Document ID: EPA-HQ-OPP-2008-0140-0026
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-09-02T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  August 19, 2008

SUBJECT:	d-Phenothrin (Sumithrin®):  Addendum to Residential Exposure
Assessment

 

PC Code:  069005	DP Barcode: 326931

Decision No.: 	Registration No.: 2596-150, 2596-151

Petition No.:  None	Regulatory Action: Reregistration

Assessment Type: ORE	Reregistration Case No.: 0426

TXR No.:  None	CAS No.: 026022-80-2

MRID No.:  None	40 CFR: NA

        	

FROM:	Becky Daiss

Biologist

Reregistration Branch 4/HED (7509C)

THROUGH:	Susan Hummel

Branch Senior Scientist

Reregistration Branch 4/HED (7509C)

TO:		Jennifer Howenstine 

Chemical Review Manager

		Reregistration Branch 3

		Special Review and Registration Division (7508C)

		       and

	Ann Sibold 

Review Manager

Insecticide Branch

	Registration Division (7505C)

	

This is an addendum to the Health Effects Division’s (HED) July 2,
2008 assessment of residential exposure and risk for d-phenothrin (B.
Daiss, D326945).  This addendum provides a refined assessment of
residential exposure from use of d-Phenothrin as a spot on treatment for
dogs and puppies.  The probabilistic assessment conducted previously for
this scenario indicated risks of concern to toddlers from incidental
ingestion of residues on pets via hand-to-mouth activity.  This refined
assessment incorporates an incidental oral toxicity endpoint which was
derived using Benchmark Dose analysis.  Based on this refined analysis,
this pet treatment scenario does not present risks of concern.  

Formulation and Use Pattern

The products assessed, EPA Reg. Nos. 2596-150 and 2596-151, are liquid
products containing 87.5% of the active ingredient d-Phenothrin.  These
products are applied to dogs and puppies to control fleas and ticks. 
They are packaged and applied in varying amounts based on the weight of
the animal.  The products are applied by squeezing the contents out of
the tube from the dog’s shoulder blades along the back to the base of
the tail.  

Toxicological Endpoint Selection

The endpoint used to conduct this assessment was derived using benchmark
dose (BMD) analysis.  Endpoints and levels of concern (LOCs) are
summarized below in Table 1.  The BMD analysis is provided in a separate
memorandum (B. Daiss, D326934, TXR0052377, 8/19/08).

Table 1. Summary of Toxicological Doses and Endpoints for d-Phenothrin
for Use in Non-Occupational Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	 LOC for
Risk Assessment	Study and Toxicological Effects

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

Intermediate-Term 

(1-6 months)	BMDL10 = 100 mg/kg/day	UFA= 10 x

UFH= 10 x

FQPA SF= 10 x

UFDB 	Residential LOC for MOE = 1000	2-generation rat reproduction
study. The NOAEL is 1000 ppm (50 mg/kg/day).  The LOAEL is 3000 ppm (150
mg/kg/day) based on decreased body weight (4-6%) and increased liver
weight in F0 and F1 parental animals, and an increase in absolute and
relative spleen weight, and decreased absolute uterine weight in F1
adults and on decreased body weight gain during lactation of F2b pups,
and decreased litter size of F1b litters at day 1, decreased absolute
heart and kidney weight in F2b males, increased relative liver weight in
male and female F2b pups.

Dermal All Durations	Dermal toxicity systemic LOAEL = not established

21/28 Dermal toxicity study in rats dermal toxicity systemic LOAEL not
established up to 1000 mg/kg/day (HDT)

BMD10 = The dose associated with a 10% change of a biological effect. 
BMDL10 = A lower one-sided confidence limit on the BMD10  UF =
uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no
observed adverse effect  level, LOAEL = lowest observed adverse effect
level, MOE = margin of exposure, LOC = level of concern, NA = Not
Applicable

Residential Exposure Assessment 

	The exposure scenario assessed for this pet application is toddler
incidental ingestion of residues on pets via hand-to-mouth after pet
treatment.  HED conducted a probabilistic assessment using Cumulative
and Aggregate Risk Evaluation System (CARES® Version 3.0;   HYPERLINK
"http://cares.ilsi.org/"  http://cares.ilsi.org/ ), a publicly available
software program for this residential exposure scenario.  The
calculations and algorithms used to estimate exposure for the various
scenarios and routes are consistent with standard Agency practice for
residential pesticide exposure assessment.  The exposure scenario was
assessed using standard EPA algorithms for exposure estimation. 
Distributional inputs were included in the probabilistic assessment
where possible.  The probabilistic assessment assumes postapplication
exposure occurs on the “day of application.”  Five thousand (5000)
product uses are assessed for each exposure scenario i.e., percentile
distributions for each scenario are generated from 5000 exposure
estimates.  A dermal exposure assessment for d-Phenothrin is not
required because dermal effects were not observed at the limit dose in
animal studies.  

	Exposure Factor Distributions

	Inputs and distributions considered for the CARES assessment are
provided below.

Many of the non-phenothrin-specific distributional inputs are based on
EPA’s n-methyl Carbamate Revised Cumulative Risk Assessment (NMCCRA),
the most recent EPA publication using probabilistic methods and
distributional inputs for residential exposure assessment (EPA, 2007). 

	Phenothrin-specific Factors

Residue Characteristics

•    Application Rate - 0.09 fl oz (2.6 mL)/ per 6000 cm2 (2230 mg
ai/animal)

•    Dissipation:  standard Agency practice for residential exposure
is to assess exposure on the “day of application”.  Therefore, use
of a 0.00001 day half-life in the CARES submission is consistent with
this practice because it is assuming no residue dissipation. 

• 	Residue Transfer:  Point estimate of 2% described used in the
deterministic assessment.  

	

	Use Pattern

• 	Indoor Monthly probability:  Equal use for each month of the year. 
This assumption is acceptable, since these probabilities are irrelevant
when assessing “day of application” exposures.

• 	Day of Week probability:  Equal use for each day of the week.  This
assumption is acceptable, since these probabilities are irrelevant when
assessing “day of application” exposures.

• 	Annual Use: Ten (10) uses per year.  This value is irrelevant for
“day of application” exposure assessment.  [500 CARES individuals
are included in a model run.  A total of 5000 products (500 x 10) are
assessed.]  

• 	Treatment Interval:  Thirty (30) day interval between treatments. 
This value is irrelevant for “day of application” exposure
assessment.  

• 	Co-occurrence Probability:  Set to zero.  Co-occurrence is
irrelevant for “day of application” exposures.

Non-Phenothrin-specific Factors

• 	Body Weight:  Correlated to randomly selected individual from the
specified subpopulation in the reference population.

• 	Exposure Duration (expressed as hours per day):  triangular
distribution (0.03, 0.108, 1.03).  

• 	Hand-to-Mouth Exposure Factors (children only)

      -		Hand-to-Mouth Events: (expressed as contacts per hour)
Triangular distribution (1, 13, 26).  

   	-  	Hand-to-Mouth Residue Transfer (i.e., saliva extraction factor)
(expressed as a percentage of hand residue):  Uniform distribution of
20% to 50%.   

  	-  	Surface Area of Hand Mouthed (cm2):  Triangular distribution (1,
7, 20).

	Probabilistic Exposure and Risk Estimates

Results of the probabilistic CARES assessment for the pet
post-application incidental oral exposure scenario are presented in
Table 2.  Risks are presented in the form of Margins of Exposure (MOEs)
by percentile of exposure.  Based on this refined analysis, this pet
treatment scenario does not present risks of concern i.e., MOEs greater
than 1000 are seen at the 99.9th percentile.  

Table 2: CARES Assessment – Sumithrin MOEs for Pet Care Spot-on
Children 1-2 years HTM Exposure – LOC/MOE = 1000

Percentile	Estimated LOC/MOE

99.9	1350

99.5	1700

99	2000

	 

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