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triflumizole (Terraguard, Procure) EPA Pesticide Fact Sheet 10/91

                           EPA PESTICIDE FACT SHEET

Name Of Chemical:     [[4-chloro-2(trifluoromethyl)phenyl]imino]-
                      2-Propoxy-ethyl-1H-imidazole
Reason for Issuance:  Registration of New Active Ingredient
Date Issued:          10-24-9l
Fact Sheet Number:    228


DESCRIPTION OF CHEMICAL
_______________________

Generic Name:  1-[1-[[4-chloro-2-(trifluoromethyl)phenyl]imino]-
               2-propoxyethyl]-1H-imidazole
Common Name:  Triflumizole
Trade Name:  Terraguard
EPA Shaughnessy Code:  128879
Chemical Abstracts Service (CAS) Number:  68694
Year of Initial Registration:  1991
Pesticide Type:  Fungicide
U.S. and Foreign Producers:  Uniroyal Chemical Company, Inc.
                             74 Amity Road
                             Bethany, CT  06525


USE PATTERNS AND FORMULATIONS
_____________________________

APPLICATION SITES:  The manufacturing use product (MP) is for use only in the 
formulation of fungicides.  The end-use product is for use in control of 
Cylindrocladium root and petiole rot on Spathiphyllum.

TYPES OF FORMULATION:  The technical grade is a white crystalline formulation 
containing 97% active ingredient.  The end-use product is a wettable powder 
containing 50% active ingredient.

TYPES AND METHODS OF APPLICATION:  The end-use product is a protectant 
fungicide to be used as a soil drench, foliar spray or through chemigation for 
control of diseases on ornamentals grown in enclosed commercial structures 
such as greenhouses, shade houses and interior scapes.

APPLICATION RATES:  For all methods of treatment for Terraguard (soil drench, 
foliar spray and/or chemigation), the pesticide is applied at the rate of 4 to 
8 oz. per 100 gallons of water.  This treatment is repeated every 2 to 4 weeks 
or as needed.  For best results use sufficient volume to ensure adequate soil 
penetration.


SCIENCE FINDINGS
________________

Summary Science Statement

     Available acute toxicity studies indicate that triflumizole is in 
Toxicity Category I (Danger) based on the primary eye irritation study with 
rabbits.

     Chronic feeding/oncogenicity studies were conducted in both the rat and 
mouse.  The chronic feeding study in the rat suggests that the liver is the 
main target organ with the ovary and kidney as secondary target organs.  
Although there was an accompanying increase in organ weights, no carcinogenic 
effects were seen.

     In the chronic feeding study in mice, the results of blood chemistry, 
organ weights and gross and histological examinations also indicate the liver 
as the target organ.

     Triflumizole did not induce either genotoxic effects or chromosomal 
aberrations in a series of mutagenicity studies.

     The teratology studies were conducted in the rabbit and rat.  In the rat 
studies, incidences of dilatation of the renal pelvis and increased 14th 
rudimentary ribs were seen.  In the rabbit, an increase in postimplantation 
losses was noted.

     Environmental fate data indicate that triflumizole has low potential for 
leaching.  Aerobic soil metabolism data indicates that triflumizole is 
degraded rapidly by soil microbes to several products of which one is CO2.  
Hydrolysis data show that the parent compound is quite stable at near neutral 
pHs and undergoes slow hydrolysis at either mild acidic or basic conditions. 
Studies also show that triflumizole has a half-life of 18 days in sandy loam 
soil under laboratory conditions.

     Ecological studies indicate triflumizole is practically non-toxic to 
honeybees and birds.  Triflumizole is categorized as being moderately toxic to 
highly toxic to fish.  Since this is a minor use registration and since 
greenhouse applications have been traditionally treated as indoor uses, the 
hazards to nontarget species and endangered species are considered to be 
minimal.


TOXICOLOGICAL CHARACTERISTICS
_____________________________

Acute Toxicity

     Acute oral toxicity in rats:          LD50 2.43 g/kg males
                                           LD50 2.05 g/kg females
                                           Toxicity Category III
     Acute dermal toxicity in rats:        LD50 is greater than 2000 mg/kg
                                           Toxicity Category III
     Acute inhalation toxicity in rats:    LC50 is greater than 3.2 mg/L
                                           Toxicity Category III
     Primary eye irritation in rabbit:     Ocular opacity; Toxicity Category I
     Primary dermal-irritation in rabbit:  Negative: No irritation observed;
                                           Toxicity Category IV
     Dermal sensitization in guinea pigs:  Positive for contact sensitization


CHRONIC STUDIES
_______________

     Rodent Feeding/Oncogenicity
     ___________________________

     A 2-year feeding/oncogenicity study with Sprague-Dawley rats was 
conducted.  Rats were fed 0, 5, 20 or 80 mg/kg/day doses of triflumizole 
equivalent to 0, 100, 400 and 1600 ppm triflumizole for 104 weeks with an 
interim sacrifice at 52 weeks.  Numerous organ weights, clinical chemistry and 
hematology parameters and microscopic changes indicate the main target organ 
is the liver, with fatty vacuolization and periacinar hepatic hypertrophy seen 
at all dose levels tested.  Ovarian organ weights as well as well-developed 
follicles indicate the ovary as a target.  Kidney weights were affected as 
well with increased cortical cysts seen in the kidneys of mid and high dose 
animals.    The NOEL is greater than 100 ppm, based on fatty vacuolization and 
periacinar hepatic hypertrophy seen at all dose levels tested.  An increase in 
tumor incidence was not noted in any treatment groups.

     A 2-year feeding/oncogenicity study with male and female mice using 
dietary concentrations of 0, 100, 400 and 1600 ppm equivalent to 0, 15, 60 and 
240 mg/kg/day was conducted.  There were interim sacrifices at 26, 54, 78 and 
104 weeks.  Major effects were seen in the liver at all doses tested.  
Clinical chemistry changes reflecting liver toxicity included changes in 
alkaline phosphatase, BUN, SGOT, SGPT and cholesterol.  Absolute and relative 
liver weights were increased at all time periods in the high dose males and 
females and in some animals of the mid dose groups.  At sacrifice, liver 
changes in all dose groups included hepatic nodules and cytoplasmic 
alterations.  The systemic NOEL was less than 100 ppm.  Although there was a 
slight increase the incidence of lymphoma in both treated males and females, 
it was judged not be compound-related.

     A 3-month feeding study in rats was conducted using dietary 
concentrations of o, 20, 200 and 2000 ppm equivalent to 0, 2, 20 and 200 
mg/kg/day.  The NOEL was 200 ppm.  The LEL was 2000 ppm (HDT) based on slight 
decrease in food consumption and body weight and changes in blood chemistry.

     A 3-month feeding study with mice was conducted using dietary 
concentrations of 0, 20, 200 and 2000 ppm equivalent to 0, 3, 30, 300 
mg/kg/day.  The NOEL was 200 ppm and the LEL was 2000 ppm based on liver 
effects.

     A 30-day feeding study with rats was conducted using dietary 
concentrations of 20, 200 and 2000 ppm equivalent to 0, 2, 20 and 200 
mg/kg/day.  The NOEL was 200 ppm and the LEL was 2000 ppm based on liver 
changes, necrosis and fatty metamorphosis.

     A 30-day feeding study with mice was conducted using dietary 
concentrations of 20, 200 and 2000 ppm equivalent to 0, 3, 30 and 300 
mg/kg/day.  The NOEL was 200 ppm and the LEL was 2000 ppm based on enlarged 
livers.

     Non-Rodent Feeding Studies
     __________________________

     A 1-year feeding study with beagle dogs using dietary concentrations of 
0, 100, 300 and 1000 ppm equivalent to 0, 2.5, 7.5 and 25 mg/kg/day was 
conducted.  The NOEL was 300 ppm and the LEL was 1000 ppm based on liver and 
blood chemistry changes.


TERATOLOGY
__________

     A teratology study using Sprague-Dawley rats was conducted by 
administering levels of 0, 10, 35 and 120 mg/kg/day by gavage.  The 
teratogenic NOEL was greater than 12 0 mg/kg/day (HDT).  The maternal NOEL in 
this test was 10 mg/kg/day and maternal LEL was 35 mg/kg/day based on 
decreased body weight and decreased water and food consumption.  The fetotoxic 
NOEL was greater than 10 mg/kg/day (LDT) based on dilation of renal pelvis.

     A complementary study was conducted using dose levels of O and 3 mg/kg: 
the NOEL was 3 mg/kg.  Another teratology study using rats was conducted using 
dose levels of 0, 3, 7, and 35 mg/kg by gavage.  The maternal NOEL was 7 
mg/kg.  The maternal LEL was 35 mg/kg based on reduced body weight gain and 
decreased food consumption.  The developmental NOEL was 7 mg/kg.  The 
developmental LEL was 35 mg/kg based on death and increase in incidence of 
14th rudimentary ribs and cervical ribs.  The A/D ratio was determined to be 
7/7 = 1.

     A teratology study was conducted in rabbits by administering dosage rates 
of 0, 50, 100 and 200 mg/kg by gavage.  The maternal NOEL was 50 mg/kg.  The 
maternal LEL was 100 mg/kg based on decreased food consumption, body weights 
and organ weights.  The developmental NOEL was greater than 50 mg/kg (LDT) 
based on decreases in fetal and placental body weights and 24-hour survivals.  
The A/D ratio was determined to be 50/greater than 50 = greater than 1.  A 
range finding study was conducted in rabbits using dose rates of 0, 10, 50, 
100, 200 and 300 mg/kg by gavage.  The maternal NOEL was 100 mg/kg.  The 
maternal LEL was 200 mg/kg based on decreased body weight and food 
consumption.  The developmental NOEL was 100 mg/kg.  The developmental LEL was 
200 mg/kg based on increased postimplantation losses.

     Another teratology study was conducted in rabbits using lower doses (O, 
5, 25 and 50 mg/kg by gavage).  There was no evidence of clear maternal 
toxicity.  The offspring showed no adverse effects.  The maternal NOEL was 
greater than 50 mg/kg and the developmental NOEL was greater than 50 
mg/kg/day.


REPRODUCTION
____________

     In a 2-generation rat reproduction study, dose levels of 0, 30, 70 and 
170 ppm in feed were used.  No parental toxicity was observed.  The parental 
NOEL was greater than 170 ppm (HDT).  The reproductive NOEL was 70 ppm.  The 
reproductive LEL was 170 ppm based on increased gestation lengths.  The 
developmental NOEL was 70 ppm.  The developmental LEL was 170 ppm based on 
reduced Fla litter size and increased fetal incidences of hydroureter and 
space between body walls and organs.

     In a 3-generation rat reproduction study, dose levels of 0, 70, 170 and 
420 ppm in feed resulted in a NOEL greater than 70 ppm (LDT) based on 
increased gestation length.  At 170 ppm there was pup mortality.  At 420 ppm, 
there was reduced body weight gain, increased length of estrous cycles, 
reduced vaginal cornification, extended gestation length and high pup 
mortality.

     Another 3-generation rat reproduction study as conducted using lower dose 
levels (0, 30, 70 and 170 ppm).  The reproduction NOEL was greater than 30 ppm 
based on increased gestation lengths at all doses tested.  The developmental 
NOEL was 70 ppm.  The developmental LEL was 170 ppm based on increased 
incidence of hydroureter and space between the body wall and organs, increased 
pup mortality and reduced pup weight.  The parental NOEL was greater than 170 
ppm (HDT).


MUTAGENICITY
____________

     Triflumizole was negative for mutagenicity in the mitotic gene conversion 
test, rec assay test, in vitro mouse micronucleus test, reverse mutation in 
Salmonella and E. coli test and unscheduled DNA synthesis test.


ENVIRONMENTAL FATE
__________________

     Environmental fate studies for leaching/adsorption/desorption show that 
unaged Carbon 14 triflumizole was slightly mobile in a column (30.4 cm length) 
of sandy soil treated with 214 micrograms (1 lb ai/A) of phenyl ring-labeled 
Carbon 14 triflumizole (radiopurity 93.4%) and leached with 63.7 column CM of 
distilled water.  Seventy-eight percent of the recovered radioactivity was 
found in the top six inches of soil.  The majority (greater than 81%) of the 
radioactivity in each soil segment was triflumizole.  This, together with the 
leachate data, indicates low potential for leaching and indicates that 
triflumizole should not pose a problem in field runoff or in contamination of 
ground water.

     Data from an aerobic soil metabolism study of Carbon 14 triflumizole in 
sandy loam soil indicate that triflumizole underwent soil degradation with a 
half-life of 18 days.  The parent compound degraded via three degradation 
intermediates to 4-chloro-2-trifluoromethylaniline, which volatilized from the 
soil and/or underwent further degradation to C02 by microorganisms.

     Hydrolysis studies show that phenyl-labeled Carbon 14 triflumizole 
(radiochemical purity greater than 99%), at 5 ppm, degraded in sterile aqueous 
0.01 M buffered solutions with half-lives of 7 to 15 days at pH 5, greater 
than 30 days at pH 7 and 3 to 17 days at pH 9 when incubated in the dark at 25 
plus or minus 1 C.  The registrant-calculated half-lives were 8 to 9 days (pH 
5), 64.6 days (pH 7) and 3.9 days (pH 9).  At 30 days posttreatment, Carbon 14 
triflumizole accounted for 73.5% of the applied radioactivity in the pH 7 
solution.  4-Chloro-alpha-alpha-alpha-trifluoro-N-2-propoxyacetyl-0-toluidine 
was identified as the major degradate at all three pHs, with maximum 
concentrations of 83.1% of the applied at pH 5, 20.8% at pH 7 and 84.0% at pH 
9.  Material balances ranged from 96 to 1O3% during the test period.


ECOLOGICAL CHARACTERISTICS
__________________________

     Studies submitted show that triflumizole is practically nontoxic to 
honeybees (LD50 greater than 160 ug per bee) and birds (LC50 greater than 
5,620 ppm and LD50 greater than 2,510 ppm).  Since it is unlikely that 
triflumizole will come into contact with these species, it is not expected to 
pose a threat to honeybees and birds (nontarget and endangered species).  
Triflumizole is categorized as being moderately toxic to highly toxic to fish.  
The expected levels of triflumizole in a farm pond are not predicted to exceed 
1/10 of the warmwater fish LC50 (1.2 ppm) which is the nontarget species 
cutoff point.  There are only two endangered fish species in Florida.  The 
shortnosed sturgeon (Acipenser brevinostrum) is in Duval and Putnam Counties.

     The Okaloosa darter (Etheostoma okaloosae) is in Walton and Okaloosa 
Counties.  None of these four counties is in southern Florida where the 
pesticide will be used.  The expected levels of triflumizole in a farm pond 
are not predicted to exceed 1/20 of the warmwater fish LC50 (1.2 ppm) which is 
the endangered species cutoff point.  Triflumizole is not expected to be a 
threat to endangered fish.  Since this is a minor use registration and 
greenhouse applications have been traditionally treated as indoor uses, the 
hazards to non-target species and endangered species is considered to be 
minimal.  All available ecological data indicate that the use of triflumizole 
on Spathiphyllum will not cause undue environmental damage.


BENEFITS
________

     This chemical has low mammalian toxicity.  Its use as a fungicide on 
ornamentals does not pose any unreasonable effect to man or the environment.  
Triflumizole is effective at low rates in controlling Cylindrocladium.


CONTACT PERSON AT EPA
_____________________

     Susan T. Lewis
     Product Manager (PM) 21
     Registration Division (H7505C)
     Environmental Protection Agency
     401 M Street SW.
     Washington, DC  20460

     Office Location and Telephone Number:
     Rm 227, CM#2
     1921 Jefferson Davis Highway
     Arlington, VA  22202 (703) 557 -1900


DISCLAIMER:  This information presented in this Pesticide Fact Sheet is for 
informational purposes only and may not be used to fulfill data requirements 
for pesticide registration and/or reregistration.