4H-3,1-benzoxazine-2,4(1H)-dione

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

14.-25.1.1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data are given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Principles of method if other than guideline:

BASF-Test

GLP compliance:

no

Remarks:

pre-GLP study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4H-3,1-benzoxazine-2,4(1H)-dione

EC Number:

204-255-0

EC Name:

4H-3,1-benzoxazine-2,4(1H)-dione

Cas Number:

118-48-9

Molecular formula:

C8H5NO3

IUPAC Name:

4H-3,1-benzoxazine-2,4(1H)-dione

Details on test material:

Isatosäureanhydrid (Isatoic anhydride); no further data

Test animals

Species:

mouse

Strain:

other: Kisslegg

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: aqueous Tylose

Details on exposure:

VEHICLE
- Concentration in vehicle: 2, 4, 8, 10, 16%
- Amount of vehicle (if gavage): 10 ml/kg bw
According to the authors, the test substance is hydrolysed by water.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

No further data.

Doses:

200, 400, 800, 1000, 1250, 1600 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: beginning, mid and end of study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 250 mg/kg bw

Mortality:

no data

Clinical signs:

dyspnea, twitching, convulsive tremor, prone position

Body weight:

no data

Gross pathology:

peritoneal adhesions, pulmonary plethora, clayish-grey coloration of the liver

Any other information on results incl. tables

Dose mg/kg	Conc. %	Animal	Dead after 1 h	24 h	48 h	7 days
1600	16	5 m 5 f	0/5 0/5	5/5 5/5	5/5 5/5	5/5 5/5
1200	10	5 m 5 f	0/5 0/5	3/5 1/5	3/5 1/5	3/5 1/5
1000	10	5 m 5 f	0/5 0/5	1/5 0/5	1/5 0/5	1/5 0/5
800	8	5 m 5 f	0/5 0/5	0/5 0/5	0/5 0/5	0/5 0/5
400	4	5 m 5 f	0/5 0/5	0/5 0/5	0/5 0/5	0/5 0/5
200	2	5 m 5 f	0/5 0/5	0/5 0/5	0/5 0/5	0/5 0/5

1600 mg/kg: 5 min after injection tremors, morphin tails, aequous secretion from the oral cavity, dyspnea. The animals died within 1.75 h.

1250-1000 mg/kg: Dyspnea right after injection, mock attacks and cry of pain. 3.5 h later survivors showed abdominal position, dyspnea and light apathy. From day 2-4 they still showed dyspnea but no symptoms from day 5 on.

800-400 mg/kg: Agitating right after injection, irregular gait, cavernous flanks, dyspnea and convulsions. From 5 hours till 2 days after injection they showed abdominal position, dyspnea and semi-closed eyes. From day 4 on they were without symptoms.

Section: died animals: blood, coloration and degeneration of the liver; sacrificed animals: blunt liver borders, peritoneal adhesions

Applicant's summary and conclusion

Executive summary:

LD50 was ca. 1250 mg/kg bw after 7 days

Groups of mice were administered a preparation of the test substance in aqueous Tylose and were observed for 7 days. The test substance was found to hydrolyse in water. Clinical signs of toxicity comprised dyspnea, twitching, convulsive tremor, and prone position. Pathology revealed peritoneal adhesions, pulmonary plethora, and clayish-grey coloration of the liver.