1-Ethoxy-2,3-difluoro-4-(trans-4-pentylcyclohexyl)-benzene

Endpoint summary

Description of key information

For irritation skin / eye, a read across to reliable GLP studies performed for a chemical analyogue according OECD TG is provided. No irritation was observed in the studies used for the read across. 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Justification for read across

Endpoint:Skin and Eye Irritation

Type of read across:one-to-one

Test Compound (with data):CAS: 174350-05-1

Dossier Compound (without data):CAS: 124729-02-6

The read across is based on the following similarity measures:

(1) Chemical similarity:
The test compound (CAS: 174350-05-1) provides all main chemical features present in the dossier compound (CAS: 124729-02-6). Both substances share typical structural features for liquid crystals, i.e. one phenyl ring coupled via single bond to a cyclohexyl ring.

Comparing dossier and test compound yields the same substitution pattern at the phenyl ring, i.e. a Fluor substitution (dossier compound: n=2, test compound: n=2) and a para ethoxy substituent.

The cylohexyl ring of both compounds shows a para alkyl substitution of different chain length (dossier cpd.: n=5; test cpd.: n=3). Thus, the only difference in terms of chemical structure is the length of the alkyl chain connected to the core structure. Overall, this almost perfect match results in a high chemical similarity score of 1.00 (Tanimoto).

(2) Physicochemical similarity
The high chemical similarity yields almost identical physicochemical key parameters relevant for bioavailability as listed in the table below.

Assay	Test Compound CAS: 174350-05-1	Dossier Compound CAS: 124729-02-6
Cyclohexyl phenyl core	yes	yes
Terminal alkyl chain at the cyclohexyl ring	propyl	pentyl
Terminal alkoxy chain at the phenyl ring	ethoxy	ethoxy
Liquid crystalline properties	yes	yes
Fluoro Substitution at the phenyl ring	yes (n=2)	yes (n=2)
Water solubility	130 µg/L (EU A.6)	30 µg/L (EU A.6)
logP	> 5.7 (OECD 117, EU A.8)	> 6.5 (OECD 117, EU A.8)
Eye irritation in vivo	negative (OECD 405)	negative (Read Across)
Skin irritation in vivo	negative (OECD 404)	negative (Read Across)

Conclusion
The Dossier Compound shows a data gap for Skin and Eye irritation; however, a chemical analogue provides data for these endpoints. Both the Dossier Compound and the Test Compound show a very high chemical similarity and almost identical physicochemical parameters leading to similar bioavailability.

Based on these finding it is justified to use the data from the chemical analogue (Skin irritation in vivo: negative (GLP, OECD TG 404); Eye irritation in vivo (GLP, OECD TG 405)) to fill the data gap for the dossier compound.

Justification for selection of skin irritation / corrosion endpoint:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 404.

Justification for selection of eye irritation endpoint:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 405.

Justification for classification or non-classification

According to the results of the irritation tests, a classification and labelling is not required for this substance.