Aziridine

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: No data on GLP compliance and it does not follow a guideline, because the only stated endpoint is the renal papillary necrosis. Intravenous route.

Data source

Reference

Reference Type:

publication

Title:

PATTERN OF RENAL CORTICAL SCARRING AFTER EXPERIMENTAL PAPILLARY NECROSIS

Author:

WHITBOURN RJ, HENRY MA, TANG JD

Year:

1984

Bibliographic source:

Pathology (1984), 16, pp. 272-277.

Materials and methods

Principles of method if other than guideline:

Intravenous injection of ethyleneimine to assess the renal papillary necrosis.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Aziridine

EC Number:

205-793-9

EC Name:

Aziridine

Cas Number:

151-56-4

Molecular formula:

C2H5N

IUPAC Name:

aziridine

Test animals

Species:

rat

Strain:

other: albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 200 g
- Diet (e.g. ad libitum): pellet diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Rats were killed at 2 and 4 d, 1, 2, 4 and 8 wk and their kidneys were removed.

Frequency of treatment:

Once

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg/kg bw

No. of animals per sex per dose:

20 animals/group (6 groups)

Control animals:

not specified

Examinations

Observations and examinations performed and frequency:

Extent of renal papillary necrosis, at the sacrifice time, at 2 and 4 d, 1, 2, 4 and 8 wk .

Results and discussion

Results of examinations

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Renal papillary necrosis developed in all animals given ethylenimine. In most animals this was severe, and there was a tendency for the extent of the lesion to increase with time.

Applicant's summary and conclusion

Conclusions:

Ethyleneimine induces three types of renal cortical damage (papillary necrosis).

Executive summary:

Three types of renal cortical damage were found in rats two months after papillary necrosis had been induced by ethyleneimine, at doses of 10 mg/kg bw, intravenous. Damage included: circumscribed areas of interstitial nephritis affecting either deep or superficial nephrons; wedge-shaped or conical scars, extending from capsule to inner medulla; widespread tubular dilatation and cyst formation with a diffuse increase in interstitial tissue, usually associated with dense fibrous repair of the papillary remnant.

In most animals the renal papillary necrosis was severe, and there was a tendency for the extent of the lesion to increase with time.