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Description of key information

The skin sensitization potential of Aluminum trioctadecanoate (637-12-7) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Aluminum trioctadecanoate (637-12-7)) was predicted to be non sensitizing to the skin of male and femaleHartleyguinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 QSAR toolbox version 3.3.and the QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3.
GLP compliance:
not specified
Type of study:
Buehler test
Specific details on test material used for the study:
- Name of test material (as cited in study report):Aluminium tristearate- Molecular formula : C18H36O2.1/3Al- Molecular weight: 877.3995 g/mol- Substance type: Organic- Physical state: Solid
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hilltop Lab Animals, Inc., Scottdale, PA.- Animal husbandry was based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.- Age at study initiation: Males ~ 6 weeks old, females ~ 8 weeks old.- Weight at study initiation: Males ~ 366-439 g, females ~ 319-380 g.- Housing: Individually in suspended stainless steel cages.- Diet (e.g. ad libitum): PMI Certified Guinea Pig Chow #5026 (Purina Mills, Inc.), provided ad libitum.- Water (e.g. ad libitum): Municipal tap water treated by reverse osmosis, provided ad libitum.- Acclimation period: At least 5 days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 60-77 ºF (16-25ºC).- Humidity (%): 23-49%.- Air changes (per hr): 10-15 air charges per hour.- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle.
Route:
epicutaneous, occlusive
Vehicle:
other: Mineral oil
Concentration / amount:
25%
Day(s)/duration:
24 hour
Route:
epicutaneous, occlusive
Vehicle:
other: Mineral oil
Concentration / amount:
25%
Day(s)/duration:
24 hour
No. of animals per dose:
20 animals
Details on study design:
No data available
Challenge controls:
yes
Positive control substance(s):
yes
Statistics:
No data available.
Reading:
other: Challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
Skin sensitization effect were observed in 6 out of 20 animals .
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 5 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 ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative 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.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds 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) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen 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 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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 OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift OR Enamine form OR Hydroxyazo form - 1,5-H shift OR Hydroxyazo form (fused rings) - 1,5-H shift OR Keto form (5-membered heteroarenes) - 1,3-H shift by Tautomers unstable

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Aromatic amines OR Phenols OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation at a carbonyl with a leaving group OR Acylation >> Direct acylation at a carbonyl with a leaving group >> Phenyl acetates OR Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines OR Pro-SN2 OR Pro-SN2 >> Pro-SN2 at chlorine OR Pro-SN2 >> Pro-SN2 at chlorine >> N-Phenylacetamides by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alpha, beta-Haloether Reactive Functional Groups OR Aromatic Amine Type Compounds OR Halogenated Aromatic Hydrocarbon Type Compounds OR Organophosphorus Type Compounds by Oncologic Primary Classification

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alpha aryloxy substituted acetic acid (9c) OR Arylethanamine-like derivatives (11a) OR Di-substituted hydrocarbons (24a) OR Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acidic [90,100] AND No pKb value by Ionization at pH = 9

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Basic [0,10) by Ionization at pH = 9

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as hours - days by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 15.6

Interpretation of results:
other: Negative
Conclusions:
The skin sensitization potential of Aluminum trioctadecanoate (637-12-7) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Aluminum trioctadecanoate (637-12-7)) was predicted to be non sensitizing to the skin of male and female Hartley guinea pig.
Executive summary:

The skin sensitization potential of Aluminum trioctadecanoate (637-12-7) was estimated by  using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Aluminum trioctadecanoate (637-12-7)) was predicted to be non sensitizing to the skin of male and female Hartley guinea pig.

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

Skin sensitization

In different studies, Aluminum trioctadecanoate (637-12-7) 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 Aluminum trioctadecanoate (637-12-7) and on human in its structurally similar read across substances zinc dioctadecanoate (557-05-1). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across substance.

The skin sensitization potential of Aluminum trioctadecanoate (637-12-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Aluminum trioctadecanoate (637-12-7)) was predicted to be non sensitizing to the skin of male and femaleHartleyguinea pig.

It is supported by experimental data conducted by American college of toxicology (Journal of the American College of Toxicology,1982) on structurally similar read across substance zinc dioctadecanoate  (557-05-1) on Human .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. Skin sensitization study for zinc dioctadecanoate  (557-05-1) was conducted on human.. In main test, one of the formulations was applied twice a day for 28 days to 52 female panelists. Each subject was then examined at baseline and one, two, three, and four weeks after application. “No sensitization potential was exhibited by the panelists using this product under conditions. Therefore zinc dioctadecanoate (557-05-1) was considered to be non sensitizing in human.

Thus based on the above predictions on Aluminum trioctadecanoate (637-12-7) as well as its read across substances and applying weight of evidence, it can be concluded that Aluminum trioctadecanoateis not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Aluminum trioctadecanoate (637-12-7) 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, Aluminum trioctadecanoate (637-12-7) can be considered as not classified for skin sensitization effects.

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