Return to Etoxazole
Index Page
Activity:
Acaricide, Ovicide (unclassified)
Structure:
Adverse
Effects:
Anemia
Body Weight Decrease
Bone
Endocrine: Adrenal
Endocrine: Prostate
Endocrine: Testicular
Genotoxic
Kidney
Liver
Mutagenicity
Environmental
Anemia
(click on for all fluorinated
pesticides)
-- Subchronic toxicity.
Effects observed at high dose levels consisted primarily of
anemia and histological changes in the adrenal
gland, liver and kidneys.
Ref: August 13, 2003. [Federal Register:
August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm
Body
Weight Decrease (click
on for all fluorinated pesticides)
Subchronic/Chronic
Toxicity
Study # 870.3200. 21-Day Dermal Tox Rat. NOAEL = 1000 LOAEL >
1000, no effects noted. 870.3700 Developmental Tox Rabbit NOAEL
= Maternal: 200 Developmental: 200 LOAEL = Maternal: 1000, based
on liver enlargement
and decreased
body weight gains and
food consumption
Developmental: 1000, based on increased
incidences of 27 presacral vertebrae and 27 presacral vertebrae
with 13 ribs (skeletal variations) in the fetuses
Ref: US EPA Pesticide Fact Sheet. August
2002.
http://www.epa.gov/opprd001/factsheets/etoxazole.pdf
Bone
(click on for all fluorinated
pesticides)
Rabbit developmental
study. Etoxazole did not produce developmental toxicity in rabbits...
A statistically significant increased incidence
of 27 presacral vertebrae with 13th ribs was observed in fetuses
at 1,000 mg/kg/day compared with controls. This finding
was within historical control range for fetal incidence but above
the historical control range for litter incidence. No dose response
was evident and the variation is considered to be equivocally
treatment related. The NOAEL for maternal and developmental toxicity
was 200 mg/ kg/day based on decreased body weight and body weight
gain, decreased food consumption, and liver enlargement at 1,000
mg/kg/day. The NOAEL for developmental toxicity was 200 mg/kg/day
based on statistically significant increased
incidence of 27 presacral vertebrae with 13th ribs in fetuses
at 1,000 mg/kg/day.
Ref:
August 13, 2003. [Federal Register: August 13, 2003 (Volume 68,
Number 156)] [Notices]. Etoxazole; Notice of Filing a Pesticide
Petition to Establish a Tolerance for a Certain Pesticide Chemical
in or on Food.
http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm
Hyperplasia of bone tissue in rats at high doses (≥5000
ppm)
Ref: November
29, 2004. Review report for the active substance etoxazole. European
Commission. SANCO/4054/2001 - rev. 3.
http://www.fluorideaction.org/pesticides/etoxazole.draft.review.eu.2004.pdf
Endocrine:
Adrenal (click
on for all fluorinated pesticides)
Subchronic toxicity.
Effects observed at high dose levels consisted primarily of
anemia and histological changes in the adrenal
gland, liver and kidneys.
Ref: August 13, 2003. [Federal Register:
August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm
Reproduction and fertility
effects (rat). Parental/Systemic
NOAEL = 20 mg/kg/ day LOAEL = 100 mg/kg/ day (M/F), based upon
increased liver weights in the P and F1 males and
increased adrenal weights in the P females Offspring/Systemic
NOAEL = 20 mg/kg/ day LOAEL = 100 mg/kg/ day (M/F), based upon
pup mortality Reproductive NOAEL = 100 mg/kg/day LOAEL = not determined.
Ref:
Federal Register: September 26, 2003. Etoxazole; Pesticide Tolerance.
Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
Endocrine:
Prostate (click
on for all fluorinated pesticides)
Subchronic/Chronic
Toxicity
-- 870.3150 90-Day Feeding Dog NOAEL = 5.33/5.42(M/F) LOAEL =
53.7/55.9 (M/F), based on clinical signs (vomiting foamy fluid
and mucous stool), clinical chemistry, increased
liver weights, and on centrilobular hepatocellular swelling in
the liver and acinar
cell atrophy in the prostate.
Ref: US EPA Pesticide Fact Sheet. August
2002.
http://www.epa.gov/opprd001/factsheets/etoxazole.pdf
Endocrine:
Testicular (click
on for all fluorinated pesticides)
Rat
chronic feeding/oncogenicity study. In the first study, etoxazole
technical was fed to male and female Sprague Dawley rats for two
years at dietary concentrations of 4, 16, and 64 mg/kg/day. A
trend toward decreased body weight gain for males at 64 mg/kg/day
in the latter half of the study was observed. Hemotology and clinical
chemistry changes, increased liver weights and hepatic enlargement
at 16 mg/kg/day or above were observed. Testicular
masses, centrilobular hepatocellular swelling and testicular interstitial
(Leydig) cell tumors occurred at or above 16 mg/kg/day. The interstitial
(Leydig) cell tumors were believed to be incidental. The NOAEL
was 4 mg/kg/day for males and 16 mg/kg/day for females.
Ref: August 13, 2003. [Federal Register:
August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm
Non-guideline 13-Week study: Effect on proliferative activity
of testicular interstitial cells
in rat. A toxic level of the test
substance did not affect the proliferative activity of testicular
interstitial cells.
Ref: Federal Register: September 26, 2003.
Etoxazole; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
Genotoxic
(click
on for all fluorinated pesticides)
Abstract: Etoxazole is a member of the diphenyl oxazoline class
of insecticide, which was newly developed for use on pome fruits,
cotton and strawberries as an acaricide. In the present study,
genotoxic effects of acaricide etoxazole (ETX) (miticide/ovicide)
were investigated using chromosome aberration (CA) test, sister
chromatid exchange (SCE) test, and micronucleus test in human
lymphocytes. ETX induced the CAs at all
concentrations (5, 10, and 20 g/ml) for 24 h and also induced
the CA at the highest concentration (20 g/ml) for 48 h only. The
inducing the CAs for 48 h treatment period was dose-dependent.
In addition, it induced the SCE at all concentrations and treatment
periods in a dose-dependent manner as well. Although ETX
decreased the mitotic index (MI) at all concentrations and treatment
periods dose-dependently, it did not decrease the replication
index (RI) when compared to the negative and solvent controls.
In addition, ETX induced the micronucleus at all concentrations
except 5 g/ml for 48 h. This inducing was dose-dependent as well.
It can be concluded that ETX has a potential
genotoxic effects in cultured human peripheral lymphocytes.
Ref: The Genotoxic Effect of the New Acaricide
Etoxazole. E. Rencüzogullari; H. Basrila; A. Kayraldiz; M.
Arslan; S. Budak Diler; M. Topaktas. Russian Journal of Genetics,
November 2004, vol. 40, no. 11, pp. 1300-1304(5).
http://www.ingentaconnect.com/content/maik/ruge/2004/00000040/00000011/00500539
Kidney
(click
on for all fluorinated pesticides)
- Subchronic toxicity.
Effects observed at high dose levels consisted primarily of
anemia and histological changes in the adrenal
gland, liver
and kidneys.
Ref: August 13, 2003. [Federal Register:
August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm
Liver
(click
on for all fluorinated pesticides)
-- 90-Day oral toxicity
rodents (rat). NOAEL = 61.8/69.0
milligrams/kilogram/ day (mg/kg/day) Male/Female (M/F) LOAEL =
183.7/204.8 mg/kg/day (M/F), based upon increases in hepatic enzyme
levels, increased liver weights and centrilobular
hepatocellular swelling in both sexes and liver enlargement in
females only
-- 90-Day oral toxicity rodents (mouse).
NOAEL = 213.6/250.5 mg/kg/day (M/F) LOAEL = 878.4/994.5 mg/kg/day
(M/F), based upon periportal hepatocellular
necrosis, increased alkaline phosphatase levels, accompanied
by increased relative liver weight, liver
enlargement, and centrilobular hepatocellular swelling
-- 90-Day oral toxicity nonrodents (dog).
NOAEL = 5.33/5.42 mg/ kg/day (M/F) LOAEL = 53.7/55.9 mg/ kg/day
(M/F), based upon clinical signs (vomiting foamy fluid and mucous
stool), clinical chemistry, increased liver
weights, and centrilobular swelling in the liver and acinar
cell atrophy in the prostate.
-- Prenatal developmental toxicity in nonrodents
(rabbit). Maternal NOAEL =
200 mg/kg/day LOAEL = 1,000 mg/kg/day based upon
liver enlargement and decreased body weight gains and food
consumption. Developmental NOAEL = 200 mg/kg/day LOAEL = 1,000
mg/kg/ day based upon increased incidences of 27 presacral vertebrae
and 27 presacral vertebrae with 13th ribs in the fetuses.
-- Reproduction and fertility effects (rat).
Parental/Systemic NOAEL = 20 mg/kg/ day LOAEL = 100 mg/kg/ day
(M/F), based upon increased liver weights
in the P and F1 males and increased adrenal weights in
the P females Offspring/Systemic NOAEL = 20 mg/kg/ day LOAEL =
100 mg/kg/ day (M/F), based upon pup mortality Reproductive NOAEL
= 100 mg/kg/day LOAEL = not determined.
-- Combined chronic toxicity/ carcinogenicity rodents (rat).
NOAEL = 64 mg/kg/day (M/F). LOAEL = not determined Equivocal evidence
of carcinogenicity.
-- Chronic toxicity nonrodents (dog).
NOAEL = 4.62/4.79 mg/kg/day (M/F). LOAEL = 23.5/23.8 mg/ kg/day
(M/F), based upon increased alkaline phosphatase activity, increased
liver weights, liver enlargement (females), and incidences of
centrilobular hepatocellular swelling in the liver.
-- 78-Week carcinogenic mouse. NOAEL = 242/243 (M/ F). LOAEL =
484/482 (M/ F), based on a slight increase in the incidence of
a fatty change in the centrilobular hepatocytes
in males.
-- The weight-of- the-evidence
from the 28-day, 90-day, 52- week interim chronic toxicity/ carcinogenicity
and the 2-year chronic toxicity/ carcinogenicity rat studies shows
that the systemic effects (mainly in the
liver) occur around the same dose levels from short- term
through long-term exposure without increasing in severity. Therefore,
results of the 28-day dermal toxicity study can be applicable
to long-term exposure.
Ref:
Federal Register: September 26, 2003. Etoxazole; Pesticide Tolerance.
Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
Subchronic/Chronic
Toxicity
-- 870.3100 90-Day Feeding Rat NOAEL
= not determined LOAEL = 300.4/336.6 (M/F), based on clinical
signs, clinical chemistry, increased liver
weights, and histopathology
-- 870.3100 90-Day Feeding Rat NOAEL
= 18.3/20.5 (M/F) LOAEL = 183.7/204.8 (M/F) based on increase
in hepatic enzyme levels, increased liver weights and centrilobular
hepatocellular swelling in both sexes and liver enlargement in
females only
-- 870.3150 90-Day Feeding Mouse
NOAEL = 213.6/250.5 (M/F) LOAEL = 878.4/994.5 (M/F), based on
periportal hepatocellular necrosis,
increased alkaline phosphatase levels, accompanied by increased
relative liver weight, liver enlargement, and centrilobular hepatocellular
swelling
-- 870.3150 90-Day Feeding Dog NOAEL
= 5.33/5.42(M/F) LOAEL = 53.7/55.9 (M/F), based on clinical signs
(vomiting foamy fluid and mucous stool), clinical chemistry, increased
liver weights, and on centrilobular hepatocellular swelling in
the liver and acinar cell atrophy in the
prostate.
-- 870.3200 21-Day Dermal Tox Rat
NOAEL = 1000 LOAEL > 1000, no effects noted. 870.3700 Developmental
Tox Rabbit NOAEL = Maternal: 200 Developmental: 200 LOAEL = Maternal:
1000, based on liver enlargement
and decreased body weight gains and food consumption Developmental:
1000, based on increased incidences of 27
presacral vertebrae and 27 presacral vertebrae with 13 ribs (skeletal
variations) in the fetuses
Ref: US EPA Pesticide Fact Sheet. August
2002.
http://www.epa.gov/opprd001/factsheets/etoxazole.pdf
Mutagenicity
(click
on for all fluorinated pesticides)
Gene mutation - in
vitro forward gene mutation assay in mouse lymphoma cells.
When tested up to cytotoxic levels, mutagenic in the presence
of S9 activation and equivocal for mutagenicity in the absence
of S9 activation.
Ref: Federal Register: September 26, 2003.
Etoxazole; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
Teeth
- (click
on for all fluorinated pesticides)
2-Year feed/ carcinogenic (rat)
. NOAEL = 1.83/2.07 mg/kg/day (M/F) LOAEL = 187/216 (M/ F), based
upon effects on the incisors including abnormal
amelogenesis. No evidence of carcinogenicity.
Ref: Federal Register: September 26, 2003.
Etoxazole; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
• Note: Definition: Amelogenesis
= the developmental process of forming tooth enamel
Abnormal amelogenesis (incisors) and hyperplasia of bone tissue
in rats at high doses (≥5000 ppm)
Ref: November
29, 2004. Review report for the active substance etoxazole. European
Commission. SANCO/4054/2001 - rev. 3.
http://www.fluorideaction.org/pesticides/etoxazole.draft.review.eu.2004.pdf
Environmental
(click
on for all fluorinated pesticides)
Ecological
Characteristics/Risk... etoxazole is considered very
highly toxic to aquatic invertebrates in acute testing.
Acute toxicity tests of etoxazole with freshwater fish are
considered invalid for reasons including solubility problems
and failure to use flow-through test methods, among others.
Additional studies are required to characterize acute toxicity
on freshwater fish. As with avian risk, however, significant
exposure to aquatic, non-target organisms is not expected
to occur. Therefore, chronic testing is not required.
Ref:
US EPA Pesticide Fact Sheet. August 2002.
http://www.epa.gov/opprd001/factsheets/etoxazole.pdf
|
A
February
15, 2005,
check at the Code
of Federal Regulations for Etoxazole: this acaricide is
permitted in or on 25
food
commodities in the United States.
The
following list identifies these crops for which EPA has set
pesticide tolerances.
Note:
September 26, 2003, US
EPA approved the first-time use of Etoxazole on food
commodities.
|
[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: 40CFR180.593]
[Page 517]
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. 180.593 Etoxazole; tolerances for residues.
(a) General. Tolerances are established for residues of the
insecticide etoxazole, 2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-
2-ethoxyphenyl]-4,5-dihydrooxazole, in or on the following
raw
agricultural commodities: |
Commodity |
Parts
Per Million |
CFR |
Apple,
wet pomace
|
0.50 |
180.593
|
Cattle,
fat
|
0.02 |
180.593
|
Cattle,
liver
|
0.01 |
180.593
|
Cotton,
gin byproducts
|
1.0 |
180.593
|
Cotton,
undelinted seed |
0.05 |
180.593
|
Fruit,
pome, group 11
This
group includes 11 commodities.
•
apple
• apple, dried pomace
• apple, juice
• apple, wet pomace
• crabapple
• fruit, pome
• loquat
• mayhaw
• pear
• pear, oriental
• quince
|
0.20 |
180.593
|
Goat, fat
|
0.02 |
180.593
|
Goat, liver
|
0.01 |
180.593
|
Horse,
fat
|
0.02 |
180.593
|
Horse,
liver
|
0.01 |
180.593
|
Milk, fat
|
0.01 |
180.593
|
Sheep,
fat
|
0.02 |
180.593
|
Sheep,
liver
|
0.01 |
180.593
|
Strawberry
|
0.50 |
180.593
|
Tangerine\1\ |
0.10 |
180.593
|
\1\There
are no U.S. registrations for use of etoxazole on tangerines
as
of September 26, 2003. |
(b)
Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect and inadvertant residues. [Reserved] |
|