N,N,4-trimethylpiperazine-1-ethylamine

Endpoint summary

Description of key information

No in vitro or in vivo skin sensitisation study with the test substance is required, as the substance is demonstrated to be corrosive to the skin. The results of skin sensitization studies with structurally similar substances are taken into account to predict the skin sensitization potential of the test substance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

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 skin corrosion (Category 1, 1A, 1B or 1C)

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

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 skin corrosion (Category 1, 1A, 1B or 1C)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

The skin sensitization potential and hazard classification for the test substance is predicted based on the results from skin sensitisation studies of structural similar substances (piperazine, aminoethylpiperazine and 1,4-dimethylpiperazine).

Three substances can be considered in supporting evidence based on their structural similarities to the test substance and the availability of data from human or animal studies: piperazine, 2 -piperazin-1 -ylethylamine (aminoethylpiperazine) and 1,4 -dimethylpiperazine. Piperazine has a structural alert of skin sensitisation which is a (di)ethylenediamine structure, while dimethylpiperazine has a N-methylated piperazine structure. Aminoethylpiperazine is a N-aminoethyl substituted piperazine, while the test substance could be considered as the N-methylate of aminoethylpiperazine. Ethylenediamine/diethylenediamine is a known structural alert of skin sensitization. Piperazine (diethylenediamine) is a skin sensitiser predicted by the guinea pig maximization test (GPMT) and human patch test. The skin sensitization potential of aminoethylpiperazine is also anticipated because not every nitrogen atom is alkylated to be tertiary amine, and the skin sensitisation potential of aminoethylpiperazine is confirmed by a GPMT study. However, results of a GPMT study for dimethylpiperazine show it is not a skin sensitiser. This suggests that N-alkylation of the ethylenediamine/diethylenediamine structure to be tertiary amine(s) significantly influence the skin sensitisation tendency. N-alkylation changes the typical structure of ethylenediamine/diethylenediamine to be tertiary amine(s) and eliminates the skin sensitisation potential. The test substances, dimethylpiperazine, aminoethylpiperazine and piperazine are corrosive to rabbit skin in animal studies. If a compound is shown to be corrosive to skin, skin sensitization tests are typically not considered relevant as corrosive effects will occur before dermal sensitization effects are induced.

Following the hypothesis that the alkylation of both nitrogen atoms in the 6 -member ring of piperazine/in the ethylenediamine structure eliminates the skin sensitization potential and based on the skin sensitisation behavior of 1,4 -dimethylpiperazine, the test substance is predicted not to be a skin sensitiser based on structural similarities to dimethylpiperazine. Hence, the test substance is considered not to be classified as skin sensitiser.

References:

- Leung HW et al (1997) Evaluation of skin sensitization and cross-reaction of nine alkyleneamines in the guinea pig maximization test. J Toxicol.-Cut and Ocular Toxicol 16(3) 189 -195

- Holness and Nethercott (1997) Results of patch testing with a special series of rubber allergens. Contact Dermatitis 36,207 -211

- Thorgeirsson A (1978) Sensitisation capacity of epoxy resin hardeners in the guinea pig. Acta Derm Venereol 58(4) 332 -336

- BASF-AG (1998) Report: 1,4 -dimethylpiperazin-Maximisation Test in guinea pigs. unpublished data. Testing laboratory: BASF AG, Department of Toxicology. Report no.: 30H0019/962217. Owner company: BASF SE. Report date: 1998 -04 -08

- Armondi SE (1990) Delayed contact hypersensitivity in guinea pigs. Testing laboratory: Pharmakon Research International, Inc., Averly, Pennsylvania 18741. Report no.: PH 424 -TX-002 -90. Owner company: Huntsman. Report date: 1990 -11 -30

- Li H (2019) Prediction of Skin Sensitization Potential and Hazard Classification for JEFFCAT(R) TAP. Internal document

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance is considered not to be classified as skin sensitizer, based on the available results with the structurally related substances and according to the CLP Regulation.