Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

EC Number:

406-250-0

EC Name:

Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Cas Number:

72619-32-0

Molecular formula:

C16H13ClF3NO4

IUPAC Name:

methyl 2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoate

Test material form:

solid

Specific details on test material used for the study:

R Enantiomer of XRD-453 Methyl Ester
Lot # AGR 259823
Purity: 98.6%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc., Kingston, New York
- Age: Nine week old
- Weight at study initiation: Males: 144.7-166.7 g; Females: 109.9- 126.2 g
- Fasting period before study: Yes
- Housing: 2 or 3 per cage
- Diet: Purina Certified Rodent Chow # 5002 (Ralston Purina Co., St. Louis, Missouri), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least one week
- Method of randomisation in assigning animals to test and control groups: Randomly assigned by weights

ENVIRONMENTAL CONDITIONS
- The animal rooms were designed to maintain adequate environmental conditions concerning temperature and humidity.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20%

Doses:

100, 500 or 1000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Careful in-life observations were made frequently the day of treatment and at least once each working day throughout the two-week observation period. Each animal was weighed the day of treatment and on test days 2, 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

Means and standard deviations of body weights were calculated. The data were evaluated for statistical outliers by a sequential test, however, outliers were not excluded from statistical procedures if found. The LD50 was calculated by nonlinear interpolation.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

623 mg/kg bw

Based on:

test mat.

Mortality:

All rats given 1000 mg/kg and four males and one female given 500 mg/kg died by test day eight

Clinical signs:

other: In-life observations of these rats and some survivors were nonspecific. These included lethargy, palpebral closure, labored respiration, rough hair coat and perineal soiling. Four males from the high dose group had red-colored perineal soiling one day pos

Gross pathology:

At necropsy, four males and one female administered 1000 mg/kg had a small amount of dark red urine in their urinary bladders and similar colored urine staining their perineal regions. The significance of these observations could not be determined; however, they are unlikely to occur in rats administered a sublethal dose.
Four male rats and one female rat treated with 500 mg/kg that died had gastric irritation (red glandular mucosa or erosions/ulcers of glandular mucosa), chromodacryorrhea and/or soiling of the perineal region by normal colored urine. The stomach changes were considered due to test material administration while the other gross observations were secondary to stress. The surviving male rat had a diffusely roughened nonglandular stomach mucosal surface (residual evidence of prior gastric irritation). Female rats that survived had no treatment-related gross changes.

Applicant's summary and conclusion

Conclusions:

Rat oral LD50 (male): 300 mg/kg
Rat oral LD50 (female): 623 mg/kg

Executive summary:

Five Fischer 344 rats per sex received 100, 500 or 1000 mg of test substance per kg body weight by single-dose gavage according to the guideline EPA Subdivision F, 81-1. Parameters examined during the two-week observation period included body weights and in-life observations. All animals were examined for gross pathologic changes.

All rats given 1000 mg/kg and four males and one female given 500 mg/kg died by test day eight. In-life observations of these rats and some survivors were nonspecific. Male and female rats given 100 mg/kg were normal throughout the observation period. All surviving rats gained weight by study termination. At necropsy, four males and one female administered 1000 mg/kg had a small amount of dark red urine in their urinary bladders and similar colored urine staining their perineal regions. The significance of these observations could not be determined; however, they are unlikely to occur in rats administered a sublethal dose. Males given 500 mg/kg and one female given 500 mg/kg that died had treatment-related gastric irritation.

Rats administered 100 mg/kg and females administered 500 mg/kg that survived had no treatment-related gross changes. The acute oral LD50 of the test substance was approximately 300 mg/kg for males and 623 mg/kg for female rats. Based on these results, the acute oral toxicity of the test substance was categorized as moderate.