N-benzyl-N-C16-18 (even numbered)-alkyl-N-methyl-C16-18 (even numbered)-alkyl-1-aminium chloride

Endpoint summary

Description of key information

The dermal irritant/ corrosive potential of the substance was assessed using:
- Two in vivo acute dermal irritation/corrosion tests performed in rabbits according to OECD 404 guideline and EU method B4) and conducted in compliance with the principles of Good Laboratory Practice regulations (Daamen, 1991, Longobardi 2002b). 
The substance was found to be highly irritating to the skin (Longobardi 2002b) to corrosive (Daamen, 1991).
The ocular irritant potential of the substance was assessed using:
- An in vivo acute eye irritation/corrosion tests performed in rabbits according to OECD 405 guideline and Good Laboratory Practices on the structural analogue 'Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides' (DHTDMAC) (Clouzeau 1991).
The substance was found to be severely irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation/corrosion:

Three studies are recorded for this endpoint. The studies of Daamen (1991) and Longobardi (2002) were reliable without restrictions and selected as a key studies. The third study (Conine 1981) is presented as supportive since the study did not follow exactly the OECD guidelinne protocol and does not provide all the useful information.

- The study of Daamen (1991) was designed to assess the potential of the test material (containing 14,1% isopropanol and 5% water) to induce skin irritation according to the OECD guideline 404 in compliance with the principles of Good Laboratory Practice regulations.

A single dose of 0.5 g of test material reduced to paste by heating to 45°C then cooling was applied to the skin of three female rabbits under a semi-occlusive dressing for a 4-hour exposure period. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then on days 7, 14, 21 and 28 in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

The mean scores over 24, 48 and 72 hours for individual animals were 2.3, 3.7, and 3.7 for erythema (with formation of eschar) and 2.3, 2.7, and 3.3 respectively for oedema. A maximal score of 4 was recorded for each animal for both parameters. The prolonged observation period until 28 days shows that the recovery is complete for 2 out 3 animals while the remaining animal showed scar tissue in 25% of the treated skin.

- The study of Longobardi (2002) was designed to assess the potential of the test material (containing 10 -15% isopropanol and 5% water) to induce skin irritation according to the OECD guideline 404 in compliance with the principles of Good Laboratory Practice regulations.

A single dose of 0.5 g of test material reduced to paste with sterile water was applied to the skin of the rabbits under a semi-occlusive dressing for a 4-hour exposure period. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then on days 7 and 14, in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

The mean scores over 24, 48 and 72 hours for individual animals were 4.0, 4.0, and 4.0 for erythema and 2.0, 2.0, and 2.0 for oedema. After 24 hours and until day 7, a severe erythema (score of 4) was observed in all animals. The animals showed also necrotic areas of the superficial layers of the skin (stratum corneum) while the dermis was not included. Well defined oedema (score of 2) was noted at the 24, 48 and 72 hour examinations. At the end of the observation period (day 14), the superficial lesions had disappeared but very slight to severe erythema was still present. Very slight oedema (score of 1) was still present in 2 of the 3 animals at the 14 day examination.

- The study of Conine (1981) considered as supportive was designed to assess the potential of the test material (no information concerning the exact composition) to induce skin irritation according to a protocol based on the OECD guideline 404 in compliance with the principles of a house quality system. A single dose of 0.5 g of the undiluted test was applied to the skin of the six rabbits under an occlusive dressing for a 4-hour exposure period. Skin reactions were observed 24 and 48 hours after removal of the dressing. The mean values of the scores for erythema and oedema were calculated for each animal. The mean scores over 24, 48 hours for all animals were 1.25 for erythema and 1.42 for oedema with a maximal score of 4 for both parameters. These changes, although light, were not reversible on day 2.

Even if the solvent Isopropanol probably enhances the uptake of the sustance, it does not interfere with the inherent toxicity of the substance itself which must be considered as skin corrosive according to the reliable studies Daamen (1991) and Longobardi (2002b) .

Eye irritation:

One study is recorded for this endpoint. The study of Clouzeau (1991) performed on the structural analogue 'Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides' (DHTDMAC) was reliable without restrictions and selected as a key study.

The potential of the strutural analogue (Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides (DHTDMAC) containing 12% isopropanol and 10% water) to induce eye irritation was assessed in 1 rabbit according to the OECD guideline 405 in compliance with the principles of Good Laboratory Practice regulations.

Taking into account the highly irritating effects observed in the acute dermal irritation/ corrosion test previously performed in rabbits, it was decided for ethical considerations, to perform the assay with one animal. A single dose of 0.1ml of the test material was instilled into one eye, the other eye was not treated and served as control.The eyes were not rinsed after administration of the test item. Ocular reactions were observed 1 hour and 24 hours later.

1 hour then 24 hours after instillation of the test substance, the ocular reactions were severe and the conjunctival chemosis (score of 4) obscured the evaluation of the reactions at the iris and cornea. The flowing of a whitish purulent substance was also noted.

Some severe ocular lesions were expected at the next reading times but taking into consideration the severity of the lesions noted after 24 hours, the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked.

Under these experimental conditions, the test material was considered as severely irritating when administered by ocular route to rabbits.

Respiratory irritation :

There is no information is available following exposure via inhalation. Inhalation may cause respiratory irritation due to the corrosive properties of the substance. However, based on the low vapour pressure, potential for inhalation of vapours is limited.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin Irritation / Corrosion:

Based on the results of the studies of Daamen (1991) and Longobardi (2002) and according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the substance should be classified Corrosive Category 1C and R34-causes burns respectively.

Eye Irritation / Corrosion:

Based on the result of the study of Clouzeau (1991) performed on the structural anlogue 'Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides' (DHTDMAC) the substance is classified Eye damage Category 1 and Xi, R41 according to the EU regulation CLP (Reg 1272/2008/EC) and directive 67/548/EEC respectively.