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Description of key information

No skin sensitisation study with zinc bis(2-ethylhexanoate) is available. In the assessment of toxicity of zinc bis(2-ethylhexanoate), read-across to the assessment entities zinc and 2-ethylhexanoic acid is applied since the ions of zinc bis(2-ethylhexanoate) determine its toxicity in biological compartments.

Zinc bis(2-ethylhexanoate) is not expected to show signs of dermal sensitisation, since its two moieties zinc and 2-ethylhexanoate have not shown any skin sensitisation potential in experimental testing.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Sensitisation

Existing data on the skin sensitisation potential of the two moieties of zinc bis(2-ethylhexanoate) are detailed below.

Zinc

The skin sensitising potential of zinc oxide (purity 99.69%) was investigated in female Dunkin Hartley guinea pigs in two well-performed maximisation tests, conducted according to Directive 96/54/EC B.6 and OECD guideline 406. Based on the results of a preliminary study, in the main studies experimental animals (10 in each test) were intradermally injected with a 20% concentration and epidermally exposed to a 50% concentration (i. e. the highest practically feasible concentration). Control animals (5 in each test) were similarly treated, but with vehicle (water) alone. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. In the first study, in response to the 50% test substance concentration skin reactions of grade 1 were observed in 4/10 experimental animals 24 hours after the challenge (40% sensitisation rate), while no skin reactions were evident in the controls. In contrast, in the second study no skin reactions were evident in the experimental animals (0% sensitisation rate), while a skin reaction grade 1 was seen in one control animal. The skin reaction observed in one control animal is probably a sign of non specific irritation (Van Huygevoort, 1999b1, 1999b2).

In a third well-performed maximisation test, conducted according to the same guidelines and with the same experimental design, another analytical grade zinc oxide was tested (Zincweiß Pharma A; purity 99.9%). The only difference with the studies described above was the intradermal induction concentration, which was 2% as for Zincweiß Pharma A this was considered the highest concentration that could reproducibly be injected. In this test no skin reactions were evident in both experimental and control animals, hence a 0% sensitisation rate for Zincweiß Pharma A. White staining of the treated skin by the test substance was observed in some animals 24 and 48 hours after challenge (Van Huygevoort, 1999a).

Human data:

In a human patch test performed with 100 selected leg-ulcer patients, 11/100 patients gave an allergic reaction with zinc ointment (60% ZnO and 40% sesame oil). However, 14/81 patients gave a positive response when treated with sesame oil alone. This study does not give any indication for a skin sensitizing potential of zinc oxide in humans (Malten and Kuiper, 1974).

The effect of zinc oxide on contact allergy to colophony was investigated. With 14 patients with earlier history of moderate patch test reactions to colophony (a patch test) with 10% ZnO (2.3 mg Zinc/cm²) with and without colophony was performed. No positive response was observed in the 14 patients when only a 10% solution of zinc oxide was used. The addition of zinc oxide to colophony decreased the allergic reaction induced by colophony (Söderberg et al., 1990).

 

2-ethylhexanoic acid

In a guinea pig maximization assay (Berol Kemi AB, 1979), 0/10 female Dunkin-Hartley guinea pigs exhibited a response 48 h after induction and challenge with 5 % (w/w) and 2 % (w/w) aqueous 2-ethylhexanoic acid solution, respectively. The intracutaneous injections were performed with 1 % (w/w) aqueous 2-ethylhexanoic acid solution. In summary, there is no evidence of a notable sensitization potential of 2-ethylhexanoic acid.

 

Table: Summary of skin sensitisation data of the zinc bis(2-ethylhexanoate) and the assessment entities.

 

(slightly soluble) zinc substances

2-ethylhexanoic acid

(CAS# 149-57-5)

Zinc bis(2-ethylhexanoate)

(CAS# 136-53-8)

Skin sensitisation

not sensitising

not sensitising

not sensitising

(read-across)

 

Zinc bis(2-ethylhexanoate) is not expected to show signs of dermal sensitisation, since the its two moieties zinc and 2-ethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, zinc bis(2-ethylhexanoate) is not to be classified according to regulation (EC) 1272/2008 as skin sensitising. Further testing is not required. For further information on the toxicity of the individual constituents, please refer to the relevant assessment entity sections in the IUCLID and CSR.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

According to the CLP regulation the hazard identification and subsequently a proposal for classification as “Respiratory sensitiser” will normally be based on human experience. In this context, hypersensitivity is normally seen as asthma, but other hypersensitivity reactions such as rhinitis/conjunctivitis and alveolitis are also considered. The condition will have the clinical character of an allergic reaction. However, immunological mechanisms do not have to be demonstrated.

The evidence could be:

a)           clinical history and data from appropriate lung function tests related to exposure to the substance, confirmed by other supportive evidence which may include:

i.             in vivo immunological test (e.g. skin prick test);

ii.            in vitro immunological test (e.g. serological analysis);

iii.           studies that indicate other specific hypersensitivity reactions where immunological mechanisms of action have not been proven, e.g. repeated low-level irritation, pharmacologically mediated effects;

iv.          a chemical structure related to substances known to cause respiratory hypersensitivity;

b)           data from one or more positive bronchial challenge tests with the substance conducted according to accepted guidelines for the determination of a specific hypersensitivity reaction.

Justification for classification or non-classification

Zinc bis(2-ethylhexanoate) is not expected to show signs of dermal sensitisation, since its two moieties zinc and 2-ethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, zinc bis(2-ethylhexanoate) is not to be classified according to regulation (EC) 1272/2008 as skin sensitising.

In long-time industrial experience in the production and handling of substance zinc bis(2-ethylhexanoate), no cases of respiratory hypersensitivity have been observed. Classification as respiratory sensitiser is not applicable.