Tetraoctylammonium bromide

Endpoint summary

Description of key information

The skin sensitization potential of Tetraoctylammonium Bromide(14866-33-2)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 Tetraoctylammonium Bromide(14866-33-2)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-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

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:

guinea pig maximisation test

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

- Name of the test material: Tetraoctylammonium bromide
- IUPAC name: Tetraoctylammonium bromide
- Molecular formula: C32H68NBr
- Molecular weight: 546.8002 g/mol
- Smiles: CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC.[Br-]
- Inchi : 1S/C32H68N.BrH/c1-5-9-13-17-21-25-29-33(30-26-22-18-14-10-6-2,31-27-23-19-15-11-7-3)32-28-24-20-16-12-8-4;/h5-32H2,1-4H3;1H/q+1;/p-1
- Substance type: Organic
- Physical form: Solid powder (off white)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

No data available

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

No skin sensitization reaction was observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN2 OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 esters 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 >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR Ionic interaction OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates >> Tetraalkylammonium ions OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Esters of organic sulfonic or sulfuric esters OR Quaternary organic ammonium compounds by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Cl by Chemical elements

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.11

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 15.1

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of Tetraoctylammonium Bromide (14866-33-2)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 Tetraoctylammonium Bromide (14866-33-2) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of Tetraoctylammonium Bromide(14866-33-2)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 Tetraoctylammonium Bromide(14866-33-2)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Skin sensitization 

In different studies, Tetraoctylammonium Bromide(14866-33-2)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in mouse for target chemical, Tetraoctylammonium Bromide(14866-33-2)and its structurally similar read across substancesDow Corning 5700 (27668-52-6)andCetrimonium chloride (112-02-7)the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of Tetraoctylammonium Bromide(14866-33-2)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 Tetraoctylammonium Bromide(14866-33-2)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Also it is further Supported by experimental study conducted by NTRL (NATIONAL TECHNICAL INFORMATION SERVICE , OT50546181, 09/01/92) to evaluate the skin sensitizing potential of read across substance Dow Corning 5700 (27668-52-6) in human . Skin sensitization test was performed by using Human repeated insult patch test (HRIPT) using 2% concentration. The test solution was freshly prepared daily. Based on the above observation Dow Corning 5700 (27668-52-6) was determined to be not sensitizing.

Also it is further 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 Ethyl butyrate (105-54-4) 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.

 Thus based on the above predictions onTetraoctylammonium Bromide(14866-33-2) as well as its read across and applying weight of evidence, it can be concluded that Tetraoctylammonium Bromide(14866-33-2) is not a skin sensitizer.

Thus comparing the above studies with the criteria of CLP regulation, Tetraoctylammonium Bromide(14866-33-2)can be considered as not classified for skin sensitization.

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, Tetraoctylammonium Bromide(14866-33-2)can be considered as not classified for skin sensitization.