Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 21, 2001 to January 02, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted following internationally accepted testing guidelines and performed according to the GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
protocol devation from 5 males and 5 females did not affect quality or outcome of study
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Specie & strain: Albino rat; Sprague-Dawley.
- Justification of Species: the rat is a rapresentative rodent species preferred by various regulatory agencies for use in an acute oral study.
- Source: Texas Animal Specialities, Humble, TX.
- Age at study initiation: 51 days males and 22 days.
- Weight at study initiation: males: 181 - 326 g; females: 199-218 g.
- Housing: 1 per cage.
- Cage type: suspended, wire bottom, stainless steel.
- Diet: PMI Feeds Inc.TM Formulab #5008; available ad libitum except for approximately 16 hours before dosing.
- Water: municipal water supply analyzed by TNRCC Water Utilities Division; available ad libitum from automatic water system.
- Quarantine period: 5 days.

ENVIRONMENTAL CONDITIONS
Set to maintain
- Temperature: 22 ± 3 °C.
- Humidity: 30 - 70 %.
- Air changes: 10-12 air change/hour.
- Photoperiod: 12 hours light/dark cycle.

IN-LIFE DATES
Animlas born in October 01 and 15, 2001. They were received by the laboratory at November 21 and December 06 and were treated with the test substance on December 19. The in-life portion of the study was termined on January 02, 2002.

No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: citric acid
Details on oral exposure:
TEST SUBSTANCE PREPARATION and ADMINISTRATION
The test substance was mixed with citric acid to produce a 40 % w/v concentration.

An individual dose was calculated for each animal based on its fasted body weight and administered by gavage at a volume of 12.6 ml/kg.
Each dose was administered using an appropriately sized singe and stainless steel ball-tipped intubation needle. The animals were returned to their cages immediately after dosing.
Doses:
5050 mg/kg (12.6 ml/kg).
No. of animals per sex per dose:
6 males and 4 females (nulliparous and non-pregnant) for a single fixed dose.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes; on Day 14 after dosing, each animal was euthanized by an overdose of CO2. All study animals were subjected to gross necropsy and all abnormalities were recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 050 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study. The estimated acute oral LD50, as indicated by the data, was determined to be greater than 5050 mg/kg.
Clinical signs:
Clinical signs included activity decrease, piloerection and respiratory chirp in both sexes, and diarrhea and sensitivity to touch in males.
Animals were asymptomatic by Day 1.
Body weight:
Body weight gain was unaffected by the administration of the test substance.
Gross pathology:
The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Any other information on results incl. tables

Reactions and Severity Time after Treatment  
hours days
MALES 1 2 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Activity decrease 6 6 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Sensitive to touch 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Diarrhea 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Piloerection 0 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Respiratory chirp 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
FEMALES  
Respiratory chirp 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Activity decrease 4 4 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Piloerection 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 is greater than 5050 mg/kg bw in males and females
Executive summary:

The test substance was evaluated for its acute oral toxicity potential in albino rats when administered as a single gavage dose at a level of 5050 mg/kg bw to males and females. No mortality occurred during the study. Clinical signs included activity decrease, diarrhea, piloerection, respiratory chirp and sensitivity to touch, which were no longer evident by Day 1. There was no effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Conclusion

The acute oral LD50 was determined to be greater than 5050 mg/kg bw