Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data to permit a meaningful evaluation of study results.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Remarks:
No guideline listed
Principles of method if other than guideline:
P-1601 as supplied was administered by gavage as a single dose to COX-SD albino rats.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): P-1601 (Oxazolidine E, BIOBANTMCS-1246 Antimicrobial)
- Physical state: Light yellow colored liquid
- Analytical purity: 94.52%
- Lot/batch No.: M4590
- Stability under test conditions: Not reported assumed to be stable under normal storage conditions

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Age was not reported
- Weight at study initiation: 211±13 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sterile deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0, 840, 1000, 1000, and 1000 mg/ml Respective to 0, 2100, 3000, 4200 and 6000 mg/kg
- Justification for choice of vehicle: Sterile Deionized Water


MAXIMUM DOSE VOLUME APPLIED:
1.5, 0.48-0.57, 0.60-0.7, 0.80-0.97 and 1.2-1.3 mL
(Set dosing volumes were not utilized)
Respective to
0, 2100, 3000, 4200 and 6000 mg/kg

Doses:
0, 2100, 3000, 4200, 6000 mg/kg/day
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
The test material was administered as a solution in sterilized deionized water by gavage as a single dose to 10 rats/sex/dose. The dose volume was varied based on the body weights of the Cox-SD rats used in the study.

Animals were observed frequently on the day of dosing, and daily thereafter for 14 days. Any unusual signs of toxicity or death were noted. Animals were subjected to a gross pathological examination as soon as possible after spontaneous death, or at the scheduled necropsy on day 14.
Statistics:
The LD50 values with 95% confidence limits, and the slope were calculated according to Finney's probit analysis.

Results and discussion

Preliminary study:
At high doses of 6000 mg/kg/day, most males and all females died within 4 hours. The females were ataxic before death.

At 4200 mg/kg/day, most of the females and 2 males died within 4 hours. Necropsy showed distended stomachs. The male survivors at 4200 mg/kg and some of the females at 2100 mg/kg showed hemorrhagic nasal discharge. At necropsy, two male rats at 2100 mg/kg and two at 3000 mg/kg showed some lung infection. The organs in all other animals were grossly normal.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
5 249 mg/kg bw
Remarks on result:
other: 4503-6673 mg/kg
Sex:
female
Dose descriptor:
LD50
Effect level:
3 674 mg/kg bw
Remarks on result:
other: 3216-4197 mg/kg
Mortality:
Mortality Data
Dose Mortality Mortality
(mg/kg) (males) (females)
0 0/10 0/10
2100 0/10 0/10
3000 0/10 1/10
4200 2/10 8/10
6000 7/10 10/10
Clinical signs:
At high doses of 6000 mg/kg/day, most males and all females died within 4 hours. The females were ataxic before death. At 4200 mg/kg/day, most of the females and 2 males died within 4 hours.
Body weight:
Average % Body weight gain was
Male: 21-25 %
Female: 9-14 %
Gross pathology:
Necropsy showed distended stomachs. The male survivors at 4200 mg/kg and some of the females at 2100 mg/kg showed hemorrhagic nasal discharge. At necropsy, two male rats at 2100 mg/kg and two at 3000 mg/kg showed some lung infection. The organs in all other animals were grossly normal.
Other findings:
None

Any other information on results incl. tables

From the data the compound appers to be more toxic to female rats than to the male rats

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the material in male rats was reported to be 5249 mg/kg (4503-6673 mg/kg), and 3674 mg/kg (3216-4197 mg/kg) in females.
Executive summary:

The test material was administered as a solution in sterilized deionized water by gavage as a single dose to 10 rats/sex/dose. The dose volume was varied based on the body weights of the Cox-SD rats used in the study.

Animals were observed frequently on the day of dosing, and daily thereafter for 14 days.
 Any unusual signs of toxicity or death were noted. Animals were subjected to a gross pathological examination as soon as possible after spontaneous death, or at the scheduled necropsy on day 14.

The LD50values with 95% confidence limits, and the slope were calucalted according to Finney's probit analysis.

At high doses of 6000 mg/kg/day, most males and all females died within 4 hours. The females were ataxic before death.

At 4200 mg/kg/day, most of the females and 2 males died within 4 hours.
 Necropsy showed distended stomachs. The male survivors at 4200 mg/kg and some of the females at 2100 mg/kg showed hemorrhagic nasal discharge. At necropsy, two male rats at 2100 mg/kg and two at 3000 mg/kg showed some lung infection. The organs in all other animals were grossly normal.

The acute oral LD50of the material in male rats was reported to be 5249 mg/kg (4503-6673 mg/kg), and 3674 mg/kg (3216-4197 mg/kg) in females.