Quaternary ammonium compounds, benzyl C12-C16 (even numbered)-alkyldimethyl chlorides

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The appearance, physical state and colour were determined according to EPA OPPTS 830.6302, .6303 and .6304 (Schulze, 2007)

Physical state at 20°C and 1013 hPa:

solid

Form:

solid: crystalline

Colour:

white

Colour intensity:

light

Crystalline, hygroscopic, sticky white solid with a faint marzipan-like odour

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The vapour pressure was determined using the isothermal thermo gravimetric effusion method according to OECD Guideline 104, EU Method A.4 and EPA OPPTS 830.7950 (Brekelmans, 2012).

Vapour pressure:

0.006 Pa

at the temperature of:

25 °C

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Based on the results of thein vivoskin and eye irritation studies, the test substance is considered to be corrosive to skin and eyes.   

Endpoint conclusion:

adverse effect observed (corrosive)

Endpoint conclusion:

adverse effect observed (irreversible damage)

Endpoint conclusion:

no study available

Skin

Study 1:A study was conducted to determine the skin irritation/corrosion potential of the test 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 an undiluted test 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 test 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 test substance, C12 -16 ADBAC (80% active), according to Federal Hazardous Substances Labelling Act. The experiment was performed on rabbits. The undiluted test 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 test 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 test substance is considered to be corrosive to rabbit skin (Wallace, 1975).

Study 3:A study was conducted to determine the skin irritation/corrosion potential of the test substance, C12-16 ADBAC (purity not specified) according to the method 'U. S. Federal Register, Vol. 41, No. 188, P. 42572’. The experiment was performed on rabbits. Six animals were treated with 0.5 mL of the test substance for 4 h under occlusive conditions. As the test proved positive for corrosion after 4 h, it was repeated in a different group of animals for an exposure period of 60 min and then for an exposure period of 3 min. Under the test conditions, the substance was corrosive to rabbit skin (Sugar, 1981).

Study 4:A study was conducted to determine the skin irritation/corrosion potential of the test substance, C12-16 ADBAC (purity not specified) according to OECD Guideline 404. The skin of albino rabbit was used in this experiment. A single 24 h, occluded application of the test substance (undiluted) to the intact and abraded skin of six rabbits produced necrosis with blanching extending beyond the entire site and severe oedema. Forty-eight hours after patch removal, each site and beyond was coriaceous and slight oedema was noted. No further observations were made. Corrosive effects were noted in all 6 rabbits. Under the study conditions, the test substance was corrosive to rabbit skin (Anspach, 1976).

Study 5:A study was conducted to determine the skin irritation/corrosion potential of the test substance, C12-16 ADBAC (25.5% active) according to a method similar to OECD Guideline 404, in compliance with GLP. The experiment was performed with a 25.5% active test substance. The objective of this study was to define a clear "non-irritant" level of administration and the maximum tolerated test concentration (irritancy, but not severe irritancy, corrosivity, toxicity or mortality) following a single topical administration to Wistar rats, and thereby select dosages for absorption, distribution and excretion study in the same strain of rat. Four groups of five male and five female Wistar rats were treated with 240 mm3 aliquot of 2.55, 1.28, 0.77 and 0.26% w/v test substance. The test site was protected by an Elizabethan collar for a period of 72 h following administration. Under the conditions of this study, the 'threshold of irritancy' of the test substance in distilled water was between 0.26 and 0.77% w/v, and the 'maximum tolerated' concentration was slightly more than 2.55% w/v. The lowest tested concentration of 0.26% w/v was non-irritant to rabbit skin (Cummins, 1991).

Study 6:A study was conducted to determine the skin irritation/corrosion of the test substance, C12-16 ADBAC (0.1% active in water) according to OECD Guideline 404. The experiment was performed to assess albino rabbits (strain not specified). Under the study conditions, a 0.1% aqueous solution of the test substance was not irritating to rabbit skin (following 24 h exposure under occluded conditions) (Hixson, 1968).

Additional irritation studies were identified for the test substance, C12-16 ADBAC (purity not specified) from literature sources. These studies were conducted with 0.1 to 1% active test substance in water in rabbits and guinea pigs. When applying 0.5 mL of the test substance on rabbit skin, concentrations of 1% or greater induced skin reactions, while 0.1% was not irritating. Exposure for 24 h to 0.1% aqueous test solution was not irritating to guinea pig skin, while the same exposure regime of 0.3% concentration caused irritation in rabbits. Also, 0.5 mL of a 0.5% aqueous test solution on the skin of nine rabbits for 24 h under the occlusive patch, resulted in barely perceptible erythema in one animal and no reactions in the others. In another study, 0.3% test solution was tested according to the same protocol. Skin irritation was not observed in any of the nine rabbits. A 0.1% aqueous solution of the test substance was applied to the skins of rabbits under plastic wrap for 5 d. At the end of the period, necrosis and varying degrees of erythema with diffuse areas of eschar and bleeding were noted. Data from published literature suggested that the test substance was corrosive to rabbit skin (BIBRA, 1989; CIR, 1989).

Also, the Biocides assessment report on C12-16 ADBAC, concluded that the test substance to be corrosive to the skin (ECHA biocides assessment report, 2015).

Therefore, based on the available information and in line with the biocides assessment report, the test substance is concluded to be corrosive to the skin.  

Eye

Study 1:A study was conducted to determine the eye irritation/corrosion potential of the test substance, C12-16 ADBAC (80% active in water) according to a method similar to OECD Guideline 405. The experiment was performed on rabbits. All six test rabbits received 0.1 mL of the undiluted test substance in one eye. The other eye remained untreated. Eyes were not washed throughout the study. After 24, 48 and 72 h, eyes were evaluated for ocular lesions according to the Draize scale. Under the conditions of the study, the test substance produced severe and irreversible damage in rabbit eyes (Wallace, 1975).

Study 2:A study was conducted to determine the eye irritation/corrosion potential of the test substance, C12-16 ADBAC (purity not specified) according to a method similar to OECD Guideline 405. The experiment was performed on New Zealand rabbits. A single application of the undiluted test substance to the eye of 6 rabbits produced severe corneal opacity, iritis, and moderate erythema and chemosis. There was a delayed occurrence of the effects, therefore, the mean values on Days 5 -7 were chosen for the evaluation. Under the study conditions, the test substance produced serious eye damage to rabbits (Sterner, 1981).

Study 3:A study was conducted to determine the eye irritation/corrosion potential of the test substance (purity not specified) according to a method similar to OECD Guideline 405. The experiment was performed on albino rabbits. A single application of the undiluted test substance to the non-irrigated eye of 6 rabbits produced severe corneal opacity, conjunctivitis and blanching of the conjunctival membranes. Iritis could not be scored due to the severe corneal opacity. Crystallization and fissuring were noted in one or two animals. The animals were observed for 3 days after application. Under the study conditions, the undiluted test substance produced serious eye damage to rabbits (Anspach, 1976).

Study 4:A study was conducted to determine the eye irritation/corrosion potential of the test substance, C12-16 ADBAC (0.1% active in water) according to a method similar to OECD Guideline 405. The experiment was performed on albino rabbits. A single application of the test substance as a 0.1% aqueous solution to the non-irrigated eye of nine rabbits produced moderate effects on the conjunctivae 1 h after application, but these had disappeared within 1 day. The animals were observed for 7 days after application. Under the study conditions, the test substance as a 0.1% aqueous solution was not irritating to the rabbit eye (Hixson, 1968).

As per CIR (1989) concentrations above 1% and higher caused severe damage of the rabbit eye upon twice daily instillation for 7 d (CIR, 1989).

The Biocides assessment report on C12-16 ADBAC, concluded the test substance to be corrosive to the eye (ECHA biocides assessment report, 2015).

Overall, based on the available information and in line with the biocides assessment report, the test substance is concluded to be corrosive to the eye.  

Based on the results of the in vivo skin and eye irritation studies, the test substance warrants a ‘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 the eye irritation endpoint is covered by the above classifications for skin effects.

With regard to respiratory tract irritation, although the test substance is very corrosive, 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).

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified