Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June-July 1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: meets basic scientific principles, well documented information, performed prior to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1969
Report Date:
1969

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
intraperitoneally in the form of 0.5 - 8% aqueous suspension with 0,5% carboxymethyl cellulose.
GLP compliance:
no
Remarks:
study performed prior to GLP standard
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in house
- Weight at study initiation: 20 (18-22) g
- Housing: single in Macrolon Type III cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

IN-LIFE DATES: From: day 1 To: day 14
Straini NMRI mice (own breed).

Total number of animals: 42 (21 males, 21 females)

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % in aqua pro injectione
Details on exposure:
intraperitoneally in the form of 0.5 - 8% aqueous suspension with 0.5% carboxymethyl cellulose.
Doses:
50, 100, 200, 400, 800, 1600 mg/kg
No. of animals per sex per dose:
Ten (5 males, 5 females) for dosages of 50, 100 & 200 mg/kg Four (2 males, 2 females) for dosages of 400, 800 and 1600 mg/kg.
Control animals:
not specified
Details on study design:
42 mice (21 females, 21 males) were exposed at dose levels of 50, 100, 200, 400, 800, 1600 mg/kg by intraperitonealed injection. Observations were recorded after 1, 7, 14 days observation period.
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 600 mg/kg bw
Based on:
test mat.
Mortality:
One male animal died 11 days after the injection of 800 mg/kg. The other animals all survived the 14-day observation period.
Clinical signs:
For up to one hour after the application, all mice showed sluggishness or sleepiness.
Thereafter, no changes were observed in relation to behavior or general condition.
Body weight:
There was no significant difference during the test.
Gross pathology:
Dissection findings:
The animal which died intercurrently showed fatty degeneration of the liver. As for the animals sacrificed at the end of the trial, 24 showed pale liver on macroscopic examination; all the other animals were unremarkable.
Other findings:
no data

Applicant's summary and conclusion

Conclusions:
Based on the results given in this study, LD50 after an observation period of 1, 7 and 14 days was in excess of 1600 mg/kg.
Executive summary:

This experiment was performed to assess the potential of acute toxicty with test article at dose levels of 50, 100, 200, 400, 800, 1600 mg/kg. The NMRI mice were exposed via intraperitoneal injection. For up to one hour after the application, all mice showed sluggishness or sleepiness. There was no significant difference during test period in all animals.One male animal died 11 days after the injection of 800 mg/kg. For the animals sacrificed at the end of the trial, 24 showed pale liver on macroscopic examination, and all the other animals were unremarkable.

In conclusion, test article presented relatively low toxicity on mice according to the experimental results, and LD50 can be considered to be greater than 1600 mg/kg.