Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Off-white powder
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: about 6 - 9 weeks
- Weight at study initiation: 210-241 grams for males and 200-230 grams for females
- Fasting period before study: 16 - 20 hours
- Housing: 5/sex/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet: Fresh Purina Rat Chow (Diet #5012) was freely available
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.2% methyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 33%

DOSAGE PREPARATION (if unusual):
The test article was mixed with 0.2% methyl cellulose to make dosing by gavage possible. The dose was based on the dry weight of the test article.
Doses:
5000 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: Animals were observed 1,2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, on days 3 and 7. at death or at termination in the survivors.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 5000 mg/kg oral dose.
Clinical signs:
There were no abnormal systemic signs noted in 9/10 animals. One female had dyspnea, lethargy, emaciation, ataxia and weight loss throughout the study period.
Body weight:
Instances of transient weight loss were noted in two females. All other animals gained weight normally.
Gross pathology:
Necropsy results were normal in 9/10 animals. Necropsy observation of animal #10-F revealed that the weight loss and abnormal systemic signs were due to a dosing error rather than to an effect of the test article.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Based on the results of this study, the oral LD50 in rats is greater than 5000 mg/kg.
Executive summary:

In a GLP compliant OECD guideline study, 5 male and 5 female Wistar rats were treated with the test substance by oral gavage administration at a dosage of 5000 mg/kg body weight. The test item was used as a 33% mixture in 0.2 % methyl cellulose. All animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, on days 3 and 7and at termination of the study. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Instances of transient weight loss were noted in two females. All other animals gained weight normally. There were no abnormal systemic signs noted in 9/10 animals. One female (#10) had dyspnea, lethargy, emaciation, ataxia and weight loss throughout the study period. Necropsy results were normal in 9/10 animals. Necropsy observation of animal #10-F revealed that the weight loss and abnormal systemic signs were due to a dosing error rather than to an effect of the test article. Therefore, the LD50 in the rat was determined to exceed 5000 mg/kg body weight.