Document ID: EPA-HQ-OPP-2006-0170-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-09-22T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF                  

PREVENTION, PESTICIDES AND 

TOXIC SUBSTANCES        

MEMORANDUM			

Date:		26-April-2006 

Subject:	Buprofezin (PC Code 275100) - Human Health Risk Assessment for
Establishment of Permanent Almond Hull, Cottonseed, and Cotton Gin
Byproduct Tolerances and Extension of the Tomato Time-limited Tolerance.
 Registration 71711-16.   DP #:  328804.  Decision #:  359609.

From:		Thomas Bloem, Chemist

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

Mark Dow, Ph.D., Biologist

Registration Action Branch 1 (RAB1)

Health Effects Division (HED) (7509C)

To:		Richard Gebken/Kevin Sweeney

Risk Management Team 10		

Registration Division (RD)

Thru:		Felicia Fort, Acting Branch Chief

P.V. Shah, Ph.D., Branch Senior Scientist

RAB1/HED (7509C)

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 and proposed buprofezin tolerances is provided in this
document.  The risk assessment, residue chemistry data review, and the
dietary risk assessment were provided by Tom Bloem (RAB1), the hazard
characterization by P.V. Shah  (RAB1), the occupational/residential
exposure assessment by Mark Dow (RAB1), and the drinking water
assessment by James Wolf of the Environmental 

ate and Effects Division (EFED).

 TOC \f 

1.0 	EXECUTIVE SUMMARY	Page 3 of  21

2.0	PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION	Page 7 of  21

3.0 	HAZARD CHARACTERIZATION	Page 8 of  21

3.1 	Hazard Profile	Page 8 of  21

3.2 	FQPA Considerations	Page 9 of  21

3.3 	Dose-Response Assessment	Page 10 of  21

4.0	EXPOSURE ASSESSMENT	Page 12 of  21

4.1	Summary of Registered Uses	Page 12 of  21

4.2	Summary of Proposed Uses	Page 12 of  21

4.3	Dietary Exposure/Risk Pathway	Page 13 of  21

4.3.1 	Food Residue Profile	Page 13 of  21

4.3.2 	Water Residue Profile Exposure/Risk Pathway	Page 16 of  21

Drinking Water Fate Assessment	Page 16 of  21

4.4  	Dietary Exposure Analyses	Page 17 of  21

4.5	Residential Exposure/Risk Pathway	Page 18 of  21

5.0	AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION	Page 18 of  21

6.0 	CUMULATIVE RISK	Page 18 of  21

7.0	OCCUPATIONAL EXPOSURE	Page 19 of  21

7.3	Restricted-Entry Interval (REI)	Page 19 of  21

8.0	DATA NEEDS/LABEL REQUIREMENTS	Page 20 of  21

8.1	Toxicology	Page 20 of  21

8.2	Residue Chemistry	Page 20 of  21

8.3	Occupational/Residential	Page 20 of  21

 

1.0 	EXECUTIVE SUMMARY tc \l1 "1.0 	EXECUTIVE SUMMARY 

HED previously recommended for time-limited almond hull, cottonseed,
cotton gin byproduct, and tomato tolerances either due to the lack of
sufficient field trial data (almond hull) or field trial data which was
conducted at an exaggerated rate (cottonseed, cotton gin byproduct, and
tomato).  As part of a residue chemistry amendment (D319815, T. Bloem,
14-Dec-2005), HED is now recommending for the establishment of permanent
almond hull, cottonseed, and cotton gin byproduct tolerances and
extension of the tomato time-limited tolerance.  

Background:  Buprofezin
(2-[(1,1-dimethylethyl)imino]tetrahydro-3(1-methylethyl)-5-phenyl-4H-1,3
,5-thiadiazin-4-one) is an insecticide which shows a high level of
activity against Homoptera spp (planthoppers, leafhoppers, whiteflies,
and scales) and is active through inhibition of chitin biosynthesis and
suppression of oviposition and/or egg hatching.  Buprofezin is currently
registered for application to numerous crops with tolerances for
residues of buprofezin ranging from 0.05 - 60 ppm (40 CFR 180.511). 
Tolerances have also been established for residues of buprofezin in/on
ruminant fat, liver, and meat byproducts at 0.05 ppm and in milk at 0.01
ppm.    Currently, there are no proposed or registered uses for
buprofezin that result in residential exposures. 

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 was 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.  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 CARC 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 endpoints 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
exposure assessment.  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.   

The table below summarizes the endpoints chosen for the exposure
scenarios assessed as part of the current document.  Due to the lack of
a comparative 28-day thyroid assay (young -vs- old), a 10x database
uncertainty factor was applied to all endpoints which are based on
thyroid effects. However, 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 uncertainty
factor for these assessments may be reduced to 3x.  Based on
toxicological considerations, the conservative residue assumptions used
in the dietary risk assessment (there are currently no residential
exposures), and the completeness of the residue chemistry and
environmental fate databases, the FQPA SF was reduced to 1x.  Therefore,
the total uncertainty factor for chronic dietary and inhalation
assessments is 300x (10x database uncertainty, 3x interspecies
variation, and 10x intraspecies variation) and the total uncertainty
factor for acute dietary and dermal assessments is 100x (10x
interspecies variation and 10x intraspecies variation). 

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: incomplete ossification and reduced
pup body weight.

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

	

NOAEL=300 mg/kg/day	

MOE1<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 

	

NOAEL=13 mg/kg/day	

MOE<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; MOE = margin of exposure

Dietary Exposure Estimates:  The acute and chronic dietary 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 USDA’s Continuing Surveys
of Food Intakes by Individuals (CSFII; 1994-1996 and 1998).  The acute
analysis assumed DEEM( (ver. 7.76) 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 PRZM-EXAMS surface drinking water
estimate resulting from application of buprofezin to citrus in Florida
(highest acute drinking water estimate).  The resulting acute exposure
estimate for females 13-49 years old was less than HED’s level of
concern (5% aPAD).  No acute endpoint was identified for the remaining
population subgroups.  

The chronic analysis assumed DEEM( (ver. 7.76) default processing
factors for all commodities and incorporated percent crop treated
estimates or projected percent crop treated estimates.  Tolerance level
or average field trial residues were assumed for all crop commodities
and 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 chronic analysis also incorporated
the chronic PRZM-EXAMS surface drinking water estimate resulting from
application of buprofezin to citrus in Florida (highest chronic drinking
water estimate).  The resulting chronic exposure estimates were less
than HED’s level of concern ((87% cPAD; children 1-2 years old were
the most highly exposed population).

Aggregate Risk Estimates:  There are no registered/proposed uses which
result in residential exposure.  Therefore, the acute and chronic
exposure estimates provided in the previous section represent aggregate
exposure. 

Occupational Estimates:  Based on the proposed use patterns, commercial
applicators are anticipated to have short- and intermediate-term dermal
and inhalation exposures and grower/applicators are anticipated to have
short- and intermediate-term dermal exposures.  No chemical-specific
data are available to assess potential exposures to pesticide handlers
for the proposed uses; therefore, the exposure assessment was conducted
using data available in Pesticide Handler Exposure Database (PHED)
Surrogate Table (ver. 1.1; 1998).  The resulting dermal (with the use of
gloves as specified on the label) and inhalation MOEs ranged from
1,800-570,000 and are therefore not of concern to HED.

There are no compound-specific data with which to estimate
post-application exposure to agricultural workers.  Therefore, estimates
of post-application exposure are based upon methodologies similar to the
Standard Operating Procedures (SOPs) for Residential Exposure Assessment
(18-Dec-1997) with revisions by the Science Advisory Council for
Exposure (ExpoSAC).  In addition, transfer coefficients used to
calculate post-application exposure are taken from the interim transfer
coefficient policy developed by HED’s ExpoSAC using propriety data
from the Agricultural Re-entry Task Force (ARTF) database (SOP 003.1).  

The memos which assessed occupational exposure to cotton, almond, and
tomato also assessed several other crops including fruit trees.  The
post-application exposure estimates were based on propping fruit trees
on the day of application as this provided the most conservative
transfer coefficient (3,000 cm2/hour) and highest application rate.  The
resulting MOEs were 250.  However, the application rates for tomato and
cotton are significantly lower than that for fruit trees and the highest
transfer coefficient for the post-harvest activities in these crops is
1,000 cm2/hour.  Propping of almond trees is unnecessary and the highest
applicable transfer coefficient is for scouting or thinning in tree nut
orchards is 500 cm2/hour.  Since reduction in transfer coefficients
leads to a proportionate increase in the MOE, the post-harvest MOEs
following treatment of almond, cotton, and tomato will be >300 and are
therefore not of concern to HED.  

Recommendations:  Provided the petitioner submits a revised Section F,
HED concludes that the toxicology, residue chemistry, and
occupational/residential databases are sufficient to support conditional
registration, extension of the tomato time-limited tolerance expiration
date, and establishment of the following permanent tolerances for
residues of buprofezin: 

almond, hulls	.	.	.	.	.	.	.	.	.	.	2.0 ppm

cotton, gin byproducts		.	.	.	.	.	.	.	.	20 ppm

cottonseed	.	.	.	.	.	.	.	.	.	.	0.35 ppm

Unconditional registration may be appropriate upon submission of data
which adequately addresses the following deficiencies:

A comparative thyroid assay in young and adult rats

radiovalidation of the livestock enforcement method

storage stability data (see page 20)

tomato magnitude of the residue data (see page 20) 

2.0	PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION tc \l1 "2.0
PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION 

Buprofezin is a miticide which causes nymphs to die at molting through
chitin biosynthesis inhibition and causes suppression of oviposition
and/or egg hatching.  Buprofezin shows a high level of activity against
Homoptera spp such as planthoppers, leafhoppers, whiteflies, and scales.

Table 1:  Test Compound Nomenclature

Compound	

 

Common name	

buprofezin

Company experimental name	

BF1

IUPAC name	

2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-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 product/(EP)	

Applaud® 70 WP (EPA Reg. No. 71711-15)

Table 2:  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 tc \l1 "3.0 	HAZARD CHARACTERIZATION 

HIARC:  HED Doc. Nos. 014093, 014221, and 051342

FQPA SFC:  HED Doc. No. 014138 

CARC:  HED Doc. No. 014045 

Conversion of time-limited tolerances to permanent tolerances requires a
review of the toxicological database.  HED has reviewed the
toxicological database and agreed with all of the previous conclusions
except for the total uncertainty factor (interspecies, intraspecies,
database uncertainty factors, FQPA SF).  HED previously concluded that a
100x uncertainty factor was appropriate for all assessments; as part of
the review associated with the current action, HED concludes that a 300x
uncertainty factor is appropriate for chronic dietary, inhalation, and
incidental oral assessments and an uncertainty factor of 100x is
appropriate for acute dietary and dermal assessments (see following
paragraphs for rationale).    

The toxicological profile for buprofezin is explained in detail in the
November 2001 human health risk assessment (T. Bloem, D284767).  The
following is a summary of the information provided in that document as
well as an explanation of the uncertainty factors.  

3.1 	Hazard Profile tc \l2 "3.1 	Hazard Profile 

The toxicological database for buprofezin is complete.  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 in this risk assessment, buprofezin qualifies for a waiver
of the 28-day inhalation toxicity study for the proposed uses [HED SOP
2002.01: Guidance: Waiver Criteria for Multiple-Exposure Inhalation
Toxicity Studies, 08/15/02].  The 28-day inhalation toxicity study is
waived for this action only.  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.

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.  Increased focal necrosis with an inflammatory
infiltrate in the liver was observed in females following dermal
subchronic exposure, as was increased acanthosis and hyperkeratosis in
skin.  

In chronic studies in the rat, an increased incidence of follicular
cell hyperplasia and hypertrophy in the thyroid of males was 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.”  Therefore, no quantification of cancer
risk is required.  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 CARC 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).  The 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.

3.2 	FQPA Considerations tc \l2 "3.2 	FQPA Considerations 

At a meeting held on October 22, 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.  The
data do not indicate a basis for concern for neurotoxicity and acute,
subchronic, and developmental neurotoxicity studies are not required.  

Based on the evidence of thyroid toxicity following subchronic and
chronic exposures to rats (histopathological lesions) and dogs
(decreases in serum thyroxine levels and increased thyroid weights), the
HIARC requested a comparative thyroid assay study in rats (young versus
adults) to determine if the thyroid effects occur at a lower dose in
young versus adult animals.  

The petitioner has not submitted the requested comparative thyroid
assay.  Based on the lack of a comparative 28-day thyroid assay (young
-vs- old), HED concludes that a database uncertainty factor of 10x
should be applied.  Further, since it has been established that rats are
more susceptible to thyroid effects than humans, HED concluded that the
interspecies uncertainty factor may be reduced to 3x.  The database
uncertainty factor 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 uncertainty factor was not applied to dermal exposure
assessments because no thyroid effects were seen in a dermal toxicity
study (thyroid effects were monitored).  Based on toxicological
considerations, the conservative residue assumptions used in the dietary
risk assessment (there are currently no residential exposures), and the
completeness of the residue chemistry and environmental fate databases,
the FQPA SF was reduced to 1x.  Therefore, the total uncertainty factor
for chronic dietary and inhalation assessments is 300x (10x database
uncertainty, 3x interspecies variation, and 10x intraspecies variation)
and the total uncertainty factor for acute dietary and dermal
assessments is 100x (10x interspecies variation and 10x intraspecies
variation). 

Table 3:  Summary of FQPA SFs for Buprofezin

	

Factor	

Rationale for the Factor	

Endpoints the Factor is Applied

LOAEL to NOAEL (UFL)	

1x	

NA1	

all

Subchronic to Chronic  (UFS)	

1x	

NA	

all

Incomplete Database (UFDB)	

10x	

data gap - comparative thyroid assay in rats (thyroid hormone
measurements; adult versus young animals)	

all dietary and occupational exposure assessments; whose endpoint is
based on thyroid effects.

Inter/Intra species variation	

100x	

default	

all dietary and occupational exposure assessments; whose endpoint is not
based on thyroid effects.

Inter/Intra species variation	

30x	

rats are more susceptible to thyroid effects than humans such that
reduction in the interspecies variation from 10x to 3x is appropriate	

all dietary and occupational exposure assessments; whose endpoint is
based on thyroid effects.

FQPA SF	

1x	

Based on the establishment of a 10x UFDB, the complete residue chemistry
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

1	NA = Not Applicable

3.3 	Dose-Response Assessment tc \l2 "3.3 	Dose-Response Assessment 

A summary of decisions made by the HIARC (15-Feb-2000 and 22-Oct-2002
meetings) concerning endpoints for dietary, residential, and
occupational risk assessments is provided in Table 4 (see next page).  

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 the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific
bases 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 has 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).

In subchronic toxicity studies in rats, buprofezin caused 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 was
reported.  In 2-generation reproduction toxicity study in rats, no
effects on reproductive parameters were observed due to treatment with
buprofezin.  When the appropriate screening and/or testing protocols
being considered under the Agency’s EDSP have been developed,
buprofezin may be subjected to additional screening and/or testing to
better characterize effects related to endocrine disruption.

Table 4:  Summary of Toxicological Dose and Endpoints for Buprofezin

Exposure

Scenario	

Dose Used in Risk Assessment, UF 	

FQPA SF* and Level of Concern for Risk Assessment	

Study and Toxicological Effects

Acute Dietary

(females 13-50 years of age)	

NOAEL = 200 mg/kg/day

UF = 100

aRfD = 2.0 mg/kg/day	

FQPA SF = 1X 

aPAD = aRfD ( FQPA SF

= 2.0 mg/kg/day	

Developmental Toxicity Study - Rats

LOAEL = 800 mg/kg/day based on incomplete ossification and reduced pup
weight.

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)	

NOAEL=1.0 mg/kg/day

UF = 300

cRfD = 0.0033 mg/kg/day	

FQPA SF = 1X 

cPAD = cRfD ( FQPA SF

= 0.0033 mg/kg/day	

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 Incidental oral 

(1-30 Days)	

NOAEL= 13.0 mg/kg/day	

Residential = NA1	

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)	

NOAEL= 13.0 mg/kg/day	

Residential = NA	

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

	

Occupational LOC for 

MOE <100 

Residential = NA	

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

	

Occupational LOC for 

MOE <100 

Residential = NA	

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	

Occupational LOC for 

MOE <100 

Residential = NA	

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

	

Occupational LOC for 

MOE <300 

Residential = NA	

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

	

Occupational LOC for 

MOE <300 

Residential = NA	

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

	

Occupational LOC for 

MOE <300 

Residential = NA 	

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	NA = Not Applicable; There are no residential uses at this time.

4.0	EXPOSURE ASSESSMENT tc \l1 "4.0	EXPOSURE ASSESSMENT 

-D273252, T. Bloem, 20-Mar-2001 (residue chemistry review)

-D296492, T. Bloem, 17-Dec-2003 (residue chemistry review)

-D304845, T. Bloem, 26-Jan-2005 (residue chemistry review)

-D319815, T. Bloem, 14-Dec-2005 (residue chemistry review)

-D328806, T. Bloem, 12-Apr-2006 (dietary exposure analysis)

-EFED memorandum:  Tier II Water Assessment for Buprofezin, including
proposed new uses.  J. Wolf. 08-JAN-2003.

4.1	Summary of Registered Uses tc \l2 "4.1	Summary of Registered Uses 

Buprofezin is currently-registered for application to almonds, banana,
citrus, cotton, cucumbers, grape, lettuce (head and leaf), tomato, melon
(cantaloupe, honeydew, watermelon, muskmelon), pumpkins, squash, snap
bean, peach, pome fruit, pistachio, avocado, guava, and several types of
tropical fruit with tolerances for residues of buprofezin ranging from
0.02 - 60 ppm (40 CFR 180.511; application rate of 0.70 - 3.16 lbs
ai/acre/season).  Tolerances have also been established for residues of
buprofezin, as a result of secondary residues, in milk (0.01 ppm),
ruminant fat (0.05 ppm), liver (0.05 ppm), and meat byproducts (0.05
ppm).  Buprofezin is not currently registered for application in the
residential setting.  

         

4.2	Summary of Proposed Uses tc \l2 "4.2	Summary of Proposed Uses 

The current risk assessment pertains to the conversion of the
time-limited almond hull (1 x 2.0 lb ai/acre; 60-day preharvest interval
(PHI)), cotton (gin byproduct and seed; 2 x 0.35 lb ai/acre; 28-day
retreatment interval (RTI); 14-day PHI) tolerances to permanent
tolerance and extending the expiration date for the tomato (2 x 0.38 lb
ai/acre; 28 day RTI; 7-day PHI) tolerance.  Therefore, there are no new
uses for this petition.

4.3	Dietary Exposure/Risk Pathway tc \l2 "4.3	Dietary Exposure/Risk
Pathway 

4.3.1 	Food Residue Profile tc \l3 "4.3.1 	Food Residue Profile 

Nature of the Residue - Plants, Livestock, and Rotational Crops:  The
HED Metabolism Assessment Review Committee (MARC) reviewed lettuce,
tomato, cotton, lemon, ruminant, and  poultry metabolism studies and the
confined rotational crop study (D264546, T. Bloem, 20-Apr-2000; D273214,
T. Bloem, 13-Mar-2001; TXR No. 0052261, T. Bloem, 10-Dec-2003).  Table 5
is a summary of the residues of concern in primary crops, livestock, and
rotational crops.  

Table 5:  Summary of MARC decisions for Buprofezin

Matrix	

Residues of Concern

	

For Risk Assessment	

For Tolerance Expression

plants	

buprofezin1,2	

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. 

Rotational crops	

buprofezin	

buprofezin

1	apple, grape, and orange processing data monitoring for residue of BF4
conjugates are requested; in the absence of these data, the residues of
concern in fruit crops and crops with an interval greater than ~50 days
from intial application to harvest are buprofezin and BF4 conjugates
(see text for procedure for estimating BF4 conjugate residues)

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 (0.12x) 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% 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 concluded the following (TXR No. 0052261, T. Bloem,
10-Dec-2003):  (1) tolerance expression for plants will include only
buprofezin; (2) for purposes of risk assessment, the residues of concern
for all proposed and registered commodities (excluding grape juice) will
include only buprofezin; (3) based on the grape processing study, the
residues of concern in grape juice are buprofezin and BF12; and (4)
residues of BF9 and BF12 should be monitored in all future field trial
and processing studies (BF9 and BF12 residue data are requested due to
the potential for these compounds to concentrate in processed
commodities).  

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.  In the interim,
for risk assessment purposes, residues of BF4 conjugates should be
estimated in/on fruit crops and crops with an extended interval between
initial application and harvest (greater than ~50 days) using the
buprofezin:BF4 conjugate residue ratio from the citrus metabolism study
(1.8x) and the buprofezin residues from the field trials. 

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 the 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 total radioactive residues
(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 can validate 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.  

Magnitude of the Residue - Plants:  The petitioner submitted and HED
has reviewed almond, cotton, and tomato field trial studies and cotton
and tomato processing studies.  Based on these data, HED made the
following conclusions. 

Almond Hull:  The petitioner initially submitted almond shell and
nutmeat residue data and HED determined that a time-limited almond hull
tolerance, based on the almond shell data, was appropriate provided the
petitioner agreed to submit almond hull residue data.  The petitioner
has submitted the requested almond hull residue data and based on these
data, HED concludes that a permanent tolerance of 2.0 ppm for residues
of buprofezin, per se, in/on almond hulls is appropriate.  A revised
Section F should be submitted.  

Cotton:  The petitioner initially submitted cotton residue data
conducted with four applications at the proposed single application rate
(5-7-day RTI; 14-day PHI) rather than the proposed two applications
(28-day RTI; 14-day PHI).  Provided the petitioner agreed to submit
additional cotton residue data, HED concluded that time-limited
tolerances were appropriate.  The petitioner submitted the requested
data, and based on these data, HED concludes that the following
permanent tolerance for residues of buprofezin are appropriate: cotton,
undelinted seed - 0.35 ppm; cotton, gin byproducts - 20 ppm.  A revised
Section F should be submitted.  

Tomato:  The petitioner initially submitted tomato residue data
conducted with four applications at the proposed single application rate
(4-10-day RTI; 7-day PHI) rather than the proposed two applications
(28-day RTI; 7-day PHI).  Provided the petitioner agreed to submit
additional tomato residue data, HED concluded that time-limited
tolerances were appropriate.  The petitioner has not submitted the
requested data but has indicated that they will be submitting in 2006 an
amendment to reduce the PHI to 1 day and will be submitting tomato
residue data from all suggested regions to support this PHI reduction. 
Therefore, HED concludes that the expiration date for the currently
established tomato tolerances may be extended. 

Magnitude of the Residue - Livestock:  The currently-established milk
and ruminant tissue tolerances are sufficient to cover secondary
residues in milk and ruminants when taking into account the almond hull
and cotton gin byproduct tolerances (these commodities are not fed to
poultry or hogs).  

Analytical Enforcement Method - Plants:  The methods used in the field
trial studies were similar to a method validated by the Analytical
Chemistry Branch (ACB; D278950, T. Bloem, 8-Nov-2001).  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 this
petition.

Analytical Enforcement Method - Livestock:  The ACB has successfully
validated method BF/11/97 for enforcement of the livestock tolerances
(D278950, T. Bloem, 8-Nov-2001) and the method was forwarded to FDA’s
Technical Editing Group for publication in a future revision of the
Pesticide Analytical Manual I (PAM I; D278952, T. Bloem, 8-Nov-2001). 
Radiovalidation of the livestock enforcement method is requested.

Rotational Crops:  Based on the cotton and tomato application scenarios
(2 x 0.38 lbai/acre; RTI =28 days; PHI = 14 days for cotton and 7 days
for tomato) and the field rotational crop data (4 x 0.38 lb ai/acre;
4-10 RTI), HED concludes that the plant-back intervals (PBIs) included
on the labels are appropriate (0-days for labeled crops, 30-days for
cereal grains, and 60 days for all remaining crops).  HED notes that the
petitioner is requested to submit buprofezin, BF12, and BF9 storage
stability data validating the storage intervals used in the field
rotational crop studies (see page 20).  

Proposed and Recommended Tolerances:  Table 6 is a summary of the HED
recommended tolerances for residues of buprofezin (revised Section F is
requested). 

Table 6:  Tolerance Summary for Buprofezin

Commodity Definition	

Tolerance (ppm)

cotton, undelinted seed	

0.35

cotton, gin byproducts	

20

almond, hulls	

2.0

tomato (time-limited)	

0.40

4.3.2 	Water Residue Profile Exposure/Risk Pathway tc \l3 "4.3.2 	Water
Residue Profile Exposure/Risk Pathway 

The MARC determined that only the parent compound, buprofezin, is of
concern in drinking water. 

Drinking Water Fate Assessment tc \l3 "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. 

Modeling and Drinking Water Estimates:  The PRZM/EXAMS (surface water)
and SCIGROW (groundwater) drinking water exposures assessments for
buprofezin are summarized in Table 7.  

Buprofezin concentrations in surface water were simulated in an Index
Reservoir, with a regional percent cropped area and 30 years of scenario
specific weather data, using the linked PRZM/EXAMS.  The maximum
concentration estimates are associated with Florida citrus use.  The
other scenarios considered were Florida avocados, California pome fruit
(plums), Georgia peaches, and Oregon apples.

del estimates a ground water concentration of less than 0.10 μg/L. 
These results are supported by the absence of buprofezin residues in the
deep soil profiles of the terrestrial field dissipation studies.



Table 7:  Estimated Drinking Water Concentrations for Buprofezin (μg/L
or ppb)

	

Acute	

Chronic	

Long-term average

Surface1	

19.2	

4.5	

3.5

Ground2	

0.1	

0.1	

0.1

1	Buprofezin concentrations estimated in Index Reservoir by PRZM/EXAMS
from use on Florida Citrus, buprofezin applied twice at the rate of 2.0
lb ai/acre with a regional PCA of 0.38

2	SCI-GROW estimate 2 applications at 2.0 lb ai/acre

4.4  	Dietary Exposure Analyses tc \l2 "4.4  	Dietary Exposure Analyses 

The acute and chronic dietary risk assessments were conducted using the
DEEM-FCID( (ver. 2.03).  DEEM-FCID incorporates food consumption data
from the USDA’s CSFII (1994-1996 and 1998).  The acute analysis
assumed DEEM( (ver. 7.76) 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 PRZM-EXAMS surface
drinking water estimate resulting from application of buprofezin to
citrus in Florida (highest acute drinking water estimate).  The
resulting acute exposure estimate for females 13-49 years old was less
than HED’s level of concern (5% aPAD).  No acute endpoint was
identified for the remaining population subgroups.  

The chronic analysis assumed DEEM( (ver. 7.76) default processing
factors for all commodities and incorporated percent crop treated
estimates or projected percent crop treated estimates.  Tolerance level
or average field trial residues were assumed for all crop commodities
and since meat and milk (LOQ tolerances) residues were only detected in
the feeding study at 6.8-9.3x the MTDB, residue in these commodities
were normalized to 1x the MTDB.  The chronic analysis also incorporated
the chronic PRZM-EXAMS surface drinking water estimate resulting from
application of buprofezin to citrus in Florida (highest chronic drinking
water estimate).  The resulting chronic exposure estimates were less
than HED’s level of concern ((87% cPAD; children 1-2 years old were
the most highly exposed population).

Table 8:  Summary of Acute Dietary Exposure and Risk

Population Subgroup	

aPAD (mg/kg/day)	

Acute (95th Percentile)

Exposure (mg/kg/day)	

%aPAD

Females 13-49 years old	

2.0	

0.108328	

5

Table 9:  Summary of Chronic Dietary Exposure and Risk

Population Subgroup	

cPAD (mg/kg/day)	

Chronic

Exposure (mg/kg/day)	

%cPAD

General U.S. Population	

0.0033	

0.001322	

40

All Infants (<1 year old)	

0.0033	

0.001844	

56

Children (1-2 years old)	

0.0033	

0.002872	

87

Children (3-5 years old)	

0.0033	

0.002414	

73

Children (6-12 years old)	

0.0033	

0.001581	

48

Youth (13-19 years old)	

0.0033	

0.001041	

32

Adults (20-49 years old)	

0.0033	

0.001211	

37

Adults (50+ years old)	

0.0033	

0.001101	

33

Females 13-49 years old	

0.0033	

0.001296	

39

4.5	Residential Exposure/Risk Pathway tc \l2 "4.5	Residential
Exposure/Risk Pathway 

There are no registered or proposed residential uses of buprofezin that
result in residential exposure.  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 tc \l1 "5.0
AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION 

Since there are no registered/proposed uses which result in residential
exposures, only acute and chronic aggregate exposure assessments,
considering exposure from food and water, are required.  Since the
dietary exposure analysis included the drinking water estimates, the
discussion and exposure estimates presented in Section 4.4 represent
aggregate acute and chronic exposure. 

6.0 	CUMULATIVE RISK tc \l1 "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 for buprofezin and any other
substances, and buprofezin does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA 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 OPP concerning common
mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA’s website at
http://www.epa.gov/pesticides/cumulative/.

7.0	OCCUPATIONAL EXPOSURE tc \l1 "7.0	OCCUPATIONAL EXPOSURE 

D273823, T. Swackhammer, 29-Mar-2001

D289514, M. Dow, 19-May-2003

D292034. M. Dow. 09-Oct-2003

HED has previously evaluated occupational exposure resulting from
application of buprofezin to almond (D273823, T. Swackhammer,
29-Mar-2001), cotton (D273823, T. Swackhammer, 29-Mar-2001; D292034. M.
Dow. 09-Oct-2003), and tomato (D273823, T. Swackhammer, 29-Mar-2001;
D289514, M. Dow, 19-May-2003; D292034. M. Dow. 09-Oct-2003).  The
application rates assessed in these documents and the current rates are
the same.  

Handler Exposure:  Based on the proposed use patterns, commercial
applicators are anticipated to have short- and intermediate-term dermal
and inhalation exposures and grower/applicators are anticipated to have
short- and intermediate-term dermal exposures.  No chemical-specific
data are available to assess potential exposures to pesticide handlers
for the proposed uses; therefore, the exposure assessment was conducted
using data available in the PHED Surrogate Table (ver. 1.1; 1998).  The
resulting dermal (with the use of gloves as specified on the label) and
inhalation MOEs ranged from 1,800-570,000 and are therefore not of
concern to HED.

Post-Application:  There are no compound-specific data with which to
estimate post-application exposure to agricultural workers.  Therefore,
estimates of post-application exposure are based upon methodologies
similar to the SOPs for Residential Exposure Assessment (18-Dec-1997)
with revisions by the ExpoSAC.  In addition, transfer coefficients used
to calculate post-application exposure are taken from the interim
transfer coefficient policy developed by HED’s ExpoSAC using propriety
data from the Agricultural Re-entry Task Force (ARTF) database (SOP
003.1).  

The memos which assessed occupational exposure to cotton, almond, and
tomato also assessed several other crops including fruit trees.  The
post-application exposure estimates were based on propping fruit trees
on the day of application as this provided the most conservative
transfer coefficient (3,000 cm2/hour) and highest application rate.  The
resulting MOEs were 250.  However, the application rates for tomato and
cotton are significantly lower than that for fruit trees and the highest
transfer coefficient for the post-harvest activities in these crops is
1,000 cm2/hour.  Propping of almond trees is unnecessary and the highest
applicable transfer coefficient is for scouting or thinning in tree nut
orchards is 500 cm2/hour.  Since reduction in transfer coefficients
leads to a proportionate increase in the MOE, the post-harvest MOEs
following treatment of almond, cotton, and tomato will be >300 and are
therefore not of concern to HED.  

7.3	Restricted-Entry Interval (REI) tc \l2 "7.3	Restricted-Entry
Interval (REI) 

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 Worker Protection Standard (WPS) REI
of 12 hours is sufficient to protect agricultural workers.

8.0	DATA NEEDS/LABEL REQUIREMENTS tc \l1 "8.0	DATA NEEDS/LABEL
REQUIREMENTS 

8.1	Toxicology tc \l2 "8.1	Toxicology 

A comparative thyroid assay in young and adult rats

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 these uses only.

8.2	Residue Chemistry tc \l2 "8.2	Residue Chemistry 

revised Section F

radiovalidation of the livestock enforcement method

tomato residue data; Extension of the time-limited tomato tolerance is
based on information submitted by the petitioner indicating that they
will be submitting tomato field trial data as specified in OPPTS
860.1500 to support a reduction in the tomato PHI to 1-day.  

The table below is a summary of the requested storage stability data. 
The adequacy of these data to validate the storage intervals for the
samples collected from the field trial, processing, feeding, and
rotational crop studies will be determined upon submission and review.  

matrix	

interval (days)	

analytes	

comments

almond nutmeat	

870	

buprofezin, BF9, BF12	

--

almond hull	

870	

buprofezin, BF9, BF12	

--

potato tuber	

870	

buprofezin, BF9, BF12	

--

wheat grain	

870	

buprofezin, BF9, BF12	

--

wheat forage	

870	

buprofezin, BF9, BF12	

--

wheat hay	

870	

buprofezin, BF9, BF12	

--

wheat straw	

870	

buprofezin, BF9, BF12	

--

grape juice	

319	

buprofezin, BF12	

--

grape raisins	

319	

buprofezin	

--

citrus oil	

455	

buprofezin	

--

whole milk	

210	

BF12, BF23	

buprofezin storage stability data already submitted (45694202.der.wpd)

ruminant liver	

210	

BF2, BF12 	

buprofezin storage stability data already submitted (45694202.der.wpd)

ruminant fat	

210	

BF2, BF12	

buprofezin storage stability data already submitted (45694202.der.wpd)

8.3	Occupational/Residential tc \l2 "8.3	Occupational/Residential 

none

RDI: RAB1 (26-Apr-2006)

T. Bloem:S10945:Potamc yard:(703)605-0217:7590C

Attachment 1:  Chemical Structures

Attachment 1: Attachment 1: Chemical Structures

compound	

structure

buprofezin; 

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옍

옍

옍

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@

@

@

@

$

@

@

B*

$

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

 

BF2 

2-tert-butylimino-5-(4-hydroxyphenyl)-3-isopropyl-1,3,5-thiadiazinan-4-o
ne	

 

BF4

2-(2-hydroxy-1,1-dimethylethylimino)-3-isopropyl-5-phenyl-1,3,5-thiadiaz
inan-4-one	

 

BF9

3-isopropyl-5-phenyl-1,3,5-thiadiazinan-2,4-dione	

 

BF12

1-isopropyl-3-phenylurea	

 

BF23

N-(4-hydroxyphenyl)acetamide	

 

((((( PAGE  21 ((((( NUMPAGES  1