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Description of key information

The skin sensitization potential ofN,N,N-triethylethanaminium chloride (56-34-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substancesN,N,N-triethylethanaminium chloride (56-34-8)was predicted to be not sensitizing to the skin of female CBA mouse.

 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached.
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4, 2017
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Justification for non-LLNA method:
No data available
Specific details on test material used for the study:
- Name of the test material: N,N,N-triethylethanaminium chloride
- IUPAC name: N,N,N-triethylethanaminium chloride
- Molecular formula: C8H20NCl
- Molecular Weight: 165.706 g/mol
- Substance type: Organic
- Smiles: [N+](CC)(CC)(CC)CC.[ClH-]
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
No data available
Vehicle:
propylene glycol
Concentration:
No data available
No. of animals per dose:
No data available
Details on study design:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Parameter:
SI
Value:
> 1.5
Remarks on result:
other: No skin sensitization reaction was observed
Cellular proliferation data / Observations:
No data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Ammonium salt by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Ammonium salt AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Nitrogen, single bonds  [N{v+5}] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion AND Cation AND Quaternary ammonium salt by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.4

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -6.88

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.25

Interpretation of results:
other: not sensitizing
Conclusions:
The skin sensitization potential of N,N,N-triethylethanaminium chloride (56-34-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances N,N,N-triethylethanaminium chloride (56-34-8) was predicted to be not sensitizing to the skin of female CBA mouse.

Executive summary:

The skin sensitization potential of N,N,N-triethylethanaminium chloride (56-34-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substancesN,N,N-triethylethanaminium chloride (56-34-8)was predicted to be not sensitizing to the skin of female CBA mouse.

 

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

Skin sensitization 

In different studies, N,N,N-triethylethanaminium chloride (56-34-8)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and mouse for target chemical N,N,N-triethylethanaminium chloride (56-34-8) and its structurally similar read across substancesCetrimonium chloride(112-02-7)andTriethylamine(121-44-8) the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of N,N,N-triethylethanaminium chloride (56-34-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances N,N,N-triethylethanaminium chloride (56-34-8)was predicted to be not sensitizing to the skin of female CBA mouse.

Supported by experimental study conducted by European Commission (Opinion on alkyl (C16, C18, C22) trimethylammonium chloride, non-preservative uses, SCCP,2007) to evaluate the skin sensitizing potential of read across substance Cetrimonium chloride(112-02-7)in guinea pig . The skin sensitization study of Cetrimonium chloride(112-02-7) was performed by Buehler test using 30 female Pirbright albino guinea pigs in treated group and 10 in control group. Doses were selected on the bases of preliminary study using 6 animals.In induction phase, induction given on day 1, using 4 % concentration in water by topical application as2 x 2 cm cellulose patch to the clipped skin of the left flank. The patch was covered with an occlusive dressing for 6 hours and removed afterwards.The second induction given on day 8 and third on day 15 using same procedure on day first. During the induction phase, the skin sites were examined for local effects 24 hours after each treatment. In challenge phase, on day 29 test substance 1% concentration in same vehicle applied on a 2 x 2 cm patch to the clipped skin of the right flank and covered with an occlusive dressing for 6 hour and evaluated 24 and 48hr after removal of occlusive dressing .All animals were observed daily for signs of systemic toxicity. Body weights were recorded on days 1 and 31.No skin sensitizing reaction observed after challenge applications no clinical effects were observed. Body weight development of the treated group was not different from that of the control group. During the induction phase, treated animals showed slight to well-defined erythema and very slight oedema at the treated skin area. After challenge, skin reactions were observed neither in the treated group nor in the control group. Hence the Cetrimonium chloride(112-02-7)was considered to be not skin sensitizing in guinea pig.

 Also it is further Supported by experimental study conducted by NTRL (NTRL report, OTS0515586,1987)to evaluate the skin sensitizing potential of read across substance Triethylamine(121-44-8) in guinea pig . The skin sensitization study of Triethylamine(121-44-8) was performed by Guinea pig maximisation test in 20male albino guinea pigs.. In induction phase, induction given using 0.1 % concentration in 0.75% saline in deionised water by intradermal route for 8 times. In challenge phase, test substance 0.1% concentration in same vehicle used given 3 weeks after last induction. No skin sensitizing reaction observed after challenge application while 8 animals died as they were not particularly healthy. Hence Triethylamine(121-44-8)was considered to be not skin sensitizing in guinea pig by Guinea pig maximisation test.

 

Thus based on the above predictions on N,N,N-triethylethanaminium chloride (56-34-8) as well as its read across and applying weight of evidence, it can be concluded that N,N,N-triethylethanaminium chloride (56-34-8) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, N,N,N-triethylethanaminium chloride (56-34-8)can be considered as not classified for skin sensitization.

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, N,N,N-triethylethanaminium chloride (56-34-8)can be considered as not classified for skin sensitization.