Registration Dossier

Administrative data

Description of key information

The influence of Folenox on the viability of human skin was tested in an in vitro skin irritation test according to OECD 439 and in an in vitro skin corrosion test according to OECD 431. Both studies were perfomed according to GLP principles. It can be concluded that Folenox is irritating in the in vitro skin irritation test and Folenox is considered to be not corrosive in the in vitro corrosion test.
The substance Folenox was screened for the eye irritation potential using the Bovine Corneal Opacity and Permeability test performed according to OECD 437 guideline and GLP principles. Based on the results, it is concluded that Folenox is not irritant or corrosive.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In an in vitro skin irritation test (according to OECD 439 guideline) using a human skin model ( EPISKIN Small Model), the influence of the test substance on the viability of human skin was tested. The test substance (25μl) as applied directly to 0.38 cm2cultured skin.

After 15 minutes, the substance was removed and cells were cultured for 42 hours. Folenox was checked for possible direct MTT reduction by adding the test substance to MTT medium. Because no colour change was observed it was concluded that Folenox did not interact with MTT.

The viability of the cells was tested by reduction of MTT. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 5% whereas the test substance showed cell viability of 16%. Since the mean relative tissue viability after exposure to the test substance was below 50%, it can be concluded that Folenox is irritating in the in vitro skin irritation test.

In an in vitro skin corrosion test (according to OECD 431 guideline) using a human skin model (EpiDerm Skin Model), the influence of the test substance on the viability of human skin was tested. The test substance (50μl) as applied directly to cultured skin. The possible corrosive potential of Folenox was tested through topical application for 3 minutes and 1 hour.

Folenox was checked for possible direct MTT reduction by adding the test substance to MTT medium. Because no colour change was observed it was concluded that Folenox did not interact with MTT.

The viability of the cells was tested by reduction of MTT. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 8 and 5% whereas the test substance showed cell viability of 94 and 98% for the 3 minutes and 1 hour exposure time respectively. Since the mean relative tissue viability for Folenox was not below 50% after 3 minutes treatment and not below 15% after 1 hour treatment Folenox is considered to be not corrosive.

Supporting in vivo study data on the substance is available but no conclusions can be drawn on the 100% substance, but 2% solution does not show irritation in humans.

Eye irritation:

The substance Folenox was screened for the eye irritation potential using the Bovine Corneal Opacity and Permeability test performed according to OECD 437 guideline and GLP principles.

The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 117 and was within the historical positive control data range. Negative and positive controls were valid and it was therefore concluded that the test conditions were adequate and that the test system functioned properly.

Folenox did not induce ocular irritation through both endpoints, opacity and permeability, resulting in a meanin vitroirritancy score of 0.6 after 12 minutes of treatment.Based on the results, it is concluded that Folenox is not irritant or corrosive in the Bovine Corneal Opacity and Permeability test. Since Folenox induced an IVIS ≤ 3, no classification is required for eye irritation or serious eye damage.

Supporting in vivo study data (performed equivalent to OECD 405) on the substance is available showing no eye irritation with a 0.5% solution.


Justification for selection of skin irritation / corrosion endpoint:
One in vitro skin irritation test and one in vitro skin corrosion test is available.

Justification for selection of eye irritation endpoint:
One in vitro eye irritation key study on the substance in available.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the results, Folenox should be classified for skin irritation category 2 and should be labelled with H315: Causes skin irritation, according to Regulation (EC) No 1272/2008.

Folenox does not have to be classified for eye irritation according to Regulation (EC) No 1272/2008.