Adverse Effects
Etoxazole
CAS No. 153233-91-1
 
 

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

On September 26, 2003, US EPA approved the first-time use of Etoxazole on food commodities -see list below.

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]

 

 
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