Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 June 1970 - 30 May 1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978
Reference Type:
study report
Title:
Unnamed
Year:
1978

Materials and methods

Principles of method if other than guideline:
The aim of the study was to investigate the effects of chronic inhalative exposure to the test substance. Reversibility of the effects was tested in the post exposure observation period.
One group of 35 rats/sex was exposed to 5 ppm of the test substance 5 hours per day, 5 days per week for 27 weeks (129 exposures) and observed until their spontaneous death. Another group of 40 rats/sex was exposed to 5 ppm of the test substance 5 hours per day, 5 days per week until all animals of the group were dead (332 exposures). The corresponding control groups were exposed to air.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Aziridine
EC Number:
205-793-9
EC Name:
Aziridine
Cas Number:
151-56-4
Molecular formula:
C2H5N
IUPAC Name:
aziridine
Details on test material:
- Name of test material (as cited in study report): Ethylenimine
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Willi Gassner (WIGA), D-8741 Sulzfeld
- Age at study initiation: no data
- Mean weight at study initiation: males 223 g, females 178 g
- Housing: 5 animals/cage
- Diet (ad libitum): Altromin R (Firma Altromin, D-4937 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1300 L chamber
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The nominal test substance vapour concentrations were verified by chemical analysis and by means of DRAEGER test tubes. 118 analytical measurements and 76 measurementy by Draeger tubes were conducted during 332 exposures, respectively. Mean measurements were 2.5 ppm by chemical analysis and 3 ppm by Draeger test tubes, respectively.
Duration of treatment / exposure:
27 weeks or until death (approx. 66 weeks)
Frequency of treatment:
5 hours/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
5 ppm (corresponding to approx. 8.9 µg/L)
Basis:
nominal conc.
No. of animals per sex per dose:
35 (subchronic) and 40 (chronic), respectively
Control animals:
yes, sham-exposed
Details on study design:
Post-exposure period: until death (subchronic satellite group)
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data


BODY WEIGHT: Yes
- Time schedule for examinations: once/week


HAEMATOLOGY: Yes
- Time schedule for collection of blood: 18 times during the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 15
- Parameters: hemoglobin, hematocrit, number of erythrocytes and leukocytes.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 18 times during the study
- Animals fasted: No data
- How many animals: 15
- Parameters: differential blood count, glutamate-pyruvate-transaminase, urea and kreatinine.


URINALYSIS: Yes
- Time schedule for collection of urine: 18 times during the study
- Parameters: pH, protein, saccharose, urobilinogene, sediment: leukocytes, erythrocytes, cristals, fat, bacteria, cylinder, epithelia: squamous epithelium, tubular epithel cells and renal epithelium.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
-Organ weights: liver, spleen, kidneys, heart, testes


HISTOPATHOLOGY: Yes
- Organs: central nervous system, pituitary gland, heart, lungs, skin, trachea, thyroid gland, liver, kidneys, adrenal glands, spleen, pancreas, mesenteric lymph nodes, stomach, intestinal tract, urinary bladder, and genitals.
- All abnormalities.
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
After exposure to the test substance no symptoms were observed except sporadic sneezing of single animals.
The test substance exposed group showed a shortened average survival time compared to the control group. Lethality was increased during exposure to the test substance.


BODY WEIGHT AND WEIGHT GAIN
The animals of both test substance exposed groups showed no reduction in body weight compared to the corresponding control groups.


HAEMATOLOGY
No changes of the measured parameters were observed compared to the control group.


CLINICAL CHEMISTRY
No changes of the measured parameters were observed compared to the control group.


URINALYSIS
No changes of the measured parameters were observed compared to the control group.

´
ORGAN WEIGHTS
no data


HISTOPATHOLOGY: NON-NEOPLASTIC and NEOPLASTIC
In the kidneys of the male animals of the test groups papillary necroses and oedema were observed. In addition, inflammatory and hyperregenerative changes of the trachea were described in test animals. The incidence of squamous epithelial metaplasia was noticeably increased in test animals compared to control animals (control group/ test group: males 1/35; females 0/2). In one female rat (test group) the formation of polyps was diagnosed. In the lungs of control and test animals squamous epithelial metaplasia accumulated. In one male test animal an adenocarcinoma of the lung was observed.
A higher incidence of breast tumours (control group/test group 32/60) in females and skin tumours in males (control group/test group 1/11) indicated a correlation with the exposure to the test substance. 5 male animals from the subchronic dose group showed carcinomas. The incidence of skin tumours in females was lower: in the test group 3 tumours including one carcinoma, in the control group 2 tumours including one carcinoma.

Effect levels

Dose descriptor:
NOAEC
Effect level:
5 ppm
Remarks on result:
not determinable
Remarks:
no NOAEC identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

In conclusion, exposure to the test substance caused reduced lifespan of the rats, histopathological changes in kidney and trachea and an increased incidence of tumours in trachea, lung, skin and breast.

Mean life span:

 

 

Subchronic

Chronic

 

Control

5 ppm

Control

5 ppm

Mean life span (d)

m

f

m

f

m

f

m

f

 

557

553

444

439

449

464

334

345

 

 

Lethality:

 

 

Subchronic

Chronic

 

Control

5 ppm

Control

5 ppm

Dead animals

m

f

m

f

m

f

m

f

 

6

3

15

6

7

3

18

7

Tumour localisation and classification:

 

 

Subchronic

Chronic

 

Control

5 ppm

Control

5 ppm

Tumour

m

f

m

f

m

f

m

f

Mamma:

 

 

 

 

 

 

 

 

adenoma

-

5

-

2

-

7

-

10

adenofibroma

-

-

-

4

-

4

-

7

fibroadenoma

-

4

-

7

-

6

2

12

fibroma

-

2

-

-

-

-

4

1

cystadenoma papilliferum

-

-

-

3

-

-

-

3

cystadenoma (papilliferum) + degeneration

-

-

-

4

-

4

-

2

carcinoma

-

-

-

4

-

-

-

1

Epidermis:

 

 

 

 

 

 

 

 

epithelioma malherbe

-

-

-

-

1

-

4

-

basalioma

-

-

-

1

-

-

-

-

syringoma

-

-

-

-

-

1

1

-

keratocanthoma invasivum

-

-

-

1

-

-

-

-

keratocanthoma invasivum + degeneration

-

-

-

-

-

-

1

-

carcinoma

-

1

5

-

-

-

-

1

Dental origin:

 

 

 

 

 

 

 

 

adamantinoma

-

-

-

-

-

-

-

1

Thyroid gland:

 

 

 

 

 

 

 

 

adenoma

3

-

-

-

4

6

4

2

carcinoma

1

1

-

-

2

6

-

2

Adrenal glands:

 

 

 

 

 

 

 

 

adenoma of the adrenal cortex

4

-

2

1

2

-

1

1

chromaffinoma

-

-

-

-

2

-

1

-

neuroblastoma/sympathoblastoma

3

-

-

-

4

1

-

1

carcinoma

-

-

-

-

-

1

1

-

Pituitary gland:

 

 

 

 

 

 

 

 

adenoma

1

5

-

*

*

11

2

*

carcinoma

-

-

-

-

-

2

-

1

Pancreas:

 

 

 

 

 

 

 

 

adenoma

1

-

-

-

1

-

-

-

Lungs:

 

 

 

 

 

 

 

 

carcinoma

-

-

-

-

-

-

1

-

Brain/ meninges:

 

 

 

 

 

 

 

 

meningenoma

-

-

-

-

-

-

2

-

malign neurinoma

-

-

-

-

-

-

-

1

gliablastoma

-

-

-

-

2

1

1

3

Uterus/vagina:

 

 

 

 

 

 

 

 

carcinoma

-

-

-

2

-

3

-

3

sarcoma

-

1

-

1

-

1

-

6

Intestines:

 

 

 

 

 

 

 

 

carcinoma

-

-

-

-

1

-

1

-

sarcoma

-

-

-

-

-

-

-

1

Kidneys:

 

 

 

 

 

 

 

 

nephroblastoma

-

1

2

2

-

1

-

1

Epididymis:

 

 

 

 

 

 

 

 

sarcoma

-

-

-

-

-

-

2

-

Liver:

 

 

 

 

 

 

 

 

hepatocellular adenoma

-

-

-

-

-

1

-

-

Subcutis:

 

 

 

 

 

 

 

 

sarcoma

-

-

2

-

-

-

2

1

Mediastinum:

 

 

 

 

 

 

 

 

sarcoma

-

1

1

-

-

1

1

-

Abdominal region:

 

 

 

 

 

 

 

 

lipoma

-

-

-

-

-

-

-

1

sarcoma

-

-

-

-

-

-

1

-

Heart:

 

 

 

 

 

 

 

 

endocardial fibroma

-

-

-

-

-

-

1

-

Ovaries:

 

 

 

 

 

 

 

 

cystoma

-

-

-

2

-

-

-

-

carcinoma

-

-

-

-

-

-

-

1

sarcoma

-

-

-

-

-

-

-

1

 

Applicant's summary and conclusion