2-(hydroxymethylamino)ethanol

Endpoint summary

Description of key information

LD50 was considered to be 1620 mg/kg (1069-2455) for amle and 1956 mg/kg (1110-3093) for female when Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from secondary literature

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute oral toxicity study of Ethanol, 2-(hydroxymethylamino) in Sprague-Dawley rats.

GLP compliance:

no

Test type:

other: No data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-(hydroxymethylamino)ethanol
- Molecular formula (if other than submission substance): C3H9NO2
- Molecular weight (if other than submission substance): 91.11 g/mole
- Substance type: Organic
- Physical state: Solid
- SMILES: OCCNCO

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Age at study initiation: 6-8 weeks

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Distilled

Details on oral exposure:

Not applicableVEHICLE
- Concentration in vehicle: 750, 1250, 2100 and 3500 mg/kg (for males), 2500, 3150, 4000 and 5000 mg/kg (for females in first study) and 600, 1200, 1800 and 2400 mg/kg (for females in second study)
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: Distilled water


DOSAGE PREPARATION (if unusual): The test material was administered orally in a single dose by means of gavage at a constant dose volume of 10 ml/kg.

Doses:

For male: 750, 1250, 2100 and 3500 mg/kg
For female: 2500, 3150, 4000 and 5000 mg/kg
For female in second study: 600, 1200, 1800 and 2400 mg/kg

No. of animals per sex per dose:

Total: 60
male:
750 mg/kg: 5
1250 mg/kg: 5
2100 mg/kg: 5
3500 mg/kg: 5
For female:
2500 mg/kg: 5
3150 mg/kg: 5
4000 mg/kg : 5
5000 mg/kg : 5
For female in second study:
600 mg/kg: 5
1200 mg/kg: 5
1800 mg/kg: 5
2400 mg/kg: 5

Control animals:

not specified

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed frequently on the day of dosing and for 14 days following. They were weighed immediately prior to dosing, 7 days after dosing and at death or sacrifice at the end of the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

The LD50 values were calculated based on the mortality pattern by probit analysis (Finney, 1971).

Sex:

male

Dose descriptor:

LD50

Effect level:

1 620 mg/kg bw

Based on:

test mat.

95% CL:

1 069 - 2 455

Remarks on result:

other: 50 % mortality observed

Sex:

female

Dose descriptor:

LD50

Effect level:

1 956 mg/kg bw

Based on:

test mat.

95% CL:

1 110 - 3 093

Remarks on result:

other: 50 % mortality observed

Mortality:

In male rat, when treated with 3500 mg/kg bw, all animals died,
When treated with 2100 mg/kg bw, 4 animals died.
When treated with 1250 mg/kg bw, 1 animal died
when treated with 750 mg/kg bw, no morality observed.
In female rats, when treated with 2500, 3150, 4000 and 5000 mg/kg, all animal died in study.
When treated with 2400 mg/kg bw, 4 animals died.
When treated with 1800 mg/kg bw, 2 animals died.
When treated with 600 and 1200 mg/kg bw, no morality observed.

Clinical signs:

other: Hyperkinesias, sedation, coma, prostration, piloerection, soiled coat, ataxia and haemodaccryorrhea were observed at 0.5 hr to 4 days after dosing.

Gross pathology:

In the first study, red stained fluid in the gut in premature decedents and in post mortem at 14 day, gas-filled gut and stomach were observed in one male rat. In the second study, No abnormalities were observed in treated female rat.

Other findings:

No data available

Mortality by dose and sex (first study):

Dose Level (mg/kg bw)	Male	Female
750	0/5	-
1250	1/5	-
2100	1/5	-
2500	-	5/5
3150	-	5/5
3500	5/5	-
4000	-	5/5
5000	-	5/5

 

Mortality by dose (female only, second study):

Dose Level (mg/kg bw)	Female
600	0/5
1200	0/5
1800	2/5
2400	4/5

 

Interpretation of results:

Toxicity Category IV

Conclusions:

LD50 was considered to be 1620 mg/kg (1069-2455) for amle and 1956 mg/kg (1110-3093) for female when Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

Executive summary:

In a Acute oral toxicity study, Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol in the concentration of 750, 1250, 2100 and 3500 mg/kg (for males), 2500, 3150, 4000 and 5000 mg/kg (for females in first study) and 600, 1200, 1800 and 2400 mg/kg (for females in second study) in Distilled water orally by gavage. In male rat, all animals died at 3500 mg/kg bw, 4 animals died at 2100 mg/kg bw, 1 animal died at 1250 mg/kg bw and no morality observed at 750 mg/kg bw. In female rats, all animal died at 2500, 3150, 4000 and 5000 mg/kg within 4 hours to 1 day. Due to the unexpected mortality in the first study, study was repeat using lower dose levels for females only. 4 animals died at 2400 mg/kg bw. 2 animals died at 1800 mg/kg bw and no morality observed at 600 and 1200 mg/kg bw within 1 day. Hyperkinesias, sedation, coma, prostration, piloerection, soiled coat, ataxia and haemodaccryorrhea were observed at 0.5 hr to 4 days after dosing. In the first study, generally lower body weight were observed than expected with one male rat having lost weight after 7 days, and another having lost weight at the end of the 14-day observation period. No effect on body weight was observed in second study. In the first study, red stained fluid in the gut in premature decedents and in post mortem at 14 day, gas-filled gut and stomach were observed in one male rat. In the second study, No abnormalities were observed in treated female rat. Therefore, LD50 was considered to be 1620 mg/kg (1069-2455) for amle and 1956 mg/kg (1110-3093) for female when Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 620 mg/kg bw

Quality of whole database:

Data is Klimisch 4 and from secondary literature

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 2-[hydroxy(methyl)amino]ethanol has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 2-[hydroxy(methyl)amino]ethanol. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a study given by (HPVIS) EPA (U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 1986), Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol in the concentration of 750, 1250, 2100 and 3500 mg/kg (for males), 2500, 3150, 4000 and 5000 mg/kg (for females in first study) and 600, 1200, 1800 and 2400 mg/kg (for females in second study) in Distilled water orally by gavage. In male rat, all animals died at 3500 mg/kg bw, 4 animals died at 2100 mg/kg bw, 1 animal died at 1250 mg/kg bw and no morality observed at 750 mg/kg bw. In female rats, all animal died at 2500, 3150, 4000 and 5000 mg/kg within 4 hours to 1 day. Due to the unexpected mortality in the first study, study was repeat using lower dose levels for females only. 4 animals died at 2400 mg/kg bw. 2 animals died at 1800 mg/kg bw and no morality observed at 600 and 1200 mg/kg bw within 1 day. Hyperkinesias, sedation, coma, prostration, piloerection, soiled coat, ataxia and haemodaccryorrhea were observed at 0.5 hr to 4 days after dosing. In the first study, generally lower body weight were observed than expected with one male rat having lost weight after 7 days, and another having lost weight at the end of the 14-day observation period. No effect on body weight was observed in second study. In the first study, red stained fluid in the gut in premature decedents and in post mortem at 14 day, gas-filled gut and stomach were observed in one male rat. In the second study, No abnormalities were observed in treated female rat. Therefore, LD50 was considered to be 1620 mg/kg (1069-2455) for amle and 1956 mg/kg (1110-3093) for female when Sprague-Dawley male and female rat were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

In another study given by (HPVIS) EPA (U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 1986), CD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol in the concentration of 416.6, 500, 600 and 750 mg/kg orally by gavage. 1 male rats were died at 720 mg/kg bw and 1 female rats were died at 500 mg/kg bw. No mortality were observed in treated male and female rat at 416.6 and 600 mg/kg bw. Therefore, LD50 was considered to be 720 mg/kg for male and 500 mg/kg bw for female when CD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

Also further supported by prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-[hydroxy(methyl)amino]ethanol. The LD50 was estimated to be 850 mg/kg bw when Bor: WISW (SPFCpb) male and female rats were orally exposed with 2-[hydroxy(methyl)amino]ethanol.

Further supported by experimental study given by (HPVIS) EPA (U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 1986), CD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol in the concentration of0, 150, 300 and 600 mg/kg in waterorally by gavage. 3 male and 5 female rats were died at 600 mg/kg bw as compared to control. No mortality were observed in treated male and female rat at 150 and 300 mg/kg bw. Therefore, LD0 was considered to be 600 mg/kg bw whenCD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage. 

This is Further supported by experimental another study given by (HPVIS) EPA (U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 1986), CD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol in the concentration of 450, 600, 800 and 1000 mg/kg orally by gavage. All male rats were died at 1000 mg/kg bw and all female rats were died at 800 and 1000 mg/kg bw. No mortality were observed in treated male and female rat at 450 and 600 mg/kg bw. Therefore, LD100 was considered to be 1000 mg/kg for male and 800 mg/kg bw for female when CD1 male and female mice were treated with 2-[hydroxy(methyl)amino]ethanol orally by gavage.

Thus based on the above studies and predictions on 2-[hydroxy(methyl)amino]ethanol, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2-[hydroxy(methyl)amino]ethanol can be classified under “Category IV” for acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2-[hydroxy(methyl)amino]ethanol, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2-[hydroxy(methyl)amino]ethanol can be classified under “Category IV” for acute oral toxicity.