4,4'-dihydroxybenzophenone

Endpoint summary

Description of key information

Skin irritation: the skin irritation potential of DHB- 4,4'-dihydroxybenzone phenone was assessed in vitro according to OECD Test Guideline 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method. After a 1h exposure on the surface of the EpiDermTM reconstructed human epidermis and a 42h post-exposure incubation time, viability of the tissues was assessed and compared to the negative control.

The percentage viability obtained was 97.3% and therefore: DHB - 4,4’-dihydroxybenzone phenone was classified as Non-Irritant to human skin.

Eye irritation: the eye irritation potential of DHB - 4,4'-dihydroxybenzone phenone was assessed in vitro according to OECD Test Guideline 492 (Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage).

After 6h exposure on the surface of EpiOcularTM reconstructed ocular epithelium and 18h post-incubation time, the viability of the tissues was assessed and compared to a negative control. The percentage viability obtained was 59.982% and therefore: DHB - 4,4'-dihydroxybenzone phenone was classified as an Irritant to the human eye.

However, because the result obtained was very close to the limit below which classification would not be required, the lower Category 2 classification has been applied as being the most appropraite in the absence of further test results.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1h exposure on the surface of the EpiDermTM reconstructed human epidermis and a 42h post-exposure incubation time.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch number: 20160804
Purity: 100%

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: cultured

Justification for test system used:

The reconstructed human epidermal model EpiDermTM (EPI-200-MatTek Corporation) consists of normal human-derived epidermal keratinocytes which have been cultured to form a multi-layered highly differentiated model of the human epidermis. It consists of organised basal, spinous and granular layers and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo.

Vehicle:

unchanged (no vehicle)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

Solid test item - single application of nominal 25mg on top of each tissue (tissues pre-wetted with 25μl PBS (Sterile Dulbecco’s Phosphate Buffered Saline).
Liquid reference items – single application 30 μl of neat test item, negative control PBS (Sterile Dulbecco’s Phosphate Buffered Saline) or positive control SDS 5% ((Sodium Dodecyl Sulphate).

Duration of treatment / exposure:

Exposure times of test and reference items: 60 ±1 minutes to the surface of the EpiDermTM skin models.

Irritation / corrosion parameter:

% tissue viability

Value:

97.3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, the skin irritation potential of DHB- 4,4'-dihydroxybenzone phenone was assessed in vitro according to OECD Test Guideline 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method.
After a 1h exposure on the surface of the EpiDermTM reconstructed human epidermis and a 42h post-exposure incubation time, viability of the tissues was assessed and compared to the negative control.
The percentage viability obtained was 97.3% and therefore: DHB - 4,4’-dihydroxybenzone phenone was classified as Non-Irritant to human skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6h exposure on the surface of EpiOcularTM reconstructed ocular epithelium and 18h post-incubation time

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch number: 20160804
Purity: 100%

Species:

human

Details on test animals or tissues and environmental conditions:

The EpiOcularTM tissue model (OCL-200 - MatTek Corporation) is composed of stratified human keratinocytes in a three-dimensional structure, reflecting the morphology and function of the human corneal epithelium found in vivo.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

Method of administration of test and reference items:
After pre-wetting tissues with 20μl PBS (Sterile Dulbecco’s Phosphate Buffered Saline) for 30 ± 2 min, single topical application of neat test item to the surface of the EpiOcularTM model; three tissues per condition (n=3).

Duration of treatment / exposure:

Exposure times of test and reference items:
Single application of a levelled spoonful (designed to hold approximately 50mg) of test item or 50μl of reference items topically on tissues for 6 hours ± 15 minutes, followed by a 25 ± 2 minutes post-treatment immersion, and 18 hours ± 15 minutes post-treatment incubation, prior to the MTT endpoint

Irritation parameter:

other: Percentage of viability (relative to negative control)

Value:

59.982

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

The test item DHB - 4,4’-dihydroxybenzone phenone reduced the viability below 60% of the negative control value after 6h of application and should be considered as Irritant to the eye.
The percentage of viability obtained with test item DHB - 4,4’-dihydroxybenzone phenone was 59.982 %, therefore it has to be considered as Irritant to the eye. However, it should be noticed that the viability result is very close to the threshold of 60%.

Interpretation of results following Prediction Model

 A test item is considered to be irritant to the eye (i.e. would require labelling as either GHS 1 or 2) if the eye model viability after exposure and post-treatment incubation is ≤60%.

 A test item is considered as a non-irritant to the eye (i.e. would not require a warning label in the European chemical classification systems) if the eye model viability after exposure and post-treatment incubation is >60%.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In this study, the eye irritation potential of DHB - 4,4'-dihydroxybenzone phenone was assessed in vitro according to OECD Test Guideline 492 (Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage).
After 6h exposure on the surface of EpiOcularTM reconstructed ocular epithelium and 18h post-incubation time, the viability of the tissues was assessed and compared to a negative control.
The percentage viability obtained was 59.982% and therefore: DHB - 4,4'-dihydroxybenzone phenone was classified as an Irritant to the human eye.
However, because the result obtained was very close to the limit below which classification would not be required, the lower Category 2 classification has been applied as being the most appropraite in the absence of further test results.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)