Registration Dossier

Administrative data

Description of key information

- skin irritation: not irritating  for the rabbit skin (OECD 404); study Giannini (2008) / Skin irritation
- eye irritation: irreversible effects on the eye (rabbit); weight of evidence approach
- respiratory irritation: no data available

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)

Additional information

- skin irritation/corrosion

Corrosion (in vitro)

An in vitro study ("Heppenheimer (2008) / Skin corrosion") was performed to assess the corrosive potential of FAT 40841/A TE by means of the Human Skin Model Test (human skin model EpiDerm™). After treatment with the test item FAT 40841/A TE the relative absorbance values were not relevantly decreased both after 3 minutes and after 1 hour treatment. Therefore, the test item is not considered corrosive.

Irritation (in vivo)

A Primary Skin Irritation Study in Rabbits was conducted according to OECD 404 (4 -Hour Semi-Occlusive Application, study Giannini (2008) / Skin irritation). No oedema was present in all animals during the whole observation period. Thus, the test item was not irritating concerning the oedema assessment. Furthermore, the test item is suggested to be not irritant concerning also erythema because a severe reaction would have been observed despite the staining and would not have disappeared completely from 24 to 48 hours. Therefore, the test item is suggested to be “not irritating” to rabbit skin.

Results from the in vitro test and the in vivo test are in line in the fact that FAT 40841/A TE shows neither corrosive nor irritating effects on mammalian skin. Accordingly no classification is necessary for this endpoint.

- eye irritation/corrosion

in vitro:

FAT 40841/A TE was tested for eye irritation/corrosion with the Bovine Corneal Opacity and Permeability Assay (BCOP) according to the SOP of Microbiological Associates Ltd. UK, Procedure Details, April 1997 (study Heppenheimer (2008) Eye irritation). The test item caused opacity and permeability of the corneas compared with the results of the negative control. The calculated in vitro score was 93.86 and therefore, the test item was classified as very severe eye irritant. The test item caused coloring of the cornea which could not be rinsed off even after stringent washing. Therefore the positive effect may be caused by the coloring effect. With the negative control (0.9% NaCl solution) neither an increase of opacity nor permeability of the corneas could be observed. The in vitro score was calculated as XX. The positive control (10% (v/v) Benzalconium chloride) showed clear opacity and distinctive permeability of the corneas and therefore, is classified as very severe eye irritant. The in vitro score was calculated as 164.27.

in vivo:

The primary eye irritation potential of FAT 40841/A TE was investigated according to OECD test guideline no. 405 (study Giannini (2009) Eye irritation Rabbit).

The individual mean scores for the conjunctivae were 0.33, 0.00 and 0.00 for reddening and 0.00, for all animals for chemosis. The instillation of FAT 40841/A TE into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae with or without discharge. These effects were reversible and were no longer evident 24 or 48 hours after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals.

The test item (blue dye) produced a slight blue staining of the eye which was visible up to the end of the observation period (21 days) in all animals. Additionally, blue test item remnants were noted in two animals at the 1-hour reading.

No clinical signs were observed throughout the observation period.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye trough irritation.

FAT 40841/A TE produced persistent blue staining of conjunctivae and sclerae, but not of cornea or iris.

The data from the in vitro test suggests that FAT 40841/A TE is a severe eye irritant (Heppenheimer (2008) Eye irritation). Nevertheless the authors propose the explanation that the high in vitro score results from the staining of the cornea by the test item rather than a truely irritating effect. This assumption is verrified by the results from the in vivo test (Giannini (2009) Eye irritation Rabbit) where only slight and transient (< 48 h) irritating effects were seen in the rabbit eye. Nevertheless in the latter study irreversible staining of conjunctivae and sclerae was found.

Based on these findings "irreversible effects on the eye" through through staining by FAT 40841/A TE cannot be precluded. Therefore a corresponding classification is necessary. Please note that this classification does not imply irritating or corrosive effects by FAT 40841/A TE but is solely triggered by the irreversible staining that results from exposure of eyes to the substance.

- inhalation:

no data available

Justification for classification or non-classification

- skin:

Based on the above stated assessment of the skin irritation potential of FAT 40841/A TE the substance does not need to be classified fort his endpoint according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- eye:

Based on the above stated assessment that irreversible effects in the eyes cannot trough staining cannot be precluded, FAT 40841/A TE is classified as having irreversible effects on the eye (R41 Risk of serious damage to eyes) according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and Category 1 (Danger; H318: Causes serious eye damage) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- inhalation:

As no data on inhalation irritation is available for FAT 40841/A TE a classification is not possible according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.