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Toxicological information

Acute Toxicity: oral

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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:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity: 99.4%
Impurities: Not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Received from Harlan Laboratories, Inc., Frederick, MD on November 6, 2013.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (10-11 weeks)
- Weight at study initiation: 194-200 grams
- Fasting period before study: overnight
- Housing: The animals were individually housed in plastic solid bottom polycarbonate cages which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g., toy) was placed in each cage. Corncob bedding (1/8 inch bed-o’cobs®) was used and was changed at least once per week.
- Diet (e.g. ad libitum): ad libitum, except during fasting period
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14-27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 43-55%
- Air changes (per hr): 13/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: test substance was 25% w/w in mixture
- Vehicle was a solution of 0.1% Tween-80 in 0.5% methylcellulose
- Amount of vehicle (if gavage): 4.5 mL for a dose level of 4,390 mg/kg and 5.3 mL for a dose level of 5000 mg/kg.


MAXIMUM DOSE VOLUME APPLIED: 5.3 mL.

DOSAGE PREPARATION (if unusual): At concentrations higher than 25% w/w, the viscosity was too high to be administered properly. Due to the high dose volume of the dose solution to be administered (23.11 and 26.32 ml/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.

CLASS METHOD (if applicable)
- Based on the estimated LD50 (4,930 mg/kg) of the test substance a Main Test was conducted using a default starting dose level of 4,390 mg/kg which was administered to one healthy female rat by oral gavage.
Doses:
One rat was dosed at 4,390 mg/kg (4.5 mL dose volume) and 3 rats were dosed at 5,000 mg/kg (5.3 dose volume).

Due to the high dose volume of the dose solution to be administered (23.11 and 26.32 ml/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.
No. of animals per sex per dose:
All rats were female. One rat was dosed at 4,390 mg/kg and 3 rats were dosed at 5,000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, Day 7, and Day 14
- Necropsy of survivors performed: yes
- Other examinations performed: Individual body weights were recorded before test substance administration (initial), on Day 7, and Day 14 (termination). Clinical signs were observed during the first several hours after dosing and at least once a daily thereafter for 14 days after dosing. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
Statistical analysis was limited to the mean density value for dosing.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Animals at both dose levels survived the 14-day observation period.
Clinical signs:
4,390 mg/kg Dose Level
- no clinical signs during 14-day observation period

5,000 mg/kg Dose Level
- all animals exhibited reduced fecal volume but recovered by Day 3
Body weight:
Animals at both dose levels gained body weight during the 14-day observation period
Gross pathology:
At both dose levels no gross abnormalities were noted for when necropsied at the conclusion of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 of the test substance is greater than 5,000 milligrams per kilogram of body weight in female rats.
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route following the test guidelines OPPTS 870.1100 and OECD 425. Under the conditions of this study, the acute oral LD50 of the test substance greater than 5,000 mg/kg of body weight in female rats.