Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Remarks:
other: repeated dosage < 30 days
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1939
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:
THE ACUTE AND SUB-ACUTE TOXICITY OF MORPHOLINE
Author:
Shea TE Jr
Year:
1939
Bibliographic source:
J. Ind. Hyg. Toxicol. 21: 236-245

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
not specified
GLP compliance:
no
Remarks:
prior to GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Morpholine
- Analytical purity: not less than 98% pure

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Details on exposure:
Route of Administration: dermal
Analytical verification of doses or concentrations:
no
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
900 mg/kg/d
Basis:

No. of animals per sex per dose:
7 animals
Details on study design:
Post-exposure period: no data given
Positive control:
No.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
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 specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
dose level: 0.9 g/kg day
Effect level:
900 mg/kg bw/day
Basis for effect level:
other: All animals died after 10-fold repeated dermal exposure to Morpholine.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

In a repeated dose dermal toxicity study (Shea, 1939), unneutralized, diluted Morpholine (1 part Morpholine, 2 parts water) was applied at a daily dose of 900 mg/kg bw to the clipped skin. All rabbits (7/7) died before the eleventh dose. Necrosis of the treated skin, and inflammation and congestion of the underlying organs were evident upon gross examination. Microscopic lesions of the liver and effects on kidneys and spleen were observed.

This study is classified as acceptable.