If you submit an electronic comment, EPA recommends that
you include your name and other contact information in the body of your
comment and with any disk or CD-ROM you submit. If EPA cannot read your
comment due to technical difficulties and cannot contact you for
clarification, EPA may not be able to consider your comment. Electronic
files should avoid the use of special characters, any form of
encryption, and be free of any defects or viruses.
    Docket: All documents in the electronic docket are listed in the
www.regulations.gov index. Although listed in the index, some
information is not publicly available, i.e., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, is not placed on the Internet and will be
publicly available only in hard copy

form. Publicly available docket materials are available either
electronically in www.regulations.gov or in hard copy at Office of
Ecosystem Protection, U.S. Environmental Protection Agency, EPA New
England Regional Office, 5 Post Office Square--Suite 100, Boston, MA.
EPA requests that if at all possible, you contact the contact listed in
the FOR FURTHER INFORMATION CONTACT section to schedule your
inspection. The Regional Office's official hours of business are Monday
through Friday, 8:30 a.m. to 4:30 p.m., excluding legal holidays.
    In addition, copies of the state's submittal are available for
public inspection during normal business hours, by appointment at the
state environmental agency: The Bureau of Air Management, Department of
Energy and Environmental Protection, State Office Building, 79 Elm
Street, Hartford, CT 06106-1630.

FOR FURTHER INFORMATION CONTACT: David Mackintosh, Air Quality Planning
Unit, U.S. Environmental Protection Agency, New England Regional
Office, 5 Post Office Square--Suite 100, (Mail Code OEP05-02), Boston,
MA 02109-3912, telephone<PHONE_NUMBER>, facsimile<PHONE_NUMBER>, email
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Throughout this document whenever ``we,''
``us,'' or ``our'' is used, we mean EPA. The following outline is
provided to aid in locating information in this preamble.

I. What action is EPA taking?
II. What is the background for this action?
III. What is included in the submittal?
IV. EPA's Evaluation of the Submittal
V. Final Action
VI. Incorporation by Reference
VII. Statutory and Executive Order Reviews

I. What action is EPA taking?

    EPA is approving a SIP revision submitted by the State of
Connecticut on April 8, 2014, concerning updates to requirements for
controlling VOC emissions from large aboveground storage tanks. The
Connecticut requirements, set out in RCSA section 22a-174-20, ``Control
of organic compound emissions,'' subsections (a), (b), (c) and (x),
were revised to be consistent with the Ozone Transport Commission (OTC)
model rule for large aboveground VOC storage tanks.

II. What is the background for this action?

    EPA last approved RCSA section 22a-174-20, ``Control of organic
compound emissions,'' subsections that addresses large aboveground
storage tanks into the Connecticut SIP on October 18, 1991 (56 FR
52205).
    On June 3, 2010, Connecticut signed an OTC Memorandum of
Understanding (MOU) committing the state to the evaluation and adoption
of an OTC model rule designed to reduce VOC emissions from large
aboveground storage tanks.
    On March 5, 2014, Connecticut revised RCSA section 22a-174-20
subsections (a), (b), (c) and (x) to update VOC emission control
requirements from large aboveground storage tanks. On April 8, 2014,
the Connecticut Department of Energy and Environmental Protection
(DEEP), submitted the newly adopted subsections to EPA as a SIP
revision.

III. What is included in the submittal?

    Connecticut's April 8, 2014 SIP submittal includes revised RCSA
section 22a-174-20, ``Control of organic compound emissions.''
Specifically, the following subsections of Connecticut's existing
regulation were revised:
    1. Subsection (a), ``Storage of volatile organic compounds and
restrictions for the Reid vapor pressure of gasoline;''
    2. subsection (b), ``Loading of gasoline and other volatile organic
compounds,'' subdivisions (1) through (4) and (17);
    3. subsection (c), ``Volatile organic compound and water
separation;'' and
    4. subsection (x), ``Control of Volatile Organic Compound Leaks
from Synthetic Organic Chemical & Polymer Manufacturing Equipment,''
subdivision (12).

IV. EPA's Evaluation of the Submittal

    RCSA section 22a-174-20, ``Control of organic compound emissions,''
subsections (a), (b), (c) and (x) have been revised to incorporate the
OTC model rules for large aboveground VOC storage tanks. Specifically,
Connecticut adopted the following substantive changes:
    1. Remove the option to use an un-domed floating roof tank to store
VOCs, clarify inspection requirements, and add requirements for roof
landing events, degassing, and cleaning operations in subsection (a);
    2. Revise the storage and transfer of VOCs to include a lower vapor
pressure floor for determining applicability and the vapor pressure is
simplified by basing it on absolute vapor pressure rather than actual
vapor pressure in subsections (a) and (b);
    3. Add a requirement for the timely repair of leaks throughout the
VOC storage and transfer facility as subdivision (b)(17);
    4. Revise the floating roof requirements for volatile organic
compound and water separators to be consistent with the floating roof
requirements for storage tanks in subsection (c) and;
    5. Revise the tank control provisions for synthetic organic
chemical and polymer manufacturing equipment to require retesting
within two days of repairs in subdivision (x)(12).
    Connecticut's revised RCSA section 22a-174-20 includes additional
and more stringent VOC emission controls than the previous SIP-approved
version of the rule, and are generally consistent with the
recommendations made within the OTC's model rule. Thus, the revised
RCSA section 22a-174-20 satisfies the anti-back sliding requirements in
Section 110(l) of the CAA and we are approving Connecticut's revised
rule into the Connecticut SIP.

V. Final Action

    EPA is approving and incorporating into the Connecticut SIP the
following revisions of RCSA section 22a-174-20, ``Control of organic
compound emissions,'' to update the control of emissions from large
aboveground storage tanks:
    (1) the amendment of subsection (a);
    (2) the withdrawal of subdivision (b)(1);
    (3) the amendment of subdivisions (b)(2), (b)(3) and (b)(4);
    (4) the addition of subdivision (b)(17);
    (5) the amendment of subsection (c); and
    (6) the amendment of subdivision (x)(12).
    The EPA is publishing this action without prior proposal because
the Agency views this as a noncontroversial amendment and anticipates
no adverse comments. However, in the proposed rules section of this
Federal Register publication, EPA is publishing a separate document
that will serve as the proposal to approve this SIP revision should
relevant adverse comments be filed. This rule will be effective January
4, 2016 without further notice unless the Agency receives relevant
adverse comments by December 3, 2015.
    If the EPA receives such comments, then EPA will publish a notice
withdrawing the final rule and informing the public that the rule will
not take effect. All public comments received will then be addressed in
a subsequent final rule based on the proposed rule. The EPA will not
institute a second comment period on the proposed rule. All parties
interested in commenting on the proposed rule should do so at this
time. If no such comments are received, the public is advised that this
rule will be effective on January 4, 2016 and no further action will be
taken on the proposed rule.

Please note that if EPA receives adverse comment on an amendment,
paragraph, or section of this rule and if that provision may be severed
from the remainder of the rule, EPA may adopt as final those provisions
of the rule that are not the subject of an adverse comment.

VI. Incorporation by Reference

    In this rule, the EPA is finalizing regulatory text that includes
incorporation by reference. In accordance with requirements of 1 CFR
51.5, the EPA is finalizing the incorporation by reference of the
Regulations of Connecticut State Agencies described in the amendments
to 40 CFR part 52 set forth below. The EPA has made, and will continue
to make, these documents generally available electronically through
www.regulations.gov and/or in hard copy at the appropriate EPA office
(see the ADDRESSES section of this preamble for more information).

VII. Statutory and Executive Order Reviews

    Under the Clean Air Act, the Administrator is required to approve a
SIP submission that complies with the provisions of the Act and
applicable Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a).
Thus, in reviewing SIP submissions, EPA's role is to approve state
choices, provided that they meet the criteria of the Clean Air Act.
Accordingly, this action merely approves state law as meeting Federal
requirements and does not impose additional requirements beyond those
imposed by state law. For that reason, this action:
     Is not a ``significant regulatory action'' subject to
review by the Office of Management and Budget under Executive Order
12866 (58 FR 51735, October 4, 1993);
     does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the Clean Air Act; and
     does not provide EPA with the discretionary authority to
address, as appropriate, disproportionate human health or environmental
effects, using practicable and legally permissible methods, under
Executive Order 12898 (59 FR 7629, February 16, 1994).
    In addition, the SIP is not approved to apply on any Indian
reservation land or in any other area where EPA or an Indian tribe has
demonstrated that a tribe has jurisdiction. In those areas of Indian
country, the rule does not have tribal implications and will not impose
substantial direct costs on tribal governments or preempt tribal law as
specified by Executive Order 13175 (65 FR 67249, November 9, 2000).
    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this action and
other required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the Clean Air Act, petitions for
judicial review of this action must be filed in the United States Court
of Appeals for the appropriate circuit by January 4, 2016. Filing a
petition for reconsideration by the Administrator of this final rule
does not affect the finality of this action for the purposes of
judicial review nor does it extend the time within which a petition for
judicial review may be filed, and shall not postpone the effectiveness
of such rule or action.
    Parties with objections to this direct final rule are encouraged to
file a comment in response to the parallel notice of proposed
rulemaking for this action published in the proposed rules section of
today's Federal Register, rather than file an immediate petition for
judicial review of this direct final rule, so that EPA can withdraw
this direct final rule and address the comment in the proposed
rulemaking. This action may not be challenged later in proceedings to
enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Ozone, Reporting and recordkeeping requirements, Volatile
organic compounds.

    Dated: August 27, 2015.
H. Curtis Spalding,
Regional Administrator, EPA New England.

    Part 52 of chapter I, title 40 of the Code of Federal Regulations
is amended as follows:

PART 52--APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS

0
1. The authority citation for part 52 continues to read as follows:

    Authority: 42 U.S.C. 7401 et seq.

Subpart H--Connecticut

0
2. Section 52.370 is amended by adding paragraph (c)(110) to read as
follows:

Sec.  52.370  Identification of plan.

* * * * *
    (c) * * *
    (110) Revisions to the State Implementation Plan submitted by the
Connecticut Department of Energy and Environmental Protection on April
8, 2014.
    (i) Incorporation by reference.
    (A) Regulations of Connecticut State Agencies, revisions to Section
22a-174-20(a), as published in the Connecticut Law Journal on May 6,
2014, effective March 7, 2014:
    (1) 22a-174-20(a);
    (2) 22a-174-20(b)(2), (b)(3), (b)(4), and (b)(17);
    (3) 22a-174-20(c); and
    (4) 22a-174-20(x)(12).
    (B) Regulations of Connecticut State Agencies, Subsection (b)(1) of
Section 22a-174-20 is removed without replacement, as published in the
Connecticut Law Journal on May 6, 2014, effective March 7, 2014.

0
3. In Sec.  52.385, Table 52.385 is amended by adding a new entry to an
existing state citation for 22a-174-20 to read as follows:

Sec.  52.385--EPA-approved  Connecticut regulations.

* * * * *

                                                         Table 52.385--EPA-Approved Regulations
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Dates
                                                   ----------------------------------    Federal Register
 Connecticut state citation      Title/subject      Date adopted by   Date approved          citation         Section 52.370     Comments/description
                                                         State            by EPA
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                                                      * * * * * * *
22a-174-20.................  Control of organic             3/5/14          11/3/15   [Insert Federal              (c)(110)   Large aboveground storage
                              compound emissions.                                      Register citation].                     tanks updates: amend (a);
                                                                                withdraw (b)(1); amend
                                                                                (b)(2), (b)(3) and
                                                                                (b)(4); add (b)(17);
                                                                                amend (c) and (x)(12).

                                                                      * * * * * * *
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[FR Doc. 2015-27900 Filed 11-2-15; 8:45 am]
 BILLING CODE 6560-50-P