Fatty acids, C16-18, zinc salts

Endpoint summary

Description of key information

No skin sensitisation study with Fatty acids, C16 -18, zinc salts is available, thus the skin sensitisation potential will be addressed with existing data on the moieties liberated upon dissolution, zinc and fatty acids, C16 -18, supported by human data on Fatty acids, C16 -18, zinc salts or structurally similar zinc salts of fatty acids.

Fatty acids, C16 -18, zinc salts is not expected to cause skin sensitisation, since the two moieties zinc and fatty acids, C16-18 have not shown any skin sensitisation potential in experimental studies. Furthermore, human data on Fatty acids, C16 -18, zinc salts and struturally similar zinc salts of fatty acids do not indicate sensitising potential as well.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Fatty acids, C16-18, zinc salts

Fatty acids, C16 -18, zinc salts is not expected to show signs of dermal sensitisation, since the two moieties zinc and fatty acids, C16-18 have not shown any skin sensitisation potential in experimental testing. Furthermore, substance-specific human data do not indicate sensitising potential as well.

Thus, Fatty acids, C16 -18, zinc salts is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments as skin sensitising.

Read-across approach and conclusion are in line with the EU risk assessment carried out on Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II–Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1): “Animal data on skin sensitisation are not available for zinc distearate. However, based on the accepted derogation and the fact that zinc oxide is not a skin sensitiser, it is consequently concluded that zinc distearate is not likely to be skin sensitising, and therefore does not need to be classified/labelled. This is supported by the fact that the use of zinc distearate in pharmaceutical and cosmetic products is without reported skin sensitisation effects.”

Further testing is not required.

Please refer to the respective assessment entity section for data on the moieties zinc and fatty acids C16 -18. In brief: 

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).

 

 

Fatty acids, C16-18

Fatty acids, C16 -18 is a mixture of palmitic (C16) and stearic (C18) acid. Palmitic and stearic acid are naturally produced by a wide range of plants and organisms. They are naturally present in butter, cheese, milk and meat. Thus, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

According to a very recent ECHA report, non-branched aliphatic fatty acids (C5-C24) “are expected to be of low toxicity by their nature (similar to high purity fatty acids of natural origin which do not need to be registered as included in Annex V to REACH). […] From a human health perspective, substances in this group are considered to have a low systemic toxicity profile with no specific target organ toxicity or CMR properties. Some have irritant and/or corrosive properties that are reflected in the classification and labelling. Risk from these properties can be avoided by implementing risk management measures in supply chains based on the correct classification and labelling products. Therefore, there is no need for further action on the substances belonging to the group of aliphatic fatty acids non-branched (C5-C24)” (ECHA, 2020: Integrated Regulatory Strategy Annual Report May 2020).

Since the dermal absorption of fatty acids decreases with increasing chain length and molecular weight, the irritating and sensitising capacity of long chain fatty acids is low (Clayton & Clayton, 1982; Madsen et al., 2001). The longer chain lengths, C14 and above, are not irritant (CIR, 1987; Madsen et al. 2001). Also, the existence of unsaturated carbon chains and carbon chain lengths of C16 to C18 contribute to a low skin irritation effect (Madsen et al., 2001)” (HERA, 2002 and references therein).

The non-sensitising properties of long chain fatty acids were demonstrated “in a skin sensitisation study in 28 volunteers, five 48-hour covered applications of 1% decanoic acid (C10) in petrolatum were made over a 10 day period. The results were negative since none gave positive reactions when challenged 10-14 days after the induction phase with a final 48-hour closed patch test using 1% in petrolatum. De Groot et al. (1988) reported that 25 subjects showed no sensitisation reactions when exposed to 5% stearic acid (C18) in petrolatum and a 1% aqueous sodium stearate solution. In two Magnusson and Kligman guinea pig maximisation tests, carried out in conformity with OECD Guideline No. 406 and EC test method B.6 as described in the Annex of EC Directive 84/449/EEC, using two different types of mixed fatty acid sodium salts, no skin sensitisation potential was demonstrated in either material (CIR, 1982) (HERA, 2002 and references therein). “

Human data with Fatty acids, C16 -18, zinc salts or structurally similar zinc salts of fatty acids

In studies in humans, two eye shadow formulations, each containing 10% Fatty acids, C16-18, zinc salts, were tested in the Schwartz-Peck Prophetic Patch assay on 202 subjects and the Draize-Shelanski Repeated Insult Patch Assay on 99 subjects. Both tests resulted in “virtually 0 reactions”. One of the formulations was applied twice daily for 28 days to 52 females. No “irritation or sensitisation” was noted when examined up to four weeks after application. Also a test on human volunteers twice a day for 28 days treated with a cosmetic formulation (eye shadow product) containing Fatty acids, C26-28, zinc salts, gave no indication on a sensitising activity.

Reliable, adequate and relevant animal and human data on slightly soluble zinc oxide indicated no skin sensitising potential. This is supported by the fact that the long-term use of Fatty acids, C16-18, zinc salts in pharmaceutical and cosmetic products has never reported skin sensitisation effects. Additionally, the moiety fatty acids, C16-18 is obtained from natural sources and excluded from the obligation to register.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Fatty acids, C16 -18, zinc salts is not expected to show signs of dermal sensitisation, since the two moieties zinc and fatty acids, C16 -18 have not shown any skin sensitisation potential in experimental testing. In addition, human data on Fatty acids, C16 -18, zinc salts and structurally similar zinc salts of fatty acids also do not indicate sensitising potential. Thus, Fatty acids, C16 -18, zinc salts is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments as skin sensitising.