Diethylammonium chloride

Endpoint summary

Description of key information

acute toxicity, oral (similar to OECD 401, RL2), male rats: LD50 = 540 mg/kg bw

acute toxicity, inhalation (similar to OECD 403, RL2), female rats: LC50 = 17300 mg/m3 (calculated)

acute toxicity, dermal (no guideline followed, RL2), male rabbits: LD50 = 582 mg/kg bw

RA from diethylamine (CAS 109 -89 -7)

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:

1950

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: data from peer-reviewed handbook

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

before 1981

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sherman

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 90-120 g
- Diet: Rockland rat diet

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 %

Doses:

252, 500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5 (m)

Control animals:

not specified

Details on study design:

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

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

540 mg/kg bw

Based on:

test mat.

95% CL:

350 - 830

Mortality:

2000 mg/kg bw: 5/5, days to death: 1, 1, 0, 1, 1;
1000 mg/kg bw: 4/5, days to death: 5, 5, 11, 1;
500 mg/kg bw. 3/5, days to death: 6, 4, 8;
252 mg/kg bw: 0/5

Clinical signs:

- sluggish
- body temperature was reduced
- one animal was narcotic.

Body weight:

inconspicous

Gross pathology:

Findings in survivors:
- congestion of the lungs, liver and kidney
- hemorrhage of the stomach
- congestion, hemorrhage or opacity of the intestine

Other findings:

The test substance caused dose and concentration dependent toxicity after a single ingestion.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute Tox. 4, H302
After oral administration to rats, the test material diethylamine (CAS: 109-89-7) shows an LD50 of 540 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

540 mg/kg bw

Based on:

test mat.

95% CL:

350 - 830

Mortality:

2000 mg/kg bw: 5/5, days to death: 1, 1, 0, 1, 1;
1000 mg/kg bw: 4/5, days to death: 5, 5, 11, 1;
500 mg/kg bw. 3/5, days to death: 6, 4, 8;
252 mg/kg bw: 0/5

Clinical signs:

- sluggish
- body temperature was reduced
- one animal was narcotic.

Body weight:

inconspicous

Gross pathology:

Findings in survivors:
- congestion of the lungs, liver and kidney
- hemorrhage of the stomach
- congestion, hemorrhage or opacity of the intestine

Other findings:

The test substance caused dose and concentration dependent toxicity after a single ingestion.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute Tox. 4, H302
Applying the RA approach, similar results are expected for the target substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

540 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

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

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 9 litres
- System of generating vapour: The test material was pumped into the top of a vertical glass evaporator tube, which was heated sufficiently to cause vaporization. Dried air was introduced through the bottom of the tube (counter-current to the sample flow) and the resultant vapor-containing atmosphere passed to the exposure chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber concnetrations were determined by adjustment of sample and/or air flow rates.
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

4000 and 8000 ppm (nominal), corresponding to 18000 mg/m3 and 36000 mg/m3 , respectively

No. of animals per sex per dose:

6 (f)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of exposure and daily thereafter.
- Frequency of weighing: just before exposure and at sacrifice
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

5 700 ppm

95% CL:

>= 4 600 - <= 7 000

Remarks on result:

other: equivalent to 17300 mg/m3 and 17.3 mg/L air

Mortality:

8000 ppm: 6/6 (3 animals within exposure, 1 animal after 2.5 h, 2 animals after 24 h)
4000 ppm: 0/6

Clinical signs:

other: 8000 ppm: gasping, nasal irritation, poor coordination, bloody nasal discharge, tonic convulsions. 4000 ppm: wet noses, eyes partly closed within 10 min, slight loss of coordination within 25 min.

Body weight:

normal development

Gross pathology:

lungs red, intestines yellow, gas and liquid filled.

Survivors: no effects

Other findings:

Inhalation, by rats, of a nominal concentration of 8000 ppm resulted in death within a few hours.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute Tox. 4, H332

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Vehicle:

other: unchanged (no vehicle)

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

5 700 ppm

95% CL:

>= 4 600 - <= 7 000

Remarks on result:

other: equivalent to 17300 mg/m3 and 17.3 mg/L air

Mortality:

8000 ppm: 6/6 (3 animals within exposure, 1 animal after 2.5 h, 2 animals after 24 h)
4000 ppm: 0/6

Clinical signs:

other: 8000 ppm: gasping, nasal irritation, poor coordination, bloody nasal discharge, tonic convulsions. 4000 ppm: wet noses, eyes partly closed within 10 min, slight loss of coordination within 25 min.

Body weight:

normal development

Gross pathology:

lungs red, intestines yellow, gas and liquid filled.

Survivors: no effects

Other findings:

Inhalation, by rats, of a nominal concentration of 8000 ppm resulted in death within a few hours.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute Tox. 4, H332
Applying the RA approach, similar results are expected for the target substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

25 922 mg/m³

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: data from peer-reviewed handbook

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 and associates, using groups of 5 male albino rabbits weighing 2.5 to 3.5 kg. 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 is removed and the rabbits are caged for the subsequent 14-day observation period.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3-5 month
- Weight at study initiation: 2.5 - 3.5 kg
- Diet (e.g. ad libitum): Rockland rabbit diet

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

0.252, 0.5, 1.0, 2.0 mL/kg bw = 179, 355, 710 and 1420 mg/kg bw (conversion in mg/kg bw based on the density d: 0.71 g/cm3 of the test substance diethylamine)

No. of animals per sex per dose:

5 (m)

Control animals:

not specified

Details on study design:

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

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

582 mg/kg bw

Based on:

test mat.

95% CL:

>= 376 - <= 895

Mortality:

1420 mg/kg bw: 5/5, days to death: 1, 1, 1, 1, 1
710 mg/kg bw: 3/5, days to death: 6, 1, 1
355 mg/kg bw: 1/5, days to death: 1
179 mg/kg bw: 0/5

Clinical signs:

Local effects: the substance caused hemorrhage and necrosis of the skin and underlying muscular layers.

Body weight:

Survivors of the 355 and 710 mg/kg bw dose group lost weight.

Gross pathology:

Animals that died: pale or mottled livers, pale, mottled or roughened surfaces of the kidneys, and congested or hemorrhagic intestines. Spleens were darkened to the point of being called black, pancreas congested and testes hemorrhagic.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

CLP: Acute Tox. 3, H311
After dermal administration to rats, the test material diethylamine (CAS: 109-89-7), shows an LD50 of 582 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

582 mg/kg bw

Based on:

test mat.

95% CL:

>= 376 - <= 895

Mortality:

1420 mg/kg bw: 5/5, days to death: 1, 1, 1, 1, 1
710 mg/kg bw: 3/5, days to death: 6, 1, 1
355 mg/kg bw: 1/5, days to death: 1
179 mg/kg bw: 0/5

Clinical signs:

Local effects: the substance caused hemorrhage and necrosis of the skin and underlaying muscular layers.

Body weight:

Survivors of the 355 and 710 mg/kg bw dose group lost weight.

Gross pathology:

Animals that died: pale or mottled livers, pale, mottled or roughened surfaces of the kidneys, and congested or hemorrhagic intestines. Spleens were darkened to the point of being called black, pancreas congested and testes hemorrhagic.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

CLP: Acute Tox. 3, H311
Applying the RA approach, similar results are expected for the target substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

582 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

There are no data available on acute toxicity properties of diethylammonium chloride (CAS 660-68-4). Thus, read-across from an appropriate structural analogue substance (diethylamine, CAS 109-89-7) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.5. Common functional groups and structural similarities combined with similar toxicokinetic properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

An acute oral toxicity study performed equivalent or similar to OECD 401 with diethylamine (CAS 109-89-7) is available (reference 7.2.1-1). In this study, groups of 5 male Sherman rats were administered single doses of the test substance at doses of 252, 500, 1000 and 2000 mg diethylamine /kg bw by oral gavage. The animals were observed for 14 days after substance administration. Following treatment 0/5, 3/5, 4/5 and 5/5 animals died within 8 days after substance application at 252, 500, 1000 and 2000 mg/kg bw, respectively. The acute oral LD50 value was considered to be 540 mg/kg. In conclusion, the derived LD50 value meets the classification criteria for classification as Acute Tox. 4 (H302) defined for acute oral toxicity according to Regulation (EC) No 1272/2008.

 

Acute dermal toxicity

An acute dermal toxicity study with diethylamine (CAS 109-89-7) is available (reference 7.2.3-1). In this study, groups of 5 male New Zealand White rabbits were treated with single doses of the pure test substance at doses of 0.252, 0.5, 1.0, 2.0 mL/kg bw, corresponding to 179, 355, 710 and 1420 mg/kg bw (conversion in mg/kg bw based on the density d: 0.71 g/cm³) for 24 h via occlusive dressing and observed for 14 days post-application. Following treatment 0/5, 1/5, 3/5 and 5/5 animals died within 6 days after substance application at 179, 355, 710 and 1420 mg/kg bw, respectively. Most animals died within the first day after application. The substance caused hemorrhage and necrosis of the skin and underlying muscular layers. Survivors of the 355 and 710 mg/kg bw dose group lost weight. The acute dermal LD50 value was considered to be 582 mg/kg. In conclusion, the derived LD50 value meets the classification criteria for classification as Acute Tox. Cat. 3 (H311) defined for acute dermal toxicity according to Regulation (EC) No 1272/2008.

 

Acute inhalation toxicity

An acute inhalation toxicity study performed equivalent or similar to OECD 403 with diethylamine (CAS 109-89-7) is available (reference 7.2.2-1). In this study, groups of 6 female Wistar rats were exposed to single nominal concentrations of 4000 and 8000 ppm test substance vapor (corresponding to 12139 and 242790 mg/m³, respectively) for 4 h via inhalation and observed for 14 days after test material exposure. At 4000 ppm, no mortality occurred during the entire study period and clinical signs of toxicity were limited to wet noses, eyes partly closed within 10 min, slight loss of coordination within 25 min. Body weight development was not affected. At 8000 ppm, 6/6 animals died (3 animals during exposure, 1 animal 2.5 h after exposure and 2 animals after 24 hours). Clinical signs noted at this concentration were gasping, nasal irritation, poor coordination, bloody nasal discharge, tonic convulsions. Necropsy examination of deceased animals revealed red lungs, intestines yellow and filled with gas and liquid. The acute inhalation LD50 value was considered to be 5700 ppm, equivalent to 17300 mg/m³and 17.3 mg/L air.

In conclusion, based on the available data, the LC50 value meets the classification criteria for Acute Tox. Cat. 4 (H332) defined for acute inhalation toxicity of vapors according to Regulation (EC) No 1272/2008.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to diethylammonium chloride, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on acute toxicity (oral and inhalation) of the source substance diethylamine are in consistency with the harmonized classification according to Regulation (EC) 1272/2008, Annex VI (Index No. 607-006-00-8). For acute toxicity dermal based on the available data, diethylamine meets the criteria for classification as Acute Tox. 3 dermal (H311).

Applying the RA-A approach classification of the target substance meets the criteria for classification as Acute Tox. 4 oral (H302) inhalation (H332) and Acute Tox. 3 dermal (H311), according to Regulation (EC) 1272/2008.