Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1967
Report Date:
1967
Reference Type:
publication
Title:
No information
Author:
Zeller H et al.
Year:
1966
Bibliographic source:
Naunyn-Schmiedeberg's Arch. Exp. Path.Pharmak. 253: 98
Reference Type:
review article or handbook
Title:
Toxikologisch-Medizinische Begruendung von MAK-Werten.
Author:
Zeller, H. et al.
Year:
1970
Bibliographic source:
XV. Internat. Kongr. Arbeitsmed., Wien 1966; cited in: DFG, Gesundheitsschaedliche Arbeitsstoffe, Weinheim.

Materials and methods

Principles of method if other than guideline:
BASF-Test (internal BASF method)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aethylenimin rein
- Analytical purity: pure (no further data)

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male/female

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: shaved rabbit back or nape (approx. 1 - 6 cm2)


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2-10 µL/kg bw
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
see "Any other information on material and methods incl. tables"
Frequency of treatment:
up to 5 times a week
Doses / concentrations
Remarks:
Doses / Concentrations:
1.66, 4.15, and 8.3 mg/kg bw (2, 5, and 10 µL/kg bw) (Recalculation bsed on relative density at 24 °C = 0.83)
Basis:
nominal per unit body weight
No. of animals per sex per dose:
1 animal/dose regime
Control animals:
no
Details on study design:
Post-exposure period: 4 and 5 weeks, respectively (1.66 and 4.15 mg/kg bw, respectively)
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: before test start, during test, and at test termination


HAEMATOLOGY: Yes
- Time schedule for collection of blood: no data
- How many animals: all animals
- Parameters examined: leukocytes, lymphocytes, erythrocytes, granulocytes


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: no data
- How many animals: all animals
- Parameters examined: urea, serum-glutamate-pyruvate-transaminase


URINALYSIS: Yes
- Time schedule for collection of urine: no data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
- 8.3 mg/kg bw: 3/3 animals dead within 1-2 days
- 4.15 mg/kg bw: no lethality
- 1.66 mg/kg bw: no lethality

Local symptoms: edema and red-brown, widespread parchment-like necrosis with confluent blood discharge


BODY WEIGHT AND WEIGHT GAIN
- 8.3 mg/kg bw: body weight decreased
- 4.15 and 1.66 mg/kg bw: no effects


HAEMATOLOGY
Blood urea was increased and a slight leukocytosis observed.


URINALYSIS
Proteinuria was noted; both erythrocytes and leukocytes were detected in the urine sediment.


HISTOPATHOLOGY: NON-NEOPLASTIC
Renal papillary necrosis and necrosis of the medulla renalis in both kidneys

Effect levels

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

After repeated application of undiluted ethylenimine on the shaved rabbit back skin edema and red-brown, widespread parchment-like necrosis with confluent blood discharge.

Repeated (3-4 times) application of 8.3 mg/kg bw test substance led to lethality in 3/3 rabbits within 1-2 days. Blood urea was increased and a slight leukocytosis was observed. Proteinuria was noted; both erythrocytes and leukocytes were detected in the urine sediment. Necropsy revealed in all of the deceased rabbits renal papillary necrosis and necrosis of the medulla renalis in both kidneys.

Repeated dermal exposure (10 times) to doses of 4.15 mg/kg bw was survived by three rabbits. Slight proteinurea, leukocytes and to a lesser degree erythrocytes in urine were observed. Blood urea values were normal. All parameters returned to normal within the post-exposure period of 5 weeks. Necropsy revealed in one animal renal papillary necrosis; the other two animals were without finding.

Repeated applications of 1.66 mg/kg bw (10 times) did not lead to mortality, clinical signs of toxicity or changes in body weight and blood urea. Only leukocyte counts were decreased, and traces of protein and leukocytes were found in urine. After the post-exposure period of 4 weeks, the rabbits were sacrificed and subjected to gross-pathological examination. Necropsy did not reveal any abnormalities.

Applicant's summary and conclusion