Registration Dossier

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:
other: This study was selected as a key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
One rat was 13 weeks old on the day of dosing. This deviation from the test guidelines did not affect the validity of the study because this rat was only a few days older than 12 weeks.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
One rat was 13 weeks old on the day of dosing. This deviation from the test guidelines did not affect the validity of the study because this rat was only a few days older than 12 weeks.
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 28 wt%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-13 weeks
- Weight at study initiation: 1163-253 g
- Fasting period before study: yes; approximately 16-18 hours prior to dosing
- Housing: singly in polycarbonate pans that contained bedding with enrichment (i.e., Shepherd's™ Cob + PLUS™).
- Diet (e.g. ad libitum): ad libitum except for fasting period prior to dosing; food was returned to the rats approximately 3-4 hours after dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26°C
- Humidity (%): 30-70% The humidity was above the targeted upper limit for one day during the study. A portable dehumidifier was used to decrease the humidity levels during this time.
- Air changes (per hr): Not Reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: Individual dose volumes were calculated using the fasted body weights obtained prior to dosing and the test substance density of 1.1 g/mL and were corrected for 28.1% purity using a factor of 3.56.
Doses:
175, 550, 1750, 5000 mg/kg
No. of animals per sex per dose:
One female each at dose levels of 175, and 550 mg/kg and 3 females each at dose levels of 1,750 or 5,000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were observed for mortality and signs of illness, injury, or abnormal behaviour daily. The rats were observed for clinical signs at the beginning of fasting, just before dosing, once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter.
-Frequency of weighing: one day prior to administration (test day -1), and on test days 0, 7, and 14.
- Necropsy of survivors performed: yes, on all animals at terminal sacrifice to detect grossly observable evidence of organ or tissue damage.
Statistics:
The Acute Oral Toxicity (OECD Test Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was used for all data analyses including: dose progression selection and the LD50.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
3 129 mg/kg bw
Based on:
act. ingr.
Mortality:
All three rats dosed at 5000 mg/kg died. There was no mortality at lower dose levels.
Clinical signs:
No clinical signs were observed in the rats dosed at 175 or 550 mg/kg and in one of the rats dosed at 1750 mg/kg. One rat dosed at 1750 mg/kg exhibited ataxia on the day of dosing and decreased muscle tone on the day of dosing and 1 and 2 days after dosing. The remaining rat dosed at 1750 mg/kg exhibited ataxia on the day of dosing. One of the rats dosed at 5000 mg/kg exhibited laboured breathing, clear ocular discharge, decreased muscle tone, prostrate posture, mydriasis, and moribundity on the day of dosing. This rat was sacrificed for humane reasons on the day of dosing. Another rat dosed at 5000 mg/kg exhibited ataxia, laboured breathing, clear ocular discharge, decreased muscle tone, low or prostate posture, and moribundity up to the day after dosing. This rat was sacrificed for humane reasons on the day after dosing. The remaining rat dosed at 5000 mg/kg exhibited ataxia, decreased muscle tone, and moribundity up to the day after dosing and was sacrificed for humane reasons on the day after dosing.
Body weight:
No biologically important body weight losses were observed in the surviving rats after dosing.
Gross pathology:
No test substance-related gross abnormalities were found.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
LD50 (female rats) > 3129 mg/kg.
Executive summary:

Following the Up-and-Down procedure, a single dose of test substance was administered by oral gavage to 1 fasted female rat each at a dose of 175 or 550 mg/kg and to 3 fasted female rats each at a dose of 1750 or 5000 mg/kg. The dose for all rats was corrected for purity. The rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. All rats were necropsied to detect grossly observable evidence of organ or tissue damage. No clinical signs were observed in the rats dosed at 175 or 550 mg/kg and in one of the rats dosed at 1750 mg/kg. One rat dosed at 1750 mg/kg exhibited ataxia on the day of dosing and decreased muscle tone on the day of dosing and 1 and 2 days after dosing. The remaining rat dosed at 1750 mg/kg exhibited ataxia on the day of dosing. One of the rats dosed at 5000 mg/kg exhibited laboured breathing, clear ocular discharge, decreased muscle tone, prostrate posture, mydriasis, and moribundity on the day of dosing. This rat was sacrificed for humane reasons on the day of dosing. Another rat dosed at 5000 mg/kg exhibited ataxia, laboured breathing, clear ocular discharge, decreased muscle tone, low or prostate posture, and moribundity up to the day after dosing. This rat was sacrificed for humane reasons on the day after dosing. The remaining rat dosed at 5000 mg/kg exhibited ataxia, decreased muscle tone, and moribundity up to the day after dosing and was sacrificed for humane reasons on the day after dosing. No biologically important body weight losses were observed in the surviving rats after dosing. No test substance-related gross lesions were found in the study. Under the conditions of this study, the estimated oral LD50 for the test substance corrected for purity was 3129 mg/kg for female rats.