Phenethyl isovalerate

Endpoint summary

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.3

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

not specified

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS- -Source: David Hall Ltd., Burton-on-Trent-Age at study initiation: 8 to 12 weeks- Weight at study initiation: 303 to 395 g- Housing: Singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.- Diet: ad libitum (Guinea pig FD1 Diet, Special Diets Ltd., Essex)- Water: Mains tap water ad libitum- Acclimation period: At least five daysENVIRONMENTAL CONDITIONS- Temperature (°C): 17 to 23 °C- Humidity (%): 30 to 70 %- Air changes (per hr): Approximately 15- Photoperiod (hrs dark / hrs light): 12 hours continuous light, 12 hours continuous darkness.

Route:

intradermal and epicutaneous

Route:

epicutaneous, occlusive

No. of animals per dose:

10 in the control group, 20 in the test group

Positive control substance(s):

yes

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Clinical observations:

Not sensitizing

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Clinical observations: Not sensitizing.

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" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] 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<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester 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 Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl esters  OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  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 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 >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  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 v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S by Chemical elements

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 Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "m"

Similarity boundary:Target: CC(C)CC(=O)OCCc1ccccc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Hydroquinones by Respiratory sensitisation

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.49

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Interpretation of results:

not sensitising

Remarks:

Migrated informationNon sensitizerCriteria used for interpretation of results: EU

Conclusions:

The test chemical Phenethyl isovalerate is not a skin sensitizer.

Executive summary:

Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guinea pigs. The test chemical Phenyethyl isovalerate is not a skin sensitizer.

As per CLP classification, the test material is not likely to classify as a skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Prediction model based estimation of skin sensitization is used to estimate the skin sensitizing nature of the test chemical Phenethyl isovalerate (CAS no 140 -26 -1). The summary is as mentioned below:

Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guinea pigs. The test chemical Phenyethyl isovalerate is not a skin sensitizer. As per CLP classification, the test material is not likely to classify as a skin sensitizer.

           

Based on the QSAR prediction done using the Danish (Q)SAR Database (2016), the skin sensitization was estimated to be negative on guinea pig and human .Thus it can be concluded that the substance Phenethyl isovalerate has negative skin sensitization effects and based on the CLP criteria for classification it can be classified as non skin sensitizer.

In skin sensitization study, maximization test was carried out on 26 volunteers (Burdock Group, 1979). The test chemical was tested at a concentration of 2% in petrolatum and produced no sensitization reactions. Based on the above value the test material does not classify as an skin sensitizer.

In another study by (Opdyke, D. L. J., 1975) with similar substance (102 -20 -5) was observed in human by maximization test. A maximization test was carried out on 25 volunteers. Phenethyl phenylacetate was tested at a concentration of 2% in petrolatum and produced no sensitization reactions. Hence Phenethyl phenylacetate is not likely to exhibit sensitization effect on the skin of humans.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance Phenylethyl isovalerate can be considered as “not sensitizing” to the skin, in accordance with the CLP criteria

Justification for selection of skin sensitisation endpoint:
Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guinea pigs. The test chemical Phenyethyl isovalerate is not a skin sensitizer. As per CLP classification, the test material is not likely to classify as a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

As per CLP classification, Phenyethyl isovalerate is not likely to classify as a skin sensitizer.