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Diss Factsheets

Administrative data

Description of key information

Key study was conducted byAnna Sonnenburg et al.(Arch Toxicol ,2015) to evaluate the skin sensitizing potential of target substance Isopropyl 4-hydroxybenzoate (4191-73-5) by in vitro experiment on humankeratinocytes.Isopropyl 4-hydroxybenzoate (4191-73-5) was assessed for its skin sensitizing potential by In-vitro method. For this purpose isloosefit coculturebased sensitization assay(LCSA)wasperformed using Human keratinocytes.Human keratinocytes were used for the study. 12-well cell culture plates were used for the cocultured of the cell. Substances were tested for three different DC-rc/KC-donor pairs to account for interindividual variability.Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. Substances were categorized as follows: half-maximal increase in CD86-expression

<12.5 μM: extreme;

 <50 μM: strong;

<100 μM: moderate;

>100 μM: weak.

The EC50 sensitization was found to be 157.84 μmol/l forIsopropyl 4-hydroxybenzoate.Therefore,Isopropyl 4-hydroxybenzoate (4191-73-5)) was considered to be sensitizing to human keratinocytes cells.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from publication.
Qualifier:
according to guideline
Guideline:
other: As mention below
Principles of method if other than guideline:
To evaluate the skin sensitizing potential of isopropyl 4-hydroxybenzoate in vitro method of loose-fit coculture-based sensitization assay(LCSA).
GLP compliance:
not specified
Type of study:
other: loose-fit coculture-based sensitization assay (LCSA)
Justification for non-LLNA method:
Not specified
Specific details on test material used for the study:
- Name of test material: Isopropyl p-hydroxybenzoate
- IUPAC name: isopropyl 4-hydroxybenzoate
- Molecular formula: C10H12O3
- Molecular weight: 180.202 g/mol
- Substance type: Organic
- Physical state: No data
Details on the study design:
Skin sensitisation (In vitro test system) - Loose-fit coculture-based sensitization assay
Keratinocytes were isolated from skin which was received as residual material from plastic surgery. Peripheral blood mononuclear cells were enriched from buffy coats by density centrifugation. Cells were cocultured in serum-free Keratinocyte growth medium 2 on 12-well cell culture plates. Increasing concentrations of test substances were tested until significant cytotoxicity or decreased solubility occurred.

Viability of cells was measured by 7-AAD staining. Each substance was tested with three different DC-rc/KC-donor pairs to account for interindividual variability

The LCSA is based on a co -culture of primary human keratinocytes and allogenic dendritic cell-related cells (DC-rc) which upregulate the expression of the maturation marker CD86 when incubated with sensitizers.
Positive control results:
At least 1.4-fold increase in CD86-expression compared to zero controls.
Key result
Run / experiment:
other: In Loose-fit coculture-based sensitization assay ,the EC50 value for test material was 157.84 μmol/l.
Parameter:
other: EC50
Remarks:
Substance concentration causing a half-maximal increase in CD86-expression
Value:
157.84
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Other effects / acceptance of results:
OTHER EFFECTS:
According to the study ,the EC50 value for test material was 157.84 μmol/l. which falls into the wekk category of skin sensitization .



ACCEPTANCE OF RESULTS:
- Acceptance criteria met for positive control: yes

For categorization of sensitizing potency, the substance concentration which led to a half-maximal increase in CD86-expression (EC50sens) was assessed. Substances

were categorized as follows: half-maximal increase in CD86-expression

<12.5 μM: extreme;

 <50 μM: strong;

<100 μM: moderate;

>100 μM: weak.

Substances failing to elicit significant rise in CD86-expression up to the maximum test concentration were deemed non-sensitizers.

Paraben

EC50sens/(μmol/l)

Categorya

Isopropyl

157.84

Weak

Interpretation of results:
other: sensitizing
Conclusions:
Isopropyl 4-hydroxybenzoate (4191-73-5) was observed for its skin sensitizing potential by Invitro method of loose-fit coculture-based sensitization assay (LCSA) .Isopropyl 4-hydroxybenzoate was considered to be sensitizing by Invitro method .
Executive summary:

Isopropyl 4-hydroxybenzoate (4191-73-5) was assessed for its skin sensitizing potential by In-vitro method. For this purpose isloosefit coculturebased sensitization assay(LCSA)was performed usingHuman keratinocytes.Human keratinocytes were used for the study. 12-well cell culture plates were used for the cocultured of the cell. Substances were tested for three different DC-rc/KC-donor pairs to account for interindividual variability.Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. Substances were categorized as follows: half-maximal increase in CD86-expression

<12.5 μM: extreme;

 <50 μM: strong;

<100 μM: moderate;

>100 μM: weak.

The EC50 sensitization was found to be 157.84 μmol/l forIsopropyl 4-hydroxybenzoate.Therefore,Isopropyl 4-hydroxybenzoate (4191-73-5)) was considered to be sensitizing to human keratinocytes cells.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Skin sensitization 

In different studies, Isopropyl 4-hydroxybenzoate (4191-73-5) has been investigated for potential of skin sensitization to a greater or lesser extent. The key study are based on in vitro experiment on humankeratinocytes. The supporting studies are based on predicted data of In vivo experiments in human and guinea pig for target chemical. The predicted data using the Danish QSAR has also been compared with the experimental data of target.

Key study was conducted byAnna Sonnenburg et al.(Arch Toxicol ,2015) to evaluate the skin sensitizing potential of target substance Isopropyl 4-hydroxybenzoate (4191-73-5) by in vitro experiment on humankeratinocytes.Isopropyl 4-hydroxybenzoate (4191-73-5) was assessed for its skin sensitizing potential by In-vitro method. For this purpose isloosefit coculturebased sensitization assay(LCSA)wasperformed using Human keratinocytes.Human keratinocytes were used for the study. 12-well cell culture plates were used for the cocultured of the cell. Substances were tested for three different DC-rc/KC-donor pairs to account for interindividual variability.Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. Substances were categorized as follows: half-maximal increase in CD86-expression

<12.5 μM: extreme;

 <50 μM: strong;

<100 μM: moderate;

>100 μM: weak.

The EC50 sensitization was found to be 157.84 μmol/l forIsopropyl 4-hydroxybenzoate.Therefore,Isopropyl 4-hydroxybenzoate (4191-73-5)) was considered to be sensitizing to human keratinocytes cells.

Another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be positive on guinea pig and human for, Isopropyl 4-hydroxybenzoate. Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for, Isopropyl 4-hydroxybenzoate (4191-73-5) estimated to be sensitizing when applied to human and guinea pig skin.

Thus based on the above key and supporting studies on Isopropyl 4-hydroxybenzoate (4191-73-5),it can be concluded thatIsopropyl 4-hydroxybenzoate (4191-73-5) is a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Isopropyl 4-hydroxybenzoate (4191-73-5) can be considered as ‘classified’ for skin sensitization.

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, Isopropyl 4-hydroxybenzoate (4191-73-5) can be considered as ‘classified’ for skin sensitization.