Fatty acids, tallow, zinc salts

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No studies are available on skin sensitisation of fatty acids, tallow, zinc salts. In accordance to Regulation (EC) No 1907/2006 Annex XI, 1.5, a read across to the structural analogue fatty acids, C16-18, zinc salts (CAS No. 91051-01-3) was conducted. Based on similar structure, physico-chemical properties (i.e. water solubility) and zinc content, the toxicological profile of the two substances is expected to be comparable. Further justification is given within the CSR chapter 5 and the read-across justification. The data available for fatty acids, C16-18, zinc salts and the supporting data available for inorganic zinc salts are discussed below.

Fatty acids, zinc salts

There are no animal studies on sensitisation available for fatty acids, zinc salts. However, in a study with human volunteers two eye shadow formulations, each containing 10% fatty acids, C16-18, zinc salts were tested by means of the Schwartz-Peck Prophetic Patch Test (202 volunteers) and the Draize-Shelanski Repeated Insult Patch Test (99 volunteers; CTFA, 1976 and 1978). Both tests resulted in “virtually 0 reactions”, thus no sensitisation was found.

Also a test on human volunteers twice a day for 28 days treated with a cosmetic formulation (eye shadow product) containing fatty acids, C16-18, zinc salts, gave no indication on a sensitising activity (CTFA, 1977). Reliable, adequate and relevant animal and human data on slightly soluble zinc oxide indicated no skin sensitising potential (see below). Furthermore, soluble zinc compound are also not considered to be sensitising as data on soluble zinc sulphate indicate no sensitisation potential (see the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006) in the technical dossier (IUCLID section 13).

Based on these results and the fact that “the use of zinc distearate in pharmaceutical and cosmetic products is without reported skin sensitisation effects” (EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN), the substance fatty acids, tallow, zinc salts is not likely to be skin sensitising and does not need to be classified.

Inorganic zinc salts

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, 1999).

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, 1999).

Human information

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).

In conclusion, taking together in a weight of evidence approach zinc oxide is considered not to be skin sensitising.

Migrated from Short description of key information:

The read-across substance fatty acids, C16-18, zinc salts as well as insoluble and soluble inorganic zinc compounds indicates, that fatty acids, tallow, zinc salts does not have skin sensitisation potential.

Justification for selection of skin sensitisation endpoint:

Hazard assessment is conducted by means of read-across from structural analogues using a weight of evidence approach from available studies.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Animal data on respiratory sensitisation are not available neither for substance Fatty acids, tallow, zinc salts nor for other zinc compounds. However, there is no information suggesting that zinc compounds may cause such effects. Taking into account the complete absence of skin sensitisation potential of zinc compounds, respiratory sensitisation is not expected to be of concern for the zinc and zinc compounds including substance fatty acids, tallow, zinc salts. Refer also to the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in the technical dossier (see IUCLID section 13) for further information.

Justification for selection of respiratory sensitisation endpoint:

Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The data on slightly soluble zinc oxide indicated no skin sensitising potential (negative in animal and human studies) therefore classification for skin sensitisation is not required according to EC criteria. Based on the assumption that zinc compounds with similar water solubility characteristics can be read across, it can be concluded that the other slightly soluble and insoluble zinc compounds are also expected to be non-skin sensitisers. This conclusion applies to fatty acids, tallow, zinc salts.

Thus, based on read-across, the substance fatty acids, tallow, zinc salts is not likely to be skin sensitising and does not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.