Registration Dossier

Administrative data

Description of key information

Skin irritation: non-irritating, eq. or sim. to OECD 404, MB Research Laboratories, Inc. 1979
Eye irritation: non-irritating, eq. or sim. to OECD 405, MB Research Laboratories, Inc. 1979

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 non-GLP study was completed under 16 CFR 1500.41 following with acceptable deviations a guideline similar to OECD 404, to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The test substance was evaluated in 6 New Zealand white rabbits. A dose of 0.5 ml test substance was applied to intact and abraded clipped dorsal skin site under a occlusive dressing for 24 hours. Skin observations were made 24 and 72 hours after patch removal. Very slight erythema and edema were noted at 24 hours in both intact and abraded skin. By 72 hours, very slight to well defined erythema and very slight edema were observed in both intact and abraded skin.

The mean score at 24 and 72h of intact skin was < 2.3 in all organisms in all response criteria (erythma/escar or odema) but effects persisted to the end of the observation period (72h). Since four or more organisms did not demonstrate a mean score greater than or equal to 2.3; there was an absence of reported significant dermal effects (e.g. alopecia, hyperplasia or scaling) and/or significant variability of responses, the substance is not considered to be irritating. Furthermore an available acute toxicity study by the dermal route which does not indicate skin irritation up to the limit dose level (2000 mg/kg body weight) The substance is not irritating to the skin. Further testing for skin irritation is unjustified.

 

Eye irritation/corrosion:

The study was performed to assess the irritancy potential of the test material to the eye following a single application in the New Zealand White rabbit. The non-GLP study was completed under 16 CFR 1500.42 following a guideline similar to OECD 405. A volume of 0.1 ml of the test material was placed into the conjunctival sac of one eye of 6 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 24, 48 and 72 hours following treatment. No corneal opacity or irritation was observed on any day and iridal irritation was observed in four animals. Conjunctival irritation was observed in all test animals on all 3 days. Under the conditions of this study the test material is considered to be an eye irritant. However, based on the applicants recalculation of the mean scores following grading at 24, 48 and 72h, 4 out of 6 organisms mean scores did not meet the EU classification criteria. Further there was complete absence of Corenal Opacity and very low order Corneal Iritis which is indicative of full reversibility of effects within 21-days. The substance has the potential to produce mild transient eye irritation but is insufficient for classification. Therefore the substance cannot be considered as an eye irritant under Regulation (EC) 1272/2008.


Justification for selection of skin irritation / corrosion endpoint:
one in vivo non-GLP compliant Klimisch 2 study. No study is selected since a Weight of Evidence determination is made based on in vivo data supported by in vivo acute dermal toxicity data at the limit dose 2000 mg/kg bw (equiv. or similar to OECD402, 1979).

Justification for selection of eye irritation endpoint:
one non-GLP study in vivo Klimisch 2 study; applicant recalculated the mean scoring and evaluated the mean and individual scoring in concluding the endpoint.

Justification for classification or non-classification

The substance does not meet classification criteria under EU Directive 67/548/EEC for dermal irritation.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for dermal irritation.

 

The substance does not meet classification criteria under EU Directive 67/548/EEC for eye irritation.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for eye irritation.

 

For skin irritation, the weight of evidence indicates that the substance has the potential to be slightly irritating however this is not sufficient for classification purpose. Human experience with the substance indicates the substance does not induce skin irritation. In vivo data indicates negative irritation in an in vivo dermal irritation study and in an in vivo acute dermal toxicity study at the limit dose of 2000 mg/kg bw. However, these studies utilised occlusive dressings (increases percutaneous absorption; potential altering of epidermal lipids, DNA synthesis, epidermal turnover, pH, epidermal morphology) resulting in a predisposition towards positive and irreversible irritation within these studies. The overall evidence by expert judgement indicates that the substance may produce transient slight irritation by the dermal route which is not sufficient for classification in accordance with the above criteria.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient mild irritating effects to the eye but which are insufficient for classification based on the applicants recalculation of the mean scoring and evaluation of the results in six organisms demonstrating that the EU criteria had not been met. Effects in vivo on corneal opacity and iritis are non-existent or very low; the substance is of demonstrated low order of acute toxicity and further; based on skin irritation studies an absence of serious effects by the dermal route – the overall evidence is indicative of transient and reversible effects on the eye.

References:

1. Guidance on Application of the CLP Criteria, ECHA, version 4.0 - November 2013.