Morpholinium toluene-4-sulphonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable 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:

The carcinogenic potential of a combination of nitrite and morpholine was assessed.

GLP compliance:

no

Remarks:

prior to GLP

Test material

Test material information

Constituent 1

Reference substance name:

Morpholine

EC Number:

203-815-1

EC Name:

Morpholine

Cas Number:

110-91-8

Molecular formula:

C4H9NO

IUPAC Name:

morpholine

Details on test material:

- Name of test material: Morpholine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system 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.