Benzyl-C12-14-alkyldimethylammonium chlorides

Endpoint summary

Description of key information

Based on the results of the read across studies, the test substance is considered to be corrosive to skin as well as eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.

Qualifier:

according to guideline

Guideline:

other: Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977.

Deviations:

no

GLP compliance:

no

Remarks:

Study performed before GLP

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

Concentration: 50 % active substance

Duration of treatment / exposure:

4h

Observation period:

24, 48 and 72h

Number of animals:

1 in pre-test; 3 in main test

Details on study design:

- An amount of 0.5 mL of undiluted test substance (50% a.i.) was applied under occluded dressing onto the skin of 1 rabbit for 3’, 30’, 60’, and 4h. The skin was washed with water upon removal. 
- Observations: 24, 48 and 72h.
- A confirmatory study was performed at 3 min and 60 min applications in 3 rabbits each.

Irritation parameter:

erythema score

Remarks:

60 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.6

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: skin corrosive

Irritation parameter:

erythema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Remarks:

60 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.9

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: skin corrosive

Irritation parameter:

edema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

Details:
After 3 min: Well-defined erythema with moderate oedema at 72h; 
After 30 min: Severe erythema (necrotic reaction) with slight oedema;
After 60 min: Moderate to severe erythema with moderate oedema at 72h;
After 4h: Severe erythema (necrotic reaction) with severe oedema. 
Primary Irritation Index: 7.0
- Main study in 3 rabbits, 2 sites each with exposure for 3 min, and another 3 rabbits for 60 min. 
Effects at 3 min: no dermal reactions at any of the six sites.
Effects at 60 min: Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other two sites.
Primary irritation index PII: 3 min: 0; 60 min: 4.5
50% active substance was corrosive to the skin

Interpretation of results:

other: Category 1B (Corrosive) based on CLP criteria

Conclusions:

Under the conditions of the study, the read across substance solution was considered to be corrosive to rabbit skin.

Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the read across substance, C12-16 ADBAC (50% active in water) according to the method 'Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977'. In this experiment, 0.5 mL of the undiluted read across substance (50% active) was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 min and 4 h. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 h. A confirmatory study was performed with 3 min or 1 h applications in 3 rabbits each. In the main study, no dermal reactions were observed at any of the 6 sites after 3 min application. Moderate erythema (mean score: 2.6) with slight oedema (mean score: 1.9) at 4 sites and areas of skin necrosis at the other 2 sites were observed following 1 h application (Primary irritation index PII: 3 min: 0; 60 min: 4.5). Under the conditions of the study, the read across substance solution was considered to be corrosive to rabbit skin (Liggit, 1982). Based on the results of the read across, a similar corrosive potential is expected for the test substance.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Labeling Act

Version / remarks:

1975

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

1. In the study, abraded and non abraded skin sites were used; however, the guideline recommends unabraded skin. 2. Exposure period was 24 h; however, guideline recommends 4 h exposure period

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

other: The test substance was applied to both abraded and intact skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Test material
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

24h

Observation period:

24 and 72h

Number of animals:

6

Details on study design:

Test site:
- Area of exposure: Back of animal
- Type of wrap if used: The patches consisted of two layers of light gauze cut in squares (2.5 cm on the side). The patches were secured to the test area by thin bands of adhesive tape and the trunk of each animal was wrapped in clear plastic trunk bands after application of the test substance.
- Type of test site: Two areas (intact and abraded) on the back of each animal placed approximately 10 cm apart

Scoring system:
- Skin reactions were scored for erythema and edema, according to Draize Woodland and Calvery scoring system.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24h and 72h

Score:

6.29

Max. score:

8

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Intact and abraded skin site

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Intact skin site

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

3.5

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Abraded skin site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

2.66

Max. score:

3

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Intact skin site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h and 72h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Abraded skin site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24/72 h

Score:

ca. 3.5 - ca. 4

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3.5 for intact and 4 for abraded skin)

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 / 72 h

Score:

ca. 3 - ca. 3.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3 for intact and 3.5 for abraded skin)

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24 / 72 h

Score:

ca. 3.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3.5 for intact and 3.5 for abraded skin)

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24 / 72 h

Score:

ca. 3.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3.5 for intact and 3.5 for abraded skin)

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24 / 72 h

Score:

ca. 3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3 for intact and 3 for abraded skin)

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24 / 72 h

Score:

ca. 3.5 - ca. 4

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 4 for intact and 3.5 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24 / 72 h

Score:

ca. 2.5 - ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 2.5 for intact and 3 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24 / 72 h

Score:

ca. 2.5 - ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 2.5 for intact and 3 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3 for intact and 3 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24/72 h

Score:

ca. 2.5 - ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 2.5 for intact and 3 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 3 for intact and 3 for abraded skin)

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24/72 h

Score:

ca. 2.5 - ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Remarks:

(mean erythema score was: 2.5 for intact and 3 for abraded skin)

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

other: see below table for details on results

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

other: see below table for details on results

Irritant / corrosive response data:

- Severe erythema and edema were observed in animals with abraded and intact skin. See below table for individual animal scores at each time point.

Table 1. Individual animal data on the skin irritation response

Rabbit no.	Reaction	24 h		72 h
		Intact	Abraded	Intact	Abraded
1	Erythema	4	4	3	4
	Edema	2	3	3	3
2	Erythema	3	4	3	3
	Edema	2	3	3	3
3	Erythema	4	4	3	3
	Edema	3	3	3	3
4	Erythema	4	4	3	3
	Edema	2	3	3	3
5	Erythema	3	3	3	3
	Edema	3	3	3	3
6	Erythema	4	4	4	3
	Edema	2	3	3	3

 

Interpretation of results:

other: Category 1B (corrosive) based on CLP criteria

Conclusions:

Based on the results of the study, the read across substance is considered to be corrosive to rabbit skin.

Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the read across substance, C12 -16 ADBAC (80% active), according to Federal Hazardous Substances Labelling Act. The experiment was performed in rabbits. The undiluted read across substance (80% active) was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 h. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 h from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the read across substance was calculated to be 6.29 and the mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). Based on the results of the study, the read across substance is considered to be corrosive to rabbit skin (Wallace, 1975). Based on the results of the read across, a similar corrosive potential is expected for the test substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

Study 1: A study was conducted to determine the skin irritation / corrosion potential of the read across substance, C12-16 ADBAC (50% active in water) according to the method 'Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977'. In this experiment, 0.5 mL of a the undiluted read across substance (50% active) was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 min and 4 h. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 h. A confirmatory study was performed with 3 min or 1 h applications in 3 rabbits each. In the main study, no dermal reactions were observed at any of the 6 sites after 3 min application. Moderate erythema (mean score: 2.6) with slight oedema (mean score: 1.9) at 4 sites and areas of skin necrosis at the other 2 sites were observed following 1 h application (Primary irritation index PII: 3 min: 0; 60 min: 4.5). Under the conditions of the study, the read across substance solution was considered to be corrosive to rabbit skin (Liggit, 1982).

Study 2: A study was conducted to determine the skin irritation / corrosion potential of the read across substance, C12 -16 ADBAC (80% active), according to Federal Hazardous Substances Labeling Act. The experiment was performed in rabbits. The undiluted read across substance (80% active) was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 h. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 h from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the read across substance was calculated to be 6.29 and the mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). Based on the results of the study, the read across substance is considered to be corrosive to rabbit skin (Wallace, 1975).

The biocides assessment reports available from RMS Italy on C12-16 ADBAC, published by the Italian authorities in June 2015, concluded that the test substance to be corrosive to the skin (ECHA biocides assessment report, 2015). Based on the results of the read acrossin vivoskin irritation studies and in line with the biocides assessment report, the test substance is considered to be corrosive to skin.  

Eye:

In accordance with Annex VII, Section 8.2, Column 2, eye irritation study does not need to be conducted because the substance is classified as corrosive to the skin.

Justification for classification or non-classification

Based on the results of the read acrossin vivoskin irritation studies, the test substance warrants a corrosive, ‘Skin Corr. 1B; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H31: Causes serious eye damage’ classification according to the EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects.  ​

With regard to respiratory tract irritation, although C12 -14 ADBAC is a very corrosive substance, its low vapour pressure prohibits the occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI; therefore, an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).