Registration Dossier

Administrative data

Description of key information

In the absence of irritation/corrosion data on target substance butyl 4-hydroxybenzoate a read-across approach was conducted on source substance isobutyl 4-hydroxybenzoate:

Skin irritation (OECD 439, OECD 435): irritating

Eye irritation (OECD 437): corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vitro
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
15 min
Value:
9.7
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Source: CAS 4247-02-3, Eurlings, 2016, RHE
Irritation / corrosion parameter:
penetration time (in minutes)
Value:
> 60
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: non-corrosive
Remarks:
Source: CAS 4247-02-3, Westerink, 2016, Corrositex
Interpretation of results:
other: Skin Irrit. 2 (H315) is required according to Regulation (EC) No 1272/2008
Conclusions:
The available data on suitable source substance isobutyl 4-hydroxybenzoate show skin irritating effects in the resonstructed human epidermis test, since the mean relative tissue viability was 9.7% after 15 min treatment (threshold for irritancy: <50%). In the Corrositex Assay the source substance did not show corrosive properties, since the mean penetration time was >60 min. Therefore, as explained in the analogue justification, the target substance butyl 4-hydroxybenzoate is considered to be skin irritating (Skin Irrit. 2, H315).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Irritation parameter:
in vitro irritation score
Remarks:
mean of 3 replicates
Run / experiment:
240 min
Value:
80
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Remarks:
Source: CAS 4247-02-3, Eurlings, 2016, BCOP
Interpretation of results:
other: Eye Dam. 1 (H318) according to Regulation (EC) No 1272/2008
Conclusions:
The source substance isobutyl 4-hydroxybenzoate induced serious eye damage in the Bovine Corneal Opacity and Permeability test, resulting in a mean in vitro irritancy score of 80 after 240 minutes of treatment. Therefore, as explained in the analogue justification, the target substance butyl 4-hydroxybenzoate is considered to be serious eye damaging (Eye Dam. 1, H318).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read-across justification

No data on the in vitro skin and eye irritation/corrosion are available for butyl 4-hydroxybenzoate. The irritation/corrosion assessment was therefore based on studies conducted with source substance isobutyl 4 -hydroxybenzoate as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance structurally closest to the target substance is chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the read across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation/corrosion in vitro

CAS 4247-02-3

There are two reliable studies on the skin irritancy potential of isobutyl 4-hydroxybenzoate. Skin irritation was tested in a guideline study according to OECD guideline 439 using reconstructed human epidermis (RHE) model (Eurlings, 2016). The relative mean tissue viability obtained after 15 min treatment with isobutyl 4-hydroxybenzoate compared to the negative control tissue was 9.7%. Since the mean relative tissue viability was below 50% after 15 min treatment isobutyl 4-hydroxybenzoate is considered to be skin irritant.

In an additionally performed Corrositex test according to OECD 435 no penetration of isobutyl 4-hydroxybenzoate was observed during the observation time of 65 min. Therefore, the substance is considered to be not skin corrosive (Westerlink, 2016).

Conclusion:

Based on available data and following the analogue approach, butyl 4 -hydroxybenzoate is considered to be skin irritating.

Eye irritation in vitro

CAS 4247-02-3

There is one reliable study available on the eye irritancy potential (Eurlings, 2016). Isobutyl 4-hydroxyparaben was tested for its eye irritant properties on bovine corneas according to OECD Guideline 437. Treatment with isobutyl 4-hydroxybenzoate resulted in a mean in vitro irritancy score of 80 after 240 minutes of treatment. Therefore, the substance is considered to cause serious eye damage.

Based on available data and following the analogue approach, butyl 4 -hydroxybenzoate is considered to cause serious eye damage.

Justification for classification or non-classification

Based on the read-across approach, the available data on skin and eye irritation meet the criteria for classification as Skin Irrit. 2 (H315) and Eye Dam. 1 (H318) according to Regulation (EC) 1272/2008.