Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

FATTY ACIDS, C14 -18 AND C16 - 18 - UNSATD., ZINC SALTS:

Based on similar structural analogy, water solubility and zinc content of Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts (CAS 67701-12-6) and Fatty acids, C16-18, zinc salts (CAS 91051-01-3), a 1:1 read-across of toxicological data of Fatty acids, C16-18, zinc salts is applied to Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts. It is furthermore assumed that during exposure Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts would be changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. A read-across of data to insoluble/ slightly soluble zinc substances based on solubility is considered in addition to read-across to data for Fatty acids, C16 -18, zinc salts. Conclusions of the assessment of slightly soluble/insoluble Zinc compounds confirm the conclusions for Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts that are based on Fatty acids, C16 -18, zinc salts data as follows:

Animal data on skin sensitisation are not available for substance Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts. 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 and the Draize-Shelanski Repeated Insult Patch Assay. 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 (CIR, 1982). 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. 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).

Thus, the substance Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts is not likely to be skin sensitising and does not need to be classified/labelled. This is supported by the fact that the long-term use of Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts in pharmaceutical and cosmetic products has never reported skin sensitisation effects.

ZINC:

Test substance

Method

Results

Remarks

Reference

Zinc sulphate

Mouselocal lymph node assay

Negative

 

2 (reliable with restrictions)

key study

 

Ikarashi Y, Tsuchiya T and Nakamura A (1992)

Zinc sulphate

Guinea pig (Dunkin-Hartley) female

Guinea pig maximization test

Negative

2 (reliable with restrictions)

supporting study

used in RAR, (EU 2004 e)

Van Huygevoort (1999 i)

Zinc oxide

Guinea pig maximization test

Negative

1 (reliable without restriction)

key study

used in RAR, (EU 2004 b)

Van Huygevoort AHBM (1999 g)

Zinc oxide

Guinea pig maximization test

 

Ambiguous

1 (reliable without restriction)

key study

 

Van Huygevoort AHBM (1999h1)

Van Huygevoort AHBM (1999h2)

Zinc sulphate (ZnSO4•7 H2O) was tested in a mouse local lymph node assay (Ikarashiet al., 1992), according to the testing methods developed by Kimberet al.,(1989 and 1990). After gentle dermal abrasion, 25ml of a 5% zinc sulphate solution in 20% ethanol was applied for three consecutive days at the dorsal side of both ears of 3 Balb/c mice. On the fourth day the animals were sacrificed and the ear-draining lymph nodes were collected. Lymph node lymphocyte proliferation was determined by tritiated thymidin incorporation. The results were compared to those of vehicle-treated controls. Zinc sulphate did not induce proliferative activity, whereas for potassium bichromate, nickel sulphate and cobalt chloride (known dermal sensitizers) positive results were obtained.

The skin sensitising potential of zinc sulphate (ZnSO4•7 H2O) was also investigated in guinea pigs. A well-performed maximisation test, conducted according to Directive 96/54/EC B.6 and OECD guideline 406, was carried out in female Dunkin Hartley guinea pigs. Based on the results of a preliminary study, in the main study 10 experimental animals were intradermally injected with a 0.1% concentration and epidermally exposed to a 50% concentration. Five control animals 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. A second challenge followed one week after the first. In response to the 50% test substance concentration, in some experimental animals and controls skin reactions of grade 1 were observed 48 hours after the first (5/10 and 2/5, respectively) and the second challenge (4/10 and 2/5, respectively). As the skin reactions were comparable among the experimental and control animals, and as there was poor consistency of the skin reactions among individual experimental animals after the first and second challenge, the observed skin reactions can be considered to be non-specific signs of irritation. Hence, it can be concluded that zinc sulphate did not induce hypersensitivity in experimental animals (Van Huygevoort, 1999i).


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, 1999h1, 1999h2).

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, 1999g).


Migrated from Short description of key information:
All available data suggests this compound does not have skin sensitisation potential.

Respiratory sensitisation

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

Considering the absence of evidence of respiratory sensitization responses in, this endpoint is not expected to be of concern for zinc and zinc compounds.


Migrated from Short description of key information:
While is no particular study addressing respiratory sensitisation in experimental animals, there is no information suggesting zinc compounds to cause such effects animals.Taking into account the complete absence of skin sensitization potential of zinc compounds, respiratory sensitisation is not expected to be of concern for the zinc and zinc compounds considered in this chemical safety report.

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, C14 -18 and C16 -18 -unsatd., zinc salts.

Thus, the substance Fatty acids, C14 -18 and C16 -18 -unsatd., zinc salts is not likely to be skin sensitising and does not need to be classified/labelled.

The data on soluble zinc sulphate indicates no sensitisation potential and therefore no classification is required according to EC criteria.Sensitisation is not expected from solublezinc chloride, zinc bis(dihydrogen phosphate), diammonium tetrachlorozincate and triammonium pentachlorozincate based on the data for zinc sulphate since the soluble zinc compounds share similar solubility characteristics.