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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1967-02-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1967
Report Date:
1967

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
BASF-Test, see details in the section "Any other information on materials and methods incl. tables".
GLP compliance:
no
Remarks:
study was performed prior to GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Morpholine (1, 4-Tetrahydrooxazin)
- Physical state: liquid
- Analytical purity: 99.2 %
- Impurities: 0.2 to 0.3 % water, 0.1 % diethylene glycol, 0.4 % n-ethylmorpholine

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult (based on body weight)
- Weight at study initiation: 180 to 288 g (male), 156 - 226 g (female)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4 and 20 %

Doses:
1600, 2000, 2500 and 3200 mL/kg bw = 1600, 2000, 2500 and 3200 mg/kg bw (conversion in mg/kg bw is based on the density d=1.00 g/cm³)
No. of animals per sex per dose:
5 animals (at 1600, 2000 and 3200 mg/kg bw)
10 animals (at 2500 mg/kg bw)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of application and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopical examination
Statistics:
Not indicated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 900 mg/kg bw
Mortality:
See details in the section "Any other information on results incl. tables".
Clinical signs:
At 3200 and 2500 mg/kg bw: squatting posture, ruffled fur, abdominal position, shallow and irregular respiration, closed eyes. After 24 hours the surviving animals showed red crusted eyes and noses, and trembling gait with delayed motion of the hind limbs.

2000 and 1600 mg/kg bw: accellerated respiration, squatting posture, red crusted noses, high stepping gait.
Body weight:
No data
Gross pathology:
Animals that died: 4x diarrhoea, 1x haemorrhagic enteritis.

Sacrificed animals: no abnormalities.

Any other information on results incl. tables

Mortality:

Dose (mg/kg bw) Gender   1 h  24 h  48 h  7 days  14 days        
3200  male  0/5 5/5 5/5 5/5  -        
3200  female  0/5 5/5 5/5 5/5  -        
2500  male  0/10 4/10 4/10 4/10 4/10        
2500  female  0/10 10/10 10/10 10/10 10/10        
2000  male  0/5 0/5 1/5 1/5  -        
2000  female  0/5 5/5 5/5 5/5 -        
1600  male  0/5 1/5 1/5 1/5 -        
1600  female  0/5 1/5 1/5 1/5  -        

The test substance caused dose dependent toxicity after a single ingestion and local irritations to exposed tissues.

Applicant's summary and conclusion

Executive summary:

In an acute oral toxicity study according to an internal BASF method (BASF AG, 1967), Sprague Dawley rats were given a single oral dose of Morpholine (99.2 %) diluted in water at 1600, 2000, 2500 or 3200 mg/kg bw. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. The oral LD50 was estimated as 1900 mg/kg bw. This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study according to OECD 401 in principle.