Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002/05/07-2002/06/14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CD/Crl:CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, D-97633 Sulzfeld

- Age at study initiation: 41 days, females; 48 days, males

- Weight at study initiation: 167-192g females, 189-203g males

- Fasting period before study: 16 hours

- Housing: cages

- Diet: ssniff R/M-HV 1530 ad libitum, feeding was discontinued ca. 16 hours before administration

- Water: ad libitum



ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 3°C

- Humidity (%): 55 ± 15

- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil for the 200 mg/kg dose
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.48 ml/kg bw


CLASS METHOD (if applicable)

- Rationale for the selection of the starting dose: The dose is selected from a series of defined dose levels. The substance is tested using a stepwise procedure, each step uses three animals of one sex. Three animals of one sex are treated at 2000 mg/kg bw. When two or three animals die, testing at 200 mg/kg bw is performed. When fewer than two animals die, the substance should be retested with 2000 mg/kg bw using three animals of the other test. If two or three animals die, testing at 200 mg/kg bw should be performed. When in this second step, fewer than two animals die, no further testing is necessary.

When the results of the test at 2000 mg/kg bw indicate need for further testing at a lower dose level. Three animals of sex 1 are treated 200 mg/kg bw. When two or three animals die, testing at 25 mg/kg bw should be performed. When fewer than two animals die, the substance should be retested with 200 mg/kg bw, using three animals of the other sex. If in this second step, two or three animals die, testing at 25 mg/kg bw should be performed. When in this second step, fewer than 2 animals die, no further testing is necessary.
Doses:
200 and 2000 mg/kg b.w.
No. of animals per sex per dose:
6M, 3F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately at 5, 15, 30 and 60 minutes, as well as at 3,6 and 24 hours after administration. Body weights were recorded before adminstration of test substance and thereafter in weekly intervals up to the end of the study, and at death.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: During the 14 day observation period, changes of skin and fur, eyes and mucous membranes, respiratory and circulatory, autonomic and central nervous system, somatomotor activity as well as behaviour pattern were observed at least once a day until symptoms subsided, thereafter each working day. Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All gross pathological changes were recorded after termination, a microscopic examination of all organs which showed evident lesions was performed.
Statistics:
No statistical analysis was performed (the method used was not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
200 - 2 000 mg/kg bw
Mortality:
2000 mg/kg bw resulted in death within 5 min of all male animals. None of the six rats employed at 200 mg/kg bw died.
Clinical signs:
2000 mg/kg bw resulted following signs of systemic toxicity; reduced motility, ataxia, reduced muscle tone, dyspnoea. All animals at 200 mg/kg bw showed signs of systemic toxicity.
Body weight:
2/3 surviving female animals gained the expected body weight within the study period, one of 3 female animals showed a body weight reduction of 12.5%. All male surviving animals gained the expected body weight within the study period.
Gross pathology:
No abnormalities were found at microscopic post mortem examination of the animals.
Other findings:
None reported.

Any other information on results incl. tables

Table 1: Number of animals dead and time range within which mortality occurred

 

Dose
(mg/kg
bw)

Mortality (# dead/total)

Time range of deaths (hours)

Male

Female

Combined

200

 0/3

0/3

0/6 

 

2000

 3/3

 

 3/3

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value within the range of 200 to 2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.