Registration Dossier

Administrative data

Description of key information

The dermal irritant/ corrosive potential of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
- Four in vivo acute dermal irritation/corrosion tests using either concentrated (97% purity) or technical grade (75 to 78% active in isopropanol/water) as a test substance. The four studies were performed in rabbits according to OECD 404 guideline in compliance with the principles of Good Laboratory Practice regulations (Hoechst AG 1996, Hoechst AG 1989a, Clouzeau 1991a, Prinsen 1989).
Whereas pure quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride is not subject to labelling requirements with regard to skin irritation, technical grade in isopropanol/water exhibited severe irritating properties up to corrosive effects on the skin.
Other available skin irritation studies were of limited value for assessing the irritant/corrosive properties of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride. For one them, the objective was to determine the primary skin irritation of dilutions of the substance which may be used in personal care produts. The purpose was to confirm that the selected dilutions were not irritating to the skin. In another study performed before implementation of Good Laboratory Practices, weanling swine was used as test species. Although weanling swine can be used for skin irritation tests, the existing database on this species is limited and the current guidelines recommend the use of albino rabbit to assess the irritant /corrosive properties of a substance.
The ocular irritant potential of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
- Two in vivo acute eye irritation/corrosion tests performed in rabbits according to OECD 405 guideline and using either concentrated (97% purity) or technical grade (78% active in isopropanol/water) as a test substance.
Pure and technical grades were 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)

Additional information

Skin irritation/corrosion:

Technical grades dihydrogenatedtallowalkyldimethylammonium chloride or dioctadecyldimethylammonium chloride (DHTDMAC or DODMAC, 75 to 78% active in isopropanol/water) as well as pure dioctadecyldimethylammonium chloride (DODMAC, 97% in water) were investigated for skin irritation/corrosion in four reliable without restriction studies.

All studies were performed according to OECD guideline 404 in compliance with Good Laboratory Practices.

In the Hoechst study (1996), pure DODMAC (97% in water ) applied to the skin of 3 rabbits under a semi-occlusive dressing, was only slightly

irritating to skin following a 4-hour exposure period.

In this study, skin reactions were observed approximately 0.5, 1 , 24, 48 and 72 hours after removal of the dressing and then on day 7, 14 in order to observe their reversibility. The mean scores over 24, 48 and 72 hours for individual animals were 2.0, 1.0, and 0.3 for erythema and 0.0, 0.0, and 0.0 for oedema. Whereas no oedema were observed following treatment, mild to moderate erythema occurred which reversed fully within the observation period of 14 days.

Based on these results, pure quaternary ammonium compounds, di-C16 -18 -alkyldimethyl, chlorides should not be subject for labelling requirements regarding skin irritation. This view is in line with the conclusions from the existing EU risk assessment on DODMAC /DHTDMAC.

In contrast, in the three studies (Hoechst 1989a, Clouzeau 1991a and Prinsen 1989) performed with technical grades DHTDMAC or DODMAC (75 to 78% active in isopropanol/water), severe skin irritation up to corrosive effects were observed after a 4 -hour exposure period under semi

-occlusive dressing. Whereas in the studies of Clouzeau (1991a) and Prinsen (1989), the observed effects were interpreted as being reversible, in the Hoechst study (1989a), slight to moderate erythema and oedema reactions increased over time until exhibition of necrosis.

In this last study (Hoechst 1989a), technical grade DODMAC (77 % active in isopropanol/water) was applied to the skin of 3 rabbits for 3 minutes or 4 hours. The skin was examined 30, 60 minutes and 24, 48 and 72 hours after removal of the dressing. Since effects were still present after 72 hours, additional readings were performed after 7 and 14 days.

After 3 minutes of exposure, a slight transient erythema was noted in 2 animals one hour and 24 hours following removal of the patches. No signs of irritation were observed after 48 hours and later.

After 4 hours of exposure, the skin of animals exhibited slight erythema and moderate oedema one hour after removal of the patches. At the 24 and 72-hour readings, moderate erythema and slight to moderate oedema were observed. Additionally the skin was leathery. Seven days p.a. moderate to severe erythema in all animals and slight oedema in one animal appeared. Swelling of the other animals could not be assessed because of induration. This was still partially the case after 14 days. In two rabbits well-defined to severe erythema and slight oedema were observed at this time point. The skin was also indurated, raised, scabbed, chapped, parchement-like and with fine or coarse scales. A scar had developed in two animals 14 days after the application.

Based on these results, technical grades in isopropanol/water should be classified as corrosive to skin. This view is in line with the conclusions from the existing EU risk assessment on DODMAC/DHTDMAC.

Eye irritation:

Technical grades dihydrogenatedtallowalkyldimethylammonium chloride (DHTDMAC, 78% active in isopropanol/water) as well as pure dioctadecyldimethylammonium chloride (DODMAC, 97% in water) were investigated for skin irritation/corrosion in two studies.

The technical grade DHTDMAC was tested In the study of Clouzeau (1991b) which was a reliable without restriction study. The potential of the test material (78% active in isopropanol/water) to induce eye irritation was assessed in 1 rabbit according to the OECD guideline 405 and the principles of Good Laboratory Practices.

As severe ocular effects were anticipated, 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 eye was 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 material 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.

The pure DODMAC (97% in water) was tested in the Hoechst study (1986b) for which only the executive summary of the study report was available. According to this executive summary, the study was conducted according to OECD guideline 405. After installation of 100 mg test substance into the eyes of rabbits severe irritation reactions were observed. Based on the results, the test material was considered as severely irritating to eyes.

Based on these results, pure quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride as well as technical grade should be classified as severely irritating to eyes.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Skin Irritation / Corrosion:

Based on the results of all available sudies on skin irritation / corrosion according to OECD guideline 404, pure quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride is not subject to labelling requirements according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC.

However, applying the same criteria, technical grade (approximately 77% active in isopropanol/water) is considered corrosive to skin and should be classified as category 1C according to CLP (Reg 1272/2008/EC) and R34 - causes burns according to DSD (directive 67/548/EEC).

Eye Irritation / Corrosion:

Based on all available results, technical grade and pure quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride should be classified Eye damage Category 1 and Xi, R41 according to EU regulation CLP (Reg 1272/2008/EC) and directive 67/548/EEC respectively. Respiratory irritation:

There is no data from inhalation studies. However, in view of the very low vapour pressure of pure quaternary ammonium compound,di-C16 -18 -alkyldimethyl, chloride, exposure by inhalation is not likely.