Morpholine

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

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

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

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

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

other: albino

Sex:

not specified

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on exposure:

undiluted morpholine and 1:2 diluted morpholine in water was tested

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

daily

Doses / concentrations

Dose / conc.:

900 mg/kg bw/day (nominal)

No. of animals per sex per dose:

7 animals

Details on study design:

For application, a portion of the fur about 3 inch wide, and entirely encircling the animal at, its midsection, was removed. A strip of absorbent cotton, 1 inch wide and about three-quarters as long as the circumference of the denuded area, was held around the animal by adhesive tape, sealing the sides of the cotton. Morpholine was applied through a window in the bandage, which was plugged after the daily application.

Positive control:

No

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Description (incidence):

Undiluted morpholine: caused the death of 2 of the 7 rabbits, the other 5 rabbits had such severe burns from the initial dose that a new series was started.

Diluted morpholune (1:2): All animals died before the eleventh dose.

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

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Diluted morpholine(1:2): Grossly the skin of all the rabbits was necrotic, having a thickened edematous area under the application. Inflammation and congestion of the underlying organs was always evident .

Undiluted morpholine: Blackened necrotic skin, inflamed and edematous derma, with severe burns of the underlying organs resulted .The other 5 rabbits had such severe burns from the initial dose that a new series was started .

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Skin: Epithelium sloughed off after 6 applications. The upper layer of the skin completely necrosed after the 9th, with congested derma and necrosed glands after the 10th

Kidney: No evidence of necrosis in any of the sections, but an abnormal amount of secretion into the tubules was increasingly evident as the series progressed.

Liver: Pale nuclei, necrosis and cell breakdown after the 4th application. Congestion and cloudy swelling becoming increasingly severe. The animal receiving the greatest number of doses had areas of fibrosis and fatty change .

Spleen: Congested in all cases with a profusion of erythrocytes .

Histopathological findings: neoplastic:

not specified

Effect levels

Key result

Dose descriptor:

other: dose level

Effect level:

900 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

mortality

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The dermal toxicity and skin absorption of Morpholine was assessed in one investigation using rabbits. Unneutralized, diluted Morpholine (1 part Morpholine, 2 parts water) was applied at a daily dose of 900 mg/kg bw to the clipped skin of the midsection of a group of 7 rabbits. All rabbits 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 included pale nuclei, necrosis, cell breakdown, congestion, cloudy swelling, and areas of fibrosis and fatty change. The kidneys had an "abnormal amount of secretion" in the tubules, and the spleen was congested with a perfusion of erythrocytes. The lung and stomach were normal under nontreated sites; however, these organs were "friable" when under the area of direct Morpholine application. The skin was necrotic and congested after the ninth and tenth application. The heart appeared normal upon microscopic examination.