Document ID: EPA-HQ-OPP-2005-0545-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-16T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC  20460

OFFICE OF PREVENTION,

PESTICIDES, AND TOXIC SUBSTANCES

MEMORANDUM

Date:		July 18, 2007

Subject:	Lambda-Cyhalothrin.  Human Health Risk Assessment for the
Proposed Food/Feed Uses of the Insecticide on Cucurbit Vegetables (Group
9), Tuberous and Corm Vegetables (Subgroup 1C), Grass Forage, Fodder,
and Hay (Group 17), Barley, Buckwheat, Oat, Rye, Wild Rice, and
Pistachios.  Petition Numbers 5F6994, 3E6593, and 6E7077.

			PC Code:			128897

			DP Numbers:			313315, 324219, 330542

			Regulatory Citation:		40CFR §180.438

			Chemical Class:		Synthetic Pyrethroid Insecticide

			Trade Names:		Warrior®, Karate®

From:		William T. Drew, Chemist and Risk Assessor

		Kim Harper, Toxicologist

		Anant Parmar, Dietary Exposure Assessor

		Registration Action Branch 2, Health Effects Division (7509P)

			and

		Mark Dow, Occupational/Residential Exposure Assessor

		Alternate Risk Integration Assessment Team

		Risk Integration Minor Use & Emergency Response Branch

		Registration Division (7505P)

Through:	Dennis McNeilly, Chemist

		Alan Levy, Toxicologist

		Margarita Collantes, Biologist

		Richard A. Loranger, Branch Senior Scientist

		Christina Swartz, Branch Chief

		Registration Action Branch 2, Health Effects Division (7509P)

To:		George LaRocca, Risk Manager

		Daniel Rosenblatt, Risk Manager

		Bonaventure Akinlosotu, Risk Manager Reviewer

		Insecticide Branch, Registration Division (7505P)



Table of Contents

  TOC \f  1.0	Executive Summary	4

2.0	Ingredient Profile	11

2.1	Summary of Registered/Proposed Uses	11

2.2	Structure and Nomenclature	  PAGEREF _Toc139000973 \h  13 

2.3	Physical and Chemical Properties	  PAGEREF _Toc139000974 \h  13 

3.0	Hazard Characterization/Assessment	14

3.1	Hazard and Dose-Response Characterization	14

3.1.1	Database Summary	14

3.1.1.1	Studies Available and Considered	14 

3.1.1.2	Mode of Action, Metabolism, Toxicokinetic Data	14

3.1.2	Toxicological Effects	15

3.1.3	FQPA	15

3.2	Absorption, Distribution, Metabolism, Excretion (ADME)	16

3.3	FQPA Considerations	17

3.3.1	Adequacy of the Toxicity Database	17

3.3.2	Evidence of Neurotoxicity	17

3.3.3	Developmental Toxicity Studies	18

3.3.4	Reproductive Toxicity Study	18

3.3.5	Pre- and/or Post-Natal Toxicity	18

3.3.5.1	Determination of Susceptibility	18     

3.3.5.2	Degree of Concern Analysis and Residual Uncertainties	19

3.3.6	Recommendation for a Developmental Neurotoxicity Study	19

3.3.7	Rationale for the UFDB	19

3.4	FQPA Safety Factor for Infants and Children	20

3.5	Hazard Identification and Toxicity Endpoint Selection	20

3.5.1	Acute Reference Dose (aRfD) - General Population	20

3.5.2	Chronic Reference Dose (cRfD) - General Population	21

3.5.3	Incidental Oral Exposure (Short- and Intermediate-Term)	21

3.5.4	Dermal Absorption	21

3.5.5	Dermal Exposure (All Durations)	21

3.5.6	Inhalation Exposure (All Durations)	23

3.5.7	Level of Concern for Margin of Exposure	24

3.5.8	Recommendation for Aggregate Exposure Risk Assessments	24

3.5.9	Classification of Carcinogenic Potential	24

3.5.10	Summary of Toxicological Doses and Endpoints	25

3.6	Endocrine disruption	27

4.0	Public Health and Pesticide Epidemiology Data	27

5.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc139001017 \h 
27 

5.1	Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc139001018 \h  27 

5.1.1	Metabolism in Primary Crops	  PAGEREF _Toc139001019 \h  27 

5.1.2	Metabolism in Rotational Crops	  PAGEREF _Toc139001020 \h  27 

5.1.3	Metabolism in Livestock	  PAGEREF _Toc139001021 \h  28 

5.1.4	Analytical Methodology	  PAGEREF _Toc139001022 \h  28 

5.1.5	Environmental Degradation	29

5.1.6	Comparative Metabolic Profile	30

5.1.7	Drinking Water Residue Profile	  PAGEREF _Toc139001027 \h  31 

5.1.8	Food Residue Profile	32

5.1.9	International Residue Limits	33

5.2	Dietary Exposure and Risk	33

5.2.1  Acute Dietary Exposure/Risk	34

5.2.2  Chronic Dietary Exposure/Risk	35

5.2.3  Cancer Dietary Risk	35

5.3	Anticipated Residue and Percent Crop Treated (%CT) Information	36

6.0	Residential (Non-Occupational) Exposure/Risk Characterization	36

6.1	Handler	37

6.2	Post-Application	37

6.3	Spray Drift	38

7.0	Aggregate Risk Assessments and Risk Characterization	39

7.1	Acute Aggregate Risk	39

7.2	Short- and Intermediate-Term Aggregate Risk	39

7.3	Long-Term Aggregate Risk	39

7.4	Cancer Risk	40

8.0	Cumulative Risk Characterization/Assessment	40

9.0	Occupational Exposure/Risk Pathway	40

9.1	Short- and Intermediate-Term Handler Risk	40

9.2	Short- and Intermediate-Term Post-Application Risk	45

10.0	Data Needs and Label Requirements	47

10.1	Toxicology	47

10.2	Residue Chemistry	47

10.3	Occupational and Residential Exposure	47

References:	48

Appendix A:  Toxicology Assessment	49

A.1	Toxicology Data Requirements	49

A.2	Toxicity Profiles	50

A.3	Executive Summaries	54

	A.4
References……………………………………………………
…………………..67

Appendix B:  Metabolism Assessment	70

B.1	Metabolism Guidance and Considerations	70

Appendix C:  Human Research References	71

 1.0	Executive Summary

	Lambda-cyhalothrin is a synthetic pyrethroid insecticide used to
control a wide range of pests on food/feed crops and livestock, as well
as in and around buildings and structures.    SEQ CHAPTER \h \r 1
Lambda-cyhalothrin is an enriched isomer of cyhalothrin.  It is
currently used on a wide range of pests (including aphids, adult
Japanese beetles, grasshoppers, and butterfly larvae) in a variety of
applications.  It may also be used for structural pest management
(termiticide), and in public health applications to control insects
(such as mosquitoes, cockroaches, ticks, and flies) which may act as
disease vectors.  Another use is as a pour-on insecticide, which is
applied down the backline of beef cattle for control of lice and horn
flies.  There are existing residential uses for lambda-cyhalothrin.  

	Syngenta Crop Protection (Syngenta) and Interregional Research Project
#4 (IR-4) have submitted petitions supporting new uses for
lambda-cyhalothrin as a microencapsulated formulation (capsule
suspension, CS) containing either 1.0 or 2.08 pounds of active
ingredient per gallon (lb ai/gal).  The   SEQ CHAPTER \h \r 1 proposed
new uses of lambda-cyhalothrin are on barley, buckwheat, oats, rye,
cucurbit vegetables, grasses, tuberous and corm vegetables, wild rice,
and pistachios.  The formulations being proposed for these uses include
a 1.0 lb ai/gal CS and a 2.08 lb ai/gal CS.  These formulations are
currently registered to Syngenta for use on a wide variety of food and
feed crops at seasonal rates of 0.06-0.48 lb ai per acre (lb ai/A). 
Tolerances are established for the combined residues of
lambda-cyhalothrin and its epimer (R157836) in/on plant and animal
commodities under 40CFR §180.438.  

Human Health Risk Assessment

Toxicology/Hazard

	The main target organ for lambda-cyhalothrin is the neuromuscular
system.  Lambda-cyhalothrin produces neurotoxicity in three species
(rats, mice, and dogs); neurotoxicity is evident in rats after oral,
dermal, and inhalation exposure.  As with other pyrethroids, inhalation
exposure appears to be the most toxic route of exposure.  The observed
neurotoxic effects are classic pyrethroid effects, and they are
toxicologically significant.  The observed liver effects in some studies
strongly suggest an adaptive response.  Lambda-cyhalothrin is classified
as “not likely to be carcinogenic to humans,” based on the lack of
evidence of carcinogenicity in mice and rats.  This classification was
determined at the HIARC meeting of 3/1/2004.  

	Developmental studies in rats and rabbits exposed to cyhalothrin
demonstrated no indication of increased quantitative or qualitative
sensitivity of rats or rabbits to in utero exposure to cyhalothrin.  No
developmental toxicity was observed in either of the developmental
toxicity studies in rats and rabbits.  Maternal toxicity was observed in
the form of clinical signs of neurotoxicity in the rat study;
additionally, reduced body weight gain and food consumption were
observed in both the rat and the rabbit studies.

	A 3-generation reproduction study exposing rats to cyhalothrin
demonstrated no indication of increased quantitative or qualitative
sensitivity of rats to post-natal exposure to cyhalothrin.  In the
3-generation reproduction study in rats, the parental/offspring No
Observed Adverse Effect Levels (NOAELs) are the same, based on decreased
parental and pup body weight and body weight gain.

	The endpoint selected for assessment of acute dietary risk is
appropriate because it is based on effects that were observed within the
first 2 days of exposure in an oral study in dogs.  The NOAEL used for
the acute dietary dose is 0.5 mg/kg, with a Lowest Observed Adverse
Effect Level (LOAEL) of 3.5 mg/kg.  The endpoint selected for assessment
of chronic dietary risk is appropriate because it is based on a chronic
oral study in dogs.  This NOAEL (0.1 mg/kg/day) is somewhat lower than
those seen in dog studies with other pyrethroids; however, transient
effects were observed in several dogs at the LOAEL of 0.5 mg/kg/day.   
SEQ CHAPTER \h \r 1 The short- and intermediate-term incidental oral
NOAELs are 0.1 mg/kg/day, based on clinical signs of neurotoxicity in
the chronic dog study at the LOAEL of 0.5 mg/kg/day.  The NOAEL for
dermal exposure is 10 mg/kg/day from a dermal toxicity study in rats,
and is based on clinical signs of neurotoxicity at the LOAEL of 50
mg/kg/day.  The NOAEL for inhalation exposure is 0.08 mg/kg/day in an
inhalation study in rats, and is based on clinical signs of
neurotoxicity at the LOAEL of 0.90 mg/kg/day.  

	No additional uncertainty factors (UFs) have been retained, so HED’s
level of concern (LOC) is a margin of exposure (MOE) of less than 100.  

FQPA Safety Factor

	

 The toxicology database is considered complete for the purposes of an
FQPA risk assessment.  Based on the developmental studies in rats and
rabbits, and the 3-generation and neurodevelopmental studies in rats,
there is no evidence of increased susceptibility.  The neurotoxicity
observed in adult animal studies raised a concern for potential
neurodevelopmental effects.  A rat neurodevelopmental toxicity (DNT)
study is available.   In this study, the lowest dose showing
neurotoxicity in the offspring (effects on mortality, body weights, body
weight gains, learning, learning and memory, and brain morphometry) is
10 mg/kg bw/day, with a NOAEL of 4 mg/kg bw/day.  Effects in offspring
and adult animals are found at a similar dose based on body weight
decreases.    It should be noted that some of the parameters evaluated
in this DNT study were regarded as acceptable but several others were
not, leading to a study classification of "unacceptable.” The study
deficiencies which, taken together, led to the unacceptable
classification include:  1) statistical analyses that adjusted for body
weights after treatment had begun, 2) an inadequate assessment of motor
activity, 3) an inadequate assessment of auditory startle in PND 61
females, and 4) missing low- and mid-dose morphometry data. 

However, it is not likely that these limitations will impact the risk
assessment for the following reasons.  The slight changes in brain
morphometry were seen at the highest dose tested. Because these changes
were slight, it is uncertain whether toxicologically significant
differences would be seen at the mid dose, and it is unlikely that
significant changes would be seen at the lowest dose tested. The
auditory startle response is considered adequate for assessment in PND
23 males/females and PND 61 males where no treatment-related effects
were seen in auditory startle response.  Only the auditory response data
for PND 61 females is inadequate. Motor activity was examined and there
did not appear to be any differences between treated and control animals
other than decreases for multiple subsessions in PND 18 males/females at
the high dose only, but due to the high variability and the lack of
habituation, these data are considered equivocal.  If a 10-fold factor
is applied to the NOAEL in the study (i.e., 4 mg/kg bw/day) to account
for the scientific limitations of the study, the resulting value is 0.4
mg/kg bw/day.  The estimate of 0.4 mg/kg/day is similar to the doses
from the chronic dog study used for risk assessment (i.e., 0.5 mg/kg/day
for acute dietary exposure scenarios and 0.1 mg/kg/day for chronic
dietary exposure scenarios).  In the exposure databases, there are also
no residual uncertainties.  The exposure assessments are based on
reliable data and reasonable worst-case assumptions, and will not likely
underestimate risks.  There was no published literature found that would
indicate a neurodevelopmental concern for lambda-cyhalothrin.  

Based on all of the considerations above, there is not a need to retain
the additional 10X safety factor for children. Application of the 10X
intraspecies uncertainty factor (which accounts for the possibility that
a subpopulation may be 10 times more sensitive than the average
individual) and a 10X interspecies factor (which accounts for the
possibility that humans may be 10 times more sensitive than animals) to
the dog NOAEL (i.e., the most sensitive species) should assure
protection of human health including children. 

Dietary Exposure (Food/Water)

	The nature of the residue in plants is sufficiently understood.  The
residues to be regulated are lambda-cyhalothrin and its epimer R157836.

	An adequate confined rotational crop study is available indicating that
significant residues (greater than 0.01 ppm) will not be present in
crops rotated 30 days after application of lambda-cyhalothrin (EFED
review; 4/6/1988).  

	Studies of lambda-cyhalothrin metabolism in ruminants and poultry have
been reviewed.  As with plants, HED has determined that the residues to
be regulated are lambda-cyhalothrin and its epimer R157836.  The other
minor animal metabolites do not need to appear in the tolerance
expression.

	Adequate gas chromatographic/electron capture detection (GC/ECD)
methods are available for enforcing tolerances on both plant (Method
PRAM 81) and animal (Method PRAM 86) commodities.  For both methods,
residues are extracted with   SEQ CHAPTER \h \r 1 acetone/hexane (1:1,
v/v), then cleaned up using liquid-liquid chromatography and Florisil
column chromatography.  Residues are determined by GC/ECD; the method
limit of quantitation (LOQ) is 0.01 ppm for each analyte. 

	The available field trial data on potatoes, cucumbers, muskmelons,
summer squash, and grasses are adequate, and support the proposed use
patterns for lambda-cyhalothrin (CS) on tuberous and corm vegetables,
cucurbit vegetables, and grasses.  The number and geographic
distribution of the field trials are adequate, and the appropriate
samples were collected at the proposed pre-harvest intervals (PHIs).  In
addition to the new field trial data, adequate field trial data are
available on rice, wheat, almonds, and pecans from previously reviewed
petitions.  The data on rice will be translated to support an identical
use on wild rice; the data on almonds and pecans will be translated to
support an identical use on pistachios; and the data on wheat will be
translated to support identical uses on barley, buckwheat, oats, and
rye.

	Adequate storage stability data are available indicating that both
lambda-cyhalothrin and R157836 are stable under frozen storage in a wide
variety of raw and processed commodities for intervals of 26-36 months. 
These data support the storage durations (2.9-8.5 months) and conditions
for samples from the field trials and processing studies submitted with
the current petitions.

	Adequate processing studies are available for potato and wheat grain;
processing data are not required for cucurbit vegetables, grass, nor
wild rice.  Separate tolerances are not required for potato processed
fractions.  However, based on the available wheat grain processing data,
separate tolerances are required for both barley and rye bran.  

	The Codex Alimentarius Commission, Mexico, and Canada have all
established maximum residue limits (MRLs) for residues of
lambda-cyhalothrin in/on a variety of raw agricultural commodities. 
Each of these regulatory bodies expresses residues in terms of only
cyhalothrin; however, the US tolerance expression includes both
lambda-cyhalothrin and its epimer R157836. For the crop uses currently
under consideration, only potatoes have existing international
tolerances, and the recommended US tolerance of 0.02 ppm will be in
harmony with the existing 0.02 mg/kg MRLs for Codex and Mexico.

he Dietary Exposure Evaluation Model (DEEM-FCID™, Version 2.03).  The
drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED), and
incorporated directly into the dietary assessment.  

	Acute Dietary Exposure Results and Characterization

	A refined acute probabilistic dietary exposure assessment was performed
for lambda-cyhalothrin to support all existing and proposed food uses,
and included drinking water exposure.  The acute dietary exposure
assessment incorporated processing factors and percent crop treated
(%CT) estimates provided by the Biological and Economic Analysis
Division (BEAD).  Acute anticipated residues were derived from PDP
monitoring data, field trial studies, and a market basket survey for
beef-fat.  

	The acute drinking water concentration in surface water of 5.35 ppb was
based on the FIRST (FQPA Index Reservoir Screening Tool) estimated peak
concentration resulting from applications to orchards.  

	The acute dietary exposure estimates for food and drinking water are
below HED’s LOC, 100% of the acute population adjusted dose (aPAD) for
the general US population and all population subgroups. 
Lambda-cyhalothrin acute dietary exposure at the 99.9th percentile for
food and drinking water is 46% of the aPAD for the general US
population, and 61% of the aPAD for all infants (<1 year old), the most
highly-exposed population subgroup.  

	Chronic Dietary Exposure Results and Characterization

	A refined chronic dietary exposure assessment was also conducted for
lambda-cyhalothrin to support all existing and proposed food uses, and
included drinking water exposure, utilizing point estimates of
anticipated residues for food and drinking water.  The chronic dietary
exposure assessment incorporated processing factors and %CT estimates
provided by BEAD.  Chronic anticipated residues were derived from PDP
monitoring data, field trial studies, and a market basket survey for
beef-fat.  

	The chronic drinking water concentration in surface water of 0.130 ppb
was based on the FIRST estimated mean concentration resulting from
applications to orchards.  

	The chronic dietary exposure estimates for food and drinking water are
below HED’s LOC, 100% of the chronic population adjusted dose (cPAD),
for the general US population and all population subgroups. 
Lambda-cyhalothrin chronic dietary exposure for food and drinking water
is 17% of the cPAD for the general US population, and 50% of the cPAD
for children (1-2 yrs old), the most highly-exposed population subgroup.
 

Residential Exposure/Risks

	The residential risk assessment evaluated existing uses for
lambda-cyhalothrin.  Existing uses on turf, in gardens, on golf courses,
and for structural pest control were qualitatively assessed, but a
quantitative calculation was only completed for post-application
exposure on treated turf because this scenario is expected to have the
highest associated exposures.  This would be protective for all
residential exposures, even the handler scenarios, because the
anticipated dose levels for children playing on treated lawns exceed
those expected for all other scenarios.  

	For post-application exposure, all residential MOES were well above the
Agency target MOE of 100 for the inhalation, dermal, and oral routes
(ranging from 700 to 15,000), and therefore do not exceed HED’s LOC. 
Additionally, when the MOEs for the three routes were aggregated, MOEs
were still not of concern (MOEs for children were 460 to 500, and the
MOE for adults was 3000).  

Aggregate Exposure/Risks

	Aggregate risk assessments (including both dietary and residential
exposure routes) for short- and intermediate-term durations were
conducted.  For these exposure durations, aggregate MOEs were greater
than the Agency target MOE of 100 (ranging from 140 to 490), and there
are thus no concerns for aggregate exposure.  For the acute and chronic
durations, the aggregate exposure and risk estimates are equivalent to
the dietary estimates, and are also not of concern.  

Occupational Exposure/Risks

	Handlers

	An MOE of 100 or more is adequate to protect occupational pesticide
handlers from exposures to lambda-cyhalothrin.   Provided mixer/loaders
wear personal protective equipment (PPE) as directed by the labels, all
MOEs are greater than 100 (ranging from 110 to 1700), except for
mixer/loaders supporting aerial applications to wild rice at a rate of
0.04 lb ai per acre (lb ai/A), and 1200 acres treated per day (A/day). 
Their exposure can be mitigated by reducing the amount of ai handled per
day, or by the use of a dust-mist respirator.  Baseline MOEs for
applicators and flaggers range from 820 to 4900.  

	Post-application

	An MOE of 100 or more is adequate to protect persons from
post-application exposures to lambda-cyhalothrin, as described in the
proposed use patterns.  Because the estimated MOEs are all greater than
100 (ranging from 520 to 13,000), post-application exposures arising
from the proposed uses do not exceed HED’s LOC.  

Environmental Justice Considerations

	Potential areas of environmental justice concerns, to the extent
possible, were considered for this human health risk assessment, in
accordance with US Executive Order 12898, Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf" 
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf .

	As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by USDA under the CSFII, and are used
in pesticide risk assessments for all registered food uses of a
pesticide.  These data are analyzed and categorized by subgroups based
on age, season of the year, ethnic group, and region of the country. 
Whenever appropriate, non-dietary exposures based on home use of
pesticide products, associated risks for adult applicators, and for
toddlers, youths, and adults entering or playing on treated areas
post-application are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

Review of Human Research

	This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical.  These studies (listed in Appendix C) have been determined to
require a review of their ethical conduct, and they have received that
review.

Additional Data Needs 

	Toxicology

Although several parameters were unacceptable in this study, as
explained in Sections 3.1.3 and 3.3.2, a repeat of this study is
unlikely to yield a lower regulatory endpoint. Thus, the database is
complete for purposes of this risk assessment. There are no data gaps
that would quantitatively impact the risk assessment.

   TC \l3 "3.3.7	Recommendation for a Developmental Neurotoxicity Study 

	  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry

	No major deficiencies were noted in the subject petitions that would
preclude the establishment of permanent tolerances for
lambda-cyhalothrin on the proposed commodities.  Only minor deficiencies
were noted pertaining to the proposed label directions and recommended
tolerance levels (listed below).  HED  SEQ CHAPTER \h \r 1  recommends
in favor of establishing permanent tolerances for lambda-cyhalothrin
residues at the levels listed in Table 1.0, below.  

	(1) Use directions for grasses should be clarified to specify that the
restriction of 0.03 lb ai/A per cutting includes pastures and rangeland
in addition to grasses grown for seed.  A minimum RTI of 30 days should
be specified for pastures and rangeland which are not cut between
applications.  In addition, the PHI for forage should be changed to 0
days, as PHIs for forage are not practical for rangeland applications.

	(2) A tolerance was not proposed in rye bran.  Based on the available
wheat residue data, a separate tolerance is required at 0.2 ppm in rye,
bran.

	(3) Based on the calculated theoretical dietary burdens (TDBs) for
livestock, and the available livestock residue studies, the current
tolerance for lambda-cyhalothrin in milk fat is too low.  An increased
tolerance should be proposed in milk fat (10 ppm).  The data also
indicate that the current tolerances in hog commodities could be lowered
to 0.2 ppm in fat, 0.01 ppm in meat, and 0.02 ppm in meat-byproducts.

	Regulatory Recommendations and Occupational and Residential Exposure 
TC \l2 "10.3	Occupational and Residential Exposure 

	The labels for Warrior® Insecticide (EPA Registration #100-1112) and
Karate® Insecticide (EPA Registration #100-1097) should state that
mixer/loaders supporting aerial applications to wild rice at a rate of
0.04 lb ai/A, and treating 1200 acres (or more) per day, are required to
use a dust-mist respirator.  

Table 1. 0	Tolerance Summary for Lambda-Cyhalothrin.

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments; Correct Commodity Definition

Barley, bran	0.2	0.2	Tolerances are based on the existing residue data
and tolerances in similar wheat commodities.

Barley, grain	0.05	0.05

	Barley, hay	2.0	2.0

	Barley, straw	2.0	2.0

	Buckwheat, grain	0.05	0.05

	Cucurbit vegetables	0.05	0.05	Vegetable, cucurbits, group 9

Grass forage, fodder, and hay	9.0	7.0	A crop group tolerance is
appropriate.

Grass forage, fodder, and hay, group 17

Hog, fat	3.0	0.2	Based on a TDB* of 0.9 ppm for swine, the maximum
expected residues are 0.16 ppm in hog fat, 0.006 ppm in hog meat, and
0.011 ppm in hog meat-byproducts.

Hog, meat	0.2	0.01

	Hog, meat-byproducts	0.2	0.02

	Milk, fat (reflecting 0.4 ppm in whole milk)	5.0	10	Based on a TDB of
10.4 ppm for dairy cattle, the maximum expected residues in milk are
0.35 ppm, equivalent to 8.8 ppm in milk fat.

Oat, grain	0.05	0.05	Tolerances are based on the existing residue data
and tolerances in similar wheat commodities.

Oat, forage	2.0	2.0

	Oat, hay	2.0	2.0

	Oat, straw	2.0	2.0

	Pistachio	0.05	0.05	Tolerance is based on existing almond and pecan
residue data, and the tolerance in the tree nut group.

Rice, wild, grain	1.0	1.0	Tolerance is based on the existing tolerance
and residue data in rice.

Rye, bran	None	0.2	Tolerances are based on the existing residue data and
tolerances in similar wheat commodities.

Rye, grain	0.05	0.05

	Rye, forage	2.0	2.0

	Rye, straw	2.0	2.0

	Tuberous and corm vegetables	0.05	0.02	Combined residues were <0.02 ppm
in/on all potato samples from all field trials conducted at 1x rate, and
from the field trial conducted at a 5x rate.  

Vegetable, tuberous and corm, subgroup 1C

* TDB = Theoretical Dietary Burden.  

  TC \l1 "1.0	Ex

ecutive Summary 2.0	Ingredient Profile

	Lambda-cyhalothrin is a synthetic pyrethroid insecticide used to
control a wide range of pests on food/feed crops and livestock, as well
as in and around buildings and structures.    SEQ CHAPTER \h \r 1
Lambda-cyhalothrin is an enriched isomer of cyhalothrin, and is
classified as a Type II pyrethroid compound.  

	Syngenta Crop Protection has submitted a petition (PP#5F6994) proposing
the use of 1.0 and 2.08 lb ai/gal CS formulations of lambda-cyhalothrin
on tuberous and corm vegetables (subgroup 1C), cucurbit vegetables
(group 9), and grasses (group 17).  In addition, IR-4 submitted two
petitions (PPs#3E6593 and 6E7077) proposing to expand the use of
lambda-cyhalothrin (CS) to include barley, buckwheat, oats, rye, wild
rice, and pistachios, based on the existing residue data and tolerances
on wheat, rice, and tree nuts.

2.1	Summary of Registered/Proposed Uses

	Table 2.1, below, summarizes the proposed use patterns and formulations
specified for the two end-use products containing lambda-cyhalothrin.

Table 2.1	Summary of Directions for Use of Lambda-Cyhalothrin.

Application Timing, Type, and Equipment	Formulation

[EPA Reg. #]	Use Rate

(lb ai/A)	Max. # Applic. per Season	Max. Seasonal Use Rate

(lb ai/A)	PHI

(Days)	Use Directions and Limitations

Cereal Grains (including Wheat, Wheat Hay, Triticale, Barley, Buckwheat,
Oats, and Rye)

Broadcast foliar applications using ground or aerial equipment	1.0 lb
ai/gal CS

[100-1112]

2.08 lb ai/gal CS

[100-1097]	0.03	2	0.06	7

[forage, hay]

30

[grain, straw]	The minimum RTI is 3 days.

Do not allow livestock to graze within 7 days of treatment.  Use a
minimum of 2 and 10 gal/A for aerial and ground applications,
respectively.

Cucurbit Vegetables

Broadcast foliar applications using ground or aerial equipment	1.0 lb
ai/gal CS

[100-1112]	0.03	6	0.18	1	The minimum RTI is 5 days.  Use a minimum of 2
and 10 gal/A for aerial and ground applications, respectively.

Grass Forage, Fodder and Hay

Broadcast foliar applications using ground or aerial equipment	1.0 lb
ai/gal CS

[100-1112]

2.08 lb ai/gal CS

[100-1097]	0.03	3	0.09	1

[forage]

7

[hay, straw, and seed screenings]	Do not apply more than 0.03 lb ai/A
per cutting.  Following application to grasses grown for seed, regrowth
may be cut for forage or hay 30 days after harvest of seed.  Use a
minimum of 2 and 7 gal/A for aerial and ground applications,
respectively.

Tuberous and Corm Vegetables

Broadcast foliar applications using ground or aerial equipment	1.0 lb
ai/gal CS

[100-1112]	0.03	4	0.12	7	The minimum RTI is 7 days.

Use a minimum of 2 and 10 gal/A for aerial and ground applications,
respectively.

Rice and Wild Rice

Broadcast foliar applications using ground or aerial equipment	1.0 lb
ai/gal CS

[100-1112]

2.08 lb ai/gal CS

[100-1097]	0.04	3	0.12	21	Do not apply more than 0.08 lb ai/A within 28
days of harvest, or more than 0.04 lb ai/A within 21 days of harvest. 
The minimum RTI is 5 days.  Do not release flood water within 7 days of
application.  Do not use treated rice fields for the aquaculture of
edible fish and crustacaea.  Do not apply as an ULV spray.  Use a
minimum of 2 gal/A for aerial applications.

Tree Nuts (including Pistachio)

Broadcast foliar applications during growing season using ground or
aerial equipment	1.0 lb ai/gal CS

[100-1112]	0.04	4	0.16	14	Do not apply more than 0.12 lb ai/A/year
post-bloom.  The minimum RTI is 5 days.  Use a minimum of 5 gal/A for
aerial applications.

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature 

Table 2.2	Lambda-Cyhalothrin Nomenclature.

Compound

	1:1 mixture of (Z)-(1R,3R), S-ester: (Z)-(1S,3S), R-ester

)-α-cyano-3-phenoxybenzyl
(1S)-cis-3-[(Z)-2-chloro-3,3,3-trifluoropropenyl]-2,2-dimethylcyclopropa
necarboxylate and (S)-α-cyano-3-phenoxybenzyl
(1R)-cis-3-[(Z)-2-chloro-3,3,3-trifluoropropenyl]-2,2-dimethylcyclopropa
necarboxylate

CAS Name	rel-(R)-cyano(3-phenoxyphenyl)methyl
(1S,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propenyl]-2,2-dimethylcyclopr
opanecarboxylate

CAS Registry Number	91465-08-6

End-use Products (EPs)	1.0 lb ai/gal CS (Warrior® Insecticide with
Zeon™ Technology; EPA Registration #100-1112)

2.08 lb ai/gal CS (Karate® Insecticide with Zeon™ Technology; EPA
Registration #100-1097)

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical
Properties 

Table 2.3	Physicochemical Properties of Lambda-Cyhalothrin. 

Parameter	Value	Reference

Melting Point/Range (°C)	49.2	D284860 1

pH	NA 2

	Density (g/cm3 at 25°C)	1.33

	Water Solubility (mg/L at 20ºC, pH 6.5)	0.005

	Solvent Solubility (g/L)	NA

	Vapor Pressure (mm Hg at 20°C)	1.5 x 10-9

	Dissociation Constant (pKa at 20°C)	>9

	Octanol/water Partition Coefficient (Log[KOW])	7.00

	UV/visible Absorption Spectrum	NA

	1. Kit Farwell, 8/15/2002.  

2. NA = Not Available.  

3.0	Hazard Characterization/Assessment  TC \l1 "3.0	Hazard
Characterization/Assessment 

	Lambda-cyhalothrin is moderately acutely toxic via the oral, dermal,
and inhalation routes (Category II).  It is also a moderate eye irritant
(Category II).  It is neither irritating to the skin nor is it a
sensitizer in the guinea pig.  Acute toxicity studies conducted with
cyhalothrin indicate that it is also Category II via the oral, dermal
(rat), and inhalation routes.  It is a moderate eye irritant without
irrigation, and a mild eye irritant with irrigation (Category III).  It
is a mild skin irritant in rats, but not an irritant in rabbits
(Category IV).  Cyhalothrin is a skin sensitizer in guinea pigs.

3.1	Hazard and Dose-Response Characterization  TC \l2 "3.1	Hazard and
Dose-Response Characterization 

	The toxicological database for lambda-cyhalothrin, when bridged with
that for cyhalothrin, indicates one major target for this chemical: the
neuromuscular system.  The neuromuscular effects are typical of
chemicals in the pyrethroid class of insecticides.  The neuromuscular
effects are consistently characterized by gait abnormalities and
salivation; these effects are observed across species, and across routes
of administration (oral, dermal, and inhalation).  A comparison of the
90-day oral study in rats with the chronic feeding study in rats
indicates that toxicity is not induced at lower dose levels when rats
are exposed over a longer period of time.  As with other pyrethroids,
the dog appears to be the most sensitive species, exhibiting gait
abnormalities at doses as low as 0.5 mg/kg/day, starting at week 2. 
Neither sex appears to be more sensitive.  In studies where the liver is
affected, it appears to be an adaptive response.

3.1.1	Database Summary  TC \l3 "3.1.1	Database Summary 

3.1.1.1	Studies Available and Considered   TC \l4 "3.1.1.1	Studies
available and considered (animal, human, general literature) 

	Through the use of bridging data, the toxicology database for
lambda-cyhalothrin has been completed using developmental, reproduction,
chronic (rodent), and oncogenicity studies conducted with cyhalothrin. 
The toxicology database for lambda-cyhalothrin, when bridged with
cyhalothrin, is complete for the purposes of this risk assessment; there
are no data gaps that would quantitatively impact the risk assessment.
The scientific quality is relatively high, and the toxicity profile of
lambda-cyhalothrin can be characterized for all effects, including
potential developmental, reproductive, and neurotoxic effects.  The data
provided no indication of increased susceptibility of rats or rabbits to
in utero and/or post-natal exposure to cyhalothrin.

3.1.1.2	Mode of Action, Metabolism, Toxicokinetic Data  TC \l4 "3.1.1.2
Mode of action, metabolism, toxicokinetic data 

	G.W. Ware (The Pesticide Book; 4th Edition; 1994; pages 62-64, 171-172)
states that, “Pyrethroids initially stimulate nerve cells to produce
repetitive discharges, and eventually cause paralysis in the insect. 
Such effects are caused by their action on the sodium channel, a tiny
hole through which sodium ions are permitted to enter the axon to cause
excitation.  These effects are produced in insect nerve cord, which
contains ganglia and synapses, as well as in giant nerve fiber axons. 
The stimulating effect of pyrethroids is much more pronounced than that
of DDT.  The exact sites of action of pyrethroids at synapses are not
known.  It is probable that the toxic action of pyrethroids is primarily
due to its blocking action on the nerve axon since this action shows a
negative temperature coefficient.  But because the cockroach ganglion is
affected by pyrethroid concentrations many fold less than are required
to block conduction in giant fibers, it also seems likely that
pyrethroids act on some aspect of synaptic function.  The fast knockdown
of flying insects could be the result of rapid muscular paralysis,
suggesting that the ganglia of the insect central nervous system are
affected.”  Pyrethroid neurotoxicity in mammalian species is also
believed to be related to their effects on the sodium conductance
channel.

3.1.2	Toxicological Effects  TC \l3 "3.1.2	Toxicological Effects 

	The main target organ for lambda-cyhalothrin is the neuromuscular
system.  Lambda-cyhalothrin produces neurotoxicity in three species
(rats, mice, and dogs); neurotoxicity is evident in rats after oral,
dermal, and inhalation exposure.  As with other pyrethroids, inhalation
exposure appears to be the most toxic route of exposure.  The observed
neurotoxic effects are classic pyrethroid effects, and they are
toxicologically significant.  The observed liver effects in some studies
appear to be an adaptive response.

	In an acute neurotoxicity study in the rats exposed to (-cyhalothrin,
clinical signs of neurotoxicity and changes in the FOB parameters were
observed; however, no treatment-related neuropathology was evident. 
Clinical signs of neurotoxicity were observed in the chronic and
subchronic dog study (gait abnormalities, muscle tremors and
convulsions, subdued behavior, head shaking, excessive salivation);
developmental rat study (gait abnormalities); subchronic mouse study
(gait abnormalities, hunched posture); 21-day dermal rat study (reduced
splay reflex, gait abnormalities, reduced stability); 21-day inhalation
rat study (gait abnormalities, salivation, paw flicking, tail erections,
lachrymation, reduced foot withdrawal, reduced righting reflex, shaking,
head flicking, reduced splay reflex, decreased visual placing response);
and 28-day rat feeding study (gait abnormalities, hunched posture, tail
erect, salivation) studies.

	Developmental studies in rats and rabbits exposed to cyhalothrin were
available for consideration.  The data demonstrate no indication of
increased quantitative or qualitative sensitivity of rats or rabbits to
in utero exposure to cyhalothrin.  No developmental toxicity was
observed in either of the developmental toxicity studies in rats and
rabbits.  Maternal toxicity was observed in the form of clinical signs
of neurotoxicity in the rat study; additionally, reduced body weight
gain and food consumption were observed in both the rat and the rabbit
studies.

	A 3-generation reproduction study exposing rats to cyhalothrin is part
of the toxicology database.  The data demonstrate no indication of
increased quantitative or qualitative sensitivity of rats to post-natal
exposure to cyhalothrin.  In the 3-generation reproduction study in
rats, the parental/offspring NOAELs are the same, based on decreased
parental and pup body weight and body weight gain.

	The requirements for oncogenicity studies in the rat and the mouse with
lambda-cyhalothrin have been satisfied by a combined
chronic/oncogenicity study in rats, and an oncogenicity study in mice,
both conducted with cyhalothrin.  Although mice should have been tested
at a higher dose, it was determined that there was not enough
toxicological concern to warrant a requirement for a new carcinogenicity
study in mice.  The chemical is classified as “not likely to be
carcinogenic to humans,” based on the lack of evidence of
carcinogenicity in mice and rats.

FQPA

            The toxicology database is considered complete for the
purposes of an FQPA risk assessment.  Based on the developmental studies
in rats and rabbits, and the 3-generation and neurodevelopmental studies
in rats, there is no evidence of increased susceptibility.  The
neurotoxicity observed in adult animal studies raised a concern for
potential neurodevelopmental effects.  A rat neurodevelopmental toxicity
(DNT) study is available.   In this study, the lowest dose showing
neurotoxicity in the offspring (effects on mortality, body weights, body
weight gains, learning, learning and memory, and brain morphometry) is
10 mg/kg bw/day, with a NOAEL of 4 mg/kg bw/day.  Effects in offspring
and adult animals are found at a similar dose based on body weight
decreases.    It should be noted that some of the parameters evaluated
in this DNT study were regarded as acceptable but several others were
not, leading to a study classification of "unacceptable.” The study
deficiencies which, taken together, led to the unacceptable
classification include:  1) statistical analyses that adjusted for body
weights after treatment had begun, 2) an inadequate assessment of motor
activity, 3) an inadequate assessment of auditory startle in PND 61
females, and 4) missing low- and mid-dose morphometry data. 

However, it is not likely that these limitations will impact the risk
assessment for the following reasons.  The slight changes in brain
morphometry were seen at the highest dose tested. Because these changes
were slight, it is uncertain whether toxicologically significant
differences would be seen at the mid dose, and it is unlikely that
significant changes would be seen at the lowest dose tested. The
auditory startle response is considered adequate for assessment in PND
23 males/females and PND 61 males where no treatment-related effects
were seen in auditory startle response.  Only the auditory response data
for PND 61 females is inadequate. Motor activity was examined and there
did not appear to be any differences between treated and control animals
other than decreases for multiple subsessions in PND 18 males/females at
the high dose only, but due to the high variability and the lack of
habituation, these data are considered equivocal.  If a 10-fold factor
is applied to the NOAEL in the study (i.e., 4 mg/kg bw/day) to account
for the scientific limitations of the study, the resulting value is 0.4
mg/kg bw/day.  The estimate of 0.4 mg/kg/day is similar to the doses
from the chronic dog study used for risk assessment (i.e., 0.5 mg/kg/day
for acute dietary exposure scenarios and 0.1 mg/kg/day for chronic
dietary exposure scenarios).  In the exposure databases, there are also
no residual uncertainties.  The exposure assessments are based on
reliable data and reasonable worst-case assumptions, and will not likely
underestimate risks.  There was no published literature found that would
indicate a neurodevelopmental concern for lambda-cyhalothrin.

 

Based on all of the considerations above, there is not a need to retain
the additional 10X safety factor for children. Application of the 10X
intraspecies uncertainty factor (which accounts for the possibility that
a subpopulation may be 10 times more sensitive than the average
individual) and a 10X interspecies factor (which accounts for the
possibility that humans may be 10 times more sensitive than animals) to
the dog NOAEL (i.e., the most sensitive species) should assure
protection of human health including children. 

 

3.2	Absorption, Distribution, Metabolism, Excretion (ADME)  TC \l2 "3.2
Absorption, Distribution, Metabolism, Excretion (ADME) 

	Metabolism studies have been conducted with cyhalothrin in both the rat
and the dog, and with lambda-cyhalothrin in the rat.  In the rat,
approximately 55% of the oral dose is absorbed.  It is extensively
metabolized when absorbed.  The urinary/fecal excretion ratio is 2.5:1.0
after subcutaneous administration.  Over 50% of the dose remained in the
carcass 7 days after a subcutaneous dose.  Metabolism results in
cleavage of the ester to cyclopropylcarboxylic acid and a phenoxybenzyl
derivative.  The distribution patterns and excretion rates in the
multiple oral dose studies are similar to the single oral dose studies. 
There is accumulation of unchanged compound in the fat upon chronic
administration.  Otherwise, cyhalothrin is rapidly metabolized and
excreted.  Cyclopropyl carboxylic acid, 3-phenoxybenzoic acid,
glucuronide conjugated 3-4'-hydroxyphenoxy benzoic acid, and a sulfate
conjugate were identified in the urine.  

	Cyhalothrin is taken up slowly by the fat, and released slowly.  It is
rapidly released by blood, kidneys, and liver.  The rates of metabolism
of both enantiomer pairs are likely identical (cyhalothrin and
lambda-cyhalothrin).  The absorption, distribution, metabolism, and
excretion patterns of lambda-cyhalothrin and cyhalothrin following a
single dose of 1 mg/kg in the male rat appear to be identical.

	In the dog, oral absorption of the C14 benzyl label was 80%, and
absorption of the C14 cyclopropyl label was 48%.  The metabolite
patterns for each half of the molecule were different, indicating
extensive cleavage of the ester bond.  Seven metabolites in the urine
were identified for the benzyl label, and 12 metabolites were identified
for the cyclopropyl label.  In the feces, a large proportion of the
radioactivity was due to unchanged compound.  Excretion in the urine and
feces was rapid (nearly all in 48 hours).

	Oral and dermal metabolism and pharmacokinetics studies were conducted
in humans.  Mild paresthesia of varying degrees was observed following
dermal dosing.  The minimal oral absorption was estimated to be from
50.35 to 56.71%.  The minimal dermal absorption was estimated to be from
0.115 to 0.122%.  The estimated dermal absorption value of 1% was
determined by rounding these values up to the nearest whole number.  No
metabolites were found near the limit of detection in plasma from the
oral dose study.  Blood was not analyzed from the dermal study.

3.3	FQPA Considerations  TC \l2 "3.3	FQPA Considerations 

3.3.1	Adequacy of the Toxicity Database  TC \l3 "3.3.1	Adequacy of the
Toxicity Database 

	Acceptable developmental studies conducted with cyhalothrin are
available in both rats and rabbits.  A 3-generation reproduction study
in rats conducted with cyhalothrin is available for FQPA consideration. 
Neurotoxicity is evident throughout the toxicology database.   A DNT
study has recently been submitted, and reviewed by the Agency. The
lowest dose showing neurotoxicity in the offspring (effects on
mortality, body weight, body weight gains, learning and memory, and
brain morphometry) is 10 mg/kg bw/day.   It should be noted that some of
the parameters evaluated in this study were regarded as acceptable but
others were not (see Sections 3.1.3 and 3.3.2 for further details).  If
a 10-fold factor is applied to the NOAEL (i.e., 4 mg/kg bw/day) to
account for the scientific limitations of the study, the resulting value
is 0.4 mg/kg bw/day.   This estimate of 0.4 mg/kg/day is similar to the
doses from the chronic dog study used for risk assessment (i.e., 0.5
mg/kg/day for acute dietary exposure scenarios and 0.1 mg/kg/day for
chronic dietary exposure scenarios).  Therefore, HED concludes that
using the NOAELs from the dog study would not underestimate risks from
dietary exposure, and consequently, the FQPA safety factor can be
reduced to 1X.  In conclusion, the toxicology database is considered
complete for the purposes of the FQPA assessment.  

3.3.2	Evidence of Neurotoxicity

	Neurotoxicity is evident in three species (rat, mouse, and dog), and
via all three routes of exposure in rats (oral, inhalation, and dermal).
 The neurotoxic effects observed (gait abnormalities, tremors,
convulsions, excess salivation) are common to the pyrethroid class of
pesticides.  Signs generally appear several hours after dosing, and
disappear by the next day; they are transitory in nature, and stop with
the removal of the test compound.

	The DNT in Wistar rats was conducted and submitted to the Agency (MRID
46449102); the calculated doses were 1.8, 4.3, and 10.0 mg/kg/day during
gestation and 4.0, 9.4, and 23.1 mg/kg/day during lactation.  The
maternal LOAEL was 10 mg/kg/day, based on decreased body weight, body
weight gains, and food consumption.  The maternal NOAEL was 4 mg/kg/day.
 At the highest dose tested, offspring had a 6% decrease in pre-cull
survival, a maximum of 12% decrease in body weights, the mean time to
completion of the water maze in PND 21 females was longer, the
proportion of successful trials in PND 21 females was lower than
controls for cut-off times ranging from 3-10 seconds, the group mean
success rate at 1.5 the straight channel swim time in PND 21 females was
decreased (NS), the proportion of successful trials for cut-off times
from 3-9 seconds in PND24 females were still decreased, and morphometric
measurement were affected up to a maximum13% difference compared to
controls.  Although Offspring neurotoxicity was seen with a LOAEL/NOAEL
of 10/4, a definitive LOAEL/NOAEL cannot be determined due to many data
insufficiencies.  The study is unacceptable due to an inadequate
assessment of motor activity, an inadequate assessment of auditory
startle in PND 61 females, missing low- and mid-dose morphometry data,
and statistical analyses that adjusted for body weights after treatment
had begun.  

3.3.3	Developmental Toxicity Studies

	The requirements for developmental studies conducted with
lambda-cyhalothrin have been satisfied by developmental studies
conducted with cyhalothrin.  The data demonstrate no indication of
increased quantitative or qualitative sensitivity of rats or rabbits to
in utero exposure to cyhalothrin.  No developmental toxicity was
observed in either of the developmental toxicity studies in rats and
rabbits.  Maternal toxicity was observed in the form of clinical signs
of neurotoxicity in the rat study; additionally, reduced body weight
gain and food consumption were observed in both the rat and the rabbit
studies.

3.3.4	Reproductive Toxicity Study

	The requirement for a reproduction study conducted with
lambda-cyhalothrin has been satisfied by a reproduction study conducted
with cyhalothrin.  The data demonstrate no indication of increased
quantitative or qualitative sensitivity of rats to post-natal exposure
to cyhalothrin.  In the 3-generation reproduction study in rats, the
parental/offspring NOAELs are the same, based on decreased parental and
pup body weight and body weight gain.

  TC \l3 "3.3.4	Reproductive Toxicity Study 

3.3.5	Pre- and/or Post-Natal Toxicity  TC \l3 "3.3.6	Pre-and/or
Postnatal Toxicity 

3.3.5.1	Determination of Susceptibility

	Based on the available developmental toxicity studies in rats and
rabbits, and the 3-generation reproduction study in rats using
cyhalothrin, there is no increased quantitative or qualitative
susceptibility to fetuses exposed in utero.  TC \l4 "3.3.6.1
Determination of Susceptibility 

3.3.5.2	Degree of Concern Analysis and Residual Uncertainties  TC \l4
"3.3.6.2	Degree of Concern Analysis and Residual Uncertainties 

	Although the developmental and reproduction studies were conducted with
cyhalothrin, and while lambda-cyhalothrin is more refined, the degree of
concern for pre- and/or post-natal susceptibility is low.  Comparing the
LOAELs from all the toxicity studies (across four species - rat, mouse,
rabbit, dog), the LOAELs from the subchronic and chronic dog studies,
based on clinical signs of neurotoxicity, are the lowest/most
conservative doses and endpoints available.  The LOAEL from the
subchronic dog study (using cyhalothrin as the test compound) is 2.5
mg/kg/day, based on clinical signs of neurotoxicity (NOAEL = 1.0
mg/kg/day).  Studies of similar duration (subchronic, developmental, and
reproduction studies) via the oral route, show that rats were adversely
affected by cyhalothrin/lambda-cyhalothrin at doses between 5.0 – 15.0
mg/kg/day, based primarily on decreased body weights and body weight
gains.  In the subchronic mouse study, mice had decreased body weight
gain and food consumption, changes in hematology and organ weights, and
minimal centrilobular hepatocyte enlargement at a dose level of 309/294
mg/kg/day M/F, respectively.  Rabbits in the developmental study using
cyhalothrin had a LOAEL of 30 mg/kg/day, based on decreased body weight
gains and food consumption.  Over a longer duration, dogs exposed to
lambda-cyhalothrin showed clinical signs at the LOAEL of 0.5 mg/kg/day
(NOAEL = 0.1 mg/kg/day), compared to the chronic rat study which showed
decreases in body weights at 12.5 mg/kg/day and the chronic mouse study
which showed clinical signs and decreased body weight at 75 mg/kg/day. 
Lambda-cyhalothrin is an enriched isomer of cyhalothrin, and many of the
cyhalothrin studies have been used to bridge the toxicology database
between the two chemicals.  Therefore, by selecting endpoints based upon
the effect of concern (neurotoxicity) in the most sensitive species
(dog) using the active ingredient lambda-cyhalothrin, the
doses/endpoints selected for risk assessment are appropriate and
protective of potential effects seen in the other species at higher dose
levels, including developmental and reproductive effects.    Since there
are no signs of increased susceptibility in rats or rabbits, the Agency
is confident that the risk to infants and children will not be
underestimated.  

3.3.6	Recommendation for a Developmental Neurotoxicity Study

	HED has received a developmental neurotoxicity study (DNT) for
lambda-cyhalothrin (MRID 46449102), which was classified as
unacceptable/guideline due to inadequacies in some of the developmental
parameters tested (see DER for more details).  If a 10-fold factor is
applied to this study’s NOAEL, (i.e., 4 mg/kg bw/day) to account for
the scientific limitations of the study, the resulting value is 0.4
mg/kg bw/day.   This estimate of 0.4 mg/kg/day is similar to the doses
from the chronic dog study used for risk assessment (i.e., 0.5 mg/kg/day
for acute dietary exposure scenarios and 0.1 mg/kg/day for chronic
dietary exposure scenarios).  Therefore, HED concludes that using the
NOAELs from the dog study would not underestimate risks to infants and
children from dietary exposure, and consequently, a repeat rat DNT study
is not required.     TC \l3 "3.3.7	Recommendation for a Developmental
Neurotoxicity Study 

3.3.7	Rationale for the UFDB 

	As discussed in section 3.3.6, HED is confident that using the NOAELs
from the chronic dog study as the basis for the acute and chronic
dietary endpoints would not underestimate risks to infants and children,
and consequently, the FQPA safety factor can be reduced to 1X.  Thus,
the toxicology database is considered complete for the purposes of this
risk assessment, and a database uncertainty factor (UFDB) is not
required.   

	

3.4	FQPA Safety Factor for Infants and Children

	The toxicology database is considered complete for the purposes of an
FQPA risk assessment.  Based on the developmental studies in rats and
rabbits, and the 3-generation study in rats, there is no evidence of
increased quantitative or qualitative susceptibility.  Using the NOAELs
from the chronic dog study would not underestimate risks to infants and
children.

	There are no residual uncertainties identified in the exposure
databases.  The acute and chronic dietary food exposure assessments
utilize anticipated residues based on USDA PDP monitoring data, field
trial data, and a beef-fat market basket survey.  Percent crop treated
data were used for many commodities in the analysis, although 100%CT was
assumed for new uses, and for existing uses where no further information
was available.  Although refined, the assessments are based on reliable
data, and will not underestimate exposure/risk.  The drinking water
exposure is based on conservative modeling estimates.  The residential
exposure assessment utilizes residential SOPs for the adult handler and
post-application scenarios, and to assess post-application exposure to
children, as well as incidental oral ingestion by toddlers.  The
residential SOPs are based on reasonable worst-case assumptions, and
will not likely underestimate exposure/risk.  

	Based on the above hazard and exposure considerations, the FQPA safety
factor can be reduced to 1X for the current lambda-cyhalothrin risk
assessment.  

3.5	Hazard Identification and Toxicity Endpoint Selection  TC \l2 "3.5
Hazard Identification and Toxicity Endpoint Selection 

3.5.1	Acute Reference Dose (aRfD) – General Population

-cyhalothrin)	

	MRID Number: 40027902

	Executive Summary: In a chronic toxicity study, beagle dogs (6
sex\dose) were given oral administration of gelatin capsules containing
lambda-cyhalothrin (96.5%) at 0, 0.1, 0.5, or 3.5 mg/kg/day, 7 days a
week for 12 months.  The test chemical had been dissolved in corn oil
prior to placement in the capsules.  The following parameters were
measured and/or recorded: daily clinical observations, body weights,
food consumption, ophthalmological examinations, clinical biochemistry,
urinalysis, gross necropsy, and microscopic examinations.

	No treatment-related toxicity was observed at 0.1 mg/kg/day.  At 0.5
mg/kg/day, 1 male and 1 female dog exhibited gait abnormalities, with
the effects seen in the male 7 hours post-dosing during week 2, and
again 2 days later (immediately after dosing), and in the female 4 times
during week 9.  Convulsions were seen in two other dogs (both males);
the convulsions appeared to be precipitated by the stress of handling or
noise.  At 3.5 mg/kg/day, the principal neurological clinical signs
following dosing were ataxia (all dogs, apparent from day 2 in 2 dogs,
observed 3-7 hours post-dosing), muscle tremors and convulsions,
occasional subdued behavior; worn or bleeding claws, regurgitation of
food during first 2 weeks, and fluid feces in all dogs.  Treatment had
no effect on body weights, hematology, clinical chemistry, urinalysis,
nor gross or histopathology.  The NOAEL is 0.1 mg/kg/day, and the LOAEL
is 0.5 mg/kg/day, based on clinical signs of neurotoxicity.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a study (83-1) in the dog.

	Dose and Endpoint for Risk Assessment: NOAEL = 0.5 mg/kg/day, based on
clinical signs of neurotoxicity (ataxia) observed from Day 2, 3-7 hours
post-dosing, seen at LOAEL = 3.5 mg/kg/day.

	Comments on Study/Endpoint/Uncertainty Factors: The endpoint selected
for assessment of acute dietary risk is appropriate because it is based
on effects that were observed within the first 2 days of exposure in an
oral study in dogs.  Based on structure-activity relationships, it is
likely that this NOAEL could be higher.  The NOAEL used for the acute
dietary endpoint is 0.5 mg/kg, with a LOAEL of 3.5 mg/kg.  With other
pyrethroids, NOAELs were closer to 1.0 mg/kg, and LOAELs were around
2.0-3.0 mg/kg.

3.5.2	Chronic Reference Dose (cRfD) – General Population  TC \l3
"3.5.3	Chronic Reference Dose (cRfD) 

	Study Selected: Chronic Dog Study (lambda-cyhalothrin)	

	MRID Number: 40027902

	Executive Summary: See Section 3.5.1.

	Dose and Endpoint for Risk Assessment: NOAEL = 0.1 mg/kg/day, based on
clinical signs of neurotoxicity (abnormal gait) in 2 dogs observed at
the LOAEL = 0.5 mg/kg/day.

	Comments on Study/Endpoint/Uncertainty Factors: The endpoint selected
for assessment of chronic dietary risk is appropriate because it is
based on a chronic oral study in dogs.  This NOAEL (0.1 mg/kg/day) is
somewhat lower than those seen in dog studies with other pyrethroids;
however, transient effects were observed in several dogs at 0.5
mg/kg/day.

3.5.3	Incidental Oral Exposure (Short- and Intermediate-Term)   TC \l3
"3.5.4	Incidental Oral Exposure (Short- and Intermediate-Term) 

	Study Selected: Chronic Dog Study (lambda-cyhalothrin)	

	MRID Number: 40027902

	Executive Summary: See Section 3.5.1.

	Dose and Endpoint for Risk Assessment: NOAEL = 0.1 mg/kg/day, based on
clinical signs of neurotoxicity (abnormal gait) in 2 dogs observed at
the LOAEL = 0.5 mg/kg/day.

	Comments on Study/Endpoint/Uncertainty Factors: This endpoint is based
on the same chronic dog study that was selected for the acute and
chronic dietary endpoints.  It is considered appropriate for both short-
and intermediate-term exposure durations because the transient effects
were observed during weeks 2 and 9.

3.5.4	Dermal Absorption

	Several dermal penetration studies are available for
lambda-cyhalothrin, one in humans, and one in rats.  The human study
indicates a dermal absorption estimate of 1%.  The rat study indicates a
dermal absorption estimate of 16%.  In the rat study, absorption ranged
from 0.24 to 15.89%.  The study authors believed that paresthesia at the
high dose caused the protective cover over the dosing site to loosen and
resulted in spreading of test material over the skin.  Thus, a
relatively high percentage of the dose was found in the carcass (16% at
24 hours exposure).  

3.5.5	Dermal Exposure (All Durations) 

	Study Selected: 21-Day Dermal Toxicity Study in Rats
(lambda-cyhalothrin)

	MRID Number: 44333802

	Executive Summary: In a repeated-dose dermal toxicity study (MRID
#44333802), lambda-cyhalothrin (96.6% ai) was applied to the clipped
skin of five albino rats/sex/dose at dose levels of 1 or 10 mg/kg/day
for 6 hours/day on 21 consecutive days.  Five rats/sex were similarly
treated with two or three applications at 100 mg/kg/day, reduced to 50
mg/kg/day for 21 consecutive days.

	Two males which were found dead after three applications of 100
mg/kg/day had reduced, moderately-atrophied seminal vesicles, and
slightly atrophied spleens.  Clinical signs indicative of neurotoxicity
were observed in the 100/50 mg/kg/day treatment groups.  Males exhibited
reduced splay reflex, downward curvature of the spine, splayed gait,
bizarre behavior, pinched-in sides, dehydration, reduced stability, and
thin appearance.  Females exhibited an increased incidence of tiptoe
gait, upward curvature of the spine, an increased incidence in signs of
urinary incontinence, urinary incontinence, chromodacryorrhea, and
reduced splay reflex.  The clinical signs commenced on day 2 of dosing. 
Body weight gains for males were significantly reduced throughout the
study; the final gain was 58% lower than the control gain.  The final
mean body weight was 19% lower than the mean control value.  Body weight
gains for females were somewhat reduced during the first half of the
study only.  Food consumption was somewhat reduced for males throughout
the study.  No dermal irritation was observed at 100/50 mg/kg/day in
either sex.  No signs of clinical toxicity or dermal irritation in the
10 or 1 mg/kg/day treatment groups were considered to be
treatment-related.  No treatment-related differences in hematology or
clinical blood chemistry parameters, organ weights, or histopathology
were observed between the treatment and control groups.  No neoplastic
tissue was observed.  The LOAEL is 50 mg/kg/day for both sexes, based on
clinical signs of toxicity, and decreased body weight and body weight
gain.  The NOAEL is 10 mg/kg/day for both males and females.

	This dermal toxicity study is classified acceptable (82-2), and
satisfies the guideline requirement for a repeated-dose dermal toxicity
study.

	Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day, based on
clinical signs of neurotoxicity (observed from Day 2), and decreased
body weight and body weight gain observed at the LOAEL = 50 mg/kg/day.

	Comments on Study/Endpoint/Uncertainty Factors: This endpoint is based
on a 21-day dermal study in the rat.  This study used the most
appropriate route of administration (dermal), and the effects of concern
(clinical signs of neurotoxicity) were observed.  Although the duration
of this study is only 21 days, it is anticipated that this study will be
protective of longer-term exposure because a comparison of the 90-day
oral study in rats with the chronic feeding study in rats indicates that
toxicity is not induced at lower dose levels when rats are exposed over
a longer period of time.  The NOAEL/LOAEL for the 90-day oral study are
2.5/12.5 mg/kg/day, based on decreased body weight gain, and the
NOAEL/LOAEL for the chronic feeding study in rats are 2.5/12.5
mg/kg/day, based on decreases in mean body weight.  No developmental
effects were observed in any of the developmental studies.  In addition,
application of the 1% dermal absorption factor to the oral NOAEL of 0.1
mg/kg/day established in the chronic dog study yields a dermal
equivalent dose of 10 mg/kg/day (0.1 ÷ 0.01 = 10.0) which is the same
dermal NOAEL used for the dermal risk assessment.  Thus, the NOAEL from
the dermal rat study is protective of effects and doses observed in
dogs.  Also, as the design of the 21-day dermal study is similar to most
of the oral studies, with respect to the neurotoxic effects of concern,
it is expected that the dermal study would detect any effects observed
in any of the oral studies.  TC \l3 "3.5.6	Dermal Exposure (Short-,
Intermediate- and Long-Term) 

3.5.6	Inhalation Exposure (All Durations) 

	Study Selected: 21-Day Inhalation Study in Rats (lambda-cyhalothrin)

	MRID Number: 41387702

	Executive Summary: In a 21-day inhalation study, 10/sex/dose SPF
Alpk:APfSD (Wistar-derived) albino rats were exposed nose-only 6
hours/day, 5 days/week for 21 days to lambda-cyhalothrin (81.5% pure) at
0, 0.3, 3.3, or 16.7 µg/L (estimated to be approximately 0, 0.08, 0.90,
or 4.5 mg/kg/day).  The MMAD ranged from 1.47 to 1.91 µm, and the GSD
ranged from 1.02 to 2.24 µm.

	No treatment-related effects were observed at 0.3 µg/L.  At 3.3 µg/L
the following were observed: salivation, lachrymation, paw flicking
(males only), tail erections, splayed gait (males only), decreased body
weight (94-95%, p < 0.05) and body weight gain (53-65%, p < 0.01)
relative to control values, increased incidence of punctate foci on the
cornea, slight reductions in cholesterol levels in females (p < 0.05),
decreased urine volume in males, slightly raised specific gravity of the
urine in both sexes, and reductions in urinary protein levels in males. 
At 16.7 µg/L, the following were observed: salivation, lachrymation,
auditory hypoaesthesia, paw flicking, tail erection, splayed gait,
decreased activity, reduced foot withdrawal (males only), head flicking,
reduced righting reflex, shaking (males only), sides pinched in, reduced
splay reflex, decreased visual placing response, absent puma reflex
(females only), ungroomed appearance (females only), tiptoe gait (males
only), respiratory noise decreased body weight (85-88%, p <0.01) and
body weight gain (<3-14%, p < 0.01) relative to control values,
decreased food consumption (46-91% ♂, 56-87% ♀) relative to control
values, changes in selected clinical chemistry values (particularly in
females), decreased urine volume, increased urine specific gravity, and
decreased urinary protein.  There was also a slight increase in the
incidence of alveolitis in high dose females.

	The NOAEL is 0.3 µg/L (0.08 mg/kg/day), and the LOAEL is 3.3 µg/L
(0.90 mg/kg/day), based on clinical signs of neurotoxicity, decreased
body weight gains, increased incidence of punctate foci in the cornea,
slight reductions in cholesterol in females, and slight changes in
selected urinalysis parameters.

	This inhalation toxicity study is classified as acceptable
(non-guideline), and does not satisfy any particular guideline
requirement.  The study is too short for a guideline study, and
individual animal data were not provided.

	Dose and Endpoint for Risk Assessment: NOAEL = 0.3 µg/L (0.08
mg/kg/day), based on clinical signs of neurotoxicity, decreased body
weight gains, increased incidence of punctate foci in the cornea, slight
reductions in cholesterol in females, and slight changes in selected
urinalysis parameters observed at the LOAEL = 3.3 µg/L (0.90
mg/kg/day).  

	Comments on Study/Endpoint/Uncertainty Factors: This endpoint is based
on a 21-day inhalation study in the rat.  This study used the most
appropriate route of administration (inhalation), and the effects of
concern (clinical signs of neurotoxicity) were observed.  No
developmental effects were observed in any of the developmental studies.
 Therefore, since the design of the 21-day inhalation study is similar
to most of the oral studies, with respect to the neurotoxic effects of
concern, it is expected that the inhalation study will reflect any other
effects observed in any of the oral studies.  Although the duration of
this study is only 21 days, it is anticipated that this study will be
protective of longer-term exposure because comparison of the 90-day oral
study in rats with the chronic feeding study in rats found that toxicity
is not induced at lower dose levels when rats are exposed over a longer
period of time.

3.5.7	Level of Concern for Margin of Exposure  TC \l3 "3.5.8	Level of
Concern for Margin of Exposure 

Table 3.5.7   Summary of Levels of Concern* for Lambda-Cyhalothrin Risk
Assessment.

Route	Short-Term

(1-30 Days)	Intermediate-Term

(1-6 Months)	Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	100	100	100

Inhalation	100	100	100

Residential Exposure

Dermal	100	100	100

Inhalation	100	100	100

Incidental Oral	100	100	100

* The level of concern is based upon a 10x intra-species variability
factor, and a 10x inter-species extrapolation 	factor.  

3.5.8	Recommendation for Aggregate Exposure Risk Assessments

	As per FQPA, 1996, when there are potential residential exposures to a
pesticide, aggregate risk assessment must consider exposures from three
major sources: oral, dermal, and inhalation exposures.  For short-,
intermediate-, and long-term aggregate risk assessments, the oral,
dermal, and inhalation exposures can be combined in this case owing to a
common toxicity endpoint (neurotoxicity).

  TC \l3 "3.5.9	Recommendation for Aggregate Exposure Risk Assessments 

3.5.9	Classification of Carcinogenic Potential

	Lambda-cyhalothrin is classified as “not likely to be carcinogenic to
humans,” based on the lack of evidence of carcinogenicity in mice and
rats.  TC \l3 "3.5.10	Classification of Carcinogenic Potential 

3.5.10	Summary of Toxicological Doses and Endpoints for
Lambda-Cyhalothrin for Use in Human Risk Assessments  TC \l3 "3.5.11
Summary of Toxicological Doses and Endpoints for [Chemical] for Use in
Human Risk Assessments 

Table 3.5.10a	Summary of Toxicological Doses and Endpoints for
Lambda-Cyhalothrin to be Used in Dietary and Non-Occupational Human 	
Health Risk Assessments.

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	RfD, PAD,
Level of Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(General Population, including Infants and Children)	NOAEL = 0.5
mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Acute RfD = 0.005 mg/kg/day

aPAD =0.005 mg/kg/day	Chronic Dog Study (lambda-cyhalothrin)

LOAEL = 3.5 mg/kg/day, based on clinical signs of neurotoxicity (ataxia)
observed from Day 2, 3-7 hours post-dosing.

Chronic Dietary

(All Populations)	NOAEL = 0.1 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Chronic RfD = 0.001 mg/kg/day

cPAD = 0.001 mg/kg/day	Chronic Dog Study (lambda-cyhalothrin)

LOAEL = 0.5 mg/kg/day, based on clinical signs of neurotoxicity
(abnormal gait) in two dogs.

Incidental Oral Short- and Intermediate-Term (1-30 days, 1-6 months)
NOAEL = 0.1 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Residential LOC for MOE < 100	Chronic Dog Study (lambda-cyhalothrin)

LOAEL = 0.5 mg/kg/day, based on clinical signs of neurotoxicity
(abnormal gait) in two dogs.

Dermal Short-Term

(All Durations)	NOAEL = 10 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Residential LOC for MOE < 100	21-Day Dermal Study in Rats
(lambda-cyhalothrin)

LOAEL = 50 mg/kg/day, based on clinical signs of neurotoxicity (observed
from Day 2), and decreased body weight and body weight gain.

Inhalation Short-Term (All Durations)	NOAEL = 0.08 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Residential LOC for MOE < 100	21-Day Inhalation Study in Rats
(lambda-cyhalothrin) LOAEL = 0.90 mg/kg/day, based on clinical signs of
neurotoxicity, decreased body weight gains, increased incidence of
punctate foci in the cornea, slight reductions in cholesterol in
females, and slight changes in selected urinalysis parameters.

Cancer (Oral, Dermal, Inhalation)	Classification: “not likely to be
carcinogenic to humans,” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data, and used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = No Observed Adverse Effect Level. 
LOAEL = Lowest Observed Adverse Effect Level.  UF = Uncertainty Factor. 
UFA = extrapolation from animal to human (inter-species).  UFH =
potential variation in sensitivity among members of the human population
(intra-species).  FQPA SF = FQPA Safety Factor.  PAD = Population
Adjusted Dose (a = acute, c = chronic).  RfD = Reference Dose.  MOE =
Margin Of Exposure.  LOC = Level Of Concern.

Table 3.5.10b	Summary of Toxicological Doses and Endpoints for
Lambda-cyhalothrin to be Used in Occupational Human Health Risk 		
Assessments.

Exposure/

Scenario	Point of Departure	Uncertainty Factors	Level of Concern for
Risk Assessment	Study and Toxicological Effects

Dermal Short-Term (All Durations)	NOAEL = 10 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Occupational LOC for MOE < 100	21-Day Dermal Study in Rats
(lambda-cyhalothrin)

LOAEL = 50 mg/kg/day, based on clinical signs of neurotoxicity (observed
from Day 2), and decreased body weight and body weight gain.

Inhalation Short-Term (All Durations)	NOAEL = 0.08 mg/kg/day	UFA = 10x

UFH = 10x

FQPA SF = 1x

	Occupational LOC for MOE < 100	21-Day Inhalation Study in Rats
(lambda-cyhalothrin)

LOAEL = 0.90 mg/kg/day, based on clinical signs of neurotoxicity,
decreased body weight gains, increased incidence of punctate foci in the
cornea, slight reductions in cholesterol in females, and slight changes
in selected urinalysis parameters.

Cancer (Oral, Dermal, inhalation)	Classification:  “not likely to be
carcinogenic to humans,” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data, and used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = No Observed Adverse Effect Level. 
LOAEL = Lowest Observed Adverse Effect Level.  UF = Uncertainty Factor. 
UFA = extrapolation from animal to human (inter-species).  UFH =
potential variation in sensitivity among members of the human population
(intra-species).  FQPA SF = FQPA Safety Factor.  MOE = Margin Of
Exposure.  LOC = Level Of Concern.

3.6	Endocrine Disruption  TC \l2 "3.6	Endocrine disruption 	

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

	In the available toxicity studies on cyhalothrin and
lambda-cyhalothrin, there was no estrogen, androgen, and/or thyroid
mediated toxicity.

  TC \l2 "3.6	Endocrine disruption 4.0	Public Health and Pesticide
Epidemiology Data

	No public health/epidemiology data were used in developing this risk
assessment.  

  TC \l2 "4.4	Other Pesticide Epidemiology Published Literature 5.0
Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization 

5.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "5.1 
Pesticide Metabolism and Environmental Degradation 

5.1.1	Metabolism in Primary Crops  TC \l3 "5.1.1	Metabolism in Primary
Crops 

	The nature of the residue in plants is adequately understood, based on
adequate cotton, cabbage, soybean, and wheat metabolism studies. 
Lambda-cyhalothrin is metabolized by cleavage of the ester linkage to
form cyclopropanecarboxylic acids and the corresponding phenoxybenzoic
acids or alcohols.  In most cases the parent compound is the principal
constituent of the residue.  However, in the cabbage metabolism study
the cis- and trans- cyclopropanecarboxylic acids were the major
constituents.  HED has concluded that the plant metabolites need not
appear in the tolerance expression at this time owing to lack of
toxicological concern, and low concentrations found from residue studies
(Memo; Pamela Hurley; 1/3/1992).  The residues to be regulated are
lambda-cyhalothrin and its epimer R157836.

5.1.2	Metabolism in Rotational Crops  TC \l3 "5.1.2	Metabolism in
Rotational Crops 

	An adequate confined rotational crop study is available indicating that
significant residues (greater than 0.01 ppm) will not be present in
crops rotated 30 days after application of lambda-cyhalothrin (EFED
review; 4/6/1988).  No additional rotational crop data are required, and
no plant-back restrictions are required on the labels, based on the
non-systemic nature of lambda-cyhalothrin, and its half-life of 10-14
days (NV920006; D185478; George Herndon; 10/8/1992).

5.1.3	Metabolism in Livestock  TC \l3 "5.1.3	Metabolism in Livestock 

	Studies of lambda-cyhalothrin metabolism in ruminants and poultry have
been reviewed.  Lambda-cyhalothrin is the major component of the residue
in animals, except in kidney and liver, where, in addition to the plant
metabolites,
3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2-hydroxymethyl-2-methylcyclopro
pane-carboxylic acid (OH-CPA) and 4-hydroxy-3-phenoxybenzoic acid
(4'-OH-3PBAcid) may be present in significant quantities.  A residue
transfer study, in which cows were fed dietary levels of 8, 25, or 80
ppm lambda-cyhalothrin, demonstrated that, at < 8 ppm, OH-CPA levels in
tissue would not exceed 0.01 ppm (PPs#2F4109, 2F4114, 7F3560, and
1F3992; M. Flood; 8/31/1992).  As with plants, HED has determined that
the residues to be regulated are lambda-cyhalothrin and its epimer
R157836.  The animal metabolites do not need to appear in the tolerance
expression.

5.1.4	Analytical Methodology  TC \l3 "5.1.4	Analytical Methodology 

	Adequate GC/ECD methods are available for enforcing tolerances for
lambda-cyhalothrin residues in plant and animal commodities.  ICI Method
81 (PRAM 81) is available for determining residues of lambda-cyhalothrin
and its epimer in plant matrices, while ICI Method 86 (PRAM 86) is
available for determining residues of lambda-cyhalothrin and its epimer
in animal matrices.  Both methods have been validated by EPA as adequate
enforcement methods.  

	For Method PRAM81, residues of lambda-cyhalothrin and R157836 are
extracted with   SEQ CHAPTER \h \r 1 acetone/hexane (1:1, v/v), and
cleaned using liquid-liquid chromatography to remove lipids, followed by
Florisil column chromatography.  Residues are then determined by GC/ECD;
the method LOQ is 0.01 ppm for both analytes.  

	For Method PRAM86, residues are extracted from milk or animal tissues
with 50% acetone/hexane.  The aqueous fraction is removed, after which
the residues are then dried over sodium sulfate, and cleaned up using a
Florisil column.  Residues are determined by GC/ECD; the method LOQ is
0.01 ppm for both analytes.  

	In the field trials submitted with the current petitions, residues of
lambda-cyhalothrin and R157836 were determined using GC/ECD methods,
which are more recent modifications of the current tolerance enforcement
method for plant commodities.  For the analysis of potatoes and cucurbit
vegetables, residues were extracted with acetone/hexane (1:1, v/v) and
sodium sulfate, filtered, and partitioned with aqueous sodium chloride. 
Residues in the resulting hexane fraction were then cleaned up using
Florisil columns, and analyzed by GC/ECD using external standards.  The
validated LOQ is 0.01 ppm for each analyte, for a combined LOQ of 0.02
ppm. 

	For the analysis of grass commodities, residues were extracted with
acetone/hexane (1:1, v/v), filtered, and cleaned up using a silica gel
solid-phase extraction (SPE) cartridge.  Residues were then analyzed by
GC/ECD using external standards.  For each grass matrix, the validated
LOQ is 0.003 ppm for lambda-cyhalothrin, and 0.007 ppm for R157836, for
a combined LOQ of 0.01 ppm.

	Each of these GC/ECD methods was adequately validated in conjunction
with the analysis of field trial samples using fortified control
samples.  Recoveries of lambda-cyhalothrin averaged 89-96% (with
standard deviations of 10-13%) from cucurbit vegetables, 85-93% (s.d.
14-17%) from grass commodities, and 90% (s.d. 10%) from potatoes. 
Recoveries of R157836 averaged 87-99% (s.d. 8-15%) from cucurbit
vegetables, 80-95% (s.d. 11-18%) from grass commodities, and 91% (s.d.
11%) from potatoes.  Apparent residues were less than the LOQ in most
controls samples, and where apparent residues were above the LOQ in
control samples, the residues were substantially less than the residues
in the associated treated samples.

5.1.5	Environmental Degradation

	The environmental fate database for lambda-cyhalothrin is substantially
complete, but it contains various supplemental studies. 
Lambda-cyhalothrin is expected to have little mobility in soil surfaces
and, therefore, leaching into groundwater is not expected to be an
important environmental fate process (average KOC = 354,100; n = 10). 
Volatilization from moist or dry surfaces is not expected to be an
important transport process.  Lambda-cyhalothrin has a relatively low
vapor pressure and Henry’s Law constant (1.5 x 10-9 mm Hg and 2.4 x
10-7 Atm-cm3/mole, respectively).  With a pKa > 9, lambda-cyhalothrin is
expected to be neutral in natural environments, but will be affected in
alkaline environments.  

	Lambda-cyhalothrin is moderately persistent in the environment, and
degrades slowly through a combination of biotic and abiotic mechanisms. 
Lambda-cyhalothrin is stable in acidic and neutral water, but hydrolyzes
under alkaline conditions (half-life of 13 days at pH 9). 
Lambda-cyhalothrin is more stable to light than the first or second
generation pyrethroids like allethrin and resmethrin, but still
undergoes some photolysis in water, with half-lives of about a month or
more in distilled water (half-life 25 days).  On soil, the half-life is
fairly stable (with little degradation on the order of ~13% in 35 days).
 It appears that the alpha cyano group stabilizes the molecule, and it
does not undergo photolysis readily.  Under both aerobic and anaerobic
soil metabolism conditions, lambda-cyhalothrin biodegrades at moderate
rates, with half-lives ranging from 12 to 72 days, but in aquatic
metabolism conditions, it biodegrades more slowly, with half-lives on
the order of about 113-142 days.  Terrestrial field dissipation studies
indicate that a combination of these mechanisms of dissipation take
place.  Half-lives of 12-64 days were observed in the field.  

	Indications are that, for synthetic pyrethroids with similar structure
to that of lambda-cyhalothrin, dissipation from plant foliage occurs
with half-lives on the order of 5-6 days, but it may be higher for the
total residues.  A low rate of volatilization was observed from leaves,
with 88% of the compound applied remaining on the leaves after 24 hours
(European Commission Review Report for the Active Substance
Lambda-Cyhalothrin; 7572/VI/97-final; 1/25/2001).  The chemical does not
translocate in the plant tissue.  Lambda-cyhalothrin is expected to be
immobile in soil environments.  Due to its low mobility, it is highly
unlikely to reach ground waters.  However, despite the protective
imposed buffer zone and buffer strip, it could reach adjacent surface
waters via spray drift or runoff events (via erosion).  Once there, the
chemical will partition with the sediment, and will linger for long
periods of time (months).  The sediment serves as a repository of the
chemical after numerous applications, in dynamic equilibrium with the
pore water and the surface water.  

	Lambda-cyhalothrin is moderately bioaccumulative (448X in the whole
body), but it depurates slowly (only 10-15% depuration after 21 days). 
It appears that situations may occur where this chemical may persist in
fish tissue for extended periods of time.

	The (±) cis- or
trans-3-(2-trifluoromethyl-2-chloro-ethenyl)-2,2-dimethylcyclopropane
carboxylic acid and 3-phenoxybenzaldehyde are the result of the
hydrolysis of the ester linkage of the pyrethroid structure.  However,
in general, the major degradates appear to be (±)cis- or
trans-3-(2-trifluoromethyl-2-chloro-ethenyl)-2,2-dimethylcyclopropane
carboxylic acid and 3-phenoxy-benzoic acid (3-PBA, or 3-PBacid, the
oxidation product of 3-phenoxybenzaldehyde).  It appears that
3-phenoxybenzaldehyde oxidizes quickly to 3-PBA.  The findings in the
field corroborate the laboratory predictions.

	Ring-hydroxylated lambda-cyhalothrin, degradate XV (see Table B.1 in
Appendix B), formed in aerobic soil microbial degradation (12% of the
applied compound at 63 days post-treatment), was included in the
drinking water assessment due to its potential toxicological concerns in
humans.  This degradate appears to degrade readily to carbon dioxide
(average t1/2 = 8.9 days; n = 3), and it appears to partition with the
sediment.  It has low mobility based on the estimated KOC value of
770,900 mL/gOC from structure activity relationship (SAR) modeling.  The
potential for groundwater contamination by this degradate is low. 
However, it is likely to reach surface water via runoff (through
erosion) after a rainfall event.

5.1.6	Comparative Metabolic Profile

	Metabolism studies have been conducted with cyhalothrin in both the rat
and the dog, and with lambda-cyhalothrin in the rat.  In the rat,
approximately 55% of the oral dose is absorbed.  It is extensively
metabolized when absorbed.  The urinary/fecal excretion ratio is 2.5:1.0
after subcutaneous administration.  Over 50% of the dose remained in the
carcass 7 days after a subcutaneous dose.  Metabolism results in
cleavage of the ester to cyclopropylcarboxylic acid and a phenoxybenzyl
derivative.  The distribution patterns and excretion rates in the
multiple oral dose studies are similar to the single oral dose studies. 
There is accumulation of unchanged compound in the fat upon chronic
administration.  Otherwise, cyhalothrin is rapidly metabolized and
excreted.  Cyclopropyl carboxylic acid, 3-phenoxybenzoic acid,
glucuronide conjugated 3-4'-hydroxyphenoxy benzoic acid, and a sulfate
conjugate were identified in the urine.  

	Cyhalothrin is taken up slowly in fat, and released slowly.  It is
rapidly released by blood, kidneys, and liver.  The rates of metabolism
of both enantiomer pairs are likely identical (cyhalothrin and
lambda-cyhalothrin).  The absorption, distribution, metabolism, and
excretion patterns of lambda-cyhalothrin and cyhalothrin following a
single dose of 1 mg/kg in the male rat appear to be identical.

	In the dog, oral absorption of the C14 benzyl label was 80%, and
absorption of the C14 cyclopropyl label was 48%.  The metabolite
patterns for each half of the molecule were different, indicating
extensive cleavage of the ester bond.  Seven metabolites in the urine
were identified for the benzyl label, and 12 metabolites were identified
for the isopropyl label.  In the feces, a large proportion of the
radioactivity was due to unchanged compound.  Excretion in the urine and
feces was rapid (nearly all in 48 hours).

	Metabolism in plants and livestock (ruminants and poultry) also
involves cleavage of the ester, resulting in formation of
cyclopropylcarboxylic acid (CPA) and phenoxybenzyl derivatives.  In
kidney and liver, the metabolites OH-CPA and 4-hydroxy-3-phenoxybenzoic
acid may be present in significant quantities.  

	Oral and dermal metabolism and pharmacokinetics studies were conducted
in humans.  Mild paresthesia of varying degrees was observed following
dermal dosing.  The minimal oral absorption was estimated to be from
50.35 to 56.71%.  The minimal dermal absorption was estimated to be from
0.115 to 0.122%.  The estimated dermal absorption value of 1% was
determined by rounding these values up to the nearest whole number.  No
metabolites were found near the limit of detection in plasma from the
oral dose study.  Blood was not analyzed from the dermal study.

5.1.7	Drinking Water Residue Profile TC \l3 "5.1.9	Drinking Water
Residue Profile 

Table 5.1.7	Summary of Estimated Drinking Water Concentrations (EDWCs)
for Lambda-			Cyhalothrin.  

Drinking Water Source[Model Used 1]	Use/Application Method[Rate Modeled]
Lambda-cyhalothrin EDWCs (ppb)	Degradate of Concern, XV EDWCs (ppb)
Total EDWCs (ppb)

Groundwater [SCI-GROW 2]

Acute and Chronic	Orchards/Ground and Aerial [0.5 lb/A]	0.00300	0.000360
0.00336

Surface Water [FIRST 3] Acute	Orchards/Ground [0.5 lb/A]	5.00	0.350	5.35

	Orchards/Aerial [0.5 lb/A]	5.00	0.298	5.30

Surface Water [FIRST] Chronic	Orchards/Ground [0.5 lb/A]	0.122	0.00758
0.130

	Orchards/Aerial [0.5 lb/A]	0.117	0.00645	0.123

1. The estimated concentrations provided in this assessment are
conservative estimates of concentrations in drinking 	water.  If dietary
risks require refinement, higher-tiered crop-specific and
location-specific models and 	modeling scenarios can be utilized.

2. The SCI-GROW (Screening Concentration In GROund Water) concentration
(ppb) represents the groundwater 	concentration that might be expected
in shallow unconfined aquifers under sandy soils. Output is used for 
both acute and chronic endpoints.

3. The FIRST (FQPA Index Reservoir Screening Tool) concentrations (ppb)
represent untreated surface water 	concentrations.  The peak day
concentration 	(over 30 years) is used for acute endpoints, and the
annual 	average concentration (over 30 years) is used for chronic
endpoints. 

	The drinking water residues used in the dietary risk assessment were
provided by EFED in a memorandum (D324222, D330149; Jose Melendez;
10/26/2006), and incorporated directly into the dietary assessment. 
Water residues were incorporated into DEEM-FCID via the food categories
“water, direct, all sources” and “water, indirect, all sources.”

	The analysis is a Tier I level drinking water analysis conducted using
the FIRST model; refinements may be available should they be needed. 
The acute level in surface drinking water was 5.35 ppb of
lambda-cyhalothrin and degradate XV; the chronic level in drinking water
was 0.130 ppb of lambda-cyhalothrin and degradate XV.  It was assumed
that the maximum application rate was used on orchards via ground
applications, with the minimum interval between applications (assumed to
be seven days).  The groundwater concentration of lambda-cyhalothrin and
degradate XV, suitable for acute and chronic purposes is 0.00336 ppb. 
The results are based on applications of lambda-cyhalothrin at the
maximum use rate to orchards.

	Comparison of results for aerial or ground applications yielded a
higher chronic concentration of lambda-cyhalothrin from the 4 ground
applications, as opposed to the 5 aerial applications.  It also yielded
higher acute and chronic results from the ground applications for the
transformation product XV.  The high use rate of the ground application
is more important than the high level of drift of the aerial
applications.  In both cases, the peak concentration was limited by the
solubility of the chemical (s = 5 ppb).  

	There are weaknesses in the data base, owing to the fact that some of
the studies are supplemental, and part of the data set for XV was
modeled through SAR; however, this is considered a conservative
(screening-level) drinking water analysis.

	SCI-GROW (Screening Concentration in Ground Water) provides the
following warning: estimated concentrations of chemicals with KOC values
greater than 9995 ml/g are beyond the scope of the regression data used
in SCI-GROW development.  If there are concerns for such chemicals, a
higher-tier groundwater exposure assessment should be considered,
regardless of the concentration returned by SCI-GROW.  The KOC input
value for lambda-cyhalothrin was 301,500 ml/g, and for its degradate,
XV, it was 770,900 ml/g.  Given that the KOC of both lambda-cyhalothrin
and the degradate, XV, are far outside the range of the KOC values used
to develop SCI-GROW, there may be high uncertainty regarding the
estimated ground water concentrations for drinking water consumption.

	There is a problem with the material balance in this assessment.  By
nature, the approach taken to estimate the parent plus degradate will
yield higher concentrations than the actual concentrations should there
be a real material balance.  This occurs because the degradate is
modeled “in addition” to the parent.  Nevertheless, EFED considers
the approach suitable for a Tier I screening-level assessment, using
Tier 1 aquatic models. Should additional refinements be required, EFED
may explore a different approach.

5.1.8	Food Residue Profile  TC \l3 "5.1.10	Food Residue Profile 

	Residue chemistry issues relevant to the proposed new uses requested in
the current petitions were reviewed in the Summary of Analytical
Chemistry and Residue Data memorandum for lambda-cyhalothrin (D313315;
William T. Drew; 12/27/2006).

	In the field trials submitted with the current petitions, the maximum
frozen storage durations were 2.9-3.6 months for muskmelons, cucumbers,
and squash, 3 months for potatoes, and 8.5 months for grass forage, hay,
straw, and seed screenings.  The available storage stability data
support the storage conditions and durations for samples from the
current field trials and processing studies.

	Adequate cattle and poultry feeding studies, and a cattle dermal
application study are available to support the existing and proposed
uses.  Based on the existing and recommended tolerances for plant
commodities, the calculated TDB for lambda-cyhalothrin residues is 10.6
ppm for beef cattle, 10.4 ppm for dairy cattle, 0.9 ppm for swine, and
1.0 ppm for poultry.  Using these TDBs and the available livestock
residue data, the maximum expected lambda-cyhalothrin residues in cattle
commodities are 0.35 ppm in whole milk (reflecting 8.8 ppm in milk fat),
2.5 ppm in fat, 0.11 ppm in muscle, 0.06 ppm in liver, and 0.15 ppm in
kidney. The maximum expected residues in hog commodities would be 0.16
ppm in fat, 0.006 ppm in meat, and 0.011 ppm in meat-byproducts.  The
maximum expected residues in poultry commodities would be 0.003 ppm in
eggs, 0.022 ppm in fat, 0.002 ppm in meat, and 0.003 ppm in
meat-byproducts.  These residue levels indicate that the current
tolerances in poultry commodities, as well as in the fat, meat, and meat
by-products of cattle, goats, horses, and sheep, are all adequate. 
However, the tolerance should be increased in milk fat (from 5 ppm to 10
ppm).  The data also indicate that the current tolerances in hog
commodities could be lowered to 0.2 ppm in fat, 0.01 ppm in meat, and
0.02 ppm in meat-byproducts.  

	Adequate confined rotational crop data are available indicating that
rotational crop restrictions and tolerances are not required for the
current or proposed uses.

	The available field trial data on potatoes, cucumbers, muskmelons,
summer squash, and grasses are adequate, and support the proposed use
patterns for lambda-cyhalothrin (CS) on tuberous and corm vegetables,
cucurbit vegetables, and grasses.  The number and geographic
distribution of the field trials are adequate, and the appropriate
samples were collected at the proposed PHIs.  Following four broadcast
foliar applications of lambda-cyhalothrin (CS) to potatoes (during tuber
development) at the 1x rate, combined residues of lambda-cyhalothrin and
R157836 were less than the LOQ (<0.02 ppm) in all potato samples
harvested at the proposed 7-day PHI.  Following six broadcast foliar
applications of lambda-cyhalothrin (CS) to representative cucurbit
vegetables (during fruit development) at the 1x rate, combined residues
at the proposed 1-day PHI were <0.02-<0.03 ppm in muskmelons and
cucumbers, and <0.02-<0.04 ppm in summer squash.  Following single
broadcast applications of lambda-cyhalothrin (CS) to grasses at the 1x
rate, combined residues were 0.13-8.04 ppm in forage harvested at 0-3
days after treatment (DAT), and <0.01-6.01 ppm in hay harvested at 5-11
DAT.  Following a single application at the 1x rate to grasses grown for
seed, combined residues were 0.35-7.80 ppm in straw, and 0.80-3.23 ppm
in seed screenings harvested at maturity, 7-19 DAT.

	In addition to the new field trial data, adequate field trial data are
available on rice, wheat, almonds, and pecans from previously reviewed
petitions.  The data on rice will be translated to support an identical
use on wild rice; the data on almonds and pecans will be translated to
support an identical use on pistachios; and the data on wheat will be
translated to support identical uses on barley, buckwheat, oats, and
rye.

	Adequate processing studies are available for potato and wheat grain;
processing data are not required for cucurbit vegetables, grass, nor
wild rice.  Based on residues in potatoes (less than the LOQ) treated at
a 5x rate, residues are unlikely to be detectable in processed
commodities from potatoes treated at 1x; therefore, separate tolerances
are not required for potato processed fractions.  However, based on the
available wheat grain processing data, in which residues concentrated by
3x in bran, separate tolerances are required for both barley and rye
bran, each at 0.2 ppm.  

International Residue Limits TC \l3 "5.1.11	International Residue Limits

	The Codex Alimentarius Commission, Mexico, and Canada have all
established maximum residue limits (MRLs) for residues of
lambda-cyhalothrin in/on a variety of raw agricultural commodities. 
These regulatory bodies express residues in terms of only cyhalothrin
(Codex) or of lambda-cyhalothrin (Canada, Mexico); none of these
tolerances include the epimer R157836 found in the U.S. tolerance
expression.  EPA includes the epimer due to it being considered as toxic
as the active ingredient and its presence at quantifiable levels in many
crops.    For the crop uses currently under consideration, only potatoes
have existing international tolerances.  Although the recommended 0.02
ppm U.S. tolerance agrees numerically with the Codex and Mexican MRLs,
strictly speaking they are not in harmony due to the different residue
definitions.

Dietary Exposure and Risk TC \l2 "5.2  Dietary Exposure and Risk 

Acute and chronic dietary (food + drinking water) exposure analyses were
conducted using the Dietary Exposure Evaluation Model (DEEM-FCID™,
Version 2.03) which uses food consumption data from USDA’s CSFII from
1994-1996 and 1998.  The dietary exposure analyses were explicated in
the Acute and Chronic Dietary (Food and Drinking Water) Exposure and
Risk Assessment memorandum for lambda-cyhalothrin (D324223; Anant
Parmar; 3/12/07).

DEEM-FCID™ default factors or, where available, factors from
processing studies) and %CT estimates provided by BEAD.  The estimated
maximum %CT (where available) for each commodity was used in the acute
dietary risk assessment; where no further information was available, and
for new uses, 100%CT was assumed.  Acute anticipated residues were
derived from PDP monitoring data, field trial studies, and a market
basket survey for beef-fat.  

	The Estimated Drinking Water Concentrations (EDWCs) for
lambda-cyhalothrin were derived from calculations based on a maximum
application rate of 0.5 lb ai/A per season to orchards (ground
application) to obtain surface water concentrations. The acute drinking
water concentration in surface water of 5.35 ppb was based on the FIRST
estimated peak concentration.  

	The acute dietary exposure estimates for food and drinking water are
below HED’s LOC, 100% of the aPAD, at the 99.9th percentile of
exposure, for the general US population and all population subgroups. 
Lambda-cyhalothrin acute dietary exposure at the 99.9th percentile for
food and drinking water is 46% of the aPAD for the general US
population, and 61% of the aPAD for all infants (<1 year old), the most
highly-exposed population subgroup.  

Table 5.2.1	Lambda-Cyhalothrin Acute Dietary (Food + Drinking Water)
Exposure Analysis.

Population Subgroup*	aPAD (mg/kg/day)	95th Percentile	99th Percentile
99.9th Percentile

Exposure Estimate (mg/kg/day)	% aPAD	Exposure Estimate (mg/kg/day)	%
aPAD	Exposure Estimate (mg/kg/day)	% aPAD

General US Population	0.005	0.000662	13%	0.001134	23%	0.002275	46%

All Infants

<1 year old	0.005	0.001308	26%	0.001855	37%	0.003031	61%

Children

1-2 years old	0.005	0.001166	23%	0.001732	35%	0.002714	54%

Children

3-5 years old	0.005	0.000908	18%	0.001403	28%	0.002534	51%

Children

6-12 years old	0.005	0.000619	12%	0.000933	19%	0.001602	32%

Youth

13-19 years old	0.005	0.000431	9%	0.000792	16%	0.002009	40%

Adults

20-49 years old	0.005	0.000614	12%	0.001136	23%	0.002636	53%

Adults

50+ years old	0.005	0.000434	9%	0.000793	16%	0.001455	29%

Females

13-49 years old 	0.005	0.000453	9%	0.000831	17%	0.001567	31%

* Values for the population with the highest risk are in bold type.  

5.2.2	Chronic Dietary Exposure/Risk  TC \l3 "5.2.2  Chronic Dietary
Exposure/Risk 

DEEM-FCID™ default factors or, where available, factors from
processing studies) and %CT estimates provided by BEAD.  The estimated
weighted average %CT (where available) for each commodity was used in
the chronic dietary risk assessment; where no further information was
available, and for new uses, 100%CT was assumed.  Chronic anticipated
residues were derived from PDP monitoring data, field trial studies, and
a market basket survey for beef-fat.  

	The chronic drinking water concentration in surface water of 0.130 ppb
was based on the FIRST estimated mean concentration resulting from a
maximum application rate of 0.5 lb ai/A per season to orchards (ground
application).  

	The chronic dietary exposure estimates for food and drinking water are
below HED’s LOC, 100% of the cPAD, for the general US population and
all population subgroups.  Lambda-cyhalothrin chronic dietary exposure
for food and drinking water is 17% of the cPAD for the general US
population, and 50% of the cPAD for children (1-2 yrs old), the most
highly-exposed population subgroup.  

Table 5.2.2	Lambda-Cyhalothrin Chronic Dietary (Food + Drinking Water)
Exposure Analysis.

Population Subgroup*	cPAD (mg/kg/day)	Exposure Estimate (mg/kg/day)	%
cPAD*

General U.S. Population	0.001	0.000173	17%

All Infants <1 year old	0.001	0.000222	22%

Children 1-2 years old	0.001	0.000503	50%

Children 3-5 years old	0.001	0.000367	37%

Children 6-12 years old	0.001	0.000222	22%

Youth 13-19 years old	0.001	0.00013	13%

Adults 20-49 years old	0.001	0.000153	15%

Adults 50+ years old	0.001	0.000125	13%

Females 13-49 years old	0.001	0.000121	12%

* Values for the population with the highest risk are in bold type.  

5.2.3	Cancer Dietary Risk  TC \l3 "5.2.3  Cancer Dietary Risk 

Lambda-cyhalothrin is classified as “not likely to be carcinogenic to
humans.”  As such, while acute and chronic dietary analyses are
required, there is no cancer risk associated with the existing or
proposed uses.  

5.3	Anticipated Residue and Percent Crop Treated (%CT) Information TC
\l2 "5.3 Anticipated Residue and Percent Crop Treated (%CT) Information 

	The registrant supported new uses on barley, oats, rye, wild rice,
buckwheat, cucurbit vegetables (crop group 9), grass forage and hay
(crop group 17), and tuberous and corm vegetables (crop group 1C).  New
field trials were carried out on potatoes, cantaloupes, cucumbers,
summer squash, and a variety of grasses.  A market basket survey was
provided by Syngenta for beef fat.  Adequate PDP monitoring data are
available for the following commodities: apples, broccoli, cauliflower,
lettuce, onions, peaches, pears, sweet bell peppers, soybeans, wheat,
sweet corn, sweet peas, and butter.  Tolerance level values were used
for the following commodities: okra, eggplant, poultry, tree nuts group
(crop group 14) except almonds and pecans, and tuberous and corm
vegetables subgroup (crop group 1C) except potatoes.  

	The screening-level estimates of agricultural uses for
lambda-cyhalothrin were provided by BEAD in the form of a
screening-level usage assessment (SLUA), based on data years 1999-2004
(SLUA; A. Halvorson; 9/17/2006).  The estimated maximum %CT for each
commodity was used in the acute dietary risk assessment, and the
estimated weighted average %CT for each commodity was used in the
chronic dietary risk assessment.  Where no further information was
available, and for new uses, 100%CT was assumed.  

6.0	Residential (Non-Occupational) Exposure/Risk 	Characterization

	Lambda-cyhalothrin uses currently include ornamental gardens, lawns,
landscapes, turf, golf courses, and general insect control (spot
treatments, and crack and crevice treatments) in, around, and on
buildings, structures, and immediate surroundings.  A review of current
labels indicates that all products, except for one aerosol can product,
are limited to use only by certified applicators.  As such, this
assessment addresses the single residential handler scenario for aerosol
can users, and post-application scenarios associated with any use in a
residential environment.  It should be noted that the residential
exposure/risk assessment is based on existing uses for
lambda-cyhalothrin because all potential residential exposures must be
considered in the calculation of aggregate risks.

	A non-occupational (residential) exposure assessment for
lambda-cyhalothrin was completed in 1997 (D238737; Pamela Hurley et al;
11/14/1997).  In the 1997 pyrethroid assessment, owing to the wide
variety of residential uses, it was agreed that flea control
(simultaneous use on pets, lawns, and indoor surfaces) would serve as a
screening-level scenario for all residential uses because it was
anticipated to represent the highest potential for residential exposure.
 However, at that time, lambda-cyhalothrin uses did not include indoor
surfaces or pets, so only exposure estimates pertaining to the lawn uses
were used as appropriate in the 1997 assessment for lambda-cyhalothrin. 

	The 1997 lambda-cyhalothrin assessment served as the basis for the
current risk calculations, which were taken from the most recent
(D284860; Kit Farwell; 8/15/2002) lambda-cyhalothrin human health risk
assessment, and detailed in the associated occupational and residential
exposure (ORE) assessment (D280103; Margarita Collantes; 8/14/2002). 
The only modifications have been adjusting the values from the 1997
assessment for appropriate absorption factors.  This represents a
definitive screening-level approach because since that time the Agency
has engaged in a series of revisions to its Standard Operating
Procedures (SOPs) for Residential Exposure Assessments (the latest on
2/22/2001).  Incorporating the revisions to the SOPs would only refine
the exposure estimates (in all cases MOEs would be higher).  

6.1   Handler tc \l3 "4.5.1   Handler 

	For the residential assessment, existing uses on turf, in gardens, on
golf courses, and for structural pest control were considered, but a
quantitative calculation was only completed for post-application
exposure on treated turf.  The Agency used a conservative
screening-level approach to address the risks associated with the use of
the aerosol can product of lambda-cyhalothrin that can be purchased and
used by homeowners.  

	In this case, a screening-level quantitative calculation was only
completed for post-application exposure on treated turf because this
scenario is expected to have the highest associated exposures of all
residential exposures (see Section 6.2, below, for more details on the
post-application assessment).  In other words, this is a lower tier
approach, and HED believes that the selected post-application assessment
on lawns for children is protective for all residential exposures (even
the aerosol can handler scenario) because the dose levels for children
playing on treated lawns are thought to exceed those expected for all
other scenarios (lawn exposures for children represents the worst case
scenario).  This approach is based on the following conservative
considerations:

(1) HED assumed that children contacted lawns immediately after
application of lawn product and thus there was no dissipation of 
residues from the treated lawn, 

	(2) HED estimated dermal exposure based on a high duration of exposure
on the lawn and an intensity of activity that results in a high degree
of contact with the treated lawn,

		(3) HED assumed that the pesticide was applied at the maximum
application rate,

	(4) post-application oral exposure for children on lawns was also
calculated, which resulted in MOEs that are not of concern (aggregate
MOE = 500); this approach is thought to provide conservative estimates
of exposure and it is not a route of consideration for adult handlers.

As noted in Section 6.2 of this document, all residential
(non-occupational) MOEs calculated using this screening-level approach
were well above the target MOE of 100.

6.2   Post-Application tc \l3 "4.5.2   Postapplication 

	The Agency uses the term “post-application” to describe exposure of
individuals that occurs as a result of being in an environment that has
been previously treated with a pesticide.  Lambda-cyhalothrin can be
used in many areas that could be frequented by the general population,
including residential areas such as lawns.  As a result, individuals can
be exposed by entering these areas if the areas have been previously
treated.  

	The post-application assessment for treatment on lawns is based on a
screening-level approach, in which children’s and adults’ exposures
to treated turf were selected as representing the highest anticipated
exposure scenarios.  In this case, the Agency believes that exposures
associated with contact to treated turf represent the high-end exposure
scenario.  Adults and children of varying ages can potentially be
exposed to dermal and inhalation routes of exposure when they contact
previously treated turf.  Children may also be exposed by incidental
non-dietary ingestion of turf.  Each of these elements was considered in
the calculation of post-application exposure to lambda-cyhalothrin on
turf.  The residential MOEs were aggregated together because, regardless
of the exposure route (dermal, inhalation, or oral), lambda-cyhalothrin
has similar adverse effects (neurotoxicity).  

	All residential (non-occupational) MOEs calculated using this
screening-level approach were well above the Agency target MOE of 100
for the inhalation, dermal, and oral routes (ranging from 700 to
15,000), and therefore do not exceed HED’s level of concern. 
Furthermore, when total MOEs were calculated (all routes added
together), MOEs still were not of concern (MOEs for children were 460 to
500, and the MOE for adults was 3000).  

	A quantitative post-application risk assessment for termiticide use was
not performed for this use.  Since the lambda-cyhalothrin used as a
termiticide (in the form of Impasse® Barrier) is placed under the
foundation (poured concrete) of houses, the potential for dermal
exposure is negligible.  The potential for post-application inhalation
exposure is also expected to be extremely minimal due to the vapor
pressure for lambda-cyhalothrin being very low (1.5 x 10-9 mm Hg).  HED
does not anticipate any significant air concentrations of
lambda-cyhalothrin accumulating.  

Table 6.2	Lambda-Cyhalothrin Residential Risk Calculations tc \l3 "     
     Table 6.   Residential Risk .

Population Subgroup	Inhalation	Dermal	Oral	Total 

MOE 4

	Exposure (mg/kg/day)	MOE 1	Exposure (mg/kg/day)	MOE 2	Exposure
(mg/kg/day)	MOE 3

	Adults	5.46E-06	15,000	2.6E-03	3800	NA 5	NA	3,000

Children [1-6 years]	1.35E-05	5,900	4.96E-03	2000	1.34E-04	750	500

Infants [<1 year]	1.68E-05	4,800	5.12E-03	2000	1.43E-04	700	460

1. Inhalation MOE = inhalation NOAEL (0.08 mg/kg/day) ( inhalation
exposure (mg/kg/day).  

2. Dermal MOE = dermal NOAEL (10 mg/kg/day) ( dermal exposure
(mg/kg/day).  

3. Oral MOE = oral NOAEL (0.1 mg/kg/day) ( oral exposure (mg/kg/day).  

4. Total MOE = 1/[(1/dermal MOE) + (1/inhalation MOE) + (1/oral MOE)].  

5. NA = Not Applicable.  

6.3   Spray Drift tc \l3 "4.5.3   Spraydrift 

	Spray drift is a potential source of exposure for residents living in
close proximity to spraying operations.  This situation is particularly
the case with aerial application.  However, to a lesser extent, spray
drift resulting from the ground application of lambda-cyhalothrin could
also be a potential source of exposure.  The Agency has been working
with the Spray Drift Task Force (a membership of US pesticide
registrants), EPA Regional Offices, State Lead Agencies for pesticide
regulation, and other parties to develop the best spray drift management
practices.  The Agency is now requiring interim mitigation measures for
aerial applications that must be placed on product labels/labeling.  The
Agency has completed its evaluation of the new database submitted by the
Spray Drift Task Force, and is developing a policy on how to
appropriately apply the data and the AgDRIFT computer model to its risk
assessments for pesticides applied by air, orchard airblast, and ground
hydraulic methods.  After the policy is in place, the Agency may impose
further refinements in spray drift management practices to reduce
off-target drift, and risks associated with pesticide application.  

7.0	Aggregate Risk Assessments and Risk Characterization

 TC \l2 "7.1	Acute Aggregate Risk 	Aggregate risk includes exposure from
non-occupational sources, including exposure from drinking water, food,
and residential pathways.  Residential exposure routes include dermal,
inhalation, and incidental oral exposure (hand-to-mouth-type inadvertent
exposure). 

7.1	Acute Aggregate Risk

	For acute aggregate risk assessments, contributions to risk include
food and water exposures.  Residential exposure is not assessed for this
time period.  Therefore, the acute aggregate exposure and risk estimates
are equivalent to the acute dietary exposure and risk estimates
discussed in Section 5.2.1, and do not exceed HED’s LOC.  

7.2	Short- and Intermediate-Term Aggregate Risk tc \l2 "5.2  Short- and
Intermediate-Term Aggregate Risk 

	Aggregate risk for short- and intermediate-term durations of exposure
includes food, drinking water, and residential exposure pathways.  	In
estimating short- and intermediate-term aggregate risk, HED combines the
chronic dietary (food and drinking water) exposure estimate, and the
total non-dietary (residential) exposure estimate for adults and
children.  The chronic dietary exposure estimate reflects average
dietary exposure, and serves as an estimate of dietary exposure that
co-occurs with potential short- and intermediate-term non-dietary
exposure to adults and children.  The residential exposure pathway
includes dermal, inhalation, and incidental oral (hand-to-mouth-type
inadvertent exposure) routes of exposure.  This aggregate risk
assessment incorporates lawn post-application exposure (the scenario
with the highest potential for exposure), and is a day-0 screening-level
assessment.  The resulting aggregate MOEs were greater than the Agency
target MOE of 100 (ranging from 140 to 490), and there were thus no
concerns for aggregate exposure.  

  SEQ CHAPTER \h \r 1 TABLE 7.2	Lambda-Cyhalothrin Short- and
Intermediate-Term Aggregate Risk Calculations.  

Population Subgroup	Dietary Exposure Estimate 1

(mg/kg/day)	Dietary

MOE 2	Inhalation MOE	Dermal MOE	Oral MOE	Aggregate MOE 3

(Dietary and

Residential)

Adults	0.000173	580	15,000	3800	NA 4	490

Children [1-2 years]	0.000503	200	5,900	2000	750	140

Infants [<1 year]	0.000222	450	4,800	2000	700	230

1. Dietary exposure = [food exposure + drinking water exposure].  

2. Dietary MOE = dietary NOAEL (0.1 mg/kg/day) ( dietary exposure
(mg/kg/day).  

3. Aggregate MOE = 1/[(1/dermal MOE) + (1/inhalation MOE) + (1/oral MOE)
+ (1/dietary MOE)].  

4. NA = Not Applicable.  

7.3	Long-Term Aggregate Risk  tc "7.4	Long-Term Aggregate Risk " \l 2 

	The dietary exposure (food and drinking water) pathway is the only
source of exposure to lambda-cyhalothrin that is expected to be of long
term (180 to 365 days).  Therefore, the long-term aggregate exposure and
risk estimates are equivalent to the chronic dietary exposure and risk
estimates discussed in Section 5.2.2, and do not exceed HED’s LOC.  

7.4	Cancer Aggregate Risk

Lambda-cyhalothrin is classified as “not likely to be carcinogenic to
humans.”  Therefore, there is no aggregate cancer risk associated with
the existing or proposed uses.  

8.0	Cumulative Risk Characterization/Assessment

	Lambda-cyhalothrin is a member of the pyrethroid class of pesticides. 
Although all pyrethroids alter nerve function by modifying the normal
biochemistry and physiology of nerve membrane sodium channels, EPA is
not currently following a cumulative risk approach (based on a common
mechanism of toxicity) for the pyrethroids. Although all pyrethroids
interact with sodium channels, there are multiple types of sodium
channels, and it is currently unknown whether the pyrethroids have
similar effects on all channels.  Nor is there a clear understanding of
effects on key downstream neuronal function (nerve excitability), nor do
we understand how these key events interact to produce their compound
specific patterns of neurotoxicity.  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.  When available, the Agency will consider this
research, and make a determination of common mechanism as a basis for
assessing cumulative risk.  Information regarding EPA’s procedures for
cumulating effects from substances found to have a common mechanism can
be found on EPA’s website at   HYPERLINK
"http://www.epa.gov/pesticides/cumulative/" 
http://www.epa.gov/pesticides/cumulative/ .

9.0	Occupational Exposure/Risk Pathway  TC \l1 "9.0	Occupational
Exposure/Risk Pathway 

	The occupational and residential exposure analyses were explicated in
the Nondietary Exposure/Risk Assessment memorandum for
lambda-cyhalothrin (D334896; Mark I. Dow; 12/26/2006).

9.1	Short- and Intermediate-Term Handler Risk  TC \l2 "9.1
Short-/Intermediate-/Long-Term/Cancer (if needed) Handler Risk 

	These products will be applied using groundboom, aerial, or chemigation
equipment.  Based on the use pattern, several major occupational
exposure scenarios were identified for lambda-cyhalothrin: 

(1) mixing/loading liquid formulations for aerial application, 

(2) mixing/loading liquid formulations for chemigation application, 

(3) mixing/loading liquid formulation for groundboom application, 

(4) applying spray with aerial equipment, 

(5) applying spray with groundboom equipment, and 

(6) flagging for aerial spray applications.  

The duration of exposure is expected to be short-duration exposure (1-30
days), and intermediate-term duration exposure (1-6 months) for all
scenarios. Long-term exposures (6 months of continuous exposure) are not
expected to occur.  

	Inhalation and dermal exposures of occupational handlers were
calculated using data from the Pesticide Handlers Exposure Database
(PHED) Version 1.1, as presented in the  PHED Surrogate Exposure Guide
(August 1998).  Defaults established by the HED’s Science Advisory
Council for Exposure (ExpoSAC) were used for acres treated per day and
body weight.  For pesticide handlers, it is HED’s standard practice to
present estimates of dermal exposure for “baseline”, which 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” plus the use of protective gloves, or
other PPE as might be necessary.  The product labels in this case direct
applicators and other handlers to wear PPE consisting of long-sleeved
shirt, long pants, shoes plus socks, chemical resistant gloves (such as
barrier laminate or viton), and protective eyewear.  Aerial applicators
(pilots) are not required to wear protective gloves or protective
eyewear.  

	There are three basic risk mitigation approaches considered appropriate
for controlling occupational exposures.  These include administrative
controls, the use of PPE, and the use of engineering controls. 
Occupational handler exposure assessments were completed by HED using
baseline attire, PPE, and engineering controls.  (Note: administrative
controls available generally involve altering application rates for
handler exposure scenarios.  These are typically not utilized for
completing handler exposure assessments.)  The baseline clothing level
scenario for occupational exposure scenarios is generally an individual
wearing long pants, a long-sleeved shirt, no chemical resistant gloves,
and no respirator.  The first level of mitigation generally applied is
PPE.  As reflected in the calculations included herein, PPE may involve
the use of an additional layer of clothing, chemical-resistant gloves,
and a respirator.  The next level of mitigation considered in the risk
assessment process is the use of appropriate engineering controls which,
by design, attempt to eliminate the possibility of human exposure. 
Examples of commonly-used engineering controls include enclosed tractor
cabs and cockpits, closed mixing/loading/transfer systems, and
water-soluble packets.

	Since the inhalation and dermal endpoints are based on similar adverse
effects (neurotoxicity and decreased body weight gains), dermal and
inhalation exposures are combined.  See Table 9.1 (below) for a summary
of estimated exposures and risks to occupational pesticide handlers.  An
MOE of 100 or more is adequate to protect occupational pesticide
handlers from exposures to lambda-cyhalothrin.   Provided mixer/loaders
wear personal protective equipment (PPE) as directed by the labels, all
MOEs are greater than 100 (ranging from 110 to 1700), except for
mixer/loaders supporting aerial applications to wild rice at a rate of
0.04 lb ai/A, and 1200 A/day.  Their exposure can be mitigated by
reducing the amount of ai handled per day, or by the use of a dust-mist
respirator (as indicated below in Table 9.1).  Baseline MOEs for
applicators and flaggers range from 820 to 4900.  

Table 9.1	Short- and Intermediate-Term Exposure and Risk Assessment For
Lambda-Cyhalothrin Handlers.  

Exposure Scenario (Scenario #)	Crop	Dermal Unit Exposure 

(mg/lb ai)	Inhalation Unit Exposure 

(µg/lb ai)	App. Rate (lb ai/A)	Amount Treated5 (Acres)	Dermal Daily
Dose6 (mg/kg/day)	Inhalation Daily Dose 6 (mg/kg/day)	Dermal MOEs 7

(UF= 100)	Inhalation MOEs 8

(UF = 100)	Total MOE 9

(UF = 100

Baseline 1  (unless indicated)	PPE-G 2	Baseline 3  (unless indicated)
80% R 4

	Baseline 1  (unless indicated)

	PPE-  G 2	Baseline 3  (unless indicated)

	80% R 4	Baseline 1   (unless indicated)	PPE-G 2	Baseline 1 (unless
indicated)	80% R 4	Baseline Dermal + Baseline Inh. (unless indicated)
PPE-G, SL Dermal + Baseline Inh.	PPE-G, SL Dermal + 80% R 4 Inh.

Mixer/Loader Exposure

Mixing/ Loading Liquid Concentrate for Aerial Application (Scenario 1)
Wild rice	2.9	0.023	1.2	0.24	0.04	1,200	2	0.016	0.00082	0.00016	5	630	97
490	4.8	84	280

	Barley, buckwheat, oats, rye	2.9	0.023	1.2	0.24	0.03	1,200	1.5	0.012
0.00062	0.00012	6.7	850	130	NA	6.4	110	NA 10

	Cucurbit vegetables, tuberous and corm vegetables	2.9	0.023	1.2	0.24
0.03	350	0.44	0.0035	0.00018	0.000036	23	2,900	440	NA	22	390	NA

Mixing/ Loading Liquid Concentrate for Chemigation Application (Scenario
2)	Barley, buckwheat, oats, rye, cucurbit vegetables, tuberous and corm
vegetables	2.9	0.023	1.2	0.24	0.03	350	0.44	0.0035	0.00018	0.000036	23
2,900	440	NA	22	390	NA

Mixing/ Loading Liquid Concentrate for Groundboom Application (Scenario
3)	Wild rice	2.9	0.023	1.2	0.24	0.03	200	0.33	0.0026	0.00014	0.000027	30
3,800	580	NA	29	510	NA

	Barley, buckwheat, oats, rye	2.9	0.023	1.2	0.24	0.03	200	0.25	0.002
0.0001	0.000021	40	5,100	780	NA	38	670	NA

Mixing/ Loading Liquid Concentrate for Groundboom Application (Scenario
3)	Cucurbit vegetables, tuberous and corm vegetables	2.9	0.023	1.2	0.24
0.03	80	0.099	0.00079	0.000041	8.2E-06	100	NA	1,900	NA	96	1,700	NA

Applicator Exposure

Applying Sprays via Aerial Equipment

(Scenario 4)	Wild rice	0.005

(eng. control 11)	No Data	0.068

(eng. control)	No Data	0.04	1,200	0.0034 (eng. control)	No Data	0.000047
(eng. control)	No Data	2,900

(eng. control)	No Data	1,700

(eng. control)	No Data	1,100

(eng. control)	NA	NA

	Barley, buckwheat, oats, rye	0.005

(eng. control)	No Data	0.068

(eng. control)	No Data	0.03	1,200	0.0026 (eng. control)	No Data	0.000035
(eng. control)	No Data	3,900

(eng. control)	No Data	2,300

(eng. control)	No Data	1,400

(eng. control)	NA	NA

	Cucurbit vegetables, tuberous and corm vegetables	0.005

(eng. control)	No Data	0.068

(eng. control)	No Data	0.03	350	0.00075 (eng. control)	No Data	0.00001
(eng. control)	No Data	13,000 (eng. control)	No Data	7,800

(eng. control)	No Data	4,900

(eng. control)	NA	NA

Applying Sprays via Groundboom Equipment (Scenario 5)	Wild rice	0.014
0.014	0.74	0.148	0.04	200	0.0016	0.0016	0.000085	0.000017	6,300	NA	950
NA	820	NA	NA

	Barley, buckwheat, oats, rye	0.014	0.014	0.74	0.148	0.03	200	0.0012
0.0012	0.000063	0.000013	8,300	NA	1,300	NA	1,100	NA	NA

	Cucurbit vegetables, tuberous and corm vegetables	0.014	0.014	0.74
0.148	0.03	80	0.00048	0.00048	0.000025	5.1E-06	21,000	NA	3,200	NA	2,700
NA	NA

Flagger Exposure

Flagging for Aerial Spray Applications (Scenario 6)	Wild rice	0.011	No
data	0.35	0.07	0.04	350	0.0022	No data	0.00007	0.000014	4,500	No data
1,100	NA	910	NA	NA

	Barley, buckwheat, oats, rye, cucurbit vegetables, tuberous and corm
vegetables	0.011	No data	0.35	0.07	0.03	350	0.0017	No data	0.000053
0.000011	6,100	No data	1,500	NA	1200	NA	NA

1. Baseline dermal = long-sleeve shirt, long pants, shoes, socks, and no
gloves or respirator (open mixing/loading or open cab or enclosed
cockpit).  

2. PPE-G dermal = baseline dermal plus chemical-resistant gloves (open
mixing/loading).  

3. Baseline inhalation = no respirator (open mixing/loading or open cab
or enclosed cockpit).  

4. 80% R inhalation = quarter-face dust/mist respirator resulting in 80%
reduction (open mixing/loading).  

5. Acres treated values are from EPA estimates of acreage that could be
treated in a single day for each exposure scenario of concern, based on
the application method, and formulation/packaging type.  

6. Daily dose (mg/kg/day) = [unit exposure (mg/lb ai)] x [absorption
(100%)] x [application rate (lb ai/acre)] x [amount treated (acres/day)]
/ [body weight (70 kg)].  

7. Dermal MOE (with UF = 100) = [dermal NOAEL (10 mg/kg/day)] / [daily
dermal dose].  

8. Inhalation MOE (with UF = 100) = [inhalation NOAEL (0.08 mg/kg/day)]
/ [daily inhalation dose].  

9. Total MOE = 1/ [1/dermal MOE] + [1/inhalation MOE].  

10. NA = Not Applicable (because MOEs do not exceed HED’s LOC at the
next lowest mitigation level).  

11. Engineering control data for enclosed cockpits used for pilots.  

	9.2	Short- and Intermediate-Term Post-Application Risk  TC \l2 "9.2
Short-/Intermediate-/Long-Term/Cancer (if needed) Postapplication Risk 

	It is possible for agricultural workers to have post-application
exposures to pesticide residues during the course of typical
agricultural activities.  HED, in conjunction with the Agricultural
Re-entry Task Force (ARTF), has identified a number of post-application
agricultural activities that may occur, and which may result in
post-application exposures to pesticide residues.  HED has also
identified Transfer Coefficients (TCs), having units of cm²/hr,
relative to the various activities, which express the amount of foliar
contact over time during each of the activities identified.  For the
proposed new uses, the highest TC (1,500 cm²/hr) occurs during
"scouting" by crop advisors in flax, leafy green vegetables, legume
vegetables, and safflower.  Therefore, as a screening-level assessment,
HED herein uses a TC of 1,500 cm²/hr.  

	The TCs used in this assessment are from an interim TC Standard
Operating Procedure (SOP) developed by HED’s ExpoSAC, using
proprietary data from the ARTF database (SOP #3.1).  It is the intended
by HED’s ExpoSAC that this SOP will be periodically updated to
incorporate additional information about agricultural practices in
crops, and new data on TCs.  Much of this information will originate
from exposure studies currently being conducted by the ARTF, from
further analysis of studies already submitted to the Agency, and from
studies in the published scientific literature.  

	Lacking compound specific dislodgeable foliar residue (DFR) data, HED
assumes 20% of the application rate is available as DFR on day zero
after application.  This is adapted from the ExpoSAC SOP #003 of
5/7/1998 (revised 8/7/2000).  

Daily dermal doset = DFRt (µg/cm2) x 1E-3 mg/µg x TC (cm2/hr) x DA x
ET (hrs)

						  BW (kg)

Where: 		t	=	number of days after application day (days), 

	DFRt	=	dislodgeable foliar residue on day “t” (µg/cm2), 

	TC	=	transfer coefficient (cm2/hr), 

	DA	=	dermal absorption factor (unitless), 

	ET	=	exposure time (hr/day), and

	BW	=	body weight (kg).  

DFRt (µg/cm2) = AR (lb ai/acre) x F x (1-D)t x 4.54E8 µg/lb x 24.7E-9
acre/cm2

Where: 		AR	=	application rate (lb ai/acre), 

             	F	=	fraction of ai retained on foliage or 20% (unitless),
and

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

See Table 9.2 (below) for a summary of post-application exposures and
risks.  An MOE of 100 or more is adequate to protect persons from
post-application exposures to lambda-cyhalothrin, as described in the
proposed use patterns.  Because the estimated MOEs are all greater than
100 (ranging from 520 to 13,000), post-application exposures arising
from the proposed uses do not exceed HED’s LOC.  



Table 9.2	Exposure and Risk Assessment for Occupational Post-Application
1 Activities.  

Proposed Crops	Use Rate

(lb ai/A)	Policy Crop Group Category	Exposure Potential	Transfer
Coefficient 2 (cm2/hour)	Activities

	DFR 3

(µg/cm2)	Daily Dose 4 (mg/kg/day)	MOE 5

Wild Rice	0.04	Field & Row Crops: Low to Medium	Low	100	Scouting	0.090
0.0010	9,700

	Medium	1,500	Scouting	0.090	0.015	650

Barley, Oats, Rye, Buckwheat	0.03	Field & Row Crops: Low to Medium	Low
100	Scouting	0.067	0.00077	13,000

	Medium	1,500	Scouting	0.067	0.012	870

Cucurbit Vegetables

	0.03	Vegetable: Cucurbit	Low	500	Irrigating, scouting, hand-weeding for
immature crops	0.067	0.0038	2600

	Medium	1,500	Irrigating, scouting, hand-weeding	0.067	0.012	870

	High	2,500	Hand-harvesting, hand-pruning, thinning	0.067	0.019	520

Tuberous and Corm Vegetables

[Potato]	0.03	Vegetable: Root & Tuber	Low

	300	Irrigating, scouting, hand-weeding for immature crops, thinning
0.067	0.0023	4,300

	Medium	1,500	Irrigation, scouting	0.067	0.012	870

Tuberous and Corm Vegetables

[All Others]	0.03	Vegetable: Root & Tuber	Low	300	Irrigating, scouting,
hand-weeding for immature crops, thinning	0.067	0.0023	4,300

	Medium	1,500	Irrigation, scouting	0.067	0.012	870

	High	2,500	Hand-harvesting	0.067	0.019	520

1. Post-application day is taken to be Day 0 for all activities (day
after treatment represents approximately 12 hours following application,
when sprays have dried).  

2. Transfer coefficient from ExpoSAC Policy Memo #003.1 "Agricultural
Transfer Coefficients" of 8/7/2000.  

3. DFR = [application rate (lb ai/acre)] x [fraction of active
ingredient that remains on the foliage when sprays have dried] x [4.54E8
µg/lb] x [24.7E-9 acre/cm2].  

4. Daily dose = [DFR (µg/cm2)] x [TC (cm2/hr)] x [conversion factor (1
mg/1,000 µg)] x [exposure time (8 hrs/day)] / [body weight (70 kg)].  

5. MOE = [NOAEL (10 mg/kg/day)] / [daily dose (mg/kg/day)].  

10.0	Data Needs and Label Recommendations  TC \l1 "10.0	Data Needs and
Label Recommendations 

	10.1	Toxicology  TC \l2 "10.1	Toxicology 			

	None

	10.2	Residue Chemistry  TC \l2 "10.2	Residue Chemistry 

	No major deficiencies were noted in the subject petitions that would
preclude the establishment of permanent tolerances for
lambda-cyhalothrin on the proposed commodities.  Only minor deficiencies
were noted pertaining to the proposed label directions and recommended
tolerance levels (listed below).  HED  SEQ CHAPTER \h \r 1  recommends
in favor of establishing permanent tolerances for lambda-cyhalothrin
residues at the levels listed in Table 1.0.  

	(1) Use directions for grasses should be clarified to specify that the
restriction of 0.03 lb ai/A per cutting includes pastures and rangeland
in addition to grasses grown for seed.  A minimum re-treatment interval
(RTI) of 30 days should be specified for pastures and rangeland which
are not cut between applications.  In addition, the PHI for forage
should be changed to 0 days, as PHIs for forage are not practical for
rangeland applications.

	(2) A tolerance was not proposed in rye bran.  Based on the available
wheat residue data, a separate tolerance is required at 0.2 ppm in rye,
bran.

	(3) Based on the calculated TDBs for livestock, and the available
livestock residue studies, the current tolerance for lambda-cyhalothrin
in milk fat is too low.  An increased tolerance should be proposed in
milk fat at 10 ppm (reflecting 0.4 ppm in whole milk).  The data also
indicate that the current tolerances in hog commodities could be lowered
to 0.2 ppm in fat, 0.01 ppm in meat, and 0.02 ppm in meat byproducts.

	10.3	Occupational and Residential Exposure  TC \l2 "10.3	Occupational
and Residential Exposure 

	The labels for Warrior® Insecticide (EPA Registration #100-1112) and
Karate® Insecticide (EPA Registration #100-1097) should state that
mixer/loaders supporting aerial applications to wild rice at a rate of
0.04 lb ai/A, and treating 1200 acres (or more) per day, are required to
use a dust-mist respirator.  

References:  TC \l1 "References: 

Carcinogenicity Determination

	GAMMA CYHALOTHRIN - 1ST Report of the Hazard Identification Assessment
Review Committee.; TXR #0052388; Jess Rowland; 3/1/2004.  

Dietary Exposure Memorandum

	Lambda-cyhalothrin:  Acute and Chronic Dietary (Food and Drinking
Water) Exposure and Risk Assessment for Section 3 Uses on Barley, Oat,
Rye, Wild Rice, Buckwheat, Pistachio, Cucurbit Vegetables (crop group
9), Grass Forage & Hay (crop group 17), and Tuberous & Corm vegetables
(crop group 1-C).; D324223; Anant Parmar; 3/12/07

Drinking Water Memorandum

	Tier I Estimated Environmental Concentrations of Lambda-Cyhalothrin and
It’s Transformation Product of Concern XV for the Use in the Human
Health Risk Assessment.; D324222, D330149; Jose Melendez; 10/26/2006.  

Occupational and Residential Exposure Memorandum

	LAMBDA-CYHALOTHRIN - Human, Nondietary Exposure/Risk Assessment for the
Proposed New Uses of Lambda-Cyhalothrin on Barley, Buckwheat, Oat, Rye,
Wild Rice, Cucurbit and Tuberous and Corm Vegetables.; D334896; Mark I.
Dow; 12/26/2006.  

	Lambda Cyhalothrin: Occupational and Residential Risk Assessment for
the use on Cereal Grains, Corn, Soybeans, Sunflowers, Sorghum, Lettuce,
Cole Crops, Onions, Garlic, Legumes, Fruiting Vegetables, Stone and Pome
Fruits, Tree Nuts, Sugar Cane, Cotton, Rice, Tobacco, Canola for Seed
and as a Termiticide.; D280103; Margarita Collantes; 8/14/2002.  

Residue Chemistry Data Review Memorandum

	Lambda-Cyhalothrin.  Petitions Requesting Permanent Tolerances
(Associated with Section 3 Registration) for Food/Feed Use of the
Insecticide on Cucurbit Vegetables (Group 9), Tuberous and Corm
Vegetables (Subgroup 1C), Grass Forage, Fodder, and Hay (Group 17),
Barley, Buckwheat, Oat, Rye, Wild Rice, and Pistachios.  Summary of
Analytical Chemistry and Residue Data.  Petition Numbers 5F6994, 3E6593,
and 6E7077; D313315, D324219, D330542; William T. Drew; 12/27/2006.  

Risk Assessment Document

	PP#0F6092.  Request for the Use of Lambda-Cyhalothrin in/on Canola,
Pome Fruits, Stone Fruits, Tree Nuts, Almond Hulls, and Tobacco. 
PP#9F4875.  Request for the Use of Lambda-Cyhalothrin on Imported
Avocados; Cereal Grains (except Rice); Fruiting Vegetables (except
Cucurbits); Peanut Hay; Peas and Beans, Dried and Succulent Shelled, and
Edible Podded; Sorghum Forage and Fodder; and Sugarcane.  New Use: 
IMPASSE Barrier Termiticide End-use Product.; D284860; Kit Farwell;
8/15/2002.  

	Risk Assessment for Extension of Tolerances for Synthetic Pyrethroids;
D238737; Pamela Hurley, John Whalan, Jeff Evans, George Herndon, Steve
Knizner; 11/14/1997.  

AppendiX A:  Toxicology Assessment

A.1	Toxicology Data Requirements TC \l2 "A.1  Toxicology Data
Requirements  

	The requirements (40 CFR §158.340) for food-use of lambda-cyhalothrin
are in Table 1, below.  Use of the new guideline numbers does not imply
that the new (1998) guideline protocols were used.

Table A.1	Toxicology Data Requirements.

Test 

	Technical

	Required	Satisfied

870.1100    Acute Oral Toxicity	

870.1200    Acute Dermal Toxicity	

870.1300    Acute Inhalation Toxicity	

870.2400    Primary Eye Irritation	

870.2500    Primary Dermal Irritation	

870.2600    Dermal Sensitization		yes

yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

yes

870.3100    Oral Subchronic (rodent)	

870.3150    Oral Subchronic (non-rodent)	

870.3200    21-Day Dermal	

870.3250    90-Day Dermal	

870.3465    90-Day Inhalation		yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

870.3700a  Developmental Toxicity (rodent)	

870.3700b  Developmental Toxicity (non-rodent)	

870.3800    Reproduction		yes

yes

yes	yes

yes

yes

870.4100a  Chronic Toxicity (rodent)	

870.4100b  Chronic Toxicity (non-rodent)	

870.4200a  Carcinogenicity (rat)	

870.4200b  Carcinogenicity (mouse)	

870.4300    Chronic/carcinogenicity		no

yes

no

no

yes	-

yes

-

-

yes

870.5100    Mutagenicity—Gene Mutation - bacterial	

870.5300    Mutagenicity—Gene Mutation - mammalian	

870.5xxx    Mutagenicity—Structural Chromosomal Aberrations	

870.5xxx    Mutagenicity—Other Genotoxic Effects		yes

yes

yes

yes	yes

yes

yes

yes

870.6100a  Acute Delayed Neurotoxicity (hen)	

870.6100b  90-Day Neurotoxicity (hen)	

870.6200a  Acute Neurotoxicity Screening Battery (rat)	

870.6200b  90-Day Neurotoxicity Screening Battery (rat)	

870.6300    Developmental Neurotoxicity		no

no

yes

no

yes	-

-

yes

-

no1

870.7485    General Metabolism	

870.7600    Dermal Penetration		yes

no	yes

yes

Special Studies for Ocular Effects

Acute Oral (rat)	

Subchronic Oral (rat)	

Six-month Oral (dog)		no	-

1  Although classified unacceptable, a repeat DNT study is not required.
 See section 3.3.6 for more details.A.2	Toxicity Profiles TC \l2 "A.2 
Toxicity Profiles 

Table A.2.1a	Acute Toxicity Profile – Lambda-cyhalothrin.

Guideline Number	Study Type	MRI

Number(s)	Results	Toxicity Category

870.1100	Acute oral - rat	00151582	LD50 = 79 mg/kg (♂)

         = 56 mg/kg (♀)	II

870.1200	Acute dermal - rat	00151583	LD50 = 632 mg/kg (♂)

         = 696 mg/kg (♀)	II

870.1300	Acute inhalation - rat	40994701	LC50 = 0.065 mg/L (♂& ♀)	II

870.2400	Acute eye irritation 	00151586	Mild irritant.	II

870.2500	Acute dermal irritation - rabbit	00151584	Not an irritant.	IV

870.2600	Skin sensitization - guinea pig	00151585	Not a sensitizer in
the guinea pig.	N/A

Table A.2.1b	Acute Toxicity Profile –Cyhalothrin 

Guideline Number	Study Type	MRID

243 mg/kg (♂)

         = 144 mg/kg (♀)	II

870.1200	Acute dermal - rat

Acute dermal - rabbit	00154865

00154865	LD50 > 1000 mg/kg                                              
                                                    (♂& ♀)

LD50 > 2 g/kg  (♂& ♀)	II

III

870.1300	Acute inhalation - rat	00150847	LC50 = 0.173 mg/L (♂)

LC50 = 0.183 mg/L (♀)	II

870.2400	Acute eye irritation 	00154868	Moderate irritant without
irrigation; mild irritant with irrigation.	III

870.2500	Acute dermal irritation - rat

Acute dermal irritation - rabbit	00154867

00154867	Mild dermal irritant

Not an irritant.	IV

IV

870.2600	Skin sensitization - guinea pig	00154866	Not a sensitizer in
the guinea pig.	N/A

Table A.2.2	Subchronic, Chronic and Other Toxicity Profile.

Guideline Number	Study Type	MRID Number/Year/ Classification /Doses
Results

NA*	28-Day oral toxicity – rat

(cyhalothrin)	00153029

1984 Acceptable non-guideline

0, 2, 10, 25, 50, 75 mg/kg/day	NOAEL: 2 mg/kg/day

LOAEL: 10 mg/kg/day (clinical signs of neurotoxicity). At higher doses,
decreases in body weight gain and food consumption, and changes in organ
weights.

NA	28-Day oral toxicity – rat

(cyhalothrin)	00154806

1984 Acceptable non-guideline

0, 0.1, 0.5, 1.0, 2.0, or 25.0 mg/kg/day	NOAEL: 1.0 mg/kg/day

LOAEL: 2.0 mg/kg/day (decreases in mean body weight gain in females).

NA	28-Day oral toxicity – mouse

(cyhalothrin)	43241901

1981 Acceptable non-guideline

0, 0.65, 3.30, 13.5, 64.2, 309 mg/kg/day (males)

0, 0.80, 4.17, 15.2, 77.9, 294 mg/kg/day (females)	NOAEL: 64.2/77.9
mg/kg/day

LOAEL: 309/294 mg/kg/day (mortality, clinical signs of toxicity,
decreases in body weight gain and food consumption, changes in
hematology and organ weights, minimal centrilobular hepatocyte
enlargement).

870.3100	90-Day oral toxicity – rat

(cyhalothrin)	00154805

1981 Acceptable

0, 0.5, 2.5, 12.5 mg/kg/day	NOAEL: 2.5 mg/kg/day

LOAEL: 12.5 mg/kg/day (decreased body weight gain in males).

870.3100	90-Day oral toxicity – rat

(lambda-cyhalothrin)	00153028

1985 Acceptable

0, 0.5, 2.5, 12.5 mg/kg/day	NOAEL: 2.5 mg/kg/day

LOAEL: 12.5 mg/kg/day (reduced body weight gain and food consumption in
both sexes, and food efficiency in females).

870.3150	26-Week feeding study – dog

(cyhalothrin)	00154795

1981 Acceptable

0, 1.0, 2.5, 10.0 mg/kg/day	NOAEL: 1.0 mg/kg/day

LOAEL: 2.5 mg/kg/day (increase in liquid feces. At 10.0 mg/kg/day,
clinical signs of neurotoxicity)

870.3200	21-Day dermal toxicity – rat

(lambda-cyhalothrin)	44333802

1989 Acceptable

0, 1, 10 mg/kg/day for 6 hours/day for 21 consecutive days; 2-3
applications at 100 mg/kg/day, reduced to 50 mg/kg/day for 21
consecutive days.	NOAEL: 10 mg/kg/day

LOAEL: 50 mg/kg/day (clinical signs of toxicity, decreased body weight
and body weight gain).

870.3200	21-Day dermal toxicity – rabbit

(cyhalothrin)	00154869

1982 Acceptable

0, 10, 100, 1000 mg/kg/day for 6 hours/day, 5 days/week, for total of 15
applications.	NOAEL: 100 mg/kg/day

LOAEL: 1000 mg/kg/day (significant weight loss).

870.3465	21-Day inhalation toxicity – rat 

(lambda-cyhalothrin)	41387702

1990 Acceptable non-guideline

0, 0.3, 3.3, 16.7 g/L (approximately 0, 0.08, 0.90, 4.5 mg/kg/day)
NOAEL: 0.08 mg/kg/day

LOAEL: 0.90 mg/kg/day (clinical signs of neurotoxicity, decreased body
weight gains, increased incidence of punctate foci in cornea, slight
reductions in cholesterol in females, slight changes in selected
urinalysis parameters).

870.3700a	Pre-natal developmental – rat

(cyhalothrin)	00154800

1981 Acceptable

0, 5, 10, 15 mg/kg/day

	Maternal NOAEL: 10 mg/kg/day

Maternal LOAEL: 15 mg/kg/day (uncoordinated limbs, reduced body weight
gain and food consumption).

Developmental NOAEL: 15 mg/kg/day (HDT)

Developmental LOAEL: > 15 mg/kg/day

870.3700b	Pre-natal developmental – rabbit

(cyhalothrin)	00154801

1981 Acceptable

0, 3, 10, 30 mg/kg/day

	Maternal NOAEL: 10 mg/kg/day

Maternal LOAEL: 30 mg/kg/day (reduced body weight gain and food
consumption).

Developmental NOAEL: 30 mg/kg/day (HDT)

Developmental LOAEL: > 30 mg/kg/day

870.3800	Reproduction and fertility effects – rat 

(cyhalothrin)	00154802

1984 Acceptable

0, 0.5, 1.5, 5.0 mg/kg/day	Parental/Offspring NOAEL: 1.5 mg/kg/day

Parental/Offspring LOAEL: 5.0 mg/kg/day (decreased parental body weight
and body weight gain during premating and gestation periods and reduced
pup weight and weight gain during lactation).

Reproductive NOAEL: 5.0 mg/kg/day (HDT).

870.4100b	Chronic toxicity – dog

(lambda-cyhalothrin)	40027902

1986 Acceptable

0, 0.1, 0.5, 3.5 mg/kg/day	NOAEL: 0.1 mg/kg/day

LOAEL: 0.5 mg/kg/day (clinical signs of neurotoxicity).

870.4200	Carcinogenicity –

mouse

(cyhalothrin)	00150842

1984 Acceptable

0, 3, 15, 75 mg/kg/day	NOAEL: 15 mg/kg/day

LOAEL: 75 mg/kg/day (increased incidence of piloerection, hunched
posture; decreased body weight gain in males).  Not oncogenic under
conditions of study. HDT was inadequate; however, a new study not
required at this time.

870.4300	Carcinogenicity – rat

(cyhalothrin)	00154803

1984 Acceptable

0, 0.5, 2.5, 12.5 mg/kg/day	NOAEL: 2.5 mg/kg/day

LOAEL: 12.5 mg/kg/day (decreases in mean body weight).  Not oncogenic
under conditions of study.

870.6200a	Acute neurotoxicity screening battery – rat

(lambda-cyhalothrin)	44861510

1999 Acceptable

0, 2.5, 10, 35 mg/kg	NOAEL: 10 mg/kg

LOAEL: 35 mg/kg (clinical observations indicative of neurotoxicity, and
changes in FOB parameters).

870.6300	Developmental neurotoxicity

(lambda-cyhalothrin)	46449102 

2004 Unacceptable

0, 25, 60, 150 ppm

0, 2, 4, 20 mg/kg/day	Maternal NOAEL: 4 mg/kg/day

Maternal LOAEL:  10 mg/kg/day (decreased body weight, body weight gain,
and food consumption).

Although Offspring neurotoxicity was seen with a LOAEL/NOAEL of 10/4, a
definitive LOAEL/NOAEL cannot be determined due to many data
insufficiencies.  (officially – for effects observed in the acceptable
parameters of the DNT study see Section 3.3.2).

870.7485	Metabolism and pharmacokinetics – rat	00151116, 00150852,
00150852,

00150852, 00153036, 00153037

1981, 1984, 1985 Acceptable when combined together.	In the rat,
approximately 55% of the oral dose is absorbed.  It is extensively
metabolized when absorbed. After subcutaneous administration, the
urinary/fecal excretion ratio is 2.5:1.0. Over 50% of the dose remained
in the carcass 7 days after a subcutaneous dose. Metabolism includes
cleavage of the ester to cyclopropylcarboxylic acid and a phenoxybenzyl
derivative. The distribution patterns and excretion rates in the
multiple oral dose studies are similar to the single oral dose studies.
There is accumulation of unchanged compound in the fat upon chronic
administration. Otherwise, cyhalothrin is rapidly metabolized and
excreted. Cyclopropyl carboxylic acid, 3 phenoxybenzoic acid,
glucuronide conjugated 3-4'- hydroxyphenoxy benzoic acid and a sulfate
conjugate were identified in the urine. Cyhalothrin is taken up slowly
by the fat and released slowly. It is rapidly released by blood,
kidneys, liver. The rate of metabolism of both enantiomer pairs are
likely identical (i.e. PP321 & PP563). The absorption, distribution,
metabolism and excretion patterns of PP321 and cyhalothrin following a
single dose of 1 mg/kg in the male rat appear to be identical.

870.7485	Metabolism and pharmacokinetics – dog	00150843, 00150852

1984 Acceptable when combined together.	In the dog, absorption of the
C14 benzyl label was 80% and absorption of the C14 cyclopropyl label was
48%. The metabolite patterns were different, indicating extensive
cleavage of the ester bond. Seven metabolites in urine were identified
for the benzyl label, and 12 metabolites for the isopropyl label. In the
feces, a large proportion of the radioactivity was due to unchanged
compound. Excretion in urine and feces was rapid (nearly all in 48
hours).

870.7600	Dermal penetration	44990402

1991 Acceptable

0.979, 0.099, 0.001 and 0.0008 mg/cm2 for 0.5, 1, 2, 4, 10, and 24
hours.	Absorption ranged from 3.46 to 15.89%.

870.7600	Dermal penetration	44333801

1984 Acceptable non-guideline

Dermal studies: 1.25 mg/50 cm2 dermal and 20 mg/800 cm2.  Dermal dose
washed quantitatively after 8 hours.  

Oral study: 5 mg	Mild paresthesia of varying degrees was observed
following dermal dosing. The minimal oral absorption was estimated to be
from 50.35 to 56.71%. The minimal dermal absorption was estimated to be
from 0.115 to 0.122%. The estimated dermal absorption value of 1% was
determined by rounding these values up to the nearest whole number. No
metabolites were found near the limit of detection in plasma from the
oral dose study. Blood was not analyzed from the dermal study.

* NA = Not Applicable.

A.3	Executive Summaries TC \l2 "A.3  Executive Summaries 

A.3.1	Subchronic Toxicity

	Non-Guideline	28-Day Oral Toxicity – Rat

	In a 28-day feeding study (MRID #00153029) in male and female SPF
AlpklAP Wistar-derived rats (16/sex/dose), cyhalothrin (PP563, 89.0%)
and PP654, an isomer mixture similar to cyhalothrin which contains both
cis and trans isomers (cyhalothrin contains only the cis isomer), were
fed in the diet at levels of 0, 20, 100, 250, 500, or 750 ppm (estimated
to be approximately 0, 2, 10, 25, 50, or 75mg/kg/day cyhalothrin, based
on use of very young animals; clinical signs upon which the NOAEL is
based started on day 3), and 500 or 750 ppm (approximately 50 or 75
mg/kg/day PP564). The animals were examined once daily for clinical
signs of toxicity.  Body weights, food consumption, hematological and
clinical chemistry parameters, ophthalmological examinations, urinalysis
parameters, organ weights, and macroscopic examinations were conducted
and/or measured.  For cyhalothrin, livers from up to 8/sex/group were
fixed in formol corrosive for microscopic examination.  The remaining
livers plus selected tissues (including sciatic nerves, brain, and
spinal cord) from 8/sex/group were fixed in formol saline for
microscopic examination.  The livers from the PP564 animals were
included in this group.  In addition, the left sciatic, and posterior
tibial nerves from 4 male and 4 female controls and high dose
cyhalothrin groups were fixed in formol glutaraldehyde for microscopic
examination.  With all remaining animals, only abnormal appearing
tissues were examined microscopically.  Livers from 6/sex/group were
taken for measurement of hepatic aminopyrine N-demethylase (APDM)
activity and electron microscopy.  Smooth endoplasmic reticulum (SER)
was quantified.

	At 20 ppm and above, a dose-related increase in APDM activity was
observed in males.  At 20 ppm, the increase was only slight (26.00
versus 22.30 tmoles HCHO/hr/g liver).  Slight hypersensitivity to touch
was observed in 4 females starting on day 2; however, this had a
variable dose-response.  At 100 ppm and above, a dose-related increase
in APDM activity was observed in females.  At 100 ppm, the increase was
only slight (14.21 versus 12.03 imoles HCHO/hr/g liver).  Clinical signs
included high stepping gait in 1 male on day 3, and slight
hypersensitivity to touch (2 males on days 2-4, 3 females on day 2) and
sound (2 males on day 23; again, variable dose-response).  At 250 ppm, 1
male and 2 females had high-stepping gait starting on day 2, 2 males had
ataxia starting on day 3, 3 males had hunched posture starting on day 4,
and 5 females had increased activity starting on day 4.  In addition,
significant decreases in mean body weight gain and food consumption
(both sexes), increases in mean relative liver weights, and decreases in
mean heart weights were observed at 250 ppm and above.  At 500 ppm and
above, high stepping gait, ataxia, hunched posture, tail erect,
increased activity, lack of grooming, and salivation were the major
dose-related clinical signs with cyhalothrin.  Reductions in serum
plasma triglyceride levels, and protein excretion levels in urine were
observed in males.  At higher dose levels, the reductions in serum
plasma triglyceride levels were observed in both sexes.  With PP564,
high stepping gait, ataxia, hunched posture, and increased activity in
females were observed, but to a lesser extent.  Reductions in serum
plasma triglyceride levels were also observed.  At 750 ppm an additional
clinical sign of loss of stability was observed in 1 male and 3 females.
 With PP564, similar clinical signs were observed as with cyhalothrin,
but to a lesser extent.  Loss of stability was not observed.

	The NOAEL for cyhalothrin is 20 ppm (2 mg/kg/day), and the LOAEL is 100
ppm (10 mg/kg/day), based on clinical signs of neurotoxicity.  At higher
dose levels, decreases in body weight gain and food consumption, and
changes in organ weights were also observed.  The NOAEL for PP564 is
less than 500 ppm (50 mg/kg/day).

	This study is classified as acceptable (non-guideline), and does not
satisfy any particular guideline requirement.

	Non-Guideline	28-Day Oral Toxicity – Rat

	In an oral toxicity study (MRID #00154806), SPF Wistar (Alderly Park
strain) rats (8/sex/dose) were dosed with cyhalothrin (89.2% ai) in the
diet at 0, 1, 5, 10, 20, or 250 ppm (approximately 0, 0.1, 0.5, 1.0,
2.0, or 25.0 mg/kg/day using a factor of 10 for young animals) for 28
days (MRID #00154806).  Animals were examined for clinical signs of
toxicity, and the following parameters were measured: body weights,
liver weights, and hepatic aminopyrene-N-demethylase (APDM) activity. 
In addition, the livers were subjected to electron microscopic
examinations.

	No effects were observed at 1, 5, and 10 ppm.  At 20 ppm and above, a
reduction in mean body weight gain was observed in females (p < 0.05;
22% less than the control value for weeks 0-4); however, body weight was
not affected.  At 250 ppm, a reduction in mean body weight gain was
observed in males (13% less than the control value for weeks 0-4).  In
addition, increases and/or proliferation in APDM (14-40%), and smooth
endoplasmic reticulum (SER) was observed in both sexes.  Relative liver
weights were increased in males (7%); however, absolute liver weights
were not affected.  

	The NOAEL is 10 ppm (1.0 mg/kg/day in females) and 20 ppm (2.0
mg/kg/day in males), and the LOAEL is 20 ppm (2.0 mg/kg/day in females),
and 250 ppm (25.0 mg/kg/day in males) based on decreases in mean body
weight gain in females at 20 ppm and above, and in males at 250 ppm, and
increases and/or proliferation in APDM and SER in both sexes at 250 ppm.

	This study is classified as acceptable (non-guideline), and does not
satisfy any particular guideline requirement.

	Non-Guideline	28-Day Oral Toxicity – Mouse

	Cyhalothrin (technical, no purity available) was tested in a 4-week
oral feeding study (MRID #43241901) in CD-l mice as a range-finding
study for the carcinogenicity study.  Twelve mice/sex/dose level were
tested at 0, 5, 25, 100, 500, or 2000 ppm in the diet (0, 0.65, 3.30,
13.5, 64.2, or 309 mg/kg/day for males, and 0, 0.80, 4.17, 15.2, 77.9,
or 294 mg/kg/day for females).

	At 2000 ppm, piloerection, abnormal gait (walking on toes), hunched
posture, increase in respiration rate, and emaciated appearance were
observed.  Six males and 3 females died during the study.  Both males
and females had a significant decrease in body weight gain over the
treatment period when compared to controls (-l g versus 5 g in controls
for males, p < 0.001, and 0 g versus 3 g in controls for females, p <
0.001) .  A decrease in food consumption was observed in both sexes
during the first week (60.8% of controls for males, and 62.5% of
controls for females), and in females for the remainder of the study
(82% of controls, p < 0.05).  Males had a slightly lower mean total
white blood cell count (6.8%).  The differential white cell count
revealed lower lymphocyte counts (58.7%), and higher neutrophil counts
(62.5% above controls), p < 0.01, for all hematological values in males
at this dose level.  Significantly higher APDM activity was observed in
both sexes (61.9% above controls for males, and 77.8% above controls for
females).  Slight increases in kidney weights (28.8% over controls for
males, p < 0.001), and liver weights (17% over controls for males, p <
0.05, and 3.1 % over controls for females) were observed.  In females,
the differences were not statistically significant.  Slightly lower
heart weights were also observed in females (87.7% of controls, p <
0.05).  Minimal centrilobular hepatocyte enlargement was observed in 2
of 12 females.

	At 500 ppm, piloerection was observed in several mice, several males
had low white blood cell counts (not statistically significant) as well
as marginally lower lymphocyte numbers (80%).  Significantly higher APDM
activity was observed in females (26.2% over controls).  Slightly higher
kidney weights were observed in males (13.5% over controls, p < 0.02),
and slightly lower heart weights were observed in females (93.0%, p <
0.05).

	At 100 ppm, piloerection was also observed in several mice.  One female
had an emaciated appearance.  Marginally lower lymphocyte numbers were
noted for males (79% of controls).  Significantly higher APOM activity
was observed in females (24.8% over controls).  Slightly higher kidney
weights were observed in males (13.0% over controls, p < 0.01), and
marginally lower heart weights were observed in females (87.7%, p <
0.01).

	The NOAEL is 500 ppm, and the LOAEL is 2000 ppm, based on mortality,
clinical signs of toxicity, decreases in body weight gain and food
consumption, changes in hematology and organ weights, and minimal
centrilobular hepatocyte enlargement.  The minimal effects observed at
500 and 100 ppm are not considered to be toxicologically significant.

	This study is not a guideline requirement, and thus does not satisfy
any guideline requirements.

	870.3100	90-Day Oral Toxicity – Rat

	In a 90-day feeding study (MRID #00154805) in male and female SPF
Alderley Park Wistar-derived rats, technical cyhalothrin (92.2% w/w
pyrethroids of which 96.8% was cyhalothrin) was fed in the diet at
levels of 0, 10, 50, or 250 ppm (estimated to be 0, 0.5, 2.5, or 12.5
mg/kg/day).  Twenty rats/sex/dose level were assigned.  The animals were
examined for clinical signs of toxicity.  Body weights, food
consumption, hematological and clinical chemistry parameters, urinalysis
parameters, organ weights, and macroscopic and microscopic observations
were recorded.  In addition, hepatic aminopyrine-N-demethylase activity
was measured.

	No significant treatment-related effects were observed at 0.5 or 2.5
mg/kg/day.  At 12.5 mg/kg/day, mean body weight (10-16% less than
controls) and body weight gain (13% less than controls) were
significantly reduced in males (p < 0.01).  Mean body weight was also
significantly reduced in females at this level, but only during the
first week (p < 0.05).  This decrease in body weight gain was
accompanied by a decrease in food consumption; however, there was no
effect on food utilization at any dose level.  Dietary palatability, and
food refusal with concurrent reduced body weight may be a factor.  A
dose-related reduction in mean red cell volume values was observed in
both sexes at all dose levels at week 13; however, a downward trend was
also observed in the controls.  Hemoglobin, hematocrit, and red blood
cell counts were elevated, indicating an opposite trend or an
accommodation.  Small isolated differences in selected clinical
chemistry parameters; however they were not dose related, or recurring
on the time basis, nor were they supported by microscopic findings. 
Hence, neither the hematological nor the clinical chemistry changes are
considered compound-related.  Hepatic aminopyrine-N-demethylase activity
was increased in both sexes at 12.5 mg/kg/day, and in the males at 2.5
mg/kg/day.  This is a reversible, compensatory change usually considered
to be adaptive rather than an adverse toxicological response.

	The NOAEL is 2.5 mg/kg/day, and the LOAEL is 12.5 mg/kg/day, based on
decreased body weight gain in males.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a subchronic oral study (§82-1) in the rat.

	870.3100	90-Day Oral Toxicity – Rat

	In a 90-day feeding study (MRID #00153028) in male and female SPF
Alk/AP Wistar-derived rats (20/sex/dose), lambda-cyhalothrin (96.5%) was
fed in the diet at levels of 0, 10, 50, or 250 ppm (0, 0.5, 2.5, or 12.5
mg/kg/day).  The animals were examined once daily for clinical signs of
toxicity.  Body weights, food consumption, hematological and clinical
chemistry parameters, urinalysis parameters, organ weights, and
macroscopic and microscopic observations were recorded.

	No treatment-related effects were observed at 0.5 mg/kg/day.  At 2.5
mg/kg/day, increased mean liver weight, and increased activity of
hepatic aminopyrine-N-demethylase (APDM) were observed in males.  This
is considered to be an adaptive response.  At 12.5 mg/kg/day,
significantly reduced body weight gain and food consumption were
observed in both sexes, as well as increased mean liver weight, and
increased APDM activity in both sexes.  There was also a slight but
statistically significant reduction in food efficiency in females at
this dose level.

	The NOAEL is 2.5 mg/kg/day, and the LOAEL is 12.5 mg/kg/day, based on
reduction in body weight gain and food consumption in both sexes, and
food efficiency in females.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a subchronic feeding study (§82-1) in the
rat.

	870.3150	180-Day Oral Toxicity – Dog

	In a 26-week oral study in male and female beagle dogs (MRID
#00154795), six dogs/sex/dose level received technical cyhalothrin
(pyrethroid content = 92.2% w/w, of which 96.8% is cyhalothrin) via oral
administration in gelatin capsules.  The test chemical had been
dissolved in corn oil prior to placement in the capsules.  The following
dose levels were tested: 0, 1.0, 2.5, or 10.0 mg/kg/day.  The following
parameters were measured and/or recorded: daily clinical observations,
body weights, food consumption, ophthalmological examinations,
neurological examinations, clinical biochemistry, urinalysis, gross
necropsy, and microscopic examinations.

	At 1.0 mg/kg/day, a slight increase in the passage of liquid feces was
observed in both sexes combined (7% over the control group).  This was
the only effect observed at this dose level and it was not considered to
be of toxicological significance.

	At 2.5 mg/kg/day, liquid feces were observed at an increased rate (26%
over the control group, both sexes combined).  No other effects were
observed.  At this dose level, due to the greater number of animals
affected, and the greater increase in incidence, the liquid feces was
considered to be a toxicological effect.

	At 10.0 mg/kg/day, liquid feces were observed at an increased rate over
the control group (both sexes).  In addition, the following effects were
observed: increase in water consumption during first 4 weeks, vomiting,
usually within a few hours following dosing, and occasional unsteadiness
and/or muscular trembling.  During week 2, head shaking, and excessive
salivation were observed in several dogs.  These signs were observed
only occasionally during the subsequent test weeks.  One male had more
severe signs.  During the second week, excessive salivation, and head
shaking were noted.  On day 14, 3 hours post-dosing, the dog was in a
state of collapse, stiff-limbed, and frothing at the mouth with the
presence of vomitus.  It recovered in 6 hours.  In the following weeks
with this dog, there were periods of head shaking, salivation, loss of
appetite, episodes of collapse, muscular spasms, marked incoordination,
vocalization, and one episode of convulsive behavior (week 8).

	The NOAEL is 1.0 mg/kg/day, and the LOAEL is 2.5 mg/kg/day, based on an
increase in incidence of liquid feces.  At 10.0mg/kg/day, liquid feces,
and clinical signs of neurotoxicity (occasional unsteadiness and/or
muscular trembling, head shaking, excessive salivation, frothing at the
mouth, stiff-limbed, episodes of collapse, muscular spasms, marked
incoordination, vocalization, and one episode of convulsive behavior in
week 8) were observed.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a subchronic oral study (§82-1) in the dog.

	870.3200	21-Day Dermal Toxicity – Rat

	In a repeated-dose dermal toxicity study (MRID #44333802),
lambda-cyhalothrin (96.6% ai) was applied to the clipped skin of five
albino rats/sex/dose at dose levels of 1 or 10 mg/kg/day for 6 hours/day
for 21 consecutive days.  Five rats/sex were similarly treated with two
or three applications at 100 mg/kg/day, reduced to 50 mg/kg/day for 21
consecutive days.

	Two males which were found dead after three applications of 100
mg/kg/day had reduced, moderately atrophied seminal vesicles, and
slightly atrophied spleens.  Clinical signs indicative of neurotoxicity
were observed in the 100/50 mg/kg/day treatment groups.  Males exhibited
reduced splay reflex, downward curvature of the spine, splayed gait,
bizarre behavior, pinched-in sides, dehydration, reduced stability, and
thin appearance.  Females exhibited an increased incidence of tiptoe
gait, upward curvature of the spine, an increased incidence in signs of
urinary incontinence, urinary incontinence, chromodacryorrhea, and
reduced splay reflex.  The clinical signs commenced on day 2 of dosing. 
Body weight gains for males were significantly reduced throughout the
study; the final gain was 58% lower than the control gain.  The final
mean body weight was 19% lower than the mean control value.  Body weight
gains for females were somewhat reduced only during the first half of
the study.  Food consumption was somewhat reduced for males throughout
the study.  No dermal irritation was observed at 100/50 mg/kg/day in
either sex.  No signs of clinical toxicity or dermal irritation in the
10 or 1 mg/kg/day treatment groups were considered to be
treatment-related.  No treatment-related differences in hematology or
clinical blood chemistry parameters, organ weights, or histopathology
were observed between the treatment and control groups.  No neoplastic
tissue was observed.  

	The LOAEL is 50 mg/kg/day for both sexes, based on clinical signs of
toxicity and decreased body weight and body weight gain.  The NOAEL is
10 mg/kg/day for males and females.

	This dermal toxicity study is classified acceptable (§82-2), and
satisfies the guideline requirement for a repeated-dose dermal toxicity
study.

	870-3200	21-Day Dermal Toxicity – Rabbit

	In a repeated-dose dermal toxicity study (MRIDs #00154869, #41062701),
cyhalothrin (90.2% ai) was applied to the clipped skin of 10 New Zealand
White rabbits/sex/dose at dose levels of 10, 100, or 1000 mg/kg/day for
6 hours/day, 5 days/week, for a total of 15 applications.  One half the
animals had abraded skin, and the other half had non-abraded skin.  The
control group consisted of 14/sex treated with 2 ml/kg/day of
polyethylene glycol 300 (PEG 300).  The rabbits were observed daily for
clinical signs of toxicity, skin irritation, and individual body
weights.  Food consumption, hematology, and clinical chemistry
measurements were also taken.  Gross necropsy, and microscopic
examinations were conducted.

	There was no difference in clinical signs of toxicity between the
abraded and non-abraded animals.  No treatment-related clinical signs of
toxicity were observed at any dose level.  Some of the clinical signs
which are similar to those normally observed with pyrethroids were due
to physical injury.  In non-abraded animals, with the exception of low
dose males, all rabbits lost weight, including the controls. 
Statistical significance in weight loss was achieved at 1000 mg/kg/day
in males.  This dose group lost 10% of their body weight.  The controls
lost <1% of their body weight.  In females, the controls lost 5% of
their body weight, and the 1000 mg/kg/day group lost 11% of their body
weight.  Food consumption in the high-dose group varied.  At times it
was less and at times it was more.  There was no consistent pattern. 
Slight to severe irritation was observed in all test groups, including
controls.  In non-abraded animals, there appeared to be an increase in
the number of animals affected by irritation starting at 100 mg/kg/day. 

	The NOAEL for dermal irritation is 10 mg/kg/day, and the LOAEL for
dermal irritation is 100 mg/kg/day.  The systemic NOAEL is 100 mg/kg/day
for both sexes.  The systemic LOAEL is 1000 mg/kg/day for both sexes,
based on significant weight loss when compared to the control groups.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a repeated dose dermal study (§82-2) in the
rabbit.

	870.3465	21-Day Inhalation – Rat

	In a 21-day inhalation study (MRID #41387702), 10/sex/dose SPF
Alpk:APfSD Wistar-derived albino rats were exposed nose-only 6
hours/day, 5 days/week, for 21 days to lambda-cyhalothrin (81.5% pure)
at 0, 0.3, 3.3, or 16.7 µg/L (estimated to be approximately 0, 0.08,
0.90, or 4.5 mg/kg/day).  The MMAD ranged from 1.47 to 1.91 µm, and the
GSD ranged from 1.02 to 2.24 µm.

	No treatment-related effects were observed at 0.3 µg/L.  At 3.3 µg/L,
the following was observed: salivation, lachrymation, paw flicking
(males only), tail erections, and splayed gait (males only); decreased
body weight (94-95%, p < 0.05) and body weight gain (53-65%, p < 0.01)
of control values; an increased incidence of punctate foci on the comea;
slight reductions in cholesterol levels in females (p < 0.05); decreased
urine volume in males, slightly raised specific gravity of the urine in
both sexes, and reductions in urinary protein levels in males.  At 16.7
µg/L, the following was observed: salivation, lachrymation, auditory
hypoaesthesia, paw flicking, tail erection, splayed gait, decreased
activity, reduced foot withdrawal (males only), head flicking, reduced
righting reflex, shaking (males only), sides pinched in, reduced splay
reflex, decreased visual placing response, absent puma reflex (females
only), ungroomed appearance (females only), tiptoe gait (males only),
respiratory noise; decreased body weight (85-88%, p < 0.01) and body
weight gain (<3-14%, p < 0.01 of control values); decreased food
consumption (46-91% ♂, 56-87% ♀ of controls); changes in selected
clinical chemistry values, particularly in females; decreased urine
volume, increased urine specific gravity, and decreased urinary protein.
 There was also a slight increase in the incidence of alveolitis in high
dose females.

	The NOAEL is 0.3 µg/L (0.08 mg/kg/day), and the LOAEL is 3.3 µg/L
(0.90 mg/kg/day), based on clinical signs of neurotoxicity, decreased
body weight gains, increased incidence of punctate foci in the cornea,
slight reductions in cholesterol in females, and slight changes in
selected urinalysis parameters.

	This inhalation toxicity study is classified as acceptable
(non-guideline), and does not satisfy any particular guideline
requirement.  The study is too short for a guideline study, and
individual animal data were not provided.

A.3.2	Pre-Natal Developmental Toxicity

	870.3700a	Pre-Natal Developmental Toxicity Study - Rat

	In a developmental toxicity study (MRID #00154800), technical
cyhalothrin (89.25%) was administered by gavage to 24 SPF CD rats/dose
at the following dose levels: 0, 5, 10, or 15 mg/kg/day during the
gestation period (days 6 through 15).  Maize oil was used as the
vehicle.

	No treatment-related effects were observed in the dams at dose levels
of either 5 or 10 mg/kg/day.  At 15 mg/kg/day, uncoordinated movements
in the limbs were observed in two dams, one from gestation days 8-10,
and the other from gestation days 12-18.  In addition, a statistically
significant reduction in mean body weight gain was observed, both during
dosing (70% of control value), and throughout the entire gestation
period (88% of control value).  The adjusted mean gestational body
weight gain was 67% of the control value.  Mean body weight gain was
comparable to the control group during the post-dosing period.  Food
consumption was also significantly reduced during gestation days 6-12
(77-91%).  No treatment-related developmental effects were observed at
any dose level.

	The maternal NOAEL is 10 mg/kg/day, and the maternal LOAEL is 15
mg/kg/day, based on uncoordinated movements in the limbs starting on
gestation day 8, and reduced body weight gain and food consumption
during the dosing period.  

	The developmental NOAEL is greater than 15 mg/kg/day (HDT).  No
developmental effects were observed.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a study (§83-3) in the rat.

	870.3700b	Pre-Natal Developmental Toxicity Study - Rabbit

	In a developmental toxicity study (MRID #00154801), technical
cyhalothrin (89.25%) was administered by gavage to 18-22 New Zealand
White rabbits/dose at the following dose levels: 0, 3, 10, or 30
mg/kg/day, during the gestation period (days 6 through 18).  Corn oil
was used as the vehicle.

	No treatment-related effects were observed in the does at dose levels
of either 3 or 10 mg/kg/day.  At 30 mg/kg/day, a statistically
significant reduction in mean body weight gain was observed from
gestation days 6-9, when compared to the control group.  Mean body
weight gain was 48% of the control value during the dosing period.  It
was 122% of the control value during the post-dosing period, and 88% of
the control value for the entire gestation period (days 0-28).  The %
adjusted mean gestational body weight gain was 59% of the control value.
 Food consumption was also significantly reduced during gestation days
6-15 (71-77%).  No treatment-related developmental effects were observed
at any dose level.

	The maternal NOAEL is 10 mg/kg/day, and the maternal LOAEL is 30
mg/kg/day, based on decreased body weight gain during the dosing period.
 

	The developmental NOAEL is 30 mg/kg/day (HDT).  No effects were
observed.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a study (§83-3) in the rabbit.

A.3.3	Reproductive Toxicity

	870.3800	Reproduction and Fertility Effects - Rat

	In the three-generation reproduction study (MRID #00154802), groups of
5 male and 30 female SPF Wistar-derived rats/dose were fed technical
cyhalothrin (89.2%) in the diet at 0, 10, 30, or 100 ppm (approximately
0, 0.5, 1.5, or 5.0 mg/kg/day).  The pre-mating periods were 12 weeks
for the F0 animals, and 11 weeks for the F1 and F2 animals.

	Parental toxicity was observed as decreased mean body weight and body
weight gain during the pre-mating and gestation periods at 5.0
mg/kg/day.  There were no other treatment-related effects.  Offspring
toxicity was observed as reduced mean pup weight and pup weight gains
during lactation, again at 5.0 mg/kg/day.  No other treatment-related
effects were observed.

	The parental/offspring systemic NOAELs are 1.5 mg/kg/day, and the
parental/offspring systemic LOAELs are 5.0 mg/kg/day, based on decreased
mean body weight and body weight gain during the pre-mating and
gestation periods, and reduced mean pup weight and pup weight gain
during lactation.  The reproductive NOAEL is 5.0 mg/kg/day (highest dose
tested).

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a multi-generation reproduction study
(§83-4) in the rat.

A.3.4	Chronic Toxicity

	870.4100a	Chronic Toxicity – Rat

	See Section A.3.5, 870.4300 (Chronic/Carcinogenicity – Rat).

	870.4100b	Chronic Toxicity - Dog

	In a chronic toxicity study (MRID #40027902), beagle dogs (6/sex/dose)
were given oral administration of gelatin capsules containing
lambda-cyhalothrin (96.5%) at 0, 0.1, 0.5, or 3.5 mg/kg/day, 7
days/week, for 12 months.  The test chemical had been dissolved in corn
oil prior to placement in the capsules.  The following parameters were
measured and/or recorded: daily clinical observations, body weights,
food consumption, ophthalmological examinations, clinical biochemistry,
urinalysis, gross necropsy, and microscopic examinations.

	No treatment-related toxicity was observed at 0.1 mg/kg/day.  At 0.5
mg/kg/day, 1 male and 1 female dog exhibited gait abnormalities, with
the effects seen in the male 7-hours post dosing during week 2, and
again 2 days later immediately after dosing, and in the female 4 times
during week 9.  Convulsions were seen in two other dogs (both males);
the convulsions appeared to be precipitated by the stress of handling or
noise.  At 3.5 mg/kg/day, the principal neurological clinical signs
following dosing were ataxia (all dogs, apparent from day 2 in 2 dogs,
observed 3-7 hours post-dosing), muscle tremors and convulsions,
occasional subdued behavior, worn or bleeding claws, regurgitation of
food during first 2 weeks, and fluid feces in all dogs.  Treatment had
no effect on body weights, hematology, clinical chemistry, urinalysis,
gross or histopathology.  

	The NOAEL is 0.1 mg/kg/day, and the LOAEL is 0.5 mg/kg/day, based on
clinical signs of neurotoxicity.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a study (§83-1) in the dog.

	A.3.5	Carcinogenicity

	870.4200	Carcinogenicity (Feeding) - Mouse

	Groups of 52/sex CD-1 mice (MRID #00150842) were fed technical
cyhalothrin (89.25%) in the diet at 0, 20, 100, or 500 ppm
(approximately 0, 3, 15, or 75mg/kg/day) for 104 weeks.  In addition, 4
satellite groups of 12 mice/sex were fed the same dietary
concentrations, and terminated at week 52.

	No treatment-related effects were observed at 3 mg/kg/day.  At 15
mg/kg/day, an increased incidence of piloerection was observed in males
between weeks 13 and 52.  This was the only observed effect at 15
mg/kg/day.  After week 52, the incidences of piloerection were
comparable to the control group.  At 75 mg/kg/day, an increased
incidence of piloerection was observed in both sexes, and hunched
posture was observed up to 78 weeks, particularly in males.  After 78
weeks, the incidences of hunched posture were similar between treated
and control groups.  Decreased body weight gain was also observed in
males during the first 13 weeks (54% of the control group).  Mean body
weight was 10 percent lower than the controls at week 13.  For the
entire two years, body weight gain in males was 77% of the control
value.

	On 2/12/1993 and 6/16/1994, the HED RfD/Peer Review Committee concluded
that cyhalothrin was not tested at a sufficiently high dose level for an
adequate carcinogenicity study in mice.  Following the decision by the
Committee, Toxicology Branch 1 (TB-1) determined that there was not
enough toxicological concern to warrant a requirement for a new
carcinogenicity study in the mouse at that time.  However, there was
sufficient concern about the adequacy of dosing in this study that
additional testing may be required in the future.  This decision was
based on data from the mouse chronic feeding/oncogenicity study, the
28-day range finding study in the mouse, and the results from mouse and
rat carcinogenicity studies conducted with similar pyrethroids.

	The 2/12/1993 RfD/Peer Review Committee also had concern over the
increased incidences of mammary tumors in females (1/52, 0/52, 7/52,
6/52).  On 6/16/1994, the HED RfD/Peer Review Committee evaluated the
study in more detail, and noted that the concurrent control value was
low when compared to historical control values.  Because of the
equivocal nature of the findings, and in view of the inadequacy of the
dose levels tested, the Committee concluded that the chemical should be
classified as a Group B chemical.

	The LOAEL for systemic chronic toxicity is 75 mg/kg/day, based on an
increased incidence of piloerection and hunched posture, and decreased
mean body weight gain in males, and the NOAEL is 15 mg/kg/day.

	Under the conditions of the study, cyhalothrin is not considered to be
oncogenic in mice. However, there is concern over the adequacy of the
dosing in the study, and additional testing may be required in the
future, particularly if new uses result in significantly higher residues
in human foods, and/or there is significantly higher occupational (or
future residential) exposure due to changes in parameters such as the
method of application.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a chronic feeding/oncogenicity study (§83-5)
in the mouse.

	870.4300	Carcinogenicity Study - Rat

	In a chronic feeding/carcinogenicity study in rats (MRID #00154803),
groups of 52 male and 52 female AlpklAP strain rats were fed 0, 10, 50,
or 250 ppm (0, 0.5, 2.5, or 12.5 mg/kg/day) cyhalothrin (89.2%) in the
diet for 2 years.  Additional groups of 20 males and females were added
to each dose level as extras, and for the purpose of interim sacrifice.

	No treatment-related effects were observed at either 0.5 or 2.5
mg/kg/day.  At 12.5 mg/kg/day, decreased mean body weight (11% for
males, and 8.5% for females) and food consumption in both sexes were
observed.  There were no neurological effects noted.  

	The LOAEL for chronic toxicity in rats is 12.5 mg/kg/day, and the NOAEL
is 2.5 mg/kg/day, based on decreases in mean body weight.  

	Under the conditions of the study, there was no indication of oncogenic
activity for this chemical.

	This study is classified as acceptable (guideline), and satisfies the
guideline requirements for a chronic feeding/oncogenicity study (§83-5)
in the rat.

A.3.6	Neurotoxicity

	870.6200	Acute Neurotoxicity Screening Battery

	In this acute oral neurotoxicity study (MRID #44861510),
lambda-cyhalothrin in corn oil was administered in a single dose by
gavage to 10 Alpk:APSD rats/sex/dose at doses of 2.5, 10, or 35 mg/kg. 
Functional observation battery (FOB) and motor activity measurements
were performed during week 1 (acclimation), day 1 (at 7 hours
post-dosing), day 8, and day 15.  Five animals/sex/group were sacrificed
by perfusion fixation, and subjected to neuropathological examination.  

	No animals died during the study.  No treatment-related changes in body
weight, body weight gain; food consumption, motor activity, or gross
pathology were observed.  No differences relative to concurrent controls
were observed in brain widths or dimensions.  No treatment- related
findings were observed in the 2.5 mg/kg group.

	At 10 mg/kg, the following clinical signs were observed (# incidences):

(1) increased breathing rate (males 5, females 5), 

(2) slight piloerection (males 1, females 3), 

(3) signs of urinary incontinence (1, females only), 

(4) upward spine curvature (2, females only), and 

(5) urinary incontinence (3, males only).  

None of the clinical signs were observed in the concurrent controls. 
The following observations were noted during the day 1 FOB: slight signs
of salivation (1, males only); slight signs of urinary incontinence (1,
females only); and slight urinary incontinence (2, males only).  None of
the clinical observations were observed in the concurrent controls. 
These findings are not considered to be adverse, and very few animals
were observed to have effects.

	At 35 mg/kg, clinical signs were similar in nature to those observed in
the FOB, and consisted of the following (# incidences): 

(1) slightly decreased activity (males 7, females 3), 

(2) ataxia (males 5, females 5), 

(3) increased breathing rate (males l6, females 13), 

(4) piloerection (males 27, females 20), 

(5) reduced stability (males 2, females 4), 

(6) sides pinched in (males 3, females 4), 

(7) signs of salivation (males 6, females 11), 

(8) signs of urinary incontinence (males 2, females5), 

(9) stains around mouth (males 4, females 3), 

(10) tiptoe gait (males 5, females 3), 

(11) un-groomed appearance (males 3, females 2), 

(12) upward curvature of the spine (males 25, females 20), and 

(13) urinary incontinence (males 5, females 7).  

	The following findings were noted during the FOB on day 1: 

(1) slightly decreased activity (2, males only), 

(2) slight ataxia (males-3, females 2), 

(3) extreme ataxia (2, females only), 

(4) lacrimation (males- 1, females-2), 

(5) slight piloerection (males-6, females-7), 

(6) moderately reduced stability (1, females only), 

(7) extremely reduced stability.  (1, females only), 

(8) moderate salivation (1, males only), 

(9) extreme salivation (males-i, females-i), 

(10) slight signs of salivation (males-6, females-4), 

(11) moderate signs of salivation (1, females, only), 

(12) sides pinched in (1, females only), 

(13) slight tip toe gait (males-4, females-I), 

(14) upward curvature of the spine (males-8, females-8), 

(15) tremors (1, females only), 

(16) slight signs of urinary incontinence (males-l, females- 1), and 

(17) slight urinary incontinence (thales-3,females-6).  

Landing foot-splay values were decreased on day 1 (121%, p < 0.05), and
decreased (p < 0.05 or 0.01) hindlimb grip strength was observed on days
1, 8, and 15 (119%, 131%, 132%) in males.  Females displayed increased
time to tail-flick on day 1 (171%, p < 0.05).  In addition, one female
was found to have minimal pigmentation of the olfactory bulb, but no
other associated pathology.  Minimal fiber degeneration of the sciatic
nerve was observed in another female.

	The LOAEL for this study is 35 mg/kg, based on clinical observations
indicative of neurotoxicity, and changes in FOB parameters.  The NOAEL
for this study is 10 mg/kg.

	This acute oral neurotoxicity study is classified as acceptable
(§81-81aI), and satisfies the guideline requirements for an acute
neurotoxicity screening battery in rats.

870.6300	Developmental Neurotoxicity Test

		In a developmental neurotoxicity study (MRID 46449102),
Lambda-cyhalothrin (87.7% a.i., batch #P31 (BX E624)) was administered
in the diet to 30 mated female Alpk:APfSD (Wistar-derived) rats/group at
nominal concentrations of 0, 25, 60 or 150 ppm from gestation day (GD) 7
through day 23 post partum.  Average doses to the animals, adjusted for
purity, were 1.8, 4.3, and 10.0 mg/kg/day, respectively, during
gestation and 4.0, 9.4, and 23.1 mg/kg/day, respectively, during
lactation.  Dietary concentrations were based on the results of a
preliminary developmental neurotoxicity study (MRID 46449101).  A
Functional Observational Battery (FOB) was performed on all dams on GDs
10 and 17 and on lactation days (LDs) 2 and 9.  On postnatal day (PND)
5, litters were culled to yield four males and four females (as closely
as possible).  Offspring, representing at least 20 litters/dose, were
allocated for detailed clinical observations and assessment of motor
activity, auditory startle response, and learning and memory.  Neural
tissues were collected from selected offspring (10/sex/dose,
representing 20 litters) on PND 12 and at study termination (PND 63). 
Pup body weights were recorded, and the age of sexual maturation was
assessed (vaginal opening in females and preputial separation in males).

		In the dams, no treatment-related effects were observed on mortality,
reproductive performance, or gross pathology.  Treatment-related
maternal toxicity included decreased (p (0.05 or 0.01) body weights,
body weight gains, and food consumption during gestation and lactation
at the high dose (150 ppm).  At this dose, absolute maternal body
weights were consistently decreased by 8-9%, compared to controls,
throughout the treatment period and persisting through LD 15.

		The maternal LOAEL is 150 ppm (10.0 mg/kg/day during gestation), based
on decreased body weight, body weight gain, and food consumption.  The
maternal NOAEL is 60 ppm (4.3 mg/kg/day during gestation).

		In offspring, no treatment-related effects were observed on clinical
signs, developmental landmarks, the functional observational battery,
brain weights, macroscopic neuropathology, or microscopic
neuropathology.

		A significant decrease (6%; p (0.01) in the number of pups surviving
from PNDs 1-5 (pre-cull), compared to controls, was observed at 150 ppm.
 Survival was unaffected by treatment with 25 or 60 ppm.  

	Pup body weights and body weight gains were consistently lower (p
(0.01) in both sexes at 150 ppm from PNDs 5-29, with a maximum decrease
in body weight of 12%, compared to controls.  

The motor activity data were considered inadequate for assessment.  Of
the control animals, habituation was only observed in PND 22 females. 
Although habituation might not be expected in PND 14 animals (e.g., the
pups’ eyes may still be closed, and their brains may not yet be
developed enough so that habituation is possible), failure for all but
one of the other control groups to properly habituate indicates a lack
of an adequate assessment of this parameter in this study.

No treatment-related effects were seen in auditory startle response in
PND 23 males or females or in PND 61 males.  In PND 61 females,
decreases in maximum auditory startle response were seen in all treated
groups for repetitions 11-50, compared to controls.  The magnitude of
the decreases were similar across all doses (i.e., the dose-response was
flat), and the decreases reached statistical significance at the low and
high doses (p ( 0.01).  However, while the behavior of the treated PND
61 females is different from the controls, it is not possible to
determine whether this difference is due to treatment or if it is
because the PND 61 control females failed to exhibit the expected
habituation.  Failure for these animals to properly habituate indicates
an inadequate assessment of auditory startle in the PND 61 females
tested in this study. Habituation was evident in PND 61 males.

		High-dose females showed differences in water maze performance on PNDs
21 and 24.  Learning was affected on PND 21, in that mean time to
completion was longer, and the proportion of successful trials was lower
than controls for cut-off times ranging from 3-10 seconds.  When the
cut-off was expressed in relation to the time taken to complete the
straight channel, the group mean success rate at 1.5 the straight
channel swim time on PND 21 was decreased, although this change was not
statistically significant.  When memory was tested on PND 24, high-dose
females showed only a slight increase in the mean time per trial,
compared to controls, but the proportion of successful trials for
cut-off times from 3-9 seconds were still decreased.  Treatment-related
effects on learning and memory were not seen in PND 59/62 females or in
males at either time point.	

At the high dose, statistically significant decreases were seen in the
molecular layer of the preculminate fissure of the cerebellum (13%), the
overall width of the hippocampus (7%), and the level 3 dorsal cortex 1
(7%) of PND 12 males.  In PND 12 females, statistically significant
decreases were observed at 150 ppm in the level 5 dorsal cortex (6%),
the level 4 dorsal cortex (7%), the thalamus width (4%), and the
thalamus/cortex width (4%).  At PND 63, a statistically significant
decrease (7%) was observed in the level 3 piriform cortex of high-dose
males.  Data for these measurements at the mid and low doses should be
provided to confirm whether or not the effects are limited to the high
dose.

	The offspring NOAEL/LOAEL cannot be determined due to the lack of brain
morphometrics at the low and mid doses, as well as inadequate
assessments of auditory startle response in PND 61 females and of motor
activity.

This study is classified Unacceptable/Guideline and does not satisfy the
guideline requirement for a developmental neurotoxicity study in rats
(OPPTS 870.6300, §83-6).  The motor activity data were considered
inadequate for assessment.  It was not possible to determine whether the
difference in auditory startle response between treated and control PND
61 females was due to treatment because the PND 61 control females
failed to exhibit the expected habituation.  Finally, morphometric data
at the mid and low doses were not available for the measurements in
which effects were observed at the high dose.

A.4	References (in MRID order)

00153029	Tinston, D.; Banham, P.; Chart, I.; et al. (1984) PP563: 28-day
Feeding Study in Rats: Summary Report: CTL Study No. PR0337: Report No.
CTL/P/1056. Unpublished study prepared by Imperial Chemical Industries,
PLC. 79 p.

00153035	Colley, J.; Dawe, S.; Heywood, R.; et al. (1984) Cyhalothrin:
Potential

		Tumorigenic and Toxic Effects in Prolonged Dietary Administration to
Mice: Addendum to Final Report: No. CTL/C/1260: No. ICI/395/83668.
Unpublished study prepared by Imperial Chemical Industries, PLC. 70 p.

00150842	Colley, J.; Dawe, S.; Heywood, R.; et al. (1984) Cyhalothrin:
Potential

		Tumorigenic and Toxic Effects in Prolonged Dietary Administration to
Mice: Final Report Vol. 3.: Rept No. ICI/395. Unpublished study prepared
by Huntingdon Research Centre, 553 p. 

00153028	Hart, D.; Banham, P.; Chart, I.; et al. (1985) PP321: 90 Day
Feeding Study in Rats: CTL Study No. PR0584: Report No. CTL/P/I 045.
Unpublished study prepared by Imperial Chemical Industries, PLC. 76 p. 

00154795	Chesterman, H.; Heywood, R.; Allen, T.; et al. (1981)
Cyhalothrin: Oral Toxicity Study in Beagle Dogs (Final Report: Repeated
Daily Dosing for 26 Weeks): Report No. ICI/326/8 162. Unpublished study
prepared by Huntingdon Research Centre. 210 p. 

00154800	Killick, M. (1981) Cyhalothrin: Oral (Gavage) Teratology Study
in the Rat: CTL Study Number RR 0170: Report No. 2661-72/208.
Unpublished study prepared by Hazleton Laboratories Europe Ltd. 171 p. 

00154801	Killick, M. (1981) Cyhalothrin: Oral (Gavage) Teratology Study
in the New Zealand White Rabbit: CTL Study Number RB 0169: Report No.
2700-72/211.  Unpublished study prepared by Hazleton Laboratories Europe
Ltd. 173 p.  

00154802	Milburn, G.; Banham, P.; Godley, M, et al. (1984) Cyhalothrin:
Three-Generation Reproduction Study in the Rat: Report No: CTL/P/906.
Unpublished study prepared by Imperial Chemical Industries PLC. 1916 p. 

00154803	Pigott, G.; Chart, I.; Godley, M., et al. (1984) Cyhalothrin:
Two Year Feeding Study in Rats: Report No: CTLJP/980: hand Individual
Animal Data Supplement: Report No: CTL/P/980So. Unpublished study
prepared by Imperial Chemical Industries. 2687 p. 

00154804	Colley, I.; Dawe, S.; Heywood, R.; et al. (1984) Cyhalothrin:
Potential

		Tumorigenic and Toxic Effects in Prolonged Dietary Administration to
Mice: (Final Report): Report No. ICI 395/83668. Unpublished study
prepared by Huntingdon Research Centre. 849 p.

00154805	Lindsay, S.; Chart, I.; Godley, M.; et al. (1981) Cyhalothrin:
90-Day Feeding Study in Rats: Report No: CTL/P/629. Unpublished study
prepared by Imperial Chemical Industries PLC. 539 p. 

00154806	Moyes, A.; Godley, M.; Hall, M., et al. (1984) Cyhalothrin:
28-Day Feeding Study in the Rat (Second Study): Summary Report: Report
No: CTL/P/1013. Unpublished study prepared by Imperial Chemical
Industries PLC. 33 p. 

00154869	Henderson, C.; Jackson, S. (1982) Cyhalothrin: Subacute Dermal
Toxicity Study in Rabbits: Report No. CTL/P/680. Unpublished study
prepared by Imperial Chemical Industries PLC. 64 p. 

	

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萏֠萑褐葞֠葠褐ᜀ40387701, Cyhalothrin: Subacute Dermal Toxicity
in Rabbits: Proj. ID CTL/P/680. Unpublished study prepared by ICI
Central Toxicology Laboratory. 5 p. 

41387702	Hext, P. (1990) Lambda-Cyhalothrin Production Material: 21-day
Sub-acute Inhalation Toxicity Study in the Rat: Lab Project Number:
CTL/P/2772: MROI 35. Unpublished study prepared by ICI Central
Toxicology Laboratory. 102 p.

43227901	Athis, J. (1994) Comments on February 1993 EPA RID/Peer Review
of Lambda-Cyhalothrin 1-Year Dog Study. Unpublished study prepared by
ICI Central Toxicology Laboratory. 14 p.

43232101	Stonard, M. (1991) First Amendment to PP321: 1-Year Oral Dosing
Study in Dogs: Lab Project Number: CTL/P/l 316. Unpublished study
prepared by ICI Central Toxicology Laboratory. 96 p.

43241901	Colley, J.C.; Dawe, S; et al. (1981) Cyhalothrin: 4-Week Dose
Range Finding Study in Mice.  CTL/C/1039 Unpublished study prepared by
Huntingdon Research Center, Huntingdon, Cambridgeshire, England

43241902	Athis, J. (1994) Comments on February 1993 EPA Rfd/Peer Review
of

		Cyhalothrin Oncogenicity/Chronic Feeding Study in Mice (Accession
Number 073214-073216). Unpublished study prepared by Zeneca
Agrochemicals. 12 p.

43241903	Athis, J.; Pigott. G. (1994) Additional Comments on February
1993 EPA

		RfD/Peer Review of Lambda-Cyhalothrin 1-Year Dog Study (MRID
#40027902). Unpublished study prepared by Zeneca Agrochemicals. 7 p. 

43245301	Athis, J. (1994) Additional Comments on February 1993 EPA
Rfd/Peer Review of Lambda-Cyhalothrin 1-Year Dog Study (MRID #40027902).
Unpublished study prepared by Zeneca Agrochemicals, Central Toxicology
Lab Cheshire, UK. 4 p.

44333802	Leah, A. (1989) Lambda-cyhalothrin: 21-Day dermal toxicity to
the rat. ICI Central Toxicology Laboratory, Alderley Park, Macclesfield,
Cheshire, UK. Laboratory Report Number CTL/P/2532. Laboratory Study
Number LR0526. June 20, 1989. Unpublished.

44861510	Brammer, A. (1999) Lambda-cyhalothrin: Acute neurotoxicity
study in rats. Central Toxicology Laboratory, Cheshire, UK. Laboratory
Project Identification Number: CTL/P/615l, Study Number: AR6699. April
13, 1999. Unpublished.

46449102	Milburn, G. M. (2004) Lambda-Cyhalothrin: Developmental
neurotoxicity study in rats.  Syngenta Limited, Alderley Park,
Macclesfield, Cheshire, UK SK 10 4TJ.  Laboratory study number RR0969;
November 3, 2004.  Unpublished.

AppendiX B:  Metabolism Assessment

B.1.	Metabolism Guidance and Considerations

Table B.1	Summary of Degradate Formation from Degradation of
Lambda-cyhalothrin.

Study Type	Source	Degradate and Maximum Concentration

Compound Ia (% Applied) 1	Compound Ib (% Applied) 2	Degradate XV (%
Applied) 3

Aqueous Photolysis	MRID #44861501	13.7 at 282 hours (cyclopropane ring).
 	7.1% at 282 hours (cyclopropane ring).  	Others: 3-phenoxybenzoic acid
was 25.0% at 247 hours; phenoxybenzaldehyde was a minor degradate (5.5%
at 247 hours).  

Aerobic Aquatic Metabolism	MRID #44861506	11.4% at 30 days in a 98 day
study, and 11.4% at 14 days in the sediment of the SL sediment system.  

	NA 4	11.4% at 30 days, and 10.6% at 30 days in the sediment of the SL
sediment system.  

Aerobic Aquatic Metabolism	MRID #44367402	14.4% at 14 days, and 0.7 to
3.3% from 4 to 30 days in the sediment of the sand sediment system.  	NA
0.4-1.3% at 0.125-7 days, and 8.7at 7 days in the sediment of the sand
sediment system.  

Terrestrial Field Dissipation	MRID #40052407	Transformation products
monitored at the two sites were reported to be at low levels.  

Data for hydrolysis, soil photolysis, aerobic soil metabolism, and
anaerobic aquatic metabolism were not available.  

1. Compound Ia =
(1RS)-cis-3(ZE)-2-chloro-3,3,3-trifluro-1-propenyl)-2,2-dimethylcyloprop
ane-carboxylate.  

2. Compound Ib =
(1RS)-trans-3-(ZE-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclo
propane-carboxylic acid.  

 α-(S) cis α-(R) α-cyano-3-(4-hydroxy-phenoxy) benzyl
3-(Z-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclo-propanecarbo
-	xylate.  

4. NA = Not Applicable.  

AppendiX C:  Human Research REFERENCES

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"halothrin in Man.; Zeneca Report #CTL/P/4208, Study #XH2429; MRID
#44333801; J.R. March, B.H. Woolen, and M.F. Wilks; 1/28/1994.  

	The Pesticide Handlers Exposure Database, Version 1.1 (Electronic
Database); The PHED Task Force, 1995; (Task Force members: Health
Canada, US Environmental Protection Agency, and the National
Agricultural Chemicals Association); released February, 1995.  

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