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Administrative data

Description of key information

SKIN IRRITATION
In an in vitro study, an in vivo study and a human study, the test material was determined to be non-irritating. In a second in vivo study, skin irritation was seen. Evaluation of the data in its entirety has resulted in the conclusion that the test material is not irritating.
EYE IRRITATION
The test material was determined to be non-irritating to the eyes of New Zealand White rabbits.
In a BCOP in vitro study, the test material was determined not to be a severe irritant or corrosive.

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 study available

Additional information

Skin Irritation

The skin irritation potential of the test material was evaluated in vitro using the EPISKIN reconstructed human epidermis model in accordance with the standardised guidelines OECD 439 and EU Method B.46 under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria detailed by Klimisch (1997).

Triplicate tissues were treated with the test material for an exposure period of 15 minutes. At the end of the exposure period, each tissue was rinsed before incubating for 42 hours after which each tissue was taken for MTT loading. After MTT loading, a total biopsy of each epidermis was made and formazan crystals were extracted out of the MTT-loaded tissues. Duplicate tissues treated with PBS served as the negative control and duplicate tissues treated with 5 % aqueous Sodium Dodecyl Sulphate in PBS served as the positive control. The optical density of all treated tissues was measured at 540 nm.

The relative mean viability of the test material treated tissues was 113 % after the 15 minute exposure period.

Under the conditions of this study, the test material was determined to be non-irritating and requires no classification in accordance with EU criteria.

 

The potential of the test material to cause in vivo irritation to the skin of New Zealand White rabbits was investigated in a procedure broadly equivalent to the standardised guideline OECD 404. It was assigned a reliability score of 2 in accordance with the criteria detailed by Klimisch (1997).

The test material was applied to the shaved backs of six rabbits at an undiluted dose of 0.5 mL. The test site was covered in an occlusive fashion for an exposure period of 4 hours.

All test sites were examined for signs of dermal irritation (oedema, erythema and/or eschar formation) and corrosivity (ulceration and/or necrosis) 30 to 60 minutes, 24, 48, and 72 hours following the end of the exposure period.

No corrosive effects or oedema were seen. Very slight erythema was observed, with the mean score over the 72 hour observation period being 0.44.

Under the conditions of this study the test material caused no corrosion or irritation to the skin of New Zealand White rabbits and therefore requires no classification in accordance with EU criteria.

 

The potential of the test material to cause in vivo irritation to the skin of New Zealand White rabbits was investigated in a second procedure broadly equivalent to the standardised guideline OECD 404. It was assigned a reliability score of 2 in accordance with the criteria detailed by Klimisch (1997).

The test material was applied to the shaved backs of six rabbits at an undiluted dose of 0.5 mL. The test site was covered in an occlusive fashion for an exposure period of 4 hours.

All test sites were examined for signs of dermal irritation (oedema, erythema and/or eschar formation) and corrosivity (ulceration and/or necrosis) 30 to 60 minutes, 24, 48, and 72 hours following the end of the exposure period.

No corrosive effects were seen. Erythema was observed, with the mean score over the 72 hour observation period being 2.0. The mean score over the 72 hour observation period for oedema was 1.7. Very slight to slight eschar formation was observed within the test sites of 5 rabbits 7 days after the test material was applied. This persisted in 4 rabbits to day 14.

Under the conditions of this study the test material caused no corrosion to the skin of New Zealand White rabbits. Some irritation was seen and it is considered that classification as Category 2 in accordance with EU criteria would be appropriate.

 

The potential of the test material to cause irritation to human skin was investigated in a study carried out in accordance with the testing laboratory’s protocol entitled “Primary Irritation Patch Test Protocol”. It was assigned a reliability score of 4 in accordance with the criteria detailed by Klimisch (1997).

0.1 mL of the undiluted test material was applied to the skin of 26 human subjects in an occlusive fashion and any adverse reactions were recorded.

The study lasted for 4 days. No detail is given as to the length of time for which the subjects were exposed to the test material.

Under the conditions of this study, the test material did not cause any irritation and as such requires no classification in accordance with EU criteria.

 

Although one of the four studies provided would suggest that classification of the test material may be appropriate, it is considered that this is outweighed by the three negative results obtained in the other studies. Furthermore, it should be noted that a distinct difference in appearance is reported for the batch of material used in the study with the positive result when compared to the description given in the remaining studies; this suggests that the result of this study represents something of an outlier, which is not considered to present an accurate reflection of the test material as currently manufactured.

 

Eye Irritation

The irritation or corrosion effects of the test material were investigated in vivo in accordance with the standardised guidelines OECD 405 and EPA OPPTS 870.2400 under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria detailed by Klimisch (1997).

0.1 mL of the test material was instilled into the eye of 3 New Zealand White rabbits. The eyes were examined 1, 24, 48 and 72 hours post administration and the animals observed for general signs of toxicity.

There were minimal eye irritation reactions in all of the test subjects at the 1 hour observation. All irritation subsided by the 24 hour observation. The overall mean scores for corneal effects, iris effects, conjunctival redness and conjunctival chemosis were all 0.0. No symptoms of toxicity were observed in the animals.

Under the conditions of this study the test material caused no irritation to the eyes of New Zealand White rabbits and therefore requires no classification in accordance with EU criteria.

In a supporting study, the eye irritation potential of the test material was evaluated in vitro using the Bovine Corneal Opacity and Permeability test (BCOP test) in accordance with the standardised guidelines OECD 437 and EU Method B.47 under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria detailed by Klimisch (1997).

Screening for the eye irritancy potential of the test material was carried out through a 10 ± 1 minutes topical application. The test material was applied undiluted (750 μL) directly on top of the corneas.

Duplicate corneas treated with physiological saline served as the negative control and duplicate corneas treated with 10 % (w/v) benzalkonium chloride in physiological saline served as the positive control. The optical density of all treated corneas was measured at 490 nm.

The test material did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 0 after 10 minutes of treatment.

Under the conditions of this study, the test material was determined not to be a severe irritant or corrosive and therefore requires no classification in accordance with EU criteria.


Justification for selection of skin irritation / corrosion endpoint:
No key study is selected as this endpoint is addressed on a weight of evidence basis. One in vitro study, two in vivo animal studies and one in vivo human study are provided.

Justification for selection of eye irritation endpoint:
Two studies are provided to address irritation effects in the eye, one conducted in vitro and the other conducted in vivo. The in vivo study is selected as key for the purposes of risk assessment on the basis that the animal study provides a more robust model.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for skin or eye irritation.