Document ID: EPA-HQ-OPP-2009-0637-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-03-31T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDES

                                                                        
                   AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:		2/17/2010

SUBJECT:	Deltamethrin.  Human Health Assessment Scoping Document in
Support of Registration 				  Review  

PC Code:  097805	DP Barcode:  D368592

Decision No.:  419121	Registration No.:  None

Petition No.:  None 	Regulatory Action: Registration Review             
Scoping Document

Risk Assessment Type:  None	Case No.: None

TXR No.:  None	CAS No.:  52918-63-5

MRID No.:  None	40 CFR:  180.435

FROM:		Douglas Dotson, Ph.D., Chemist

		Edward Scollon, Ph.D., Toxicologist 

		Margarita Collantes, Biologist

		Risk Assessment Branch II

		Health Effects Division (7509P)

		Office of Pesticide Programs

THROUGH:	Christina Swartz, Branch Chief

		Risk Assessment Branch II

		Health Effects Division (7509P)

		Office of Pesticide Programs

TO:		Jill Bloom, Chemical Review Manager

		Pesticide Reevaluation Division (7508P)

		Office of Pesticide Programs

Attached is the Health Effects Division’s (HED) human health risk
assessment scoping document for deltamethrin to support registration
review.

Executive Summary

The Health Effects Division Deltamethrin Risk Assessment team has
evaluated the database and the most recent human health risk assessments
for the insecticide, deltamethrin,
(1R,3R)-R-cyano(3-phenoxyphenyl)methyl
3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate.  HED
performed this evaluation in order to determine the scope of work
necessary to support the established tolerances and existing
registrations.  The primary sources of information for this evaluation
were:  1) the most recent human health risk assessment performed to
evaluate several proposed agricultural uses and existing residential
uses, 2) a response to a recent tolerance petition for a new
agricultural use, and 3) updates to the toxicity, exposure, and usage
databases that were made in association with the recent tolerance
petition.

Deltamethrin is a broad-spectrum pyrethroid insecticide that is
registered in the U.S. for direct application to a wide variety of
food/feed crops, for use on stored grains, and for use in food/feed
handling establishments.  Two emulsifiable concentrate (EC) formulations
of deltamethrin are currently registered to Bayer CropScience for use on
a variety of food/feed crops.  In addition, numerous formulations are
registered for use in residential outdoor, indoor, pet, and paint
additive products.

One of the other pyrethroids, tralomethrin, is very similar to
deltamethrin structurally.  Tralomethrin breaks down into deltamethrin
through debromination (loss of a Br2 molecule and formation of a double
bond) and, therefore, they are considered to be the same with respect to
mammalian toxicity and endpoint selection for risk assessment. 
Tralomethrin is registered for use in a wide variety of residential
settings and on a small number of crops.  While this scoping document
does not directly address tralomethrin data requirements, the most
recent aggregate risk assessment for deltamethrin is protective for
tralomethrin with respect to dietary as well as residential exposure
pathways.  The assessment is protective for tralomethrin because the
dietary assessment included both tralomethrin and deltamethrin crop
uses, and because the use rates and potential residential exposures for
deltamethrin are greater than those for tralomethrin.  HED is currently
preparing a separate scoping document for tralomethrin.

Toxicology

The hazard characterization of deltamethrin was recently revised (E.
Scollon, D367616, 8/13/2009).  No additional studies have been submitted
to the Agency since the revision.  The toxicology database for
deltamethrin is adequate for risk assessment.  Acceptable studies
include subchronic and chronic studies in rats, mice, and dogs;
developmental studies in rats and rabbits; a reproduction study in rats;
and acute, subchronic, and developmental neurotoxicity studies in rats. 
Sufficient studies are also available to assess dermal exposure,
metabolism, and mutagenicity.  As part of the new EPA Part 158 data
requirements, an immunotoxicity study in rats and/or mice is required.

The target organ system for deltamethrin is the nervous system.  In
rats, mice, and dogs, effects included salivation, unsteadiness,
convulsions, altered posture, hypersensitivity to sound, and decreased
motor activity.  Increased duration of dosing did not either
significantly lower the NOAEL for the neurotoxic effects or increase the
severity of these effects, most likely because of rapid metabolism and
elimination.  Decreases in body weight and body weight gain were also
noted in subchronic, chronic, and reproductive studies.  There was no
evidence of systemic or local effects in rats when deltamethrin was
applied dermally.

In the prenatal developmental studies in rats and rabbits and in the
developmental neurotoxicity (DNT) study, deltamethrin had no adverse
effects on offspring in the absence of maternal effects. Evidence of
qualitative susceptibility was found in the reproduction study as
increased deaths and signs of neurotoxicity in the F1 generation.  The
qualitative increase in toxicity was likely due to an increase in
deltamethrin intake as the pups were weaned and their immature
deltamethrin clearance mechanisms.  Furthermore, the increase in
qualitative susceptibility was only noted at a dose 20-fold greater than
the NOAEL selected for the acute and chronic dietary reference dose. 
Therefore, despite evidence of increased qualitative susceptibility, a
10x safety factor for susceptibility is not warranted based on the
results of the 2-generation rat study because the endpoint and dose
selected for risk assessment would be protective.  However, several
literature studies provided evidence of susceptibility in that there
were age-dependent toxicokinetic differences between young and adult
animals.  As a result, HED concluded there was residual uncertainty for
post-natal toxicity, and the FQPA 10x Safety Factor was retained for all
exposure scenarios involving postnatal exposure of infants and children.
 No additional safety factor was necessary for adult or potentially
pregnant populations.

There was no evidence of carcinogenicity in the combined
chronic/carcinogenicity study in rats or in the carcinogenicity study in
mice.  Deltamethrin is classified as “not likely to be carcinogenic to
humans.”  In a battery of mutagenicity studies, there was no evidence
of a mutagenic effect.  

Decreased motor activity with a calculated NOAEL of 1 mg/kg/day from an
acute oral study (Wolansky, et al, 2006) was selected for deltamethrin
risk assessment.  The dose and endpoint are considered to be applicable
for all exposure scenarios and durations because the rapid elimination
of deltamethrin from the body precludes bioaccumulation, and no
additional toxicity would be expected with increased dosing duration.  A
traditional uncertainty factor of 100x (10x for interspecies
extrapolation and 10x for intraspecies variation) was applied.  As the
10x FQPA Safety Factor was retained for population subgroups comprised
of infants and children, the uncertainty factor is 1000x for all
exposure scenarios involving these subgroups, and 100x for all other
populations.

The pyrethroids, as a group, including deltamethrin, have been
determined to share a common mechanism of toxicity.  A cumulative risk
assessment has not yet been performed because the Agency is currently
examining approaches for completing this type of assessment.  However,
future actions involving deltamethrin should consider the impact of the
evolving cumulative risk assessment.  

Dietary Exposure

The dietary exposure database is adequate to support the registration
review of deltamethrin.  No additional data are required.  The most
recent dietary exposure analysis performed for deltamethrin includes
deltamethrin residues that might be present in commodities for which
tralomethrin is registered (i.e., broccoli, cottonseed, head lettuce,
leaf lettuce, soybeans, and sunflowers).  If a new drinking water
assessment is performed during registration review, the updated
estimated drinking water concentrations will be used in the dietary
exposure assessment.

The chronic dietary (food and drinking water) risks are not of concern
for the existing uses of deltamethrin.  The acute dietary (food and
drinking water) risks are of concern for the existing uses of
deltamethrin for the population subgroups comprised of infants and
children.  These population subgroups and their corresponding %aPAD
values are:  all infants (110% aPAD), children 1-2 (130% aPAD), children
3-5 (140% aPAD), and children 6-12 (110% aPAD).  During registration
review, monitoring data and new percent crop treated estimates should be
used to refine the acute dietary exposure analysis.  It is likely that
these refinements will result in dietary risk estimates that are below
HED’s level of concern for all population subgroups.

Residential Exposure

≥ 100 and were not of concern.  Postapplication exposures resulting
from use of deltamethrin on lawns are not of concern for either adults
or children.  For adults, there are no risks of concern resulting from
postapplication indoor exposure scenarios.  However, there were dermal
and oral postapplication scenarios for children that had risks of
concern. 

Hand-to-mouth exposure estimates were refined in the 2004 risk
assessment (Memo, D262496, D. Dotson, et al., 11/15/2004) with the
submission of a chemical-specific hand press study.  HED is aware that
the registrant is planning on submitting a probabilistic CARES
assessment which is being performed for the purpose of refining the
residential exposure and risk estimates.  Furthermore, as a result of
the revisions to HED’s Residential Standard Operating Procedures
(SOPs), the parameters and algorithms for dermal, inhalation, and
hand-to-mouth exposure calculations will likely change.  These changes
could result in significantly different exposure estimates for indoor
surface and treated pet collar postapplication exposure estimates. 
Therefore, during registration review, HED will conduct a new
residential exposure assessment that incorporates any potential changes
in endpoint selection, uncertainty factors, and new methods or policies
for estimating exposure associated with residential use patterns.

Occupational Exposure

Occupational handler and postapplication inhalation exposures were
assessed in the 2004 risk assessment for use of deltamethrin on a
variety of agricultural and residential settings.  A cursory review of
the occupational handler and postapplication dermal exposure scenarios
(with the exception of the plastic foam insulation panels) using the
dermal NOAEL has also been performed.  All other occupational scenarios
resulted in dermal and inhalation MOEs ≥ 100, and are not of concern.

During registration review, revised occupational handler and
postapplication assessments should be conducted based on updated doses
and endpoints for dermal and inhalation risk assessment.  These
assessments may include additional and more detailed review of the
submitted risk assessment for the foam insulation product.

Introduction

HED evaluated the most recent human health risk assessments for
deltamethrin to determine if sufficient data are available and if
updates are needed to support registration review.  To perform this
evaluation, HED considered the following documents and assessments:  1)
the most recent human health risk assessment performed to evaluate
several proposed agricultural uses and existing residential uses (Memo,
D262496, D. Dotson, et al., 11/15/2004), 2) a response to a tolerance
petition for a new agricultural use (Memo, D335134, D. Dotson, et al.,
8/11/2009, 3) updates to the toxicity, exposure, and usage databases
that were made in association with the proposed new use, and 4) the
latest Agency science policies and risk assessment methodologies.  The
structure of deltamethrin, as well as its chemical names and other
identifiers can be found in the chemical identity table attached to this
document (Attachment 1).

Deltamethrin is a broad-spectrum pyrethroid insecticide that is
registered in the U.S. for direct application to a wide variety of
food/feed crops, for use on stored grains, for use in food/feed handling
establishments, and for a variety of residential uses.  Two emulsifiable
concentrate (EC) formulations of deltamethrin are currently registered
to Bayer CropScience for use on food and feed crops.  One is a 1.5 pound
active ingredient per gallon (lb ai/gal) EC (Decis 1.5EC Insecticide,
EPA Registration #264-1011), and the other is a 0.2 lb ai/gal EC (Decis
0.2EC Insecticide, EPA Registration #264-1007).

Tolerances are established under 40 CFR §180.435 for residues of
deltamethrin that result from agricultural uses as well as food and feed
handling establishment uses.  For all commodities, tolerances are
established in terms of parent deltamethrin and its major metabolites,
trans deltamethrin and alpha-R deltamethrin.  The CAS names of these
compounds are as follows:  deltamethrin
[(1R,3R)-3-(2,2-di-bromovinyl)-2,2-dimethylcyclopropanecarboxylic acid
(S)-alpha-cyano-3-phenoxybenzyl ester, trans deltamethrin [( S )- alpha
-cyano-m-phenoxybenzyl(1R,3S)-3-(2,2-dibromovinyl)-2,2-dimethylcycloprop
anecarboxylate], and alpha-R-deltamethrin
[(R)-alpha-cyano-m-phenoxybenzyl-(1R ,3R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate].  During
registration review, the residues of concern for tolerance enforcement
will be re-assessed.

During registration review, the tolerance expression should be revised
so that it addresses both coverage and measurement.  The tolerance
expression should be revised as follows:  Tolerances are established for
residues of deltamethrin, including its metabolites and degradates, in
or on the commodities in the table below.  Compliance with the tolerance
levels specified below is to be determined by measuring only
deltamethrin and the residues of concern established during registration
review.  

One of the other pyrethroids, tralomethrin, is very similar to
deltamethrin structurally.  Tralomethrin breaks down into deltamethrin
through debromination (loss of a Br2 molecule and formation of a double
bond).  Tralomethrin is registered for use in a wide variety of
residential settings and on a small number of crops (40 CFR §180.422).

Hazard Identification/Toxicology

Deltamethrin is a pyrethroid pesticide that causes neurotoxicity in
insects and mammals by a similar mechanism of action, the modulation of
nerve axon sodium channels.  Pyrethroids interfere with the ability of
the nervous system to relay nerve transmissions resulting in tremors,
whole body convulsions, or excessive salivation, among other effects.  

The hazard characterization for deltamethrin has recently been updated
(Memo, D367616, E. Scollon, 8/13/2009).  Major revisions included the
selection of new endpoints for risk assessment and the incorporation of
a dermal assessment.  No new studies have been submitted since the last
update.  For a complete review of the toxicology and historical
decisions, see Memo, D367616, E. Scollon, 8/13/2009.  Briefly, the
toxicology database for deltamethrin is robust but not complete.  In
accordance with the new 40CFR Part 158 data requirements for
conventional pesticide registration, an immunotoxicity study in rats
and/or mice is now required.  Because the immune system is highly
complex, studies not specifically conducted to assess immunotoxic
endpoints are inadequate to characterize a pesticide’s potential
immunotoxicity.  While data from hematology, lymphoid organ weights, and
histopathology in routine chronic or subchronic toxicity studies might
offer useful information on potential immunotoxic effects, these
endpoints alone are insufficient to predict immunotoxicity.  The
Deltamethrin Registration Review Team recommends that, once all data
have been received and reviewed, the points of departure and uncertainty
and safety factors used for risk assessment purposes be reexamined and a
new risk assessment performed, if necessary.

Deltamethrin has moderate acute toxicity via the oral (category II) and
inhalation (II/III) routes of exposure and minimal toxicity via the
dermal (category III) route of exposure.  It is minimally irritating to
the eye (category III) and non-irritating to the skin (category IV).  It
is not a skin sensitizer.

Deltamethrin targets the nervous system.  In guideline animal studies,
effects in the rat, dog, and rabbit included salivation, unsteadiness,
convulsions, altered posture, hypersensitivity to sound, and decreased
motor activity.  Increased duration of dosing did not significantly
lower the NOAEL for the neurotoxic effects and it did not increase the
severity of these effects.  In fact, neurotoxicity effects were
identified in the chronic and subchronic rat studies within hours to
days of initial dosing, but decreased over several weeks.  Decreases in
body weight and body weight gain were also noted in subchronic, chronic,
and reproductive studies.  Additionally, there was no evidence of
systemic or local effects in rats when deltamethrin was applied
dermally.  Low toxicity via the dermal route is most likely due to the
low potential for dermal absorption through the skin.

In the prenatal developmental studies in rats and rabbits and in the DNT
study, deltamethrin had no adverse effects on fetuses or offspring in
the absence of maternal effects.  There was evidence of qualitative
susceptibility in the reproduction study as increased deaths and signs
of neurotoxicity in the F1 generation.  The qualitative increase in
toxicity was correlated with:

1) an increase in deltamethrin intake as the pups were weaned and began
consuming greater quantities of dosed chow and, 2) immature clearance
mechanisms for deltamethrin in the pups.  Furthermore, the increase in
qualitative susceptibility was only noted at 21.6 mg/kg/day, 20-fold
greater than the NOAEL selected for the acute and chronic dietary
reference dose (1 mg/kg/day).  Therefore, despite evidence of increased
qualitative susceptibility, a 10x safety factor for susceptibility is
not warranted based on the results of the 2-generation rat study because
the endpoint and dose selected for risk assessment would be protective. 
Despite the lack of quantitative and qualitative susceptibility found in
the guideline studies, the 10x FQPA Safety Factor was retained for all
exposure scenarios involving infants and children.  The decision to
retain the factor was based on residual uncertainty for post-natal
toxicity because of age-dependent toxicokinetic data that were found in
literature studies.

Several literature studies indicate that infants and children might be
more susceptible to deltamethrin toxicity as a result of post-natal
exposure.  Young rats are quantitatively susceptible to deltamethrin
toxicity at doses greater than 4 mg/kg.  The enzymes accounting for the
metabolism of deltamethrin either are not present in the same levels in
children as they are in adults, or they are not as active in children. 
Similarly, enzyme profiles in infants and children are less developed
than they are in adults and can be highly variable in quantity and
activity, especially in infants.  Until sufficient evidence is available
demonstrating that infants and children have the capacity to metabolize
deltamethrin in a manner comparable to the way in which adults
metabolize it, quantitative susceptibility is being assumed.

Decreased motor activity observed in an acute oral study in rats
(Wolansky et al., 2006) was selected as the endpoint for deltamethrin
risk assessment.  The NOAEL for this study was 1 mg/kg/day.  The
endpoint and dose are considered to be applicable for all exposure
scenarios and durations because the rapid elimination of deltamethrin
from the body precludes bioaccumulation, and no additional toxicity
would be expected with increased dosing duration.  In the past,
deltamethrin risk assessments did not include a dermal assessment
because a dermal toxicity study indicated there were no toxic effects up
to the limit dose; however, the dermal toxicity study was conducted in
adult rats and does not consider potential pup susceptibility. 
Therefore, a dermal endpoint and dose were selected for infants/children
in the revised hazard characterization.  In addition, as the dermal
study did not assess neurotoxic parameters, a dermal assessment was also
conducted for adults based on the endpoint selected from the Wolansky
study, and a dermal absorption factor of 1%.  The default uncertainty
factor of 100x (10x for interspecies extrapolation and 10x for
intraspecies variation) was applied to all exposure scenarios. 
Therefore, as the 10x FQPA Safety Factor was retained for population
subgroups comprised of infants and children, the uncertainty factor is
1000x for all exposure scenarios involving these subgroups, and 100x for
all other populations.

There was no evidence of carcinogenicity in the combined
chronic/carcinogenicity study in rats or the carcinogenicity study in
mice.  Deltamethrin is classified as “not likely to be carcinogenic to
humans.”  In a battery of mutagenicity studies, there was no evidence
of a mutagenic effect.  

Tralomethrin is structurally similar to deltamethrin.  It is metabolized
into deltamethrin and shares the same major metabolites in vivo. 
Additionally, tralomethrin endpoints for dietary, occupational, and
residential exposure scenarios are similar, or equivalent, to those for
deltamethrin and are based upon a combined tralomethrin/deltamethrin
toxicity database.

The summary tables of toxicity endpoints from the most recent update of
the hazard characterization (Memo, D367616, E. Scollon, 8/13/2009) are
provided in Attachment 2.

During registration review, the toxicity database should be reconsidered
based on the registered uses.  Endpoints, doses, and safety factors
should be determined in order to assess risks associated with all
potential exposure scenarios.  This re-evaluation should consider all
additional studies received since the RED and those now required as part
of the new Part 158 data requirements.

Conclusions for Hazard Identification/Toxicology

An immunotoxicity study is required and should be submitted in
conjunction with registration review.  During registration review, the
toxicity database should be re-evaluated based on the results of the
immunotoxicity study and any other data received in conjunction with the
registered uses.  Endpoints, doses, and safety factors should be
determined in order to assess risks associated with all potential
exposure scenarios.

Dietary Exposure

Deltamethrin kills insects on contact and through ingestion.  It is used
to control numerous insect pests on field crops.  It is also used to
control apple and pear suckers, aphids (on apples, plums, and hops),
caterpillars (on Brassica crops), pea moths, plum fruit moths, winter
moths (on apples and plums), and codling and tortrix moths (on apples). 
In addition, it is used in glasshouses to control aphids, mealy bugs,
scale insects and whitefly on cucumbers, tomatoes, peppers, potted
plants, and ornamentals.  Formulations include emulsifiable concentrates
(EC), wettable powders (WP), flowable formulations (F), and granules
(G).  There are no known incompatibilities with other common
insecticides and fungicides.

Deltamethrin is a broad-spectrum pyrethroid insecticide that is
registered in the U.S. for direct application to a wide variety of
food/feed crops, for use on stored grains, and for use in food/feed
handling establishments.  Two emulsifiable concentrate (EC) formulations
of deltamethrin are currently registered to Bayer CropScience for these
uses.  One is a 1.5 pound active ingredient per gallon (lb ai/gal) EC
(Decis 1.5EC Insecticide, EPA Registration #264-1011), and the other is
a 0.2 lb ai/gal EC (Decis 0.2EC Insecticide, EPA Registration
#264-1007).  Technical deltamethrin is made up predominantly of the cis
isomer, which comprises on the order of 99% of the technical material.

Tolerances are established under 40CFR §180.435 for residues of
deltamethrin that result from agricultural uses as well as use in food
and feed handling establishments.  For all commodities, tolerances are
established in terms of parent deltamethrin and its major metabolites,
trans deltamethrin and alpha-R deltamethrin.  Although the 40CFR refers
to trans and alpha-R deltamethrin as metabolites, they are, in fact,
isomers of cis-deltamethrin as well as metabolites of it.  During
registration review, the tolerance expression will be revised so that it
addresses both coverage and measurement.  The tolerance expression
should be revised as follows:  Tolerances are established for residues
of deltamethrin, including its metabolites and degradates, in or on the
commodities in the table below.  Compliance with the tolerance levels
specified below is to be determined by measuring only deltamethrin and
the residues of concern established during registration review.  

odel (DEEM-FCID™ Version 2.03) to conduct the most recent acute and
chronic aggregate dietary (food and drinking water) risk assessments for
deltamethrin.  This model incorporates consumption data from the
USDA’s Continuing Survey of Food Intakes by Individuals taken between
1994 and 1996 along with a supplemental children’s survey taken in
1998.  Anticipated residues based on field trial data and estimates of
percent crop treated were used in both the acute and chronic dietary
risk assessments.  Empirical and DEEM default processing factors were
used for the various processed commodities.  Deltamethrin was classified
as “not likely to be carcinogenic to humans.”  As a result, a cancer
dietary risk assessment was not conducted.   

The estimated acute dietary exposure to deltamethrin resulted in an
estimated risk equivalent to 8.7% of the aPAD (acute population adjusted
dose) for the general U.S. population at the 99.9th percentile of
exposure.  The acute dietary risks are of concern for the existing uses
of deltamethrin for the population subgroups comprised of infants and
children.  These population subgroups and their corresponding %aPAD
values are:  all infants (110% aPAD), children 1-2 (130% aPAD), children
3-5 (140% aPAD), and children 6-12 (110% aPAD).  During registration
review, monitoring data and new percent crop treated estimates should be
used to refine the acute dietary exposure analysis.

The estimated chronic dietary exposure to deltamethrin resulted in an
estimated risk equivalent to <1% of the cPAD (chronic population
adjusted dose) for the general U.S. population.  The most highly exposed
population subgroup was Children 1-2 years old, which utilized 11% of
the cPAD    

EFED recommended that modeled estimates of residues in drinking water be
used in the most recent dietary risk assessment.  If a new drinking
water assessment is performed during registration review, the updated
estimated drinking water concentrations will be used in the dietary
exposure assessment.

Conclusions to Dietary Exposure

The dietary exposure database is adequate to support the existing
registrations and tolerances.  No new residue chemistry data are
required.  A new drinking water assessment will be conducted during
registration review.  In addition, a revised dietary risk assessment
will need to be conducted.  It will include the revised estimated
drinking water concentrations, any changes in toxicological endpoints,
and refinements to the residue levels and percent crop treated estimates
used in the assessment.  These refinements will likely result in dietary
risk estimates that are below HED’s level of concern for all
population subgroups.

Residential Exposure

Deltamethrin is used in numerous residential settings.  It is formulated
as various indoor and outdoor end-use products for both broadcast as
well as crack and crevice application.  Included among its uses are pet
collars and insecticidal paint additives.  These products are formulated
as ready-to-use sprays, dusts, liquids, and granules.  The products are
applied by a wide range of application methods including hose-end
sprayers, push-type spreaders, shaker cans, aerosol cans, low/high
pressure hand wands, backpack sprayers, paint brush/rollers, and airless
sprayers.  Tralomethrin application rates in residential settings are
all equal to, or lower than, the deltamethrin application rates for the
same uses.  As a result, the most recent risk assessment for
deltamethrin is protective for tralomethrin exposures.

With the exception of the pet collar scenario, all residential exposure
assessments for deltamethrin were conducted using the current version of
the SOPs for residential exposure assessment.  However, the Agency has
recently undertaken a major revision of these SOPs, the proposed new
exposure assessment assumptions, data and algorithms were presented to
the Agency’s Science Advisory Panel (SAP) in October, 2009.  HED is
currently evaluating the SAP’s response and recommendations, and is
not routinely using the proposed SOP revisions.

Handlers

tion MOEs ≥ 100, and were not of concern.

Postapplication 

Residential postapplication exposure scenarios can occur as a result of
deltamethrin’s use as a broadcast and crack and crevice application to
lawns and indoor surfaces, its use in treated pet collars, and its use
in insecticidal paints and termiticides (Memo, D335134, D. Dotson and M.
Collantes, 8-13-09).  Postapplication re-entry into treated areas can
result in dermal, inhalation, and incidental oral (i.e., hand-to-mouth,
for children only) exposures.

Potential postapplication dermal exposure resulting from the use of
deltamethrin on lawns is not of concern for either adults or children. 
All dermal MOEs were greater than or equal to 100 for adults and greater
than or equal to 1000 for children.  In addition, for adults, all indoor
scenarios resulted in dermal and inhalation MOEs ≥ 100 and were not of
concern.  

Postapplication scenarios that resulted in risks of concern were:  1)
dermal and oral (hand-to-mouth) children’s exposure resulting from
indoor broadcast and crack and crevice application of sprays ranging
from 0.06% to 0.02% in concentration; and 2) oral (hand-to-mouth)
children’s exposure resulting from broadcast application to lawns. 

Pet Collars

Both adults’ and children’s exposures from the use of a treated pet
collar result in risks of concern (Current Guidance for Residential
Exposure Risk Assessment for Pet Insecticide Treatments, D350531, W.
Britton, 1/14/2009).  The details regarding calculations of the amount
of ai in the pet collar, as well as the MOEs, are presented in the
appendixes of this document.  While adult handler’s risks for applying
a pet collar are not of concern, scenarios with risk concerns include
adults’ and children’s dermal post-application exposure resulting
from use of treated pet collars and children’s oral (hand-to-mouth)
exposure resulting from treated pet collars.

 to HED (MOE ≤ 1,000).  However, as explained in the 2004 risk
assessment (Memo, D262496, D. Dotson, et al., 11/15/2004), HED considers
ingestion of granules to be an episodic event, not routine behavior.  As
granular ingestion does not occur on a regular basis, HED’s concern
for human health is related to acute poisoning rather than short or
intermediate-term residue exposure.  While HED continues to conclude
that exposure from granular ingestion is likely to be very low, risk
from this scenario should be re-examined in light of the new target MOE
of 1000.

Combined Residential Risk Estimates

	

Residential scenarios consist of dermal and hand-to-mouth
postapplication exposures for toddlers resulting from lawn and indoor
broadcast application of deltamethrin and contact with treated pets from
use of treated dog collars.  As the dermal and oral postapplication
exposure to toddlers resulting from broadcast application to lawns
represent lower risks of concern than the worst case scenario (indoor
postapplication exposures), they are not included in the combined
residential exposure and risk estimates.  The combined residential
exposure resulted in a total MOE of 140 for indoor broadcast application
and 24 for treated pet collars.  Based on the current estimated chronic
exposure from food and water, a combined residential MOE of 1,100 (i.e.,
including dermal and hand-to-mouth exposure) is needed to reach an
aggregate (dietary + residential) risk estimate that is below HED’s
level of concern (i.e., to reach an aggregate MOE of >1000).  Therefore,
current combined residential risk estimates are of concern to HED. 
Table 1 provides a summary of the combined residential indoor broadcast
and treated pet collar exposures and risks.

Table 1.  Combined Residential (Toddler) Exposure and Risk Estimates 

Postapplication

Scenarios	Daily Dose

(mg/kg/day) 1	MOE 2	Combined

MOE 3

Indoor Broadcast

Toddler Dermal surface	0.0028	350	

140

Toddler Hand-to-Mouth 	0.0044	230

	Treated Pet Collar

Toddler - Dermal	0.042	24	15

Toddler – Hand-to-Mouth	0.0224	45

	

	1 Daily Dose for Indoor Broadcast use see Memo, D307927, M. Collantes,
10/14/2004 (Table 7)

	   Daily Dose for Pet Collar:  see Table A.5.b in Attachment 5	

	

	2 Toddler Dermal MOE = NOAEL (1 mg/kg/day)	 

       	               	Dermal Dose

					

	Toddler Oral MOE = NOAEL (1 mg/kg/day)

       	                  	Oral Dose					       	 

	3 Toddler Combined MOE = 1/(dermal dose + oral dose)

Conclusions for Residential Exposure

As a result of the revisions to HED’s Residential SOPs, the parameters
and algorithms for dermal, inhalation, and hand-to-mouth exposure
calculations will likely change, and could result in significantly
different estimates of indoor surface and treated pet collar
postapplication exposures.  Postapplication exposure scenarios cannot be
refined without additional chemical-specific data (i.e. pet collar
study) and incorporation of the revised residential SOP algorithms in
the registration review process.  Furthermore, the registrant plans to
submit a probabilistic CARES assessment for the purpose of refining the
residential exposure and risk estimates.  The input parameters and
results of the CARES assessment should be considered during registration
review. 

Aggregate Risk Assessment

HED has identified aggregate risks of concern based on acute dietary
risks of concern for children, and residential risks of concern for both
adults and children.  During registration review, an updated aggregate
risk assessment will be conducted, taking into consideration any changes
that are made to 1) the toxicological doses and endpoints that are
selected, 2) the estimated drinking water concentrations, 3) the % crop
treated estimates for food commodities, and 4) the potential refinements
for residential exposure estimates for adults and children.

Occupational Exposure 

Occupational handler and postapplication inhalation exposures were
assessed in the 2004 risk assessment (Memo, D262496, D. Dotson, et al,
11/15/04) for use of deltamethrin on a variety of agricultural crops,
stored grain bins and warehouses, and commercial products including
termiticides, insecticidal paint additives, and insecticidal plastic
foam insulation.  A cursory review of the occupational handler and
postapplication dermal exposure scenarios (with the exception of the
plastic foam insulation panels) using the dermal NOAEL has also been
performed.  All occupational scenarios resulted in dermal and inhalation
MOEs ≥ 100 and are not of concern.  

In support of the use of plastic foam insulation panels, the registrant,
Dow Chemical Company, submitted a screening risk assessment document
(MRID 45345802), that was reviewed to verify the potential absorbed dose
based on information provided in the study report.  However, as there
was no dermal endpoint in 2003, dermal exposure assessment was not
performed for this scenario.  Furthermore, HED currently does not have
unit exposures to assess this handler exposure scenario in order to
determine exposure resulting from construction workers installing foam
insulation containing deltamethrin.

Conclusions for Occupational Exposure Assessment

During registration review, revised occupational handler and
postapplication assessments should be conducted based on updated doses
and endpoints for dermal and inhalation risk assessment.  These
assessments may include additional and more detailed review of the
submitted risk assessment for the foam insulation product.

Public Health and Pesticide Epidemiology Data 

HED has prepared an incident report for deltamethrin (Memo, D369651, M.
Hawkins, et al., 11/24/2009).  For this evaluation, both the OPP
Incident Data System (IDS) and the Centers for Disease Control and
Prevention/National Institute for Occupational Safety and Health
(CDC/NIOSH) Sentinel Event Notification System for Occupational Risk
(SENSOR) database were consulted for poisoning incident data.  

For IDS, HED identified 118 case reports allegedly attributable to
deltamethrin reported to the IDS between 2002 and 2008.  Among the case
reports, the majority of the reported symptoms involved upper
respiratory and dermal effects.  Upper respiratory effects include
symptoms such as shortness of breath, asthma, respiratory distress,
respiratory irritation, coughing/choking, difficulty breathing, sinus
problems, chest congestion and pain and combination effects.  Most of
the incidents were not severe.  However, a patient could exhibit
multiple symptoms.  There does not appear to be a change in reported
incidents over time.

For the NIOSH SENSOR database, there are 120 cases reported. Cases that
involve deltamethrin alone and where exposure was determined to be
definite, probable, or possible, were reviewed in detail.  These
selection criteria resulted in the inclusion of 65 cases.  For these
cases, there were no fatalities.  Fifty-eight of the cases were
classified as low severity and 7 were classified as moderate severity. 
Eighteen of the deltamethrin cases involved minors (less than18 years
old).  The health effects most often reported include: gastrointestinal
(46%), neurological (44%), respiratory (37%), dermal (35%), and ocular
(23%).  A patient could report various symptoms.  

In twelve cases, people were exposed through spray drift.  Ten workers
and two children were exposed by spray drift from an adjacent field
sprayed with deltamethrin.  All reported neurological (headache) and
gastrointestinal symptoms (nausea and/or vomiting).  It appears that
there was an increase in incidents in 2002; however, twelve of these
incidents were the drift incidents mentioned above, that occurred at the
same time and place.  With the exception of the 2002 incidents, there
does not appear to be a change in reported incidents over time.

In general, both the IDS and NIOSH SENSOR queries for deltamethrin
resulted in moderately large numbers of case reports.  However, most of
these incidents were of low severity, and no patterns or trends were
discerned among the reported cases.  Subsequently, it is not clear human
incident data warrant further analysis for the risk assessment and/or
risk management of deltamethrin.  The Agency will continue to monitor
the incident information and if a concern is triggered, additional
analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

Tolerances are established for residues of deltamethrin in or on food
and feed commodities under 40CFR §180.435.  Tolerances have been
established for numerous individual commodities and several crop groups.
 In addition, deltamethrin has been registered for use on stored grains
and in food/feed handling establishments.  For all commodities,
tolerances are established in terms of parent deltamethrin and its major
metabolites trans deltamethrin and alpha-R deltamethrin.  A summary
table of international MRLs can be found in Attachment 4.

Canada has not established any MRLs for deltamethrin; however, there are
numerous uses in British Columbia and/or Eastern Canada.  Mexico has
established MRLs based on the U.S. tolerances.  These MRLs are at the
same level as the U.S. tolerances and are as follows:  1 ppm for the
cereal grains group, 0.1 ppm for soybeans, 0.04 ppm for cottonseed, and
0.2 ppm for crambe, rapeseed, and tomatoes.  Codex has established
numerous MRLs for deltamethrin.  Several of the commodities with Codex
MRLs also have U.S. tolerances; however, many of them do not.  In many
cases, the U.S. tolerances are the same as, or higher than, the Codex
MRL.  There are a few commodities for which the U.S. tolerance is lower
than the Codex MRL, however.  Codex has a MRL of 2 ppm for cereal
grains, whereas the U.S. tolerance is 1.0 ppm.  Codex has a MRL of 1 ppm
for pulses (dry beans, including soybeans), whereas the U.S. tolerance
for soybeans is 0.1 ppm.  Codex has a MRL of 0.5 ppm for the fat of
cattle, goat, horse, and sheep, whereas the U.S. tolerance is 0.05 ppm. 
Finally, the Codex MRL for poultry fat is 0.1 ppm, whereas the U.S.
tolerance is 0.05 ppm.  

In effect, harmonization of tolerances with Canada and Mexico is not an
issue because Canada has not established any MRLs for deltamethrin, and
the Mexican MRLs are already harmonized with the U.S. tolerances.  There
are harmonization issues with Codex.  These differences will be
addressed during registration review.

Environmental Justice

Potential areas of environmental justice concerns, to the extent
possible, were considered in the most recent human health risk
assessment, in accordance with U.S. Executive Order 12898, “Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations,”   HYPERLINK
"http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2-6-EO_12898
envjustice.pdf" 
http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2-6-EO_12898
envjustice.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 the USDA under the Continuing
Survey of Food Intakes by Individuals (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.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups, and
exposure assessments are performed when conditions or circumstances
warrant.

The Office of Pesticide Programs (OPP) typically considers the highest
potential exposures from the legal use of a pesticide when conducting
human health risk assessments, including, but not limited to, people who
obtain drinking water from sources near agricultural areas, the
variability of diets within the U.S., and people who might be exposed
when harvesting crops.  Should these highest exposures indicate
potential risks of concern, OPP further refines the risk assessments to
ensure that the risk estimates are based on the best available
information.

Endocrine Disruptor Screening Program 

As required under FFDCA section 408(p), EPA has developed the Endocrine
Disruptor Screening Program (EDSP) to determine whether certain
substances (including pesticide active and other ingredients) may have
an effect in humans or wildlife similar to an effect produced by a
“naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  The EDSP employs a two-tiered approach
to making the statutorily required determinations.  Tier 1 consists of a
battery of 11 screening assays to identify the potential of a chemical
substance to interact with the estrogen, androgen, or thyroid (E, A, or
T) hormonal systems.  Chemicals that go through Tier 1 screening and are
found to have the potential to interact with E, A, or T hormonal systems
will proceed to the next stage of the EDSP where EPA will determine
which, if any, of the Tier 2 tests are necessary based on the available
data.  Tier 2 testing is designed to identify any adverse endocrine
related effects caused by the substance and establish a dose-response
relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA is issuing test orders/data
call-ins for the first group of 67 chemicals, which contains 58
pesticide active ingredients and 9 inert ingredients.  This list of
chemicals was selected based on the potential for human exposure through
pathways such as food and water, residential activity, and certain
post-application agricultural scenarios.  This list should not be
construed as a list of known or likely endocrine disruptors.

Deltamethrin is not among the group of 58 pesticide active ingredients
on the initial list to be screened under the EDSP.  Under FFDCA sec.
408(p) the Agency must screen all pesticide chemicals.  Accordingly, EPA
anticipates issuing future EDSP test orders/data call-ins for all
pesticide active ingredients. 

For further information on the status of the EDSP, the policies and
procedures, the list of 67 chemicals, the test guidelines, and the Tier
1 screening battery, please visit the Agency’s website: 
http://www.epa.gov/endo/.

Cumulative Risk Assessments 

Deltamethrin is a member of the pyrethroid class of insecticides.  This
class also includes permethrin, cypermethrin, cyfluthrin, fluvalinate,
bifenthrin, fenpropathrin, and lambda-cyhalothrin, among others.  EPA
developed a draft science policy document on the proposed common
mechanism of toxicity for naturally-occurring pyrethrins and synthetic
pyrethroids (Proposed common mechanism grouping for the pyrethrins and
pyrethroids, draft, May 19, 2009;   HYPERLINK
"http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000
064809a62df" 
http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000
64809a62df  ).  This document was supported by the FIFRA Scientific
Advisory Panel (SAP) and EPA will finalize the policy document on the
pyrethroid common mechanism of toxicity taking into account the SAP
comments.  Pesticides with a common mechanism of toxicity are subject to
cumulative risk assessment under the FQPA.  Research is ongoing by
EPA’s Office of Research and Development (ORD) to make improvements to
the SHEDS Probabilistic Exposure Model which are important for the
cumulative risk assessment.  EPA ORD is also developing
physiologically-based pharmacokinetic models for several pyrethroids. 
The status of both of these research modeling efforts will be reviewed
by the FIFRA SAP in July, 2010.  For information regarding EPA’s
efforts to evaluate the risk to pyrethroids, refer to   HYPERLINK
"http://www.epa.gov/pesticides/cumulative/" 
http://www.epa.gov/pesticides/cumulative/ .

Human Studies

Past deltamethrin risk assessments relied in part on data from studies
in which adult human subjects were intentionally exposed to a pesticide
to determine their dermal and inhalation exposure.  Many such studies,
involving exposure to many different pesticides, comprise generic
pesticide exposure databases such as the Pesticide Handlers Exposure
Database (PHED), the Agricultural Reentry Task Force (ARTF) Database,
and the Outdoor Residential Exposure Task Force (ORETF) Database.  EPA
has reviewed all the studies in these multi-pesticide generic exposure
databases, and on the basis of available evidence has found them to have
been neither fundamentally unethical nor significantly deficient
relative to standards of ethical research conduct prevailing when they
were conducted.  There is no regulatory barrier to continued reliance on
these studies, and all applicable requirements of EPA’s Rule for the
Protection of Human Subjects of Research (40 CFR Part 26) have been
satisfied.

Data Requirements

To support registration review, an immunotoxicity study should be
submitted for deltamethrin.  This study is a new requirement under the
40CFR Part 158 data requirements for registration of a pesticide (food
and non-food uses).  For purposes of refining postapplication dermal and
oral exposures resulting from use of pet collars, a pet collar residue
transfer study is required.  This study should measure the amount of
active ingredient that can transfer from the treated animal to the hands
of individuals contacting the animal.

References 

Author(s)	Barcode/TXR No.	Date	Title

D. Dotson,

N. McCarroll, A. Levy, & M. Collantes	D262496	11/15/2004	PP#s 0F6080 and
1E6232: Human Health Risk Assessment for the Proposed Section 3 Uses of
Deltamethrin on Various Crops and Residential Scenarios

Douglas Dotson	D284297	11/12/2004	Acute Probabilistic and Chronic
Dietary Exposure Assessments for the Section 3 Registration Action  

William Drew	D338791	3/4/2008	Deltamethrin.  Tolerance Petition   SEQ
CHAPTER \h \r 1 Requesting the Establishment of Permanent Tolerances
(Associated with Section 3 Registration) for Food Use of the Insecticide
on Flax.  Request for a Label Amendment Increasing the Use Rate on
Soybeans.  Summary of Analytical Chemistry and Residue Data

E. Scollon & M. Collantes	D367616	8/13/2009	Deltamethrin.  Updated
Hazard Characterization

D. Dotson &

M. Collantes	D335134	8/13/2009	Deltamethrin.  Response to Tolerance
Petition for Use on Flax

Margarita Collantes	D274950	7/18/2003	Occupational and Residential
Exposure and Risk Assessment for Proposed Uses of Deltamethrin on
Brassica Vegetables; Bulb, Root and Tuber Vegetables; Cucurbit
Vegetables, Fruiting Vegetables, Leafy Vegetables; Tall Field Row Crops
(Corn, Sorghum, and Sunflower); Low Field Row Crops (Soybean); Deciduous
Fruit Trees (Pome, Starfruit, and Stone); Stored Grain, Tree Nuts,
Termiticides and Insecticidal Paint  

M. Hawkins, J. Cordova,

& S. Recore	D369651	11/24/2009	Updated Review of Deltamethrin Incident
Reports

Versar	MRID 45345802	07/28/02	Review of Screening Risk Assessment:
Potential Dermal Exposure from Handling Plastic Foam Insulation
Containing Deltamethrin

M. Wolansky,  C. Jennings, & M. Crofton	MRID

47885701	2006	Relative Potencies for Acute Effects of Pyrethroids on
Motor Function in Rats, Toxicol. Sci., 89(1): 271-277

Attachments

Attachment 1.  Chemical Identity Table

Attachment 2.  Deltamethrin Endpoint Selection Tables

Attachment 3.  DCI Justification for Immunotoxicity Study

Attachment 4.  International Residue Limit Status

Attachment 5.  Residential Postapplication Exposure and Risk Estimates



Attachment 1.  Chemical Identity Table

.  

Chemical Identity

Compound	Chemical Structure

           

Common Name	cis-deltamethrin

Molecular Formula	C22H19Br2NO3

Molecular Weight	505.24

Company Experimental Name	AEF108569

IUPAC Name	(S)-α-cyano-3-phenoxybenzyl
(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate

CAS Name	(1R,3R)-R-cyano(3-phenoxyphenyl)methyl
3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate

CAS Number	52918-63-5

End-use Products (EPs)	Decis 1.5EC (EPA Registration #264-1011), Decis
0.2EC (EPA Registration #264-1007)

Attachment 2.  Deltamethrin Endpoint Selection Tables

Summary of Toxicological Doses and Endpoints for Deltamethrin for Use in
Human Risk Assessments

Table A.2.a.  Summary of Toxicological Doses and Endpoints for
Deltamethrin for Use 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, excluding Infants and Children)
NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=1x

	Acute RfD = 0.01 mg/kg/day

aPAD = 0.01 mg/kg/day	The endpoint, decreased motor activity in male
rats, is taken from an acute oral study (Wolansky et al., 2006).   

Using a nonlinear exponential threshold additivity model, a NOAEL (aka
threshold dose) was obtained by fitting motor activity data across 7
dose groups; 0, 0.03, 0.1, 0.3, 1, 3, and 10 mg/kg.  The NOAEL is an
estimate of the highest no-effect dose level at which treated rats would
not display any decrease in motor activity.

Supported by subchronic rat, subchronic dog and chronic dog studies with
NOAELs of 1mg/kg/day and LOAELs of 2.5 or 10 mg/kg/day based on signs of
neurotoxicity including unsteadiness, tremors and jerking movements,
salivation, and chewing on extremities (chronic dog only).

Acute Dietary (Infants and Children)	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=10x	Acute RfD = 0.01 mg/kg/day

aPAD = 0.001 mg/kg/day	Decreased motor activity in adult male rats
(Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Acute Dietary

(Females 13-49 years of age)	N/A	N/A	N/A	No appropriate endpoint
available

Chronic Dietary (All populations, excluding infants and children)	NOAEL=
1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=1x	Chronic RfD = 0.01 mg/kg/day

aPAD = 0.01 mg/kg/day	Decreased motor activity in adult male rats
(Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Chronic Dietary (Infants and children)	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=10x	Chronic RfD = 0.01 mg/kg/day

aPAD = 0.001 mg/kg/day	Decreased motor activity in adult male rats
(Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

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

UFH=10x

FQPA SF=10x	Residential LOC for MOE = 1000	Decreased motor activity in
adult male rats (Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Dermal

(General population excluding infants and children)

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=1x

DAF: 1%	Residential LOC for MOE = 100

	Decreased motor activity in adult male rats (Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Dermal

(Infants and children)

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=10x

DAF: 1%*	Residential LOC for MOE = 1000

	Decreased motor activity in adult male rats (Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Inhalation

(General population excluding infants and children)

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=1x

IAF: 100%	Residential LOC for MOE = 100

	Decreased motor activity in adult male rats (Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

Inhalation

(Infants and children)

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF=10x

IAF: 100%	Residential LOC for MOE = 1000

	Decreased motor activity in adult male rats (Wolansky et al., 2006).

See Acute Dietary-General population for supporting information.

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 (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  FQPA SF = FQPA Safety Factor.  PAD = population
adjusted dose (a = acute, c = chronic).  RfD = reference dose.  MOE =
margin of exposure.  LOC = level of concern.

*  DAF: 1%:  1% dermal absorption is based on preliminary review of the
following two sources:  (1)  MRID 41917502, Dermal Absorption of (Carbon
14)-Capture 2 EC (FMC 54800) in the Rat: Lab Project Number: P01896:
A90-3165: A490- 0723, Unpublished study prepared by Biological Test
Center, Braun, R. (1990), and (2)  In Vitro Dermal Absorption of
Pyrethroid Pesticides in Rat and Human Skin.  The Toxicologist, 90(1),
Hughes, M. and B. Edwards, 2006



Table A.2.b.  Summary of Toxicological Doses and Endpoints for
Deltamethrin

for Use in 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

Dermal

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

DAF: 1%	MOE = 100

	The endpoint, decreased motor activity in male rats, is taken from an
acute oral study (Wolansky et al., 2006).   

Using a nonlinear exponential threshold additivity model, a NOAEL (aka
threshold dose) was obtained by fitting motor activity data across 7
dose groups; 0, 0.03, 0.1, 0.3, 1, 3, and 10 mg/kg.  The NOAEL is an
estimate of the highest no-effect dose level at which treated rats would
not display any decrease in motor activity.

Supported by subchronic rat, subchronic dog and chronic dog studies with
NOAELs of 1mg/kg/day and LOAELs of 2.5 or 10 mg/kg/day based on signs of
neurotoxicity including unsteadiness, tremors and jerking movements,
salivation, and chewing on extremities (chronic dog only).

Inhalation

All Durations	NOAEL= 1 mg/kg/day	UFA= 10x

UFH=10x

IAF: 100%	MOE = 100

	Decreased motor activity in adult male rats (Wolansky et al., 2006).

See Dermal for supporting information.

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 (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  MOE = margin of exposure.  LOC = level of concern.

       Attachment 3.  DCI Justification for Immunotoxicity Study

Guideline Number: 870.7800

Study Title:  Immunotoxicity

Rationale for Requiring the Data

This is a new data requirement under 40 CFR Part 158 as a part of the
data requirements for registration of a pesticide (food and non-food
uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional
immunotoxicity testing and is designed to evaluate the potential of a
repeated chemical exposure to produce adverse effects (i.e.,
suppression) on the immune system. Immunosuppression is a deficit in the
ability of the immune system to respond to a challenge of bacterial or
viral infections such as tuberculosis (TB), Severe Acquired Respiratory
Syndrome (SARS), or neoplasia.  Because the immune system is highly
complex, studies assessing functional immunotoxic endpoints are helpful
in fully characterizing a pesticide’s potential immunotoxicity.  These
data will be used in combination with data from hematology, lymphoid
organ weights, and histopathology in routine chronic or subchronic
toxicity studies to characterize potential immunotoxic effects.  

Practical Utility of the Data

How will the data be used?

These animal studies can be used to select endpoints and doses for use
in risk assessment of all exposure scenarios and are considered a
primary data source for reliable reference dose calculation.  For
example, animal studies have demonstrated that immunotoxicity in rodents
is one of the more sensitive manifestations of TCDD
(2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive,
and endocrinologic toxicities.  Additionally, the EPA has established an
oral reference dose (RfD) for tributyltin oxide (TBTO) based on observed
immunotoxicity in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making? 

If the immunotoxicity study shows that the test material poses either a
greater or a diminished risk than that given in the interim decision’s
conclusion, the risk assessments for the test material may need to be
revised to reflect the magnitude of potential risk derived from the new
data.

 

If the Agency does not have the data, a 10X database uncertainty factor
might be applied for conducting a risk assessment from the available
studies.

 

Attachment 4.  International Residue Limit Status

Summary of US and International Tolerances and Maximum Residue Limits
for Deltamethrin 

US	Canada2	Mexico3	Codex

Residue Definition: 

40CFR§180.435

deltamethrin [(1 R ,3 R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid ( S )-
alpha -cyano-3-phenoxybenzyl ester and its major metabolites, trans
deltamethrin [( S )- alpha -cyano- m
-phenoxybenzyl(1R,3S)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarbo
xylate] and alpha-R -deltamethrin [( R )- alpha -cyano- m
-phenoxybenzyl-(1 R ,3 R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate] 	None

	deltamethrin	Sum of deltamethrin, alpha-R- and trans-deltamethrin
(1R-[1alpha(R*),3alpha]]-3-(2,2-dibromoethenyl)-2,2-dimethyl-cyclopropan
ecarboxylic acid, cyano(3-phenoxyphenyl)methyl ester and
[1R-[1alpha(S*),3beta]]-3-(2,2-dibromoethenyl)-2,2-dimethyl-cyclopropane
carboxylic acid, cyano(3-phenoxyphenyl)methyl ester)(fat-soluble).

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Commodity	US	Canada	Mexico	Codex

Almond, hulls	2.5	None

Apple, wet pomace	1.0

	Artichoke, globe	0.5

	Barley, bran	5.0

	Cattle, fat	0.05

	Cattle, meat	0.02

	0.5 (fat)

Cattle, meat byproducts	0.05

	0.03 (*) kidney, liver

Corn, field, forage	0.7

	Corn, field, refined oil	2.5

	Corn, field, stover	5.0

	Corn, pop, stover	5.0

	Corn, sweet, forage	10

	Corn, sweet, kernel plus cob with husks removed	0.03

	0.02 (*)

Corn, sweet, stover	15

	Cotton, refined oil	0.2

	Cotton, undelinted seed	0.04

0.04

	Egg	0.02

	0.02 (*)

Fruit, pome, Group 11	0.2

	0.2 apple

Goat, fat	0.05

	Goat, meat	0.02

	0.5 (fat)

Goat, meat byproducts	0.05

	0.03 (*) kidney, liver

Grain, aspirated fractions	65

	Grain, cereal, Group 15, except sweet corn	1.0

1 barley

1 corn

1 millet

1 oat

1 rice

1 sorghum

1 wheat	2 Po

Hog, fat	0.05

	Horse, fat	0.05

	Horse, meat	0.02

	0.5 (fat)

Horse, meat byproducts	0.05

	0.03 (*) kidney, liver

Lychee1	0.2

	Milk, fat (reflecting 0.02 ppm in whole milk)	0.1

	

0.05 F

Nut, tree, Group 14	0.1

	0.02 (*) hazelnuts

0.02 (*) walnuts

Onion, bulb	0.1

	0.05

Onion, green	1.5

	Poultry, fat	0.05

	Poultry, meat	0.02

	0.1 (fat)

Poultry, meat byproducts	0.02

	0.02 (*)

Radish, tops	4.0

	Rapeseed	0.2

0.2

	Rice, hulls	2.5

	Rye, bran	5.0

	Sheep, fat	0.05

	Sheep, meat	0.02

	0.5 (fat)

Sheep, meat byproducts	0.05

	0.03 (*) kidney, liver

Sorghum, grain, forage	0.5

	Sorghum, grain, stover	1.0

	Soybean, seed	0.1

0.1

	Soybean, hulls	0.2

	Starfruit1	0.2

	Sunflower, seed	0.1

	0.05 (*)

Tomato	0.2

	Tomato, paste	1.0

	Tomato, puree	1.0

	Vegetable, cucurbit, Group 9	0.2

	0.2

Vegetable, fruiting, Group 8	0.3

0.2 tomato	0.3 tomato

Vegetable, root, except sugar beet, Subgroup IB	0.2

	0.02 carrot

0.01 (*) radish

Vegetable, tuberous and corm, Subgroup IC	0.04

	Wheat, bran	5.0

	5 PoP

Citrus fruits

0.02

Field pea dry

1 Po	

Flowerhead brassica

0.1

Grapes

0.2

Leafy vegetables

2

Leek

0.2		

Legume vegetables

0.2

Lentil dry

1 Po		

Mushrooms

0.05

Olives

1		

Potato

	0.04	0.01 (*)

Pulses [dry beans]

	1	1 Po

Stone fruits

0.05

Strawberry

0.2		

Tea, green and black

5

Wheat flour

0.3 PoP

Wheat wholemeal

2 PoP

1There are no U.S. registrations for use of deltamethrin on starfruit
and lychee. 

2While there are no tolerances in Canada, there are numerous uses in
British Columbia and /or Eastern Canada:  alfalfa, Brassica vegetables,
corn, potatoes, canola, mustard, pasture, sunflower, tomato, wheat,
barley, oats, flax,  lentils, sugarbeets, strawberry, blueberry,
asparagus, apple, kale, peach, onion, pear, pepper..

3Mexico defers to US tolerances and/or Codex MRLs for its export
purposes.

3Po = postharvest; (*) = absent at the limit of quantitation.; F =
measured in milk fat;   PoP = postharvest processed commodity

US:

(2) A tolerance of 0.05 ppm is established for residues of the
insecticide deltamethrin (1 R ,3 R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid ( S
)-alpha-cyano-3-phenoxybenzyl ester and its major metabolites, trans
deltamethrin ( S )-alpha-cyano- m -phenoxybenzyl-(1 R ,3 R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate and alpha- R
-deltamethrin[( R )-alpha-cyano- m -phenoxybenzyl-(1 R ,3 R
)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate] as follows:	
	

(i) In or on all food/feed items (other than those covered by a higher
tolerance as a result of use on growing crops) in food/feed handling
establishments.

(ii) The insecticide may be present as a residue from application of
deltamethrin in food handling establishments, including food service,
manufacturing and processing establishments, such as restaurants,
cafeterias, supermarkets, bakeries, breweries, dairies, meat
slaughtering and packing plants, and canneries, feed handling
establishments including feed manufacturing and processing
establishments, in accordance with the following prescribed conditions:

(A) Application shall be limited to general surface and spot and/or
crack and crevice treatment in food/feed handling establishments where
food/feed and food/feed products are held, processed, prepared and
served. General surface application may be used only when the facility
is not in operation provided exposed food/feed has been covered or
removed from the area being treated. Spot and/or crack and crevice
application may be used while the facility is in operation provided
exposed food/feed is covered or removed from the area being treated
prior to application. Spray concentration shall be limited to a maximum
of 0.06 percent active ingredient. Contamination of food/feed or
food/feed contact surfaces shall be avoided.

Attachment 5.  Residential Postapplication Exposure and Risk Estimates

In order to provide a summary of the residential risks, focusing on
those for which there is a risk concern, HED has used the previously
calculated exposures, along with the revised LOC for adult and
children’s residential exposure.  The updated exposure and residential
risk estimates for the individual exposure pathways are provided in
Tables A.5.a through A.5.d, below.

Table A.5.a.  Deltamethrin Residential Postapplication Exposure of
Children

Scenario	Exposure

(mg/kg/day)	Projected Risk Estimates

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瑹▋Ѐ0.01% Sprays	0.00074	1,400

Indoor Crack & Crevice

Dermal

0.06 – 0.03% Sprays	0.0023 – 0.0011	430 - 870

0.02% Sprays	0.000768	1300

Hand-to-Mouth

0.06 – 0.02% Sprays	0.0036 – 0.0012	280 - 830

0.01% Sprays	0.0006	1,700

Ingestion of Paint Chips

Bug Juice Paint Additive (Reg. No. 4733211) 	2,000

Table A.5.b.  Deltamethrin Residential Dermal Handler Exposure to
Deltamethrin 4% Pet Collar 

Application Rate 1 (mg ai/treatment)	Dermal Absorption Factor % 
Fraction of A.I. Applied 	Exposure 2

(mg/kg/day)	MOE 3

1008	0.01	0.01	0.00144	700

1.  Application Rate = based on product net weight of 0.9 ounces =
28,000 mg x 0.9 ozs x 0.04 % ai. = 1008 mg ai

2.  Exposure (mg/kg/day) = (AR * DA * F)/ BW 

3.  MOE = NOAEL (1 mg/kg/day)/Exposure (mg/kg/day)

Table A.5.c.  Deltamethrin Residential Dermal Postapplication Exposure
to Deltamethrin 4% Pet Collar 

AR 1

 (mg ai/ trtmnt)	SApet 2	FAR 3	SAhug 4	DAF %	Dose 5 (mg/kg/day)	MOE 6

Adult

1008	5986	0.2	5625	0.01	0.027 	37

Toddler

1008	5986	0.2	1875	0.01	0.042	24

1.  Application Rate = based on product net weight of 0.9 ounces =
28,000 mg x 0.9 oz x 0.04 % a.i. = 1008 mg ai

2.  SA pet = surface area of a treated dog (5986 cm2/ animal)

3.  FAR	= fraction of the application rate available as transferable
residue (0.20), or fraction determined from a chemical-specific petting
study

4.  SA hug = surface area of a child hug (5625 cm2 (adult), 1875 cm2
(toddlers))

5.  Dose (mg/kg/day) = [((AR * FAR) / (SA pet)) * (SA hug) * (DA)] 

			                 BW (kg)

6. MOE = NOAEL (1 mg/kg/day)/Exposure (mg/kg/day)

Table A.5.d.  Deltamethrin Residential Oral Postapplication Exposure to
Deltamethrin 4% Pet Collar 

AR 1

 (mg ai/ trtmnt)	SApet 2	FAR 3	SAL 4	SA hands 5	Frequency 6	Dose7

(mg/kg/day)	MOE 8

Toddler

1008	5986	0.2	0.5	20	1	0.0224	45

1.  Application Rate = based on product net weight of 0.9 ounces =
28,000 mg x 0.9 oz x 0.04 % a.i. = 1008 mg ai

2.  SA pet = surface area of a treated dog (5986 cm2/ animal)

3.  FAR	= fraction of the application rate available as transferable
residue (0.20), or fraction determined from a chemical-specific petting
study

4. SAL	= saliva extraction factor (50%)

5.  SA hands = surface area of a child’s hands (20 cm2)

6.  Freq	= frequency of hand-to-mouth events (1 event/day)

7.  Dose (mg/kg/day) = [((AR * FAR) / SApet)) * (SAL) * SAhands * Freq)]

BW (kg)

8. MOE = NOAEL (1 mg/kg/day)/Exposure (mg/kg/day)

Deltamethrin Registration Review Human Health Assessment Scoping
Document

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