2,2-(1,4-phenylene)bis((4H-3,1-benzoxazine-4-one)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 92/69/EC Annex V, B7

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2-(1,4-phenylene)bis((4H-3,1-benzoxazine-4-one)

EC Number:

418-280-1

EC Name:

2,2-(1,4-phenylene)bis((4H-3,1-benzoxazine-4-one)

Cas Number:

18600-59-4

Molecular formula:

C22H12N2O4

IUPAC Name:

2-[4-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-4H-3,1-benzoxazin-4-one

Test animals

Species:

other: Sprague-Dawley rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 1% methylcellulose

Details on oral exposure:

Method of administration: gavage

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Control animals:

not specified

Results and discussion

Results of examinations

Details on results:

Clinical observations:
There were no clinical signs or mortalities, nor any adverse treatment-related changes in body weight (gain), food and water consumptions.

Laboratory findings:
No adverse treatment-related changes in haematology or biochemistry.

Effect in organs:
Liver weight (adjusted for body weight) was statistically significantly increased (dose-dependently) in male rats given 150 and 1000 mg/kg bw/day. In the 1000 mg/kg group the increased liver weight was accompanied by an increased incidence of congestion (incidences were 1/5 and 4/5 in males of the control group and the 1000 mg/kg group, respectively.)
Microscopic examination of the testes reveled vacuolation of the Sertoli cells of some tubules in 0/5, 1/5, 2/5 and 3/ 5 males of the groups given 0, 15, 150 and 1000 mg/kg bw, resp..

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

15 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

15 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified