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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: 95.7%

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, NewYork
- Age at study initiation: 9 weeks
- Weight at study initiation: Males: 174.0-188.4 g; Females: 133.0-140.4 g
- Fasting period before study: No
- Housing: Individually
- 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 : Animals were randomly assigned by weight

ENVIRONMENTAL CONDITIONS
- Animal room was designed to maintain adequate environmental conditions concerning temperature and humidity

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Trunk
- Type of wrap: Plastic wrap covered by a stretch bandage taped

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was washed with mild soap and water, rinsed thoroughly and dried with a soft disposable towel.
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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: A careful in-life observation was made and recorded frequently the day of dosing and at least once each working day throughout the two-week observation period. Routine monitoring on weekends/holidays was limited to animal husbandry procedures required to ensure the availability of feed and water. The rats were weighed the day of treatment and on test days 2, 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

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

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: The rats were normal throughout the observation period, with the exception of two males which were lethargic with palpebral closure on test day two only.

Gross pathology:

All animals were within normal limits at necropsy.

Applicant's summary and conclusion

Conclusions:

Rat dermal LD50 (male/female): >2000 mg/kg

Executive summary:

Five Fischer 344 rats per sex received a single, dermal 24-hour exposure to 2000 mg of undiluted test substance per kg body weight according to the EPA guideline Subdivision F, 81-2. Parameters examined during the two-week observation period included body weights and in-life observations. All animals were examined for gross pathologic changes.

All animals survived the 2000 mg/kg limit test established by the guidelines and therefore no other dose level was tested. The rats were normal throughout the observation period, with the exception of two males which were lethargic with palpebral closure on test day two only. All rats gained weight by study termination and were within normal limits at necropsy.

It was concluded that, under the conditions of this study, the acute dermal LD50 of the test substance was greater than 2000 mg/kg for male and female rats.

Based on these results, the acute dermal toxicity of the test substance was categorized as low.