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Description of key information

The skin sensitization potential of Butyl 12-acetoxyoctadec-9-enoate (140-04-5) 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. Butyl 12-acetoxyoctadec-9-enoate(140-04-5) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
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:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Specific details on test material used for the study:
- Name of test material (as cited in study report): butyl 12-acetoxyoctadec-9-enoate
- Molecular formula: C24H44O4
- Molecular weight: 396.6076 g/mol
- Smiles notation: CCCCCC[C@H](C\C=C/CCCCCCCC(=O)OCCCC)OC(=O)C
- InChl : 1S/C24H44O4/c1-4-6-8-15-18-23(28-22(3)25)19-16-13-11-9-10-12-14-17-20-24(26)27-21-7-5-2/h13,16,23H,4-12,14-15,17-21H2,1-3H3/b16-13-/t23-/m1/s1
- Substance type: Organic
- Physical state: Liquid
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lebeau breeding centre, Gambais, France
- Age at study initiation: approx. 5 weeks
- Weight at study initiation: male mean 436 g, female mean 423 g
- Housing: individual housing in polycarbonate cages
- Diet: guinea pigs sustenance ref. 106 (U.A.R., Villemoisson-sur-Orge, France), ad libitum
- Water: tap water, ad libitum
- Acclimation period: for a minimal period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
25% at intradermal induction, 100% at epidermal induction
Day(s)/duration:
48 hour
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50%
Day(s)/duration:
48 hour
No. of animals per dose:
Treatment group: 20 (10 males and 10 females)
Control group: 10 (5 males and 5 females)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Intradermal induction on day 1. On day 7 a local irritation was induced using 0.5 mL of a 10 % sodium laurylsulphate in vaseline. On day 8 a epidermal induction was performed with 0.5 mL vehicle or 0.5 mL test substance. The dermal applications were held in place for 48 hours under occlusive dressing.
- Test groups: 20 animals treated with test substance
- Control group: 10 animals treated with vehicle only
- Site: the scapular region of both sides
- Concentrations: 0.1 mL of 25% dilution of the test substance in paraffin oil in the presence of Freund' adjuvant was used for intradermal induction and 0.5 mL of the undiluted (100%) test substance was used for epidermal induction.
- Duration: 10 days

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 12 days after the last induction treatment
- Exposure period: 24 h under occlusive dressing
- Test groups: 20 animals treated with test substance
- Control group: 10 animals treated analogous to the test groups
- Site: the right flank was treated with the test substance; the left flank was treated with vehicle.
- Concentrations: 0.5 mL of a 50% solution in paraffin oil
- Evaluation (hr after challenge): 48 h after removal of the dressing
Challenge controls:
Yes
Positive control substance(s):
no
Statistics:
No data available.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No sensitization effect was observed.
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 6 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 ("j" and ( not "k") )  )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acetoxy AND Alkene AND Allyl AND Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Allyl AND Carboxylic acid ester 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] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Carbonyl, aliphatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester 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 OECD

Domain logical expression index: "f"

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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> Alicyclic ketones by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Salicylates by rtER Expert System ver.1 - USEPA

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.27

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 15.4

Interpretation of results:
other: Non sensitizer
Conclusions:
The skin sensitization potential of Butyl 12-acetoxyoctadec-9-enoate (140-04-5) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Butyl 12-acetoxyoctadec-9-enoate(140-04-5) was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pig.
Executive summary:

The skin sensitization potential of Butyl 12-acetoxyoctadec-9-enoate (140-04-5) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Butyl 12-acetoxyoctadec-9-enoate(140-04-5) was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pig.

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

Skin sensitization

In different studies, Butyl 12-acetoxyoctadec-9-enoate (140-04-5) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea pig for target chemical disodium Butyl 12-acetoxyoctadec-9-enoate (140-04-5) and its structurally similar read across substances Dodeca-1,3-dien-1-yl acetate (54364-62-4)andMethyllaurate (111-82-0). The predicted data using the OECD QSAR toolbox and DANISH QSAR have also been compared with the experimental data of read across.

The skin sensitization potential of Butyl 12-acetoxyoctadec-9-enoate (140-04-5) 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. Butyl 12-acetoxyoctadec-9-enoate(140-04-5) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

Another Prediction done by Danish QSAR (2017), to evaluate the skin sensitization potential of Butyl 12-acetoxyoctadec-9-enoate(140-04-5) .Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for Butyl 12-acetoxyoctadec-9-enoate(140-04-5) estimated to be not sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted byEuropean Food Safety Authority (EFSA, DAR, 2008) on structurally similar read across substance Dodeca-1,3-dien-1-yl acetate (54364-62-4)on guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. The skin sensitization study of Dodeca-1,3-dien-1-yl acetatewas performed  by Guinea pig maximization test using Pirbright white , DunkinHartley HOE DHPK (SPF-LAC)BO guinea pig .In induction phase , intradermal injection :0.1ml FCA , 5% test substance in olive oil DAB9 and test substance formulation in FCA were used ,after 24hr reading was noted .after one week epicutaneous application of 0.3 g of test substance ( 75% test substance in olive oil DAB 9)was applied for 48 hr as occlusive patch. Reading noted after 48 hr.In challenge phase, 21 days after intradermal injection0.15 g test substance formulation(50%test substance in vehicle) was applied at two different site for a period of 24hr .reading were performed after 24 and 48hr after removal of patch . No sensitization was observed.In addition, 13/20 animals showed very slight oedema. From above finding it is considered that Dodeca-1,3-dien-1-yl acetate was  considered to be not sensitizing in guinea pig.

It is further supported by an experimental study conducted  by Mr. Takashi Ikeda, (SIDS Initial Assessment Report for CoCAM ,2013)on structurally similar read across substance Methyllaurate (111-82-0)on guinea pigs.The skin sensitization study of Methyllauratewas performed in Dunkin-Hartley guinea pig by Guinea pig maximization test.In induction phase, intradermal injection of 50% dilution of test substance was given, after that for epidermal induction100% test substance concentration used. In challenge phase, 20% concentration of test substance used for application result was observed after 24hr and 48hr. No skin sensitization reaction was observed in 10 test animals. Hence it is concluded that Methyllaurate (111 -82 -0) was negative skin sensitizer in guinea pig.

.

Thus based on the above predictions on Butyl 12-acetoxyoctadec-9-enoate (140-04-5) as well as its read across substances and applying weight of evidence, it can be concluded that Butyl 12-acetoxyoctadec-9-enoate is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Butyl 12-acetoxyoctadec-9-enoate (140-04-5) can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, Butyl 12-acetoxyoctadec-9-enoate (140-04-5) can be considered as not classified for skin sensitization effects.