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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
no data
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:
1970
Report date:
1970

Materials and methods

Principles of method if other than guideline:
dynamic inhalation in accordance with Niessen et al (1963). Arch Toxicol 20: 44
internal standard procedure
GLP compliance:
no
Remarks:
pre-GLP study
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
Isatoic anhydride, technical grade; no further data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male and female rats (Wistar II SPF)
- Source: Winkelmann, Kirchborchen
- Age at study initiation: no data
- Weight at study initiation: ca. 145 g
No further data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other: DMSO / Lutrol (1:1)
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation system in accordance with Niessen et al (1963). Arch Toxicol. 20: 44.
The aerosol was generated by spraying.
No further data

TEST ATMOSPHERE
- Brief description of analytical method used: spectrophotometry at 316 µM, 10-mm layer of test substance
- Samples taken from breathing zone: no data

VEHICLE (if applicable)
- Justification for use and choice of vehicle: no data
- Composition of vehicle: DMSO / Lutrol (1:9)
No further data.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
spectrometry (319 µm)
Duration of treatment / exposure:
28 days
Frequency of treatment:
4 hours per day, 5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.0116; 0.071 mg/L
Basis:
analytical conc.
No. of animals per sex per dose:
10 males and 10 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
no post-exposure
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes, behaviour
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: No

FOOD EFFICIENCY: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY, CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the exposure period
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5/sex/group
- Parameters examined: hemoglobin, erythrocyte count, leukocyte count, thrombocyte count, hematocrit, HbE value, mean corpuscular volume, prothrombin time, liver function test (GOT, GPT, SDH), kidney function test (serum urea, serum creatinine)

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No
After termination of exposure, animals were anesthetised and sacrificed by exsanguination. The following organs were weighed and examined macroscopically: thyroid, heart, lungs, liver, spleen, kidneys, adrenals, testes, ovaries
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
No signs of intoxication were observed.

BODY WEIGHT AND WEIGHT GAIN
Body weight gain of treated rats was not statistically significantly different from concurrent vehicle controls.

HAEMATOLOGY, CLINICAL CHEMISTRY
Hematological and clinical-chemical values as well as those for liver function test and kidney function test were within the normal range for all groups.

ORGAN WEIGHTS
Relative liver weights and absolute and relative lung weights were statistically significantly increased in high dose females. However, no information is given whether these changes were considered substance/treatment-related. No other significant changes in organ weights were reported.

GROSS PATHOLOGY
No pathological changes were noted for the organs of treated rats.

Effect levels

Dose descriptor:
NOEL
Effect level:
0.012 mg/L air
Sex:
male/female
Basis for effect level:
other: Increased liver and lung weights in higher doses

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

Groups of 10 male and 10 female Wistar rats were exposed to the test substance at analytical concentrations of 0.0116 and 0.071 mg/L for 4 weeks (4 h/d, 5 d/w). A control group was exposed to the concurrent vehicle, (DMSO/ Lutrol, 1:1). Observations/examinations included behaviour, body weight gain, selected hematological and clinical-chemical parameters, organ weights and gross pathology.

In high dose females, absolute and relative lung weights and relative liver weights were statistically increased. No other changes were noted. A histopathological examination was not carried out.