Registration Dossier

Administrative data

Description of key information

SKIN
- Key study: Sanders A (2010a) CAS No 78-04-6: ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT. Testing laboratory: Harlan Laboratories Ltd, Shardlow Business, London Road, 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.: 4100/3380
Supporting studies:
Warren N (2010b) 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.: 3109/0050. Report date: 2010-08-18
Warren N (2010b) 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.: 3109/0051. Report date: 2010-08-03
EYE
- Key study: Sanders A (2010b) CAS 78-04-6 Acute Eye Irritation in the Rabbit Testing laboratory: Harlan Laboratories Limited, Shardlow Business Park, London Road, Shardlow, Derbyshire, DE72 2GD, UK Report no: 41002803 Owner company: Organo Tin REACH Consortium c/o, ReachCentrum, Avenue E. Van Nieuwenhuyse 6, B-1160 Brussels, BELGIUM
Supporting information
Warren, N (2010c) ASSESSMENT OF OCULAR IRRITATION POTENTIAL USING THE SKINETHIC RECONSTITUTED HUMAN CORNEAL EPITHELIUM 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.: 3109/0052. Report date: 2010-09-03

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 irritation/corrosion:

The key study, Sanders (2010a), was provided as the key study as the only in vivo data available which contained observations during the course of the study sufficient for assessment. As the study was performed to GLP, and to the OECD guideline 402 the irritation parameters was considered to have been conducted in line with good scientific principles and therefore adequate for assessment. The study was therefore assigned a reliability score of 2 in line with the criteria outlined in Klimisch (1997). Initially, two animals (one male and one female) were given a single, 24‑hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Signs of dermal irritation noted during the study were very slight to well-defined erythema, haemorrhage of the dermal capillaries, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal bleeding, crust formation, glossy skin and scar tissue. The reactions noted in one female were indicative of dermal corrosion. Animals showed expected gains in bodyweight over the study period, except for three males and one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. One other male showed no gain in bodyweight during the first week but expected gain in bodyweight during the second week.

 

The following two in vitro studies were provided as supporting information:

Skin corrosivity was evaluated in vitro by Warren N (2010a), the study was performed to a current validated guideline and in compliance with GLP and as such assigned a reliability score of 1 in line with the criteria of Klimisch (1997). 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.

 

Skin irritancy was evaluated in vitro by Warren N (2010b), the study was performed to a current validated guideline and in compliance with GLP and as such assigned a reliability score of 1 in line with the criteria of Klimisch (1997). 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. (Method B.46). The test material was considered to be Non-Irritant (NI).

 

Eye Irritation:

Eye irritation of the substance was evaluated in the key in vivo study, Sanders 2010b. The study was performed to the current internationally accepted guideline and in compliance with GLP and was therefore assigned a reliabiltiy score of 1 in accordance with the criteria outlined in Klimisch (1997). The study was performed to assess the irritancy potential of the test item (dibutyltin maleate) to the eye of the New Zealand White rabbit. The study was performed to the guidelines OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002) and Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008. A single application of the test item to the non-irrigated eye of three rabbits produced scattered or diffuse or translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted were a pale area on the conjunctival membrane and/or petechial haemorrhage of the nictitating membrane. Other ocular effects noted in one treated eye were blepharitis and blood stained discharge. Due to worsening reactions and signs of pain and discomfort, one animal was killed for humane reasons immediately after the 72-Hour observation, in accordance with Company policy and current UK Home Office guidelines. These severe reactions in one animal justifies the classification with 'R41', respectively, although the median scores trigger a lower classification.

 

The following in vitro was provided as supporting information for the endpoint eye irritation:

Warren N (2010c) was performed to a good scientific standard to a pre-validated method, in line with GLP. The study was assigned a reliability score of 2. 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. According to the protocol followed the test material was considered to be a Non-Irritant (NI).


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation/corrosion

Due to the nature and severity of effects seen in the available in vivo data, under the Directive 67/548/EEC, the substance should be classified with R34 (causes burns) and labelled with hazard symbol “C” for corrosive substances, and accordingly under the Regulation (EC) No 1272/2008, the substance should be classified as hazardous substance to the skin Category 1C, and labelled with H314: Causes severe skin burns and eye damage with the signal word “Danger”.

.

Eye irritation

Due to the nature and severity of the effects seen in the available in vivo study, under the Directive 67/548/EEC, the substance should be classified as R41 (Risk of serious damage to eyes), and accordingly under the Regulation (EC) No 1272/2008, the substance should be classified as a Category 1 irritant and thus should be labelled with 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..