Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to a guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
substance purity not given
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): monoethanolamine
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-300g
- Fasting period before study: over night

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.25, 0.50, 1.0, 2.0, 4.0 ml/kg bw (based on a density of 1.018 g/ml: 254, 509, 1018, 2036, 4072 mg/kg bw)
No. of animals per sex per dose:
5 males and 5 females (0.25-2.0 ml/kg dosing groups)
2 males (4.0 ml/kg dosing group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: on day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights
Statistics:
LD50 values and the estimated LD50 slopes were calculated by the moving average method (Thompson 1947; Weil 1983).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 089 mg/kg bw
Remarks on result:
other: based on a density of 1.018 g/ml
Sex:
male
Dose descriptor:
LD50
Effect level:
1.19 mL/kg bw
95% CL:
0.79 - 1.8
Sex:
female
Dose descriptor:
LD50
Effect level:
1.07 mL/kg bw
95% CL:
0.72 - 1.59
Mortality:
Dose (ml/kg) Numbers of Animals Dead Time of Death
(M,F)
0.25 0,0 N/A
0.50 1,0 12 days
1.0 1,2 1 or 2 days
2.0 5,5 4 hrs to 1 day
4.0 2 (M) 3 hrs

All deaths occurred relatively rapidly after dosing (within 2 days), except for one male rat that died after 12 days after a dose of 0.5 ml/kg. Both of the male rats receiving monoethanolamine at the maximum peroral dosage of 4.0 ml/kg died after 3 hours. One female in the 2.00 ml/kg group died after 4 hours.


Clinical signs:
MALES
Dosage (ml/kg) Signs of Toxicity
4.00 sluggishness at 15 min; slight piloerection at 1 hr. death at 3 hr.
2.00 sluggishness at 1.5 hr; slight piloerection at 2 hr.
1.00 slight red crust on perinasal fur, slight red crust on periocular fur (of 2); slight brown stain on periurogenital fur (of 1) at 1 day. Affected survivors recovered at 2 days.
0.50 one animal with slight sluggishness at 30 min, red crust at perinasal fur at 1 day; pallor, slight emaciation at 11 days; kyphosis, u nkempt appearance, red crust on periocular fur at 12 days (death).
0.25 none noted

FEMALES
Dosage (ml/kg) Signs of Toxicity
2.00 marked sluggishness at 15 min; piloerection, slight kyphosis, lacrimation at 3 hr; unsteady gait, marked sluggishness and lacri mation at 4 hr; death of one at 4 hr.
1.00 sluggishness at 1.0 hr; piloerection, slight lacrimation at 4 hr; red crust on perinasal fur, red crust on periocular fur, slight wetne ss of periurogenital fur (in 2)* at 1 day (*the presence of occult blood in discharge was verified by use of Hemastix Reagent Strips [Ames]); emaciation of 2 at 6 days, persisting through 14 days; recovery of 1 survivor at 2 days.
0.50 sluggishness, slight lacrimation at 4.0 hr; red crust on perinasal and periocular fur at 2 days; emaciation in 1 at 6 days, persisting through 14 days; recovery of 4 at 2 days.
0.25 none noted
Body weight:
Nothing abnormal reported.
Gross pathology:
MALES
Dosage (ml/kg) Gross Pathology
4.00 lungs pale red; stomachs, intestines dark red.
2.00 lungs of 1 mottled light and dark red; stomachs, intestines distended, filled with dark red liquid.
1.00 in deceased, stomach, intestines red; stomach filled with clear red liquid; in survivors, kidneys mottled dark red.
0.50 in deceased, stomach severely distended, filled with brown liquid; emaciation; in survivors, nothing remarkable.
0.25 nothing remarkable

FEMALES
Dosage (ml/kg) Gross Pathology
2.00 lungs mottled or bright red; stomachs, intestines dark red, filled with red liquid.
1.00 in deceased, glandular portion of stomachs dark red; in survivors, livers of 2 adhered to glandular portion of stomachs ; stomachs distended with gas; kidneys dark red.
0.50 liver of 1 adhered to glandular portion of stomach; stomach of 1 distended with gas; kidneys of 1 dark red.
0.25 nothing remarkable

Any other information on results incl. tables

The LD50 values (with confidence limits if calculated) in males and females were 1.19 (0.79 - 1.80) ml/kg and 1.07 (0.72 - 1.59) ml/kg, respectively. The slopes of the curves were 3.84 and 4.96 for males and females, respectively.

Applicant's summary and conclusion