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Abstracts
Activity:
Fungicide
(azole)
ACTIVITY:
Fungicide
(azole)
Synonyms for
Triflumizole [BSI:ISO] - CAS No. 68694-11-1
• (E)-4-Chloro-alpha,alpha,alpha-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine
• 1-(1-((4-Chloro-2-(trifluoromethyl)phenyl)imino)-2-propoxyethyl)-1H-imidazole
• 4-Chloro-alpha,alpha,alpha-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine
Structure
for CAS No. 99387-89-0 |
Structure
for CAS No. 68694-11-1 |
|
|
Adverse Effects:
Anemia
Body
Weight Decrease
Bone
Endocrine:
Ovary
Endocrine:
Vaginal
Kidney
Liver
Reproductive Toxicant
Environmental
As
of February 12, 2005, this fungicide is permitted
in or on 49
food commodities in the United
States - see list at bottom of page.
August
23, 2002. US EPA approved an Emergency Exemption for residues
of Triflumizole in or on Filbert at 0.05 ppm in the state
of Oregon only.
The Exemption will expire on June 30, 2004.
Ref: Federal Register: August
23, 2002 (Volume 67, Number 164). Triflumizole; Pesticide
Tolerance for Emergency Exemption. Final Rule.
http://www.fluorideaction.org/pesticides/triflumizole.fr.aug.23.2002.htm
|
Anemia
(click
on for all fluorinated pesticides)
--
Chronic toxicity nonrodents (dog): LOAEL = Males: 34.10 mg/kg/day;
Females: 35.17 mg/ kg/daybased on increased alkaline phosphatase
activity and a mild, macrocytic anemia in
males, increased absolute and relative liver weights in
both sexes, and on macroscopic findings in the liver of both sexes.
Ref: Federal Register: June 12, 2002. Triflumizole;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.June12.2002.htm
Body
Weight Decrease
(click
on for all fluorinated pesticides)
-- Reproduction and
fertility effects (rat): ... Parental/Systemic: LOAEL = 21 mg/kg/
day based on decreased body weight and overall
body weight gain, increased relative liver
weights, and increased mortality in females.
Ref: Federal Register:
June 12, 2002. Triflumizole; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.June12.2002.htm
Bone
(click
on for all fluorinated pesticides)
-- Prenatal Maternal
developmental in rodents (rat): Developmental NOAEL = 10 mg/kg/
day LOAEL = 35 mg/kg/ day based on decreased numbers of viable
fetuses, increased dead or resorbed fetuses, increased numbers
of late resorptions, decreased fetal body weight, and
increased incidences of cervical ribs.
-- Prenatal Maternal developmental in nonrodents (rabbit): Developmental
NOAEL = 50 mg/kg/ day LOAEL = 100 mg/kg/ day based on decreased
24-hour survival, decreased placental weights, and
increased fetal and litter incidences of lumbar ribs.
Ref: Federal Register: June 12, 2002. Triflumizole;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.June12.2002.htm
-- 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.
Ref: Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
Endocrine:
Ovary (click
on for all fluorinated pesticides)
-- 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...
-- 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...
-- 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.
Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
-- Endocrine disruption.
In the rat reproduction study there was an increase in placental
weight in females at the high dose level of 170 ppm. There was
also a biologically significant increase
in gestation length in high dose F0 and F2 females (F1a
and F3a intervals). The NOAEL for endocrine effects is 70 ppm
(3.5 mg/kg/day).
Ref: [Federal Register: July 6, 2001 [Notices]
[Page 35623-35628]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food. http://www.fluoridealert.org/pesticides/Triflumizole.FR.July6.2001.htm
-- Two three-generation reproduction studies in rats (when
considered together) with a reproductive toxicity NOEL of 30 ppm
(1.5 mg/kg/day) and a reproductive toxicity LEL of 70 ppm (3.5
mg/kg/day). Triflumizole is considered a
reproductive toxicant.
Ref: Federal Register: November 16, 1994.
Pesticide Tolerances and Feed Additive Regulations for Triflumizole.
Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.Nov.16.1994.htm
Endocrine:
Vaginal
(click
on for all fluorinated pesticides)
-- 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.
Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
Kidney
(click
on for all fluorinated pesticides)
-- Reproduction and
fertility effects (rat): Reproductive NOAEL = not identified LOAEL
= 3.5 mg/kg/ day based on increased gestation
length in P. Offspring NOAEL = 8.5 mg/kg/ day LOAEL = 21
mg/kg/ day based on decreased pup body weight, survival indices,
and litter sizes and a slight increased incidence of hydronephrosis
in F1a pups.
Ref: Federal Register: June 12, 2002. Triflumizole;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.June12.2002.htm
-- 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...
-- 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.
Ref: Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
Liver
(click on for all fluorinated
pesticides)
-- Reproduction and
fertility effects (rat): ... Parental/Systemic: LOAEL = 21 mg/kg/
day based on decreased body weight and overall body weight gain,
increased relative liver weights,
and increased mortality in females.
-- Chronic toxicity nonrodents (dog): LOAEL = Males: 34.10 mg/kg/day;
Females: 35.17 mg/ kg/daybased on increased alkaline phosphatase
activity and a mild, macrocytic anemia
in males, increased absolute and relative liver
weights in both sexes, and on macroscopic findings in the
liver of both sexes.
-- Carcinogenicity (mouse): LOAEL = Males: 67.4 mg/kg/day; Females:
86.1 mg/ kg/day based on microscopic lesions of the liver.
No evidence of carcinogenicity.
-- 90-Day oral toxicity rodents (rats): LOAEL = Males: 176.5 mg/kg/day;
Females: 217.9 mg/ kg/daybased on increased kidney and liver
weights and the accumulation of fat droplets in the
liver.
Ref: Federal Register: June 12, 2002. Triflumizole;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.June12.2002.htm
-- 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...
-- 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...
-- 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 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.
Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
Abstract: The hepatotoxic
effects of 22 pesticides were studied. Hepatocytes, mitochondria,
and microsomes were prepared from Sprague-Dawley-rats and incubated
with the test substances in-vitro ... Hepatic
mitochondrial respiration was affected by ...
triflumizole (68694-11-1).
Ref: Effects of pesticides on isolated
rat hepatocytes, mitochondria, and microsomes II; by YAMANO T,
MORITA S. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY;
28 (1). 1995. 1-7.
Reproductive
Toxicant (click
on for all fluorinated pesticides)
-- Two three-generation
reproduction studies in rats (when considered together) with a
reproductive toxicity NOEL of 30 ppm (1.5 mg/kg/day) and a reproductive
toxicity LEL of 70 ppm (3.5 mg/kg/day). Triflumizole
is considered a reproductive toxicant.
Ref: Federal Register: November 16, 1994.
Pesticide Tolerances and Feed Additive Regulations for Triflumizole.
Final Rule. http://www.fluoridealert.org/pesticides/Triflumizole.FR.Nov.16.1994.htm
-- 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.
Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
-- Endocrine disruption.
In the rat reproduction study there was an increase in placental
weight in females at the high dose level of 170 ppm. There was
also a biologically significant increase
in gestation length in high dose F0 and F2 females (F1a
and F3a intervals). The NOAEL for endocrine effects is 70 ppm
(3.5 mg/kg/day).
Ref: [Federal Register: July 6, 2001 [Notices]
[Page 35623-35628]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food. http://www.fluoridealert.org/pesticides/Triflumizole.FR.July6.2001.htm
Environmental
(click
on for all fluorinated pesticides)
Abstract: Laboratory bioassays were conducted
to determine the contact honey
bee toxicity of commercial and candidate
neonicotinoid insecticides. The nitro-substituted compounds
were the most toxic to the honey bee in our laboratory studies
with LD50 values of 18 ng/bee for imidacloprid, 22 ng
for clothianidin, 30 ng for thiamethoxam, 75 ng
for dinotefuran and 138 ng for nitenpyram. The cyano-substituted
neonicotinoids exhibited a much lower toxicity with LD50
values for acetamiprid and thiacloprid of 7.1 and 14.6 g/bee,
respectively. Piperonyl butoxide, triflumizole
and propiconazole increased
honey bee toxicity of acetamiprid 6.0-, 244-
and 105-fold and thiacloprid 154-, 1,141-
and 559-fold, respectively, but had a minimal effect
on imidacloprid (1.70, 1.85 and 1.52-fold, respectively).
The acetamiprid metabolites, N-demethyl acetamiprid, 6-chloro-3-pyridylmethanol
and 6-chloro-nicotinic acid when applied topically, produced
no mortality at 50 g/bee. These results suggest that
P450s are an important mechanism for acetamiprid and thiacloprid
detoxification and their low toxicity to honey bees. When
honey bees were placed in cages in forced contact with alfalfa
treated with acetamiprid and the synergist, triflumizole,
in combination at their maximum recommended application
rates, no mortality was detected above that of the control.
Ref: Mechanism
for the differential toxicity of neonicotinoid insecticides
in the honey bee, Apis mellifera; by Takao Iwasa, Naoki
Motoyama, John T. Ambrose and R.M.R. Michael Roe. Crop Protection;
Volume 23, Issue 5 , May 2004, Pages 371-378.
PAN
Pesticides Database - Chemical Toxicity Studies on Aquatic
Organisms.
Acute Aquatic Ecotoxicity Summaries for Triflumizole on
All Taxa Groups. http://www.pesticideinfo.org/List_AquireAcuteSum.jsp?Rec_Id=PC34923
|
|
|
|
|
Fish |
|
|
|
Bleak |
Alburnus
alburnus |
400.0 |
Highly
Toxic |
Bluegill |
Lepomis
macrochirus |
36.0 |
Very
Highly Toxic |
Rainbow
trout,donaldson trout |
Oncorhynchus
mykiss |
445.0 |
Highly
Toxic |
Molluscs |
|
|
|
Snail |
Biomphalaria
glabrata |
10.0 |
Very
Highly Toxic |
Zooplankton |
Harpacticoid
copepod |
Nitocra
spinipes |
8.00 |
Very
Highly Toxic |
|
A
February 12, 2005, check at the Code
of Federal Regulations for Triflumizole: this fungicide
is permitted in or on 49
food commodities in the United States. The
following list identifies the crops for which EPA has set
pesticide tolerances.
|
[Code
of Federal Regulations]
[Title 40, Volume 22]
[Revised as of July 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR180.476]
[Page 470]
TITLE 40--PROTECTION OF ENVIRONMENT
CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)
PART 180_TOLERANCES AND EXEMPTIONS FROM TOLERANCES FOR PESTICIDE
CHEMICALS
IN FOOD--Table of Contents
Subpart C_Specific Tolerances
Sec. 180.476 Triflumizole; tolerances for residues.
(a) General. (1) Tolerances are established
for the combined
residues of the fungicide triflumizole, 1-(1-((4-chloro-2-
(trifluoromethyl)phenyl)imino)-2-propoxyethyl)-1H-imidazole,
and its
metabolites containing the 4-chloro-2-trifluoromethylaniline
moiety,
calculated as the parent compound, in or on the following
food commodities: |
Commodity |
As
of
October 15, 2003
Parts
per Million
PPM |
As
of
February 12,
2005
Parts
per Million
PPM |
CFR |
Apple,
pomace |
2.0 |
2.0 |
180.476 |
Apple |
0.5 |
0.5 |
180.476 |
Cherry,
sweet |
1.5 |
1.5 |
180.476 |
Cherry,
tart |
1.5 |
1.5 |
180.476 |
Grape |
2.5 |
2.5 |
180.476 |
Grape
pomace |
15.0 |
15.0 |
180.476 |
Grape,
raisin waste |
Not
listed this way |
10.0 |
180.476 |
Pear |
0.5 |
0.5 |
180.476 |
Raisin
waste |
10.0 |
Not
listed this way |
180.476 |
Strawberry |
2.0 |
2.0 |
180.476 |
Vegetable,
cucurbit, Group 9
This
group includes 20 commodities:
balsam
apple
balsam pear
balsam pear
cantaloupe
chayote, fruit
cucumber
cucumber, chinese |
cucurbits
gherkin, west indian
gourd, edible
melon
melon, citron
muskmelon |
pumpkin
squash
squash, summer
squash, winter
vegetable, cucurbit, group
watermelon
waxgourd, chinese |
|
0.5 |
0.5 |
180.476 |
2)
Tolerances are established for the combined
residues of the
fungicide triflumizole, 1-(1-((4-chloro-2-
(trifluoromethyl)phenyl)imino)-2-propoxyethyl)-1H-imidazole,
the
metabolite 4-chloro-2-hydroxy-6-trifluoromethylaniline sulfate,
and
other metabolites containing the 4-chloro-2-trifluoromethylaniline
moiety, calculated as the parent compound, in or on
the following food
commodities of animal origin: |
Cattle,
fat |
Not
listed |
0.5 |
180.476 |
Cattle,
meat |
Not
listed |
0.05 |
180.476 |
Cattle,
meat byproducts |
Not
listed |
0.5 |
180.476 |
Egg |
Not
listed |
0.05 |
180.476 |
Goat,
fat |
Not
listed |
0.5 |
180.476 |
Goat,
meat |
Not
listed |
0.05 |
180.476 |
Goat,
meat byproducts |
Not
listed |
0.5 |
180.476 |
Hog,
fat |
Not
listed |
0.5 |
180.476 |
Hog,
meat |
Not
listed |
0.05 |
180.476 |
Hog,
meat byproducts |
Not
listed |
0.5 |
180.476 |
Horse,
fat |
Not
listed |
0.5 |
180.476 |
Horse,
meat |
Not
listed |
0.05 |
180.476 |
Horse,
meat byproducts |
Not
listed |
0.5 |
180.476 |
Milk |
Not
listed |
0.05 |
180.476 |
Poultry,
fat |
Not
listed |
0.05 |
180.476 |
Poultry,
meat |
Not
listed |
0.05 |
180.476 |
Poultry,
meat byproducts |
Not
listed |
0.1 |
180.476 |
Sheep,
fat |
Not
listed |
0.5 |
180.476 |
Sheep,
meat |
Not
listed |
0.05 |
180.476 |
Sheep,
meat byproducts |
Not
listed |
0.5 |
180.476 |
(b)
Section 18 emergency exemptions. Time-limited
tolerances are
established for the residues of triflumizole (1-(1-((4-chloro-2-
(trifluoromethyl)phenyl)imino)-2-propoxyethyl)-1H-imidazole)
and its
metabolites containing the 4-chloro-2-trifluoromethylaniline
moiety,
calculated as the parent in connection with use of the pesticide
under
section 18 emergency exemptions granted by EPA. The tolerances
are
specified in the following table, and will expire and are
revoked on the
dates specified. |
Commodity
|
As
of
October 15, 2003
Parts
per Million
PPM |
As
of
February 12,
2005
Parts
per Million
PPM |
Expiration/
revocation date |
Filbert |
0.05 |
- |
6/30/04 |
(c)
Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved] |
|