Fenpyroximate (AkariTM 5SC) NYS DEC Letter - Registration of
Active Ingredient 5/03
Fenpyroximate (AkariTM 5SC) NYS DEC Letter - Registration of
Active Ingredient 5/03
New York State Department of Environmental Conservation
Division of Solid and Hazardous Materials
Bureau of Pesticides Management, 9th Floor
625 Broadway Albany, New York 12233-7254
Phone: (518) 402-8788 FAX: (518) 402-9024
May 27, 2003
RETURN RECEIPT REQUESTED
Ms. Marie A. Maks
Manager, Regulatory Affairs
Nichino America Incorporated
4550 New Linden Hill Road, Suite 501
Wilmington, Delaware 19808
Dear Ms. Maks:
Registration of the New Active Ingredient Fenpyroximate, Contained in the Pesticide Product AkariTM 5SC
Miticide/Insecticide (EPA Reg. No. 71711-4)
The New York State Department of Environmental Conservation (Department)
has reviewed your application,
received December 11, 2002, to register the above-mentioned product in New York State.
The product contains the new
active ingredient fenpyroximate.
The application was deemed complete for purposes of review on January 30,
2003 and a registration
decision is due by June 27, 2003.
AkariTM 5SC contains the new active ingredient fenpyroximate (tert-butyl
(E)-alpha-(1,3-dimethyl-5-phenoxyprazol-4-ylmethylenaminoxy)-p-toluate). AkariTM 5SC
is a contact miticide used for the
control of spider mites on greenhouse ornamental, floral and foliage crops; indoor
ornamental plantings and
plantscapes. Fenpyroximate was granted reduced risk status on May 18, 1999 for the
control of spider mites on indoor
greenhouse ornamentals. For resistance management, this product is not to be used in
successive miticide applications
in the same greenhouse. At least two different chemicals with different modes of
action are to be used between
treatments with AkariTM 5SC. Resistance management strategies also recommend that
application rates lower than
recommended on the label are not to be used and for best results, no more than two
applications of AkariTM 5SC per
growing season, or per crop cycle (whichever is longer), be used.
The Department has reviewed the information submitted to date in
support of the application for
registration of AkariTM 5SC Miticide/Insecticide (EPA Reg. No. 71711-4).
The active ingredient, fenpyroximate, was moderately toxic by the
oral and inhalation routes of exposure
and slightly toxic by the dermal route of exposure in acute toxicity laboratory
animal studies. This active ingredient
was not irritating to the skin or eyes (tested on rabbits). It was a slight to
moderate skin sensitizer (tested on
guinea pigs) by one test method, but was not sensitizing by another test method.
The formulated product AkariTM 5SC
Miticide/Insecticide was not very toxic in acute oral, dermal or inhalation
exposure studies in laboratory animals.
AkariTM 5SC Miticide/Insecticide was not a dermal irritant or sensitizer; however,
it did cause moderate to severe, but
reversible, eye irritation.
Fenpyroximate caused some toxicity in subchronic animal feeding
studies. In a 90-day rat feeding study,
fenpyroximate caused decreased body weight gain at 6.6 milligrams per kilogram
body weight per day (mg/kg/day); the
no-observed-effect-level (NOEL) was 1.3 mg/kg/day. In a 90-day dog feeding study,
fenpyroximate caused a slight
decrease in heartbeat (bradycardia) and an increase in the incidence of diarrhea
in both sexes at 2 mg/kg/day; a NOEL
was not established in this study. Fenpyroximate at this dose level also caused
reduced food consumption, body weight,
and body weight gain, as well as emaciation and torpor in females. In a 21-day
dermal toxicity study in rabbits,
fenpyroximate caused reduced body weights, reduced body weight gain, and reduced
food consumption in both sexes and an
increase in absolute liver weights as well as a possible increase in hepatocellular
necrosis in females at 1,000
mg/kg/day; the NOEL was 300 mg/kg/day.
Fenpyroximate caused some toxicity in chronic animal feeding studies.
In a one-year dog feeding study,
fenpyroximate caused diarrhea, bradycardia, and decreases in cholesterol, body
weight gain and food consumption in
males, and vomiting, diarrhea, excessive salivation, and decreased cholesterol
in females at a dose of 15 mg/kg/day;
the NOEL was 5 mg/kg/day. In a chronic feeding/oncogenicity study in mice, decreased
body weight gain and food
consumption were reported at doses of 9.5 mg/kg/day for males and 10 mg/kg/day for
females; the respective NOELS were
2.4 mg/kg/day and 2.5 mg/kg/day. In a chronic feeding/oncogenicity study in rats,
decreased body weight was the only
reported effect at 3.1 mg/kg/day in males and 3.8 mg/kg/day in females; the
respective NOELs were 0.97 mg/kg/day and
1.2 mg/kg/day. The United States Environmental Protection Agency (USEPA), Office
of Pesticide Programs established a
reference dose (RfD) for fenpyroximate of 0.01 mg/kg/day based the NOEL of 0.97
mg/kg/day from this chronic rat feeding
study and an uncertainty factor of 100 to account for interspecies extrapolation
and human variability. This RfD has
not yet been adopted by the USEPA's Integrated Risk Information System (IRIS).
Fenpyroximate caused some developmental toxicity in offspring of
laboratory animals at doses that also
caused maternal toxicity. In a rat study, fenpyroximate caused an increase in
the fetal incidence of additional
thoracic ribs at 25 mg/kg/day; the NOEL was 5 mg/kg/day. Maternal toxicity,
characterized by marginal depression in
body weight and food consumption, occurred at 25 mg/kg/day; the NOEL was 5
mg/kg/day. In a rabbit study, no
treatment-related effects were reported for maternal or developmental toxicity
at doses up to 5 mg/kg/day, the highest
dose tested. In a multi-generation reproduction study in rats, fenpyroximate
caused decreased body weights during the
pre-mating period at 6.6 mg/kg/day in males and 8.6 mg/kg/day in females; the
NOELS were 2.0 mg/kg/day and 2.4
mg/kg/day, respectively. Reproductive toxicity was characterized by decreased
lactational weight gain in both
generations of pups at 8.6 mg/kg/day; the NOEL was 2.4 mg/kg/day.
Fenpyroximate did not cause oncogenic effects in rat or mouse
chronic feeding studies. This compound was
also negative in a number of genotoxicity studies. The USEPA classified
fenpyroximate as "not likely" to be
carcinogenic to humans.
The USEPA conducted an occupational risk assessment for dermal
and inhalation exposures to fenpyroximate
from use in an enclosed greenhouse. For determining margins of exposure (MOEs),
the USEPA compared estimated short-term
and intermediate-term dermal exposures to a NOEL of 300 mg/kg/day from the
21-day dermal toxicity study in rabbits.
Short-term inhalation exposures were compared to a NOEL of 5 mg/kg/day from
the developmental toxicity study in rats,
and intermediate-term inhalation exposures were compared to a NOEL of 1.5
mg/kg/day (rather than a NOEL of 1.3
mg/kg/day as denoted earlier in our review) from the 90-day rat feeding study.
For commercial mixer/loader/applicators,
MOEs ranged between 1,200 for combined short-term dermal and inhalation exposures
and 2,800 for intermediate-term
dermal and inhalation exposures. These estimates assumed a maximum application
rate of 0.34 pounds fenpyroximate per
acre. It was also assumed that workers wore gloves, a long-sleeved shirt and
pants as per label requirements. The MOE
for post-application occupational exposure (cutting and harvesting of indoor
ornamental plants) was estimated to be
490. Generally, the USEPA considers MOEs of 100-fold or greater to provide
adequate worker protection.
The available information indicates that fenpyroximate was slightly
to moderately toxic in acute studies,
but was not irritating to the eyes or skin. AkariTM 5SC Miticide/Insecticide was
not very acutely toxic, but was a
moderate to severe eye irritant. Fenpyroximate caused some effects in subchronic
and chronic toxicity studies, and
caused some developmental effects in the rat, but not the rabbit. Fenpyroximate
was not oncogenic or genotoxic and was
classified by the USEPA as "not likely" to be a human carcinogen. Greenhouse
workers applying AkariTM 5SC
Miticide/Insecticide and handling treated plants would be expected to have the
greatest exposure to this pesticide
product and its active ingredient fenpyroximate. However, the USEPA's occupational
risk assessment determined that
workers would have adequate MOEs. To mitigate the potential for eye injury from
AkariTM 5SC Miticide/Insecticide, the
product's label requires the use of protective eyewear. In addition, post-application
impacts to air within greenhouses
from use of AkariTM 5SC Miticide/Insecticide should not be a concern as fenpyroximate
has a low vapor pressure (5.63 X
10-8 millimeters of mercury at 25 degrees Celsius) and the product does not contain
volatile petroleum-based solvents.
Finally, the USEPA determined that AkariTM 5SC could be an effective tool in
resistance management and granted
fenpyroximate reduced risk pesticide status for the labeled use.
AkariTM 5SC is 5% fenpyroximate,
a substituted pyrozole. Its mode of
action is to interfere with mitochondrial electron transport. More specifically, it
targets proton-translocating NADH:Q
oxidoreductase and blocks ubiquinone reduction, similar to rotenone.
Technical fenpyroximate water solubility is slightly pH dependant. Its
solubility is 21.4, 23.1, and 29.8
parts per billion (ppb) at pHs 5, 7, and 9, respectively. It has low vapor pressure,
5.6 x 10-8 mmHg; volatilization
will not contribute significantly to dissipation. Its octanol/water
partition coefficient, Kow, is relatively high at 102,330 suggesting a potential to
bioaccumulate. A Bluegill Sunfish
accumulation study summary gives bioconcentration factors, BCF, of 656X, 2746X, and
1601X, for edible tissue, nonedible
tissue, and whole fish respectively.
Fenpyroximate is moderately toxic to mammals on an acute basis and is
practically non-toxic to birds. The
indoor greenhouse use pattern requires a much reduced set of aquatic organism toxicity
tests. Those submitted show
fenpyroximate to be very highly toxic to all organisms tested with LC50 values in the
low 1 to 4 ppb range. No honeybee
or aquatic plant study results were submitted.
From the limited environmental fate data submitted it appears
fenpyroximate may be relatively persistent
and exhibit low post-application mobility. Its hydrolysis half-life, T,,2, is 226 days
at pH 7 and aerobic soil T1/2s
ranged from 35 to 161 days. Fenpyroximate photolyses readily, aqueous photolysis T1/2
equals 1.5 hours. In column
leaching studies using three soils (sand, loamy sand, and sandy loam) parent
fenpyroximate, 0.27% of that applied, was
only detected in the leachate collected from the sand soil.
No fish or wildlife exposure is anticipated from this use pattern. As such,
no adverse effects to fish or
wildlife resources are anticipated from labeled greenhouse use of AkariTM 5 SC.
Nichino America, Inc. anticipates submitting an application in September
2003 for fenpyroximate use on
apples and grapes in New York State. The majority of the requisite environmental fate
and ecological effects study
results will be submitted at that time.
The maximum application rate of AkariTM 5SC is 0.68 lb ai/a/year as a
foliar application, applied in two
applications. The inerts do not appear to be solvent carriers.
The Department's environmental fate staff stated the following:
Hydrolysis: EPA found this study acceptable. Fenpyroximate had
half-lives of 180, 226 and 221 days
pHs 5, 7, and 9, respectively.
Solubility: Fenpyroximate is soluble in water at a level of 0.023 mg/l at pH 7.
Aqueous Photolysis: EPA found this study acceptable. Aqueous
photolysis is a major degradative
pathway. The half-life is very short at 1.5 hours. Two major degradates were found,
M-1 [tert-butyl (Z)-a-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy-p-toluate]
and M-11 01,3-dimethyl-5-phenoxypyrazole-4-carbonitirile) were found at 59.8% and
22.2% respectively. M-1 then degraded with a half-life of 12.7 hours.
Soil Photolysis: No studies were performed.
Aerobic Soil Metabolism: Two aerobic soil metabolism studies
were submitted (MRIDs # 44781017 and
44847910). Both studies were unacceptable and did not meet Subdivision N Guidelines
for 162-1 for many reasons. On the
first, the reviewer calculated half-lives were 159
days and 35 to 46.5 days. The registrant calculated half-lives were 16.9, 10.1, and
21.3 days in clay loam, silt loam
and loam soils, respectively. In the second study, the reviewer calculated half-life
was 161 days, and the registrant
calculated half-life was 159 days.
Adsorption/Desorption: One adsorption/desorption study was
performed (MRID #44847911). The study
was unacceptable and did not meet the Subdivision N Guidelines for 163-1 because the
soils were autoclaved to sterilize
them, and this is not an acceptable procedure. However, the adsorption Kocs of the
soils were 40,000, 50,000, 40,000
and 44,000 for sand, sandy loam, clay loam and loam respectively. The desorption Kocs
were 37,000, 44,000, 64,000 and
37,000 for sand, sandy loam, clay loam and loam respectively. Sterilization has been
shown to alter the physical and
chemical properties of the soil that affect the adsorption and desorption of chemicals.
Since the Kocs range from
37,000 to 64,000, the Department believes the chemical would still be immobile, even
with a significantly lower Koc.
The Notice of Registration, dated September 27, 2000, indicated that this study had
to be provided by September 27,
2003 [3 years].
Aged Leaching: Three aged leaching studies were submitted
(MRIDs # 44781018, 44781019, and
44781020). All three studies were unacceptable and did not meet Subdivision N Guidelines
163-1 for several reasons. No
mobility data were presented in the summary. The Notice of Registration, dated
September 27, 2000, indicated that this
study had to be provided by September 27, 2003 [3 years].
Terrestrial Field Dissipation: No studies were performed.
EPA Comments: To support indoor use, generally the only
environmental fate data required is a
hydrolysis study. This study was submitted and found to be acceptable. A photolysis
study was also submitted and found
to be acceptable. There are no other acceptable environmental fate data for this
chemical. Because this pesticide is
very highly acutely toxic to fish and aquatic invertebrates, the following
environmental fate data will be required, on
a confirmatory basis, to provide a basic exposure profile for this pesticide:
Guideline 162-1 Aerobic Soil Metabolism
and Guideline 163-1 Adsorption/Desorption (Batch Equilibrium).
There are no chemical specific federal or State drinking
water/groundwater standards for fenpyroximate.
Based on its chemical Structures, fenpyroximate falls under the 50 microgram
per liter (/.cg/L) New York State drinking
water standard for "unspecified organic contaminants" (10NYCRR Part 5, Public Water Systems).
Given the very high Kocs, the foliar application, and the fact
that this product is labeled for
greenhouse use, the Department's environmental staff have no objection to the
registration of this product as labeled.
However, if the company wishes to add outdoor uses to the label, they should
be prepared to submit the aerobic
metabolism and leaching and adsorption studies and DERs at that time.
AkariTM 5SC Miticide/Insecticide should not have an adverse effect
on the health of workers or the
general public, the fish and wildlife resources, or the ground and surface water
of New York State when used as labeled.
Therefore, the Department hereby accepts for general use registration
in New York State AkariTM 5SC
Miticide/Insecticide (EPA Reg. No. 71711-4) which contains the new active
Enclosed are your Certificate of Registration and New York State
stamped "ACCEPTED" label.
Nichino America, Inc. is reminded that if New York State registration
is requested for this product or
for any other product which contains fenpyroximate with an increased application
rate and/or expanded use sites, the
product will be considered a Major Change in Labeling and the Department will
require an extensive review.
If you have any questions, please contact Mr. Samuel Jackling,
Chief of our Pesticide Product
Registration Section, at (518) 402-8768.
Maureen P. Serafini
Bureau of Pesticides Management
cc: w/enc. - N. Kim/D. Luttinger - NYS Dept. of Health
G. Good/W. Smith - Cornell University, PMEP
R. Zimmerman/R. Mungari - NYS Dept. of Ag and Markets