Document ID: EPA-HQ-OPP-2006-0875-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-02-06T05:00Z

Interregional Research Project Number 4 (IR-4)  

[Contact: Sidney Jackson, 703-305-7610]

PP # 7E7298

EPA has received pesticide petitions (PP 7E7298) from IR-4, 681 U.S.
Highway #1 South, North Brunswick, NJ 08902-3390 proposing, pursuant to
section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(d), to amend 40 CFR 180.466, by establishing tolerances for
residues of the insecticide fenpropathrin, alpha-cyano-3-phenoxybenzyl
2,2,3,3-etramethylcyclopropanecarboxylate in or on the following raw
agricultural commodities: Caneberry Subgroup 13-07A at 12 parts per
million (ppm) and olives at 5 ppm.  EPA has determined that the
petitions contain data or information regarding the elements set forth
in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
support granting of the petitions. Additional data may be needed before
EPA rules on the petitions.

A. Residue Chemistry

    1. Plant metabolism. The plant metabolism of fenpropathrin has been
studied in five different crop plant species: Cotton, apple, tomato,
cabbage, and bean. Each of the studies involved foliar treatment of the
plants under either greenhouse or field conditions. In all studies the
total toxic residue is best defined as parent, fenpropathrin. The
primary metabolic pathway for fenpropathrin in plants is similar to that
in mammals. There are no qualitatively unique plant metabolites.

    2. Analytical method. Adequate analytical methodology is available
to detect and quantify fenpropathrin at residue levels in numerous
matrices. The methods use solvent extraction and partition and/or column
chromatography clean-up steps, followed by separation and quantitation
using capillary gas liquid chromatography (GLC) with FID. 

The extraction efficiency has been validated using radiocarbon samples
from the plant and animal metabolism studies. The enforcement methods
have been validated at independent laboratories and by EPA. The limit of
quantification (LOQ) for fenpropathrin in raw agricultural commodity
samples is usually 0.01 ppm.

    3. Magnitude of residues. Residue data has been submitted for
caneberry and olives and the requested tolerances are adequately
supported.

B. Toxicological Profile

An assessment of the toxic effects caused by fenpropathrin is discussed
in III. A. and III. B. of the Federal Register dated September 23, 2005
(OPP-2005-0133) (FRL-7738-7).  In addition, additional toxicological
studies have been completed and will be submitted to reduce the
uncertainty factor associated with fenpropathrin.

    1. Animal metabolism. Four metabolites were found in the urine of
rats dosed with alcohol labeled fenpropathrin. The major metabolites
were the sulfate conjugate of 3-(4'-hydroxyphenoxy)benzoic acid and
3-phenoxybenzoic acid (22-44% and 3-9% of the administered dose,
respectively). The major urinary metabolites of the acid-labeled
fenpropathrin were TMPA-glucuronic acid and TMPA-CH2OH (11-26% and 6-10%
of the administered dose, respectively). None of the parent chemical was
found in urine.

The major elimination products in the feces included the parent chemical
(13-34% of the administered dose) and four metabolites. The fecal
metabolites (percentage of administered dose) included
CH2OH-fenpropathrin (9-20%), 4'-OH-fenpropathrin (4-11%),
COOH-fenpropathrin (2-7%), and 4'-OH-CH2OH-fenpropathrin (2-7%). There
are no qualitatively unique plant metabolites. The primary aglycones are
identical in both plants and animals; the only difference is in the
nature of the conjugating moieties employed.

    2. Metabolite toxicology. The metabolism and potential toxicity of
the small amounts of terminal plant metabolites have been tested on
mammals. Glucoside conjugates of 3-phenoxy-benzyl alcohol and
3-phenoxybenzoic acid, administered orally to rats, were absorbed as the
corresponding aglycones following cleavage of the glycoside linkage in
the gut. Normal metabolic pathways rapidly and completely eliminated the
free or reconjugated aglycones. The glucose conjugates of
3-phenoxybenzyl alcohol and 3-phenoxy-benzoic acid are less toxic to
mice than the corresponding aglycones.

    3. Endocrine disruption. No special studies to investigate the
potential for estrogenic or other endocrine effects of fenpropathrin
have been performed. However, as referenced above (see toxicological
profile), a large and detailed toxicology database exists for the
compound including studies acceptable to the Agency in all required
categories. These studies include evaluations of reproduction and
reproductive toxicity and detailed pathology and histology of endocrine
organs following repeated or long-term exposure. These studies are
considered capable of revealing endocrine effects and no such effects
were observed.

C. Aggregate Exposure

    1. Dietary exposure. Chronic and acute dietary exposure analyses
were performed for fenpropathrin using anticipated residues, and
accounting for proportion of the crop treated. The crops included in the
analyses are the raw agricultural commodities cottonseed, currants,
peanuts, strawberries, soybeans, lingonberry, juneberry, salal, and
grapes, and the crop groupings succulent shelled pea (6B), head and stem
brassica 

(5A), fruiting vegetables (8), cucurbit vegetables (9), citrus fruits
(10), bushberry (13B) and pome fruits (11); processed products from
these crops; and the resulting secondary residues in meat, milk, and
eggs. Soybeans (and soybean products) were entered into the analyses
using tolerance-level residues and 1% of the crop treated for chronic
assessments, and 2% of the crop treated for acute assessments. 
Proportion of crop treated was assumed to be equal for all crops in a
crop grouping.

Based on the minimal dietary intake of olives and caneberries, the
magnitude of uses currently registered, and current aPAD and cPAD
levels, it is not necessary to complete an additional dietary analysis
to include these uses.  Also, additional toxicological studies have been
completed and will be submitted to reduce the uncertainty factor
associated with fenpropathrin.  None of the studies lowered the
endpoints utilized in the risk assessment.  

    i. Food--a. Acute. Acute dietary exposure was calculated for the
U.S. population, females (13+), males (20+ years) and five children
subgroups. At the 99.9th percentile of exposure, the acute population
adjusted dose (aPAD) of 0.06 milligrams/kilogram body weight/day (mg/kg
bwt/day) is not exceeded.

    b. Chronic. Chronic dietary exposure was calculated for the U.S.
population and 25 population subgroups. Chronic dietary exposure was at
or below 0.6% of the chronic population adjusted dose (cPAD) of 0.025
mg/kg bwt/day, with apples being the commodity contributing the most to
chronic exposure. Generally speaking, the Agency has no cause for
concern if total residue contribution for published and proposed
tolerances is less than 100% of the cPAD.

    ii. Drinking water. Since fenpropathrin is applied outdoors to
growing agricultural crops, the potential exists for fenpropathrin to
reach ground water or surface water that may be used for drinking water.
To further quantify exposure from drinking water, potential surface
water and ground water concentrations for fenpropathrin were estimated
using First Index Reservoir Screening Tool (FIRST) and Screening
Concentration in Groundwater (SCI-GROW) modeling. Use on citrus, the
most intense field use, was modeled. SCI-GROW modeling indicated that
fenpropathrin would not be detected in ground water. FIRST modeling of
potential surface water concentrations of fenpropathrin yielded annual
average parts per billion (0.833 ppb) and peak day (1.030 ppb)
concentrations. These estimated drinking water environmental
concentrations (DWEC) could be used for chronic and acute exposures,
respectively.

    2. Non-dietary exposure. No endpoints of concern were identified by
the Health Effects Division, Hazard Identification Assessment Review
Committee for dermal or inhalation exposures of any duration. Thus, no
risk assessment is needed.

D. Cumulative Effects

     There are numerous other pesticidal compounds, pyrethroids and the
natural pyrethrins, that are structurally related to fenpropathrin and
may have similar effects on animals. In consideration of potential
cumulative effects of fenpropathrin and other substances that may have a
common mechanism of toxicity, there are currently no available data or
other reliable information indicating that any toxic effects produced by
fenpropathrin would be cumulative with those of other chemical
compounds, or other pyrethroids. Thus, only the potential risks of
fenpropathrin have been considered in this assessment of aggregate
exposure and effects.

     Valent will submit information for EPA to consider concerning
potential cumulative effects of fenpropathrin consistent with the
schedule established by EPA at 62 FR 42020 (August 4, 1997) (FRL-5734-6)
and other EPA publications pursuant to the Food Quality Protection Act.

E. Safety Determination

    1. U.S. population--i. Acute. The potential acute exposure from food
to the U.S. population and various non-child/infant population subgroups
provide values well below the aPAD. In a conservative policy, the Agency
has no cause for concern if total acute exposure calculated for the
99.9th percentile is less than 100% of the aPAD.  Acute DWLOC values are
not exceeded by modeled DWEC values. It can be concluded that there is a
reasonable certainty that no harm will result to the overall U.S.
population and many non-child/infant subgroups from aggregate, acute
exposure to fenpropathrin residues.

    ii. Chronic. Using the dietary exposure assessment procedures, the
calculated chronic dietary exposure resulting from residue exposure from
existing and proposed uses of fenpropathrin is minimal. The estimated
chronic dietary exposure from food for the overall U.S. population and
many non-child/infant subgroups ranges from 0.6% (children 1-6 years
old, 0.000155 mg/kg bwt/day) to 0.1% (several groups) of the cPAD.
Generally, the Agency has no cause for concern if total residue
contribution is less than 100% of the cPAD. Chronic drinking water
levels of concern (DWLOC) values are not exceeded by modeled drinking
water estimated concentration (DWEC) values. It can be concluded that
there is a reasonable certainty that no harm will result to the overall
U.S. population and many non-child/infant subgroups from aggregate,
chronic dietary exposure to fenpropathrin residues.

2. Infants and children. The estimated chronic dietary exposure from
food to infant and child subgroups ranges from 0.6% children 1-6 years
old, 0.000155 mg/kg bwt/day to 0.1% nursing infants, 0.000026 mg/kg
bwt/day of the cPAD. Generally, the Agency has no cause for concern if
total residue contribution is less than 100% of the cPAD. Chronic 

DWLOC values are not exceeded by modeled DWEC values. It can be
concluded that there is a reasonable certainty that no harm will result
to infant and child subgroups of the U.S. population from aggregate,
chronic exposure to fenpropathrin residues.

F. International Tolerances

186	

FENPROPATHRIN

Main uses	

8	

INSECTICIDE/ACARACIDE

JMPR	

83

ADI	

0.03 mg/kg body weight (1993)

RESIDUE

	

Fenpropathrin (fat soluble)

Commodity	

	

	

	

Code

	

Name	

MRL (mg/kg)	

Step	

JMPR	

CCPR

MM	

0812	

Cattle meat	

    0.5  (fat)    	

CXL	

	

(1997)

ML	

0812	

Cattle milk	

    0.1  F	

CXL	

	

(1997)

MO	

0812	

Cattle, Edible offal of	

    0.05	

CXL	

	

(1995)

SO	

0691	

Cotton seed	

    1	

CXL	

	

(1995)

OC	

0691	

Cotton seed oil, Crude	

    3	

CXL	

	

(1995)

VO	

0440	

Egg plant 	

    0.2	

CXL	

	

(1997)

PE	

0112	

Eggs	

    0.01  (*)	

CXL	

	

(1995)

VC	

0425	

Gherkin	

    0.2	

CXL	

	

(1995)

FB	

0269	

Grapes	

    5	

CXL	

	

(1997)

VO	

0445	

Peppers, Sweet	

    1	

CXL	

	

(1995)

FP	

0009	

Pome fruits	

    5	

CXL	

	

(1995)

PM	

0110	

Poultry meat	

    0.02  (fat)	

CXL	

	

(1995)

PO	

0111	

Poultry, Edible offal of	

    0.01  (*)	

CXL	

	

(1995)

VO

	

0448

	

Tomato

	

    1	

CXL	

	

(1995)

There are small differences between the Section 408 tolerances and the
Codex MRL values for secondary residues in animal products. These minor
differences are mainly caused by differences in the methods used to
calculate animal feed dietary exposure. The only substantial difference
between the US tolerance and the Codex MRL value is for tomatoes. The
JMPR reviewer required that the MRL exceed the highest field residue
value rounded up to unit value. The EPA reviewer agreed with Valent that
one set of field residue samples was possibly compromised by the
presence of a high rate processing treatment nearby. High outliers were
ignored, and the tolerance was set at 0.6 ppm.