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Description of key information

The skin sensitization potential of 3-phenylpropanoic acid (501-52-0) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 3-phenylpropanoic acid (501-52-0) was predicted to be non sensitizing to the skin of Hartley guinea pig

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:
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
Justification for non-LLNA method:
Not specified.
Specific details on test material used for the study:
Name of the test chemical: 3-phenylpropanoic acid
Molecular weight: 150.176 g/mol
Molecular formula: C9H10O2
SMILES: c1(CCC(O)=O)ccccc1
Substance type: Organic
Physical State: Solid
Species:
guinea pig
Strain:
Hartley
Sex:
not specified
Details on test animals and environmental conditions:
No data available.
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal injection: 10%Topical induction: 20%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
20%
Day(s)/duration:
24 hour
No. of animals per dose:
Test group: 15
Control group: 6
Details on study design:
MAIN STUDYA.
INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 7 days and 14 days
- Test groups: 15 animals
- Control group: 6 animals
- Site: No data available
- Frequency of applications: on day 0 and 7
- Duration :No data available
:- Concentrations: 10% iteradermal,20% Epicutaneous

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 7 day
- Exposure period: 24 h
- Test groups: 15 animals
- Control group: 6 animals
- Site: Nalve Skin Site
- Concentrations: 20%
- Evaluation (hr after challenge):24
Challenge controls:
6 animals
Positive control substance(s):
not specified
Statistics:
No data available.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
No skin sensitization effect 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 5 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 "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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 Aromatic Carbon [C] 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: "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 Aromatic Carbon [C] 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 Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Organic disulfides OR Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.13

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.79

Interpretation of results:
other: not sensitising
Conclusions:
The skin sensitization potential of 3-phenylpropanoic acid (501-52-0) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 3-phenylpropanoic acid (501-52-0) was predicted to be non sensitizing to the skin of Hartley guinea pig.
Executive summary:

The skin sensitization potential of 3-phenylpropanoic acid (501-52-0) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 3-phenylpropanoic acid (501-52-0) was predicted to be non sensitizing to the skin of Hartley guinea pig.

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

Skin sensitization

In different studies, 3-phenylpropanoic acid (501-52-0) 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 and human for target chemical 3-phenylpropanoic acid (501-52-0) and its structurally similar read across substances in humans for Benzyl formate (104-57-4) andbenzyl butyrate (103-82-2). 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 3-phenylpropanoic acid (501-52-0) 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. 3-phenylpropanoic acid (501-52-0) was predicted to be non sensitizing to the skin of Hartley guinea pig.

Another Prediction done by Danish QSAR (2017), to evaluate the skin sensitization potential of 3-phenylpropanoic acid (501-52-0).Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 3-phenylpropanoic acid (501-52-0)estimated to be not sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted by D.L.J.Opdyke.(Food and Cosmetics Toxicology,1973) )on structurally similar read across substance Benzyl formate (104-57-4 ) onhumans .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 potential was evaluated for Benzyl formate in human. A maximization test was carried out on 25 humans at 10%Benzyl formate in petrolatum. The substance Benzyl formate is considered to be not sensitizing to human. Therefore Benzyl formate (104-57-4 ) was considered to be non sensitizing in human.

It is further supported by an experimental study conducted  by D. McGinty; C.S. Letizia; A.M. Api (Food and Chemical Toxicology, 2012)on structurally similar read across substancebenzyl butyrate (103-82-2)on humans .A maximization test for benzyl butyrate (103-82-2) was carried out on 25 healthy male patients with 4% (2760µg/cm2) in petrolatum. The test material was applied on the forearms of all 25 subjects for five alternate days for 48 h periods. The patch sites were pretreated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. After a 10 day rest period, challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was pretreated for 1 h with 10% SLS. The challenge site was evaluated at 48 and 72 hour. No sensitization reactions were observed. Therefore Benzyl butyrate was considered to be not sensitizing to the skin of humans.

Thus based on the above predictions on 3-phenylpropanoic acid (501-52-0) as well as its read across substances and applying weight of evidence, it can be concluded that 3-phenylpropanoic acid is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3-phenylpropanoic acid (501-52-0) 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, 3-phenylpropanoic acid (501-52-0) can be considered as not classified for skin sensitization effects.