Document ID: EPA-HQ-OPP-2006-0889-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-22T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES, AND

TOXIC SUBSTANCES

MEMORANDUM

Date:			10/2/06

Subject:	Pyriproxyfen Human Health Risk Assessment Use on Numerous
Crops.  IR-4 Tolerance Plan (Reduced Data Set Translations). PP# 6E7033,
DP#: 332761.  PC Code 129032.  Decision #: 364813.

From:			W. Cutchin, Acting Branch Senior Scientist

	Alternative Risk Integration Team (ARIA)

	Technical Review Branch (TRB) 

	Registration Division (RD)(7505P)

		and

				M. Dow, Ph.D, Biologist 

				ARIA Team

				Risk Integration Minor Use and Emergency Response Branch 

	RIMUIERB/RD (7505P)

Through:		G. Kramer, Ph.D., Senior Chemist

	Registration Action Branch (RAB1)

	Health Effects Division (HED) (7509P)

To:				D. Rosenblatt, RM 05 

				RIMUIERB/RD (7505P)

Table of Contents

  TOC \f  1.0  EXECUTIVE SUMMARY	  PAGEREF _Toc147551771 \h  3 

2.0  PHYSICAL/CHEMICAL PROPERTIES	  PAGEREF _Toc147551772 \h  8 

3.0  HAZARD CHARACTERIZATION	  PAGEREF _Toc147551773 \h  9 

3.1.	Dose Response Assessment	  PAGEREF _Toc147551774 \h  9 

4.0  EXPOSURE ASSESSMENT AND CHARACTERIZATION	  PAGEREF _Toc147551775 \h
 13 

4.1  Summary of Registered Uses	  PAGEREF _Toc147551776 \h  13 

4.2  Summary of Proposed Uses	  PAGEREF _Toc147551777 \h  13 

4.3  Dietary Exposure/Risk Pathway	  PAGEREF _Toc147551778 \h  18 

4.4  Water Exposure and Risk Pathway	  PAGEREF _Toc147551779 \h  27 

4.5  Dietary-Exposure Analysis	  PAGEREF _Toc147551780 \h  28 

4.6  Residential Exposure and Risk Pathway	  PAGEREF _Toc147551781 \h 
28 

5.0  AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION	  PAGEREF
_Toc147551782 \h  29 

6.0  CUMULATIVE RISK	  PAGEREF _Toc147551783 \h  31 

7.0  OCCUPATIONAL EXPOSURE	  PAGEREF _Toc147551784 \h  32 

7.1  Handler Exposure	  PAGEREF _Toc147551785 \h  32 

7.2  Post-Application Worker Exposure	  PAGEREF _Toc147551786 \h  32 

7.3  Restricted Entry Interval	  PAGEREF _Toc147551787 \h  32 

7.4  Incidents	  PAGEREF _Toc147551788 \h  32 

8.0  DEFICIENCIES/DATA NEEDS	  PAGEREF _Toc147551789 \h  33 

8.1  Toxicology	  PAGEREF _Toc147551790 \h  33 

8.2  Chemistry	  PAGEREF _Toc147551791 \h  33 

8.3  Occupational/Residential	  PAGEREF _Toc147551792 \h  33 

 

1.0  EXECUTIVE SUMMARY tc \l1 "1.0  EXECUTIVE SUMMARY 

The Interregional Research Project No. 4 (IR-4) submitted a petition for
the establishment of permanent tolerances for residues of the
insecticide pyriproxyfen
[2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine] in conjunction with
requests for amended Section 3 registrations of formulations containing
pyriproxyfen for use on a variety of crops.  The petitioner is proposing
the establishment of the following permanent tolerances for residues of
pyriproxyfen per se:

Commodity

	Tolerance

Vegetable, root and tuber, group 1	0.15 ppm

Vegetable, leaves of root and tuber, group 2	2.0 ppm

Vegetable, bulb, group 3, 

     except Onion, dry bulb 	0.70 ppm

Vegetable, leafy, except Brassica, group 4 	2.0 ppm

Vegetable, legume, group 6 	0.20 ppm

Vegetable, foliage of legume, group 7 	2.0 ppm

Caneberry, subgroup 13A 	1.0 ppm

Grain, cereal, group 15 	1.1 ppm

Grain, cereal, forage, fodder and straw, 

     group 16 	1.1 ppm

Animal feed, nongrass, group 18, forage 	0.70 ppm

Animal feed, nongrass, group 18, hay	1.1 ppm

Animal feed, nongrass, group 18, seed	2.0 ppm

Artichoke, globe	2.0 ppm

Asparagus 	2.0 ppm

Banana 	0.20 ppm

Cacao bean 	0.02 ppm

Canola, seed 	0.20 ppm

Coffee 	0.02 ppm

Cranberry 	1.0 ppm

Date 	0.30 ppm

Kiwifruit 	0.10 ppm

Pawpaw  	1.0 ppm

Peanut 	0.20 ppm

Pineapple 	0.30 ppm

Pomegranate 	0.20 ppm

Safflower, seed 	0.20 ppm

Sesame, seed 	0.20 ppm

Sugarcane 	1.1 ppm

Tea  	0.02 ppm

Watercress 	2.0 ppm

 

Hazard Assessment

Pyriproxyfen is of low acute toxicity, since all acute studies place
pyriproxyfen in Toxicity Category III or IV.  Pyriproxyfen is not a
dermal sensitizer.  No significant systemic toxicity was observed in
either the 21-day dermal toxicity study in rats or the 28-day inhalation
toxicity study in rats.  Subchronic and chronic toxicity studies in
mice, rats and dogs indicate that the liver and kidney are the principal
target organs with slight anemia occurring in the rodent species.  There
was no evidence of increased susceptibility to rat and rabbit fetuses in
prenatal developmental toxicity studies, or to rat offspring in the
2-generation rat reproduction study.  No evidence of developmental
toxicity was seen in special studies that evaluated pyriproxyfen
toxicity following perinatal and prenatal exposure in rats.  There was
no evidence of carcinogenicity in either a 78-week mouse feeding study
or in the 2-year rat chronic/carcinogenicity study.  Pyriproxyfen is
classified as a "Group E" chemical - no evidence of carcinogenicity to
humans.  Pyriproxyfen is negative for mutagenic activity in a battery of
mutagenicity studies conducted with both the parent or metabolites. 
However, an in vivo cytogenetic assay with pyriproxyfen technical is
absent in the database and is considered a data gap.  Pyriproxyfen was
absorbed, metabolized, and rapidly excreted, primarily in the feces, in
the rat metabolism study.  There were no effects of gender, dose, or
label position on absorption or elimination in the rat metabolism study.

Dose Response Assessment and Food Quality Protection Act (FQPA) Decision

The Hazard Identification Assessment Review Committee (HIARC) met on
October 14, 1997 and November 20, 2001 to select endpoints for risk
assessment and to evaluate the potential for increased susceptibility of
infants and children from exposure to pyriproxyfen (TXR Nos. 012372 and
0050412).  The HED FQPA Safety Factor Committee (SFC) met on December 7,
1998 to evaluate the hazard and exposure data for pyriproxyfen and
recommended that the FQPA safety factor (as required by FQPA of August
3, 1996) be removed in assessing the risk posed by this chemical (TXR
No. 013028).  This decision was based on the absence of evidence of
quantitative and qualitative increased susceptibility of the young
demonstrated by in utero prenatal exposure in rat and rabbit
developmental studies and pre/postnatal exposure in the rat 2-generation
reproduction study.  The potential for increased susceptibility of
infants and children from exposure to pyriproxyfen evaluated by the
HIARC and FQPA SFC conforms to the current 2002 OPP 10X guidance
document. 

Risk assessments were conducted for the specific exposure scenarios
listed below.  An acute reference dose (aRfD) was not established for
females 13-50 years old or the general population, because acute oral
effects attributed to a single-dose exposure could not be identified in
the toxicology database, including maternal toxicity in the
developmental toxicity studies.  Therefore, an acute risk assessment is
not required.  The chronic reference dose (cRfD) of 0.35 mg/kg/day was
determined on the basis of decreased body weight and changes in clinical
chemistry parameters in two co-critical rat toxicity studies (subchronic
and chronic).  Since the special FQPA SF has been reduced to 1X, the
chronic population-adjusted dose (cPAD) is equal to the cRfD.

Based on the decisions made by the HIARC and the FQPA SFC, the level of
concern for occupational dermal and inhalation exposure is 100.  The
RfD/Peer Review Committee classified pyriproxyfen as "Group E" chemical,
no evidence for carcinogenicity to humans, based on the absence of
evidence of carcinogenicity in male and female rats as well as in male
and female mice.  Therefore, a cancer risk assessment is not required. 
Short- and intermediate-term dermal endpoints were not selected since
there was no systemic toxicity up to the limit dose of 1,000 mg/kg/day
in the 21-day dermal toxicity study in rats.  The long-term dermal
endpoint was based on the systemic toxicity no-observed adverse-effect
level (NOAEL) of 35.1 mg/kg/day from the two co-critical (subchronic and
chronic) rat feeding studies.  Short- and intermediate-term inhalation
endpoints were not selected, based on the inhalation toxicity NOAEL of
0.482 mg/L (138 mg/kg/day in males and 162 mg/kg/day in females) and the
lack of significant toxicity at the lowest-observed adverse-effect level
(LOAEL) of 1.0 mg/L in the 28-day inhalation toxicity study in rats. 
The long-term inhalation endpoint was based on the systemic toxicity
oral NOAEL of 35.1 mg/kg/day from the two co-critical (subchronic and
chronic) rat feeding studies.  An inhalation-absorption factor of 100%
was used for route-to-route extrapolation.  A common toxicity endpoint
(decreases in body weight and alterations in clinical pathology
parameters) was identified for the oral, dermal (oral equivalent) and
inhalation (oral equivalent) routes; therefore, these routes can be
combined for the appropriate populations for long-term aggregate risk
assessment.  Risk assessments were performed for the following exposure
scenarios:

chronic dietary	

NOAEL = 35.1 mg/kg/day	

cRfD and cPAD = 0.35 mg/kg/day

long-term dermal	

oral NOAEL = 35.1 mg/kg/day	

Target MOE = 100 (occupational)

long-term inhalation	

oral NOAEL =35.1mg/kg/day	

Target MOE =100 (occupational)

Residue Chemistry Exposure

No new residue field trial data were submitted with this petition. 
IR-4’s proposals for the new tolerances were presented to HED’s
Chemistry Science Advisory Council (ChemSAC) on June 22, 2006.  The SAC
agreed with the petitoner’s proposals.  ARIA recommends for all the
proposed tolerances except for those for which confirmatory data are
required since, as of the date of this review, the confirmatory data
have not been received.  The tolerance for the residues of pyriproxyfen
on vegetable leaves of root and tuber, group 1; vegetable, leafy, except
Brassica, group 4; vegetable, foliage of legume, group 7; artichoke,
globe; asparagus; kiwifruit; and watercress cannot be established at
this time.  In addition, IR-4 has proposed a tolerance vegetable,
legume, group 6.  The data have been reviewed and a tolerance of 0.20
ppm was recommended for the residues of vegetable, legume, group 6 ( 
SEQ CHAPTER \h \r 1 PP#s 4F6847, 3E6596, 3E6596, 3E6750, 4E6866, 4E6865
& 3E6582, DP Num: 312387, 312389, 312391, 312460 and 312463, G. Kramer,
7/15/05).  The tolerance request is no longer required.  The commodity
definition, vegetable, bulb, group 3, except onion dry bulb is
incorrect.  The correct definition is: vegetable, bulb, group 3, except
onion, bulb. The tolerance definition should be corrected in Section F.

Associated with the proposed tolerances are processed commodities of
regulatory interest.  Since no new processing data were submitted with
this petition, the theoretical processing factors or processing factors
from the Agency’s pyriproxyfen database are used to calculate a
tolerance value.  Tolerances are required for all the processed
commodities which have higher estimated tolerance levels than the
associated RAC.   Tolerances are required for beet, dry pulp at 3.0 ppm;
potato granules/flakes, chips, and wet peel, all at 0.75 ppm; rice,
hulls at 5.5 ppm; coffee, instant at 0.10 ppm; and pineapple, process
residue at 1.1 ppm.

Some of the raw agricultural commodities (RAC) for which tolerances are
requested and some of the associated processed commodities are livestock
feed items of regulatory interest. However, there are not sufficient
changes in dietary burdens to require increases in livestock tolerances
at this time. 

Occupational Exposure and Risk Estimates

Based on the proposed use patterns, commercial handlers and private
growers are expected to have short-term dermal and inhalation exposures.
 However, since no short- or intermediate-term dermal or inhalation
endpoints were selected by HIARC, no occupational exposure assessment
was conducted. 

Residential Exposure and Risk Estimates

Pyriproxyfen is the active ingredient in many registered residential
products for flea and tick control (home environment and pet treatments)
as well as products for ant and roach control (indoor and outdoor
applications).  Formulations include carpet powders, foggers, aerosol
sprays, liquids (shampoos, sprays and pipettes for pet treatments),
granules, bait (indoor and outdoor), and impregnated materials (pet
collars).  Adults and toddlers could potentially be exposed to
pyriproxyfen residues on treated carpets, floors, upholstery, and pets;
however, since the HIARC did not select any short-term dermal or
inhalation endpoints, only a post-application residential assessment was
conducted.  Toddlers are anticipated to have higher exposures than
adults from treated home environments and pets due to their behavior
patterns.

Short-, intermediate-, and long-term toddler hand-to-mouth exposures
(consisting of petting treated animals and touching treated
carpets/flooring) were assessed; long-term dermal exposures were also
assessed for products with anticipated efficacy of more than 6 months
(carpet powders and pet collars).  Toddler exposures to combined
treatment scenarios, where a pet owner treats the home environment and
the pet in the same period (such as carpet powder and pet shampoo
treatments), were also assessed.  All residential exposures assessed do
not exceed ARIA’s level of concern (margins of exposure (MOEs) <100).

Dietary Exposure Estimates 

An unrefined (tolerance-level residues, 100% crop treated, and default
processing factors) chronic dietary exposure analysis was conducted
using the Dietary Exposure Evaluation Model software with the Food
Commodity Intake Database (DEEM-FCID(, Version 2.0), which incorporates
consumption data from the USDA’s Continuing Surveys of Food Intake by
Individuals (CSFII), 1994-1996 and 1998.  The chronic dietary food
exposure estimates were less than ARIA’s level of concern (<100% cPAD)
for the general U.S. population and all population subgroups. 
Specifically, the chronic dietary risk estimates occupied 10% or less of
the cPAD for the general U.S. population and all population subgroups.

Drinking Water

Since ARIA does not have ground or surface water monitoring data to
calculate quantitative aggregate exposure, estimates of pyriproxyfen
levels in surface and ground water were made using computer modeling. 
The estimated drinking water concentrations (EDWCs) for surface water
(from Pesticide Root Zone Model/Exposure Analysis Modeling System
(PRZM/EXAMS)) are 2.15 and 0.40 ppb for the peak and long-term
scenarios, respectively.  The EDWC for ground water (from SCI-GROW
(Screening Concentration in Ground Water) modeling) is 0.006 ppb to be
used for both acute and chronic scenarios.  Drinking water was
incorporated directly into the dietary assessment

Exposure Scenarios and Risk Conclusions

Including all existing and proposed uses, human-health risk assessments
have been conducted for the following exposure scenarios: chronic
dietary exposure (food and water) and chronic aggregate exposure (food,
water, and residential); short- and intermediate-term aggregate exposure
(food, water, and residential); and short-, intermediate-, and long-term
residential exposure.  A cancer aggregate risk assessment was not
performed since pyriproxyfen has not been classified as a potential
carcinogen.  All aggregate exposure and risk estimates are below
ARIA’s level of concern.

Recommendation for Tolerances and Registration 

Provided the revised Section F is submitted, the toxicological and
residue chemistry databases, as well as the aggregate risk assessments,
support conditional registration of the requested new uses and
establishment of the following permanent tolerances for residues of
pyriproxyfen [2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine] per se:

Commodity

	Tolerance

Vegetable, root and tuber, group 1	0.15 ppm

Beet, sugar, dried pulp	3.0 ppm

Potato, granules/flakes	0.75 ppm

Potato, chips	0.75 ppm

Potato, wet peel	0.75 ppm

Vegetable, bulb, group 3, 

     except onion, bulb 	0.70 ppm

Caneberry, subgroup 13A 	1.0 ppm

Grain, cereal, group 15 	1.1 ppm

Rice, hulls	5.5 ppm

Grain, cereal, forage, fodder and straw, 

     group 16 	1.1 ppm

Animal feed, nongrass, group 18, forage ppm	0.70 ppm

Animal feed, nongrass, group 18, hay	1.1 ppm

Animal feed, nongrass, group 18, seed	2.0 ppm

Banana 	0.20 ppm

Cacao bean, dried bean 	0.02 ppm

Canola, seed 	0.20 ppm

Coffee bean, green bean	0.02 ppm

Coffee, instant	0.10 ppm

Cranberry 	1.0 ppm

Date 	0.30 ppm

Pawpaw  	1.0 ppm

Peanut 	0.20 ppm

Pineapple 	0.30 ppm

Pineapple, process residue	1.1 ppm

Pomegranate 	0.20 ppm

Safflower, seed 	0.20 ppm

Sesame, seed 	0.20 ppm

Sugarcane 	1.1 ppm

Tea  	0.02 ppm

ARIA recommends that conversion of conditional registration to
unconditional registration may be considered upon submission of the
following toxicology data:

An in vivo cytogenetic study (OPPTS Guideline No. 870.5385) with
pyriproxyfen technical.

Summary of Deficiencies:

Revised Section F

An in vivo cytogenetic study (OPPTS Guideline No. 870.5385) with
pyriproxyfen technical.

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

Table 2.a  Test Compound Nomenclature

Pyriproxyfen	

Common name	

Pyriproxyfen

Company experimental name	

S-71639, S-31183

IUPAC name	

4-phenoxyphenyl (RS)-2-(2-pyridyloxy)propyl ether

CAS name	

2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine

CAS #	

95737-68-1

End-use products/(EP)	

Knack® IGR, Distance® IGR, Esteem® IGR, Esteem® 35 WP IGR, and
Esteem® Ant Bait

Table 2.b  Physicochemical Properties of the Technical Grade Test
Compound

Parameter	

Value

Melting point/range	

45-47 (C

pH 	

6.4 (20(C)

Density	

1.24 (25 (C)

Water solubility ( 25(C)	

0.367 ppm

Solvent solubility (mg/L at 20(C)	

76700 (Hexane)

Solvent solubility (mg/L at 20(C)	

60100 (Methanol)

Vapor pressure at 20(C	

1.0 x 10-7 mm/Hg

Dissociation constant (pKa)	

NA*

Octanol/water partition coefficient Log(KOW)	

5.37

UV/visible absorption spectrum	

288 and 330 nm

* Not Available.

3.0  HAZARD CHARACTERIZATION tc \l1 "3.0  HAZARD CHARACTERIZATION 

A detailed hazard characterization for pyriproxyfen was presented in
HED’s previous risk assessment (DP Num: 286556, W. Donovan, 11/20/02).
 The doses and toxicological endpoints selected for various exposure
scenarios for this risk assessment are summarized in Table 3.1.

3.1.	Dose Response Assessment tc \l2 "3.1.	Dose Response Assessment 

Table 3.1  Summary of Toxicological Dose and Endpoints for Pyriproxyfen
Used in Human Risk Assessment1

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 old and general population	

none	

none	

An appropriate endpoint attributable to a single oral dose was not
available in the data base, including maternal toxicity in the
developmental toxicity studies.

Chronic Dietary

all populations	

NOAEL= 35.1 mg/kg/day

UF = 100

Chronic RfD = 0.35 mg/kg/day	

FQPA SF = 1X 

cPAD = cRfD

             FQPA SF

= 0.35 mg/kg/day	

Subchronic toxicity and chronic toxicity (feeding) - rat

(co-critical)

LOAEL = 141.28 mg/kg/day based on decreased body weight and clinical
pathology results.

Short-Term Incidental, Oral (1-30 days)

Residential	

Oral Maternal NOAEL = 100 mg/kg/day	

LOC for MOE = 100	

Rat developmental toxicity study

Maternal LOAEL = 300 mg/kg/day based on decreased body weight, body
weight gain, and food consumption, and increased water consumption

Intermediate-Term Incidental, Oral (1-6 months)

Residential	

Oral NOAEL = 35.1 mg/kg/day	

LOC for MOE = 100	

Subchronic toxicity and chronic toxicity (feeding) - rat

(co-critical)

LOAEL = 141.28 mg/kg/day based on decreased body weight and clinical
pathology results.

Short-, and Intermediate-Term Dermal (1-30 days and 1-6 months)

(Occupational/

Residential)	

none	

none	

Based on the systemic toxicity NOAEL of 1,000 mg/kg/day (limit dose) in
the 21 day dermal toxicity study in rats, quantification of dermal risks
is not required.  In addition, no developmental concerns (toxicity) were
seen in either rats or rabbits. 

Long-Term

Dermal (6 months-lifetime)

(Occupational/

Residential)	

Oral NOAEL= 35.1 mg/kg/day (dermal absorption rate = 30%)

	

LOC for MOE = 100 	

Subchronic and chronic toxicity (feeding) - rat

(co-critical)

LOAEL = 141.28 mg/kg/day based decreased body weight and clinical
pathology results

Short-, and Intermediate-Term Inhalation (1-30 days and 1-6 months)

(Occupational/

Residential)	

none	

none	

Based on the absence of significant toxicity at the LOAEL of 1.0 mg/L
(limit dose), the quantification of inhalation risks is not required. 
In addition, no developmental concerns (toxicity) were seen in either
rats or rabbits. 

Long-Term Inhalation (6 months-lifetime)

(Occupational/

Residential)	

Oral study NOAEL= 35.1 mg/kg/day

(inhalation absorption rate = 100%)	

LOC for MOE = 100	

Subchronic and chronic toxicity (feeding) - rat

(co-critical) 

LOAEL = 141.28 mg/kg/day based on decreased body weight and clinical
pathology results

Cancer (oral, dermal, inhalation)	

Cancer classification ("Group E") 	

Risk Assessment not required	

No evidence of carcinogenicity 

1 UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no
observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD =
reference dose, LOC = level of concern, MOE = margin of exposure

Acute Dietary Endpoint:  An aRfD for females 13-50 years old or the
general population, including infants and children, was not selected
because an acute oral endpoint attributed to a single-dose exposure
could not be identified in the hazard database, including maternal
toxicity in the developmental toxicity studies.

Chronic Dietary Endpoint:  The cRfD of 0.35 mg/kg/day was determined on
the basis of two co-critical rat toxicity studies (subchronic and
chronic).  Rats are the most sensitive species tested with pyriproxyfen.
 A UF of 100 (10-fold for interspecies extrapolation and 10-fold for
intra species variability) was applied to the NOAEL of 35.1 mg/kg/day to
derive the cRfD.  The NOAEL of 35.1 mg/kg/day is based on decreased body
weight and clinical chemistry parameters observed in the 90-day and
2-year studies at the LOAEL of 141.28 mg/kg/day.  The FQPA safety factor
of 1X is applicable for chronic dietary risk assessment.  Therefore, the
cPAD also equals 0.35 mg/kg/day.

Carcinogenicity:  In accordance with the Agency’s 1986 Guidelines for
Carcinogenic Risk Assessment, the RfD/Peer Review Committee classified
pyriproxyfen as a "Group E" chemical- negative for carcinogenicity to
humans.  This classification is based on the lack of evidence of
carcinogenicity in mice and rats.

Short-Term Incidental, Oral Endpoint:  The short-term incidental oral
endpoint was selected from the maternal toxicity findings in the rat
developmental study.  The NOAEL/LOAEL is 100/300 mg/kg/day based on
decreased body weight, body weight gain, and food consumption and
increased water consumption.  Additionally, the oral systemic toxicity
in the dams is appropriate to the population of concern (infants and
children) and occurs over a 10-day exposure period which is appropriate
for the comparative duration (1-30 days) of the short-term exposure
scenario.

Intermediate-Term Incidental, Oral Endpoint:  The intermediate-term
incidental oral endpoint was selected from the systemic toxicity
(decreased body weight gain and clinical chemistry effects) produced in
two co-critical (subchronic and chronic) rat feeding studies.  The
NOAEL/LOAEL is 35.1/141.28 mg/kg/day based on systemic toxicity observed
in both co-critical 90-day and 2-year rat feeding studies.  The oral
route of exposure and duration of the subchronic and chronic rat feeding
studies are appropriate for the intermediate-term incidental oral
exposure scenario.  The dose/endpoint is appropriate for the population
(infants and children) and since the effects were seen after 90 days,
the effects are appropriate for the duration (intermediate) of concern.

Short- and Intermediate-Term Dermal Endpoint:  The short- and
intermediate-term dermal endpoints were not chosen since no dermal or
systemic toxicity was observed in the 21-day dermal toxicity study at
the limit dose of 1000 mg/kg/day.  In addition, no developmental
concerns (toxicity) were seen either in rats or rabbits.  Therefore, no
hazard was identified and quantification of dermal risk is not required.

Long-Term Dermal Endpoint:  The long-term dermal endpoint was chosen
from the co-critical 90-day and 2-year rat studies.  The NOAEL/LOAEL for
the co-critical rat studies is 35.1/141.28 mg/kg/day and is appropriate
for the long-term dermal risk assessment, since the selected NOAEL/LOAEL
is the lowest from any study, and the exposure scenarios (>6 months) is
comparable to the duration of the rat studies, when considering
estimated exposure between the rat and human.  Dermal penetration was
estimated to be 30% by the extrapolation method of comparing the
maternal toxicity LOAEL of 300 mg/kg/day in the rat developmental
toxicity oral study and the dermal NOAEL of 1,000 mg/kg/day in the
21-day dermal study.  Thus, a dermal-penetration factor of 30% was used
for the route-to-route extrapolation in this dermal risk assessment,
since an oral study was selected for the endpoint.

Short- and Intermediate-Term Inhalation Endpoints:  The short- and
intermediate-term inhalation endpoints were not selected because of the
lack of significant toxic effects in the 28-day inhalation toxicity
study in rats.  In this study, the systemic NOAEL was 0.482 mg/L based
on salivation, sporadic decreases in body weight and increased lactate
dehydrogenase (LDH) levels at the inhalation toxicity LOAEL of 1.0 mg/L.
 In addition, no developmental concerns (toxicity) were seen either in
rats or rabbits.  Therefore, no hazard was identified and quantification
of inhalation risks is not required.  Additionally, the 28-day
inhalation exposure period adequately evaluates the 6-month maximum
inhalation exposure period in humans for these scenarios based on a
comparison of the periods for exposure estimates between the rat and
humans.

  

Long-Term Inhalation Endpoints:  The long-term inhalation endpoint was
chosen from the co-critical 90-day and 2-year rat studies.  The
NOAEL/LOAEL for the co-critical rat studies is 35.1/141.28 mg/kg/day and
is appropriate for the long-term dermal risk assessment, since the
selected NOAEL/LOAEL is the lowest from any study, and the exposure
scenarios (>6 months) are comparable to the duration of the rat studies,
when considering estimated exposure between the rat and human. Since an
oral route was used, an inhalation-absorption factor of 100% of oral
absorption was used to convert the inhalation exposure component
(µg/ai/day) and the application rate to an oral equivalent dose
(mg/kg/day).

3.2  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).

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

4.0  EXPOSURE ASSESSMENT AND CHARACTERIZATION tc \l1 "4.0  EXPOSURE
ASSESSMENT AND CHARACTERIZATION 

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

There are currently several end-use products of pyriproxyfen with
food/feed uses that are registered to Valent USA Corporation: three
emulsifiable concentrates (EC), a wettable powder (WP), and an ant bait
granular formulation.  These formulations are registered for use on
cotton, fruiting vegetables, citrus fruits, pome fruits, stone fruit,
bushberry, tree nuts, lychee, guava and related tropical fruits, and are
marketed under the trade names Knack® IGR [0.86 lb/gal EC; EPA Reg. No.
59639-95], Distance® IGR [0.86 lb/gal EC; EPA Reg. No. 59639-96],
Esteem® IGR [2.9 lb/gal EC; EPA Reg. No. 59639-104], Esteem® 35 WP IGR
[35% WP; EPA Reg. No. 59639-115], and Esteem® Ant Bait [0.5% w/w; EPA
Reg. No. 59639-114].  The maximum seasonal use is 0.020-0.219
lb/ai/acre.  There is a maximum of two applications (at least 2-16 weeks
retreatment interval (RTI)) per season.  The single application rate is
0.01-0.109 lb ai/acre with 0- to 21-day preharvest intervals (PHIs).

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

Table 4.2  Summary of Directions for Use of Pyriproxyfen

Applic. Timing, Type, and Equip.	

Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	

PHI

(days)	

Use Directions and Limitations

Artichoke, Globe

Foliar application ground equipment	Knack® IGR [59639-95]

Esteem® 35 WP IGR [59639-115]	0.0672	2	0.134	7	RTI = 14 days

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Asparagus

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0672	2	0.134	7	RTI = 14 days

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Banana and Plantain

Foliar application ground or aerial equipment	Knack® IGR [59639-95]
Esteem® 35 WP IGR [59639-115]	0.109	3	0.327	14	RTI = 14 days

By air: 3-10 gpa

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Berries

Foliar application ground or aerial equipment	Knack® IGR [59639-95]
Esteem® 35 WP IGR [59639-115]	0.109	2	0.218	7	RTI = 14 days

By air: min 5 gpa

By ground: min 50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.109	2	0.218	1	RTI = 12-16 weeks

Bulb Vegetables

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0672	2	0.134	3	RTI = 14 days

By ground: 20-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Cacao Bean

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Canola (seed only)

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Cereal Grains

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Coffee

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Cranberry

Foliar application ground or aerial equipment	Knack® IGR [59639-95]
Esteem® 35 WP IGR [59639-115]	0.109	2	0.218	7	RTI = 14 days

By air: min 5 gpa

By ground: min 20 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.109	2	0.218	1	RTI = 12-16 weeks

Dates

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Kiwi Fruit

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.109	2	0.218	30	RTI = 14 days

By ground: min 45 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.109	2	0.218	1	RTI = 12-16 weeks

Leafy Vegetables (except Brassica) 

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0672	2	0.134	14	RTI = 14 days

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Legume Vegetable (Succulent or Dried)

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0672	2	0.134	7	RTI = 14 days

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Nongrass Animal Feed

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Pawpaw

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.109	3	0.327	14	RTI = 14 days

By ground: 100-400 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.109	3	0.327	1	RTI = 12-16 weeks

Peanuts

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Pineapple

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0672	2	0.134	1	RTI = 21 days

By ground: 20-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

Pomegranate

Foliar application ground or aerial equipment	Knack® IGR [59639-95]
Esteem® 35 WP IGR [59639-115]	0.109	3	0.327	14	RTI = 14 days

By air: 3-10 gpa

By ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.109	3	0.327	1	RTI = 12-16 weeks

Root and Tuber Vegetables

Foliar application ground equipment	Knack® IGR [59639-95] Esteem® 35
WP IGR [59639-115]	0.0545	2	0.109	3	RTI = 14 days

By ground: 20-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0545	2	0.109	1	RTI = 12-16 weeks

Safflower

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Sesame

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Sugarcane

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Tea

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.02	2	0.04	1	RTI = 12-16 weeks

Watercress

Foliar application ground or aerial equipment	Knack® IGR [59639-95]
Esteem® 35 WP IGR [59639-115]	0.0672	2	0.134	7	RTI = 14 days

By air or ground: 10-50 gpa

Broadcast ground or aerial equipment	Esteem® Ant Bait IGR [59639-114]
0.0672	2	0.134	1	RTI = 12-16 weeks

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

Nature of the Residue - Plants:  Adequate metabolism studies for
pyriproxyfen are available on apples (DP Num: 238190, W. Donovan,
12/7/98), cotton (DP Num: 228556, J. Garbus, 5/6/97), and tomatoes (DP
Num: 253836, W. Donovan, 3/25/99).  Based on these studies, the
Metabolism Assessment Review Committee (MARC) determined that the
residue of concern in plants is pyriproxyfen per se (DP Num: 250953, W.
Donovan and W. Dykstra, 11/19/98). 

Nature of the Residue - Livestock:  Ruminant and poultry metabolism
studies have previously been submitted and reviewed (PP#6F4737, DP Num:
228556, J. Garbus, 5/6/97) in conjunction with a petition for cotton. 
The HED MARC determined that should future crop uses increase the
maximum theoretical dietary burden (MTDB) to the point that tolerances
are needed in livestock commodities, the residue of concern will be
pyriproxyfen and the free and sulfate forms of 4'-OH-PYR.

Residue Analytical Methods:  In conjunction with the crop field trial
studies, the petitioner submitted adequate concurrent recovery data for
a gas chromatography/nitrogen-phosphorus detector (GC/NPD) method
(RM-33P-1-3a or 9.66 V 1) used to determine residues of pyriproxyfen
in/on the subject crops.  The method has undergone an adequate
radiovalidation, independent laboratory validation (ILV) trial, petition
method validation (PMV) trial (DP Num: 257337, W. Donovan, 7/1/99), and
has been forwarded to the FDA for inclusion in PAM Vol. II (DP Num:
258406, W. Donovan, 8/5/99).  The GC/NPD method RM-33P-1-3a is adequate
for enforcement of the recommended tolerance levels for residues of
pyriproxyfen per se in/on the subject crops.  As tolerances for residues
of pyriproxyfen in livestock commodities are not required at this time,
enforcement methodology for determining residues in livestock are not
required.

Magnitude of the Residue - Plants:  No new data were submitted with this
petition.  IR-4’s proposals for the new tolerances were presented to
HED’s ChemSAC on June 22, 2006.  The SAC’s determinations as well as
the current status of each proposed tolerance is discussed below.

Vegetable, root and tuber, group 1

IR-4 has proposed a tolerance of 0.15 ppm on vegetable, root and tuber,
group 1 using the supporting data from dry bulb onion (PP# 3E6750). 
Considering the supporting data, the ChemSAC agreed with the proposed
tolerance.  A tolerance for the residues of pyriproxyfen on vegetable,
root and tuber, group 1 at 0.15 ppm should be established.  

Vegetable, leaves of root and tuber, group 2

IR-4 has proposed a tolerance of 2.0 ppm on vegetable, leaves of root
and tuber, group 2

using the tolerance established at 2.0 ppm on Brassica, leafy greens,
subgroup 5B and a future residue study on celery with 8 trials in 2005
to provide confirmatory data.  Considering the supporting data, the
ChemSAC agreed with the proposed tolerance.  However, as of the date of
this review, the confirmatory data have not been received.  A tolerance
for the residues of pyriproxyfen on vegetable, leaves of root and tuber,
group 1 cannot be established at this time.  The tolerance request
should be removed from Section F.  The issue should be revisited when
the data are submitted. 

Vegetable, bulb, group 3, except onion, dry bulb

IR-4 proposed a tolerance of 0.70 ppm on vegetable, bulb, group 3,
except onion dry bulb

using the tolerance established on 0.70 ppm for onion, green which in
turn was based on grass, forage (PP# 4F6847).  Considering the
supporting data, the ChemSAC agreed with the proposed tolerance.  A
tolerance for the residues of pyriproxyfen on vegetable, bulb, group 3,
except onin, bulb at 0.70 ppm should be established.

Vegetable, leafy, except Brassica, group 4

IR-4 has proposed a tolerance of 2.0 ppm on vegetable, leafy, except
Brassica, group 4

using the tolerance established at 2.0 ppm on Brassica, leafy greens,
subgroup 5B and a future residue study on celery with 8 trials in 2005
to provide confirmatory data.  Considering the supporting data, the
ChemSAC agreed with the proposed tolerance.  However, as of the date of
this review, the confirmatory data have not been received.  A tolerance
for the residues of pyriproxyfen on vegetable, leafy, except Brassica,
group 4 cannot be established at this time.  The tolerance request
should be removed from Section F.  The issue should be revisited when
the data are submitted. 

Vegetable, legume, group 6

IR-4 has proposed a tolerance of 0.20 ppm based on the residue data
developed on the representative crops for subgroup 6A.  A petition
proposing a tolerance for pyriproxyfen on vegetable, legume, edible
podded, subgroup 6A; pea and bean, succulent shelled, subgroup 6B; and
pea and bean, dried shelled, except soybean, subgroup 6C, PP# 3E6596. 
This petition was accompanied by two data volumes, MRID# 45940001
(pyriproxyfen on edible-podded peas) and MRID# 45940002 (pyriproxyfen on
snap beans).  The data has been reviewed and a tolerance of 0.20 ppm was
recommended for the residues of vegetable, legume, group 6 (  SEQ
CHAPTER \h \r 1 PP#s 4F6847, 3E6596, 3E6596, 3E6750, 4E6866, 4E6865 &
3E6582, DP Num: 312387, 312389, 312391, 312460 and 312463, G. Kramer,
7/15/05).  Since the requested tolerance has already been established,
the tolerance request should be removed from Section F.

Vegetable, foliage of legume, group 7

IR-4 has proposed a tolerance of 2.0 ppm on vegetable, foliage of
legume, group 7 using the tolerance established at 2.0 ppm Brassica,
leafy greens, subgroup 5B and a future residue study on celery with 8
trials in 2005 to provide confirmatory data.  Considering the supporting
data, the ChemSAC agreed with the proposed tolerance.  However, as of
the date of this review, the confirmatory data have not been received. 
A tolerance for the residues of pyriproxyfen on vegetable, foliage of
legume, group 7 cannot be established at this time.  The tolerance
request should be removed from Section F.  The issue should be revisited
when the data are submitted. 

Caneberry, subgroup 13A

IR-4 has proposed a tolerance of 1.0 ppm using the tolerance established
at 1.0 ppm for caneberry, subgroup 13A based on the tolerance for
bushberry subgroup 13B  (PP# 2E6353).  Considering the supporting data,
the ChemSAC agreed with the proposed tolerance.  A tolerance for the
residues of pyriproxyfen on caneberry, subgroup 13A at 1.0 ppm should be
established.

Grain, cereal, group 15

IR-4 has proposed a tolerance of 1.1 ppm on grain, cereal, group 15
using the tolerance established at 1.1 ppm on grass, forage (PP#
4F6847).  Considering the supporting data and the proposed use as an ant
bait only, the ChemSAC agreed with the proposed tolerance.  A tolerance
for the residues of pyriproxyfen on grain, cereal, group 15 at 1.1 ppm
should be established.

Grain, cereal, forage, fodder and straw, group 16

IR-4 proposed a tolerance of 1.1 ppm on grain, cereal, forage, fodder
and straw, group 16 using the tolerance established at 1.1 ppm on grass,
forage (PP# 4F6847).  Considering the supporting data and the proposed
use only as an ant bait, the ChemSAC agreed with the proposed tolerance.

A tolerance for the residues of pyriproxyfen on grain, cereal, forage,
fodder and straw, group 16 at 1.1 ppm should be established.

Animal feed, nongrass, group 18

IR-4 proposed tolerances of 0.70, 1.1, and 2.0 ppm on animal feed,
nongrass, group 18, forage, hay, and seed, respectively, using the
tolerances established at 0.70, 1.1, and 2.0 ppm on grass, forage, hay,
and seed (PP# 4F6847).  Considering the supporting data, the ChemSAC
agreed with the proposed tolerance.  Tolerances for the residues of
pyriproxyfen on animal feed, nongrass, group 18, forage, hay, and seed
at 0.70, 1.1, 2.0 ppm respectively should be established.  

Artichoke, globe

IR-4 has proposed a tolerance of 2.0 ppm on artichoke, globe using the
tolerance established at 2.0 ppm on Brassica, leafy greens, subgroup 5B
and a future residue study on celery with 8 trials in 2005 to provide
confirmatory data.  Considering the supporting data, the ChemSAC agreed
with the proposed tolerance.  However, as of the date of this review,
the confirmatory data have not been received.  A tolerance for the
residues of pyriproxyfen on artichoke, globe cannot be established at
this time.  The tolerance request should be removed from Section F.  The
issue should be revisited when the data are submitted.

Asparagus

IR-4 has proposed a tolerance of 2.0 ppm on asparagus using the
tolerance established at 2.0 ppm on Brassica, leafy greens, subgroup 5B
and a future residue study on celery with 8 trials in 2005 to provide
confirmatory data.  Considering the supporting data, the ChemSAC agreed
with the proposed tolerance.  However, as of the date of this review,
the confirmatory data have not been received.  A tolerance for the
residues of pyriproxyfen on asparagus cannot be established at this
time.  The tolerance request should be removed from Section F.  The
issue should be revisited when the data are submitted.

 

Banana

IR-4 has proposed a tolerance of 0.20 ppm on banana using the tolerance
established at 0.20 ppm on vegetable, fruiting, group 8.  Considering
the supporting data, the ChemSAC agreed with the proposed tolerance.  A
tolerance for the residues of pyriproxyfen on banana at 0.20 ppm
respectively should be established.

Cacao bean

IR-4 has proposed a tolerance of 0.02 ppm on cacao bean using the
tolerance established at 0.02 ppm on nut, tree, group 14.  Considering
the supporting data and the proposed use only as an ant bait, the
ChemSAC agreed with the proposed tolerance.  A tolerance for the
residues of pyriproxyfen on cacao bean at 0.02 ppm should be
established.

Canola, seed

IR-4 has proposed a tolerance of 0.20 ppm on canola using the tolerance
established at 0.20 ppm on bean, succulent.  Considering the supporting
data and the proposed use only as an ant bait, the ChemSAC agreed with
the proposed tolerance.  A tolerance for the residues of pyriproxyfen on
canola at 0.20 ppm should be established.

Coffee

 IR-4 has proposed a tolerance of 0.02 ppm on coffee using the tolerance
established at 0.02 ppm on nut, tree, group 14.  Considering the
supporting data and the proposed use only as an ant bait, the ChemSAC
agreed with the proposed tolerance.  A tolerance for the residues of
pyriproxyfen on coffee at 0.02 ppm should be established.

Cranberry

IR-4 has proposed a tolerance of 1.0 ppm on cranberry using the
tolerance established at 1.0 ppm on bushberry, subgroup 13B. 
Considering the supporting data, the ChemSAC agreed with the proposed
tolerance.  A tolerance for the residues of pyriproxyfen on cranberry at
1.0 ppm should be established.

Date

IR-4 has proposed a tolerance of 0.30 ppm on date using the tolerance
established at 0.30 ppm on fig.  Considering the supporting data, the
ChemSAC agreed with the proposed tolerance.  A tolerance for the
residues of pyriproxyfen on date at 0.30 ppm should be established. 

Kiwifruit

IR-4 has proposed a tolerance of 0.10 ppm on kiwifruit using the
tolerance established on starfruit and a future residue study on
kiwifruit with 3 trials in 2005 to provide confirmatory data. 
Considering the supporting data, the ChemSAC agreed with the proposed
tolerance.  However, as of the date of this review, the confirmatory
data have not been received.  A tolerance for the residues of
pyriproxyfen on kiwifruits cannot be established at this time.  The
tolerance request should be removed from Section F.  The issue should be
revisited when the data are submitted.

Pawpaw

IR-4 has proposed a tolerance of 1.0 ppm on pawpaw using the tolerance
established at 1.0 ppm on fruit, stone, group 12.  Considering the
supporting data, the ChemSAC agreed with the proposed tolerance.  A
tolerance for the residues of pyriproxyfen on pawpaw at 1.0 ppm should
be established. 

Peanut

IR-4 has proposed a tolerance of 0.20 ppm on peanut using the tolerance
established at 0.20 ppm on vegetable, legume, group 6.  Considering the
supporting data and the proposed use only as an ant bait, the ChemSAC
agreed with the proposed tolerance.  A tolerance for the residues of
pyriproxyfen on peanut at 0.20 ppm should be established. 

Pineapple

IR-4 has proposed a tolerance of 0.30 ppm on pineapple using the
tolerance established at 0.30 ppm on fruit, citrus, group 10. 
Considering the supporting data, the ChemSAC agreed with the proposed
tolerance.  A tolerance for the residues of pyriproxyfen on pineapple at
0.30 ppm should be established. 

Pomegranate

IR-4 has proposed a tolerance of 0.20 ppm on pomegranate using the
tolerance established at 0.20 ppm on vegetable, fruiting, group 8. 
Considering the supporting data, the ChemSAC agreed with the proposed
tolerance.  A tolerance for the residues of pyriproxyfen on pomegranate
at 0.20 ppm should be established.

Safflower, seed

IR-4 has proposed a tolerance of 0.02 ppm on safflower, seed using the
tolerance established at 0.02 ppm on bean, succulent.  Considering the
supporting data and the proposed use only as an ant bait, the ChemSAC
agreed with the proposed tolerance.  A tolerance for the residues of
pyriproxyfen on safflower, seed at 0.02 ppm should be established. 

Sesame, seed

IR-4 has proposed a tolerance of 0.02 ppm on sesame, seed using the
tolerance established at 0.02 ppm on bean, succulent.  Considering the
supporting data and the proposed use only as an ant bait, the ChemSAC
agreed with the proposed tolerance.  A tolerance for the residues of
pyriproxyfen on sesame, seed at 0.02 ppm should be established.

Sugarcane

IR-4 has proposed a tolerance of 1.1 ppm on sugarcane using the
tolerance established at 1.1 ppm on grass.  Considering the supporting
data and the proposed use only as an ant bait, the ChemSAC agreed with
the proposed tolerance.  A tolerance for the residues of pyriproxyfen on
sugarcane at 1.1 ppm should be established.

Tea

IR-4 has proposed a tolerance of 0.02 ppm on tea using the tolerance
established at 0.02 ppm on nut, tree, group 14.  Considering the
supporting data and the proposed use only as an ant bait, the ChemSAC
agreed with the proposed tolerance.  A tolerance for the residues of
pyriproxyfen on tea at 0.02 ppm should be established. 

Watercress

IR-4 has proposed a tolerance of 2.0 ppm on watercress using the
tolerance established at 2.0 ppm on Brassica, leafy greens, subgroup 5B
and a future residue study on celery with 8 trials in 2005 to provide
confirmatory data.  Considering the supporting data, the ChemSAC agreed
with the proposed tolerance.  However, as of the date of this review,
the confirmatory data have not been received.  A tolerance for the
residues of pyriproxyfen on watercress cannot be established at this
time.  The tolerance request should be removed from Section F.  The
issue should be revisited when the data are submitted.

Magnitude of the Residue - Livestock:  

Ruminants

An adequate cattle feeding study has been previously reviewed (DP Num:
238190, W. Donovan, 12/7/98).  In lactating cows which were dosed at 3,
9, and 30 ppm for 28 consecutive days, nondetectable (<0.01 ppm)
residues of pyriproxyfen and its metabolites 4'-OH-PYR, POP, and
2,5-OH-pyridine were observed in whole milk (3, 9, and 30 ppm dose
levels), and liver (30 ppm dose level).  Detectable pyriproxyfen
residues (0.01-0.02 ppm) and nondetectable residues (<0.01 or <0.02 ppm)
of  4'-OH-PYR, POP, and 2,5-OH-pyridine were present in cream at the 30
ppm dose level.  Dectectable 2,5-OH-pyridine residue levels were also
found in liver samples collected on day 28 at the 30 ppm dose level. 
Fat and muscle were only analyzed for pyriproxyfen and 4'-OH-PYR. 
Nondetectable residues (<0.01 ppm) of pyriproxyfen and 4'-OH-PYR were
observed in muscle at the 30 ppm dosing level; detectable pyriproxyfen
residues (0.05-0.07 ppm) and residues of 4'-OH-PYR below the LOD (<0.01
ppm) were present in fat at the 30 ppm dosing level.  Residues of
pyriproxyfen were nondetectable (<0.01 ppm) in fat at the 3 ppm dosing
level and detectable (0.01-0.03 ppm) at the 9 ppm dosing level;
4'-OH-PYR was not analyzed for in these samples.  The highest residue
levels of pyriproxyfen (0.05-0.07 ppm) were observed in fat at the
highest dose level (30 ppm).

The last calculated maximum theoretical dietary burden (MTDB) for beef
and dairy cattle included soybean, seed at 0.20 ppm and grass forage at
0.70 ppm.  The MTDB for beef and dairy cattle were determined to be 1.91
and 1.51 ppm, respectively.  HED concluded that tolerances would not be
required for residues of pyriproxyfen in ruminant commodities provided
that no additional uses on livestock feed items are proposed (PP#s
4F6847, 3E6596, 3E6596, 3E6750, 4E6866, 4E6865 & 3E6582, DP Num: 310072,
316784, 316788, 316800, 316798, 316802 & 314308, G. Kramer, 6/30/05). 
Reasonable cattle diets were constructed using the existing and proposed
feed items (personal communication, J. Stokes and B. Schnieder,
9/19/06).  The revised dietary calculation changes the dietary burden to
1.06 ppm for beef cattle and 1.81 ppm for dairy cattle.  Extrapolation
from the feeding study indicates that residues of pyriproxyfen can be
expected to be <0.01 ppm on all cattle commodities including milk and
cream.  No detectable pyriproxyfen residues are expected on ruminant
commodities from the proposed uses; therefore, tolerances are not
required for residues of pyriproxyfen in ruminant commodities at this
time. 

Poultry

In conjunction with the petition for use on cotton (PP#6F4737, DP Num:
228556, 228925, & 228926, J. Garbus, 5/6/97), HED concluded that
secondary residues in poultry and eggs are unlikely in light of the
poultry metabolism study results.  In the poultry metabolism study,
conducted at a feeding level of 10 ppm (2500X), the maximum total
radioactive residues (TRR) were 0.926 ppm in fat, 0.095 ppm in meat,
0.75 ppm in liver, 0.861 ppm in kidney, and 0.29 ppm in egg.  The
conclusion was based on an MTDB of 0.004 ppm. 

The last calculated MTDB for poultry included soybean, seed at 0.20 ppm
and cottonseed meal at 0.05 ppm was determined to be 0.05 ppm.  HED
concluded that tolerances would not be required for residues of
pyriproxyfen in livestock commodities provided that no additional uses
on livestock feed items are proposed (PP#s 4F6847, 3E6596, 3E6596,
3E6750, 4E6866, 4E6865 & 3E6582, DP Num: 310072, 316784, 316788, 316800,
316798, 316802 & 314308, G. Kramer, 6/30/05).  A reasonable poultry diet
was constructed using the existing and proposed feed items in (personal
communication, J. Stokes and B. Schnieder, 9/19/06).  The revised
dietary calculation changes the poultry dietary burden to 0.92 ppm. 
Extrapolation from the metabolism study indicates that residues of
pyriproxyfen can be expected on poultry commodities.  However, the
expected residues are less than the previously established 0.10 ppm
tolerance as a result of the food handling establishment use; therefore,
an increase in the tolerances on poultry commodities is not required at
this time.  Ant further increase in the MTDB to poultry will likely
trigger a requirement of a poultry feeding study.

Swine

A reasonable swine diet was constructed using the existing and proposed
feed items (personal communication, J. Stokes and B. Schnieder,
9/19/06).  The revised dietary calculation changes the swine dietary
burden to 0.97 ppm.  Since the residues on swine commodities would be
calculated using the cattle feeding study, the highest dietary burden
calculated for swine is less than that of cattle, and no detectable
cattle residues are expected, it is unlikely any detectable residues
would be found in swine commodities from the proposed uses.  Therefore,
at this time no pyriproxyfen tolerances are required for swine
commodities. 

Processed Food and Feed:  Many of the proposed tolerances are for RACs
which have associated processed food/feed items of regulatory interest. 
Since no new processing data were submitted with this petition, the
theoretical processing factors (OPPTS GLN 860.1520) and, where possible,
processing factors from the Agency’s pyriproxyfen database for similar
commodities were considered.  Where both theoretical and translated
processing factors were available for a commodity, the lowest of the
factors is used to calculate a tolerance value.  A revised Section F is
required for beet, dry pulp at 3.0 ppm; potato granules/flakes, chips,
and wet peel at 0.75 ppm; rice, hulls at 5.5 ppm; coffee, instant at
0.10 ppm; and pineapple, process residue at 1.1 ppm.

Tolerance Summary:  Permanent tolerances for pyriproxyfen have been
established for a variety of commodities under 40 CFR §180.510.  There
are currently no established Codex, Canadian, or Mexican maximum residue
limits (MRLs) for pyriproxyfen.  Since no new data were included with
this submission, the methodology formulated by the NAFTA MRL/Tolerance
Harmonization Workgroup for calculating statistically-based pesticide
tolerances was not used. 

Table 4.3  Tolerance Summary for Pyriproxyfen

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)

Vegetable, root and tuber, group 1	0.15	0.15

Beet, sugar, dried pulp	None	3.0

Potato, granules/flakes	None	0.75

Potato, chips	None	0.75

Potato, wet peel	None	0.75

Vegetable, leaves of root and tuber, group 2	2.0	None

Vegetable, bulb, group 3, 

     except onion, bulb 	0.70	0.70

Vegetable, leafy, except Brassica, group 4 	2.0	None

Vegetable, legume, group 6 	0.20	None

Vegetable, foliage of legume, group 7 	2.0	None

Caneberry, subgroup 13A 	1.0	1.0

Grain, cereal, group 15 	1.1	1.1

Rice, hulls	None	5.5

Grain, cereal, forage, fodder and straw, 

     group 16 	1.1	1.1

Animal feed, nongrass, group 18, forage 	0.70	0.70

Animal feed, nongrass, group 18, hay	1.1	1.1

Animal feed, nongrass, group 18, seed	2.0	2.0

Artichoke, globe	2.0	None

Asparagus 	2.0	None

Banana 	0.20	0.20

Cacao bean, dried bean 	0.02	0.02

Canola, seed 	0.20	0.2

Coffee bean, green bean	0.02	0.02

Coffee, instant	None	0.10

Cranberry 	1.0	1.0

Date 	0.30	0.30

Kiwifruit 	0.10	None

Pawpaw  	1.0	1.0

Peanut 	0.20	0.20

Pineapple 	0.30	0.30

Pineapple, process residue	None	1.1

Pomegranate 	0.20	0.02

Safflower, seed 	0.20	0.20

Sesame, seed 	0.20	0.02

Sugarcane 	1.1	1.1

Tea  	0.02	0.02

Watercress 	2.0	None

4.4  Water Exposure and Risk Pathway tc \l2 "4.4  Water Exposure and
Risk Pathway 

The following information concerning the environmental fate and drinking
water assessment of pyriproxyfen was provided by EFED (DP Num: 285273,
James K. Wolf and Kevin J. Costello, 11/6/02).  At the present time,
surface and ground water monitoring data are not available.

Ground and Surface Water EDWCs:  The HED MARC determined that the
residue of concern in water is pyriproxyfen per se.  Drinking water
estimates include surface water EDWCs based on the linked PRZM/EXAMS
models and the SCI-GROW groundwater regression model, which was
developed from studies with different hydrology and study conditions. 
Both models assumed a maximum seasonal application rate of 0.11 lb ai/A,
3 times per year (citrus and stone fruit).  

ground water estimate:		0.006 ppb (acute and chronic)

surface water estimate:		2.15 ppb; peak concentration

0.40 ppb; long-term average

EFED provided a new drinking water assessment for the additional uses of
pyriproxyfen, but the new maximum value (0.34 ppb for chronic) was less
than the previously-calculated values shown above (DP Num: 313009, Lucy
Shanaman, 6/6/05).

4.5  Dietary-Exposure Analysis tc \l2 "4.5  Dietary-Exposure Analysis 

An acute dietary exposure analysis was not conducted since acute doses
or endpoints were not selected for the general U.S. population
(including infants and children) or the females 13-50 years old
population subgroup.  A cancer dietary risk assessment was not performed
because no evidence of carcinogenicity has been found for pyriproxyfen. 
A chronic dietary risk assessment was conducted using the DEEM-FCID(
(ver. 2.0) model which uses food consumption data from the USDA’s
CSFII from 1994-1996 and 1998.  The Tier 1 chronic analysis assumed 100%
crop treated, DEEM( 7.81 default processing factors and tolerance-level
residues for all commodities.  Drinking water was incorporated directly
in the dietary assessment using the long-term mean concentration for
surface water generated by the PRZM-EXAMS model.  The resulting chronic
dietary risk estimates were less than 10% of the cPAD for the U.S.
population and all population subgroups (Table 4.5).  The chronic
dietary exposure and risk estimates (food + water) were estimated at 3%
of the cPAD for the U.S. population and 10% of the cPAD for the most
highly-exposed population subgroup (children 1-2 years old) and are thus
below ARIA’s level of concern (<100% cPAD).  

Table 4.5  Summary of Dietary Exposure and Risk for Pyriproxyfen

Population Subgroup	

Acute Dietary	

Chronic Dietary	

Cancer

	

Dietary Exposure (mg/kg/day)	

% aPAD	

Dietary Exposure

(mg/kg/day)	

% cPAD	

Dietary Exposure

(mg/kg/day)	

Risk

General U.S. Population	

N/A	

N/A	0.011114	3	

N/A	

N/A

All Infants (< 1 year old)

	0.015576	5

Children 1-2 years old

	0.034843	10

Children 3-5 years old

	0.028120	8

Children 6-12 years old

	0.017172	5

Youth 13-19 years old

	0.010298	3

Adults 20-49 years old

	0.008411	2

Adults 50+ years old

	0.007418	2

Females 13-49 years old

	0.008338	2

4.6  Residential Exposure and Risk Pathway tc \l2 "4.6  Residential
Exposure and Risk Pathway 

Pyriproxyfen is the active ingredient in many registered residential
products for flea and tick control (home environment and pet treatments)
as well as products for ant and roach control (indoor and outdoor
applications).  Formulations include carpet powders, foggers, aerosol
sprays, liquids (shampoos, sprays and pipettes for pet treatments),
granules, bait (indoor and outdoor), and impregnated materials (pet
collars).  A review of information pertaining to residential exposure to
pyriproxyfen is available in a separate memo (DP Num: 281982, T.
Swackhammer, 5/2/02). 

5.0  AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION tc \l1 "5.0 
AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION 

Aggregate risk assessments were performed for the following: short-term
aggregate exposure (food, drinking water, and residential non-dietary
oral exposure), intermediate-term aggregate exposure (food, drinking
water, and residential non-dietary oral exposure) and chronic aggregate
exposure (food, drinking water, and residential non-dietary oral and
dermal exposure).  An acute aggregate exposure analysis was not
conducted since no acute doses or endpoints were selected for the
general U.S. population (including infants and children) or the females
13-50 years old population subgroup.  A cancer aggregate risk assessment
was not performed because there is no evidence of pyriproxyfen
carcinogenicity.  

5.1	Short-Term Aggregate Risk (food + drinking water + residential)

In aggregating short-term risk, ARIA considered background
chronic-dietary exposure (food + water) and short-term, residential
non-dietary oral exposures (hand-to-mouth exposures by toddlers
following applications around the home and on pets for flea and tick
control-carpet powder and pet shampoo).  Since HIARC did not select a
short-term dermal endpoint, a dermal-exposure assessment is not included
in the short-term aggregate assessment.  The total short-term dietary
and residential aggregate MOEs range from 1200 to 14000.  As these MOEs
are greater than 100, the short-term aggregate risk does not exceed
ARIA’s level of concern.  Table 5.1 summarizes the short-term
aggregate exposure to pyriproxyfen residues.

Table 5.1 Short-Term Aggregate Risk Calculations

Population	

Short-Term Scenario

	

NOAEL

mg/kg/day	

Target

MOE1	

Max

Exposure2

mg/kg/day	

Chronic

Dietary Exposure

mg/kg/day	

Residential Oral Exposure3

mg/kg/day	

Aggregate MOE (dietary and residential)4

General U.S. Population	

100	

100	

1.0	0.011114	

-	

9000

All Infants (<1 year old)

 year old) y years year old	

100	

100	

1.0	0.015576	

0.04832	

1600

Children 1-2 years old   	

100	

100	

1.0	0.034843	

0.04832	

1200

Children 3-5 years old	

100	

100	

1.0	0.028120	

0.04832	

1300

Children 6-12 years old	

100	

100	

1.0	0.017172	

0.04832	

1500

Youth  13-19 years old    	

100	

100	

1.0	0.010298	

-	

9700

Adults 20-49 years old	

100	

100	

1.0	0.008411	

-	

12000

Females 13-49 years old	

100	

100	

1.0	0.007418	

-	

14000

Adults 50+ years old	

100	

100	

1.0	0.008338	

-	

12000

1 Basis for the target MOE: inter- and intra-species uncertainty factors
totaling 100 and FQPA SF (1X).

2 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE

3 Residential Exposure = Oral exposure represents sum of hand-to-mouth
exposure to carpet powder and pet shampoo residues (see DP Num: 281982,
T. Swackhammer, 5/2/02).   Sample calculation: (carpet powder exposure
component = 0.00261) + (pet shampoo exposure component = 0.04571) =
0.04832 mg/kg/day.

4 Aggregate MOE = [NOAEL ( (Chronic Food Exposure + Residential
Exposureoral only)].

5.2  Intermediate-Term Aggregate Risk (food + drinking water +
residential)

In aggregating intermediate-term risk, ARIA considered background
chronic dietary exposure (food + water) and intermediate-term,
residential non-dietary oral exposures (by toddlers following flea and
tick control applications around the home and on pets for products with
labeled efficacies of more than 30 days-carpet powder and pet shampoo). 
Since HIARC did not select an intermediate-term dermal endpoint, a
dermal-exposure assessment is not included in the intermediate-term
aggregate assessment.  The total intermediate-term dietary and
residential aggregate MOEs range from 430 to 4700.  As these MOEs are
greater than 100, the intermediate-term aggregate risk does not exceed
ARIA’s level of concern.  Table 5.2 summarizes the intermediate-term
aggregate exposure to pyriproxyfen residues.

.

Table 5.2  Intermediate-Term Aggregate Risk Calculations

Population	

Intermediate-Term Scenario

	

NOAEL

mg/kg/day	

Target

MOE1	

Max

Exposure2

mg/kg/day	

Chronic

Dietary Exposure

mg/kg/day	

Residential Oral Exposure3

mg/kg/day	

Aggregate MOE (dietary and residential)4

General U.S. Population	

35.1	

100	

0.351	0.011114	

-	

3200

All Infants (<1 year old)	

35.1	

100	

0.351	0.015576	

0.04695	

560

Children 1-2 years old	

35.1	

100	

0.351	0.034843	

0.04695	

430

Children 3-5 years old	

35.1	

100	

0.351	0.028120	

0.04695	

470

Children 6-12 years old	

35.1	

100	

0.351	0.017172	

0.04695	

550

Youth  13-19 years old    	

35.1	

100	

0.351	0.010298	

-	

3400

Adults 20-49 years old	

35.1	

100	

0.351	0.008411	

-	

4200

Females 13-49 years old	

35.1	

100	

0.351	0.007418	

-	

4700

Adults 50+ years old	

35.1	

100	

0.351	0.008338	

-	

4200

1 Basis for the target MOE: inter- and intra-species uncertainty factors
totaling 100 and FQPA SF (1X).

2 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE

3 Residential Exposure = Oral exposure represents sum of hand-to-mouth
exposure to carpet powder and pet shampoo residues (see DP Num: 281982,
T. Swackhammer, 5/2/02).  Sample calculation: (carpet powder exposure
component = 0.00124) + (pet shampoo exposure component = 0.04571) =
0.04695 mg/kg/day

4 Aggregate MOE = [NOAEL ( (Chronic Food Exposure + Residential
Exposureoral only)].

5.3 	Chronic Aggregate Risk (food + drinking water + residential)

In aggregating chronic risk, ARIA considered background chronic dietary
exposure (food + water) and long-term, residential non-dietary oral and
dermal exposures (by toddlers following flea and tick control
applications around the home and on pets for products with labeled
efficacies of more than 6 months-carpet powder and pet collar).  Since
HIARC did not select a long-term oral endpoint for pyriproxyfen, the
chronic aggregate risk was performed using the chronic dietary endpoint.
 A long-term post-application residential assessment was performed for
toddlers only since they are anticipated to have the higher exposures
than adults from treated home environments and pets due to their
behavior patterns (see Science Advisory Council for Exposure (ExpoSAC)
meeting minutes, 1/10/02).  The total chronic dietary and residential
aggregate MOEs range from 570 to 4700.  As these MOEs are greater than
100, the chronic aggregate risk does not exceed ARIA’s level of
concern.  Table 5.3 summarizes the chronic aggregate exposure to
pyriproxyfen residues.

Table 5.3  Chronic Aggregate Risk .

Population	

Chronic Scenario

	

NOAEL

mg/kg/day	

Target

MOE1	

Max

Exposure2

mg/kg/day	

Chronic

Dietary Exposure

mg/kg/day	

Residential Dermal Exposure

mg/kg/day	

Residential Oral Exposure3

mg/kg/day	

Aggregate MOE (dietary and residential)4

General U.S. Population	

35.1	

100	

0.351	0.011114	

-	

-	

3200

All Infants (<1 year old)	

35.1	

100	

0.351	0.015576	

0.02574	

0.001448	

820

Children 1-2 years old	

35.1	

100	

0.351	0.034843	

0.02574	

0.001448	

570

Children 3-5 years old	

35.1	

100	

0.351	0.028120	

0.02574	

0.001448	

640

Children 6-12 years old	

35.1	

100	

0.351	0.017172	

0.02574	

0.001448	

790

Youth  13-19 years old	

35.1	

100	

0.351	0.010298	

-	

-	

3400

Adults 20-49 years old	

35.1	

100	

0.351	0.008411	

	

	

4200

Females 13-49 years old	

35.1	

100	

0.351	0.007418	

-	

-	

4700

Adults 50+ years old	

35.1	

100	

0.351	0.008338	

-	

-	

4200

1 Basis for the target MOE: inter- and intra-species uncertainty factors
totaling 100 and FQPA SF (1X).

2 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE

3 Residential Exposure = Dermal exposure represents sum of exposure to
carpet powder and pet collar residues; oral exposure represents sum of
hand-to-mouth exposure to carpet powder and pet collar residues (see
D281982, T. Swackhammer, 5/2/02).  Sample calculations:  (carpet powder
dermal exposure component = 0.02346) + (pet collar dermal exposure
component = 0.00228) = 0.02574 mg/kg/day; (carpet powder hand-to-mouth
exposure component = 0.001238) + (pet collar hand-to-mouth exposure
component = 0.00021) = 0.001448 mg/kg/day.

4 Aggregate MOE = [NOAEL ( (Chronic Food Exposure + Residential
Exposuredermal + oral)].

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 pyriproxyfen and any other
substances, and pyriproxyfen does not appear to produce a toxic
metabolite produced by other substances.  For the purposes of this
tolerance action, therefore, EPA has not assumed that pyriproxyfen has a
common mechanism of toxicity with other substances.  For information
regarding EPA’s efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA’s 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 

Handler Exposure tc \l2 "7.1  Handler Exposure 

The personal-protective equipment (PPE) for applicators and other
handlers of Esteem® IGR, 0.86 lb ai/gal EC is coveralls over short
pants and short-sleeved shirt OR long-sleeved shirt, long pants,
chemical-resistant gloves, chemical-resistant footwear,
chemical-resistant headgear for overhead spraying and chemical-resistant
apron for cleaning equipment.  The PPE for the 35% WP is long-sleeved
shirt, long pants, waterproof gloves and shoes plus socks.  For the ant
bait, the label directs applicators and other handlers to wear a
long-sleeved shirt, long pants, waterproof gloves and shoes plus socks.

Based upon the proposed use patterns, ARIA expects pesticide handler
exposures to be short-term (1-30 days).  The HED ExpoSAC maintains that
it is possible for occupational pesticide handlers to experience
intermediate-term (1-6 months) exposures.  ARIA does not anticipate any
long-term (> 6 months) exposures for pesticide handlers.  Since there
are no short-term or intermediate-term dermal or inhalation
toxicological endpoints identified and since ARIA does not expect
long-term exposures, exposure and risk assessments are not necessary for
the proposed uses and are therefore not presented here.  

7.2  Post-Application Worker Exposure tc \l2 "7.2  Post-Application
Worker Exposure 

It is possible the agricultural workers may experience post-application
exposure to pesticides during the conduct of typical agricultural
activities.  The exposure is typically the result of foliar dislodgeable
residues of a pesticide.  In this case, since there are no dermal
(short- or intermediate-term) toxicological endpoints identified, it is
not necessary to conduct assessments of post-application exposure and
risk.  ARIA does not expect agricultural workers to experience long-term
(greater than six months) exposures during the conduct of typical
agricultural activities.

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

Pyriproxyfen is classified as Toxicity Category III for acute dermal and
inhalation toxicity and Category IV for acute oral, primary eye and skin
irritation and it is not a skin sensitizer.  The Worker Protection
Standard interim REI is 12 hours for compounds in Toxicity Categories
III and IV for the acute effects noted above.  Therefore, a 12 hour REI
is sufficient to protect agricultural workers re-entering treated areas.

7.4  Incidents tc \l2 "7.4  Incidents 

T. Swackhammer (DP Num: 281982, 5/2/02) indicated that:  “A search of
OPP’s Incident Data Reporting System (12/27/01) revealed a total of
131 records in the database, mainly related to adverse reactions by
treated pets to flea and tick control products containing pyriproxyfen
together with other active ingredients (permethrin, pyrethrins, etc.). 
Records of adverse reactions noted for humans primarily comprised of
skin rashes/hives, headaches, or asthma attacks.  However, the incident
summaries note that the products contained multiple active ingredients
in addition to pyriproxyfen.  Therefore, the adverse reactions cannot be
directly related to pyriproxyfen.” 
R晥牥湥散琠⁯桴⁥湉楣敤瑮䐠瑡⁡敒潰瑲湩⁧祓瑳浥
⠠⼹㘲〯⤲椠摮捩瑡獥琠敨猠慴畴⁳慨⁳潮⁴档湡敧⹤
഍⸸‰䐠䙅䍉䕉䍎䕉⽓䅄䅔丠䕅卄琓⁣汜‱㠢〮†䕄䥆
䥃久䥃卅䐯呁⁁䕎䑅ᕓ഍潔楸潣潬祧ግ捴尠㉬∠⸸‱吠
硯捩汯杯ᕹ

●	An in vivo cytogenetic study (OPPTS Guideline No. 870.5385) with
pyriproxyfen technical.

8.2  Chemistry tc \l2 "8.2  Chemistry 

Revised Section F

Occupational/Residential

 tc \l2 "8.3  Occupational/Residential 

none

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DP Num: 332800, W. Cutchin, 10/2/06

EFED memos, DP Num: 285273, J. Wolf & K. Costello; 11/6/02 and DP Num:
313009, L. Shanaman; 6/6/05

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