Quaternary ammonium compounds, bis(C16-18 and C18-unsatd. alkyl)dimethyl, chlorides

Endpoint summary

Description of key information

There are no reliable data on DTDMAC itself available. Read-across was performed using data from the structural closely related quaternary ammonium compound DHTDMAC (CAS No. 92129-33-4). Using read-across is scientifically justified by the structural similarities as well as the comparable physico-chemical properties. There are two valid animal studies available for assessment purposes. DHTDMAC was tested in the maximization test according to Magnusson and Kligman. Both tests revealed no indications of a skin sensitizing potential of the tested dialkyldimethylammonium chloride. Based on the results of these studies it can be anticipated that DTDMAC is also not a skin sensitizer. This view is supported by a human repeated insult patch test (HRIPT) with technical grade DHTDMAC (approximately 75% active in isopropanol/water). In this human volunteer study, the test material produced no reactions at challenge treatment which were indicative of skin sensitization. In summary it can be concluded, that on the basis of results with structural closely related analoguous quaternary dialkyldimethylammonium compounds, DTDMAC with high probability is devoid of skin sensitizing properties.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No reliable data is available on DTDMAC itself with regard to skin sensitization. However, a read-across approach based on SAR (structure-activity-relationship) considerations is used as predictive tool to evaluate potential sensitization properties of DTDMAC. Two valid guideline studies are available on a structurally very closely related quaternary ammonium compound which can be used for comparison by read-across. Read-across is scientifically justified because of close structural similarities and comparable physical-chemical properties. Clustering quaternary ammonium compounds for assessment purposes was also considered appropriate by the U.S. EPA for registration purposes under FIFRA because of similar toxicological profiles of dialkyldimethylammonium chlorides. Considering the overall toxicity profile revealed during this exercise it becomes apparent that it is mainly depending on the chain-length (distribution) and the degree of saturation of the alkyl groups which may affect the reactivity of the molecules.

Read-across was performed to dihydrogenatedtallowalkyldimethylammonium chlorid (DHTDMAC). This structural analogue quaternary ammonium compound was tested in guinea pigs using the maximization method according to Magnusson and Kligman. The study was conducted according to OECD guideline 406 in compliance with the principles of Good Laboratory Practices. Based on the results from pre-testing, intradermal induction was performed using 0.04%. The dermal induction as well as challenge treatment was conducted using 0.1% of the test material in physiological saline as vehicle. Based on the study results no indication of a skin sensitizing potential was observed. The sensitization incidence was 0%.

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. One control animal showed also oedema. In the treated group, the incidence and severity 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. Two 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, one animal showed an erythema grade 1 at 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.

Technical grade DHTDMAC (approximately 75% active in isopropanol/water) was also investigated in a human repeated insult patch test (HRIPT) in 84 human volunteers. They received insult patches loaded with 0.5 mL of 2% (v/v) test substance in distilled water three times per week for 3 consecutive weeks. No skin reactions indicative of sensitization were recorded after the challenge treatment.

Taking into account all available data on dialkyldimethylammonium chlorides for read-across, the closely structural related ditallowalkyldimethylammonium chloride (DTDMAC) is not considered a skin sensitiser. This view is supported by negative results of Guinea pig studies and a human repeated insult patch test with structural closely related quaternary dialkyldimethylammonium compounds, which all have not shown reactions indicative of skin sensitizing properties.

Justification for classification or non-classification

Based on the results performed on the structural analogueDHTDMAC, no indications of significant skin sensitizing properties exists for the class of dialkyldimethylammonium chlorides. Based hereupon no classification as skin sensitizer is indicated for ditallowalkyldimethylammonium chloride (DTDMAC).