fenpropathrin (Danitol) Pesticide Petition Filing 7/98
[Federal Register: August 5, 1998 (Volume 63, Number 150)]
[Notices]
[Page 41835-41844]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05au98-77]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-818; FRL-6017-1]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-818, must
be received on or before September 4, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
[[Page 41836]]
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow the instructions under ``SUPPLEMENTARY
INFORMATION.'' No confidential business information should be submitted
through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:
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Office location/
Product Manager telephone number Address
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Sidney Jackson................ Rm. 268, CM #2, 703- 1921 Jefferson
305-7610, e- Davis Hwy,
mail:jackson.sidney@e Arlington, VA
pamail.epa.gov.
Beth Edwards.................. Rm. 206, CM #2, 703- Do.
305-5400, e-mail:
edwards.beth@epamail.
epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-818] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: July 23, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summary announces the
availability of a description of the analytical methods available to
EPA for the detection and measurement of the pesticide chemical
residues or an explanation of why no such method is needed.
3. Valent U.S.A. Company
PP 7F3485, 1F3949, 6F4648
EPA has received a request from Valent U.S.A. Company, 1333 North
California Boulevard, Suite 600, Walnut Creek, CA 94596-8025 proposing
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 346a(d), to amend 40 CFR 180.466 by establishing tolerances
for residues of fenpropathrin, alpha-cyano-3-phenoxybenzyl 2,2,3,3-
tetramethylcyclopropanecarboxylate, in or on the raw agricultural
commodities pome fruit (crop group 11) and grapes at 5.0 ppm, head and
stem brassica (crop group 5A) at 3.0 ppm, citrus fruit (crop group 10)
at 2.0 ppm, melons (crop group 9A) at 0.5 ppm, and in the processed
products citrus oil at 50 ppm, raisins at 10 ppm, and dried citrus pulp
at 4.0 ppm. The tolerances were first proposed in response to pesticide
petitions PP 7F3485, 1F3949, and 6F4648. EPA has determined that the
request contains 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
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
Background Information and Use Profile
Fenpropathrin is the active ingredient in DANITOL 2.4 EC Spray (EPA
Reg. No. 59639-35) and TAME 2.4 EC Spray (EPA Reg. No. 59639-77). To
support DANITOL use, tolerances have been established on cottonseed;
cottonseed oil; meat, meat byproducts, and fat of cattle, goats, hogs,
horses, sheep and poultry; eggs; milkfat; peanuts; peanut hay;
strawberries; and tomatoes. A time limited tolerance on red currants
has been established to support a Section 18 in the state of Washington
with an expiration date of December 31, 1998. The pending tolerances
that are the subject of this notice of filing are on grapes and on the
crop groups pome fruits (11), citrus (10), head and stem brassica (5A),
and melons (9A), with associated processing products citrus oil,
raisins, and dried citrus pulp.
Fenpropathrin is a pyrethroid insecticide with broad spectrum
activity on insects and mites. When formulated as the product DANITOL
2.4 EC Spray the product is registered for agricultural use on outdoor
terrestrial food crops. A separate fenpropathrin product, TAME 2.4 EC
Spray, is registered for commercial, professional non-food use on
indoor and outdoor ornamental and nursery stock. There are no uses
registered for professional indoor pest control, termite prevention,
homeowner use, or turf application.
The products are applied as dilute emulsions in water directly to
plants to control harmful insects and mites. In agriculture, depending
on the crop and pest, the use rates vary from 0.15 to 0.4 pounds of
active ingredient per acre (lb. ai./a), with a maximum total use on all
crops of 0.8 lb. ai./a per season. Pre-harvest intervals (phi) range
from 21-days on cotton to 1-day on citrus. Plant metabolism studies
have shown that the plant and animal residues are best defined as
parent fenpropathrin. Because of the mode of application and short phi,
finite residues of fenpropathrin are often found on treated
agricultural commodities requiring tolerances above the 0.01 ppm limit
of quantitation of the residue analytical methodology. However,
analyses of RAC samples from plants treated at the
[[Page 41839]]
maximum application rates, and minimum retreatment intervals and phi
demonstrate that anticipated residues are much below tolerance levels.
In addition, it has been demonstrated that fenpropathrin is not plant
systemic and that residues occur only on plant parts that have been
directly treated.
A. Residue Chemistry
Summary. An extensive plant and animal metabolism data base
demonstrates that the appropriate definition of aged fenpropathrin
residue is parent. Ruminant and poultry metabolism followed by feeding
studies have shown that the ratios of residues in feed to secondary
residues in animal products are very low in most commodities, with
higher (but still relatively low) ratios in body fat and milk fat. This
section will describe metabolism and field residue data supporting the
establishment of tolerances for residues of fenpropathrin in or on the
raw agricultural commodities pome fruit (crop group 11) and grapes at
5.0 ppm, head and stem brassica (crop group 5A) at 3.0 ppm, citrus
fruit (crop group 10) at 2.0 ppm, melons (crop group 9A) at 0.5 ppm,
and in the processed products citrus oil at 50 ppm, raisins at 10 ppm,
and dried citrus pulp at 4.0 ppm The approved analytical method is
capillary gas-liquid chromatography with flame ionization detection.
1. Plant metabolism. The plant metabolism of fenpropathrin has been
studied in five different crop plant species: cotton, apple, tomato,
cabbage, and bean. Radiocarbon labeling has been in the cyclopropyl
ring of the acid, in the aryl rings of the alcohol, and in the nitrile
of fenpropathrin, a cyanohydrin ester. The permutations of radiocarbon
label position and plant species yield a total of 17 separate, reviewed
studies. Each of the studies involved foliar treatment of the plants
under either greenhouse or field conditions and, while the actual
treatment conditions and times to harvest and analyses varied from
study to study, the results of the many studies are remarkably
consistent. The total toxic residue is best defined as parent,
fenpropathrin.
Fenpropathrin remains associated with the site of application and
only traces are found in seeds (e.g., bean or cotton) or in other parts
of the plant not directly exposed to the application. Much of the
parent residue can be removed from the plant material with a mild
hexane/acetone or hexane rinse, demonstrating that the residue is
located on or near the outside surface of the plant material. The
primary metabolic pathway for fenpropathrin in plants is similar to
that in mammals. There are no qualitatively unique plant metabolites;
the primary aglycones are identical in both plants and animals.
2. Analytical method. Adequate analytical methodology is available
to detect and quantify fenpropathrin (and its metabolites) 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 column gas-liquid
chromatography with flame ionization detection. 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
quantitation for fenpropathrin in raw agricultural commodity samples is
0.01 ppm.
3. Magnitude of residues--i. Pome fruit (Crop Group 11). The
proposed section 408 tolerance for fenpropathrin in/on Pome Fruit (Crop
Group 11) is 5.0 ppm. The proposed tolerance will permit finite
residues of fenpropathrin on pome fruit -- apple, pear, oriental pear,
crabapple, and related fruits -- as a result of application of DANITOL
2.4 EC Spray to orchards. The field residue data to support a
fenpropathrin tolerance on the pome fruit crop grouping includes data
on apples from 26 sites and pears from 18 sites providing data from 44
sites across the U.S. The mean residue from all samples is 1.83 ppm. In
the subset of samples that exactly fit the proposed use pattern the
average residue is 0.83 ppm (n = 16, <greek-s>n -1 = 0.55 ppm) with a
maximum value of 1.8 ppm.
ii. Apples. The residue data base from apples that supports the
proposed crop group tolerance includes all samples from field residue
studies that were treated two or more times at 0.4 lb. ai./a with a 14-
day phi. These experiments were performed over 5- years at 26 sites in
10 states. There were 38 separate treatments yielding 73 separate,
treated samples for analysis. The average residue was 2.15 ppm (n =
73,<greek-s>n -1 = 1.37 ppm). These data do not include supporting
information at higher or lower rates, and harvested at different phi.
In the 38-treatment data base there are only four treatments with only
two applications that are completely consistent with the proposed use
pattern that is limited to a maximum single application rate of 0.4 lb.
ai./a, a seasonal maximum of 0.8 lb. ai./a, and a 14 phi. The highest
average residue (HAR) found in these crop field trials for
fenpropathrin on apples was 1.13 ppm. The average residue was 0.77 ppm
(n = 8, <greek-s>n -1 = 0.40). Data obtained by separate analyses of
peelings and pulp demonstrated that the bulk of fenpropathrin residues
were located on the peeling of the apples.
Five apple processing studies were performed. These studies
demonstrated that fenpropathrin residues did not concentrate in apple
juice (concentration factor all <<1, average = 0.06), but did
concentrate in wet pomace (average concentration factor = 3.05). No
additional tolerance for the processed product wet apple pomace is
needed because the HAR times the average concentration factor for wet
pomace is less than the proposed tolerance of 5 ppm (1.13 ppm x 3.05 =
3.45 ppm).
iii. Pears. The residue data base from pears that supports the
proposed crop group tolerance includes all samples from field residue
studies that were treated two or more times at 0.4 lb. ai./a with a 14-
day phi. These experiments were performed over 4-years at 18 sites in 5
states. There were 30 separate treatments yielding 60 separate, treated
samples for analysis. The average residue was 1.44 ppm (n = 60,
<greek-s>n -1 = 1.01). This does not include supporting information at
higher or lower rates, and harvested at different phi. In the 30-
treatment data base there are only four treatments with only 2
applications that are completely consistent with the proposed use
pattern, which is the same as in apples, and is limited to a maximum
single application rate of 0.4 lb. ai./a, a seasonal maximum of 0.8 lb.
ai./a, and a 14-day phi. The HAR found in these crop field trials for
fenpropathrin on pears was 1.8 ppm. The average residue was 0.88 ppm (n
= 8, <greek-s>n -1 = 0.69).
iv. Grapes. The proposed section 408 tolerance for fenpropathrin on
grapes is 5 ppm. The residue data base that supports the tolerance
includes all samples from field residue studies that were treated 4-
times at 0.2 lb. ai./a with a 21-day phi. Excluded from the calculation
of the tolerance, and the chronic and acute exposure analyses is data
from one site that were demonstrated to be outliers (The analytical
determinations were very high, more than six sigma above the mean of
the other determinations). These experiments were performed over 4-
years at 14 sites in 4 states. There were 14 separate treatments
yielding 28 separate, treated samples for analysis. The average residue
was 1.06 ppm (n = 28, <greek-s>n -1 = 0.71). This does not include
supporting information at higher or lower rates, different numbers of
applications, or different phi. The HAR
[[Page 41840]]
found in crop field trials for fenpropathrin on grapes was 3.1 ppm.
Four processing studies yielding raisins and juice, and 5
additional studies yielding grape juice only (total of 9), were
performed. These studies demonstrated that fenpropathrin residues were
greatly reduced in grape juice (concentration factor all <<1, average =
0.06), but did concentrate in raisins (average concentration factor =
1.76). An additional tolerance for the processed product raisins is
needed because the HAR times the average concentration factor for
raisins is greater than the proposed tolerance of 5 ppm (3.1 ppm x 1.76
= 5.55 ppm). A Section 408 tolerance for fenpropathrin on raisins of 10
ppm is proposed.
v. Citrus. The proposed Section 408 tolerance for fenpropathrin on
citrus fruit (Crop Group 10) is 2 ppm. The residue data base from
citrus that supports the tolerance includes all samples from field
residue studies that were completely consistent with the proposed use
pattern of 2 applications at 0.4 lb. ai./a with a 1-day phi. In
oranges, the experiments were performed over 5-years at 13 sites in 4
states. There were 13 separate treatments yielding 24 separate, treated
samples for analysis. The average residue in oranges was 0.39 ppm (n =
24, <greek-s>n -1 = 0.35 ppm). In grapefruit, the experiments were
performed in a single year at 7 sites in 3 states. There were 7
separate treatments yielding 14 separate, treated samples for analysis.
The average residue in grapefruit was 0.29 ppm (n = 14, <greek-s>n -1 =
0.13 ppm). In lemons, the experiments were performed in a single year
at 3 sites in 2 states. There were 3 separate treatments yielding 6
separate, treated samples for analysis. The average residue in lemons
was 0.52 ppm (n = 6, <greek-s>n -1 = 0.06 ppm).
For the overall crop grouping citrus fruits the average residue was
0.37 ppm (n = 44, <greek-s>n -1 = 0.28 ppm). The HAR found in all
citrus crop field trials meeting the proposed use pattern for
fenpropathrin on citrus was 1.2 ppm. These overall citrus data only
include data from samples that are consistent with the proposed use
pattern, and do not include supporting information at higher or lower
rates, and harvested at different phi. Data obtained by separate
analyses of peelings and pulp from oranges demonstrated that the bulk
of fenpropathrin residues were located on the peeling, exterior, of the
oranges.
There are two processing studies performed in citrus (oranges) with
processing to juice, dried citrus pulp, and citrus oil. The studies
demonstrated that fenpropathrin did not concentrate in juice
(concentration factor all <<1), but did concentrate in dried citrus
pulp (average concentration factor = 2.6), and in citrus oil (average
concentration factor = 40.5). Thus it can be calculated from the HAR
that residues of 3.12 ppm (1.2 x 2.6) could occur in dried citrus pulp
and 48.6 ppm (1.2 x 40.5) could occur in citrus oil. Since residues
could be present in the not ``ready to eat'' commodities at levels
(3.12, 48.6 ppm) appreciably higher than the proposed RAC tolerance of
2 ppm, tolerances are being proposed. After rounding, the proposed
tolerances are 4.0 ppm for dried citrus pulp, and 50.0 ppm for citrus
oil.
vi. Melons (Cantaloupe). The proposed Section 408 tolerance for
fenpropathrin in/on melons (crop group 9A) is 0.5 ppm. The field
residue data that support this proposal come from 10 locations in 7
states. At these ten locations there was a total of 14 separate trials,
yielding 36 separate, treated samples for analysis. Samples from
treatments that were consistent with the proposed maximum use pattern -
- 0.2 lb. ai./a, 4 applications, 7-day spray interval, 7-day pre-
harvest interval -- gave 20 separate samples for analysis. The mean of
the 20 determinations is 0.175 ppm (n = 20, <greek-s>n-1 = 0.077 ppm)
and a maximum value of 0.31 ppm. Separate analyses of pulp and rind
demonstrated that the bulk of the residues were present on the rind.
vii. Head and Stem Brassica. A proposed Section 408 tolerance of
3.0 ppm is proposed for fenpropathrin in/on Head and stem brassica
(crop group 5A) -- cabbage, cauliflower, broccoli, brussels sprouts,
and related non-leafy brassica. The field residue data to support a
fenpropathrin tolerance on the crop grouping head and stem brassica
includes data on broccoli from 7 sitesand cabbage from six sites
providing data from 13 sites across the U.S. Samples from trials that
were consistent with the proposed maximum use pattern for the crop
group -- the first application at 0.2 lb. ai./a and 2 additional
applications at 0.3 lb. ai./a (a total application of 0.8 lb. ai./a),
7-day spray interval, 7-day pre-harvest interval -- gave a mean residue
of 0.62 ppm(n = 26, <greek-s>n-1 = 0.69) with a maximum value of 2.8
ppm.
viii. Broccoli. Field residue data come from 7 locations in 4
states. At these locations there were a total of 8 separate trials
yielding 28 separate, treated samples for analysis. Samples from trials
that were consistent with the proposed maximum use pattern gave 14
separate samples for analysis. The mean of the 14 determinations is
0.369 ppm (n = 14, <greek-s>n-1 = 0.157 ppm)and a maximum value of 0.58
ppm.
ix. Cabbage. Field residue data come from 6 locations in 6 states.
At these six locations there was a total of 7 separate trials yielding
26 separate, treated samples for analysis. Trials that were consistent
with the proposed maximum use pattern gave 12 separate samples for
analysis. The mean of the determinations is 0.92 ppm (n = 12,
<greek-s>n-1 = 0.93 ppm) and a maximum value of 2.8 ppm. Analyses of
cabbage heads with wrapper leaves removed demonstrated that the bulk of
the residue was on the exterior of the cabbages with a mean residue of
0.04 ppm (n = 12, <greek-s>n-1 = 0.05 ppm) and a maximum value of 0.19
ppm.
x. Secondary residues. Residues in animal feed may transfer to
animal products, meat, milk, and eggs, used in human food. The existing
tolerances on meat and meat by-products of cattle, goats, hogs, horses
and sheep at 0.1 ppm, fat of cattle, goats, hogs, horses and sheep at
1.0 ppm, milk fat (reflecting 0.08 ppm in whole milk) at 2.0 ppm, and
poultry meat, fat, meat by-products and eggs at 0.05 ppm are, adequate
to allow the addition of the proposed uses. Both chronic and acute
dietary assessments show very low residue contribution from secondary
residues in animal products to all population sub-groups.
B. Toxicological Profile
Summary. The existing registrations and tolerances of fenpropathrin
are supported at EPA by a complete toxicology data base. Toxicity
endpoints of concern have been identified by the Agency's Health
Effects Division, Hazard Identification Assessment Review Committee
(Meeting July 17, 1997; Revised Memorandum November 14, 1997). The
identified endpoints are an acute dietary of 6.0 mg/kg/day (systemic)
and a chronic dietary of 2.5 mg/kg/day (RfD = 0.025 mg/kg/day, UF =
100). No endpoints of concern were identified by the Committee for
occupational or residential, dermal or inhalation exposures of any
duration. Further, in the Revised Memorandum of November 14, 1997, the
Committee concluded that an additional safety factor, beyond 100 was
not needed to account for special sensitivity of infants and children
to fenpropathrin. In a separate action, fenpropathrin has been
evaluated for carcinogenicity by the HED RfD/Peer Review Committee. In
a Memorandum from Dr. G. Z. Ghali to Mr. G. La Rocca dated March 18,
1993, it was concluded that in valid studies with adequate doses that
the compound ``did not alter the spontaneous tumor
[[Page 41841]]
profile in both rats and mice''. Fenpropathrin was classified as Group
E.
1. Acute toxicity. Oral LD<INF>50</INF> in the rat is 54.0
milligram/kilogram (mg/kg) for males and 48.5 mg/kg for females -
Toxicity Category I; dermal LD<INF>50</INF> is 1,600 mg/kg for males
and 870 mg/kg for females - Category II; acute inhalation (impossible
to generate sufficient test article vapor or aerosol to elicit
toxicity) - Category IV; primary eye irritation (no corneal
involvement, mild iris and conjunctival irritation) - Category III; and
primary dermal irritation (no irritation) - Category IV. Fenpropathrin
is not a sensitizer.
2. Genotoxicity. Studies on gene mutation and other genotoxic
effects: An Ames Assay was negative for Salmonella TA98, TA100, TA1535,
TA1537, and TA1538; and E coli WP2uvrA (trp-) with or without metabolic
activation. Sister Chromosome Exchange in CHO-K1 Cells - there were no
increases in sister chromatid exchanges seen in the CHO-K1 cells
treated with S-33206 or the DMSO vehicle. Cytogenetics in vitro (CHO/
CA) - negative for chromosome aberrations (CA) in Chinese hamster ovary
(CHO) cells exposed in vitro to toxic doses ( > 30 nanogram) without
activation; and to limit of solubility (1,000 nanogram) with
activation. In Vitro Assay in Mammalian Cells - equivocal results - of
no concern. DNA Damage/Repair in Bacillus subtilis - not mutagenic or
showing evidence of DNA damage at > 5,000 nanogram/paper disk.
3. Reproductive and developmental toxicity. In a developmental
toxicity study in rats, pregnant female rats were dosed by gavage on
gestation days 6-15 at 0 (corn oil control) 0.4, 1.5, 2.0, 3.0, 6.0, or
10.0 mg/kg/day. The maternal no observed adverse effect level (NOAEL)
is 6 mg/kg/day; maternal LEL is 10 mg/kg/day based on death,
moribundity, ataxia, sensitivity to external stimuli, spastic jumping,
tremors, prostration, convulsions, hunched posture, squinted eyes,
chromodacryorrhea, and lacrimation; developmental NOAEL is > 10 mg/kg/
day.
In a developmental toxicity study in rabbits, pregnant female New
Zealand rabbits were dosed by gavage on gestation days 7 through 19 at
0, 4, 12, or 36 mg/kg/day. Maternal NOEL is 4 mg/kg/day; maternal LEL
is 12 mg/kg/day based on grooming, anorexia, flicking of the forepaws;
developmental NOEL is > 36 mg/kg/day (HDT).
A 3-generation reproduction study was performed in rats. Rats were
dosed with fenpropathrin at concentrations of 0, 40, 120, or 360 ppm
(0, 3.0, 8.9, or 26.9 mg/kg/day in males; 0, 3.4, 10.1, or 32.0 mg/kg/
day in females, respectively). Parents (male/female): Systemic NOEL =
40 ppm (3.0/3.4 mg/kg/day). Systemic LEL = 120 ppm (8.9/10.1 mg/kg/day)
based on body tremors with spasmodic muscle twitches, increased
sensitivity and maternal lethality; reproductive NOEL = 120 ppm (8.9/
10.1 mg/kg/day). Reproductive LEL = 360 ppm (26.9/32.0 mg/kg/day) based
on decrease mean F1B pup weight, increased F2B loss. Pups (male/
female): Developmental NOEL = 40 ppm (3.0/3.4 mg/kg/day). Developmental
LEL = 120 ppm (8.9/10.1 mg/kg/day) based on body tremors, increased
mortality.
4. Subchronic toxicity. In a subchronic oral toxicity study, rats
were dosed at concentrations of 0, 3, 30, 100, 300, or 600 ppm in the
diet. The lowest effect level (LEL) is 600 ppm (30 mg/kg/day) based on
body weight (bwt) reduction (female), body tremors, and increased brain
(female) and kidney (male) weights. The NOEL is 300 ppm (15 mg/kg/day).
In a subchronic oral toxicity study, dogs were dosed at
concentrations of 0, 250, 500, or 1,000 ppm in the diet. A 1,000 ppm
dog was sacrificed moribund during the third week after having tremors
and showing other signs of poisoning caused by the test article.
Because of this death, the dose for this group was reduced to 750 ppm
for the remainder of the study. The LOEL is 250 ppm (7.25 mg/kg/day)
based on signs of GI tract disturbance. There was no NOEL -- note dog
chronic, below)
In a 21-day dermal toxicity study, rabbits were dosed 5-days/week
for 3 weeks on abraded or unabraded skin at doses of 0, 500, 1,200, or
3,000 mg/kg/day. There were no dose-related effects on bwt, food
consumption, clinical pathology, gross pathology, or organ weights.
Trace or mild inflammatory cell infiltration was seen in the intact and
abraded skin in all groups, including controls, and was attributed to
the test article. The systemic NOEL is > 3,000 mg/kg/day. Local
irritation only.
Although a 21-day dermal toxicity study in rabbits is available the
Agency has determined that rats are the most sensitive species to
ascertain the dermal toxicity potential of pyrethroid insecticides.
Although these data are lacking, EPA has sufficient toxicity data to
support these tolerances and these additional studies are not expected
to significantly change the risk assessment.
5. Chronic toxicity. In a 1-year feeding study, dogs were dosed at
0, 100, 250, or 750 ppm in the diet. The systemic LEL is 250 ppm (6.25
mg/kg/day) based on tremors in all dogs. The neurologic NOEL is 100 ppm
(2.5 mg/kg/day); the systemic NOEL is 100 ppm (2.5 mg/kg/day).
In a chronic feeding/carcinogenicity study, rats were dosed at 0,
50, 150, 450, or 600 ppm in the diet (0, 1.93, 5.71, 17.06, or 22.80
mg/kg/day in males, and 0, 2.43, 7.23, 19.45, or 23.98 mg/kg/day in
females). There was no evidence of carcinogenicity at any dose up to
and including 600 ppm. The systemic NOEL (male) is 450 ppm (17.06 mg/
kg/day). The systemic NOEL (female) is 150 ppm (7.23 mg/kg/day).
Systemic LEL (male) is 600 ppm highest dose tested (HDT) based on
increased mortality, body tremors, increased pituitary, kidney, and
adrenal weights. The systemic LEL (female) is 450 ppm (19.45 mg/kg/day)
based on increased mortality and body tremors.
In a chronic feeding/carcinogenicity study, mice were dosed at 0,
40, 150, or 600 ppm in the feed (0, 3.9, 13.7, or 56.0 mg/kg/day in
males, and 0, 4.2, 16.2, or 65.2 mg/kg/day in females). Mortality was
highest during the final quarter of the study, but the incidence was
similar in all dosed and control groups. No other indications of
toxicity or carcinogenicity were seen. The systemic NOEL is <ls-thn-eq>
600 ppm (HDT; male/female, 56.0/65.2 mg/kg/day). text.
6. Animal metabolism. In a metabolism study in rats, animals were
dosed with radiolabelled fenpropathrin radiolabelled in either the
alcohol or acid portion of the molecule. Rats received 14 daily oral
low-doses of 2.5 mg/kg/day of unlabelled fenpropathrin followed by a
15th dose of either the alcohol or acid radiolabelled fenpropathrin.
Groups of rats received a single dose of either of the 2 radiolabelled
test articles at 2.5 mg/kg or 25 mg/kg. No clinical signs were seen in
any rats.
The major biotransformations included oxidation at the methyl group
of the acid moiety, hydroxylation at the 4'-position of the alcohol
moiety, cleavage of the ester linkage, and conjugation with sulfuric
acid or glucuronic acid.
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
[[Page 41842]]
metabolites. The fecal metabolites (and the 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.
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. The
free or reconjugated aglycones were rapidly and completely eliminated
by normal metabolic pathways. The glucose conjugates of 3-phenoxybenzyl
alcohol and 3-phenoxy-benzoic acid are less toxic to mice than the
corresponding aglycones.
7. Endocrine disruption. No special studies to investigate the
potential for estrogenic or other endocrine effects of fenpropathrin
have been performed. However, as summarized above, a large and detailed
toxicology data base 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. Toxicity endpoints of concern have been
identified by the Agency's Health Effects Division, Hazard
Identification Assessment Review Committee (July 17, 1997). The
identified endpoints are a Chronic Dietary of 2.5 mg/kg/day (RfD =
0.025 mg/kg/day, UF = 100) and an Acute Dietary of 6.0 mg/kg/day
(systemic). Thus, both chronic and acute dietary exposure and risk
analyses are necessary.
2. Food. 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, tomatoes, pome fruits, citrus, grapes, head and stem
brassica, and melons; processed products from these crops; and the
resulting secondary residues in meat, milk, and eggs. A report along
with a supplemental report of these exposure/risk analyses has been
submitted to the Agency including a detailed description of the
methodology and assumptions used.
Chronic dietary exposure was calculated for the U.S. population and
26 population subgroups. The results from several representative
subgroups are listed below. Chronic dietary exposure was at or below
1.7 % of the reference dose with grapes and apples the commodities
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 RfD.
Summary of Chronic Dietary (Food) Exposures to Fenpropathrin Residues
------------------------------------------------------------------------
Exposure(mg/ Percent
Population Subgroup kg bw/day) ofRfD
------------------------------------------------------------------------
Total U.S. Population (all seasons) 0.000165 0.7
Females (13+/Nursing) 0.000285 1.1
Non-Hispanic other than B/W 0.000246 1.0
Children (1-6 Years) 0.000435 1.7
All Infants (<1 Year Old) 0.000193 0.8
Non-Nursing Infants (<1 Year Old) 0.000127 0.5
Nursing Infants (<1 Year Old) 0.000351 1.4
------------------------------------------------------------------------
Acute dietary exposure was calculated for the U.S. population,
Females (13+/Pregnant/Not Nursing), and five children subgroups. The
sub-population, Females (13+/Pregnant/Not Nursing), was included
because the toxicity endpoint for acute dietary exposure identified by
the Agency is based on clinical signs of toxicity in the dams from the
rat developmental toxicity study. The calculated exposures and margins
of exposure (MOE) for the higher exposed proportions of the subgroups
are listed below. In all cases, margins of exposure exceed one-hundred.
Calculated Acute Dietary Exposures to Fenpropathrin Residues in Food (per-capita days)
----------------------------------------------------------------------------------------------------------------
99th Percentile 99.9th Percentile
-----------------------------------------------------
Population Subgroup Exposure(mg/ Exposure(mg/
kg bw/day) MOE kg bw/day) MOE
----------------------------------------------------------------------------------------------------------------
U.S. Population........................................... 0.003296 1,821 0.010173 590
Females (13+/Pregnant/NotNursing)......................... 0.002737 2192 0.005595 1072
Children 1-6.............................................. 0.008461 709 0.020678 290
Children 7-12............................................. 0.005322 1,127 0.012195 492
All Infants............................................... 0.002963 2,025 0.029691 202
Nursing Infants (<1)...................................... 0.007142 840 0.050337 119
Non-Nursing Infants (<1).................................. 0.001874 3,202 0.004863 1,234
----------------------------------------------------------------------------------------------------------------
It should be noted that the numbers of individuals in the dietary
survey of some population subgroups is small. These ``under
represented'' subgroups are weighted to account for their proportions
in the total U.S. Population and in various geographic and ethnic
subpopulations. If in these under represented subgroups there are
individuals with unusual dietary consumption patterns anomalous Monti
Carlo selected diets will occur at the lower probability exposures
(e.g. 99th and 99.9th percentiles) often times leading to
unrealistically high calculated exposures. Such is the case for Nursing
Infants (<1). Two of these babies were reported to be fed raw grapes.
In one case, one nursing infant was reported to consume 310 grams of
raw grapes in a single day. This is a very unusual diet for any infant.
Because of this dietary anomaly, and the weighting factor for this
population subgroup, the
[[Page 41843]]
MOE for nursing infants approaches 100.
3. Drinking water. Since fenpropathrin is applied outdoors to
growing agricultural crops, the potential exists for fenpropathrin or
its metabolites to reach ground or surface water that may be used for
drinking water. Because of the physical properties of fenpropathrin,
the Agency has determined that it is unlikely that fenpropathrin or its
metabolites can leach to potable groundwater.
To further quantify potential exposure from drinking water, surface
water concentrations for fenpropathrin were estimated using GENEEC 1.2.
The average 56-day concentration predicted in the simulated pond water
was 0.22 ppb. The residence time of fenpropathrin in surface water has
been measured and is short. In pond studies, fenpropathrin half-lives
in the water column were less than 1.5 days, thus this 56-day modeled
half-life probably considerably overestimates any real surface water
concentration. Using standard assumptions about bwt and water
consumption, the chronic exposure from this drinking water would be 6.3
x 10-6 and 2.2 x 10 -5 mg/kg bw/day for adults and children,
respectively; less than 0.09 % of the RfD for children. Based on this
worse case analysis, the contribution of water to the dietary risk is
negligible.
4. Non-dietary exposure. Fenpropathrin, as the product TAME 2.4 EC
Spray, is registered for professional non-food use both indoors and
outdoors on ornamentals and non-bearing nursery fruit trees.
Fenpropathrin has no animal health, homeowner, turf, termite, indoor
pest control, or industrial uses. Quantitative information concerning
human exposure from this ornamental use is not available, but exposure
to the general public from this use of fenpropathrin is expected to be
minimal. It is important to note that no endpoints of concern were
identified by the Health Effects Division, Hazard Identification
Assessment Review Committee for occupational or residential, dermal or
inhalation exposures of any duration. Thus, no risk assessment is
needed.
D. Cumulative Effects
Section 408(b)(2)(D)(v) requires that the Agency must consider
``available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments. For
most pesticides, although the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way.
There are numerous other pesticidal compounds, pyrethroids and
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. 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) and other
EPA publications pursuant to the Food Quality Protection Act.
E. Safety Determination
The Food Quality Protection Act of 1996 introduces a new standard
of safety, a reasonable certainty of no harm. To make this
determination, at this time the Agency should consider only the
incremental risk of fenpropathrin in its exposure assessment. Since the
potential chronic and acute exposures to fenpropathrin are small (<<
100 % of RfD, MOE <ls-thn-eq> 100) the provisions of the FQPA of 1996
will not be violated.
1. U.S. population--i Chronic exposure. Using the dietary exposure
assessment procedures described above for fenpropathrin, 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 is 1.1 [Females (13+/Nursing), 0.000285 mg/
kg bw/day] to 0.4 % of the RfD. Addition of the small but worse case
potential chronic exposure from drinking water (calculated above)
increases exposure by only 6.3 x 10-6 mg/kg bw/day, and the maximum
occupancy of the RfD from 1.14 % to 1.16 %. Generally, the Agency has
no cause for concern if total residue contribution is less than 100 %
of the RfD. 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 exposure to
fenpropathrin residues.
ii. Acute. The potential acute exposure from food to the U.S.
population and various non-child/infant population subgroups (shown
above) provide MOE values greatly exceeding 100. Addition of the worse
case, but very small ``background'' dietary exposure from water is not
sufficient to change the MOE values significantly (see table below). In
a conservative policy, the Agency has no cause for concern if total
acute exposure calculated for the 99.9th percentile yields a MOE of 100
or larger. 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.
Aggregate U.S.Poulation Acute Dietary Exposure
------------------------------------------------------------------------
99.9th
Exposure(mg/ Percentile
Source of Exposure kgbw/day) Margin
ofExposure
------------------------------------------------------------------------
Chronic Water................................ 0.000006 -
99.9th Percentile Acute Exposure -- Food..... 0.010173 589.8
99.9th Percentile Aggregate Acute Exposure
Food + Water................................ 0.010179 589.4
------------------------------------------------------------------------
2. Infants and children. Safety Factor for Infants and Children: In
assessing the potential for additional sensitivity of infants and
children to residues of fenpropathrin, FFDCA section 408 provides that
EPA shall apply an additional margin of safety, up to ten-fold, for
added protection for infants and children in the case of threshold
effects unless EPA determines that a different margin of safety will be
safe for infants and children.
The toxicological data base for evaluating pre- and post-natal
toxicity for fenpropathrin is complete with respect to current data
requirements. There are no special pre- or post-natal toxicity concerns
for infants and children, based on the results of the rat and rabbit
developmental toxicity studies or the 3-generation reproductive
toxicity study in rats. EPA HED Hazard
[[Page 41844]]
ID Committee (Revised Memorandum, November 14,1997) has concluded that
reliable data support use of the standard 100-fold uncertainty factor
and that an additional uncertainty factor is not needed for
fenpropathrin to be further protective of infants and children.
3. Chronic risk. Using the conservative exposure assumptions
described above, the percentage of the RfD that will be utilized by
dietary (food only) exposure to residues of fenpropathrin ranges from
0.5 % for Non-Nursing Infants (<1 year old), up to 1.7 % for Children
(1 - 6 years). Addingthe worse case potential incremental exposure to
infants and children from fenpropathrin in drinking water ( 2.2 x 10 -5
mg/kg bw/day) to the chronic dietary exposure from food (0.000435 mg/kg
bw/day) does not materially increase the aggregate, chronic dietary
exposure and only increases the occupancy of the RfD by 0.09% to 1.8 %
for Children (1 - 6 years). EPA generally has no concern for exposures
below 100% of the RfD because the RfD represents the level at or below
which daily aggregate dietary exposure over a lifetime will not pose
appreciable risks to human health. It can be concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate, chronic exposure to fenpropathrin residues.
4. Acute. The potential acute exposure from food to the various
child and infant population subgroups (shown above) provide MOE values
exceeding 100. Addition of the worse case, but very small
``background'' dietary exposure from water (2.2 x 10 -5 mg/kg bw/day)
is not sufficient to change the MOE values significantly (see table
below). In a conservative policy, the Agency has no cause for concern
if total acute exposure calculated for the 99.9th percentile yields a
MOE of 100 or larger. It can be concluded that there is a reasonable
certainty that no harm will result to infants and children from
aggregate, acute exposure to fenpropathrin residues.
Aggregate Nursing Infants (> 1 Year) Acute Dietary Exposure
------------------------------------------------------------------------
99.9th
Exposure Percentile
Source of Exposure (mg/kg bw/ Margin of
day) Exposure
------------------------------------------------------------------------
Chronic Water................................. 0.000022 -
99.9th Percentile Acute Exposure - Food....... 0.050337 119.2
99.9th Percentile Aggregate Acute Exposure
Food + Water................................. 0.050359 119.1
------------------------------------------------------------------------
F. Safety Determination Summary
Aggregate acute or chronic dietary exposure to various sub-
populations of children and adults demonstrate acceptable risk.
Aggregate chronic dietary exposures to fenpropathrin occupy
considerably less than 100% of the RfD, and all aggregate acute dietary
MOE values exceed 100. Chronic and acute dietary risk to children from
fenpropathrin should not be of concern. Further, fenpropathrin has no
other uses, such as animal health, indoor pest control, homeowner use
or turf applications, that could lead to unique, enhanced exposures to
vulnerable sub-groups of the population. It can be concluded that there
is a reasonable certainty that no harm will result to the U.S.
Population or to any sub-group of the U.S. population, including
infants and children, from aggregate chronic or aggregate acute
exposures to fenpropathrin residues resulting from approved and pending
uses.
G. International Tolerances
Codex Maximum Residue Limits
186 -- FENPROPATHRIN
Main uses -- 8 -- INSECTISCIDE/ACARACIDE
JMPR -- 83
ADI -- 0.03 mg/jg body weight (1993)
RESIDUE -- Fenpropathrin (fat soluble)
----------------------------------------------------------------------------------------------------------------
Commodity
-----------------------------------------------------------------------------------------------------------------
Code Name MRL (mg/kg) Step JMPR CCPR
----------------------------------------------------------------------------------------------------------------
MM 0812............................ Cattle meat 0.5 (fat) 6 93 ...........
ML 0812............................ Cattle milk 0.1 F 6 93 ...........
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 6 93 ...........
PE 0112............................ Eggs 0.01 (*) CXL ........... (1995)
VC 0425............................ Gherkin 0.2 CXL D (1995)
FB 0269............................ Grapes 5 6 93 ...........
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)
V0 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. (Beth
Edwards)
[FR Doc. 98-20769 Filed 8-4-98; 8:45 am]
BILLING CODE 6560-50-F
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are for convenience only; no endorsement of products is intended, nor is
criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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