Alcohols, C13-15

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Alcohols, C13-15 was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Alcohols, C13-15 was predicted to be not sensitizing to the skin of male/female Hartley guinea pigs.

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:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Type of study:

Buehler test

Specific details on test material used for the study:

- Name of test material: Alcohols, C13-15
- IUPAC name: Alcohols, C13-15
- Molecular formula: C13H280 + C15H32O
- Molecular weight: 208.78 g/mole
- Substance type: Organic
- Physical state: Liquid

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

5

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions 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 highest mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" )  and "c" )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and "h" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Long chain alcohols by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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: "e"

Referential boundary: The target chemical should be classified as Ethylenglycolethers OR Halogenated alkanes  OR Ketones OR Primary and secondary aliphatic amines OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.11

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.74

Interpretation of results:

other: Negative

Conclusions:

Alcohols, C13-15 was predicted to be not sensitizing to the skin of male/female Hartley guinea pigs.

Executive summary:

The skin sensitization potential of Alcohols, C13-15 was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Alcohols, C13-15 was predicted to be not sensitizing to the skin of male/female Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Several studies were performed to ascertain the extent of dermal sensitization caused by Alcohols, C13-15in living organisms. These studies include in vivo studies in guinea pigs as well as predicted data for the target chemical as well its structurally similar read across chemicals, Dodecan-1-ol [CAS: 112-53-8], Undecan-1-ol (CAS No: CAS no: 112-42-5), Cetyl alcohol[CAS: 36653-82-4]. Thepredicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Alcohols, C13-15 was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Alcohols, C13-15 was predicted to be not sensitizing to the skin of male/female Hartley guinea pigs.

An Open Epicutaneous Test (OET) was performed by G. Klecak (Curr. Probl. Derm., vo1.14, pp.152-171 (Karger, Basel 1985)) was performed on guinea pigs to assess the skin sensitization potential of the structurally similar read across chemical,Dodecan-1-ol [CAS: 112-53-8]. The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4 %.

On day 1 during induction, 0.1 ml of the Dodecan-1-ol (CAS No: 112-53-8) was applied at concentrations of 4 % in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week.

To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 4%.Thus, Dodecan-1-ol (CAS No: 112-53-8) was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).

These results are supported by a Draize test performed by G. Klecak et.al [Journal of the Society of Cosmetic Chemists, Vol. 28, No. 2, 53-64; 1977] on Himalayan white-spotted guinea pigs (male and female) to determine the skin sensitization potential of the structurally similar read across chemical, Undecan-1-ol[CAS: 112-42-5]. 6-8 Himalayan white-spotted guinea pigs (male and female) received a dose of 0.05 ml of a 0.1 % solution of the chemical tested in isotonic saline intradermally on day 0 and further doses of 0.1 ml each were injected on 9 alternate days (total dose = 0.95 mg). The treated animals and untreated controls were challenged intradermally with 0.05 ml of a 0.1 per cent solution on days 35 and 49. The evaluation criterion was the mean diameter of the popular reactions.

None of the treated animals showed positive skin reactions. Hence, Undecan-1-ol (CAS no: 112-42-5) was considered to be not sensitizing to the skin of Himalayan white-spotted guinea pigs.

The above results are supported by Patch tests performed by Antonella Tosti et.al [Contact Dermatitis, 1996, 35(5), 287-289] on humans to investigate the frequency of sensitization caused by the structurally similar read across chemical, cetyl alcohol[CAS: 36653-82-4].Department of Dermatology, University of Bologna patch tested a series of 5 fatty alcohols on 146 patients to investigate the frequency of sensitization caused by them.

These patients, who had previously been tested with GIRDCA Standard series, were selected because their clinical lesions or histories indicated topical preparations as the possible source of their contact dermatitis. 34 patients (25 female and 9 male) aged from 14 to 72 years showed a positive patch test to fatty alcohols, of which 33 to oleyl alcohol. 30% cetyl alcohol in petrolatum was patch tested by applying on the skin of the 34 patients for 2 days using Finn Chambers on Scanpor tape. The readings were made at days 2, 3 and 7.

Cetyl alcohol 30% in petrolatum did not cause any allergic reactions to skin of 34 human volunteers.

Hence, cetyl alcohol can be considered to be not skin sensitizer.

Based on the available data for the target chemical, structurally similar read across substances, Alcohols, C13-15 is not likely to cause any dermal sensitization. Hence, by applying the weight of evidence approach, Alcohols, C13-15 can be considered not sensitizing to skin and classified under the category “Not Classified” as per CLP criteria.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data forAlcohols, C13-15 indicates that it is not likely to cause any dermal sensitization to skin.

Alcohols, C13-15 can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.