PMEP Home Page --> Pesticide Active Ingredient Information --> Herbicides, Growth Regulators and Desiccant --> fatty alcohol to monuron (Telvar) --> fluthiacet-methyl (action) --> fluthiacet-methyl (Action) NYS DEC Letter - Withdrawal of Application for Registration 7/00

fluthiacet-methyl (Action) NYS DEC Letter - Withdrawal of Application for Registration 7/00

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.