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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meet basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Induction of Malignant Tumors in Rats by Simultaneous Feeding of Nitrite and Secondary Amines (Induktion maligner Tumoren bei Ratten durch gleichzeitige Verfütterung von Nitrit und sckundärcn Aminen).
Author:
Sander J & Bürkle G
Year:
1969
Bibliographic source:
Z. Krebsforsch. 73: 54-66

Materials and methods

Principles of method if other than guideline:
other: no data
GLP compliance:
no
Remarks:
prior to GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Morpholine

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 120 ± 3 g
- Diet: Altromin

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: Altromin (standard diet)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
56 Days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
500 mg/kg/d
Basis:

No. of animals per sex per dose:
7 animals
Control animals:
yes, plain diet
Details on study design:
Post-exposure period: After 270 days had elapsed, all animals of the test group were sacrificed; no further data

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: in regular intervals
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Not specified.

Results and discussion

Results of examinations

Details on results:
No animal of the test group and of the control group died within the study period of 56 days.
After 270 days had elapsed, all animals of the test group were sacrificed, the only symptom was moderate adiposis of the liver.

Effect levels

Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: liver findings

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:
In a repeated dose toxicity study in Sprague-Dawley rats (Sander & Bürkle, 1969), Morpholine was added to feed for eight weeks. Seven rats took in a daily average of 0.5 g/kg bw. This dosage did not kill the animals. After 270 days had elapsed, the only symptom was moderate adiposis of the liver. Damage caused by subchronic oral intake of Morpholine depended markedly on the individual dose and route of administration. This study is classified as acceptable.