Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: 


Three studies are available for evaluation of skin irritation potential of the substance. The skin irritation potential of the substance was evaluated in a study conducted according to the patch test technique as described in the “Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics” (1959) of the US Association of Food and Drug Officials (AFDO). the substance was applied to each side of the shaved flank region of 6 Russian breed rabbits in quantities of 0.5 ml. The shaved skin area on the left side was slightly scarified just before treatment. A gauze patch of 2.5 x 2.5 cm laden with test substance was applied immediately to the prepared skin. The patch was covered with an impermeable foil of 5x5 cm, which was fixed to the body of the animals with adhesive tape. The gauze patches were removed 24 hours after application. The reaction of the skin was appraised upon removal during an observation period of 9 days. A slight erythema without oedema was observed with the intact skin. Hence, the substance does not warrant classification as per the Regulation EC No. 1272/2008.


In another supporting study, the substance was observed to cause slight irritation, however it does not warrant classification as per the Regulation EC No 1272/2008 for skin irritation, as the scores were below the threshold values.


A study with repetitive skin exposure with the substance is available. In this study, the substance was found to cause increasing moderate to marked irritation when applied repeatedly to the rabbit skin. However, as the exposure was repeated for consecutive 5 days and the exposure duration was 24 hours for each application, this was considered to be a deviation from the guideline and hence the study was disregarded.


 


Eye irritation


Three studies are available for evaluation of eye irritation potential of the substance.


A study was performed to determine the eye irritation for the substance according to Hazardous Substances Regulations” under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification. 100 mg of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with warm water for 1 minute. The rabbits were examined and the scored for the effects on eye 1, 24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary. A mild to severe conjunctival reaction was seen in all treated eyes one hour after application of the compound. This had improved slightly by 24 hours. The unwashed eyes did not show very much change after this until day 10 when small areas of necrosis were seen in the nictitating membranes. These were still present at termination (day 14). The washed eyes however, had returned to normal by day 6 (2/3) and day 10 (1/3). A corneal reaction consisting of slight opacity and damage to the superficial epithelium was seen in all treated eyes at one hour. This was still present at 24 hours and thereafter, the eyes returned to normal by 48 hours (2/3 washed eyes), 72 hours (2/3 unwashed eyes) and 6 days (1/3 washed, 1/3 unwashed eyes). Increased folding of the iris was seen in all unwashed eyes at 24 hours. These had returned to normal by 48 hours (1/3) and 72 hours (2/3). The testing has been carried out with eyes of 3 rabbits washed after 30 seconds, while remaining 3 rabbits never received any washing. However, the modern guidelines correctly recommend “If the solid test substance has not been removed from the eye of the test animal by physiological mechanisms at the first observation time point of 1 hour after treatment, the eye may be rinsed with saline or distilled water.” Further the washing/flushing the eyes after exposure is a more realistic scenario for workers, as such an exposure will lead to an attempt to flush out the substance entered in the eye as soon as possible. Hence, not washing the eyes at all is considered to be an elevated testing condition, and the results obtained with such an exposure are not considered for hazard assessment. In line with the above argument, the findings of necrosis of the nictitating membranes of unwashed eyes seen in this study, is not considered for the hazard conclusion. The scoring for washed eyes is below the threshold of the classification, hence, the substance is classified as not an eye irritant.


In two other supporting studies though, the substance was shown to be a non-irritant to the eyes. However, considering the results from the available studies, the substance the substance is considered to be not an eye irritant.

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

Justification for classification or non-classification

The substance did not cause irritation to the skin or eyes, hence it does not warrant the classification according to the CLP (Regulation EC No 1272/2008) criteria.