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Administrative data

Description of key information

The LD50 values for acute oral toxicity is 1089 mg/kg bw in rats.

The LD50 values for acute dermal toxicity is 2504 mg/kg bw in rats.

The LC50 value for acute inhalation toxicity for 6 hours exposure duration, was established to exceed 1300 mg/m3, corresponding to a recalculated value for 4 hours of 1487 mg/m3.

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
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
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).
Key result
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 mlLkg. 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, unkempt 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 lacrimation 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 wetness 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

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.

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 089 mg/kg bw
Quality of whole database:
similar OECD TG 401

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Substance concentration was not measured.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five animals per sex were exposed to substantially saturated vapor for 6 hours using a static exposure system.
GLP compliance:
yes
Test type:
other: inhalation hazard test
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: none
- Diet: commercial appropriate diet ad libitum
- Water: municipal water ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The vapor was produced by enclosing approximately 100 g of the test material in a sealed 100 to 151 liter animal chamber for approximately 18 hours under static conditions. A mixing fan periodically agitated the chamber atmosphere to aid in distribution of the vapour. Oxygen was added, as needed to maintain a chamber oxygen content of approximately 20%. The temperature was maintained at 25 degrees C.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.3 mg/L air
Exp. duration:
6 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
ca. 1.3 mg/L air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Value derived from theoretical saturated vapor concentrations of monoethanolamine at room temperature and was not measured during the experiment.
Mortality:
There were no deaths noted for males or females exposed to the highest concentration achievable for 6 hours.
Clinical signs:
other: There were no signs of toxicity noted for males or females exposed to the highest concentration achievable for 6 hours.
Body weight:
Nothing abnormal reported.
Gross pathology:
The necropsy findings noted nothing remarkable in males or females.

The theoretical saturated vapor concentration of monoethanolamine at room temperature is 520 ppm (1.3 mg/L). The LC50 is greater than 520 ppm (Reviews of Environmental Contamination and Toxicology, Vol. 149, 1997.)

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1 487 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
1.0, 2.0 or 4.0 mL/kg
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
Groups of five animals per sex (2-3 kg) were subjected to 24 hours of contact with monoethanolamine (1.0, 2.0, or 4.0 mL/kg) which was retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze was wrapped around the trunk over the sample to prevent leakage. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period. Doses were varied by adjusting the volume of the test material. After the contact period, excess fluid was removed to diminish ingestion. Observations for toxicity and skin reactions were made at one hour, 7 days, and 14 days after the contact period. Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to termination). LD50 values and the estimated LD50 slopes were calculated by the moving average method (Thompson, 1947; Weil, 1983) and are based on a 14-day observation period. At death or termination, each animal was subjected to a gross pathologic evaluation.
Preliminary study:
The LD50 value for males was 2.46 mlLkg (2504 mg/kg) with a 95% confidence level of 1.79 - 3.39 mL/kg (1822 - 3451 mg/kg) and a slope of 5.60. The LD50 value for females was 2.83 mL/kg (2881 mg/kg) with a 95% confidence level of 1.61 - 4.98 mL/kg (1639 - 5070 mg/kg) and a slope of 3.89.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 504 mg/kg bw
95% CL:
>= 1 822 - <= 3 451
Sex:
female
Dose descriptor:
LD50
Effect level:
2 881 mg/kg bw
95% CL:
>= 1 639 - <= 5 070
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2.46 - <= 2.83 mL/kg bw
Mortality:
The numbers of deaths at each dose were as follows:

Dose (mL/kg) Numbers of Animals Dead Time of Death
(M/F)
4.0 5,4 1-2 days
2.0 1,1 2, 13 days
2.0 0,0 N/A

Deaths occurred within two days, except for one female that died at 13 days.
Clinical signs:
MALES
4.00 mL/kg dosing group:
erythema, edema, necrosis, ecchymosis at 1day; prostration in 1 animal at 1 day.
2.00 mL/kg dosing group:
erythema, edema at 1 to 7 days or death; necrosis at 1 to 14 days or death; ecchymosis at 1 day, persisting on 1 to ulceration at 7 or 14 days; desquamation, alopecia on 1 at 14 days; scabs at 14 days; sluggishness at 1 day or at 7 days; emaciation of 1 at 7 days; recovery of 2 survivors after 2 days.

1.00 mL/kg dosing group:
erythema at 1 day; persisting on 1 through 7 days; edema at 1 to 7 days; ecchymosis on 1 at 1 day; necrosis at 1 to 14 days; scabs, ulceration at 7 to 14 days. No signs of systemic toxicity.

FEMALES
4.00 mL/kg dosing group:
erythema, edema, ecchymosis at 1 day to death; necrosis at 1 day to death, persisting on 1 through 14 days; scabs, ulcerations on 1 at 7 to 14 days; sluggishness at 1 day; recovery of 1 at 2 days.

2.00 mL/kg dosing group:
erythema, edema at 1 to 7 days; necrosis at 1 to 14 days; ecchymosis at 1 day; scabs at death or termination; ulceration at 7 to 14 days; sluggishness in 2 at 1 day; abdominal distension in 1 at death; recovery of affected survivor at 2 days.

1.00 mL/kg dosing group:
erythema at 1 day; edema at 1 to 7 days; necrosis at 1 to 14 days; ecchymosis on 1 at 1 day; scabs, ulceration at 7 to 14 days; desquamation on 1 at 14 days; abdominal distension and emaciation (in 1), audible breathing in 1 at 14 days.
Body weight:
Nothing abnormal reported.
Gross pathology:
MALES
4.00 mL/kg dosing group:
lungs salmon-colored; trachea of 1 animal dark red; thymus of 1 animal mottled dark red; large intestines of 1 animal hemorrhaged.

2.00 mL/kg dosing group:
in deceased animal, lungs mottled salmon-colored and bright red; in survivors, lungs bright pink, salmon-colored or mottled bright pink to dark red.

1.00 mL/kg dosing group: lungs of 1 animal dark red.

FEMALES
4.00 mL/kg dosing group:
in deceased animals, lungs salmon-colored to dark red, with dark red foci; thymus of 1 dark red; intestines hemorrhaged; in survivor, nothing remarkable.

2.00 mL/kg dosing group:
in deceased animal, stomach, intestines liquid and gas-filled; small intestines hemorrhaged; in survivors, lungs salmon-colored to red; kidneys of 1 with a pitted surface; intestines of 1 gas-filled.

1.00 mL/kg dosing group:
lungs salmon-colored to dark red, 1animal with dark red foci; stomachs and intestines of 2 animals liquid and/or gas filled; small intestines of 1 animal hemorrhaged; abdominal cavity of 1 animal liquid-filled.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 504 mg/kg bw

Additional information

The study of Union Carbide Cooperation (1988) was selected as key study for all three relevant routes of exposure, as it was considered to be a reliable study using methods comparable to the respective OECD guidelines. Furthermore, regarding acute oral and inhalation exposure, BASF supporting studies are available. The oral LD50 was 1089 mg/kg bw in rats. In a supporting study from BASF (1966) an LD50 of 1515 mg/kg bw in rats was reported.

In an inhalation study performed with Sprague Dawley rats the LC50 for 6 hours exposure was > 520 ppm (1.3 mg/L or 1300 mg/m3) (Union Carbide, 1988), based on the theoretical saturated vapor concentration of MEA at room temperature. Using modified Haber's law (Cnx t = constant) and using n = 3 as a default value in accordance with Chapter R.7.4.4.1 of REACH Guidance on information requirements and chemical safety assessment for extrapolation from longer to shorter exposure duration, the 4 h LC50 is calculated to be > 1487 mg/m3. Although this value is below the limit for classification, it corresponded to the highest attainable concentration in the study at which no mortality or signs of toxicity were observed. Also no mortalities were reported upon exposure of rats to saturated vapor concentrations of MEA for 8 h (BASF, 1966) and to 0.136 mg/L for 7 h (BASF, 1978).

The dermal LD50 was 2504 mg/kg bw in male rats and 2881 in female rats (Unione Carbide, 1988).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is considered to be classified for acute oral tox. cat. 4 (H302: Harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776. Classification for acute inhalation and dermal toxicity is not warranted based on the selected key studies (rat inhalation LC50 (4 h) > 1487 mg/m3 and rat dermal LD50 = 2504 mg/kg bw). Nevertheless, the substance is already legally binding classified for all exposure routes regarding acute toxicity (H302, H312 and H332) according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation).