1-{4-[2-(benzyloxy)ethoxy]phenyl}-1,2-diphenylbutane-1,4-diol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

Remarks:

other: in silico

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Principles of method if other than guideline:

Several computational tools are nowadays available for applying in silico approaches. Among them, for QSAR predictions the following were selected and used:
- ACD/Percepta for the prediction of acute oral toxicity, skin and eye irritation, gene mutation (Ames test), micronucleus in vivo (rodent), carcinogenicity rat and mouse composite, acute aquatic toxicity (Daphnia), octanol-water partition coefficient (logKow)
-Toxtree for the prediction of skin and eye irritation, skin sensitization, gene mutation (Ames test), micronucleus in vivo (rodent) and biodegradation (ready)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol

EC Number:

939-875-7

Molecular formula:

C31H32O4

IUPAC Name:

1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol

Test animals

Species:

rabbit

Strain:

not specified

Test system

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Results and discussion

In vivo

Results

Irritation parameter:

other: irritation

Remarks on result:

other: Not irritant; Reliable

Any other information on results incl. tables

ACD/Percepta

ACD/Percepta model for skin irritation calculates the probability for a chemical to cause moderate or above irritation to skin of rabbit at a standard dose of 100 mg and 500 mg respectively. It lists all the rules that are applicable and are used in the calculation, it highlights the structural fragments corresponding to the listed rules on the molecule of interest and it provides a list of up to five most similar structures from the training set with the experimental values of their standard Draize test result and references.

ACD/Percepta predicted 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol not irritant since no structural fragment was identified as potentially skin irritant.

Toxtree

Skin irritation was also predicted by Toxtree, which predicts skin irritation based on the Bundesinstitut für Risicobewertung Institute (BfR, Germany) exclusion/inclusion rules. The BfR exclusion rules for skin irritation/corrosion are based on physicochemical cut-off values to identify chemicals that do not exhibit eye irritation or corrosion potential. The parameters used for defining eye irritation rules are: lipid solubility, octanol water partition coefficient, aqueous solubility, melting point and molecular weight (Gerner I., et al., 2000, ATLA 28; Gerner I., et al., 2004, QSAR Comb. Sci. 23). Toxtree predicted 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol not irritant since, it meets the exclusion rule defined for structures containing all type of atoms and with a melting point > 200◦C, and no structural alert was identified (Hulzebos E, Walker JD, Gerner L and Schlegel K, Use of structural alerts to develop rules for identifying chemical substances with skin irritation or skin corrosion potential, QSAR & Combinatorial Science 2005, 24, 332-342).

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The skin irritation of 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol was predicted employing two different in silico approaches: the QSAR model as provided by ACD/Percepta and the decision rule system provided by Toxtree. The two approaches were employed in order to apply a consensus analysis to enhance the reliability of the prediction. The two predictions were in agreement leading to the conclusion that 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol is NOT SKIN IRRITITANT.