http://pmep.cce.cornell.edu/profiles/herb-growthreg/fatty-alcohol-monuron/fluthiacet-methyl/fluthiacet_let_700.html
New York State Department of Environmental Conservation
Division of Solid and Hazardous Materials
Bureau of Pesticides Management, Room 498
Pesticide Product Registration Section
50 Wolf Road, Albany, New York 12233-7257
Phone: (518) 457-7446 - FAX: (518) 485-8990
Website: www.dec.state.ny.us/website/dshm/pesticid/pesticid.htm
July 7, 2000
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Jerry Harrison
Manager
State Registration and Regulatory Support
Novartis Crop Protection, Inc.
P.O. Box 18300
Greensboro, NC 27419-8300
Dear Mr. Harrison:
Re: Withdrawal of Application for Registration
of the New Active Ingredient -
Fluthiacet-methyl Contained in Action Herbicide (EPA Reg. No.
100-806)
Novartis Crop Protection, Inc. submitted an application for the
registration of the above
mentioned pesticide product on June 30, 1999. Action Herbicide
contains the active
ingredient, fluthiacet-methyl, and is labeled for use in post-emergence
control of
velvetleaf and certain other broadleaf weeds in soybeans at a
maximum rate of three
ounces of product per acre per year (or 0.009 lb a.i./A /year).
Because fluthiacet-methyl
is an active ingredient not contained in any pesticide product
registered for use in New
York State, this active ingredient required review by the Department
prior to registration.
On August 30, 1999 the application was determined to be incomplete.
On September 7, 1999,
Novartis Crop Protection sent additional data and on September
8, 1999 the application was
determined complete with the registration decision date of February
5, 2000. However, the
registration decision date was reprioritized at the request of
Novartis Crop Protection,
Inc. to allow other Novartis products to be reviewed during this
time slot. The registration
decision date was reset for July 1, 2000.
During the Departments' review of your application for registration
of fluthiacet-methyl in
New York State, our reviewers discussed the implications of registration
of this new active
ingredient in our State. The available information on fluthiacet-methyl
and
the formulated product, Action Herbicide, indicates that the estimated
dietary and
occupational risks posed by its use are within the USEPA acceptable
range for a
pesticide product that has carcinogenic potential. It
is our position that registration
of a product classified as "likely to be a human carcinogen"
is not warranted unless it
either replaces a product that poses greater risks or the need
for the product is
significant. New York State currently has many product
registered for use on soybeans.
The Department cannot endorse registration of this product unless
there is a demonstrable
need.
During our telephone conversation in which we conveyed our concerns
to you regarding
registration of Action Herbicide, you indicated that Novartis
Crop Protection would
prefer to withdraw the registration at this time. On June 22,
2000, the Department
received a faxed copy of your letter requesting the voluntary
withdrawal of your
application without prejudice to future application for registration
of the above
mentioned pesticide product. The Department accepts this request.
Enclosed for your information is a synopsis of our review. This
review is based on the
above product as labeled. If, in the future, Novartis Crop Protection
should reapply for
registration of fluthiacet-methyl, for this use, on soybeans or
for another use,
the application must address the need for this product and/or
provide additional
mitigating information.
If you have any, questions on this matter, please contact Betty
Seeley, of my staff at
(518) 457-7446.
Sincerely,
Francis X. Hegener
Acting Chief
Pesticide Product Registration Section
Enclosure
cc: w/enc.- G. Good/W. Smith, Cornell PMEP
R. Zimmerman/R. Mungari, NYS Dept. of Ag & Mkts.
N. Kim/D. Luttinger, NYS Dept. of Health
SYNOPSIS OF DEPARTMENTAL REVIEW
NEW ACTIVE INGREDIENT- FLUTHIACET-METHYL
July 7, 2000
INTRODUCTION
Novartis Crop Protection, Inc. submitted an application for the
registration of new active
ingredient - fluthiacet-methyl contained in the pesticide product
Action Herbicide
(EPA Reg. No. 100-806) on June 30, 1999 Action
Herbicide contains 4.75% of the active
ingredient, fluthiacet-methyl, and is labeled for use in
post-emergence control of
velvetleaf and certain other broadleaf weeds in soybeans at a
maximum rate of 3 ounces of
product er acre per year (or 0.009 lb a.i./A/year). Because fluthiacet-methyl
is an active
ingredient not contained in any pesticide product registered for
use in New York State,
this active ingredient required review by the Department prior
to registration.
On August 30, 1999 the application was determined to be incomplete.
On September 7, 1999,
Novartis Crop Protection sent additional data and on September
8, 1999 the application was
determined complete with the registration decision date of February
5, 2000. However, the
registration decision date was reprioritized at the request of
Novartis Crop Protection,
Inc. to allow other Novartis products to be reviewed during this
time slot. The revised
registration decision date was July 1, 2000.
The application was reviewed for potential health, ecological
and groundwater impacts
on New York State. A discussion of the implications of registration
of fluthiacet-methyl,
as labeled, follows:
Health Effects
Neither fluthiacet-methyl nor the Action Herbicide product was
very acutely toxic to
laboratory animals via the oral, dermal or inhalation routes of
exposure and they were
not very irritating to animal eyes or skin. These materials were
not skin sensitizers.
In an acute oral neurotoxicity study, rats given fluthiacet-methyl
at the highest dose
tested, 2,000 milligrams per kilogram per day (mg/kg/day) displayed
no neurotoxic effects.
In a chronic feeding/oncogenicity study
with fluthiacet-methyl in mice, non-cancer
liver
effects (centrilobular necrosis and cell degeneration, histiocytic
pigmentation) were
reported at 1.0 mg/kg/day for males and 1.2 mg/kg/day for females.
The no-observed-effect
level (NOEL) was 0.1 mg/kg/day for both male and female mice.
A rat chronic
feeding/oncogenicity study reported liver
and pancreatic toxicity in males at 130 mg/kg/day
and liver toxicity in females at 154 mg/kg/day; the respective
NOEs were 2.1 and
2.5 mg/kg/day. In a one-year dog
study, decreases in body weight gain and
mean red blood
cell volume, as well as liver effects (hepatocyte degeneration)
were reported at 145
mg/kg/day for females and 582 mg/kg/day for males; the respective
NOEs were 30.3 and
57.6 mg/kg/day. The U.S. Environmental Protection Agency (USEPA)
calculated an oral
reference dose (RfD) for fluthiacet-methyl of 0.001 mg/kg/day
based on the NOEL from
the chronic feeding/oncogenicity mouse study (0.1 mg/kg/day) and
an uncertainty factor
of 100.
In a developmental study conducted in rats, no maternal nor developmental
toxicity was
reported at a dose of 1,000 mg/kg/day, the highest dose tested.
In a developmental study
in rabbits, a slight non-significant
increase in incidence of irregularly shaped
sternebrae was observed in fetuses of pregnant animals
who were administered
fluthiacet-methyl during organogenesis at a dose of 1,000 mg/kg/day;
the USEPA identified
300 mg/kg/day as the NOEL. No maternal toxicity was noted, even
at 1,000 mg/kg/day,
the highest dose tested. In a two-generation reproduction study
in rats, decreases in
mean litter weights were observed when parental males and females
were fed 313 and 383
mg/kg/day of fluthiacet-methyl, respectively; the respective reproductive
NOELs were
31.8 and 37.1 mg/kg/day. Parental male and female toxicity, characterized
by liver
effects, was reported at 31.8 and 37.1 g/kg/day, respectively;
the respective NOELs
were l.6 and 1.9 mg/kg/day.
Fluthiacet-methyl caused cancer in both
rats and mice exposed for their lifetimes. In
male rats,
there was a significant increasing trend for exocrine pancreatic
adenomas,
a significant increasing trend and pair-wise comparison at the
high dose (219 mg/kg/day)
for pancreatic islet cell adenomas,
and a significant increasing trend for combined
pancreatic islet cell adenomas and carcinomas. There was
no evidence of carcinogenicity
in female rats. In male mice, there
was a significant increasing trend for liver
adenomas, carcinomas and combined adenomas/carcinomas.
There was also a significant
pair-wise increase for liver adenomas in the 32 mg/kg/day
groups, for liver carcinomas
in the 10 and 32 mg/kg/day groups and for combined
liver adenomas/carcinomas in the 10
and 32 mg/kg/day groups. For female mice,
there was a significant increasing trend
for
liver adenomas and combined adenomas/carcinomas, but not
for carcinomas alone. There
was no significant pair-wise comparisons for tumors in female
mice at any dose level.
Fluthiacet-methyl was positive in some genotoxicity
studies (structural chromosomal
aberrations), but was negative in other genotoxicity tests
(gene mutation and DNA damage).
Based on this evidence, the USEPA's Health Effects Division Cancer
Assessment Review
Committee classified fluthiacet-methyl as "likely
to be a human carcinogen" and calculated
a cancer potency slope factor for this compound of 0.207 (mg/kg/day)-1
using data on
heptacellular tumors in mice.
The USEPA established a tolerance for the residues of fluthiacet-methyl
in or on soybeans
at 0.01 parts per million. The USEPA estimated that dietary exposure
to the residues of
fluthiacet-methyl on soybeans would be less than 0.1 percent of
the RfD for the general
U.S. population and 0.6 percent of the RfD for the highest exposure
group, non-nursing
infants. This chronic exposure analysis is based on the assumption
that 25 percent of
crops are treated and contain tolerance level residues. Based
on the chronic dietary
exposure estimate and the cancer slope factor of 0.207 (mg/kg/day)-1,
an increased
lifetime cancer risk of 2.06 x 10-7 can be calculated for the
general U.S. population.
This value is less than the risk level that the USEPA generally
considers to be acceptable
cancer risk (1 x 10-6) for the general population.
The USEPA also evaluated worker risk from the use of Action Herbicide.
This risk
assessment calculated an increased cancer risk to range from 6.6
x 10-7 to 6.5 x 10-8.
These values are within what the USEPA generally considers to
be acceptable (1 x 10-4 or less)
for occupational exposures. Details of this risk assessment were
not provided.
There are no chemical specific federal or State drinking water/groundwater
standards for
fluthiacet-methyl or its degradates. Based on chemical structure,
fluthiacet-methyl and
its degradates fall under the 50 micrograms per liter New York
State drinking water
standard for "unspecified organic contaminants" (10
NYCRR Part 5 -Public Water Systems).
The New York State drinking water standard for the sum of "unspecified
organic
contaminants" and "principal organic contaminants"
is 100,ug/L. Using the USEPA derived
cancer potency slope factor of 0.207 (mg/kg/day)-1 and 6 NYCRR
Part 702.4 procedures for
deriving ambient water quality standards and guidelines based
on oncogenic effects, the
ambient water - lity value associated with a one in one million
increased lifetime cancer
risk is 0.17 ug/L for fluthiacet-methyl. This value should be
used to derive a screening
value for comparison to estimated impacts to groundwater and surface
water.
Neither fluthiacet-methyl nor the Action herbicide product was
very toxic, irritating or caused skin
sensitization following acute exposures in laboratory animals.
Also, fluthiacet-methyl
did not show any significant developmental or reproductive effects.
However,
fluthiacet-methyl caused several non-cancer
effects at relatively low doses. In
addition, the active ingredient caused liver tumors in mice
and pancreatic tumors in
rats exposed over their lifetime
and the USEPA classified fluthiacet-methyl as "likely
to be a human carcinogen". While the estimated dietary
and occupational risks posed by
Action Herbicide are within the USEPA acceptable range, concerns
exist for registering
a pesticide product that has carcinogenic potential unless either
the needs for the
product are significant or it replaces products that pose greater
risks.
Ecological Effects
The potential does exist for algal toxicity
to occur within marinas through use of this
product. However, as labeled, and given its use rate and potential
market share, this is
unlikely.
Environmental Fate and Groundwater Impacts
Hydrolysis of fluthiacet-methyl and its free acid derivative
were stable at pHs of 5, 7
and 9. During aqueous photolysis the half-life of fluthiacet-methyl
was about five days,
and for the suite (fluthiacet-methyl and its degradates) the half-life
was about eleven
days plus or minus three days. During soil photolysis the half-life
of fluthiacet-methyl was
about a third to a half of a day, and for the suite about eleven
days plus or minus two
days. During aerobic soil metabolism studies, fluthiacet-methyl
indicated a half-life of
one to two days and the suite seven days plus or minus three days.
During absorption/desorption studies fluthiacet-methyl had Koc
ranges from 95.4 to 1985 in
sand. Its K.. c in loam is 169, in silt loam 216, and in clay
157. During aged leaching
fluthiacet-methyl was very mobile while its degradates were mobile
to very mobile.
Available environmental fate studies reported
that fluthiacet-methyl and some of its
degradates (CGA-300403, CGA-300404 and CGA-3270666) have soil
adsorption coefficients
(Koc's) of 448, 36-66, 110-160 and 24-45, respectively. These
Koc's indicate a high soil
mobility and therefore a high capacity to leach through soil and
contaminate groundwater.
While no USEPA Data Evaluation Record (DER) reports were submitted
for terrestrial field
dissipation studies, according to a USEPA memo dated 3/4/98, the
half-life is on the
order of a few hours to a few days, while for the suite, a field
dissipation of six days
was found in a study in Georgia, and eight days in a study in
Illinois. Given the very
low application rate of Action Herbicide (maximum of about 4 grams
fluthiacet-methyl per
acre per year) and the rapid degradation, impacts to groundwater
may be low.
The USEPA commented that the proposed use of fluthiacet-methyl
on soybeans at 0.00892 lb
ai/A/year presents a favorable environmental fate profile. The
principle reasons are that
this compound and the suite of herbicidally equivalent degradates,
even though very mobile
collectively, are relatively short-lived, are not expected to
bio-concentrate significantly,
and in relation to potential exposure and ecological toxicity
to non-target species, the
maximum annual use rate is meaningfully low. However, while the
numerous other
degradates/metabolites are not expected to present concerns, the
cumulative role of trace
remnants of all pesticides and degradates is never certain.
The little sorption to soil combined with the relatively short
effective half-life means
that for several days post-application there is high potential
for movement via runoff
water and leaching. However, given the very low-application rate,
there does not appear
to be any significant long term impact to ground or surface water
from the labeled use of
this product.
Conclusion
The available information on fluthiacet-methyl and the formulated
product, Action Herbicide,
indicates that the estimated dietary and occupational risks posed
by its use are within
USEPA acceptable range for a pesticide product that has carcinogenic
potential. However,
registration of a product classified as "likely to be a human
carcinogen" is not warranted
unless it either replaces a product that poses greater risks or
the need for the product is
significant. New York State currently has many products registered
for use on soybeans.
The Department cannot endorse registration of this product unless
there is a demonstrable
need.