Ethanaminium, 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethyl-, esters with C16-18 and C18-unsatd. fatty acids, chlorides

Endpoint summary

Description of key information

Human data on the acute toxicity of MDEA-Esterquat C16-18 and C18 unsatd. are not available.
In rats, mice and rabbits the substance is practically non-toxic with an oral LD50 of > 10 000 mg/kg bw and a dermal LD50 of > 2000 mg/kg bw. The NOAEL for acute oral toxicity is 10 000 mg/kg bw in the rat and 3160 mg/kg bw in mice. The NOAEL for acute dermal toxicity in the rabbit is 2000 mg/kg bw.
In the Irwin dose-range study in mice, at the highest dose of 10 000 mg/kg bw one animal showed indications for CNS depression and died after 1 day. No effects were recorded at any time during the study at lower doses of 316, 1000 and 3160 mg/kg bw.
Generation of inhalable particles such as dust or aerosols is not relevant under the specific operational conditions. Vaporisation needs not to be considered due to the very low vapour pressure of < 10-7 kPa. Therefore, inhalation is not a relevant route of exposure and testing by the inhalation route is not appropriate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-03-17 to 1986-04-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

other: Up down followed by limit test at 10,000 mg/kg bw

Limit test:

yes

Specific details on test material used for the study:

- Physical state: Solid
- Purity test date: 1986-01-22
- Expiration date of the lot/batch: 1986-06-01
- Storage condition of test material: Room temperature

Species:

rat

Strain:

other: BCR:WISW

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma WickeImann, Versuchstierzucht, 4791 Borchen 1, Gartenstraße 300
- Age at study initiation: Not available
- Weight at study initiation: Male= 200 to 227 gm, female= 150 to 160.8 gm
- Fasting period before study: 18-20 hours
- Housing: Collection caging in Makrolon type III/ max.5 rats
- Diet (e.g. ad libitum): Ssniff-R Alleindiät fur Ratten pellets
- Water (e.g. ad libitum): ad libitum,Aqua fontana as for human consumption
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +- 2°C
- Humidity (%): 50 to 85 % different from guideline (30 - 70 %)
- Air changes (per hr): Not avialable
- Photoperiod (hrs dark / hrs light): 12 hours daily


IN-LIFE DATES: From: 1986-03-17 To: 1986-04-11

Route of administration:

oral: gavage

Vehicle:

other: Oleum arachidis

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 % dilution in oleum arachidis
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not available
- Lot/batch no. (if required): E-2819.01
- Purity: 80 % DEEDMAC


MAXIMUM DOSE VOLUME APPLIED: 5.7 ml


DOSAGE PREPARATION (if unusual): None


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

500 mg /kg bw
10000 mg /kg bw

No. of animals per sex per dose:

1 animal for 500 mg/kg bw
1 animal for 10000 mg/kg bw (up and down method)
5 males and 5 females for 10000 mg/kg bw (limit test)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 4 days for the preliminary study and 14 days for the main study
- Frequency of observations and weighing: Daily for observation ,Weighed at day 0 and at day 14 .
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed during the study at a limit dose of 10000 mg/kg bw.

Clinical signs:

other: Two of the treated animals showed slight piloerection during the first hour after application. Afterwards, they showed a normal disposition.The other animals appeared normal during the entire testing period.

Gross pathology:

No abnormality was observed during terminal necropsy.

Other findings:

- Organ weights: none
- Histopathology: None
- Potential target organs: None
- Other observations:None

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of MDEA-Esterquat C16-18 and C18 unsatd. is >10000 mg/kg bw. This test material is considered to be practically non-toxic.

Executive summary:

In an acute oral toxicity study comparable to now deleted OECD guideline 401, groups of fasted,WISW rats 5 males and 5 females were given a single oral dose of  

MDEA-Esterquat C16-18 and C18 unsatd. (40 % w/w a.i.) in oleum arachidis at a dose of 10 000  mg/kg bw.

oral LD50       Males >  10 000 mg/kg bw

                       Females >  10 000 mg/kg bw

                       Combined > 10 000 mg/kg  bw

 No mortality occurred in this limit test.

MDEA-Esterquat C16-18 and C18 unsatd. is practically non-toxic based on the LD50 combined of > 10 000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight. A slight piloerrection was observed in 2/10 animals during the first hour after application. Afterwards they showed a normal disposition.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-March

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

4 male mice were used per dose group and the animals were observed for 7 instead of 14 days.

GLP compliance:

yes

Test type:

other: Irwin-Dose Range Study

Limit test:

no

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK limited
- Age at study initiation: Not available
- Weight at study initiation: 20-24 gm
- Fasting period before study: ~18 hrs prior to the test
- Housing: Not available
- Diet (e.g. ad libitum): Not available
- Water (e.g. ad libitum): ad libitum except during the observation period
- Acclimation period: Not available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%): Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available


IN-LIFE DATES: Not available

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable


MAXIMUM DOSE VOLUME APPLIED: 40 ml/Kg


DOSAGE PREPARATION (if unusual): Not applicable


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

10000 mg/kg, 3160 mg/kg, 1000 mg/kg, 316 mg/kg

No. of animals per sex per dose:

Four male mice per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Observed daily during a 7- day post-dose period
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, mortality

Statistics:

Not applicable

Preliminary study:

None

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

>= 10 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: One animal died at the 10 000 mg/kg dose.

Mortality:

At the 10000 mg/Kg dose, one animal died overnight between days 1 and 2

Clinical signs:

other: At 10000 mg/Kg: All mice show slight apathy between 10 and 20 minutes after dosing. The animal which died between day 1 and 2 showed the following symptoms: After 30 minutes of dosing: Slight sign of apathy, decrease in alertness, abdominal respiration,

Gross pathology:

Not applicable

Other findings:

- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of MDEA-Esterquat C16-18 and C18 unsatd. is > 10000 mg/kg bw. This test material is considered to be practically non-toxic.

Executive summary:

In an acute oral toxicity Irwin dose-range study comparable to now deleted OECD guideline 401, groups of fasted, CD-1 mice 4 males were given a single oral dose of MDEA-Esterquat C16-18 and C18 unsatd. (40 % w/w a.i.) in oleum arachidis at a dose of 316, 1000, 3160 and 10 000  mg/kg bw and observed for 7 days.

Oral LD50Males >  10 000 mg/kg bw

     

MDEA-Esterquat C16-18 and C18 unsatd. is practically nontoxic based on the LD50 of > 10 000 mg/kg bw.

All mice dosed with 10000 mg/kg bw of test substance showed slight apathy between 10 and 20 minutes after dosing. In addition, one animal in this group showed further indication of CNS depression during the 30 and 90 minute observations. This animal appeared normal during the 150 and 300 minute observations however it died overnight between days 1 and 2.

No other effects were recorded at any stage of the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

OECD guideline study, no deviations, GLP

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study 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:

1986-03-26 to 1986-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): FV base E2819.01
- Diethylester dimethyl ammonium chloride
- Substance type: Waxy
- Physical state: White Solid
- Storage condition of test material: Room temperature

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm
- Age at study initiation: Not available
- Weight at study initiation: 2.02 - 3.28 kg
- Fasting period before study: Not available
- Housing: Single caging in battery of cages size: 40 cm high, 45 cm wide, 50 cm long with paper roll disposal system
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 2 degree C
- Humidity (%): 50-85%
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): 12 hours daily, light-dark cycle


IN-LIFE DATES: From: 1986-03-26 To: 1986-04-04

Type of coverage:

occlusive

Vehicle:

other: Oleum arachidis

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal trunk
- % coverage: 15 X 10 cm
- Type of wrap if used: The treated area was covered with gauze pads and the body was wrapped into a rubberized cloth.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): If necessary, with lukewarm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 40% a.i.
- Constant volume or concentration used: no
- For solids, paste formed: no


VEHICLE
- Amount(s) applied (volume or weight with unit): Not available
- Concentration (if solution): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (male/female)

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily for observations and Body weights were taken on first and fourteenth day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality

Clinical signs:

other: The test substance did not induce any clinical-toxicological symptoms. Slight to moderate erythema and mainly moderate edema were observed at the treatment sites up to day 3 which resolved afterwards.

Gross pathology:

Necropsies performed on all animales at termination exhibited no gross pathological findings.

Other findings:

- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None

Skin assessments made at 24 hrs, 3, 7 and 14 days revealed that 2 mg/kg MDEA-Esterquat produced moderate skin irritation. Slight (3/6 rabbits) to moderate (3/6 rabbits) erythema and moderate edema at the 24 hour reading; slight (5/6 rabbits) to moderate (1/6 rabbits) erythema and slight (3/6 rabbits) to moderate (3/6 rabbits) at day 3. These skin responses resolved at day 7. No atonia, desquamation, fissuring, eschar or exfloliation was observed in the animals in this study.

Erythema and Edema observations at Treated Site

Animal #	Erythema (24 hr)	Edema (24 hr)	Erythema (3 days)	Edema (3days)	Erythema (7days)	Edema (7 days)	Erythema (14 days)	Edema (14 days)
93 (M)	2	2	1	2	0	0	0	0
72 (M)	1	1	1	0	0	0	0	0
83 (M)	1	2	1	2	0	0	0	0
791 (F)	2	2	2	1	0	0	0	0
792 (F)	2	2	1	1	0	0	0	0
799 (F)	1	2	1	2	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

MDEA-Esterquat C16-18 and C18 unsatd. is practically non - toxic.

Executive summary:

In an acute dermal toxicity study (comparable to OECD guideline 402), groups of 3 male and female New Zeeland With rabbits were dermally exposed to MDEA-Esterquat C16-18 and C18 unsatd.  (40 % a.i) in oleum arachidis for 24 hours to10 x 15 cm of body surface area at doses of 2000 mg/kg bw.  Animals then were observed for14days.

 

Dermal LD₅₀              Males              > 2000 mg/kg bw

                                  Females          > 2000 mg/kg bw

                                  Combined      > 2000 mg/kg bw

 

No mortality occurred in this limit test.

 

MDEA-Esterquat C16-18 and C18 unsatd.  is practically non – toxic in this study.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

Slight (1) to moderate (2) erythema and mainly moderate (2) edema with partly decreased intensity were observed at the treatment sites from 24 hours up to the 72 hours after treatment and were fully reversible within 7 days. The mean score were 1.3 for erythema and 1.75 for edema (after 24 and 72 hours). The applied scores of 1 and 2 for erythema and edema were comparable to the scores of the Draize method.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

OECD guideline study, no deviations, GLP

Additional information

Acute oral toxicity

Two studies for acute oral toxicity are available, one limit test in rats and an Irwin dose-range study in mice. Furthermore, there is a dermal study available performed in rabbits.

In an acute oral toxicity study comparable to OECD Guideline 401 (24. Feb. 1987, now deleted) rats were dosed once with 10 000 mg/kg bw MDEA-Esterquat C16-18 and C18 unsatd.  and observed for 14 days. No mortality occurred in this limit test. There were no treatment related clinical signs, necropsy findings or changes in the body weight.

The second study with mice was performed as an Irwin dose-range finding study with oral application of 316, 1000, 3160 and 10 000 mg/kg bw of MDEA-Esterquat C16-18 and C18 unsatd.  and with an observation period of 7 days. All mice dosed with 10 000 mg /kg bw showed slight apathy between 10 and 20 minutes after dosing. In addition, one animal in this group showed further indication of CNS depression when observed at 30 and 90 minutes after treatment. This animal appeared normal during the observations performed at 150 and 300 minutes; however it died overnight between day one and day two. No other treatment related clinical signs, were recorded in the remaining animals at any time during the study. Necropsy was not performed after study termination; changes in body weights were not recorded.

MDEA-Esterquat C16-18 and C18 unsatd.  is practically non-toxic based on the oral LD50 of > 10 000 mg/kg bw obtained in the two studies.

Acute dermal toxicity

In an acute dermal toxicity study according to OECD Guideline 402 (24 April 2002) New Zealand White rabbits were dermally exposed to MDEA-Esterquat C16-18 and C18 unsatd.  (40 % a.i.) in oleum arachidis. Treatment occurred on an area of 10 x 15 cm of body surface at doses of 2000 mg/kg bw for 24 hours. Animals were observed for 14 days afterwards.

No mortality occurred in this limit test. There were no treatment related clinical signs, necropsy findings or changes in body weight. Slight to moderate erythema and mainly moderate edema with partly decreasing intensity were observed at the treatment sites up to day 3 and were fully reversible within 7 days. MDEA-Esterquat C16-18 and C18 unsatd.  is practically non-toxic based on the dermal LD50 of > 2000 mg/kg bw determined in this study.

Acute inhalation toxicity

Inhalation is not a relevant route of exposure to MDEA-Esterquat C16-18 and C18 unsatd. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used.

MDEA-Esterquat C16-18 and C18 unsatd. is a waxy solid paste. Generation of inhalable particles such as dust or aerosols is therefore not to be expected. Vaporization needs not to be considered due to the substance’s very low vapour pressure of < 10-7 kPa. Regarding use in commercial products, both professional and consumer, the substance is sold in liquid formulations in concentrations that range between < 5 and 15 %. For use, the commercial product is further diluted with water to a concentration of approximately 0.1 - 1 % (worst case assumption). The substance is not manufactured into any spray or aerosol product applications. Therefore formulation of the substance into the commercial products where it is present does not result in any likely possibility of airborne exposure. For further information please refer to the exposure scenarios in chapter 9 and 10.

Given that acute toxicity is unlikely to occur based on low acute toxicity via the oral and dermal route, as well as on low exposure levels, testing by the inhalation route is scientifically not necessary according to REACH Regulation Annex XI 1 and 3.

 

Based on the available information, the acute toxicity of MDEA-Esterquat C16-18 and C18 unsatd. is low for all three routes of administration. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

According to GHS Regulation EC No 1272/2008, a classification for MDEA-Esterquat C16-18 and C18 unsatd. is not required and labelling is not necessary.