Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

ZINC DILAURATE:

Data on skin sensitisation are not available for zinc dilaurate. Data on other zinc compounds are used, as it is assumed that after intake zinc dilaurate is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The toxic potential of the fatty acid chain, i.e. laurate, is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

Thus, the following read-across concept has been developed:

Zinc dilaurate is a zinc salt of a medium-chained fatty acid containing 12 C-atoms. Thus, read-across of data available for zinc salts of longer-chained (C16-18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc dilaurate (C12). Sensitisation is therefore addressed with data read-across from longer-chained (C16-18) fatty acids as well as supporting information from slightly soluble/insoluble zinc compounds.

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, C16 -18, 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 (see below). Furthermore, soluble zinc compounds are also not considered to be sensitising as data on soluble zinc sulphate indicate a complete absence of a sensitisation potential (see the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006).

Thus, the substance zinc dilaurate 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 zinc dilaurate in pharmaceutical, cosmetic and other consumer products has never reported any skin sensitisation effects.

Read-across approach and conclusion are in accordance to the conclusions on sensitisation of a structural analogue (i.e. Fatty acids, C16-18, zinc salts) in the 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.

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).

References:

[EU RAR Zinc distearate (CAS-No.: 557-05-1 & 91051-01-3 EINECS-No.: 209-151-9 & 293-049-4) Part II - Human Health (Final report, May 2008;http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1)]

[Ikarashi Y, Tsuchiya T and Nakamura A (1992). Detection of contact sensitivity of metal salts using the murine local lymph node assay. Toxicol. Lett. 62: 53-61.]

[Kimber I and Weisberger C (1989). A murine local lymph node assay for the identification of contact allergens. Arch Toxicol 63: 274-282.]

[Kimber I, Hilton J and Botham PA (1990). Identification of contact allergens using the murine local lymph node assay: comparisons with the Buehler occluded patch test in guinea pigs. J Appl Toxicol 10: 173-180.]

 [Van Huygevoort AHBM (1999 g). Assessment of contact hypersensitivity to Zincweiß Pharma A in the albino guinea pig (maximisation-test). Project 263429. NOTOX B.V., ‘s-Hertogenbosch, The Netherlands.]

[Van Huygevoort AHBM (1999 h1). Assessment of contact hypersensitivity to zinc oxide in the albino guinea pig (maximisation-test). Project 254339. NOTOX B.V., ‘s-Hertogenbosch, The Netherlands.]

[Van Huygevoort AHBM (1999 h2). Assessment of contact hypersensitivity to zinc oxide in the albino guinea pig (maximisation-test). (An extension of NOTOX Project 254339). Project 261214. NOTOX B.V., ‘s-Hertogenbosch,The Netherlands.]

[Van Huygevoort AHBM (1999 i). Assessment of contact hypersensitivity to zinc sulphate heptahydrate in the albino guinea pig (maximisation-test). Project 254328. NOTOX B.V., ‘s-Hertogenbosch, The Netherlands.]


Migrated from Short description of key information:
According to experience from use of the substance in pharmaceutical as well as cosmetic products and from reliable, adequate and relevant read-across data, zinc dilaurate is not likely to be skin sensitising.

Respiratory sensitisation

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

Animal data on respiratory sensitisation are not available neither for zinc dilaurate nor for other zinc compounds. However, there is not any information suggesting zinc compounds to cause such effects. Taking the complete absence of skin sensitisation potential of zinc compounds into account, respiratory sensitisation is not expected to be of concern for zinc and zinc compounds including zinc dilaurate. See also the Chemical Safety Assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1.


Migrated from Short description of key information:
While there is not a particular study addressing respiratory sensitisation in experimental animals, there is also not any information suggesting zinc compounds to cause such effects. Taking the complete absence of skin sensitisation potential of zinc compounds into account, respiratory sensitisation is not expected to be of concern for zinc and zinc compounds including zinc dilaurate.

Justification for classification or non-classification

Animal data on skin sensitisation are not available for zinc dilaurate. The use in cosmetic products is without reported skin sensitisation effects. The data on slightly soluble zinc oxide indicate a lack of a skin sensitising potential (negative in animal and human studies). Assuming that data of zinc compounds with similar water solubility can be read-across, it can be concluded that slightly soluble or insoluble zinc compounds including zinc dilaurate are non-skin sensitisers. Furthermore, data on soluble zinc sulphate indicate the lack of any sensitisation potential. Thus, human data as well as reliable, adequate and relevant read-across data do not suggest any intrinsic sensitising activity of zinc dilaurate. Therefore, zinc dilaurate does not need to be classified/labelled regarding sensitisation in accordance with Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.