Dodecanenitrile

Endpoint summary

Description of key information

Skin sensitisation:

The skin sensitization potential of Dodecanenitrile (CAS No: 2437-25-4) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Dodecanenitrile (CAS No: 2437-25-4) was estimated to be not sensitizing to the skin of Dunkin-Hartley White guinea pigs. Based on the estimated result Dodecanenitrile (CAS No: 2437-25-4) failed to induce skin sensitisation effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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 version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): Dodecanenitrile
- Molecular formula: C12H23N
- Molecular weight: 181.321 g/mole
- Smiles notation: C(CCCCCC)CCCCC#N
- InChl: 1S/C12H23N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-11H2,1H3
- Substance type: Organic
- Physical state: colourless liquid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

No data available

Challenge controls:

No data available

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization 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 8 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 ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Cyano, aliphatic attach [-C#N] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Nitrile 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 Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases >> Pyrimidines and Purines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR SN2 OR SN2 >> Cyanoalkylation of proteins via the nucleophilic substitution at sp3-carbon atom of cyanohydrins OR SN2 >> Cyanoalkylation of proteins via the nucleophilic substitution at sp3-carbon atom of cyanohydrins >> Cyanohydrins OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Thiocyanate formation via the nucleophilic-type substitution at the disulfide bond of proteins and enzymes OR SN2 >> Thiocyanate formation via the nucleophilic-type substitution at the disulfide bond of proteins and enzymes >> Cyanohydrins by Protein binding by OASIS v1.4

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups (nested)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Alkyl halide by Organic Functional groups (nested)

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.305

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.62

Interpretation of results:

other: not sensitising

Conclusions:

The substance Dodecanenitrile (CAS No: 2437-25-4) was estimated to be not sensitizing to the skin of Dunkin-Hartley White guinea pigs. Based on the estimated result Dodecanenitrile (CAS No: 2437-25-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of Dodecanenitrile (CAS No: 2437-25-4) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Dodecanenitrile (CAS No: 2437-25-4) was estimated to be not sensitizing to the skin of Dunkin-Hartley White guinea pigs. Based on the estimated result Dodecanenitrile (CAS No: 2437-25-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemicalDodecanenitrile (CAS No: 2437-25-4) to observe the potential for skin sensitisation to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical Dodecanenitrile (CAS No: 2437-25-4) and its closest read across substance using log Pow as the primary descriptor 2,2'-Azobis(isobutyronitrile) (CAS No: 78 -67 -1) and 2,2'-Azobis(2 -methylbutyronitrile) (CAS No: 13472 -08 -7). The predicted data using the OECD QSAR toolbox and Danish QSAR database has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of Dodecanenitrile (CAS No: 2437-25-4) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Dodecanenitrile (CAS No: 2437-25-4) was estimated to be not sensitizing to the skin of Dunkin-Hartley White guinea pigs. Based on the estimated result Dodecanenitrile (CAS No: 2437-25-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

According to Danish QSAR database, the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Dodecanenitrile (CAS No: 2437-25-4)(CAS No: 98 -97 -5). Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, Dodecanenitrile (CAS No: 2437-25-4) was considered to be not sensitizing.

 

The OECD SIDS -United Nations Environmental Programme (UNEP, 1999) reported The Guinea pig maximisation test on Dunkin-Hartley guinea pigs for readacross substance 2,2'-Azobis(isobutyronitrile)(CAS No: 78-67-1) in accordance with OECD Guideline No. 406 and EC Guideline 92/69/E.E.C., B6. In the induction, each guinea pigs received 0.1 % in paraffin oil or the vehicle was injected intradermaly in the dorsal region between the shoulders on day 1. On day 7, the same region received a topical application of sodium lauryl sulfate in vaseline in order to induce local irritation. On day 8, topical application of undiluted substance (500 mg) or the vehicle to this same site was performed with an occlusive dressing for 48 hours. Animals were challenged after rest period of 12 days, by a topical application of undiluted substance (500 mg) and the vehicle to the right and the left flank, respectively. This application was held for 24 hours with an occlusive, hypoallergenic dressing. Skin reaction was evaluated approximately 24 and 48 hours after challenge application. Since none of the treated guinea pigs showed any sign of skin sensitization reaction, the chemical2,2'-Azobis(isobutyronitrile)(CAS No: 78-67-1) wasconsidered to be not sensitizing to theskin of on Dunkin-Hartley guinea pigs.

 

The above results were further supported by the Dermal Sensitization test for the readacross substance 2,2'-Azobis(2-methylbutyronitrile) (CAS No: 13472-08-7) on Duncan Hartley guinea pigs performed by U. S. Environmental Protection Agency (EPA) Office of Pollution Prevention and Toxics (OPPT) Risk Assessment Division (RAD) ;2002.The induction phase for sensitization consisted of a series of 4 sacral intradermal injections of 0.1 mL of a 1.0%2,2'-Azobis(2-methylbutyronitrile)suspension in dimethyl phthalate (DMP), 1 each week. After a 13-day rest period, the test guinea pigs were challenged for sensitization by applying and lightly rubbing in 0.05 mL of an 80% and an 8% suspension of the test substance in DMP on shaved intact shoulder skin. At the same time 10 unexposed guinea pigs (controls) of the same age received identical topical application. Reactions were observed at 24 and 48 hours.None of the test guinea pigs showed a sensitization response. Hence the chemical 2,2'-Azobis(2-methylbutyronitrile) (CAS No: 13472-08-7) wasconsidered to be not sensitizing to theskin of Duncan Hartley guinea pigs.

 

Thus on the basis of available data for thetarget chemical Dodecanenitrile (CAS No: 2437-25-4) and its closest read across substance using log Pow as the primary descriptor 2,2'-Azobis(isobutyronitrile)(CAS No: 78-67-1) and 2,2'-Azobis(2-methylbutyronitrile) (CAS No: 13472-08-7),it can be concluded thatchemical Dodecanenitrile (CAS No: 2437-25-4) is unable to cause skin sensitization and considered as non skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance Dodecanenitrile (CAS No: 2437-25-4) and its closest read across substance using log Pow as the primary descriptor 2,2'-Azobis(isobutyronitrile) (CAS No: 78-67-1) and 2,2'-Azobis(2-methylbutyronitrile) (CAS No: 13472-08-7) were observed in various studies. From the results obtained from these studies it is concluded that the chemical Dodecanenitrile (CAS No: 2437-25-4) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.