Registration Dossier

Administrative data

Description of key information

MDEA has a low acute oral, inhalation and dermal toxicity. The oral LD50 is 4680 mg/kg bw in rats. In inhalation risk tests with rats no mortality was observed after 6 and 8 hours exposure to a saturated MDEA vapour atmosphere. The LD50 for the dermal route is > 2000 mg/kg bw in rabbits.

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF-Test. The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 180 - 260 g; female: 144 - 210 g
Route of administration:
oral: gavage
Vehicle:
water
Doses:
200, 1600, 3200, 4000, 5000, 6400 mL/kg bw (208, 1664, 3328, 4160, 5200, 6656 mg/kg bw; conversion into mg/kg is based on the density d= 1.04 g/cm3 -according to BASF internal data)
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
A test group consisting of 10 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observation period also were subjected to necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 680 mg/kg bw
Remarks on result:
other: Conversion into mg/kg is based on the density d= 1.04 g/cm3
Mortality:
The test substance caused systemic toxicity including mortality in a dose dependent manner.
See details in remarks on results.
Clinical signs:
3328 - 6656 mg/kg bw: immediately squatting posture, ruffled fur and gasping. On the next day some animals showed bloody eyes and noses, ruffled fur and gasping.
1664 mg/kg bw: immediately squatting posute, ruffled fur and gasping.
Body weight:
no data
Gross pathology:
Animals that died: all animals had smeared snouts and urogenital tracts. 11x droopy gastrointestinal tract with bloody content
Sacrificed animals: 8x bronchitis and bronchiectasis.

Mortality:

 Dose (mg/kg bw)  Gender  Conc.(%)   1 h  24 h  48 h   7 days
 6656  male 30  0/10  7/10  7/10  7/10
 6656  female 30  0/10  10/10  10/10  10/10
5200  male 30  0/10  3/10 3/10  3/10
5200  female 30  0/10  10/10  10/10  10/10
4160  male 30  0/10  2/10  2/10  2/10
4160  female 30   0/10   5/10   6/10   6/10
3328  male 30   0/10   1/10   1/10   1/10
3328  female 30   0/10    0/10   0/10   0/10
1664  male 20    0/10    0/10   0/10   0/10
1664 female   20  0/10   0/10   0/10   0/10
208  male  2   0/10   0/10   0/10  0/10 
208  female  2   0/10   0/10   0/10   0/10
The test substance caused systemic toxicity including mortality in a dose dependent manner.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 680 mg/kg bw
Quality of whole database:
similar to OECD TG 401

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline available
Principles of method if other than guideline:
Acute toxicity study in which Sprague-Dawley albino rats were exposed in groups of 5 to saturated vapor atmospheres for 6 h.
GLP compliance:
not specified
Test type:
other: Inhalation Risk Test
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Sprague-Dawley albino rats were exposed in groups of 5 to saturated vapour atmospheres for 6 h. The static generation procedure involved placing approximately 50 g of test material into a 120 L exposure chamber and sealing for approximately 18 h. Animals were then introduced into the exposure chamber by means of a gasketted drawer which limited leakage of vapor. The dynamic conditions involved passing filtered compressed air through the test material contained in a gas washing bottle and transferring the vapor atmosphere to a 120 L chamber containing the rats.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
saturated vapor
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: during exposure, immediately following exposure, and thereafter daily for 2 weeks
- Frequency of weighing: before exposure and at 7 and 14 d post-exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
other: Inhalation Risk Test
Exp. duration:
6 h
Remarks on result:
other: a saturated vapour of MDEA caused no mortality
Mortality:
no mortality occured
Clinical signs:
other: no significant signs of toxicity observed
Body weight:
no data
Gross pathology:
no data

No mortality was observed when 5 rats were exposed for 6 hours to an atmosphere that has been saturated at room temperature with the volatile part of the compound.

 

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
BASF-Test: Test was performed in principle as described in OECD Guideline 403.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 183 g (mean)
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (room temperature). 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glassdisc in a glass cylinder for 8 h.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
saturated vapor
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
Key result
Sex:
male/female
Dose descriptor:
other: Inhalation Risk Test
Exp. duration:
8 h
Remarks on result:
other: an atmosphere saturated with vapours of the volatile components of MDEA at room temperature caused no mortality
Mortality:
No mortality occured.
Clinical signs:
other: No symptoms observed.
Body weight:
The animals gained normal weight.
Gross pathology:
No abnormalities observed.

In the study report and the raw data no substance loss but an increase in substance weight was recorded. This is an indication that the test substance is hygroscopic and only a marginal fraction of the test substance might be volatile. From a toxicologists point of view it is doubtful whether the animals were exposed to the test substance by inhalation and which concentration the generated vapour was of.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Risk Inhalation tests

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 - 3.0 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
Material was applied to the clipped dorsal trunk skin and maintained in occlusive contact for 24 h by gauze which was placed over the dose, covered with impervious polyethylene sheeting, and retained with VETRAP bandaging tape. Animals were examined for signs of toxic and/or pharmacologic effects daily and for local skin effects at 17 and 14 d after removal of the occlusive dressing. Animals were weighted before dosing and at days 7 and 14 post dosing. All animals were subjected to gross necropsy examination.

Clinical signs daily during the observation period (14 d).
- Local skin effects observations: 1 hr, 7 d, 14 d after removal of occlusive dressing.
- Gross pathological examinations on all animals.
- Body weights were recorded before dosing, and 7 and 14 d post dosing.
Statistics:
moving average method
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
10 244 mg/kg bw
95% CL:
>= 7 436 - <= 14 144
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
11 336 mg/kg bw
95% CL:
>= 9 339 - <= 13 822
Mortality:
- No. of deaths: not indicated.
- Time of death: 1 to 12 days after administration (males) and 3 to 11 days after administration (females)
Clinical signs:
Signs, which were few, included sluggishness, unsteady gait, emaciation and prostration, all of which developed by the end of the dosing period. Survivors usually recovered from these effects between 3 and 5 days after the start of dosing.
Body weight:
Animals lost weight during the first post dosing week, with partial recovery during the second week.

Gross pathology:
Necropsy of animals that died revealed dark red mottled lungs, dark red livers and mottled kidneys. Most survivors at necrospy did not reveal any gross pathology, but a few showed red mottled lungs and dark red livers.
Other findings:
erythema and oedema with ecchymosis, necrosis and ulceration was observed until the end of the observation period. During week 2 local desquamation, alopecia and scarring had developed
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
not specified
Vehicle:
not specified
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
not specified
Details on study design:
EXAMINATIONS: 2-week observation period
mortality/clinical signs/body weight: frequency not indicated
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths
Clinical signs:
No effects
Body weight:
animals regained pretreatment weight within the 2-week observation period
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline followed
Principles of method if other than guideline:
Penetration of rabbit skin is estimated by a technique closely to the one-day cuff method of Draize. The test substance was applied for 24 hours under occlusive conditions.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 to 3.5 kg
Type of coverage:
occlusive
Vehicle:
not specified
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
4
Control animals:
not specified
Details on study design:
The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film. The animals are immobilized during the 24 hour contact period, after which the film was removed and the rabbits are caged for the subsequent 14 day observation period.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5 990 mg/kg bw
95% CL:
>= 3 570 - <= 10 070
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
similar to OECD TG 402

Additional information

Acute oral toxicity

In an acute oral toxicity study comparable to OECD TG 401, 10 rats/sex/dose were exposed to 208 - 6656 mg/kg bw MDEA by gavage and observed for 7 days. The LD50 was determined to be 4680 mg/kg bw for males and females. No deaths occurred at doses of 1664 mg/kg bw or below (BASF SE, 1969).

Acute inhalation toxicity

The available data were assessed using a weight of evidence (WoE) approach. Information from an inhalation risk test showed no mortality in rats after an 8 h exposure to a saturated MDEA vapour atmosphere (BASF AG, 1969). In addition, no mortality was observed after a 6 h exposure to a saturated atmosphere of the test substance (Ballantyne and Leung, 1996). Due to its low vapour pressure (0.0027 hPa, at 25°C), exposure by inhalation can be regarded as negligible. Therefore, acute toxicity is considered low after inhalation exposure.

Acute dermal toxicity

The available data which was assessed using a weight of evidence (WoE) approach showed that the acute dermal toxicity of MDEA was low. All studies (Ballantyne and Leung, 1996a; Smyth, 1954; The Dow Chemical Company 1983) report a LD50 of > 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral and dermal toxicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.