7a-ethyldihydro-1H,3H,5H-oxazolo[3,4-c]oxazole

Acute Toxicity: oral

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

7a-ethyldihydro-1H,3H,5H-oxazolo[3,4-c]oxazole

EC Number:

231-810-4

EC Name:

7a-ethyldihydro-1H,3H,5H-oxazolo[3,4-c]oxazole

Cas Number:

7747-35-5

Molecular formula:

C7H13NO2

IUPAC Name:

7a-ethyl-tetrahydro-1H-[1,3]oxazolo[3,4-c][1,3]oxazole

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 or test system 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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 249 mg/kg bw

Remarks on result:

other: 4503-6673 mg/kg

Effect levels 2

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:

other: 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.

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.