Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitisation potential of quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride was investigated in guinea pigs and human volunteers using either technical grade or pure dioctadecyldimethylammonium chloride (DODMAC) or dihydrogenated tallowalkyldimethylammonium chloride (DHTDMAC).

Five studies were recorded for this endpoint. Amongst them, the study of Ligget and Seaber (1982) and the Hoechst study (1989b) were maximisation tests conducted in guinea pig. Although the Hoechst study was conducted according to OECD guideline 406 and Good Laboratory Practices, the existing EU risk assessment on DODMAC considers that the far too low concentrations used in this study make the test not appropriate to conclude on the sensitising potential of the substance. The study of Ligget & Seaber was comparable to OECD guideline 406 and identified as a key study.

Three studies were performed in human volunteers. The study of Smith (1980) was reliable with restrictions. This study was well documented and met generally accepted scientific principles. The study of Smith (1980) was identified as the key study and supported by the results of the study published by Meneghini et al (1995) and the study of Procter and Gamble reported in the existing EU risk assessment on DODMAC (2002).

In the study of Ligget and Seaber(1982), the potential of the substance to induce delayed contact hypersensitivity was assessed in guinea pigs using the technical grade dihydrogenatedtallowdimethylammonium chloride (78% active in isopropanol/water). The study was performed according to a method equivalent to the OECD guideline 406 and a statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was provided.

The induction phase was realized both by intradermal route on day 1 (Test substance 0.1 % v/v in water for injection) and by cutaneous route on day 8 (Test substance 10% v/v in distilled water ) in 2 groups of guinea pigs: 15 males for control group and 15 males for treated group. The challenge phase was realized on day 22 by cutaneous application of the test substance at 2.5% and 1% v/v in distilled water on two sites on the left flank . the cutaneous reactions were scored 24 ,48 and 72 hours after the challenge phase.

After the challenge application with 2.5 % v/v of the test substance in distilled water, erythema grade 1 or 2 were observed in 7, 4 and 3 controls animals at the 24, 48 and 72-hours readings respectively. 1 control animal showed also oedema. In the treated group, the incidence and severitiy of the cutaneous reactions were quite similar: 10, 7 and 5 treated animals showed erythema grade 1 or 2 at the 24, 48 and 72-hours readings. 2 treated animals showed oedema.

After the challenge application with 1% v/v of the test substance, an erythema ( grade 1 or 2) was observed in 3 ,2 and 1 out the 15 animals of the treated group at the 24, 48 and 72-hour readings respectively. In the control group, 1animal showed an erythema grade 1at the 24 -hour reading.

The persistent cutaneous reactions observed in 3/15 animals of the treated group after the challenge application may be attributable to delayed contact hypersensitivity but as the cutaneous reactions were more confined to the 24 hour examination, they were more consistent with irritation than delayed contact hypersensitivity.

Therefore, the cutaneous reactions observed in 3/15 animals (20%) of the treated groups were considered as irritative response and the substance was not considered as a skin sensitiser.

The Smith study (1980) was a human repeat insult patch test performed with a 75% aqueous dilution of the test substance according to the method based on that of Shelanski and Shelanski. A total of 84 volunteers took part in the test. The panel included 77 women and 7 men ageing from 18 to 61 years and more. 73 panellists completed the full test.

A patch loaded with 0.5 ml of 2% v/v test material in distilled water was applied down the dorsal surface of the upper arm of each subject. Subjects were instructed to keep the patches dry and to remove and discard them after 24 hours. Patches were applied on Monday, Wednesday and Friday of the first 3 weeks, called the "induction" or "insult" period. Patches were re-applied to the same site unless reaction to a substance or adhesive necessitated relocation, in which case an adjacent location was chosen.

The test sites were scored before application of each subsequent patch and on the fourth Monday after the final insult patch.14 days after the final insult patch, challenge patches were applied to both arms of each subject. Scoring were done 48 and 96 hours after patch removal.

The test material caused some degree of irritation in most volunteers and therefore it was concluded that test conditions were conducive to the induction of a sensitised state should such be likely to occur in the panellists. The concentration of the material was maintained throughout the study. The test material produced no reaction at challenge which was indicative of skin sensitisation. Therefore, it was concluded that the substance was not sensitising in humans.

The publication of Meneghini et al (1995) reported a study on contact dermatitis caused by irritants and /or sensitising agents in housewives and cleaners occupationally exposed to new detergents and hygiene products in the domestic and extradomestic environment in Italy.

In this study, the first step was to collect generic data on the use of the products and possible complaints by means of a questionnaire published in a weekly magazine. Nearly, 2000 women answered, indicating 824 different products as alleged noxious agents for skin.

The second part of the investigation was carried out at the dermatology centers involved in the study according to a standard design which included eliciting the history of occupational and non-occupational exposures, medical and dermatological history, clinical examination with special regard to the patterns of hand eczema and other cutaneous feature and diagnostic patch tests, combined with the above examination, to differentiate irritant from allergic reactions.

The study included 1 719 female subjects selected on the basis of their working activity as housewife or professional cleaner, exposed to contact with household and hygiene products: 1 100 of them were patients affected with hand contact dermatitis; 619 women with other mild diseases (cutaneous or mucosal) were considered as controls.

Within this study, several substances were tested among them a 0.1% aqueous solution of distearyldimethylammonium chloride. Judged on the basis of information from producers, this distearyldimethylammonium chloride was considered as technical grade containing < 79% DHTDMAC, approximately 12% isopropanol and 10 -12% water. As the publication provided detailed results only with substances eliciting positive reactions in patch tests, it can be assumed that the patch test results were negative for this substance.

In a human repeat insult patch test performed by Procter and Gamble and reported in the existing EU risk assessement of DODMAC(2002), one hundred thirty-six human volunteers were tested with a 2.5% aqueous solution of dihydrogenatedtallow dimethylammonium chloride. All applications were by 24-hour contact occlusive patches according to the following scheme: Patches were applied three times a week for the first three weeks, called the "induction" or "insult" period. Seventeen days after the final insult patch, challenge patches were applied. A total of one hundred twenty-seven volunteers completed the full test and the conclusion of the test was based on these volunteers.There were few incidence of irritation during the induction, no delayed contact hypersensitivity was observed at challenge (i.e no subjects exhibited reaction scores of grade 1 or greater during challenge). In conclusion, in the 127 volunteers that completed the full test, the test material produced no reaction at challenge which was indicative of skin sensitisation.


Migrated from Short description of key information:
The skin sensitisation potential of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
- A Human repeat insult patch test performed according to a method based on that of Shelanski and Shelanski (Smith, 1980)
- Two other supporting studies performed in humans volunteers (Meneghini et al, 1995- Procter and Gamble reported in the existing EU risk assessment of DODMAC, 2002)
- A Magnusson and Kligman test performed in guinea pigs according to a method equivalent to the OECD guideline 406. A statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was provided.
Based on the results of both studies, quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride is not considered to be a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Additional information:

No information on the sensitising potential of the substance via the inhalation route is available. As quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride is not considered as a sensitizer via the dermal route the risk that the substance is a respiratory sensitizer is regarded as negligible. The molecular structure of quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride does not contain toxicophore indicating a concern for sensitisation and the likelihood for exposure via inhalation is very low based on the high boiling point and very low vapor pressure of the substance.


Migrated from Short description of key information:
No data are avaible concerning the respiratory sensitisation potential of the substance.

Justification for classification or non-classification

Skin sensitisation:

According to the result of the human repeat insult patch test (Smith 1980) supporting by the two others studies performed in human volunteers (Meneghini et al, 1995 - procter and Gamble reported in the EU RAR on DODMAC, 2002) and the guinea-pig maximization test result (Ligget and Seaber, 1982), quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride is not classified for skin sensitisation.

Respiratory sensitisation:

No information on the sensitising potential of the substance via the inhalation route is available. As quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride is not considered as a sensitizer via the dermal route the risk that the substance is a respiratory sensitizer is regarded as negligible. Based on this reasoning the substance does not need to be classified for respiratory sensitization according to the criteria laid down in EU regulation (EC) n°1272/2008 (CLP) and EU Directive 67/548/EEC.