Dibutylbis(pentane-2,4-dionato-O,O')tin

Endpoint summary

Description of key information

Skin Irritancy/Corrosivity:
The following study was submitted as the key study:
Sanders, A (2010) ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT. Testing Laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Organo Tin REACH Consortium, c/o ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160, Brussels, BELGIUM. Report No.: 3109/0061
Two in vitro studies were provided as supporting information:
Warren, N (2010) IN VITRO SKIN CORROSION IN THE EPISKIN(TM) RECONSTITUTED HUMAN EPIDERMIS MODEL Testing Laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Organo Tin REACH Consortium, c/o ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160, Brussels, BELGIUM. Report No.: 3109/0036
Warren, N (2010) DETERMINATION OF SKIN IRRITATION POTENTIAL USING THE EPISKIN(TM) RECONSTITUTED HUMAN EPIDERMIS MODEL Testing Laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Organo Tin REACH Consortium, c/o ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160, Brussels, BELGIUM. Report No.: 3109/0037
Eye irritancy
The following study was provided as the key study:
Sanders A (2010) RABBIT ENUCLEATED EYE TEST Testing Laboratory: Harlan Laboratories Limited, Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK. Owner company: Organo Tin REACH Consortium, c/o ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160, Brussels, BELGIUM. Report No.: 3109/0063
The three in vitro studies, were assigned a reliability score of 1 as both were conducted to GLP and to a relevant validated in vitro method. The acute dermal toxicity study, Sanders A (2010), was assigned a reliability  score of 2. The study was performed in compliance with GLP, however the method employed was not comparable to a standard in vivo skin irritation/corrosion test.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin: This endpoint was addressed with the submission of an acute dermal toxicity study which included observations of local effects suitable for assessment under this endpoint. This was the only available in vivo study which included demonstratable effects. Two further in vitro studies were provided as supporting information.

Sanders A (2010) was provided as the key study. The study was performed to GLP and as it was performed to the standard guidelines for acute dermal toxicity, the observations of local dermal effects were considered to have been performed in line with good scientific principles and therefore assigned a reliability score of 2 according to the criteria outlined in Klimisch (1997). As the only available in vivo study, with clear demonstrable effects, the study was selected as the key study. The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat (Performed to OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008). Two animals (one male and one female) were given a single, 24‑Hour, semi‑occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Signs of dermal irritation noted were well-defined erythema, very slight oedema, loss of skin elasticity, hardened dark brown/black coloured scab, small superficial scattered scabs, scab cracking, scab lifting at edges to reveal dried blood, further deep scabbing or glossy skin, scab undulating, dried blood, thickening of the skin and scar tissue. Adverse skin reactions prevented accurate evaluation of erythema and oedema at both test sites during the study. The reactions were considered to be indicative of dermal corrosion.

- The Warren (2010), study investigating skin corrosivity (designed to meet the requirements of the OECD Guideline for the Testing of Chemicals No. 431 “In Vitro Skin Corrosion: Human Skin Model Test” (adopted 13 April 2004).) was assigned a reliability rating of 1 was assigned according to the criteria of Klimisch, 1997 as this was conducted to a guideline study and GLP. The purpose of this test was to evaluate the corrosivity potential of the test material using the EPISKIN(TM) in vitro Reconstituted Human Epidermis (RHE) Model after treatment periods of 3, 60 and 240 minutes. This method was designed to meet the requirements of the OECD Guideline for the Testing of Chemicals No. 431 “In Vitro Skin Corrosion: Human Skin Model Test” (adopted 13 April 2004).

The test material was considered to be Non-Corrosive to the skin and accredited the EU risk phrase of No label and a UN packing group Non-Corrosive.

- The Warren (2010) study investigating skin irritancy (according to a validated in vitro method following the EPISKIN^TM reconstituted human epidermis model.) was assigned a reliability rating of 1 was assigned according to the criteria of Klimisch, 1997 as this was conducted to a validated in vitro method and GLP. The purpose of this test was to evaluate the skin irritation potential of the test material using the EPISKIN(TM) reconstituted human epidermis model after a treatment period of 15 minutes followed by a post exposure incubation period of 42 hours.

The test material was considered to be Irritant (I).

Eye: The following in vitro study was provided to assess the irritancy of the test item to the eye, the results of the study were considered adequate to fulfil the data requirement and sufficient for classification and labelling purposes.

- One key was available for the assessment of this endpoint (Sanders, 2010). The study was performed using a validated in vitro method using enucleated rabbit eyes.

A reliability score of 1 was assigned to the study according to the criteria outlined in Klimisch, 1997, as this was conducted to GLP and a validated method. The purpose of the study was to assess the ocular irritancy potential of the test material in the rabbit following application onto the cornea of the enucleated eye. The results of the study are believed to be of value in predicting the ocular irritation potential of the test material in man. Following assessment of the data, the test material was considered to have the potential to cause severe ocular irritancy in vivo.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin corrosivity:

The test material was considered to be corrosive to the skin. The substance was assigned a classification of Category 1C Corrosive with the risk phrase H314 and the signal "Danger" under the regulation (EC) No.: 1272/2008 and accordingly under the directive 67/548/EEC as C (corrosive) R34 (Causes burns).

Eye:

Following assessment of the in vitro data for all endpoints, the test material was considered to have the potential to cause severe ocular irritancy in vivo.

The data indicates that the substance may be considered severely irritating to the eyes and so it will therefore be classified as R41: Risk of serious damage to eyes according to the criteria set out in Directive 67/548/EEC and as a Category 1 irritant and so will have the hazard statement H318: causes serious eye damage and the 'Danger' symbol.

However, according to Section 3.2.6.2 of Directive 67/548/EEC when a substance is classified as R34, the risk of severe damage to eyes is considered implicit and R41 is not included in the label. Likewise under the regulation (EC) No.: 1272/2008, Section 3.3.2.3 skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1) and hence H318 is not included in the label.

Note: If discrimination between R36 and R41 is not possible in an in vitro eye study, then R41 must be chosen. (Gallegos & Worth (IHCP, 2007); Testing strategies for the prediction of skin and eye irritation and corrosion for regulatory purposes; European Commission, Directorate General, Joint Research Centre; EUR 22881 EN).