Benzododecinium chloride

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 ADBAC, can be considered to be 344 mg/kg bw and 2730 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

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements.

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:

other: 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 a

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 a.i./kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC (50 -80% active),n albino rats. The test 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. No 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 the conditions of the study, the LD50 of the test substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active test substance, the LD50 was determined to be 344 mg/kg bw (Wallace, 1975). Based on the results of the read across study, the LD50 of the test substance, C12 ADBAC, can be considered to be 344 mg a.i./kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June, 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

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

Specific details on test material used for the study:

- Analytical purity: >93%
- Stability under test conditions: Test substance is hydrolytically and photolytically stable under the conditions of this study and has been shown to be stable in aqueous, alcohol and alcohol/aqueous solutions for extended periods, e.g. at least five years under standard laboratory conditions.

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:

other: 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 a

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

Under the conditions of the study, the LD50 of the test substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active test substance, the LD50 was determined to be 344 mg a.i./kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC (50-80% active), in albino rats. The test 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. No 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 the conditions of the study, the LD50 of the test substance is considered to be 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active test substance, the LD50 is determined to be 344 mg a.i./kg bw (Wallace, 1975).

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

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Clinical signs:

other:

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:

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

Justification for type of information:

Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements.

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:

other: 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

Conclusions:

Based on the results of the read across study, the acute dermal LD50 of the test substance was considered 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 (50 -80% active), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The test 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 test substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for 80% purity of the active substance, the LD50 is calculated to be 2730 mg a.i./kg bw (Levenstein, 1977). Based on the results of the read across study, the acute dermal LD50 of the test substance, C12 ADBAC, can also be considered to be at 2730 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 730 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

A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC(50 -80% active),n albino rats. The test 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. No 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 the conditions of the study, the LD50 of the test substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active test substance, the LD50 was determined to be 344 mg a.i./kg bw (Wallace, 1975). Based on the results of the read across study, similar LD50 is expected for the test substance. This is further supported by an oral LD50 value of 400 mg/kg bw identified for the test substance from the public literature (ChemIDplus, 2019).

Dermal

A study was conducted to determine the acute dermal toxicity of the read across substance, C12-16 ADBAC (50 -80% active), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The test 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 study conditions, the acute dermal LD50 of the test substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for 80% purity of the active substance, the LD50 is calculated to be 2730 mg/kg bw (Levenstein, 1977). Based on the results of the read across study, similar acute dermal LD50 is expected for the test substance.  

Inhalation

The substance is imported and placed on market as 50% aqueous solution. Due to it physical state and low vapour pressure (1.4E-7 Pa at 20°C), it will not be available as vapours for inhalation under ambient conditions. In case inhalable forms of the substance are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures due to its corrosive potential are implemented to control exposure. Further, as discussed in the toxicokinetic section, the absorption potential following inhalation exposure is expected to be similar to the oral route, due to the ionic nature and high-water solubility of the test substance. Therefore, testing via inhalation route will less likely result in any additional hazard identification and further testing involving vertebrate animals may be omitted, in accordance with Annex VIII (8.5) and Annex XI (1.2) of the REACH regulation.

 

Justification for classification or non-classification

Based on the results of the read across studies, C12 ADBAC is considered to be classified for the oral route as Acute tox. 4; H302: Harmful if swallowed classification and not classified for the dermal route according to EU CLP criteria (Regulation EC 1272/2008)