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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 6-April-2006

**[MEMORANDUM]{.underline}**

SUBJECT: Bifenthrin: Human Health Risk Assessment for Proposed Uses on
Cilantro, Leafy *Brassica* Greens (subgroup 5b), Tuberous and Corm
Vegetables (Subgroup 1c), Dried Shelled Peas and Beans (except Soybean)
(Subgroup 6c) and Tobacco. PC Code: 128825, DP Barcodes: DP310088,
DP310089, DP310874, DP313738, DP313817, DP313818.

> Regulatory Action: Section 3 Registration Action
>
> Risk Assessment Type: Single Chemical Aggregate

FROM: Mary Clock-Rust, Biologist

George Kramer, Ph.D., Chemist

Sarah Levy, M.S., Chemist

Mark I. Dow, Ph.D., Biologist

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

Registration Action Branch 1 (RAB1)

Health Effects Division (HED) (7509C)

and

Sheila Piper, Chemist

Chemistry and Exposure Branch (CEB)

HED (7509C)

THROUGH: PV Shah, Ph.D., Branch Senior Scientist

RAB1

HED (7509C)

TO: George LaRocca, Chemical Review Manager

Barbara Madden, Minor Use Team

Registration Division (RD, 7505C)

The Interregional Research Project No. 4 (IR-4) and the FMC Corporation
have requested registration of the insecticide bifenthrin for use on
cilantro (coriander) and tuberous and corm vegetables (Subgroup 1c)
(Arracacha, arrowroot, Chinese artichoke, Jerusalem artichoke, edible
canna, cassava (bitter and sweet), chayote (root), chufa, dasheen
(taro), ginger, leren, potato, sweet potato, tanier, turmer, yam bean,
true yam), dried shelled peas and beans (subgroup 6c) and Leafy
*Brassica* Greens (Subgroup 5b). FMC also requests a label amendment for
use on tobacco. This memorandum serves as the HED's estimates of
exposure and risk to humans from the proposed applications of
bifenthrin.

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 the proposed uses of bifenthrin in/on cilantro, tuberous and
corm vegetables, dried beans and peas, leafy *Brassica* and label
amendment use of tobacco.

A summary of the findings and an assessment of human health risk
resulting from the proposed uses of bifenthrin are provided in this
document. The hazard characterization was provided by P.V. Shah (RAB1);
the residue chemistry review was provided by George Kramer and Sarah
Levy (RAB1); the dietary exposure assessment was provided by Sheila
Piper (CEB); the occupational/residential exposure assessment was
provided by Mark Dow (RAB1); the drinking water assessment was provided
by Jose Melendez of the Environmental Fate and Effects Division (EFED);
the aggregate exposure and risk assessment were provided by Mary
Clock-Rust (RAB1).

**1.0 Executive Summary**

Reference:

***Revised Preliminary HED Chapter for the Bifenthrin Tolerance
Reassessment Eligibility Decision (TRED). PC Code: 128825 DP Barcode:
D283796.* J. Liccione. 12/04/2002.**

*Background*

Bifenthrin is a neurotoxic insecticide acting through direct contact and
ingestion, having a slight repellent effect. The primary biological
effects of bifenthrin and other pyrethroids on insects and vertebrates
are inhibition of the voltage-gated Ca2+ channels coupled with a
stimulatory effect on the voltage-gated Na+ channels. All pyrethroids
act as axonic poisons, affecting both the peripheral and central nervous
systems, and share similar modes of action. Pyrethroids, including
bifenthrin, stimulate repetitive action in the nervous system by binding
to voltage-gated sodium channels, prolonging the sodium ion permeability
during the excitatory phase of the action potential**.** This action
leads to spontaneous depolarizations, augmented neurotransmitter
secretion rate and neuromuscular block, which ultimately results in
paralysis of the insect.

Bifenthrin, formulated as an emulsifiable concentrate (EC) or wettable
powder (WP), and granular (G) has permanent tolerances for foliar use
on/in artichoke, imported banana, head and stem *Brassica* vegetables,
cabbage, caneberry, field and sweet corn, cotton, eggplant, citrus,
cucurbits, grape, herbs, hops, lettuce, nuts, succulent bean and pea,
pear, bell and non-bell pepper, rapeseed, spinach, strawberry, tomato
and edible podded legumes.

Current tolerances (ranging from 0.05-10 ppm) are established in 40 CFR
§180.442(a) for various plant commodities and livestock for bifenthrin
(2-methyl \[1,1'-biphenyl\]-3-yl)

methyl-3-(2-chloro-3,3,3,-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate.
Time-limited tolerances for orchard grass and sweet potato roots (0.05
ppm) have been established in conjunction with Section 18 Emergency
Exemptions \[40 CFR §180.442(2b)\]. A tolerance of 0.05 ppm is
established for residues of bifenthrin in food handling establishments
\[40 CFR §180.442(2)\]

A Tolerance Reassessment Eligibility Decision (TRED) was issued for
bifenthrin in 2002 (reference above). The TRED examined all registered
uses of bifenthrin. The background information and conclusions reported
in the 2002 TRED (including exposure from dietary, occupational and
residential uses) have been summarized and incorporated into this risk
assessment. For more details, see the 2002 TRED or relevant memoranda
for each section.

*Hazard Characterization*

Bifenthrin has a moderate order of acute toxicity via the oral route
(Category II) and a low order of acute toxicity via the dermal route
(Category III) of exposure. There are no acute inhalation studies on
bifenthrin technical; however, acceptable studies on the end-use
products are available. Bifenthrin has a low vapor pressure. It is
neither an eye nor skin irritant, nor is it a dermal sensitizer.

Bifenthrin produces characteristic pyrethroid neurotoxicity. Tremors
have been observed in developmental toxicity studies in the rat and
rabbit, a 2-generation rat reproduction toxicity study, subchronic
toxicity studies in the rat and dog, acute and subchronic neurotoxicity
rat studies, a 21-day toxicity dermal rat study, chronic oral toxicity
studies in the rat and dog, and a mouse oncogenicity study. The
subchronic and chronic oral toxicity studies in dogs and rats
demonstrate neurotoxicological responses of similar magnitude. Staggered
gait and exaggerated hindlimb flexion were noted in a 21-day dermal
toxicity study in the rat. The neurotoxicity of bifenthrin has been
supported by the results of acute and subchronic neurotoxicity studies
in the rat. FOB findings were observed in these neurotoxicity studies.
FOB findings consisted of tremors, abnormal posture, splayed hindlimbs,
staggered gait, altered activity, altered landing foot-splay, twitching,
uncoordinated movement/ataxia, and convulsions.

Bifenthrin is neither a developmental nor a reproductive toxicant.
Bifenthrin has been evaluated for potential developmental effects in the
rat (following gavage or dietary administration) and in the rabbit
(gavage administration). Maternal toxicity included neurological effects
(tremors in rats and rabbits; head and forelimb twitching in rabbits).
There were no developmental effects of biological significance in either
species.

The potential reproductive toxicity of bifenthrin was examined in a
two-generation reproduction study in the rat. Tremors were noted only in
females of both generations with one parental generation rat observed to
have clonic convulsions. Administration of bifenthrin did not result in
reproductive or offspring toxicity.

Bifenthrin was negative in most tests for mutagenicity. It was
marginally mutagenic with and without S9 activation in the mouse
lymphoma forward gene mutation assay. This finding has not been
confirmed in a repeat test. There is also inconclusive, but presumptive,
evidence that bifenthrin was mutagenic in the S9-activated phase of the
Chinese Hamster Ovary Cell (CHO) gene mutation assay, however, this
study was classified as unacceptable.

There was no conclusive evidence of carcinogenic potential of bifenthrin
in the rat. A mouse oncogenicity study provided some evidence for
carcinogenic potential in this species. In the mouse oncogenicity study,
high-dose (81.3 mg/kg/day) males showed a highly significant increased
incidence of urinary bladder tumors. Other findings in the mouse study
included a dose-related trend of increased combined incidences of
adenoma and adenocarcinoma of the liver (males only), and increased
incidences of bronchioalveolar adenomas and adenocarcinomas of the lung
in females at some, but not all dose levels relative to their controls.
HED's Carcinogenicity Peer Review Committee (CPRC) has characterized
bifenthrin as Category C (possible human carcinogen) primarily on the
basis of a mouse study in which the Cancer Assessment Review Committee
(CARC) (1992) recommended that for the purpose of risk characterization,
the reference dose (RfD) approach should be used for quantification of
human cancer risk.

Several dermal absorption studies on bifenthrin are available; each
study was considered acceptable for regulatory purposes when taken in
conjunction with the other studies. The Hazard Identification and Review
Committee (HIARC) recommended a dermal absorption rate of 25% based on
the weight-of the-evidence available for structurally related
pyrethroids.

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

The HED Hazard Identification and Assessment Review Committee (HIARC)
met on June 25, 2002 to select endpoints for risk assessment and to
evaluate the potential for increased susceptibility of infants and
children from exposure to bifenthrin. No appropriate acute dietary
endpoints were available to quantify risk to females 13-50 years of age
from a single-dose administration of bifenthrin. However, an acute
reference dose (aRFD) of 0.033 mg/kg/day, relevant to the general
population including infants and children, and based on observation of
mortality (females only), clinical and Functional Observation Battery
(FOB) findings, and differences in motor activity, was selected from an
acute neurotoxicity study in rats for acute risk assessment. The acute
RfD is based on the no-observed adverse effect level (NOAEL) of 32.8
mg/kg/day divided by an uncertainty factor (UF) of 1000 (10x for
interspecies extrapolation, 10x for intraspecies variations, and 10x for
an incomplete database for lack of a developmental neurotoxicity study.

HIARC concluded that, based on reliable data, an additional traditional
database UF of 3X is required for all repeated-dose exposure scenarios
to address deficiencies in the databases for bifenthrin (*i.e.*, the
lack of a developmental neurotoxicity study (DNT) because existing data
indicate that the results of the DNT study might impact the current
toxicology endpoint selection and RfDs). An UF~DB~ of 10X is applied to
single dose exposure scenarios (*i.e.*, acute RfD) to account for the
lack of the DNT.

The short- and intermediate-term incidental oral and inhalation
endpoints are based on observations of an increased incidence of tremors
in male and female dogs in a 90-day oral toxicity study. A chronic
dietary RfD of 0.004 mg/kg/day was determined from the 1-year oral dog
study that demonstrated increased incidence of tremors in both sexes.
The chronic RfD is based on the NOAEL of 1.3 mg/kg/day divided by an UF
of 300 (10x for interspecies extrapolation, 10x for intraspecies
variations, and 3x for an incomplete database for lack of a
developmental neurotoxicity study). The results of the 1-year dog
toxicity study were also the basis for the determination of the
long-term inhalation endpoint. An inhalation absorption default factor
of 100% was used for risk assessment purposes, since the endpoint was
derived from an oral study. The 21-day rat dermal toxicity study was
used to select short-, intermediate- and long-term dermal endpoints;
clinical signs included staggered gait and exaggerated hindlimb flexion.

The Food Quality Protection Act (FQPA) requires the Agency to consider
potential special sensitivity to infants and children from exposure to
bifenthrin. The HED FQPA Safety Factor Committee (SFC) met on July 15
and 22, 2002 to evaluate the hazard and exposure data for bifenthrin
with regard to making a decision on the additional safety factor for the
protection of infants and children. Acceptable developmental studies in
the rat and rabbit revealed no increased susceptibility of rat or rabbit
fetuses following *in utero* exposure to bifenthrin. In addition, there
was no evidence of increased susceptibility of young rats in the
reproduction study with bifenthrin.

The 1X safety factor has been applied to all dietary and residential
non-dietary exposure scenarios. The acute and chronic RfD modified by a
FQPA Safety Factor is a population adjusted dose (PAD). Therefore, the
acute PAD (aPAD) for bifenthrin is 0.033 mg/kg/day, and the chronic PAD
(cPAD) for bifenthrin is 0.004 mg/kg/day.

The FQPA Committee noted that there were no residual uncertainties in
the exposure databases. The dietary food exposure assessment was refined
using percent crop treated (CT) information, and anticipated residue
(AR) values calculated from the available monitoring data and field
trial results. Dietary drinking water exposure is based on conservative
modeling estimates, and the HED Residential standard operating
procedures (SOPs), in conjunction with some chemical specific data, were
used to assess residential handler and post-application exposure to
adults and children. These assessments will not underestimate the
exposure and risks posed by bifenthrin.

*Dietary Exposure Assessment*

Acute and chronic dietary exposure and risk assessments were conducted
using the Dietary Exposure Evaluation Model-Food Commodity Intake
Database (DEEM-FCID™, Version 2.03) which uses food consumption data
from the U.S. Department of Agriculture's (USDA) Continuing Surveys of
Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. Number
range CHAPTER

*Acute Dietary Exposure and Risk*

A Tier 3, acute probabilistic dietary exposure and risk assessment was
conducted for all registered (and pending) food uses and drinking water.
ARs were developed based on 1998-2003 USDA's Pesticide Data Program
(PDP) monitoring data, Food and Drug Administration (FDA) data, or field
trial data for bifenthrin. ARs were further refined using %CT data and
processing factors where appropriate.

EFED calculated the ground and surface drinking water Tier 1 estimated
drinking water concentrations (EDWCs) for bifenthrin using the screening
concentration in ground water (SCI-GROW) and FQPA Index Reservoir
Screening Tool (FIRST) models. EECs in ground water were estimated as
0.003 ppb and 0.014 ppb in surface water. The acute drinking water
concentration of bifenthrin in surface water (0.014 ppb) is based on the
application of bifenthrin to lettuce at the highest application rate
(0.5 lb ai/A/season).

The acute dietary exposure estimates for food and drinking water [are
below HED's level of concern]{.underline} (\<100% aPAD) at the 99.9^th^
percentile of exposure. Bifenthrin dietary exposure at the 99.9^th^
percentile for food and drinking water for the U.S. population is 21% of
the aPAD and 41% of the aPAD for children 1-2 yrs, the most highly
exposed population subgroup. These estimates include drinking water.

*Chronic Dietary Exposure and Risk*

A refined chronic dietary exposure assessment was also conducted for the
supported food uses of bifenthrin and drinking water using single point
estimates of anticipated bifenthrin residues for food and drinking
water. The estimated surface water concentration of 0.014 ppb, based on
application to lettuce at the highest application rate, was also used
for the chronic dietary assessment.

The chronic dietary exposure estimates for food and drinking water [are
below HED's level of concern]{.underline} (\<100% cPAD) for the U.S.
population and all population subgroups. Bifenthrin dietary exposure for
food and drinking water for the U.S. population is 6% of the cPAD and
18% of the cPAD for children 1-2 yrs, the most highly exposed population
subgroup. These estimates include drinking water.

*Cancer Dietary Risk*

The CARC (1992) recommended that for the purpose of risk
characterization, the reference dose (RfD) approach should be used for
quantification of human risk. The chronic exposure analysis revealed
\<100% RfD, and it is assumed that the chronic dietary endpoint is
protective for cancer dietary exposure.

*Residential Exposure and Risk*

Bifenthrin has both indoor and outdoor residential uses. Adults are
potentially exposed to bifenthrin residues during residential
application of bifenthrin. Adults and children are potentially exposed
to bifenthrin residues after application (post-application) of
bifenthrin products in residential settings. Risk estimates were
generated for residential handler exposures, and potential
post-application contact with lawn, soil, and treated indoor surfaces
using HED's Draft SOPs for Residential Exposure Assessment, and
dissipation data from a turf transferable residue (TTR) study. These
estimates are considered conservative, but appropriate, since the study
data were generated at maximum application rates.

*Residential Handler Risk Estimates*

Short- to intermediate-term dermal and inhalation exposures may occur
for residential handlers of bifenthrin products. Although residential
handler risks from inhalation exposures to bifenthrin gas/vapor are
considered unlikely, since the vapor pressure of bifenthrin is low,
inhalation exposure was assessed for aerosols/particulates during
residential mixing, loading, and application of granular products.
Short- and intermediate-term handler MOEs estimated for combined dermal
and inhalation exposures were ≥ 300, and therefore, do not exceed HED's
level of concern.

*Residential Post-Application Risk Estimates*

Adults and children may be potentially exposed to bifenthrin residues
after application of bifenthrin products in residential settings. Short-
and intermediate-term post-application dermal exposures for adults, and
short- and intermediate-term post-application dermal and incidental oral
exposures for children are anticipated. Risk estimates were generated
for potential contact with lawn, soil, and treated indoor surfaces.
Short- and intermediate-term risks estimated for post-application
exposure do not exceed HED's level of concern for adults and children.
Combined oral and dermal exposures do not exceed HED's level of concern
for short-term exposures for children. Combined adult handler and
post-application risk estimates (inhalation and dermal) associated with
homeowner applied liquids do not exceed HED's level of concern.

*Aggregate Risk*

Because there is the potential for short- and intermediate-term,
non-dietary post-application exposure of children and adults to
bifenthrin when used as a residential treatment, aggregate risk was
assessed. Short- and intermediate-term aggregate (dietary + residential)
MOEs for the general U.S. population and any subpopulation of the
general U.S. population are at least 340. This value does not exceed
HED's level of concern (MOE \>300). Chronic (\>6 months) non-dietary
post-application exposure to bifenthrin as a residential treatment is
considered unlikely; therefore, chronic aggregate risk assessments were
not performed.

*Occupational Handler Risk*

Based upon the proposed use pattern, HED expects the most highly exposed
occupational pesticide handlers (mixers, loaders, applicators) to be 1)
mixer/loader using open pour loading of liquids; 2) mixer/loader using
open pour loading of granules; 3) an aerial applicator and 4) an
applicator using open-cab, ground-boom spray equipment. Estimates for
short- and intermediate-term occupational risks were calculated.
Provided that mixer/loaders wear protective gloves, all MOEs are above
100. The lowest MOE for occupational handlers was 650 for mixer/loaders
supporting aerial application. Therefore, the estimated risks for
occupational handlers do not exceed HED's levels of concern (MOE \>100).

*Occupational Post-Application Risk*

Based on the proposed use pattern, HED has calculated post-application
exposure and risk for workers exposed to bifenthrin residues following
treatment. Workers engaging in activities such as hand harvesting,
topping, stripping and irrigation activities were assessed. Standard
assumptions were incorporated into the assessment to reflect
conservative risk estimates. The MOE for the theoretically most highly
exposed post-application agricultural activity is 410, and does not
exceed HED's level of concern. All other identified post-application
activities are expected to have lower exposures and therefore greater
MOEs.

*HED Recommendations*

The tolerances proposed by the registrants in the current petitions are
listed below, along with HED's recommended tolerance levels. Number
range CHAPTER

Provided revised Sections B and F are submitted, the residue chemistry
and toxicology databases support unconditional registration and
permanent tolerances for the following:

+----------------------+-----------+------------+----------------------+
| Crop Commodity       | Proposed  | R          | Comments             |
|                      | Tolerance | ecommended |                      |
|                      | (ppm)     | Tolerance  | Number range         |
|                      |           | (ppm)      | CHAPTER(*correct     |
|                      |           |            | commodity            |
|                      |           |            | definition*)         |
+----------------------+-----------+------------+----------------------+
| Tuberous and corm    | 0.1       | 0.05       | *Vegetable, tuberous |
| vegetables, subgroup |           |            | and corm, subgroup   |
| 1C                   |           |            | 1C*                  |
+----------------------+-----------+------------+----------------------+
| *Brassica*, leafy    | 3         | 3.5        |                      |
| greens, subgroup     |           |            |                      |
| 5B^1^                |           |            |                      |
+----------------------+-----------+------------+----------------------+
| Turnip greens^1^     | 3         | 3.5        | *Turnip, greens*     |
+----------------------+-----------+------------+----------------------+
| Pea and bean, dried  | 0.1       | 0.15       | *Pea and bean, dried |
| shelled, except      |           |            | shelled, except      |
| soybean, subgroup    |           |            | soybean, subgroup    |
|                      |           |            | 6C*                  |
+----------------------+-----------+------------+----------------------+
| Cilantro, leaves     | 5.0       | 6.0        | *Coriander, leaves*  |
+----------------------+-----------+------------+----------------------+
| Cilantro, dried      | 30.0      | 25         | *Coriander, dried    |
| leaves               |           |            | leaves*              |
+----------------------+-----------+------------+----------------------+
| Coriander, seed      | 5.0       | 5.0        |                      |
+----------------------+-----------+------------+----------------------+

^1^ Number range CHAPTERTurnip greens will be removed from Crop Group 2:
Leaves of root and tuber vegetables group \[40 CFR 180.41 (2)\], and
will become a member of Crop Group 5: *Brassica* leafy vegetables \[40
CFR 180.41 (5)\]. It will also be a member of Crop Subgroup 5B: Leafy
*Brassica* greens (Commodity Reviewers Guide, B. Schneider,
14-JUN-2002). Until that time, "turnip, greens" should have a separate
tolerance.

**Revised Sections F with the correct tolerance levels and commodity
definitions should be submitted where appropriate.**

**2.0 Ingredient Profile**

1.  **Summary of Proposed Uses**

## There are currently four bifenthrin end-use products (EPs) registered to FMC for use on food/feed crops. One is a 2 lb/gal EC formulation marketed under the trade name Capture^®^ 2EC Insecticide/Miticide (EPA Reg. No. 279-3069) and another is a 1.15% G formulation marketed under the trade name Capture^®^ 1.15G Insecticide (EPA Reg. No. 279-3244). IR-4 is supporting the use of the 2 lb/gal EC on tuberous and corm vegetables (subgroup 1C), Brassica leafy greens (subgroup 5B), dried peas and beans (subgroup 6C), cilantro, and the use of the 1.15% G on tuberous and corm vegetables. FMC is also proposing amending the label for the 2 lb/gal EC to include a non-food/feed use on tobacco. Example labels were provided and the proposed use directions are summarized below in Table 2.1.

**Table 2.1 Summary of Proposed Use Directions for Bifenthrin.**

+-----------------+---------+------+--------+--------+-----+--------+
| Application     | Form    | Si   | Max    | Max.   | PHI | Use    |
| Timing, Type    | ulation | ngle | Number | Se     | (Da | Dire   |
| and Equipment   |         | rat  | Applic | asonal | ys) | ctions |
|                 | \[EPA   | e(lb | ations | Appli  |     | and    |
|                 | reg.    | a    | per    | cation |     | Limit  |
|                 | No.\]   | i/A) | Season | Rate   |     | ations |
|                 |         |      |        | (lb    |     | ^1^    |
|                 |         |      |        | ai/A)  |     |        |
+=================+=========+======+========+========+=====+========+
| ### Tu          |         |      |        |        |     |        |
| berous and Corm |         |      |        |        |     |        |
|  Vegetables (Cr |         |      |        |        |     |        |
| op subgroup 1C) |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| In-furrow       | 1.15% G | 0.3  | 1      | 0.5    | 21  | The    |
| application at  |         |      |        |        |     | m      |
| planting        | \[279-  |      |        |        |     | inimum |
|                 | 3244 \] |      |        |        |     | RTI is |
| Ground          |         |      |        |        |     | 21     |
| equipment       | or      |      |        |        |     | days.  |
|                 |         |      |        |        |     |        |
|                 | 2       |      |        |        |     |        |
|                 | lb/gal  |      |        |        |     |        |
|                 | EC      |      |        |        |     |        |
|                 |         |      |        |        |     |        |
|                 | \[279   |      |        |        |     |        |
|                 | -3069\] |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Directed foliar | 2       | 0.1  | 2      |        |     |        |
| applications    | lb/gal  |      |        |        |     |        |
| during tuber    | EC      |      |        |        |     |        |
| formation       |         |      |        |        |     |        |
|                 | \[279   |      |        |        |     |        |
| Ground          | -3069\] |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| ### *Brassi     |         |      |        |        |     |        |
| ca* leafy Green |         |      |        |        |     |        |
| s (subgroup 5B) |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Post-emergence  | 2       | 0.1  | 4      | 0.4    | 7   | The    |
| broadcast       | lb/gal  |      |        |        |     | m      |
| foliar          | EC      |      |        |        |     | inimum |
| applications    |         |      |        |        |     | RTI is |
|                 | \[279   |      |        |        |     | 7 days |
| Ground or       | -3069\] |      |        |        |     |        |
| aerial          |         |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| ### Dried Bean  |         |      |        |        |     |        |
| s (subgroup 6C) |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Post-emergence  | 2       | 0.1  | 3      | 0.3    | 14  | No     |
| broadcast       | lb/gal  |      |        |        |     | m      |
| foliar          | EC      |      |        |        |     | inimum |
| applications    |         |      |        |        |     | RTI is |
|                 | \[279   |      |        |        |     | spe    |
| Ground or       | -3069\] |      |        |        |     | cified |
| aerial          |         |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| **Dried Peas    |         |      |        |        |     |        |
| (subgroup 6C)** |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Post-emergence  | 2       | 0.1  | 2      | 0.2    | 14  | A      |
| broadcast       | lb/gal  |      |        |        |     | m      |
| foliar          | EC      |      |        |        |     | inimum |
| applications    |         |      |        |        |     | RTI is |
|                 | \[279   |      |        |        |     | not    |
| Ground or       | -3069\] |      |        |        |     | spe    |
| aerial          |         |      |        |        |     | cified |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| ### Cilan       |         |      |        |        |     |        |
| tro (Coriander) |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Post-emergence  | 2       | 0.1  | 5      | 0.5    | 3   | The    |
| broadcast       | lb/gal  |      |        |        |     | m      |
| foliar          | EC      |      |        |        |     | inimum |
| applications    |         |      |        |        |     | RTI is |
|                 | \[279   |      |        |        |     | 7      |
| Ground or       | -3069\] |      |        |        |     | days.  |
| aerial          |         |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| ### Tobacco     |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Pre-transplant  | 2       | 0.1  | 1      | NS     | NS  | Apply  |
| soil            | lb/gal  |      |        |        |     | pr     |
| application     | EC      |      |        |        |     | e-tran |
|                 |         |      |        |        |     | splant |
| Ground          | \[279   |      |        |        |     | soil   |
| equipment       | -3069\] |      |        |        |     | appli  |
|                 |         |      |        |        |     | cation |
|                 |         |      |        |        |     | and    |
|                 |         |      |        |        |     | bro    |
|                 |         |      |        |        |     | adcast |
|                 |         |      |        |        |     | foliar |
|                 |         |      |        |        |     | applic |
|                 |         |      |        |        |     | ations |
|                 |         |      |        |        |     | in a   |
|                 |         |      |        |        |     | m      |
|                 |         |      |        |        |     | inimum |
|                 |         |      |        |        |     | of 10  |
|                 |         |      |        |        |     | gal/A, |
|                 |         |      |        |        |     | and    |
|                 |         |      |        |        |     | water  |
|                 |         |      |        |        |     | drench |
|                 |         |      |        |        |     | appli  |
|                 |         |      |        |        |     | cation |
|                 |         |      |        |        |     | in     |
|                 |         |      |        |        |     | 50-200 |
|                 |         |      |        |        |     | gal/A  |
+-----------------+---------+------+--------+--------+-----+--------+
| At transplant   |         | 0.1  | 1      |        | NS  |        |
| water drench    |         |      |        |        |     |        |
| application     |         |      |        |        |     |        |
|                 |         |      |        |        |     |        |
| Ground          |         |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+
| Broadcast       |         | 0.05 | NS     |        | NS  |        |
| foliar          |         |      |        |        |     |        |
| applications up |         |      |        |        |     |        |
| to and          |         |      |        |        |     |        |
| including       |         |      |        |        |     |        |
| lay-by          |         |      |        |        |     |        |
|                 |         |      |        |        |     |        |
| Ground          |         |      |        |        |     |        |
| equipment       |         |      |        |        |     |        |
+-----------------+---------+------+--------+--------+-----+--------+

^1^ Crops with bifenthrin tolerances may be rotated at any time, and all
other corps may be rotated 30 days following the final bifenthrin
application.

NS = not specified.

Number range CHAPTER*Conclusions.* The proposed use directions for
tuberous and corm vegetables, leafy *Brassica* greens, dried peas and
beans, and cilantro are adequately supported by the available field
trials on potatoes, mustard greens, dried beans and peas, and cilantro;
however, the use directions for dried beans and peas should be amended
to specify a minimum RTI of 7 days. The available tobacco field trials
will also support the use of the EC formulation on tobacco; however, the
use directions should be amended to specify the maximum number of foliar
applications allowed and the maximum seasonal use rate. The available
tobacco field trials will support use of the 2 lb/gal EC as either a
broadcast pre-plant soil application at up to 0.1 lb ai/A or an
in-furrow water drench application at transplant at up to 0.1 lb ai/A,
followed by a single broadcast foliar application up to lay-by at up to
0.1 lb ai/A, for a maximum seasonal use rate of 0.2 lb ai/A. These data
will also support the use of the 1.15% G formulation to tobacco as a
single broadcast pre-plant soil application at up to 0.1 lb ai/A. **A
revised Section B should be submitted.**

**2.2 Structure and Nomenclature**

**Table 2.2 Nomenclature of Bifenthrin**

+-------------------+--------------------------------------------------+
| Compound          | ![](media/image2.wmf){width="2.75in"             |
|                   | height="1.0256944444444445in"}                   |
+-------------------+--------------------------------------------------+
| Common name       | Bifenthrin                                       |
+-------------------+--------------------------------------------------+
| Company           | Capture^®^                                       |
| experimental      |                                                  |
| names             |                                                  |
+-------------------+--------------------------------------------------+
| Molecular weight  | 422.88                                           |
+-------------------+--------------------------------------------------+
| IUPAC name        | 2-methylbiphenyl-3-ylmethy                       |
|                   | l(*Z*)-(1*RS*,3*RS*)-3-(2-chloro-3,3,3-trifluoro |
|                   | prop-1-enyl)-2,2-dimethylcyclopropanecarboxylate |
|                   |                                                  |
|                   | or                                               |
|                   |                                                  |
|                   | 2-methylbiphenyl-3-ylmet                         |
|                   | hyl(*Z*)-(1*RS*)-cis-3-(2-chloro-3,3,3-trifluoro |
|                   | prop-1-enyl)-2,2-dimethylcyclopropanecarboxylate |
+-------------------+--------------------------------------------------+
| CAS name          | *rel*-2-methyl(1,1\'-biphenyl)-3-yl)             |
|                   | meth                                             |
|                   | yl(1*R*,3*R*)-3-((1*Z*)-2-chloro-3,3,3-trifluoro |
|                   | -1-propenyl)-2,2-dimethylcyclopropanecarboxylate |
+-------------------+--------------------------------------------------+
| CAS \#            | 82657-04-03                                      |
+-------------------+--------------------------------------------------+
| End-use           | 2.0 lb/gal EC and 1.5% G                         |
| products/EP       |                                                  |
+-------------------+--------------------------------------------------+

**2.3 Physical and Chemical Properties**

**Table 2.3 Physicochemical Properties of the Technical Grade
Bifenthrin**

+--------------------------+--------------------------+-----------------+
| Parameter                | Value                    | Reference       |
+==========================+==========================+=================+
| Melting range            | 68-70.6ºC                | Product         |
|                          |                          | Chemistry       |
|                          |                          | Chapter of TRED |
+--------------------------+--------------------------+-----------------+
| pH                       | NA                       |                 |
+--------------------------+--------------------------+-----------------+
| Density at 24°C          | 1.26 g/mL                |                 |
+--------------------------+--------------------------+-----------------+
| Water solubility         | \<0.1 g/L               |                 |
+--------------------------+--------------------------+-----------------+
| Solvent solubility       | 8.9 in heptane and       |                 |
| (g/100 mL)               | methanol                 |                 |
|                          |                          |                 |
|                          | 125 in acetone,          |                 |
|                          | chloroform, ether,       |                 |
|                          | methylene chloride, and  |                 |
|                          | toluene                  |                 |
+--------------------------+--------------------------+-----------------+
| Vapor pressure (Pa) at   | 2.41 x 10^-5^            |                 |
| 25°C                     |                          |                 |
+--------------------------+--------------------------+-----------------+
| Dissociation constant    | NA                       |                 |
| (pK~a~)                  |                          |                 |
+--------------------------+--------------------------+-----------------+
| Octanol/water partition  | \>1 x 10 ^6^             |                 |
| coefficient) Kow         |                          |                 |
+--------------------------+--------------------------+-----------------+
| UV/visible absorption    | NA                       |                 |
| spectrum                 |                          |                 |
+--------------------------+--------------------------+-----------------+

NA = Not available

3.  **Hazard Characterization/Assessment**

References:

***BIFENTHRIN - 3rd Report of the Hazard Identification Assessment
Review Committee*. TXR No. 0051570. B. Tarplee. 2/19/2003.**

***Revised Preliminary HED Chapter for the Bifenthrin Tolerance
Reassessment Eligibility Decision (TRED)*. PC Code: 128825 DP Barcode:
D283796. J. Liccione. 12/04/2002.**

Bifenthrin is a non-systemic insecticide/miticide in the class of
synthetic pyrethroids. It is registered for use on a variety of crops
for the control of insect pests.

Bifenthrin is classified as Category II for acute oral toxicity, and
Category III for acute dermal toxicity. There are no acute inhalation
studies on bifenthrin technical. It is not an eye or skin irritant, or a
dermal sensitizer.

Bifenthrin produces characteristic pyrethroid neurotoxicity. Tremors
have been observed in developmental toxicity studies in the rat and
rabbit, a 2-generation rat reproduction study, subchronic toxicity
studies in the rat and dog, acute and subchronic neurotoxicity rat
studies, a 21-day dermal rat study, chronic oral studies in the rat and
dog, and oncogenicity rat and mouse studies. FOB findings were observed
in the acute and subchronic neurotoxicity studies in the rat.

There is no evidence of increased susceptibility of rats or rabbits to
*in utero* and/or postnatal exposure to bifenthrin.

Bifenthrin was negative in most tests for mutagenicity. It was
marginally mutagenic with and without S9 activation in the mouse
lymphoma forward gene mutation assay. This finding has not been
confirmed in a repeat test. There is also inconclusive, but presumptive
evidence that bifenthrin was mutagenic in the S9-activated phase of the
CHO gene mutation assay (unacceptable study).

The CPRC has characterized bifenthrin as Category C (possible human
carcinogen) primarily on the basis of a mouse study in which the
high-dose (600 ppm) males showed a highly significant increased
incidence of urinary bladder tumors. Other findings in the mouse study
included a dose-related trend of increased combined incidences of
adenoma and adenocarcinoma of the liver (males only), and increased
incidences of bronchioalveolar adenomas and adenocarcinomas of the lung
in females at 50, 200 and 600 ppm (but not 500 ppm) relative to their
controls. The CARC (1992) recommended that for the purpose of risk
characterization, the reference dose (RfD) approach should be used for
quantification of human cancer risk.

**3.1 Hazard and Dose-Response Characterization**

The acute toxicity profile for bifenthrin is presented below in Table
3.1.4. The full toxicological profile is presented in Attachment 1 to
this memo. A summary of the toxicology of bifenthrin is discussed below.

*Subchronic Toxicity*

The database for subchronic toxicity is considered incomplete due to the
lack of a DNT study. The available subchronic oral toxicity studies in
rats and dogs demonstrated the neurotoxicity of bifenthrin. Tremors were
observed in rats fed doses equal to or greater than 100 ppm (7.5
mg/kg/day for males; 8.5 mg/kg/day for females) bifenthrin for 90 days.
Male and female dogs administered (via gelatin capsule) bifenthrin at
doses equal to or greater than 4.42 mg ai/kg/day for up to 13 weeks
exhibited tremors. Ataxia was noted in male dogs at 8.84 and 17.7 mg
ai/kg/day, and in female dogs at 4.42 mg ai/kg/day. Languidness occurred
primarily at 17.7 mg ai/kg/day in both sexes, but also occasionally at
8.84 mg ai/kg/day. All of these symptoms occurred more frequently during
the last 3 weeks of the study. Other dose-related clinical signs
included blinking, mydriasis, nystagmus, lacrimation, and polypnea
(increased rate of respiration) in the two highest dose groups. One
high-dose female appeared thin and/or dehydrated during the final weeks
of the study. A non-statistically significant, but possibly
treatment-related, reduction in mean body weight gain was noted in
females at 17.7 mg ai /kg/day (0.6 kg) relative to the controls (1.3
kg).

*Neurotoxicity*

Bifenthrin produces characteristic pyrethroid neurotoxicity. Tremors
have been observed in developmental toxicity studies in the rat and
rabbit, a 2-generation rat reproduction study, subchronic toxicity
studies in the rat and dog, acute and subchronic neurotoxicity rat
studies, a 21-day dermal rat study, chronic oral studies in the rat and
dog, and oncogenicity rat and mouse studies. Staggered gait and
exaggerated hindlimb flexion were noted in a 21-day dermal toxicity
study in the rat. The neurotoxicity of bifenthrin has been supported by
the results of acute and subchronic neurotoxicity studies in the rat.
FOB findings were observed in these neurotoxicity studies. FOB findings
consisted of tremors, abnormal posture, splayed hindlimbs, staggered
gait, altered activity, altered landing foot-splay, twitching,
uncoordinated movement/ataxia, and convulsions. The HIARC concluded that
there is a concern for developmental neurotoxicity resulting from
exposure to bifenthrin. The DNT study is required based on evidence of
neurotoxicity observed in the developmental toxicity, 2-generation
reproduction, acute and subchronic neurotoxicity, subchronic and chronic
oral toxicity, and dermal toxicity studies. The requirement of a DNT
study for bifenthrin is consistent with HIARC's conclusion for other
pyrethroids, e.g., permethrin, cyfluthrin, and cypermethrin.

*Chronic Toxicity*

The database for chronic toxicity is considered complete. No additional
data are required at this time. The results of chronic toxicity studies
support the finding of neurotoxicity for bifenthrin. Tremors were
observed in both a 1-year feeding study in the dog (LOAEL = 2.7 mg
ai/kg/day for both sexes; NOAEL = 1.3 mg ai/kg/day for both sexes), in a
combined chronic toxicity/oncogenicity dietary study in the rat (LOAEL =
6.1 mg ai/kg/day for females; NOAEL = 3.0 mg ai/kg/day for males), and
in a combined chronic toxicity/oncogenicity dietary study in the mouse
(LOAEL = 25.6 mg ai/kg/day in males; NOAEL = 6.7 mg ai/kg/day in males).

*Developmental Toxicity*

A complete developmental toxicity database exists for bifenthrin. The
available data provided no indication of increased susceptibility of
(quantitative or qualitative) rats or rabbits to *in utero* and/or
postnatal exposure to bifenthrin. In the prenatal developmental (gavage)
toxicity study in rats, a slight increase in the incidence of
"hydroureter without hydronephrosis" was observed in fetuses at the
highest dose tested (2 mg/kg/day); maternal toxicity (tremors) was also
observed at this dose level, and the maternal and developmental NOAELs
were equivalent at 1 mg/kg/day. This effect was not observed in the
prenatal developmental (dietary) toxicity study in rats; maternal
toxicity was evident at 15.5 mg ai/kg/day as tremors and decreased food
consumption, body weight gains, and adjusted (for gravid uterine weight)
body weight gains. In the prenatal developmental toxicity study in
rabbits, there was no evidence of developmental toxicity at the highest
dose tested (8 mg/kg/day). Head and forelimb twitching was observed at
the maternal LOAEL of 4 mg/kg/day; the maternal NOAEL was established at
2.67 mg/kg/day.

*Reproductive Toxicity*

Bifenthrin is not a reproductive toxicant and there is no evidence of
increased susceptibility of offspring. In an acceptable two-generation
reproduction study in rats, no evidence of toxicity was noted in the
offspring at dietary levels up to 100 ppm (5 mg/kg/day). Parental
toxicity (tremors and decreased body weights) was observed at 100 ppm (5
mg/kg/day), with a NOAEL of 60 ppm (3.0 mg/kg/day).

*Carcinogenicity*

There was no conclusive evidence of carcinogenic potential of bifenthrin
in the rat. A mouse oncogenicity study provided some evidence for the
carcinogenic potential of bifenthrin in this species. In the mouse
oncogenicity study, high-dose males showed a highly significant
increased incidence of urinary bladder tumors. Other findings in the
mouse study included a dose-related trend of increased combined
incidences of adenoma and adenocarcinoma of the liver (males only), and
increased incidences of bronchioalveolar adenomas and adenocarcinomas of
the lung in females at 50, 200 and 600 ppm (but not 500 ppm) relative to
their controls. The CRPC has characterized bifenthrin as Category C
(possible human carcinogen) primarily on the basis of the mouse study.
Other findings in the mouse study included a dose-related trend of
increased combined incidences of adenoma and adenocarcinoma of the liver
(males only), and increased incidences of bronchioalveolar adenomas and
adenocarcinomas of the lung in females at some, but not all, doses
relative to their controls. The CARC (1992) recommended that for the
purpose of risk characterization, the reference dose (RfD) approach
should be used for quantification of human cancer risk.

*Mutagenicity*

Bifenthrin was negative in most tests for mutagenicity. It was
marginally mutagenic with and without S9 activation in the mouse
lymphoma forward gene mutation assay. This finding has not been
confirmed in a repeat test. There is also inconclusive, but presumptive,
evidence that bifenthrin was mutagenic in the S9-activated phase of the
CHO gene mutation assay; however, this was an unacceptable study.

*Metabolism*

Bifenthrin is absorbed by the oral route and eliminated primarily in the
feces (about 70% within 48 hours). Approximately 10% of the administered
doses were excreted in the urine. Nearly all the administered dose was
eliminated in urine and feces within 7 days indicating no retention in
the body. Very little of the administered radioactive dose is expired as
14C-CO2. The major metabolic route of radiolabeled bifenthrin is
hydrolysis of the ester linkage with oxidation of the resulting alcohol
to the acid. Protein binding of radioactive components or metabolites
increases with time.

*Dermal Absorption*

Several dermal absorption studies on bifenthrin are available; each
study is considered acceptable for regulatory purposes when taken in
conjunction with the other studies. The HIARC recommended a dermal
absorption rate of 25% based on the weight-of the-evidence available for
structurally related pyrethroids.

**Table 3.1.4 Acute Toxicity Profile -- Bifenthrin**

  --------------------------- ---------- ------------------------- ------------
  **Guideline No./Study       **MRID     **Results**               **Toxicity
  Type**                      No.**                                Category**

  870.1100/Acute oral         0013519    LD~50~ = 70.1 mg/kg (♂);  II
  toxicity                               53.8 mg/kg (♀)            

  870.1200/Acute dermal       00132520   LD~50~ \> 2,000 mg/kg     III
  toxicity                                                         

  870.1300/Acute inhalation   46029703   Data waived. Acceptable   IV
  toxicity                               atmosphere could not be   
                                         generated with product.   

  870.2400/Primary eye        00132522   Non-irritant              IV
  irritation                                                       

  870.2500/Primary dermal     00132521   Non-irritant              IV
  irritation                                                       

  870.2600/Dermal             00132523   Not a sensitizer          N/A
  sensitization                                                    
  --------------------------- ---------- ------------------------- ------------

**3.2 FQPA Considerations**

**3.2.1 Adequacy of the Toxicity Database**

The HIARC concluded that the toxicology database for bifenthrin is not
complete for FQPA assessment. On June 25, 2002, the HIARC requested that
a developmental neurotoxicity study in rats be conducted with
bifenthrin.

**3.2.2 Evidence of Neurotoxicity**

The HIARC concluded that there is a concern for neurotoxicity resulting
from exposure to bifenthrin. This is based on the observation of
neurotoxicity (clinical signs) in the acute neurotoxicity, subchronic
neurotoxicity, 2-generation reproduction, developmental toxicity, dermal
toxicity, subchronic toxicity and chronic toxicity studies. In addition,
FOB findings were observed in the acute and subchronic neurotoxicity
studies.

**3.2.2.1 Acute Neurotoxicity Study**

In an acute oral neurotoxicity study (MRID 44862102), bifenthrin (FMC
54800 technical, 93.7% ai; FMC Ref. No. PL97-592) was administered by a
single gavage dose to 10 Sprague-Dawley rats/sex/dose at doses of 0, 10,
35 or 75 mg/kg, or 0, 9.4, 32.8, or 70.3 mg ai/kg/day (2 control males
and 2 control females were removed from the study due to an unspecified
dosing error, leaving 8/sex). The FOB assessment and motor activity
testing were performed during the pretest interval, and on days 0, 7 and
14. Five animals/sex/group were perfused *in situ* for neurohistological
examination at day 14 and brain, central and peripheral nervous system
tissues from control and high dose animals were examined
microscopically.

At 75 mg/kg, two females died on day 0, shortly after dosing. The
following clinical signs were observed in males after dosing (#
incidences): decreased feces (1 vs. 0 control); staggered gait (1 vs. 0
control); tremors (1 vs. 0 control); and twitching (3 vs. 0 control).
Females displayed the following clinical signs following dosing (#
incidences): abdominogenital staining (2 /2 died vs. 0 control); clonic
convulsions (1 treated/died vs. 0 control); chromorhinorrhea (2 /2 died
vs. 0 control); and tremors (3 \[2 died\] vs. 0 control). All clinical
signs of toxicity were resolved in survivors by study day 2.

The following FOB home cage observations were noted on day 0 at 6-8 hrs
postdosing: whole body tremors (1 male, 1 female/died vs. 0 control);
abnormal mobile posture (1 male vs. 1 control); uncoordinated
movement/ataxia (1 male vs. 0 control); splayed hindlimbs (1 male vs. 0
control); convulsions (2 females/2 died vs. 0 control); tense/rigid
during handling (1 male, 4 females/2 died vs. 0 controls); and unusual
posture (immobile; 1 female/died vs. 0 control). Day 0 FOB open field
observations included the following: localized spasms/twitching (2 males
vs. 0 control); whole body tremors (2 males, 2 females/ 1 died treated
vs. 0 control); staggered gait (1 male vs. 0 control); abnormal posture
(mobile; 1 male vs. 0 control); uncoordinated movement/ataxia (1 male
vs. 0 control); splayed hindlimbs (1 male vs. 0 control); increased
activity (1 female vs. 0 control); decreased activity (1 female/died vs.
0 control); convulsions (2 females/1 died vs. 0 control); walking on
toes (1 female vs. 0 controls); and unusual immobile posture (1
female/died vs. 0 control). Landing foot-splay values were decreased in
males during the day 0 FOB (↓15%, p≤0.05). No treatment-related
differences from controls were observed in the FOB assessment in
survivors on study days 7 and 14. Mean motor activity was decreased in
males on day 0 (↓36%, not statistically significant), while motor
activity in the females was increased on days 0 and 14 (↑23% and ↑18%,
respectively; not statistically significant), although the day 14
increase was not considered biologically significant. No
treatment-related differences were observed in body weights, body weight
gains, gross observations or neuropathological examinations in any
treated group (the latter only examined in control and high dose
groups). No treatment-related findings were observed at 10 or 35 mg/kg.

The LOAEL for this study is 75 mg/kg (70.3 mg ai/kg/day) based on
mortality (females only), clinical and FOB findings and differences in
motor activity. The NOAEL for this study is 35 mg/kg (32.8 mg
ai/kg/day).

**3.2.2.2 Subchronic Neurotoxicity Study**

In this subchronic oral neurotoxicity study (MRID 44862103), FMC 54800
technical (Bifenthrin, 93.7% ai, batch PL97-592) was administered
continuously in the diet for 13 weeks to 10 Sprague-Dawley rats/sex/dose
at doses of 50, 100 or 200 ppm (equivalent to \[M/F\] 0/0, 2.9/3.7,
6.0/7.2 or 11.8/14.6 mg/kg).

At 100 ppm, tremors were observed during clinical examinations in 8 (28
incidences) males and 10 (119 incidences) females. Twitching was
observed in 4 (4 incidences) males and 2 (5 incidences) females. During
the open field portion of the FOB, tremors were observed in all females
following 4 weeks of treatment. In addition, females displayed decreased
(p≤0.05) hindlimb grip strength during weeks 8 and 13 (↓22-25%). One
female died on day 52 as a result of kidney inflammation; however, this
death was not considered treatment related.

At 200 ppm, tremors were observed during clinical examinations in 10
(311 incidences) males and 10 (336 incidences) females. Twitching was
also observed in 10 (76 incidences) males and 10 (96 incidences)
females. During the open field FOB, tremors were observed in all males
and females following 4 weeks of treatment. In addition, females
displayed increased arousal when compared to concurrent controls (3
treated vs. 1 control). Females displayed decreased (p≤0.05 or 0.01)
forelimb grip strength (↓20-31%) and hindlimb grip strength (↓18-36%),
and increased landing foot-splay values (↑21-28%) during weeks 4, 8 and
13. In addition, decreased forelimb grip strength was observed in males
at week 4 (↓27%, not statistically significant), but not at later times.

No treatment-related differences were observed at any dose level in body
weights, body weight gains, food consumption, home cage FOB examination,
motor activity measurements, or gross or neuropathological examinations.

The LOAEL for this study is 100 ppm (equivalent to 6.0 mg/kg/day in
males and 7.2 mg/kg/day in females) based on neuromuscular findings
(tremors, changes in grip strength and landing foot-splay). The NOAEL is
50 ppm (equivalent to 2.9 mg/kg/day in males and 3.7 mg/kg/day in
females).

**3.2.2.3 Evidence of Neurotoxicity From Other Related Studies**

**3.2.3 Developmental Toxicity Studies**

**3.2.3.1 Rat**

*Developmental Rat Studies*

In a **pilot developmental study** (MRID 00154482), bifenthrin (88.35%
ai) in corn oil was administered via gavage to mated female
Sprague-Dawley rats (10/sex/dose) at dose levels of 0, 0.5, 1.0, 2.0, or
2.5 mg/kg/day FMC 54800 during days 6-15 of gestation. These doses are
equivalent to 0, 0.44, 0.88, 1.77, and 2.2 mg ai/kg/day. Three of 10
rats at 2.5 mg/kg/day died on days 14-15. Tremors were noted in all 10
rats at 2.5 mg/kg/day (days 6-15) and in 9/10 at 2.0 mg/kg/day (days 7
through 18). Two of the rats administered 2.5 mg/kg/day also exhibited
clonic convulsions. Mean body weight gains were depressed at 2.5
mg/kg/day throughout the study, and food consumption was lower (↓20%) at
this dose level during days 6-13. There were no differences in mean body
weight gains or food consumption in the lower dose groups with respect
to the controls. There were no treatment-related differences from
controls in the number of implantations or litter size. The mean number
of resorptions was similar in the lower dose groups; at 2.5 mg/kg/day it
was somewhat higher, but this was attributable to an excessive number of
resorptions in a single rat.

The maternal LOAEL is 1.77 mg ai/kg/day (2.0 mg/kg/day) based on
sporadic tremors (gestation days 7-18) and 30% mortality at 2.2 mg
ai/kg/day (2.5 mg/kg/day). The maternal NOAEL is 0.88 mg ai/kg/day (1.0
mg/kg/day). The developmental LOAEL and NOAEL were not determined;
fetuses were not examined.

In a **second developmental study** in rats (MRID 00141201), bifenthrin
(88.35% ai) (as FMC 54800 technical) in corn oil was administered via
gavage to pregnant female Sprague-Dawley rats (25/dose) at dose levels
of 0, 0.5, 1.0, or 2.0 mg/kg/day, which is equivalent to 0, 0.44, 0.88,
and 1.77 mg ai/kg/day, or with 250 mg/kg/day aspirin (positive control)
in 2% carboxymethylcellulose during days 6-15 of gestation.

Maternal toxicity was characterized as tremors in 18/25 dams at 1.77 mg
ai/kg/day (2.0 mg/kg/day) during days 10-19. There were no deaths during
the study, and no significant differences between groups or dose-related
trends with respect to mean maternal body weight gains or food
consumption were noted.

The maternal LOAEL is 1.77 mg ai/kg/day (2.0 mg/kg/day) based on the
incidence of tremors. The maternal NOAEL is 0.88 mg ai/kg/day (1.0
mg/kg/day).

Slight developmental toxicity was noted at 1.77 mg ai/kg/day (2.0
mg/kg/day) and was characterized as an increased fetal and litter
incidence of "hydroureter without hydronephrosis." Although not
statistically significant, the incidence of hydroureter was double that
of the vehicle control and the lower dose groups (3.55% versus 0% in
controls and low dose groups). Also, 5 fetuses from dams at 1.77 mg
ai/kg/day (2.0 mg/kg/day) (from five different litters) had "hydroureter
without hydronephrosis," a finding that was not present in controls or
any of the other exposure groups. There were no other treatment-related
malformations or variations noted at any dose level. There were no group
differences or dose-related trends with respect to pregnancy rates,
numbers of corpora lutea, implantation sites and resorptions, litter
sizes, sex ratios, fetal body weights, or viability. The positive
control gave the appropriate responses of increased early resorptions,
depressed fetal body weights, external, visceral, and skeletal
malformations and variations.

The developmental LOAEL is 1.77 mg ai/kg/day (2.0 mg/kg/day) based on
the increased fetal and litter incidence of hydroureter without
hydronephrosis. The developmental NOAEL is 0.88 mg ai/kg/day (1.0
mg/kg/day).

This developmental toxicity study in the rat is classified as
acceptable-guideline and satisfies the guideline requirement for a
developmental toxicity study (OPPTS 870.3700) in the rat.

Comments: The original DER presented fetal incidence data for
hydroureter (with hydronephrosis and without hydronephrosis separated).
Litter incidence data were not provided. The reviewer notes that litter
incidence of "hydroureter without hydronephrosis" is 0/23, 0/24, 0/25,
and 5/23; the litter incidence of "hydroureter with hydronephrosis" is
3/23, 2/24, 2/24 and 2/23. The original DER concluded based on fetal
incidence data, "the increased incidence of hydroureter without
associated hydronephrosis is equivocal, but without further information
it is being interpreted as indicating a slight fetotoxic effect at 2
mg/kg/day." The reviewer notes that the litter incidence of hydroureter
without hydronephrosis was also slightly increased. A pilot rat
developmental study (MRID 00154482) did not include gross necropsies,
soft tissue or skeletal examination on fetuses. Hydroureter was not
reported in the rabbit developmental study, or in the prenatal
developmental toxicity (dietary) study in rats (MRID 45352301). No
historical control data were presented.

In **another developmental toxicity study** (MRID 45352301), bifenthrin
(95.3% ai; Lot/Batch #PL99-0108) was administered orally in the diet to
25 female Sprague-Dawley CD rats/group at dose levels of 0, 30, 60, 90,
or 200 ppm (equivalent to 0, 2.5, 5.0, 7.4, and 16.3 mg/kg/day or 0,
2.4, 4.8, 7.1 or 15.5 mg ai/kg/day when adjusted for purity) on
gestation days (GD) 6 through 20. All dams were sacrificed on GD 20 and
their fetuses were removed by cesarean and examined.

No animals died during the study. When compared to concurrent controls,
no treatment-related changes were observed in gross pathology, the
number of corpora lutea, number of implantations, number of live and
dead fetuses, number of resorptions, fetal weights, sex ratios, or
post-implantation losses.

At 200 ppm, clinical signs, indicative of neurotoxicity, were observed.
These signs included tremors (22/25), observed from days 9-20;
hypersensitivity to sound (5/25), observed from days 18-20; splayed
hindlimbs (1/25), observed from days 15-20; and piloerection (1/25)
observed at day 19. None of these findings was observed in any control
animal. A negative trend (p≤0.05) in body weight gains was observed
during GDs 6-9, 15-18, and 18-20 with a decrease of 44, 17, and 14%,
respectively, at 200 ppm relative to controls. In addition, a negative
trend (p≤0.001) was observed in adjusted (for gravid uterine weight)
body weight gain with a 22% decrease at 200 ppm when compared to
controls. Food consumption was decreased at 200 ppm at the beginning (GD
6-9) and end (GD 18-20) of treatment (↓11-12%, relative to controls). In
addition, a negative trend (p≤0.05) was observed during GDs 6-9, 9-12,
18-20, and for the overall treatment interval (GD 6-20).

Dose-dependent (p≤0.05 for negative trend) decreases in food consumption
were observed; however, the decreases that were noted at doses below 200
ppm did not result in decreased body weight gains and were considered
not to be toxicologically important.

The maternal LOAEL is 200 ppm (equivalent to 16.3 mg/kg/day or 15.5 mg
ai/kg/day) based on clinical signs and decreased food consumption, body
weight gains, and adjusted (for gravid uterine weight) body weight
gains. The maternal NOAEL is 90 ppm (equivalent to 7.4 mg/kg/day or 7.1
mg ai/kg/day).

No treatment-related developmental findings were noted at any dose
tested.

The developmental toxicity LOAEL was not observed. The developmental
toxicity NOAEL is 200 ppm.

**3.2.3.2 Rabbit**

*Developmental Rabbit Study*

In a developmental study (MRID 00145997), bifenthrin (88.35% ai) in corn
oil was administered via gavage to pregnant female New Zealand White
rabbits (20/dose) at dose levels of 0, 2.67, 4.0, or 8.0 mg/kg/day FMC
54800 technical (equivalent to 0, 2.36, 3.5, and 7.1 mg ai/kg/day) or
with 3.0 g/kg/day 6-aminonicotinamide (positive control) in 2%
carboxymethylcellulose via IP injection during days 7-19 of gestation.
Maternal toxicity was characterized at 7.1 mg ai/kg/day (8.0 mg/kg/day)
as tremors in 17/20 rabbits (observed during days 12-23) and twitching
of the head and forelimb in 14/20 rabbits (observed during days 13-20).
In addition, one rabbit in the 7.1 mg ai/kg/day group displayed clonic
convulsions and loss of muscle control during days 17 and 18. At 3.5 mg
ai/kg/day (4.0 mg/kg/day) head and forelimb twitching was noted in 4/20
rabbits (observed during days 8-16). There were no treatment-related
deaths in the does; however, 10 rabbits died during the study and 9 of
these deaths (including 3 vehicle control animals) were attributed to
Pasteurella multocida. There were no apparent treatment-related
differences in mean body weight gains in the does or pregnancy rates;
data excluded those with infection. There were no gross or microscopic
findings attributable to exposure to the test material.

The maternal LOAEL is 3.5 mg ai/kg/day (4.0 mg/kg/day) based on the
treatment-related incidence of head and forelimb twitching. The maternal
NOAEL is 2.36 mg ai/kg/day (2.67 mg/kg/day). There was no developmental
toxicity demonstrated at any dose level.

There were no treatment-related effects on the number of live fetuses,
fetal weights, implantations, resorptions, external, visceral or
skeletal malformations and variations. The positive control gave the
appropriate responses of increased early resorptions, reduced number of
live fetuses, increased external, visceral, and skeletal malformations
and variations.

A developmental LOAEL was not observed. The developmental NOAEL is ≥7.1
mg ai/kg/day (8.0 mg/kg/day).

**3.2.4 Reproductive Toxicity Study (Rat)**

In a 2-generation study (MRID 00157225), liquified bifenthrin (88.35%
ai) mixed with acetone was administered in the diet to TAC(SD)fBR rats
(25/sex/dose) at dose levels of 0, 30, 60, or 100 ppm as FMC 54800
technical (approximately equivalent to 0, 1.5, 3.0 and 5.0 mg/kg/day). P
generation females at 100 ppm had lower mean body weights (↓4%, p\<0.05)
at week 17 (after gestation and lactation), significantly lower body
weights during the first lactation (days 7 and 14) period; and lower
body weight gains during the second gestation and lactation periods
(statistically significant only on lactation day 14, ↓5% body weight and
↓34% for body weight gain, p\<0.01). There was no correlation between
lower body weight and frequency of tremors. Lower body weights in
females at 60 ppm (although not statistically significant) frequently
paralleled body weight depression at 100 ppm. There were no clinical
signs or effects on body weight at 30 ppm. There were no significant
differences in mean body weights between treated F1animals and controls.
In the high-dose P generation females, there was a statistically
significant increase in absolute and relative brain weights. Mean
absolute ovary weights were slightly decreased (↓9%, p\<0.05 or ↓12%,
p\<0.01) at 60 and 100 ppm, respectively, in the F1 parental generation;
however, ovary-to body-weight ratios were unaffected. In the 100 ppm
group F1b female progeny, absolute adrenal and heart weights were
statistically elevated compared to control values. Significantly
elevated absolute ovary and ovary/brain weights were also observed in
these animals. There were no treatment-related gross or microscopic
findings in either adults or progeny. In either the P or F1 generations,
there were no treatment-related effects on reproductive parameters
(mating, male fertility, female fertility and gestation indices), and
there were no treatment-related gross or microscopic findings in either
sex.

The parental LOAEL is 100 ppm (5.0 mg/kg/day) based on the incidence of
tremors and marginally lower body weights in P and F1 generation females
during gestation and lactation. The parental NOAEL is 60 ppm (3.0
mg/kg/day). A reproductive and offspring LOAEL was not observed. The
reproductive and offspring NOAEL is 100 ppm (5.0 mg/kg/day).

Comments: The original DER identified the 60 ppm dose as a LOAEL based
on decreased absolute ovarian weight; however, the DER also indicated
that the decreased F1 absolute ovarian weight is "equivocal as it was
only observed in F1 adult females and not in F1b or F2b weanlings)," and
"when ovary-to-body weight ratios for F1 females are examined, none of
the FMC 54800 exposed groups are statistically different from controls
for this parameter." The reviewer agrees, and notes the lack of
histopathology effects. The reviewer considers the 60 ppm dose level as
a NOAEL.

A range-finding study summarized in the DER indicates that excessive
fetotoxicity occurred at 10 mg/kg/day (all pups from 2 of the 4 litters
at 10 mg/kg/day died within 14 days of birth) and body weight gains were
decreased during lactation at 2.5, 5, and 10 mg/kg/day.

**3.2.5 Additional Information from Literature Sources**

None.

**3.2.6 Pre-and/or Postnatal Toxicity**

The HIARC concluded that there is not a concern for pre- and/or
postnatal toxicity resulting from exposure to bifenthrin.

**3.2.6.1 Determination of Susceptibility**

Based on the results in a developmental toxicity studies in rats and
rabbits, there was no quantitative or qualitative evidence of increased
susceptibility of rat or rabbit fetuses to *in* *utero* exposure to
bifenthrin.

Based on the results in a 2-generation reproduction study in rats, there
was no quantitative or qualitative evidence of increased susceptibility
of neonates (as compared to adults) to bifenthrin.

**3.2.6.2 Degree of Concern Analysis**

There are no concerns or residual uncertainties for pre and/or
post-natal toxicity following exposure to bifenthrin.

Based upon the above-described data, no special FQPA safety factor is
needed (*i.e.* 1X) since there are no residual uncertainties for pre
and/or post natal toxicity.

The Special FQPA Safety Factor recommended by the HIARC **assumes** that
the exposure databases (dietary food, drinking water, and residential)
are complete and that the risk assessment for each potential exposure
scenario includes all metabolites and/or degradates of concern and does
not underestimate the potential risk for infants and children.

**3.2.7 Recommendation for a DNT Study**

The HIARC concluded that there is a concern for DNT resulting from
exposure to bifenthrin. A DNT study has been submitted and is under
review. The UF~DB~ may change pending the results of the recently
submitted DNT study.

On January 22, 2003, based on the weight of evidence presented, the
HIARC reaffirmed the previous conclusion that a DNT (DNT) study
conducted with bifenthrin in rats is required. HIARC determined that a
10X database UF (UF~DB~) is needed to account for the lack of the DNT
when assessing acute (single dose) exposure scenarios since the
available (acute) data provide no basis to support reduction or removal
of the default 10X factor. The following points were considered in this
determination:

-   It is assumed that the DNT study will be conducted at dose levels
    similar to those used in the rat reproduction study with bifenthrin
    wherein the offspring NOAEL was 5.0 mg/kg/day (no effects were
    observed in offspring at the highest dose tested). But that the DNT
    would not be conducted at dose levels higher than 10 mg/kg/day since
    a range-finding study indicates excessive fetotoxicity occurred at
    this dose (all pups from 2 of the 4 litters at 10 mg/kg/day died
    within 14 days of birth).

-   It is likely that the results of the DNT study will impact the
    currently selected acute regulatory dose since the NOAEL used to
    establish the acute Reference dose for dietary risk assessment (33
    mg/kg/day) is higher (more than 5-fold) than the offspring NOAEL in
    the rat reproduction study conducted with Bifenthrin (5.0
    mg/kg/day).

    Given these circumstances, HIARC does not have sufficient reliable
    data justifying selection of an additional safety factor for the
    protection of infants and children lower than the default value of
    10X for single dose exposure scenarios. Therefore, a UF~DB~ of 10X
    will be applied to single dose exposure scenarios (i.e., acute RfD)
    to account for the lack of the DNT study with bifenthrin.

    HIARC further determined that for repeated dose exposure scenarios a
    3X database UF (UF~DB~) is adequate to account for the lack of the
    DNT based on the following considerations:

-   As stated above, the DNT study will likely be conducted at dose
    levels similar to the rat reproduction study.

-   The results of the DNT study are not expected to impact the current
    regulatory doses selected for repeated exposure scenarios since the
    NOAELs used for these risk assessment endpoints (e.g., 1.3 mg/kg/day
    for chronic RfD) are approximately 5-fold lower than the offspring
    NOAEL (5.0 mg/kg/day) in the rat reproduction study conducted with
    bifenthrin.

    Although the results of the DNT are not expected to impact the
    current regulatory dose given the 3-fold difference observed in the
    rat and dog studies, HIARC does not have sufficient reliable data to
    apply no additional safety factor. Rather, HIARC believes that the
    5X difference between the offspring NOAEL in the rat reproduction
    study and the NOAELs used for risk assessment endpoints provides
    reliable data supporting a 3X. The use of a 3X provides roughly a
    10-fold difference between the NOAEL associated with the identified
    effects in the rat necessitating the DNT study and the NOAELs used
    for setting regulatory doses.

    Therefore, a UF~DB~ of 3X will be applied to repeated dose exposure
    scenarios (i.e., chronic RfD, short- and intermediate-term
    incidental oral, and short-, intermediate-, and long-term dermal and
    inhalation) to account for the lack of the DNT study with
    bifenthrin.

**3.3 Hazard Identification and Toxicity Endpoint Selection**

The strengths and weaknesses of the bifenthrin toxicology database were
considered during the process of toxicity endpoint and dose selection.
The selected toxicity endpoints are summarized in Table 3.5.

**Table 3.3 Summary of Toxicological Doses and Endpoints for
Bifenthrin**

+------------+--------------+--------------------+--------------------+
| **Exposure | **Dose Used  | **FQPA SF^1^ and   | **Study and        |
| Scenario** | in Risk      | Level of Concern   | Toxicological      |
|            | Assessment,  | for Risk           | Effects**          |
|            | UF**         | Assessment**       |                    |
+============+==============+====================+====================+
| Acute      | NOAEL = 32.8 | FQPA SF = 1X       | Acute              |
| Dietary-   | mg ai/kg     |                    | neurotoxicity      |
|            |              | aPAD = [acute      | study in rats.     |
| general    | UF = 1000    | RfD]{.underline}   | LOAEL = 70.3       |
| p          |              |                    | mg/kg/day based on |
| opulation, | Acute RfD =  | FQPA SF            | observations of    |
| including  | 0.033        |                    | mortality (females |
| infants    | mg/kg/day    | = 0.033 mg/kg/day  | only), clinical    |
| and        |              |                    | and FOB findings   |
| children   |              |                    | and differences in |
|            |              |                    | motor activity.    |
+------------+--------------+--------------------+--------------------+
| Chronic    | NOAEL = 1.3  | FQPA SF = 1X       | 1-year oral        |
| Dietary-   | mg ai/kg/day |                    | toxicity in dogs.  |
|            |              | cPAD =             | LOAEL = 2.7        |
| general    | UF = 300     | [cRfD]{.underline} | mg/kg/day based on |
| p          |              |                    | observations of    |
| opulation, | Chronic RfD  | FQPA SF            | increased          |
| including  | = 0.004      |                    | incidence of       |
| infants    | mg/kg/day    | = 0.004 mg/kg/day  | tremors in both    |
| and        |              |                    | sexes.             |
| children   |              |                    |                    |
+------------+--------------+--------------------+--------------------+
| Short-Term | NOAEL= 2.21  | Residential MOE =  | 90-day oral        |
|            | mg ai/kg/day | 300                | toxicity study in  |
| (1-30      |              |                    | dogs. LOAEL = 4.42 |
| days)      | UF = 300     |                    | mg/kg/day based on |
|            |              |                    | observations of    |
| Incidental | MOE= 300     |                    | increased          |
| Oral       |              |                    | incidence of       |
|            |              |                    | tremors in both    |
|            |              |                    | sexes.             |
+------------+--------------+--------------------+--------------------+
| Interme    | NOAEL= 2.21  | Residential MOE =  | 90-day oral        |
| diate-Term | mg ai/kg/day | 300                | toxicity study in  |
| (1-6       |              |                    | dogs. LOAEL = 4.42 |
| months)    | UF = 300     |                    | mg/kg/day based on |
| Incidental |              |                    | observations of    |
| Oral       | MOE= 300     |                    | increased          |
|            |              |                    | incidence of       |
|            |              |                    | tremors in both    |
|            |              |                    | sexes.             |
+------------+--------------+--------------------+--------------------+
| Short-Term | Dermal NOAEL | Residential MOE =  | 21-day dermal      |
|            | = 47         | 300                | study in rats.     |
| (1-30      | mg/kg/day    |                    |                    |
| days)      |              | Occupational MOE = | LOAEL = 93         |
|            |              | 100                | mg/kg/day based on |
| Dermal     |              |                    | observations of    |
|            |              |                    | clinical signs     |
|            |              |                    | (staggered gait    |
|            |              |                    | and exaggerated    |
|            |              |                    | hindlimb reflex).  |
+------------+--------------+--------------------+--------------------+
| Interme    | Dermal NOAEL | Residential MOE =  | 21-day dermal      |
| diate-Term | = 47         | 300                | study in rats.     |
| (1-6       | mg/kg/day    |                    |                    |
| months)    |              | Occupational MOE = | LOAEL = 93         |
| Dermal     |              | 100                | mg/kg/day based on |
|            |              |                    | observations of    |
|            |              |                    | clinical signs     |
|            |              |                    | (staggered gait    |
|            |              |                    | and exaggerated    |
|            |              |                    | hindlimb reflex).  |
+------------+--------------+--------------------+--------------------+
| Long-Term  | Dermal NOAEL | Residential MOE =  | 21-day dermal      |
|            | = 47         | 300                | study in rats.     |
| (\>6       | mg/kg/day    |                    |                    |
| months)    |              | Occupational MOE = | LOAEL = 93         |
|            |              | 100                | mg/kg/day based on |
| Dermal     |              |                    | observations of    |
|            |              |                    | clinical signs     |
|            |              |                    | (staggered gait    |
|            |              |                    | and exaggerated    |
|            |              |                    | hindlimb reflex).  |
+------------+--------------+--------------------+--------------------+
| Short-Term | NOAEL= 2.21  | Residential MOE =  | 1-year oral        |
|            | mg ai/kg/day | 300                | toxicity in dogs.  |
| (1-30      |              |                    | LOAEL = 2.7        |
| days)      | UF = 300     | Occupational MOE = | mg/kg/day based on |
|            |              | 100                | observations of    |
| Inhalation | MOE= 300     |                    | increased          |
|            |              |                    | incidence of       |
|            |              |                    | tremors in both    |
|            |              |                    | sexes.             |
+------------+--------------+--------------------+--------------------+
| Interme    | NOAEL= 2.21  | Residential MOE =  | 1-year oral        |
| diate-Term | mg ai/kg/day | 300                | toxicity in dogs.  |
| (1-6       |              |                    | LOAEL = 2.7 mg     |
| months)    | UF = 300     | Occupational MOE = | ai/kg/day based on |
| Inhalation |              | 100                | observations of    |
|            | MOE= 300     |                    | increased          |
|            |              |                    | incidence of       |
|            |              |                    | tremors in both    |
|            |              |                    | sexes.             |
+------------+--------------+--------------------+--------------------+
| Long-Term  | NOAEL= 2.21  | Residential MOE =  | 1-year oral        |
|            | mg ai/kg/day | 300                | toxicity in dogs.  |
| (\>6       |              |                    | LOAEL = 2.7        |
| months)    | UF = 300     | Occupational MOE = | mg/kg/day based on |
|            |              | 100                | observations of    |
| Inhalation | MOE= 300     |                    | increased          |
|            |              |                    | incidence of       |
|            |              |                    | tremors in both    |
|            |              |                    | sexes.             |
+------------+--------------+--------------------+--------------------+
| Cancer     | **Class      |                    |                    |
| (oral,     | ification:** |                    |                    |
| dermal,    | **Category   |                    |                    |
| i          | C**          |                    |                    |
| nhalation) | (possible    |                    |                    |
|            | human        |                    |                    |
|            | carcinogen). |                    |                    |
|            | No Q~1~\*    |                    |                    |
|            | has been     |                    |                    |
|            | derived. RfD |                    |                    |
|            | approach     |                    |                    |
|            | recommended  |                    |                    |
|            | for cancer   |                    |                    |
|            | assessment.  |                    |                    |
+------------+--------------+--------------------+--------------------+

UF = uncertainty factor, FQPA SF = Special FQPA Safety Factor, NOAEL =
no observed adverse effect level, LOAEL = lowest observed adverse effect
level, RfD = reference dose (a = acute, c = chronic), PAD = population
adjusted dose, MOE = margin of exposure, LOC = level of concern, N/A =
Not Applicable

^1^Refer to Section 3.4

**3.3.1 Acute Reference Dose (aRfD) - Females age 13-49**

HIARC determined that no appropriate acute dietary endpoint was
available to quantify risk to females 13-50 years of age from a
single-dose administration of bifenthrin.

A developmental toxicity study in rats (gavage) with a developmental
NOAEL of 0.88 mg ai/kg/day (1.0 mg/kg/day) based on the increased fetal
and litter incidence of hydroureter without hydronephrosis seen at the
LOAEL of 1.77 mg ai/kg/day (2.0 mg/kg/day) was considered as an endpoint
for aRfD for females age 13-49. However, this evidence was considered as
equivocal since the litter incidence of "hydroureter without
hydronephrosis" is 0/23, 0/24, 0/25, and 5/23; the litter incidence of
"hydroureter with hydronephrosis" is 3/23, 2/24, 2/24 and 2/23. In
addition, this effect was not observed in a dietary developmental
toxicity study in rats using the same strain of rats. Therefore, HIARC
concluded that the endpoint (hydroureter/hydronephrosis) is not
appropriate for this risk assessment.

**3.3.2 Acute Reference Dose (aRfD) - General Population**

Acute dietary endpoints were available to quantify risk to the general
population, including infants and children. For this scenario, an acute
reference dose (aRFD) of 0.033 mg/kg/day was determined on the basis of
an acute neurotoxicity study in rats and the application of an UF of
1000 (10x for interspecies extrapolation, 10x for intraspecies
variation, and 10x for incomplete database for lack of a DNT study). The
NOAEL in this study was 32.8 mg ai/kg/day and the LOAEL was 70.3 mg
ai/kg/day based on mortality (females), clinical and FOB findings and
differences in motor activity. Although a lower NOAEL for an effect
(*i.e.*, tremors in dams) associated with a single dose exposure was
observed in a developmental gavage study, the vehicle (corn oil) used in
this study enhanced the toxicity of bifenthrin. There is evidence that,
in the case for bifenthrin, corn oil can enhance its toxicity. This
evidence is based on the results of comparative studies of the acute
oral LD50 of bifenthrin following oral gavage as either a corn oil
vehicle or as an undiluted technical material to rats. These comparative
studies demonstrate increased lethality from bifenthrin exposure in a
corn oil vehicle. In the acute neurotoxicity study in rats, bifenthrin
was administered undiluted by gavage, making this study more suitable
than the developmental gavage study (with corn oil as vehicle) for risk
assessment purposes. Therefore, the acute neurotoxicity study was
selected for the acute reference dose, and the aRfD is 0.033 mg/kg/day.

**3.3.3 Chronic Reference Dose (cRfD)**

A cRfD of 0.004 mg/kg/day was determined on the basis of the one-year
oral study in dogs and the application of an UF of 300 (10x for
interspecies extrapolation, 10x for intraspecies variation, and 3x for
incomplete database for lack of a DNT study). The NOAEL in this study
was 1.3 mg ai/kg/day and the LOAEL was 2.7 mg ai/kg/day based on
observations of increased incidence of tremors in both sexes.

**3.3.4 Incidental Oral Exposure (Short- and Intermediate-Term)**

A NOAEL of 2.21 mg ai/kg/day was selected from the 90-day oral study in
dogs, and used for short- and intermediate-term incidental oral and
short- and intermediate-term inhalation risk assessments. This NOAEL was
based on observations of increased incidence of tremors in males and
females at the LOAEL of 4.42 mg ai/kg/day. The HIARC concluded that the
selected dose/endpoint is appropriate for the population and durations
of concern. For the inhalation scenarios, an inhalation absorption
factor of 100% (default value assuming equivalent inhalation and oral
absorption) was used for route-to-route extrapolation.

**3.3.5 Dermal Absorption**

Several dermal absorption studies on bifenthrin were available; each
study was considered acceptable for regulatory purposes when taken in
conjunction with the other studies. The HIARC recommended a dermal
absorption rate of 25% based on the weight-of the-evidence available for
structurally related pyrethroids. However, since a dermal toxicity study
was used for the assessment of short- and intermediate-term dermal risk,
the dermal absorption factor was not used.

**3.3.6 Dermal Exposure (Short- and Intermediate-Term)**

A NOAEL of 47 mg/kg/day was selected from the 21-day dermal study in
rats. The LOAEL of 93 mg/kg/day was based on observations of clinical
signs (staggered gait and exaggerated hindlimb flexion). The HIARC
determined that the dermal toxicity study is appropriate for short-,
intermediate- and long-term dermal exposures and durations because,
besides route specificity, the subchronic and chronic oral toxicity
studies in dogs and rats demonstrate neurotoxicity of similar magnitude.
Since a dermal toxicity study is selected for dermal risk assessment, a
dermal absorption factor is not required.

**3.3.7 Inhalation Exposure (Short and Intermediate-Term)**

A NOAEL of 2.21 mg/kg/day was selected from the 90-day oral study in
dogs, and used for short- and intermediate-term inhalation risk
assessments. This NOAEL was based on observations of increased incidence
of tremors in males and females at the LOAEL of 4.42 mg/kg/day. The
HIARC concluded that the selected dose/endpoint is appropriate for the
population and durations of concern. An inhalation absorption factor of
100% (default value assuming equivalent inhalation and oral absorption)
was used for route-to-route extrapolation.

The results of the one-year oral dog study were selected for the
long-term inhalation risk assessment. The NOAEL in this study was 1.3
mg/kg/day and the LOAEL was 2.7 mg/kg/day based on observations of
increased incidence of tremors in both sexes. An inhalation absorption
factor of 100% (default value assuming equivalent inhalation and oral
absorption) was used for route-to-route extrapolation.

**3.3.8 Level of Concern for Margin of Exposure**

The target MOEs for occupational and residential exposure risk
assessments are as follows:

+---------------+-----------------+---+-----------------+---+-----------------+
| **Route**     | **Duration**    |   |                 |   |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
|               | **Short-Term**  | * |                 | * |                 |
|               |                 | * |                 | * |                 |
|               | **(1-30 days)** | I |                 | L |                 |
|               |                 | n |                 | o |                 |
|               |                 | t |                 | n |                 |
|               |                 | e |                 | g |                 |
|               |                 | r |                 | - |                 |
|               |                 | m |                 | T |                 |
|               |                 | e |                 | e |                 |
|               |                 | d |                 | r |                 |
|               |                 | i |                 | m |                 |
|               |                 | a |                 | * |                 |
|               |                 | t |                 | * |                 |
|               |                 | e |                 |   |                 |
|               |                 | - |                 | * |                 |
|               |                 | T |                 | * |                 |
|               |                 | e |                 | ( |                 |
|               |                 | r |                 | \ |                 |
|               |                 | m |                 | > |                 |
|               |                 | * |                 | 6 |                 |
|               |                 | * |                 | M |                 |
|               |                 |   |                 | o |                 |
|               |                 | * |                 | n |                 |
|               |                 | * |                 | t |                 |
|               |                 | ( |                 | h |                 |
|               |                 | 1 |                 | s |                 |
|               |                 |   |                 | ) |                 |
|               |                 | - |                 | * |                 |
|               |                 | 6 |                 | * |                 |
|               |                 | M |                 |   |                 |
|               |                 | o |                 |   |                 |
|               |                 | n |                 |   |                 |
|               |                 | t |                 |   |                 |
|               |                 | h |                 |   |                 |
|               |                 | s |                 |   |                 |
|               |                 | ) |                 |   |                 |
|               |                 | * |                 |   |                 |
|               |                 | * |                 |   |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
| *             |                 |   |                 |   |                 |
| *Occupational |                 |   |                 |   |                 |
| (Worker)      |                 |   |                 |   |                 |
| Exposure**    |                 |   |                 |   |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
| **Dermal**    | 100^a^          | 1 |                 | 1 |                 |
|               |                 | 0 |                 | 0 |                 |
|               |                 | 0 |                 | 0 |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
| *             | 100             | 1 |                 | 1 |                 |
| *Inhalation** |                 | 0 |                 | 0 |                 |
|               |                 | 0 |                 | 0 |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
| **Residential |                 |   |                 |   |                 |
| (Non-Dietary) |                 |   |                 |   |                 |
| Exposure**    |                 |   |                 |   |                 |
+---------------+-----------------+---+-----------------+---+-----------------+
| **Oral**      | 300             |   | 300             |   | 300             |
+---------------+-----------------+---+-----------------+---+-----------------+
| **Dermal**    | 300             |   | 300             |   | 300             |
+---------------+-----------------+---+-----------------+---+-----------------+
| *             | 300             |   | 300             |   | 300             |
| *Inhalation** |                 |   |                 |   |                 |
+---------------+-----------------+---+-----------------+---+-----------------+

> ^a^ based on the conventional UF of 100X (10X for interspecies
> extrapolation and 10X for intraspecies variation)

9.  **Recommendation for Aggregate Exposure Risk Assessments**

The toxicity endpoints selected for these routes of exposure may be
aggregated as follows: for short-, intermediate- and long-term aggregate
exposure risk assessments, the oral, dermal and inhalation (oral
equivalent) routes can be combined because of the common toxicity
endpoints (clinical signs of neurotoxicity) via these routes.

10. **Classification of Carcinogenic Potential**

There was no conclusive evidence of carcinogenic potential of bifenthrin
in the rat. A mouse oncogenicity study provided some evidence for the
carcinogenic potential of bifenthrin in this species. In the mouse
oncogenicity study, high-dose males showed a highly significant
increased incidence of urinary bladder tumors. Other findings in the
mouse study included a dose-related trend of increased combined
incidences of adenoma and adenocarcinoma of the liver (males only), and
increased incidences of bronchioalveolar adenomas and adenocarcinomas of
the lung in females at 50, 200 and 600 ppm (but not 500 ppm) relative to
their controls. The CPRC has characterized bifenthrin as Category C
(possible human carcinogen) primarily on the basis of the mouse study.
Other findings in the mouse study included a dose-related trend of
increased combined incidences of adenoma and adenocarcinoma of the liver
(males only), and increased incidences of bronchioalveolar adenomas and
adenocarcinomas of the lung in females at some, but not all, doses
relative to their controls. The CARC (1992) recommended that for the
purpose of risk characterization, the reference dose (RfD) approach
should be used for quantification of human risk.

**3.4 Endocrine disruption**

EPA is required under the Federal Food, Drug, and Cosmetic Act (FFDCA),
as amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate." Following recommendations
of its Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system. EPA also adopted EDSTAC=s recommendation
that the Program include evaluations of potential effects in wildlife.
For pesticide chemicals, EPA will use the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and, to the extent that effects
in wildlife may help determine whether a substance may have an effect in
humans, FFDCA authority to require the wildlife evaluations. As the
science develops and resources allow, screening of additional hormone
systems may be added to the Endocrine Disruptor Screening Program
(EDSP). Bifenthrin database did not indicate any endocrine mediated
effects. When additional appropriate screening and/or testing protocols
being considered under the Agency's EDSP have been developed, bifenthrin
may be subjected to further screening and/or testing to better
characterize effects related to endocrine disruption.

**4.0 Dietary Exposure/Risk Characterization**

**4.1 Pesticide Metabolism and Environmental Degradation**

**4.1.1 Metabolism in Primary Crops and Livestock**

**4.1.1.1 Metabolism in Primary Crops**

**Bifenthrin TRED, Number range CHAPTERS. Levy, 21-AUG-2002; DP#
283808**

45794202.der

Number range CHAPTERThe nature of bifenthrin residues in plants is
adequately understood based on the available metabolism studies on corn,
cotton, and apple. HED previously determined that for purposes of
tolerance expression and risk assessment, the residue of concern in
cotton and apple commodities is bifenthrin *per se* (Memos, M. Flood,
24-DEC-1987 and N. Dodd, 02-JUL-1987). After re-examining the cotton and
apple metabolism data and additional corn metabolism data, the HED
Metabolism Committee (Memo, M. Flood, 23-JUL-1993) reaffirmed that the
residue of concern in plant commodities is bifenthrin *per se*.

In conjunction with the petition for use on tuberous and corm
vegetables, IR-4 has submitted an additional metabolism study on
potatoes reflecting both soil and foliar applications of \[^14^C\]
bifenthrin. The potato study is adequate and the results from the
metabolism study support HED's previous determination that the residue
of concern is bifenthrin *per se.*

Number range CHAPTER

**4.1.1.2 Metabolism in Livestock**

**Bifenthrin TRED, Number range CHAPTERS. Levy, 21-AUG-2002; DP#
283808**

Adequate ruminant and poultry metabolism studies are available depicting
the metabolism of bifenthrin radiolabeled in either the phenyl or
cyclopropyl ring. Based on these data, the HED Metabolism Committee (M.
Flood, 8/2/93) concluded that the residue of concern in livestock
commodities is bifenthrin *per se.*

**4.1.2 Metabolism in Rotational Crops**

**Bifenthrin TRED, Number range CHAPTERS. Levy, 21-AUG-2002; DP#
283808**

Adequate confined and field rotational crop studies are available. Based
on the confined study, HED has concluded that the residue of concern in
rotational crops is the parent compound only.

**4.1.3 Analytical Methodology**

Adequate gas chromatography (GC)/electron-capture detection (ECD)
methods are available for enforcing tolerances of bifenthrin in plant
and livestock commodities. The available methods for plant commodities
generally involve extraction of the sample with acetone, partitioning
with hexane, purification using a Florisil column, and analysis of
residues by GC/ECD. The limit of quantitation (LOQ) for these methods is
0.05 ppm. Samples from the current field trials and the potato
processing study were analyzed using methods that are modifications to
one of the current enforcement methods (P-2550 M), with variations in
extraction solvents and detection methods. Residues of bifenthrin in/on
mustard greens and cilantro (leaves and seeds) were determined using a
GC/ECD method (FMC Report P-2132). For this method, residues are
extracted with hexane, concentrated, and cleaned up using a Florisil
column, then analyzed by GC/ECD. Residues in/on potato fractions and
dried beans and peas were determined using a GC/mass-selective detection
(MSD) method (FMC Report P-3426). For this method, residues are
extracted with acetone, concentrated, and purified by silica-gel
solid-phase extraction (SPE). The residues are then analyzed by GC/MSD,
using the m/z 181 ion for quantitation. Residues in/on green tobacco
were determined using a related GC/MSD method (FMC Report P-3457). For
this method, residues are extracted with acetone/water, partitioned into
hexane, and cleaned up with a SPE column, and analyzed by GC/MSD. For
each of the above methods, the LOQ for bifenthrin is 0.05 ppm, and the
reported limit of detection (LOD) is 0.01 ppm. Each of these methods was
adequately validated in conjunction with analysis of samples from the
field trials or processing study.

4.  **Environmental Degradation**

*Tier I Estimated Environmental Concentrations of Bifenthrin for the Use
in the Human Health Risk Assessment.* 02/07/2006. J. Melendez

Number range CHAPTERThe environmental fate database for bifenthrin is
complete enough to characterize drinking water exposure. The submitted
data indicate that bifenthrin is relatively persistent under both
laboratory and field conditions. Bifenthrin is relatively immobile in
four soils tested. Due to its low mobility, bifenthrin is not likely to
reach subsurface soil environments (lower microbial activity) or ground
waters. Various terrestrial field dissipation studies confirm that
bifenthrin remains mostly in the upper soil level. Due to its low
solubility and high level of binding it appears that bifenthrin would
remain bound to the soils during run-off events and it may reach surface
waters [if]{.underline} the run-off event is accompanied by erosion.

The HED Metabolism Assessment Review Committee (MARC) concluded that the
parent compound, bifenthrin *per se*, should be the residue of concern
for drinking water risk assessment based on its persistence and the
absence of major degradates in laboratory studies (HED Doc. No.
0050887).

**4.1.5 Food Residue Profile**

The field trials on potatoes, mustard greens, dried beans and peas,
cilantro, and tobacco are Number range CHAPTERadequate. An adequate
number of trials were conducted reflecting the proposed use patterns in
the appropriate geographic regions, and the appropriate commodities were
collected at the proposed PHIs. Samples were analyzed using adequate
analytical methods, and the sample storage intervals are supported by
the available storage stability data.

Following an at-planting soil application and two foliar applications of
bifenthrin at 1x the proposed rate, residues were \<0.05 ppm (\<LOQ)
in/on all potatoes harvested at 21 days after the final treatment (DAT).
Residues on mustard greens harvested 6-7 DAT were \<0.05-2.05 ppm
following four foliar applications of bifenthrin (EC) totaling \~0.4 lb
ai/A (1x). In the dried bean and pea field trials, residues on dried
beans harvested 13-15 DAT were \<0.05-0.10 ppm following three foliar
applications of bifenthrin (EC) totaling 0.3 lb ai/A (1x), and residues
on dried peas harvested 14-15 DAT were \<0.05 ppm following two foliar
applications of bifenthrin (EC) totaling 0.2 lb ai/A (1x). Following
five foliar applications of bifenthrin (EC) to cilantro totaling \~0.5
lb ai/A (1x), residues at 3 DAT were 1.98-4.83 ppm in/on fresh leaves,
14.93-16.25 ppm in/on dried leaves, and 3.66-3.69 ppm in/on seeds. In
the tobacco field trials, residues of bifenthrin were \<0.05 ppm in/on
all green tobacco samples harvested at normal maturity following either
a preplant or at-transplanting application of bifentrhin (EC or G) at
0.1 lb ai/A and a single foliar application of bifenthrin (EC) at 0.05
or 0.10 lb ai/A (1x).

[]{.mark}

The available potato processing study is adequate. Because bifenthrin
residues were \<LOQ (\<0.05 ppm) in all samples from the potato field
trials and in potato tubers and all processed fractions from the
processing study conducted at a 3x rate, HED concludes that residues of
bifenthrin in wet peel are unlikely to exceed the LOQ when bifenthrin is
applied at a 1x rate. Therefore, a separate tolerance will be not be
required for residues in/on processed potato fractions. In addition, a
comparison of residues in/on fresh and dried cilantro leaves indicates
that there is a 5.7x processing factor for dried cilantro leaves. Based
on highest-average field-trial (HAFT) residues of 3.96 ppm in/on fresh
leaves, the maximum expected residues in/on dried cilantro leaves would
be 22.6 ppm.

The proposed tolerances for plant commodities will not have any impact
on the current tolerances for livestock commodities. The only proposed
crop use with any regulated livestock feedstuffs is potato (processed
potato waste and culls), and the addition of these commodities to
livestock diets will not increase the dietary exposure of livestock
calculated in the Bifenthrin Number range CHAPTERTolerance Reassessment
Eligibility Decision (TRED) (S. Levy, 22-AUG-2002; DP#283808).

Adequate confined and field rotational crop studies are available to
support the proposed uses. Based on the results of these rotational crop
studies, HED concludes that the current rotational crop plant-back
interval is acceptable and that tolerances for rotated crops are not
necessary.

**4.1.5.1 Tolerance Summary**

[]{.mark}

The tolerances proposed by the registrants in the current vegetable
petitions are listed below in Table 5.1.5.1, along with HED's
recommended tolerance levels. Number range CHAPTER The appropriate
tolerance levels were calculated using the methodology formulated by the
NAFTA MRL/Tolerance Harmonization Workgroup for calculating
statistically-based pesticide tolerances for plant commodities based on
field trial residue data (Attachment 2). Number range CHAPTER Maximum
likelihood estimation (MLE) techniques were used to supplement the dried
bean dataset. Based on visual inspection of the probability plot, the
lognormality assumption was rejected \[HED Science Advisory Council for
Chemistry (ChemSAC) meeting of 3/8/06\]. The value derived by the
California Method (0.15 ppm) was thus deemed to be appropriate.
**Revised Sections F with the correct tolerance levels and commodity
definitions should be submitted where appropriate.**

The available potato data will support a tolerance of 0.05 ppm on
tuberous and corm vegetables (subgroup 1C), and the mustard green data
will support a tolerance of 3.5 ppm on leafy *Brassica* vegetables
(subgroup 5B). The data on dried beans and peas will support a tolerance
of 0.15 ppm on shelled dried beans and peas, excluding soybean (subgroup
6C). The data on cilantro (coriander) will support separate tolerances
of 5 ppm in/on coriander leaves and seed. Based on the HAFT residues
observed for coriander leaves (3.96 ppm) and the observed processing
factor of 5.7x for dried leaves, the maximum expected residues in/on
dried leaves would be 22.6 ppm, which will support at tolerance of 25
ppm for dried coriander leaves.

[]{.mark}

**[Table 4.1.5.1. Tolerance Summary for Bifenthrin Number range
CHAPTER]{.mark}**

+----------------------+-----------+------------+----------------------+
| Crop Commodity       | Proposed  | R          | Comments             |
|                      | Tolerance | ecommended |                      |
|                      | (ppm)     | Tolerance  | Number range         |
|                      |           | (ppm)      | CHAPTER(*correct     |
|                      |           |            | commodity            |
|                      |           |            | definition*)         |
+----------------------+-----------+------------+----------------------+
| Tuberous and corm    | 0.1       | 0.05       | *Vegetable, tuberous |
| vegetables, subgroup |           |            | and corm, subgroup   |
| 1C                   |           |            | 1C*                  |
+----------------------+-----------+------------+----------------------+
| *Brassica*, leafy    | 3         | 3.5        |                      |
| greens, subgroup     |           |            |                      |
| 5B^1^                |           |            |                      |
+----------------------+-----------+------------+----------------------+
| Turnip greens^1^     | 3         | 3.5        | *Turnip, greens*     |
+----------------------+-----------+------------+----------------------+
| Pea and bean, dried  | 0.1       | 0.15       | *Pea and bean, dried |
| shelled, except      |           |            | shelled, except      |
| soybean, subgroup    |           |            | soybean, subgroup    |
|                      |           |            | 6C*                  |
+----------------------+-----------+------------+----------------------+
| Cilantro, leaves     | 5.0       | 6.0        | *Coriander, leaves*  |
+----------------------+-----------+------------+----------------------+
| Cilantro, dried      | 30.0      | 25         | *Coriander, dried    |
| leaves               |           |            | leaves*              |
+----------------------+-----------+------------+----------------------+
| Coriander, seed      | 5.0       | 5.0        |                      |
+----------------------+-----------+------------+----------------------+

^1^ Number range CHAPTERTurnip greens will be removed from Crop Group 2:
Leaves of root and tuber vegetables group \[40 CFR 180.41 (2)\], and
will become a member of Crop Group 5: *Brassica* leafy vegetables \[40
CFR 180.41 (5)\]. It will also be a member of Crop Subgroup 5B: Leafy
*Brassica* greens (Commodity Reviewers Guide, B. Schneider,
14-JUN-2002). Until that time, "turnip, greens" should have a separate
tolerance.

**4.1.6 International Residue Limits**

Number range CHAPTERThe Codex Alimentarius Commission has established
maximum residue limits (MRLs) for residues of bifenthrin in/on various
commodities. Codex MRLs are expressed in terms of bifenthrin *per se*,
as are U.S. tolerances. The only established Codex MRL relevant to the
current petitions is for potato at 0.05 mg/kg (See attached
International Residue Limits Status sheet). As the recommended tolerance
of tuberous and corm vegetables is also 0.05 ppm, this tolerance is in
harmony with the Codex MRL for potato. There are no equivalent Canadian
or Mexican MRLs for the tolerances being requested in the current
petition.

**4.1.7 Drinking Water Residue Profile**

***Tier I Estimated Environmental Concentrations of Bifenthrin for the
Use in the Human Health Risk Assessment.* 02/07/2006. J. Melendez**

*Residues of Concern in Drinking Water*

The HED MARC concluded that the parent compound, bifenthrin *per se*,
should be the residue of concern for drinking water risk assessment
based on its persistence and the absence of major degradates in
laboratory studies (HED Doc. No. 0050887).

*Drinking Water Estimates*

The EDWCs for bifenthrin were calculated based on a maximum application
rate of 0.5 lb ai/A/season. The acute drinking water concentration in
surface water is 0.0140 ppb of bifenthrin, based on aerial applications
to lettuce. The cancer/chronic drinking water concentration is 0.0140
ppb (based on applications of lettuce, highest application rate). The
SCI-GROW generated EDWC is 0.00300 ppb of bifenthrin, which is
recommended for use, both for acute and chronic exposures. Because of
the very low solubility of bifenthrin, the EDWCs did not exceed 0.0140
ppb (the solubility of bifenthrin).

**Table 4.1.7. Tier 1 Estimated Drinking Water Concentrations for
Bifenthrin**

  ------------------- -------------------- --------------- ---------------
  **DRINKING WATER    **USE (rate          **MAXIMUM       
  SOURCE (MODEL       modeled)**           ESTIMATED       
  USED)**                                  DRINKING WATER  
                                           CONCENTRATION   
                                           (EDWC) ( ppb)** 

  Groundwater         Lettuce (0.5 lb.     Acute and       0.00300
  (SCI-GROW)          ai/A/season)         Chronic         

  Surface water       Lettuce (0.5 lb.     Acute           0.0140
  (FIRST)             ai/A/season)                         

                      Lettuce (0.5 lb.     Chronic         0.0140
                      ai/A/season)                         
  ------------------- -------------------- --------------- ---------------

**4.2 Dietary Exposure and Risk**

Acute and chronic dietary exposure and risk assessments were conducted
using the Model (DEEM-FCID™, Version 2.03) which uses food consumption
data from the U.S. Department of Agriculture's CSFII from 1994-1996 and
1998. Number range CHAPTERThe analyses were performed as part of a
registration action; (1) to support Interregional Research Project No. 4
(IR-4) tolerance petitions for pending uses on dried peas and beans,
cilantro, *Brassica* leafy vegetables, and tuberous and corm vegetables;
(2) to include drinking water estimates; and (3) to support the new
acute toxicological endpoint.

1.  **Acute Dietary Exposure and Risk**

The acute dietary exposure estimates for food and drinking water [are
below HED's level of concern]{.underline} (\<100% aPAD) at the 99.9^th^
percentile of exposure (see Table 4.2.1). Bifenthrin dietary exposure at
the 99.9^th^ percentile for food and drinking water for the U.S.
population is 21% of the aPAD and 41% of the aPAD for children 1-2 yrs,
the most highly exposed population subgroup.

**Table 4.2.1. Results of Bifenthrin Acute Dietary (Food + Drinking
Water) Exposure Analysis Using DEEM FCID**

  ---------------------------------------------------------------------------
  Population Subgroup           aPAD          99.9th           
                                (mg/kg/day)   Percentile       
  ----------------------------- ------------- ---------------- --------------
                                              Exposure         \% aPAD
                                              (mg/kg/day)      

  General U.S. Population       0.033         0.006953         21

  All Infants (\< 1 year old)   0.033         0.012335         37

  Children 1-2 years old        0.033         0.013472         41

  Children 3-5 years old        0.033         0.011708         35

  Children 6-12 years old       0.033         0.004966         15

  Youth 13-19 years old         0.033         0.006087         18

  Adults 20-49 years old        0.033         0.004808         15

  Adults 50+ years old          0.033         0.005373         16

  Females 13-49 years old       0.033         0.004567         14
  ---------------------------------------------------------------------------

1.  **Chronic Dietary Exposure and Risk**

The chronic dietary exposure estimates for food and drinking water [are
below HED's level of concern]{.underline} (\<100% cPAD) for the U.S.
population and all population subgroups (Table 4.2.2). Bifenthrin
dietary exposure for food and drinking water for the U.S. population is
6% of the cPAD and 18% of the cPAD for children 1-2 yrs, the most highly
exposed population subgroup.

**Table 4.2.2: Summary of Dietary Exposure and Risk for Bifenthrin**

+-------------------+-----------+------------+------------+----------+
| **Population      | **Acute   |            | **Chronic  |          |
| Subgroup**        | Dietary** |            | Dietary**  |          |
|                   |           |            |            |          |
|                   | **(99.9th |            |            |          |
|                   | Perc      |            |            |          |
|                   | entile)** |            |            |          |
+===================+===========+============+============+==========+
|                   | **Dietary | **% aPAD** | **Dietary  | **%      |
|                   | Exposure  |            | Exposure** | cPAD**   |
|                   | (mg/      |            |            |          |
|                   | kg/day)** |            | **(mg      |          |
|                   |           |            | /kg/day)** |          |
+-------------------+-----------+------------+------------+----------+
| General U.S.      | 0.006957  | 21         | 0.000228   | 6        |
| Population        |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| All Infants (\< 1 | 0.012335  | 37         | 0.000369   | 9        |
| year old)         |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| **Children 1-2    | **0       | **41**     | **         | **18**   |
| years old**       | .013472** |            | 0.000715** |          |
+-------------------+-----------+------------+------------+----------+
| Children 3-5      | 0.011708  | 35         | 0.000489   | 12       |
| years old         |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| Children 6-12     | 0.004966  | 15         | 0.000272   | 7        |
| years old         |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| Youth 13-19 years | 0.006087  | 18         | 0.000166   | 4        |
| old               |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| Adults 20-49      | 0.004805  | 15         | 0.000196   | 5        |
| years old         |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| Adults 50+ years  | 0.005373  | 16         | 0.000173   | 4        |
| old               |           |            |            |          |
+-------------------+-----------+------------+------------+----------+
| Females 13-49     | 0.004564  | 14         | 0.000144   | 4        |
| years old         |           |            |            |          |
+-------------------+-----------+------------+------------+----------+

**5.0 Residential (Non-Occupational) Exposure/Risk Characterization**

***Bifenthrin: REVISED Residential Exposure Assessment and
Recommendations for the Tolerance Reassessment Eligibility Decision
(TRED) Document.* S. Weiss. D286358. 10/25/2002.**

Bifenthrin products are available to homeowners for indoor and outdoor
application to residential premises. Adults and children may be
potentially exposed to bifenthrin residues resulting from application.

Potential exposure and risk to residents (or "homeowners") have been
assessed previously by HED. Information for this section was adapted
from previous residential assessment for bifenthrin performed in 2002
(see reference below). Since completion of the last residential
assessment, no product cancellations have occurred that would alter the
conclusions. A summary of the exposure and risk resulting from
residential uses of bifenthrin is provided below. These exposure
estimates were used in the aggregate risk assessment which appears in
Section 7.0 of this document.

**5.1 Residential Handler Exposure**

End use products containing bifenthrin are formulated as
ready-to-use-sprays, emulsified concentrates, wettable powders,
granulars, pelletized tablets, and pressurized liquids.

The current maximum application rates of granulars and liquids by lawn
care operators (LCOs) are 0.4 and 0.3 lb ai/acre, respectively. For
liquid and granular formulations applied by homeowners, the maximum rate
is 0.2 lb ai/acre. In a letter to the Agency dated September 16, 2002,
FMC agreed to lower the maximum rate for all turf uses to 0.2 lb
ai/acre. Bifenthrin products may be applied by pest control operators
(PCOs) and homeowners in and around homes as a spray in concentrations
of up to 0.06%. The majority of residential labels do not specify
frequency of application.

On October 25, 2002, HED performed a residential exposure and risk
assessment for the use of bifenthrin (see reference above). A summary of
the uses and the results of the assessment are summarized below. For
more details and for the results of all exposure scenarios, please see
the original residential exposure assessment.

Short- and intermediate-term exposures may occur for residents applying
bifenthrin products. Chronic exposures are not anticipated for
residential handlers. The exposure and risk for residential handlers
were assessed using the revised draft SOPs for Residential Exposure
Assessment, and includes surrogate data from the Pesticide Handlers
Exposure Database (PHED), Outdoor Residential Exposure Task Force
(ORETF). Since PHED and ORETF do not include data for ready-to-use spray
bottle application, data from a proprietary study were used to estimate
exposure (MRID 447393-01).

The major exposure scenarios for non-occupational (residential) handler
exposures are as follows:

\* Mixing/loading/applying Liquids for Low Pressure Handwand Application

\* Mixing/loading/applying Liquids for Hose-end Sprayer Application

\* Mixing/loading/applying Liquids for Backpack Sprayer Application

\* Paintbrush Application

\* Loading/applying Granulars for Belly Grinder Application

\* Loading/applying Granulars for Push-type Spreader Application

\* Applying Granulars with Bare Hands

\* RTU Spray Bottle Application

The most likely residential handler exposure scenario resulting in the
highest exposure and risk is for mixing/loading and applying liquids
using a hose-end broadcast sprayer. The short- and intermediate-term MOE
for this use is 2900 (dermal and inhalation MOEs were summed).

This use does not exceed HED's level of concern. Short- and
intermediate-term risks estimated for residential handlers **and** for
post-application exposure do not exceed HED's level concern. Long-term
exposure is not expected.

2.  **Residential Post-application Exposure**

Adults and children may be potentially exposed to bifenthrin residues
after application of bifenthrin products in residential settings. Short-
and intermediate-term post-application dermal exposures for adults, and
short- and intermediate-term post-application dermal and incidental oral
exposures for children are anticipated. Long-term exposure is not
expected. Risk estimates were generated for potential contact with lawn,
soil, and treated indoor surfaces using HED's Draft SOPs for Residential
Exposure Assessment, and for the lawn scenarios, dissipation data from a
chemical specific TTR study. Indoor surface residues in homes were based
on crack and crevice data collected for bifenthrin and malathion. These
estimates are considered conservative screening level estimates, but
appropriate, since the study data were adjusted to reflect maximum
application rates.

**Table 5.2 Summary of Residential Post-Application Exposure Scenarios
for Bifenthrin**

+----------+--------------+----------+------------+------------------+
| Exposure | Population   | Route of | Short-Term | I                |
| Scenario |              | Exposure | MOE        | ntermediate-Term |
|          |              |          |            | MOE              |
+----------+--------------+----------+------------+------------------+
| Indoor:  | Adults       | Dermal   | 3100       | 3100             |
| High     |              |          |            |                  |
| Contact  |              |          |            |                  |
| Activity |              |          |            |                  |
+----------+--------------+----------+------------+------------------+
|          | Toddlers     | Dermal   | 1800       | 1800             |
+----------+--------------+----------+------------+------------------+
| Outdoor: | Adults       | Dermal   | 2300       | 4500             |
|          |              |          |            |                  |
| High     |              |          |            |                  |
| Contact  |              |          |            |                  |
| Activity |              |          |            |                  |
| on       |              |          |            |                  |
| T        |              |          |            |                  |
| urfgrass |              |          |            |                  |
+----------+--------------+----------+------------+------------------+
|          | Toddler      | Oral and | 740 Oral   | 1600 Oral        |
|          |              | Dermal   |            |                  |
|          |              |          | 1400       | 2700 Dermal      |
|          |              |          | Dermal     |                  |
+----------+--------------+----------+------------+------------------+

**5.3 Other (Spray Drift)**

Spray drift is always a potential source of exposure to residents nearby
to spraying operations. This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for bifenthrin.
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation and
other parties to develop the best spray drift management practices. On a
chemical by chemical basis, the Agency is now requiring interim
mitigation measures for aerial applications that must be placed on
product labels/labeling. The Agency has completed its evaluation of the
new database submitted by the Spray Drift Task Force, a membership of
U.S. pesticide registrants, and is developing a policy on how to
appropriately apply the data and the AgDRIFT7 computer model to its risk
assessments for pesticides applied by air, orchard airblast and ground
hydraulic methods. After the policy is in place, the Agency may impose
further refinements in spray drift management practices to reduce
off-target drift with specific products with significant risks
associated with drift.

**6.0 Aggregate Risk Assessments and Risk Characterization**

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

Short-term aggregate risk assessment is required for bifenthrin due to
the potential for residential exposure. The common toxicological effect
observed across the oral and dermal routes of exposure is clinical signs
of neurotoxicity. An aggregate MOE was calculated by taking the inverse
of the sum of inverse MOEs for dietary and non-dietary (incidental oral
and dermal) exposure pathways.

**6.1 Acute Aggregate Risk**

No acute residential/recreational exposures are expected and since the
dietary assessment included food and water, the exposures in Table 5.2.1
represent aggregate exposures. The values are below HED's level of
concern.

**6.2 Short- and Intermediate-term Aggregate Risk**

Because there is the potential for short- and intermediate-term,
non-dietary exposure of children and adults to bifenthrin as a
residential treatment (indoors and outdoors), it is appropriate to
aggregate these exposures with dietary (food and water) exposure. Adults
can be exposed through the residential application of bifenthrin via
dermal and inhalation routes and through post-application exposure via
the dermal route (treated turf). Children might be exposed following
application in residential settings via dermal and oral routes. HED
believes that if a toddler were to be exposed to bifenthrin granules, it
would most likely be episodic, that is, a one-time occurrence and not
likely to be repeated. Therefore, this episodic scenario was not
aggregated with dietary exposure.

Residential exposure and risk have been summarized based on HED
residential risk assessments for the existing uses of bifenthrin. Those
scenarios resulting in the highest exposure and risk for adults and
children have been summarized in Table 6.2. These exposures were used to
calculated short- andintermediate-term aggregate risk by combining
residential exposure with that from dietary sources.

**Table 6.2** Summary of Residential Risk Scenarios Resulting in Highest
Exposure and Risk for Bifenthrin

+-------+---------+--------------+-------------+---------------------+
| Popul | E       |              | Route of    | Short-Term MOE      |
| ation | xposure |              | Exposure    |                     |
|       | S       |              |             |                     |
|       | cenario |              |             |                     |
+-------+---------+--------------+-------------+---------------------+
| A     | H       | Handler      | Dermal and  | 97,000 Inhalation   |
| dults | ose-end |              | Inhalation  |                     |
|       | Sprayer |              |             | 3000 Dermal         |
|       | Appl    |              |             |                     |
|       | ication |              |             |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         | Post         | Dermal      | 2300                |
|       |         | -Application |             |                     |
+-------+---------+--------------+-------------+---------------------+
|       | Liquid  | Handler      | Dermal and  | 23,000 Inhalation   |
|       | Str     |              | Inhalation  |                     |
|       | uctural |              |             | 600 Dermal          |
|       | Wood    |              |             |                     |
|       | Tr      |              |             |                     |
|       | eatment |              |             |                     |
|       | with    |              |             |                     |
|       | Pai     |              |             |                     |
|       | ntbrush |              |             |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         | Post         | No exposure |                     |
|       |         | -Application | expected    |                     |
|       |         |              | due to low  |                     |
|       |         |              | ac          |                     |
|       |         |              | cessibility |                     |
|       |         |              | to treated  |                     |
|       |         |              | areas       |                     |
|       |         |              | (termite    |                     |
|       |         |              | control).   |                     |
+-------+---------+--------------+-------------+---------------------+
|       | Indoor: | Handler      | Dermal and  | 210,000 Inhalation  |
|       |         |              | Inhalation  |                     |
|       | Liquid  |              |             | 14,000 Dermal       |
|       | Crack   |              |             |                     |
|       | and     |              |             |                     |
|       | Crevice |              |             |                     |
|       | Spray   |              |             |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         | Post         | Dermal      | 3100                |
|       |         | -Application |             |                     |
+-------+---------+--------------+-------------+---------------------+
| To    | O       | Post         | Hand-to-    | 740                 |
| ddler | utdoor: | -Application | Mouth/Oral  |                     |
|       |         |              |             |                     |
|       | High    |              |             |                     |
|       | Contact |              |             |                     |
|       | A       |              |             |                     |
|       | ctivity |              |             |                     |
|       | on      |              |             |                     |
|       | Tu      |              |             |                     |
|       | rfgrass |              |             |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         |              | Mouthing    | 3000                |
|       |         |              | Treated     |                     |
|       |         |              | Turf        |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         |              | Soil        | 220,000             |
|       |         |              | Ingestion   |                     |
+-------+---------+--------------+-------------+---------------------+
|       |         |              | Dermal      | 1400                |
+-------+---------+--------------+-------------+---------------------+

1\. Combined MOE for handlers since dermal and inhalation endpoints
(clinical signs of same \[1/(1/MOE-dermal)+(1/MOE-inhalation)\].

The short- and intermediate-term NOAEL for non-dietary **oral** exposure
is based on the 90-day oral toxicity study in dogs (NOAEL = 2.21
mg/kg/day). The short- and intermediate-term NOAEL **dermal** exposure
is based on the 21-day dermal toxicity study in the rat (NOAEL = 47
mg/kg/day). The common toxicological effect observed across the oral and
dermal routes of exposure is clinical signs of neurotoxicity. The
aggregate LOC (MOE) is 300.

The results of the short- and intermediate-term aggregate risk
assessment for various subpopulations based on age are reported in Table
6.2.1. Short- and intermediate-term aggregate (dietary + residential)
MOEs for the general US population and any subpopulation of the general
US population are \>300 and do not exceed HED's level of concern.

**Table 6.2.1. Short- and Intermediate-Term Aggregate Risk for
Bifenthrin**

+-------------+---------+---------+-------------+---------+-----------+
| **P         | **      | **Non-  | **Dermal    | **Inh   | **        |
| opulation** | Dietary | dietary | MOE^3^**    | alation | Aggregate |
|             | M       | Oral    |             | M       | MOE^5^**  |
|             | OE^1^** | M       |             | OE^4^** |           |
|             |         | OE^2^** |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| General US  | 9700    | N/A     | 600         | 23,000  | 550       |
| population  |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| All infants | 6000    | 590     | 1400        | N/A     | 390       |
|             |         |         |             |         |           |
| (\<1 yr     |         |         |             |         |           |
| old)        |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Children    | 3100    | 590     | 1400        |         | 370       |
| 1-2 yrs.    |         |         |             |         |           |
| Old         |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Children    | 4500    | 590     | 1400        |         | 380       |
| 3-5 yrs.    |         |         |             |         |           |
| Old         |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Children    | 8100    | N/A     | 1400        |         | 1200      |
| 6-12 yrs.   |         |         |             |         |           |
| Old         |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Youth 13-19 | 13,000  |         | 1400        |         | 1300      |
| yrs. Old    |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Adults      | 11,000  |         | 600         | 23,000  | 550       |
| 20-49 yrs.  |         |         |             |         |           |
| Old         |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Adults 50+  | 13,000  |         | 600         | 23,000  | 560       |
| yrs. Old    |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+
| Females     | 15,000  |         | 510         | 23,000  | 480       |
| 13-49 yrs.  |         |         |             |         |           |
| Old         |         |         |             |         |           |
+-------------+---------+---------+-------------+---------+-----------+

1 Dietary MOE = \[(short- or intermediate-term oral NOAEL)÷(chronic
dietary exposure)\]; NOAEL=2.21 mg/kg/day; chronic dietary (food +
water) exposures (see Table 5.2.2) were utilized as surrogates for
short- and intermediate-term exposures

2 Non-dietary oral MOE = \[(short- or intermediate-term oral NOAEL)÷(sum
of all high-end incidental oral residential exposure)\]; NOAEL=2.21
mg/kg/day; chronic dietary (food + water) exposures (see Table 4.2.2)
were utilized as surrogates for short- and intermediate-term exposures.

3 Dermal MOE = \[(short- or intermediate-term dermal NOAEL)÷(high-end
dermal residential exposure)\]; NOAEL=47 mg/kg/day; structural wood
treatment (paintbrush application) used for adult estimates

4 Inhalation MOE = \[(short- or intermediate-term inhalation
NOAEL)÷(high-end dermal residential exposure)\]; NOAEL=2.21 mg/kg/day

5 Aggregate MOE (dietary and residential) = 1÷\[(1÷Dietary MOE) +
(1÷Non-dietary oral MOE) + (1÷Dermal MOE) + (1÷Inhalation MOE)\]; values
expressed to 2 significant figures; Inhalation MOE based on adult
residential handler exposure (intermediate-term not likely).

**6.3 Long-term (Chronic) Aggregate Risk**

A chronic (non-cancer) aggregate risk assessment was not performed,
because chronic residential exposure to bifenthrin (*i.e.*, \>6 months)
is not considered likely to occur.

**6.4 Cancer Risk**

The CARC (1992) recommended that for the purpose of risk
characterization, the reference dose (RfD) approach should be used for
quantification of human risk. The chronic exposure analysis revealed
\<100% RfD, and it is assumed that the chronic dietary endpoint is
protective for cancer dietary exposure.

**7.0 Cumulative Risk Characterization/Assessment**

Bifenthrin is a member of the pyrethroid class of pesticides. EPA is not
currently following a cumulative risk approach based on a common
mechanism of toxicity for the pyrethroids. Although all pyrethroids
alter nerve function by modifying the normal biochemistry and physiology
of nerve membrane sodium channels, available data show that there are
multiple types of sodium channels and it is currently unknown whether
the pyrethroids as a class have similar effects on all channels or
whether modifications of different types of sodium channels would have a
cumulative effect. Nor do we have a clear understanding of effects on
key downstream neuronal function, e.g., nerve excitability, or how these
key events interact to produce their compound specific patterns of
neurotoxicity. Without such understanding, there is no basis to make a
common mechanism of toxicity finding. There is ongoing research by the
EPA's Office of Research and Development and pyrethroid registrants to
evaluate the differential biochemical and physiological actions of
pyrethroids in mammals. This research is expected to be completed by
2007. When available, the Agency will consider this research and make a
determination of common mechanism as a basis for assessing cumulative
risk. For information regarding EPA's procedures for cumulating effects
from substances found to have a common mechanism on EPA's website at
<http://www.epa.gov/pesticides/cumulative/>.

**8.0 Occupational Exposure/Risk Pathway**

**8.1 Short-/Intermediate-Term Handler Risk**

Based upon the proposed use pattern, HED expects the most highly exposed
occupational pesticide handlers (mixers, loaders, applicators) to be 1)
mixer/loader using open pour loading of liquids; 2) mixer/loader using
open pour loading of granules; 3) an aerial applicator and 4) an
applicator using open-cab, ground-boom spray equipment. HED believes
most exposure durations will be short-term (1 - 30 days). However, the
Science Policy Council for Exposure (ExpoSAC) maintains that it is
possible for commercial applicators to be exposed to intermediate-term
exposure durations (1 - 6 months). Therefore estimates for short- and
intermediate-term risks are presented.

It is expected that some private applicators may perform all tasks, that
is, mix, load and apply the material. However, HED ExpoSAC draft SOP (29
March 2000) directs that although the same individual may perform all
tasks, in some cases they shall be assessed separately.

The available exposure data for combined mixer/loader/applicator
scenarios are limited in comparison to the monitoring of these two
activities separately. These exposure scenarios are outlined in the PHED
Surrogate Exposure Guide (August 1998). HED has adopted a methodology to
present the exposure and risk estimates separately for the job functions
in some scenarios and to present them as combined in other cases. Most
exposure scenarios for hand-held equipment (such as hand wands, backpack
sprayers, and push-type granular spreaders) are assessed as a combined
job function. With these types of hand held operations, all handling
activities are assumed to be conducted by the same individual. The
available monitoring data support this and HED presents them in this
way. Conversely, for equipment types such as fixed-wing aircraft,
groundboom tractors, air-blast sprayers, or high-pressure handwand
sprayers, the applicator exposures are assessed and presented separately
from those of the mixers and loaders. By separating the two job
functions, HED determines the most appropriate levels of PPE for each
aspect of the job without requiring an applicator to wear unnecessary
PPE that might be required for a mixer/loader (e.g., chemical resistant
gloves may only be necessary during the pouring of a liquid
formulation).

No chemical specific data were available with which to assess potential
exposure to occupational pesticide handlers. The estimates of exposure
to pesticide handlers are based upon surrogate study data available in
the PHED (v. 1.1, 1998). For pesticide handlers, it is HED standard
practice to present estimates of dermal exposure for "baseline" that is,
for workers wearing a single layer of work clothing consisting of a long
sleeved shirt, long pants, shoes plus socks and no protective gloves as
well as for "baseline" and the use of protective gloves or other PPE as
might be necessary. The proposed product label involved in this
assessment directs applicators and other handlers who may be exposed to
the dilute through application or other tasks must wear: long-sleeved
shirt and long pants, chemical resistant gloves, such as barrier
laminate, nitrile, neoprene or viton rubber and shoes plus socks.
Handlers who may be exposed to the concentrate through mixing, loading,
application or other tasks must wear; long-sleeved shirt and long pants,
chemical resistant gloves such as barrier laminate, nitrile, neoprene or
viton rubber, shoes plus socks and protective eye wear.

Since single application rates for the proposed uses range from 0.1 lb
ai/acre to 0.3 lb ai/acre, those uses with the higher application rate
were assessed in the table below (potatoes). Since the dermal effects
are derived from a 21-day dermal study, there are no adjustments made
for dermal absorption. HED asssumes 100% inhalation absorption.

See Table 9.1 for a summary of estimated exposures and risks. In this
case, the toxicological effects are similar (*i.e.*, neurological) for
the dermal and inhalation routes although they were identified from
different studies. Therefore, MOEs are expressed as Combined MOEs.

**Table 8**.1 Occupational Exposure and Risk Estimates for Proposed Uses
of Bifenthrin

+----------------+----------+---+-------------+---+------------+-------------+---+
| Unit           | Acres    | A |             | M |            | Combined    |   |
| Exposure^1^    | Tr       | v |             | O |            | MOE^5^      |   |
|                | eated^2^ | e |             | E |            |             |   |
| ^(mg\ ai/lb\   |          | r |             | ^ |            |             |   |
|  ai\ handled)^ |          | a |             | 4 |            |             |   |
|                |          | g |             | ^ |            |             |   |
|                |          | e |             |   |            |             |   |
|                |          | D |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | i |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | y |             |   |            |             |   |
|                |          | D |             |   |            |             |   |
|                |          | o |             |   |            |             |   |
|                |          | s |             |   |            |             |   |
|                |          | e |             |   |            |             |   |
|                |          | ^ |             |   |            |             |   |
|                |          | 3 |             |   |            |             |   |
|                |          | ^ |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | ^ |             |   |            |             |   |
|                |          | ( |             |   |            |             |   |
|                |          | m |             |   |            |             |   |
|                |          | g |             |   |            |             |   |
|                |          | \ |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | i |             |   |            |             |   |
|                |          | / |             |   |            |             |   |
|                |          | k |             |   |            |             |   |
|                |          | g |             |   |            |             |   |
|                |          | \ |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | b |             |   |            |             |   |
|                |          | w |             |   |            |             |   |
|                |          | / |             |   |            |             |   |
|                |          | d |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | y |             |   |            |             |   |
|                |          | ) |             |   |            |             |   |
|                |          | ^ |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| *Mixer/Loader  |          |   |             |   |            |             |   |
| -- Liquids --  |          |   |             |   |            |             |   |
| Open Pour --   |          |   |             |   |            |             |   |
| Supporting     |          |   |             |   |            |             |   |
| Aerial         |          |   |             |   |            |             |   |
| Applications*  |          |   |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Dermal:        | 350      |   | Dermal:     | N |            | NG: 11      |   |
|                | A        |   |             | G |            |             |   |
| SLNG: 2.9 HC   | cres/Day |   | NG: 4.35    | : |            | WG: 650     |   |
|                |          |   |             | 1 |            |             |   |
| SLWG: 0.023 HC |          |   | WG: 0.0345  | 1 |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          |   |             | W |            |             |   |
|                |          |   |             | G |            |             |   |
|                |          |   |             | : |            |             |   |
|                |          |   |             | 1 |            |             |   |
|                |          |   |             | 4 |            |             |   |
|                |          |   |             | 0 |            |             |   |
|                |          |   |             | 0 |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Inhal: 0.0012  |          |   | Inhal:      | I |            |             |   |
|                |          |   | 0.0018      | n |            |             |   |
|                |          |   |             | h |            |             |   |
|                |          |   |             | a |            |             |   |
|                |          |   |             | l |            |             |   |
|                |          |   |             | : |            |             |   |
|                |          |   |             | 1 |            |             |   |
|                |          |   |             | 2 |            |             |   |
|                |          |   |             | 0 |            |             |   |
|                |          |   |             | 0 |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| *Mixer/Loader  |          |   |             |   |            |             |   |
| -- Granules -- |          |   |             |   |            |             |   |
| Open Pour*     |          |   |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Dermal:        | 350      | D |             |   | NG: 3700   | NG: 700     |   |
|                | A        | e |             |   |            |             |   |
| SLNG: 0.0084   | cres/Day | r |             |   | WG:4500    | WG: 730     |   |
| LC             |          | m |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
| SLWG: 0.0069   |          | l |             |   |            |             |   |
| MC             |          | : |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | N |             |   |            |             |   |
|                |          | G |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 1 |             |   |            |             |   |
|                |          | 2 |             |   |            |             |   |
|                |          | 6 |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | W |             |   |            |             |   |
|                |          | G |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 1 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 4 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Inhal: 0.0017  |          | I |             |   | Inhal: 870 |             |   |
|                |          | n |             |   |            |             |   |
|                |          | h |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 2 |             |   |            |             |   |
|                |          | 5 |             |   |            |             |   |
|                |          | 5 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| *Aerial        |          |   |             |   |            |             |   |
| Applicator^6^* |          |   |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Dermal:        | 350      | D |             |   | NG: 6300   | NG: 4900    |   |
|                | A        | e |             |   |            |             |   |
| SLNG: 0.0050   | cres/Day | r |             |   |            |             |   |
|                |          | m |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | N |             |   |            |             |   |
|                |          | G |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 7 |             |   |            |             |   |
|                |          | 5 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Inhal:         |          | I |             |   | Inhal:     |             |   |
| 0.000068       |          | n |             |   | 22,000     |             |   |
|                |          | h |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 1 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| *Applicator -- |          |   |             |   |            |             |   |
| Open Cab --    |          |   |             |   |            |             |   |
| Ground Boom*   |          |   |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Dermal:        | 200      | D |             |   | NG: 3900   | NG: 1800    |   |
|                | A        | e |             |   |            |             |   |
| SLNG: 0.014    | cres/Day | r |             |   | WG: 3900   | WG: 1800    |   |
|                |          | m |             |   |            |             |   |
| SLWG: 0.014    |          | a |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | S |             |   |            |             |   |
|                |          | L |             |   |            |             |   |
|                |          | N |             |   |            |             |   |
|                |          | G |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 1 |             |   |            |             |   |
|                |          | 2 |             |   |            |             |   |
|                |          |   |             |   |            |             |   |
|                |          | S |             |   |            |             |   |
|                |          | L |             |   |            |             |   |
|                |          | W |             |   |            |             |   |
|                |          | G |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 1 |             |   |            |             |   |
|                |          | 2 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+
| Inhal: 0.00074 |          | I |             |   | Inhal:     |             |   |
|                |          | n |             |   | 3500       |             |   |
|                |          | h |             |   |            |             |   |
|                |          | a |             |   |            |             |   |
|                |          | l |             |   |            |             |   |
|                |          | : |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | . |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 0 |             |   |            |             |   |
|                |          | 6 |             |   |            |             |   |
|                |          | 3 |             |   |            |             |   |
+----------------+----------+---+-------------+---+------------+-------------+---+

1\. Unit exposure = mg/lb ai handled; taken from PHED Surrogate Exposure
Guide (v. 1.1, 8/1998) SLNG=single layer PPE, no gloves; SLWG=single
layer PPE with gloves. HC=high confidence data; MC=medium confidence
data; LC=low confidence data.

2\. Acres treated are derived from ExpoSAC Policy No. 9.1, revised
9/25/2001.

3\. Average Daily Dose (ADD) = Unit Exposure\*Application Rate\*Acres
Treated ÷ 70 kg body weight.

4\. MOE=Margin of Exposure (MOE) = NOAEL ÷ ADD.

5\. Margins of Exposure may be combined when the dermal and inhalation
toxicological effect is the same but derived from different studies. The
convention used to combine is: 1 ÷ \[(1/MOE-DERMAL ) +
(1/MOE-INHALATION)\]

6\. Pilots are not required to wear protective gloves.

A MOE of 100 is adequate to protect occupational pesticide handlers.
Provided that mixer/loaders wear protective gloves, all MOEs are \> 100.
Therefore the estimated risks do not exceed HED's levels of concern.

1.  **Short-/Intermediate-Term Post-application Risk**

There is typically the possibility for agricultural workers to
experience post-application exposure to dislodgeable pesticide residues.
In conjunction with the Agricultural Re-Entry Task Force (ARTF), HED has
identified a number of agricultural work activities that may result in
post-application, re-entry exposure to pesticides. In addition, HED has
identified surrogate Transfer Coefficients (TCs) in units of cm²/hr
derived from exposure studies relative to "standard" agricultural work
activities but which were conducted to assess exposure to other
compounds.

Not all of the identified post-application work activities are listed
here. However, the activities associated with the highest TCs are
summarized in Table 9.2.

**Table 8**.2 Transfer Coefficients Associated With Proposed Uses of
Bifenthrin

  ----------------------- ----------------------- -----------------------
  Crop                    Activity                Transfer Coefficient
                                                  (cm^2^/hr)

  Leafy green vegetables  Hand Harvesting         2500
  (cilantro)                                      

  *Brassica* leafy greens                         2500

  Beans, Peas - dried,                            2500
  shelled                                         

  Tobacco                 Hand Harvesting,        2000
                          Topping, Stripping      

  Roots and tuber         Irrigation activities,  1500
  (potatoes)              Scouting                
  ----------------------- ----------------------- -----------------------

Since there are no chemical specific data with which to assess
post-application exposures to agricultural workers, HED uses TCs
identified from surrogate studies in conjunction with the assumption
that 20% of the rate of application is available as dislodgeable foliar
residue (DFR) on day zero after application. Although hand harvesting
(cilantro, leafy greens and peas and beans) has a TC of 2,500, the rate
of application is 0.1 lb ai/A. The rate of application for potato is 0.3
lb ai/A which results in a higher exposure despite a slightly lower TC.
Therefore, as a "worse case", screening level assessment, a TC of 1500
cm²/hr is used in conjunction with an application rate of 0.3 lb ai/A.

The TCs used in this assessment are from an interim TC policy developed
by HED's ExpoSAC using proprietary data from the ARTF database (policy
\# 3.1 Revised 7 AUG 2000). It is the intention of HED's ExpoSAC that
this policy will be periodically updated to incorporate additional
information about agricultural practices in crops and new data on TC's.
Much of this information will originate from exposure studies currently
being conducted by the ARTF, from further analysis of studies already
submitted to the Agency, and from studies in the published scientific
literature. The following convention may be used to estimate
post-application exposure to agricultural workers.

Surrogate Dislodgeable Foliar Residue:

DFR = application rate \* 20% available as dislodgeable residue \* 4.54
x 108µg/lb \* 2.47 x 10-8 A/cm2 or 1.08 x 10-3 ft2/cm²

and the Average Daily Dose

ADD = DFR (µg/cm2) \* TC (cm2/hr) \* hr/day \* 0.001 mg/µg \* 1/70 kg bw

∴ 0.3 b ai/A \* 0.20 \* 4.548 µg/lb \* 2.47-8 A/cm² = 0.673 g/cm2 and

0.673 µg/cm^2^ \* 1500 cm^2^/hr \* 8 hr/day \* 0.001 mg/µg \* 1/70 kg bw
= 0.12 mg/kg bw/day

Since MOE = NOAEL ÷ ADD then 47 mg/kg bw/day ÷ 0.12 mg/kg bw/day = 410

The MOE for the theoretically most highly exposed post-application
agricultural activity is

410 (greater than100), and does not exceed HED's level of concern. All
other identified post-application activities are expected to have lower
exposures therefore greater MOEs.

HED notes that in the occupational exposure assessment which is the
basis of this section, a discrepancy was discovered relative to the
application rate for tobacco (stated as 0.3 lb ai/acre). The correct
application rate for tobacco is 0.1 lb ai/acre.

**RESTRICTED ENTRY INTERVAL (REI)**

HED is not aware of possible REIs proposed for cilantro, tobacco and
tuberous and corm vegetables. The restricted entry intervals for
bifenthrin are variable, depending upon crop site and to some extent
upon activity. The shortest REI is 24 hours for caneberries
(mechanically harvested), beans (for processing only), field corn (grown
for seed), peas (for processing only), sweet corn (for processing only)
and "other crops" (*i.e.*, meaning crops not mentioned on the label with
an otherwise specified REI). Other REIs vary from 4 days to 18 days and
generally seem associated with crops harvested for the "fresh" market.
Based upon the conservative estimate of post-application exposure and
risk described above, HED believes a REI of 24 hours is adequate to
protect agricultural workers from post-application exposures to
bifenthrin from the proposed new uses.

**9.0 Data Needs and Label Requirements**

**9.1 Toxicology**

The HIARC identified a data gap pertaining to subchronic inhalation
toxicity, and recommended a 90-day inhalation toxicity study be
conducted. However, based on the acute inhalation toxicity category
(IV), the low vapor pressure and inhalation MOEs for the proposed new
uses (870-2200), HED concludes that it is appropriate to waive the
requirement for the 28-day inhalation toxicity exposure **for this
action and for these proposed uses only**.

**9.2 Residue Chemistry**

-   *revised Section F* -- see Table 4.1.5.1

-   *revised Section B* -- see Section 2.1

    3.  **Occupational and Residential Exposure**

None.