2-dimethylaminoethanol

Endpoint summary

Description of key information

Acute toxicity oral: Pharmakon Research International, Inc. Waverly, PA 18471, 1991; according the OECD 401; Sprague Dawley rats, 800, 1200 and 2500 mg/kg bw.
Acute toxicity inhalation: Ballantyne & Leung, 1992; Acute Toxicity and Primary Irritancy of Alkylalkanolamines, Vet Human Toxicol 38 (6) Dec. 1996; similar to the OECD 403, rats, 1668, 2408 and 3311 actual measured concentrations; BASF AG. 1969; Industrial hygiene orientating investigation; similar to the OECD 403, rats, rat were exposed sequentially to vapours for 10 and 30 min, 1 h, 3 h and 7 h

Acute toxicity dermal: Acute Exposure Dermal Toxicity. Pharmakon Research International, Inc., 1992; New Zealand White rabbit, 3000 mg/kg/bw limit test

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was performed according to following guidelines: OECD 401,EPA FR, Vol. 50, No.188 (September 27, 1985) and in compliance with to the GLP Regulations. No significant deviations can be observed from the study guidelines, which could have an impact on the performed study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

purity and storage condition not reported

Qualifier:

according to guideline

Guideline:

other: EPA FR Vol.50,No.188,1985

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: young adults
- Weight at study initiation: 229-325 g
- Fasting period before study: yes
- Housing:individually in stainless steel 1/2" wire mesh cages, sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council
- Diet (e.g. ad libitum): Wayne Teklad Lab Blox, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: min. 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12h dark/12h light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

800, 1250 and 2000 mg/kg

No. of animals per sex per dose:

5 per sex per dose

Control animals:

other: not required according to the OECD 401

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at 1,4 and 24 hours after dosing and once daily through Day 14. Viability: once a day. Body weights: d0, d7 and d14 or when found dead.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 calculations performed via Litchfield and Wilcoxon on Pharmacological Calculations System, version 4.1.

Preliminary study:

dose-range-finding study: 3 groups x 2 rats (1 ♂ and 1♀, fasted): dose levels 500, 2500 and 5000 mg/kg, orally by gavage.
The rats were observed at approximately 1, 4, 24, 48 and 72 hours after dosing for pharmacological and toxicological effects.
0/2 animals died at the 500mg/kg dose level. 2/2 animals died at both the 2500 and 5000 mg/kg dose levels.
Based upon these results , dose levels for a definitive LD50 were determined.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 182.7 mg/kg bw

95% CL:

907 - 1 542.2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 203.2 mg/kg bw

95% CL:

816 - 1 774.2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 220.1 mg/kg bw

95% CL:

725.6 - 2 051.6

Mortality:

-2/10 animals died at the 800 mg/kg dose level.
-5/10 animals died at the 1250 mg/kg dose level.
-9/10 animals died at the 2000 mg/kg dose level.

Clinical signs:

other: -decreased activity and muscle tone, ptosis, abnormal gait, abnormal stance, chromodacryorrhea, diarrhea, tremors, prostration and dyspnea

Gross pathology:

Necropsy of the animals dying on study revealed fluid-filled and distended stomachs and intestines.
No visible lesions were observed in animals at terminal necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Based on the results from the Acute Exposure Oral Toxicity in rats, the Definitive Acute Oral LD50 in males and females for 6398-36-1, was determined to be 1182.7 mg/kg (95% CL of 907.0 to 1542.2 mg/kg). The LD50 in males was determined to be 1203.2 mg/kg (95%CL of 816.0 to 1774.2 mg/kg). The LD50 in females was determined to be 1220.1 mg/kg (95%CL of 725.6 to 2051.6 mg/kg).

Executive summary:

Dimethylethanolamine was administered by gavage to Sprague Dawley rats at doses 800, 1200 and 2500 mg/kg bw. The animals were observed daily for toxicological effects through the day 14. The test material caused dose-dependent mortalities in the exposed animals. Decreased activity and muscle tone, ptosis, abnormal gait, abnormal stance, chromodacryorrhea, diarrhea, tremors, prostration and dyspnea were observed in treated animals. Necropsy of the animals dying on study revealed fluid-filled and distended stomachs and intestines. No visible lesions were observed in animals at terminal necropsy.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 182.7 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported, published 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

The description of the test method is insufficient to compare in details with the OECD guideline (because it is a publication).

GLP compliance:

no

Test type:

other: Acute Inhalation Toxicity (OECD 403)

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1600, 2500 and 3300 ppm

No. of animals per sex per dose:

5

Control animals:

no

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 641 ppm

95% CL:

862 - 3 125

Exp. duration:

4 h

Remarks on result:

other: times to death ranged from 1 to 12 day

For the DMEA 4-h LC50 study, the mean (±SD) analytically measured chamber vapor concentrations were 1668 ±138, 2408 ± 178 and 3311 ± 156 ppm. The respective nominal concentrations, calculated from a knowledge of the total DMEA used and air flow rates, were 1799, 2657 and 3138 ppm. The corresponding A/N ratios were 0.93, 0.91 and 1.06 which indicated good generation conditions and little loss of material by chamber leak or adsorption on equipment. Signs were seen at all exposure concentrations and included blepharospasm, salivation, decreased activity and peroral/perinasal/peri-ocular encrustation. Animals lost weight during the first postexposure week, with some regain during the second week for surviving males exposed to 1668 ppm but not for females (Table 1).

TABLE 1. Body weights of rats acutely exposed to vapor from DMEA
Sex	Exposure Concentration (ppm)	Body Weight (g) as Mean ±SD^a
		Pre-exposure	7 Days	14 Days
Male	3311	283 ± 5	198	228
	2408	259 ± 11	162	175
	1668	258 ± 12	218 ± 41	281 ± 57
Female	3311	253 ± 5	117 ± 17	192
	2408	241 ± 6	165 ± 1	168 ± 31
	1668	246 ± 8	176 ± 33	189
^aValues without SD are for only one survivor.

Mortalities for the various exposure concentrations are shown in Table 2. These data allowed the calculation of a combined-sex 4-h LC 50 of 1641 ppm (95% confidence limit 862-3125 ppm). Times to death ranged 1 to 12 d postexposure with, in general, the shorter times to death occurring with the higher concentration (Table 2). There were no deaths during exposure. Necropsy of animals that died revealed dark red lungs, liver and kidneys. Sacrificed survivors did not show any gross pathology.

TABLE 2. Mortality data for rats acutely exposed for 4-hr to DMEA vapor.
Exposure Concentration (ppm)	Sex	Mortality^a	Deaths at Postexposure Day
			1	2	3	4-6	7-9	10-12
3311	M	4/5	0	4	0	0	0	0
	F	4/5	1	0	0	1	1	1
2408	M	4/5	2	0	1	1	0	0
	F	3/5	0	1	1	1	0	0
1668	M	2/5	0	1	0	0	0	1
	F	3/5	0	0	0	0	1	2
^aExpressed as (Number Dying)/(Number Exposed).

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The signs seen during this study were principally those of irritation to the eye and respiratory tract. After 4 h exposure to 1668 ppm of DMEA, 2 of 5 male rats and 3 of 5 female rats died within 12 days. Thus, it is appropriate that respiratory protective equipment be worn if it is anticipated that overexposure to the vapor could occur.

Executive summary:

The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MMEA), N,N,-dimethylethanolamine (DMEA), N, N ,-dimethyIisopropanolarnine (DMIPA), N-methyldiethanoIamine (MDEA), and tert-butyldiethanolamine (BDEA).

Exposure to a saturated vapor from DMEA (vapor pressure 4.0 torr) for 8 h did not produce any mortalities. However, in a 4-h LC50 study it was possible to determine an LC50 of 1641 ppm. The difference between the 2 studies most probably reflects the mode of exposure. In the static study, equilibration of the atmosphere was overnight, and it is possible that losses of vapor may have occurred from adsorption of material onto the chamber walls. In contrast, in the LC50 study vapor was generated dynamically and continually transferred to the exposure chamber, The signs seen during this study were principally those of irritation to the eye and respiratory tract.

Irritant effects may develop from exposure to vapors from DMEA.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14. Nov. 1968 - 03. Dec 1968

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented report which meets basic scientific principles.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

BASF Test

Principles of method if other than guideline:

Method: BASF-Test: Test was performed in principle as described in OECD Guideline 403.
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 10 and 30 min, 1 h, 3 h and 7 h. The documentation of clinical signs was performed over a period of 14 days.

GLP compliance:

no

Test type:

other: similar to the OECD Guideline 403

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 167 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

Remarks on duration:

10 min, 30 min, 1 h, 3 h, 7 h

Concentrations:

7 h exposure: 24.6 mg/L
3 h exposure: 24.7 mg/L
1 h exposure: 27.2 mg/L
30 min exposure: 27.2 mg/L
10 min exposure: 31.8 mg/L

No. of animals per sex per dose:

7 h, 3 h, 1 h, 30 min exposure: 3
10 min exposure: 6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: days 0, 7
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

other: severity of effects after different exposure times

Effect level:

other: 31.8, 27.2, 24.7 and 24.6 mg/L

Based on:

act. ingr.

Remarks on result:

other: 10 min, 30 min, 1, 3 and 7 hours

Mortality:

7 h exposure: 3 females died on day 1 and 3 males within 24 h of exposure.
3 h exposure: 1 female died 5h post exposure and 1 female within 24 h of exposure. 2 males and 1 female died 5 days post exposure.
1 h exposure: 1 female died within 24 and 1 male within 48 h post exposure.
30 min exposure: 1 female died within 2 days of exposure.

Clinical signs:

other: 7 h exposure: severe irritation of mucous membranes, partially bloody nasal discharge, gasping, heavy corrosion of eyes and snouts. 4 h post exposure extrem decelerated and intermittent respiration was noted. 3 h exposure: severe irritation of mucous memb

Body weight:

The surviving animals gained weight.

Gross pathology:

Animals that died:
7 h exposure: serous smeared fur, acute swelling of lungs and distinct meteorism, swolen gastrointestinal tract.
3 h exposure: serous/blood smeared snouts, 2x hyperemia of lungs, 3x ectasia of gastrointestinal tract.
1 h exposure: serous/bloody smeared snouts, increase tracheal secretion.

Sacrificed animals: bronchitis and bronchiectasis, vicarious emphysema.

Mortality:

Time:
10 min exposure	0/12
30 min exposure	1/6
1 h exposure	2/6
3 h eposure	5/6
7 h exposure	6/6

The inhalation of a highly saturated vapor-air mixture represents anacute hazard (mortality within 60 minutes).

There is indication that the test substance causes local irritation including the respiration tract.

Interpretation of results:

other: see CSR

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

DMAE caused severe irritations of respiratory airways and incrasing mortality at exposure durations of 30 min, 3 h and 7 h.

Executive summary:

Rats were exposed to the vapours of dimethylethanolamine. The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of the 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 10 and 30 min, 1 h, 3 h and 7 h. The documentation of clinical signs was performed over a period of 14 days.

The test material caused dose-dependent deaths. After 10 min of exposure heavy escape attempts, irritation of mucous membranes and dyspnoea were observed, however, no animals died. The effects and mortality severed with the prolongation of the exposure time. Severe irritation of mucous membranes, partially bloody nasal discharge, gasping, heavy corrosion of eyes and snouts were noted in animals exposed 7 hours to DMAE. In this group all animals died.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 983 mg/m³ air

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:

Nov 1991 - Jan 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according OECD 402 guideline. GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: EPA FR, Vol.50 188, September 27, 1985

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CAMM Research Lab Products, Wayne, New Jersey
- Weight at study initiation: 8-12 weeks
- Weight at study initiation: 1.930-2.315 kg
- Housing: individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council
- Diet (e.g. ad libitum): Purina Rabbit Chow H.F., ad libitum,
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h dark/12h light

IN-LIFE DATES: From: 1991-11-01 To: 1991-11-15

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of trunk (clipped free of fur)
- % coverage: no data
- Type of wrap if used: rubber dam and an elastic bandage to retard evaporation

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with water and gauze
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg
- Constant volume or concentration used: yes

VEHICLE not applicable

Duration of exposure:

24 hours

Doses:

3000 mg/kg

No. of animals per sex per dose:

10 (5 ♂ and 5 ♀)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: daily through 14 days, body weight: d0, d7 and d14
- Necropsy of survivors performed: yes

Statistics:

Statistics were calculated using Systat by Systat, Inc. Version 4.1, Evanston, IL.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 3 000 mg/kg bw

Remarks on result:

other: no mortality

Mortality:

- 0/10 animals died at the 3000 mg/kg dose level

Clinical signs:

other: - decreased activity, abnormal stance and abnormal gait - necrosis of the skin at the application sites

Gross pathology:

- severe irritation of underlying muscle at the application sites was observed in all animals at terminal necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the observations made in the Acute Exposure Dermal Toxicity Study in rabbits, the estimated acute dermal LD50 for 6398-36-1, Order #91-018, in males and females was determined to be greater than 3000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

3 000 mg/kg bw

Additional information

Acute toxicity: oral

In the GLP acute oral study DMAE caused dose-dependent mortalities in the exposed animals (Pharmacon, 1991). Decreased activity and muscle tone, ptosis, abnormal gait, abnormal stance, chromodacryorrhea, diarrhoea, tremors, prostration and dyspnoea were observed in treated animals. Necropsy of the animals dying on study revealed fluid-filled and distended stomachs and intestines, but in the surviving animals there were no visible lesions at necropsy. LD50 was determined to be 1182.7 mg/kg bw.

In a supporting study (BASF AG, 1969) DMAE was administered at higher doses than in the key study. The dose range was (5696, 2848, 2225, 1780, 1424 mg/kg bw). The in-life effects were similar to those observed in the key study. Gross pathology revealed dilated stomach and distinctive gastrorrhagia, bloody content in gastrointestinal tract, serous/blood smeared snouts. LD50 was 2140 mg/kg/bw. A similar LD50 value of 2083 mg/kg/bw was established for rats in another supporting study (Ballantyne and Leung, 1992). In this study, all deaths occurred overnight following dosing. Signs of toxicity (with times to onset) included sluggishness (2 min to 2 h), lacrimation (1.5 h to 1 d), chromodacryorrhea (1 d), diarrhoea (30 min), kyphosis (1.5 h to 1 d) and prostration (1 d). It is probable that systemic toxicity and local irritation of the gastrointestinal tract were both factors in the acute lethal peroral toxicity of the test material. The gross pathological features included marked congestion of the stomach and small intestine with blood in the lumen of the gastrointestinal tract. Necropsy of animals that died revealed distended stomachs containing blood and having dark red or purple discoloration of the glandular portion. Intestines contained blood and had variable degrees of congestion. Lungs in general showed dark red mottling. Survivors had no gross pathology at necropsy.

DMAE is moderately toxic if ingested.

Acute toxicity: inhalation

Ballantyne and Leung exposed Wistar rats to vapour of DMAE during 4 hours (Ballantyne and Leung, 1996). The irritation to the eyes and respiratory tract were the common observations. Rats from all exposure groups exhibited lacrimation, excessive salivation, ocular, oral, nasal discharge and encrustation, respiratory difficulties and decreased motor activity. Discolored lungs, liver, kidneys, and spleen were observed in rats that died and in two high-dose survivors. Survivors in the low-and mid-dose groups did not have exposure-related macroscopic lesions at the end of 14 -days observation period. LC50 was determined to be 1641 ppm (5983 mg/m³).

In the BASF acute inhalation supporting study rats inhaled DMAE during either 10 min, 30 min, 1, 3 and 7 hours (BASF AG, 1969). The analytically determined actual concentrations tested were 31.8, 27.2, 24.7 and 24.6 mg/L, respectively. The test material caused dose-dependent deaths. After 10 min of exposure heavy escape attempts, irritation of mucous membranes and dyspnoea were observed, however, no mortalities occurred. These effects and mortality severed with the prolongation of the exposure time. Severe irritation of mucous membranes, partially bloody nasal discharge, gasping, heavy corrosion of eyes and snouts were noted in animals exposed 7 hours to DMAE. In this group all animals died. In conclusion, severe irritation of respiratory tract and corrosion of eyes occurred in the treated animals, however, only the severity of effects could be monitored during the different exposure times. LD50 was not determined because the concentration range did not allowed to calculate it.

Acute toxicity: dermal

In the GLP-acute dermal study DMAE was applied occlusive to the rabbit’s skin for 24 hours (Pharmacon, 1992). The animals were observed for signs of toxicity during 14 days. The test material produced no mortalities in 10 animals examined. Decreased activity, abnormal stance and abnormal gait, necrosis of the skin at the application sites were observed in the treated animals. Severe irritation of underlying muscle at the application sites was observed in all animals at terminal necropsy. LD0 (discriminating dose) was >= 3000 mg/kg/bw.

Ballantyne and Leung (1996) determined DMAE as having moderate acute percutaneous lethal toxicity in New Zealand White rabbits. In general, deaths occurred within a few days of the start of epicutaneous dosing, but later deaths were seen more frequently (all animals died within 12 days). Signs, which were few, included sluggishness, unsteady gait, emaciation and prostration, all of which developed by the end of the dosing period. Animals lost weight during the first postdosing week, with partial recovery during the second week On removal of the occlusive dressing there was moderate to severe erythema and edema with ecchymoses, necrosis and ulceration. These effects, in general, persisted to the end of the observation period. During the second postapplication week local desquamation, alopecia and scarring had developed. Necropsy of animals that died revealed dark red mottled lungs, dark red livers and mottled kidneys. Most survivors at necropsy did not reveal any gross pathology, but a few showed red mottled lungs and dark red livers. LD50 acute dermal was determined to be 1219 mg/kg/bw (Leung and Ballantyne, 1996).

 

Justification for classification or non-classification

DMAE represents an acute hazard if administered to rats orally or by inhalation. In the available studies, dermal application of DMAE to the skin of rabbits did not always produce mortality in treated animals but signs of severe skin Irritation and worsening in general condition in treated animals indicate a dermal acute toxicity hazard.

Due to the oral LD50 value of 1187 mg/kg bw, the dermal LD50 value of 1219 mg/kg bw supported by the observed bad general state in animals treated with 3000 mg/kg bw in the key study, and LC50 of 6.0 mg/L classification is warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008:

According to GHS:

Acute toxicity - oral: Cat.4;

Acute toxicity - dermal: Cat.4;

Acute toxicity - inhalation: Cat 3.