Quaternary ammonium compounds, C12-14-alkyl[(ethylphenyl)methyl]dimethyl, chlorides

Endpoint summary

Description of key information

Based on the results of the read across studies, the oral and dermal LD50 values of the test substance, C12-14 ADEBAC, can be considered to be 344 mg/kg bw and 2300 mg/kg bw respectively.​

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:

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

Adequacy of study:

key study

Study period:

June, 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Acute oral toxicity was determined by oral administration of the test substance to nine dose groups of male and female rats and subsequent observations of clinical signs and mortality for 14 days. The LD50 was calculated from the mortality data recorded in the study.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
- Age at study initiation: Young adult rats
- Weight at study initiation: 200-300 g
- Fasting period before study: 24h
- Diet: Ad libitum
- Water: Ad libitum

Route of administration:

oral: gavage

Vehicle:

other: Propylene glycol for 1 mL/kg bw and lower doses and undiluted test substance for doses 2 mL/kg bw and above dose levels.

Details on oral exposure:

Vehicle:
- Amount of vehicle: Propylene glycol for 1 mL/kg bw and all lower doses. Higher doses were administered undiluted.

Doses:

0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 and 16.0 mL/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14d
- Frequency of observations: Daily
- Necropsy of survivors performed: No

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

0.43 mL/kg bw

Based on:

test mat.

95% CL:

>= 0.39 - <= 0.47

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

344 mg/kg bw

Based on:

act. ingr.

Mortality:

0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw dose levels respectively. All animals in the higher dose groups (0.50 to 16.00 mL/kg bw) died during the study period.

Clinical signs:

All animals dosed at 0.25 to 0.50 mL/kg bw exhibited lethargy and slight to moderate diarrhea. The severity of the symptoms increased proportionately to the dose level received. Surviving animals returned to normal within 5 days of dosing. Animals dosed at 1.0 or 2.0 mL/kg bw were extremely lethargic. The animals dosed from 4.0 to 16.0 mL/kg bw lapsed into coma within minutes of dosing.

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

Based on the results of the read across study, the LD50 of the test substance can be considered to be 344 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC (active: >93%), in albino rats. The read across substance was administered to groups of five fasted male and female albino rats at 0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 or 16.0 mL/kg bw. Propylene glycol was used as vehicle for 1 mL/kg and all lower doses. Doses of 2 mL/kg bw and above were administered as received. Animals were observed for 14 d post-dosing. Neither post-mortem nor histopathological examinations were performed. 0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw, respectively. All animals in the higher dose levels died during the study period. Under study conditions, the LD50 of the read across substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active read across substance, the LD50 was determined to be 344 mg/kg bw (Wallace, 1975). Based on the results of the read across study, similar oral LD50 is expected for the test substance, C12-14 ADEBAC.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

supporting study

Study period:

July 22, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, comparable to scientific principles/standards.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

No guidelines were in force when the study was undertaken.

Deviations:

yes

Remarks:

No body weights were measured and no post mortem examinations were performed

GLP compliance:

no

Test type:

other:

Limit test:

no

Species:

rat

Strain:

other: Wistar derived albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

30 young wistar derived albino rats: 5 Male and 5 female in each dose group
Weight: 200-300 g
The animals were housed in mesh bottom cages and fasted 24 h before dosing, with free supply of food and water after dosing

Route of administration:

oral: gavage

Vehicle:

water

Doses:

50, 500 and 5000 mg/kg bw (25, 250 and 2500 mg a.i./kg bw)

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

Post exposure period: 14 days
Mortality examination: Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 850 mg/kg bw

Based on:

test mat.

Remarks:

LD50 425 mg a.i./kg bw

Mortality:

Reported in table

Clinical signs:

Not reported

Body weight:

Not determined

Gross pathology:

Not determined

Other findings:

Not determined

Mortality reported:

Dose levels (mg/kg)	Mortality	Group size (5/sex)
50	0	10
500	2	10
5000	10	10

Interpretation of results:

other: Category 4 based on EU CLP criteria

Conclusions:

Based on the results of the read across study, the oral LD50 value for the test substance, C12 -14 ADEBAC, can also be expected to be at 425 mg/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the read across substance, C12-18 ADEBAC (active: 50%). No guideline was followed, as no guideline was in force when the study was undertaken. Five male and five female rats per group were dosed at 50, 500 or 5000 mg/kg bw (i.e., 25, 250 and 2500 mg a.i./kg bw). Water was used as the vehicle. Rats were observed for 14 d post-dosing. No post-mortem or histopathology examinations were performed. Doses of read across substance ≥500 mg/kg were lethal to rats within 2 d of dosing. No animals died at the lowest dose level of 50 mg/kg/bw. Under study conditions, the LD50 of the read across substance was determined to be 850 mg/kg bw (425 mg a.i./kg bw) (Bailey 1976). Based on the results of the read across study, similar oral LD50 is expected for the test substance, C12-14 ADEBAC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

344 mg/kg bw

Quality of whole database:

Study well documented, meets generally accepted scientific principles, acceptable for assessment

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

August 26, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Weight: 1.5-3 kg bw
Animals were maintained under standard laboratory conditions for a minimum of seven days, prior to the administration of the test substance

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Dose route: Topical occluded; abraded skin

Duration of exposure:

Post exposure period: 24 hours with test substance, 14 days after removal of dressing

Doses:

0.5, 1.0, 2.0, 2.52, 3.96 g a.i./kg bw

No. of animals per sex per dose:

5/group (mixed sex)

Control animals:

no

Details on study design:

Examinations made:
Clinical signs: Yes
Mortality: Yes
Bodyweight: Yes
Other examinations: A complete gross necropsy was performed on all animals

Statistics:

The LD50 together with 95% confidince limits was determined, where possible, by the method of Litchfield and Wilcoxin (1949): Acute Toxicity, J. Pharm. Exp. Ther., 96-99.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 300 mg/kg bw

Based on:

act. ingr.

95% CL:

ca. 1 460 - ca. 3 630

Mortality:

Refer the table 1

Clinical signs:

Depression was noted in 1 an 2 animals in the 2000 and 3960 mg/kg dose groups, respectively.

Body weight:

Refer the table 2

Gross pathology:

Gross necropsy observations were recorded; however no consistent findings were noted.

Mortality: Table - 1

Dose levels (g/kg)	Mortality (# Dead/# Dosed)	% mortality
0.5	0/5	0
1.0	1/5	20
2.0	3/5	60
2.52	2/5	40
3.96	2/8	40

Body weight: Table - 2

Dose levels (g/kg)	Animal #	Bodyweight (kg)
		Initial	Final
0.5	1	2.59	2.94
	2	2.19	2.56
	3	1.76	1.92
	4	2.37	2.52
	5	1.72	1.49
1.0	1	1.68	1.78
	2	1.82	1.86
	3	2.15	1.98
	4	2.15	2.17
	5	1.96	1.62
2.0	1	2.28	1.49
	2	2.13	2.00
	3	1.80	1.43
	4	1.37	1.73
	5	1.71	1.12
2.52	1	2.14	1.88
	2	1.66	1.42
	3	1.44	1.62
	4	1.77	1.78
	5	2.20	1.30
3.96	1	1.96	1.25
	2	2.41	2.25
	3	1.89	1.52
	4	2.11	1.29
	5	1.63	1.35

Interpretation of results:

other: Category 4 based on EU CLP criteria

Conclusions:

Based on the results of the read across study, the dermal LD50 value for the test substance, C12-14 ADEBAC, can also be considered to be at 2300 mg/kg.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, C12-18 ADEBAC (active: 50%), according to the method described by Hagan et al 1959 (Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp. 17-25, 1959) and similar to the OECD 402 guideline. A total of twenty-five rabbits were used to conduct the study. Each rabbit was given a single dose of the read across substance at dose levels ranging from 500 to 2960 g a.i./kg bw. Applications were made to the skin, mildly shaved and abraded under 1”x1” gauze patches over 10% of the body surface. After dosing, the sites were covered with an impermeable plastic wrapping for 24 h. After removal of the dressing, the test sites were gently cleansed and the animals were observed for 14 d for toxic effects. Depression was noted in 1 and 2 animals in the 2000 and 3960 mg a.i./kg bw dose groups, respectively. Gross necropsy observations were recorded; however no consistent findings were noted. Under study conditions, LD50 for the read across substance was determined to be 2300 mg/kg bw with 95% confidence limits of 1460 to 3630 mg/kg bw (Palanker 1976). Based on the results of the read across study, similar dermal LD50 is expected for the test substance, C12-14 ADEBAC.  

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

1. In the study, 4 animals/sex/test group were used; however, the guideline recommends 5 animals of one sex in each test group. 2. Abraded and non abraded skin sites were used; however, guideline recommends unabraded skin. 3. Gross necropsy was not perfor

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
- Weight at study initiation: 2.2 – 3.4 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Test site
- Area of exposure: Back of animal (10% of body surface)
- Type of wrap if used: The test sites were covered with gauze and each animal was wrapped in a sleeve after application of the test substance
- Type of test site: Intact and abraded (half of the test animals in each sex, i.e., 2 animals/sex/group had their skin abraded on one side )

Removal of the test substance
- Washing (if done): After removal of the dressing, animals were washed with warm water and dried.
- Time after start of exposure: After 24h

Test material
- Amount(s) applied (volume or weight with unit): 3,4 and 5 mL/kg bw
- Concentration (if solution): Undiluted (as received)
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

3,4 and 5 mL/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14d
- Frequency of observations and weighing: The animals were observed for clinical signs, mortality and body weight (at the start of the experiment and at termination (Day 14)).
- Necropsy of survivors performed: No

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3.56 mL/kg bw

Based on:

test mat.

95% CL:

>= 3.01 - <= 4.2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 730 mg/kg bw

Based on:

act. ingr.

Mortality:

Mortality observed at each dose levels:
3 mL/kg bw: 1/8
4 mL/kg bw: 6/8
5 mL/kg bw: 7/8

Clinical signs:

Severe erythema and oedema was observed post dosing at the sites of application for all animals in all groups. In the 3 mL/kg bw dose group (i.e., surviving animals), the erythema was followed by thickening of the skin and eschar formation across the back.

Body weight:

A decrease in bodyweight was observed in all surviving animals in all the treatment groups.

Conclusions:

Based on the reasults of the study, the acute dermal LD50 of the test substance was found to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for purity of the active substance, the LD50 was calculated to be 2730 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, C12-16 ADBAC (active: 80%), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The read across substance was applied to twelve male and twelve female rabbits (4 animals/sex/test group) at dose levels of 3, 4 and 5 mL/kg bw (single application) on the abraded and intact skin of the back. The test sites were covered with gauze and each animal was wrapped in a sleeve after application for a 24 h period. After removal of the dressing, animals were washed with warm water and dried. The animals were observed for clinical signs and mortality for 14 d. Body weights were determined at the start of the experiment and at termination (Day 14). In the study, 1/8, 6/8 and 7/8 animals died at 3, 4 and 5 mL/kg bw, respectively. Under the conditions of the study, the acute dermal LD50 of the read across substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for purity of the active substance, the LD50 is calculated to be 2730 mg a.i./kg bw (using density of 0.96) (Levenstein, 1977). Based on the results of the read across study, similar dermal LD50 is expected for the test substance, C12-14 ADEBAC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 300 mg/kg bw

Quality of whole database:

Due to the corrosive effect, there is a danger of irreversible damage to the skin upon exposure to the undiluted solution. Toxicity is secondary to the local tissue damage, rather than the result of percutaneously absorbed material. Comparable to guideline study with acceptable restrictions.

Additional information

Oral

Study 1:A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC (active: >93%), in albino rats. The read across substance was administered to groups of five fasted male and female albino rats at 0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 or 16.0 mL/kg bw. Propylene glycol was used as vehicle for 1 mL/kg and all lower doses. Doses of 2 mL/kg bw and above were administered as received. Animals were observed for 14 d post-dosing. Neither post-mortem nor histopathological examinations were performed. 0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw, respectively. All animals in the higher dose levels died during the study period. Under study conditions, the LD50 of the read across substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active read across substance, the LD50 was determined to be 344 mg/kg bw (Wallace, 1975).

Study 2:A study was conducted to determine the acute toxicity of the read across substance, C12-18 ADEBAC (active: 50%). No guideline was followed, as no guideline was in force when the study was undertaken. Five male and five female rats per group were dosed at 50, 500 or 5000 mg/kg bw (i.e., 25, 250 and 2500 mg a.i./kg bw). Water was used as the vehicle. Rats were observed for 14 d post-dosing. No post-mortem or histopathology examinations were performed. Doses of read across substance ≥500 mg/kg were lethal to rats within 2 d of dosing. No animals died at the lowest dose level of 50 mg/kg/bw. Under study conditions, the LD50 of the read across substance was determined to be 850 mg/kg bw (425 mg a.i./kg bw) (Bailey 1976).

Overall, based on the results of the read across studies, the oral LD50 value of the test substance is considered to range between 344-425 mg/kg bw. As a conservative approach, the lower LD50 value of 344 mg/kg bw has been considered further for hazard/risk assessment.​

Dermal

Study 1: A study was conducted to determine the acute dermal toxicity of the read across substance, C12-16 ADBAC (active: 80%), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The read across substance was applied to twelve male and twelve female rabbits (4 animals/sex/test group) at dose levels of 3, 4 and 5 mL/kg bw (single application) on the abraded and intact skin of the back. The test sites were covered with gauze and each animal was wrapped in a sleeve after application for a 24 h period. After removal of the dressing, animals were washed with warm water and dried. The animals were observed for clinical signs and mortality for 14 d. Body weights were determined at the start of the experiment and at termination (Day 14). In the study, 1/8, 6/8 and 7/8 animals died at 3, 4 and 5 mL/kg bw, respectively. Under the conditions of the study, the acute dermal LD50 of the read across substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for purity of the active substance, the LD50 is calculated to be 2730 mg a.i./kg bw (using density of 0.96) (Levenstein, 1977). Based on the results of the read across study, similar dermal LD50 is expected for the test substance, C12-14 ADEBAC.

Study 2: A study was conducted to determine the acute dermal toxicity of the read across substance, C12-18 ADEBAC (active: 50%), according to the method described by Hagan et al 1959 (Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp. 17-25, 1959) and similar to the OECD 402 guideline. A total of twenty-five rabbits were used to conduct the study. Each rabbit was given a single dose of the read across substance at dose levels ranging from 500 to 2960 g a.i./kg bw. Applications were made to the skin, mildly shaved and abraded under 1”x1” gauze patches over 10% of the body surface. After dosing, the sites were covered with an impermeable plastic wrapping for 24 h. After removal of the dressing, the test sites were gently cleansed and the animals were observed for 14 d for toxic effects. Depression was noted in 1 and 2 animals in the 2000 and 3960 mg a.i./kg bw dose groups, respectively. Gross necropsy observations were recorded; however no consistent findings were noted. Under study conditions, LD50 for the read across substance was determined to be 2300 mg a.i./kg bw with 95% confidence limits of 1460 to 3630 mg/kg bw (Palanker 1976).

Overall, based on the results of the read across studies, the dermal LD50 value of the test substance is considered to range between 2300-2730 mg/kg bw. As a conservative approach, the lower LD50 value of 2300 mg/kg bw has been considered further for hazard/risk assessment.​

Inhalation

The substance is a solid with a low vapour pressure at room temperature. It is placed on market only as a solution. Due to its physical state and physical chemical properties it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e. g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.​

Justification for classification or non-classification

Based on the results of the read across studies, C12-14 ADEBAC warrants ‘Acute tox. 4; H302: Harmful if swallowed’ and ‘Acute tox. 4; H312: Harmful in contact with skin’ classifications for oral and dermal routes respectively, according to the EU CLP criteria (Regulation 1272/2008/EC). ​​