Quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 corrosive to the skin

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Based on the results from the in vivo irritation studies, the test substance is considered to be corrosive to skin as well as eyes.

Endpoint conclusion:

adverse effect observed (corrosive)

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin irritation

A study was conducted to determine the skin irritation potential of the test substance, C12-18 DAQ (75% active in hydroalcoholic solution) according to guideline of Association of Food and Drug Officials of the US, based on Draize, 1965.The test substance was applied to four test sites per rabbit (2 abraded and 2 intact) under an occlusive dressing for 24 h. Skin irritation was scored according to Draize, at patch removal, 72 and 96 h and 7 d later. Blanching of the test sites was observed in all of the animals at 24, 72 and 96 h. Five rabbits exhibited blanching of the test sites at 7 d. Subcutaneous haemorrhage was observed within the test sites of all animals at the 72 and 96 h and 7 d observations. Eschar formation was observed within the test sites of all animals at the 7 d observation. The primary dermal irritation index (the average of the 24 and 72 hour primary dermal irritation scores) was 7.5.Oedema scores on intact skins were 3.75, 4 at 24, 72 h and on abraded skins were 3.67, 3.92 at 24, 72 h, respectively. Erythema scores on intact skins were 3.42, 3.92 at 24, 72 h and on abraded skins were 3.5, 4 at 24, 72 h, respectively. Under the study conditions, the test substance was considered to be skin corrosive in rabbits (Thompson, 1980).

Astudy was conducted to determinethe skin irritation potential of the read across substance, DDAC (80% active in hydroalcoholic solution), according to OECD Guideline 404, in compliance with GLP.In the study,0.5 mL read across substance samples were applied under occlusive patches for both 3 and 60 min on the clipped skin of 3 rabbits. Residual read across substance was removed using cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water. The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d.After 3 min exposure, very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at all the treated sites at the 48 and 72 h observations. Very slight oedema was noted at one treated site at the 24 ad 48 h observations and at two treated sites at the 72 h observation. On Day 7 and 14, some hyperkeratinisation (2/3) and desquamation (1/3) was still present.After 1 h exposure, a light brown discolouration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites 1 h after the removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observations. Blanching and moderate erythema extending up to approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctuate eschar surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7.On Day 14 sunken eschar was noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1 h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7. The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14 (Guest, 1987). Based on the results of the read across study, the test substance is considered to be corrosive to skin in rabbits.

Further, read across studies with C18 DAQ, which have been reviewed in the EU RAR (EU, 2002) are described below: 

In a test with rabbits according to OECD guidelines 404, moderate skin irritation was detected for C18 DAQ (purity approx. 97%): Three albino rabbits were tested with 0.5 g of the substance pasted with isotonic saline using semi-occlusive patches. All animals revealed mild to moderate erythema (mean scores for 24, 48 and 72 observation periods: 2/1/0.3) that reversed within 14 days. In addition, the treated skin areas were sporadically dry-rough, discolored light brown and demonstrated fine or coarse scales during the observation period of 14 days. Edema were not seen (Hoechst AG 1986c, 1986d, unpublished reports).

Another study with technical grade C18 DAQ, containing 77% dimethyldioctadecylammonium chloride, 11.3% isopropanol and 11.7% water, however, caused corrosion after a 4-hours contact with the skin of rabbits: A test with 6 rabbits according to OECD 404 (semi-occlusive application of 0.5 ml for 4 hours) resulted in moderate irritation, the effects increased after the day of application till exhibition of severe necrosis after a 14-day observation time (Hoechst AG 1989a, unpublished report).

Overall, based on the available information, the test substance is considered to be corrosive to skin.

Eye irritation

A study was performed to determine the eye irritation potential of the test substance, C12 -18 DAQ(75% active in hydroalcoholic solution),according to the method equivalent or similar to OECD 405.Two groups of New Zealand white rabbits were used to in the study.0.1 mL test substance was instilled into the eye of 9 rabbits (leaving the other eye untreated as a control).In one group (with 3 animals) the eyes were washed after 30 sec exposure and in the other group (with 6 animals) the eyes were not flushed. Readings (according to Draize) were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used. Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72 and 96 h and 7 and 14 d readings and in three animals at 21 d. Hypopyon was observed in four animals at 7 d. Red ocular discharge was exhibited in three animals at the 7 d and two animals at 14 d. Panopthalmitis was exhibited by one animal at 14 d and by all animals at 21 d.Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits (Thompson, 1980).

Based on the results of thein vivoskin irritation studies with the test and read across substances, the test substance warrants a corrosive, ‘Skin Corr. 1C; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H318: Causes serious eye damage’ classification according to 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 the dialkyl quats are very corrosive substances, the low vapour pressure prohibits occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI and additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).