Registration Dossier

Administrative data

Description of key information

Acute toxicity oral: BASF AG, 1965. Industrial hygiene orientating investigation.Report No. XV/126. Comparable to the OECD guideline 401.
Acute toxicity dermal: BASF AG, 1981. Industrial hygiene orientating investigation.Report No. 79/561. Comparable to the OECD guideline 402.
Acute toxicity inhalation: BASF AG, 1965. Industrial hygiene orientating investigation.Report No. XV/126. Comparable to the OECD guideline 403.

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
Study period:
22 Jun 1965 - 20 Jul 1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
BASF-Test
Principles of method if other than guideline:
BASF-Test. See further details in remarks on materials and methods.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
other: US-rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 148 - 230 g; females: 112 - 150 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5, 2, 8, 16, 20 %


Doses:
25, 200, 800, 1600, 2000, 2500 and 3200 µl/kg bw (23.5, 188, 752, 1504, 1880, 2350 and 3008 mg/kg bw - conversation into mg/kg bw is based on the density: d=0.94 g/cm3)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 880 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: conversion in mg/kg is based on the density: d=0.94 g/cm3
Mortality:
See details in remarks on results.
Clinical signs:
3008 mg/kg bw: abdominal position, irregular, accelerated respiration, staggering, calm behavior, chewing compulsions.
2350 mg/kg bw: calm behavior, staggering, chewing compulsions, gasping, dyspnoea. After 24 h squatting posture, ruffled fur, irregular respiration
1880 mg/kg bw: high stepping gait, staggering, smeared fur, diarrhea.
1504 mg/kg bw: dyspnoea, chewing compulsion, partially calm behavior. After 24 h crusted eyes and ruffled fur.
23.5, 188 and 752 mg/kg bw: after application calm behavior.
Body weight:
no data
Gross pathology:
3008 mg/kg bw: 1 x intestinal atony.
1880 mg/kg bw: 1 animal with distended ulceration with phlegmone and abscess of the entire glandular stomach. 1 x intestinal irritation.

Mortality:

 Dose (mg/kg bw)  Gender  conc. %  1 h  24 h  48h  day 7  day 14
 3008  male 20 0/5   5/5 5/5  5/5 5/5
 3008  female 20  0/5 4/5 5/5 5/5 5/5 
 2350  male 20 0/5 2/5 3/5 3/5  3/5 
 2350  female 20 0/5 4/5 5/5 5/5 5/5 
1880  male 20 0/5  1/5  1/5 1/5 2/5 
1880  female 20 0/5 1/5 1/5 4/5 4/5 
1504  male 16 0/5  1/5  1/5 1/5 1/5 
 1504 female  16  0/5 1/5  1/5 1/5 1/5 
 752  male 8 0/5  0/5  0/5  0/5 0/5 
 752  female 8 0/5  0/5  0/5 0/5 0/5 
 188  male  2 0/5 0/5 0/5  0/5

0/5 

 188  female  2 0/5 0/5 0/5 1/5 1/5 
 23.5  male  0.5  0/5 0/5 0/5  0/5  0/5  
 23.5  female  0.5  0/5   0/5 0/5 0/5 0/5  

The application of the test substance caused systemic toxicity, including mortality, in a dose dependent manner.

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The application of the test substance caused systemic toxicity, including mortality, in a dose dependent manner.
Executive summary:

In an acute oral study a test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of MMEA (BASF AG, 1965, XV/126). The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.
At low doses (23.5 188 and 752 mg/kg bw), calm behavior was observed by treated animals. Dyspnoea, chewing compulsion, partially calm behavior occurred after application of 1504 mg/kg bw.
 After 24 h, crusted eyes and ruffled fur. At high doses (1880, 2350 and 3008 mg/kg bw), dyspnoea, high stepping gait, staggering, smeared fur, diarrhea, calm behavior, chewing compulsions and gasping were observed. After 24 h squatting posture, ruffled fur, irregular accelerated respiration and abdominal position were still present.
At 1880 mg/kg bw: 1 animal had distended ulceration with phlegmone and abscess of the entire glandular stomach and intestinal irritation. At the highest dose, intestinal atony was observed in one animal.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 880 mg/kg bw
Quality of whole database:
Moderate (2 studies available)

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
Study period:
22. Jun 1965 - 30. Jun 965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
BASF-Test
Principles of method if other than guideline:
BASF-Test. See further details in remarks on material and methods.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 192 g (mean)
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
In the raw data no substance loss but an increase in substance weight was recorded.
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
other: Inhalation Risk Test
Effect level:
other: Inhalation Risk Test
Exp. duration:
8 h
Mortality:
No mortality occured.
Clinical signs:
Eye and nose discharge.
Body weight:
The animals gained weight.
Gross pathology:
No abnormalities.

The inhalation of a enriched/saturated vapor-air-mixture caused no mortality within 8 h.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Eye and nose discharge were only the abnormalities noted.
Executive summary:

The acute inhalation test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (room temperature) (BASF AG, 1965, XV/126). 6 rats per sex were exposed sequentially to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days.
No mortalities occurred during the observation period. The animals gained weight. Eye and nose discharge were only the abnormalities noted. Gross pathology revealed no signs of toxicity. LC50was not identified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
Moderate (2 studies available)

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
Study period:
08 Nov 1979 - 23 Nov 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
BASF-Test
Principles of method if other than guideline:
BASF test. Further details in remarks on material and methods.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Hagemann, Extertal, Germany
- Weight at study initiation: male: 267 g (mean); female: 185 g (mean)
- Diet: Herilan MRH-Kraftfutter (H. Eggersmann, Rinteln), ad libitum
- Water: tap water ad libitum

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 cm2
- Type of wrap if used: inert foil.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was washed off with warm water and dried with cellulose.
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 8 days
- Frequency of observations: daily
- Frequency of weighing: day 0, 4, 7, 12
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occured.
Clinical signs:
Systemic toxicity: Dyspnoea, apathy, staggering, salivation, cry of pain, poor general state.

Local irritation:
After 24 h soft anemic necrosis, severe edema, pea-size 3 mm deep ulcers.
After 7 days parchment-like necrosis, slight edema, wrinkles.
After 14 days leathery-like necrosis wrinkles partially open and weeping.
Body weight:
Initially the male animals lost slightly weight and the females only gained marginal weight (see details in table in remarks on results).
Gross pathology:
No abnormalities.

Weight (g):

 Dose (mg/kg bw)

 Gender  day 0  day 4  day 7  day 12    
 2000  male  267 262  288 311    
 2000  female  185 186 200 212    

No mortality occured during the 14 -day observation period in both sexes.

There is indication that the test substance causes local irritation to the exposed tissue.

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
If administered dermally in rats, MMEA caused systemic toxicity.
Executive summary:

The acute dermal toxicity of 2-methylaminoethanol was determined for White Vienna rabbits (BASF AG, 1981). For this purpose, the product was applied once for 24 hours to the clipped skin of the back and flank (area about 50 cm²) unchanged in a dose of 2000 mg/kg. The treated area of skin was then covered with an inert foil, which was secured in position with adhesive tape. The bandage was removed after an exposure period of 24 hours; subsequently, the test substance was washed off with warm water and dried with cellulose. The LD50was determined taking into account the DOT guidelines, but it was not established precisely.
No mortalities occurred during the study. Following signs of systemic toxicity were observed by treated animals: dyspnoea, apathy, staggering, salivation, cry of pain and poor general state. After 24 hours, soft anemic necrosis, severe edema, pea-size 3 mm deep ulcers appeared. After 7 days these ailments progressed to parchment-like necrosis, slight edema and wrinkles. After 14 days, leathery-like necrosis wrinkles partially open and weeping was still present in the treated animals. Gross pathology revealed no abnormalities.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Moderate (2 studies available)

Additional information

Acute toxicity oral:

In an acute oral study a test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of MMEA (BASF AG, 1965, XV/126). The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.
At low doses (23.5, 188 and 752 mg/kg bw), calm behavior was observed by treated animals. Dyspnoea, chewing compulsion, partially calm behavior occurred after application of 1504 mg/kg bw.
 After 24 h, crusted eyes and ruffled fur. At high doses (1880, 2350 and 3008 mg/kg bw), dyspnoea, high stepping gait, staggering, smeared fur, diarrhea, calm behavior, chewing compulsions and gasping were observed. After 24 h squatting posture, ruffled fur, irregular accelerated respiration and abdominal position were still present.
At 1880 mg/kg bw: 1 animal had distended ulceration with phlegmone and abscess of the entire glandular stomach and intestinal irritation. At the highest dose, intestinal atony was observed in one animal.

Similar findings were observed by Ballantyne and Leung (1996). LD50 of 1908 mg/kg bw for males and 1391 mg/kg bw for females were established in this study. MMEA was considered to be moderately toxic if administered peroral to rats (Ballantyne and Leung, 1996).

Conclusion: the application of the test substance caused systemic toxicity, including mortality, in a dose dependent manner.

Acute toxicity dermal:

The acute dermal toxicity of 2-methylaminoethanol was determined for White Vienna rabbits (BASF AG, 1981). For this purpose, the product was applied once for 24 hours to the clipped skin of the back and flank (area about 50 cm²) unchanged in a dose of 2000 mg/kg. The treated area of skin was then covered with an inert foil, which was secured in position with adhesive tape. The bandage was removed after an exposure period of 24 hours; subsequently, the test substance was washed off with warm water and dried with cellulose. The LD50was determined taking into account the DOT guidelines, but it was not established precisely.
No mortalities occurred during the study. Following signs of systemic toxicity were observed by treated animals: dyspnoea, apathy, staggering, salivation, cry of pain and poor general state. After 24 hours, soft anemic necrosis, severe edema, pea-size 3 mm deep ulcers appeared. After 7 days these ailments progressed to parchment-like necrosis, slight edema and wrinkles. After 14 days, leathery-like necrosis wrinkles partially open and weeping was still present in the treated animals. Gross pathology revealed no abnormalities.

Acute toxicity inhalation:

The acute inhalation test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (room temperature) (BASF AG, 1965, XV/126). 6 rats per sex were exposed sequentially to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days.
No mortalities occurred during the observation period. The animals gained weight. Eye and nose discharge were only the abnormalities noted. Gross pathology revealed no signs of toxicity. LC50was not identified.

Conclusion:

By sustained contact with the skin, MMEA showed a potential for percutaneous systemic toxicity. Acute dermal rabbit LD50is more than 2000 mg/kg bw in the BASF (BASF, 1981) study and less than 2000 by Ballantyne and Leung (Ballantyne and Leung, 1996). There were significant differences in LD50values between males and females. The test substance is considered to be of moderate acute percutaneous toxicity.It was not possible to identify a LC50in the inhalation studies because no mortalities occurred. As seen from all symptoms in the acute studies, MMEA caused irritation of gastrointestinal tract, severe skin irritations with necrosis and slightly irritation of upper airways.




Justification for selection of acute toxicity – oral endpoint
Well-documented study report (similar to OECD 401)

Justification for selection of acute toxicity – inhalation endpoint
Well-documented study report (similar to OECD 403)

Justification for selection of acute toxicity – dermal endpoint
Well-documented study report (similar to OECD 402)

Justification for classification or non-classification

The classification is warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations No 1272/2008.

DSD: Xn, R21/22 Harmful, Harmful in contact with skin and if it swallowed

GHS:

Acute toxicity - oral: Cat 4;

Acute toxicity -dermal: Cat 4.

STOT SE Cat.3, H335:may cause respiratory irritation, C>=5%