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Description of key information

Skin irritation

An OECD guideline 439 test concluded that 4 -PhenoxyPhenol is classified as irritating or corrosive to skin due to the absence of information on a skin corrosion test.

The result of the OECD QSAR Toolbox (read-across approach) indicates that 4 -Phenoxyphenol is predicted as not irritating/ corrosive.

Consequently, 4 -Phenoxyphenol is considered as not corrosive and the final result of the OECD guideline n°439 test is irritant. 4 -Phenoxyphenol is classified as skin irritant (H315).

This classification is confirmed by the results of the OECD guideline n°429 (LLNA) and n°402 (Acute Toxicity Dermal) which indicate:

- 4 -Phenoxyphenol has to be considered as not excessively irritant at 60% (OECD n°429)

- no corrosive/ irritant effect has been observed (OECD n°402)

Eye irritation

QSAR Toolbox 4.2 predicted that 4 -Phenoxyphenol has a MMAS (Modified Maximum Average Score) equal of 37.6. From some of the statistical analyses (ECETOC TRA, Report n°48 - June 1998), all the substances that have a MMAS range between 30-40 are classified H319 (irritating to eyes).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: n°batch 20180328
- Expiration date of the lot/batch: March 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Reactivity of the test substance with MTT : Yes (no direct interaction and there is no need to add non-specific coloration controls to the study)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: SkinEthic RHE® model
Details on test system:
Test model :
- Source: EPISKIN - reconstructed human epidermis - supplied by SkinEthic Laboratories, Nice, France
- batch: 18-RHE-060
- Received : 05 June 2018
- Maintenance medium : Episkin SA, batch No. 18 SMM 021
- Quality control : histological observation, cell viability and barrier fucton integrity test
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- 3 replicates

NEGATIVE CONTROL
- 3 replicates

POSITIVE CONTROL
- 3 replicates

REMOVAL OF TEST SUBSTANCE
- Washing: Yes with 25 x 1 mL of DPBS (Dutscher - Batch No. 9120318).
- Time after start of exposure: 42 minutes

OBSERVATION
The cell viability was quantified by measurement of the cell succinate dehydrogenase activity
The measured Optical Density (OD), after extraction from tissues, are proportional to the number of living cells.

SCORING SYSTEM:
For each tissue, OD values and calculated percentage cell viability data for the test item, positive and negative controls,
Duration of treatment / exposure:
42 minutes
Duration of post-treatment incubation (if applicable):
42 hoours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Value:
ca. 2.1
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
1.7%
Remarks on result:
positive indication of irritation
Remarks:
mean score from three replicates

Assessment of the skin irritation – individual and average values of OD after 42 minutes exposure

 

Application: 16 mg of the test item on 0.50 cm² human skin model

 

 

OD

Mean OD/ disc

Mean OD/ product

Viability %

Mean Viability %

SD viability

Conclusion

Negative control

1

0.646

0.598

108.0

100

7.0

7.0

-

2

0.573

95.8

3

0.575

96.2

Positive control

1

0.010

0.010

1.7

1.7

0.1

0.1

Irritant

2

0.011

1.8

3

0.010

1.7

Test item

1

0.010

0.012

1.7

2.1

0.4

0.4

Irritant or corrosive

2

0.015

2.5

3

0.012

2.0

Interpretation of results:
other: Irritant or corrosive
Conclusions:
The mean percent viability of the treated tissues was 2.1%, versus 1.7% in the positive control (5% Sodium Dodecyl Sulfate).
In accordance with the Regulation EC No. 1272/2008 and in absence of information on skin corrosion, the test item Paraphenoxyphenol has to be classified in Category 2 “Irritating to skin” or in Category 1 “Corrosive”.
Executive summary:

In accordance with the OECD guideline n°439, the test item Paraphenoxyphenol was applied as supplied, during 42 minutes, at the dose of 16 mg, to 3 living Reconstructed Human epidermis (SkinEthic RHE® model) previously moistened with 10 μL of distilled water. The application was followed by a rinse with 25 mL of DPBS and a 42 hours post-incubation period at 37°C, 5% CO2. Cell viability was then measured by enzymatic conversion of the vital dye MTT into a blue formazan salt that was quantitatively measured after extraction from tissues.

The mean percent viability of the treated tissues was 2.1%, versus 1.7% in the positive control (5% Sodium Dodecyl Sulfate).

In accordance with the Regulation EC No. 1272/2008 and in absence of information on skin corrosion, the test item Paraphenoxyphenol has to be classified in Category 2 “Irritating to skin” or in Category 1 “Corrosive”.

Endpoint:
skin irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
supporting study
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:
1. SOFTWARE and Model
OECD QSAR ToolBox 4.2

2. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : O(c(ccc(O)c1)c1)c(cccc2)c2
NAME : Phenol, 4-phenoxy-
CAS Number : 831-82-3

3. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL AND APPLCABILITY DOMAIN
See https://www.qsartoolbox.org/

4. ADEQUACY OF THE RESULT
See "QPRF_Classification-Skin-Irritation_PhenoxyPhenol-ToolBow_V1" in attached justification
Guideline:
other: REACH guidance on QSARs R.6
GLP compliance:
no
Specific details on test material used for the study:
SMILES : O(c(ccc(O)c1)c1)c(cccc2)c2
Irritation parameter:
other: Classification
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Not irritating

Based on the OECD QSAR Toolbox (read-across approach), 4-Phenoxyphenol is predicted as not irritating.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the OECD QSAR Toolbox (read-across approach), 4-Phenoxyphenol is predicted as not irritating.
Executive summary:

Based on the OECD QSAR Toolbox (read-across approach), 4-Phenoxyphenol is predicted as not irritating.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
key study
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 adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE and Model
OECD QSAR ToolBox 4.2

2. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : O(c(ccc(O)c1)c1)c(cccc2)c2
NAME : Phenol, 4-phenoxy-
CAS Number : 831-82-3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL AND APPLCABILITY DOMAIN
See https://www.qsartoolbox.org/

5. ADEQUACY OF THE RESULT
The MMAS value is used for the CLP classification after comparison with substances with the same MMAS range
Guideline:
other: REACH guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: QSAR Toolbox 4.2
- Model description: see field 'Justification for type of information"
- Justification of QSAR prediction: see field 'Attached justification'
GLP compliance:
no
Specific details on test material used for the study:
SMILES : O(c(ccc(O)c1)c1)c(cccc2)c2
Species:
rabbit
Irritation parameter:
other: MMAS
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 37.6
Remarks on result:
other: QSAR predicted value
Irritation parameter:
other: MMAS
Basis:
mean
Score:
> 14.1 - < 61.1
Remarks on result:
other: QSAR predicted value

QSAR Toolbox 4.2 predicted that 4 -Phenoxyphenol has a MMAS (Modified Maximum Average Score) equal of 37.6

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
QSAR Toolbox 4.2 predicted that 4 -Phenoxyphenol has a MMAS (Modified Maximum Average Score) equal of 37.6.
From some of the statistical analyses (ECETOC TRA, Report n°48 - June 1998), The MMAS were divided into three categories:
- MMAS <25; no/mild irritation
- 25≤ MMAS <59; moderate irritation
- MMAS ≥59; and strong irritant
And on the basis of ECETOC TRA, Report n°48, all the substances that have a MMAS range betwwen 30-40 are classified H319 (irritating to eyes).
4-Phenoxyphenol is a moderate irritant classified H319 (Category 2 - Irritating to eyes)
Executive summary:

QSAR Toolbox 4.2 predicted that 4 -Phenoxyphenol has a MMAS (Modified Maximum Average Score) equal of 37.6.

From some of the statistical analyses (ECETOC TRA, Report n°48 - June 1998), The MMAS were divided  into  three  categories:  

  • MMAS <25; no/mild  irritation
  • 25≤ MMAS <59; moderate irritation
  • MMAS ≥59; and strong irritant

And on the basis of ECETOC TRA, Report n°48, all the substances that have a MMAS range betwwen 30-40 are classified H319 (irritating to eyes).

4-Phenoxyphenol is a moderate irritant classified H319 (Category 2 - Irritating to eyes)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a conservative approach since no data is available for the respiratory tract and since

  • the substance is classified irritant for skin and for eyes,
  • and, due to their size, the particle can deposit in the respiratory tract

the classification STOT SE Cat. 3, H335 (May cause respiratory irritation) is proposed.

Justification for classification or non-classification

On the basis of the key studies, 4 -phenoxyphenol has be classified, according to the CLP regulation :

  • Skin irritation (Skin Irrit. Cat. 2, H315 - causes skin irritation)
  • Eye irritation (Eye irritation Cat. 2, H319 - causes eye irritation)
  • Specific Target Organ Toxicity (STOT SE Cat. 3, H335 - May cause respiratory irritation)