Registration Dossier

Administrative data

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2012-03-28 to 2012-04-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
During the MTT assay isopropanol / 2 N HCl 49:1 (v/v) should have been used as extractant solution. Due to inattention isopropanol without HCl was used as extractant solution. Due to Harlan CCR’s experimental experience concerning formazan salt extraction with and without acidifying of isopropanol, and due to the long extraction period of nearly three days, the risk of inadequate extraction is minimized. Therefore, the described deviation did not have a detrimental impact on the outcome of the study.
Justification for type of information:
Zircon, cadmium yellow is a zircon-type oxide/pigment with the main structural element ZrSiO4 (Zr in an dodecahedral O environment) which forms a strong and inert matrix. Zr and Si are the main components with percentages of ~46% w/w and 15% w/w respectively. The amount of Cd as component is about 2% w/w.

The read-across substance Silicic acid, zirconium salt, cadmium pigment encapsulated is a zircon-type pigment as well with an identical crystallographic structure and a very similar composition. Zr content is ~46% w/w and the Si content is ca. 14% w/w. Cd is present in about 4.7% w/w. Minor amounts of Se and S (1.53 and 1.04% w/w, respectively) are present as well.

Besides the obvious structural analogy the solubility of both pigments in aqueous and physilogical media are as follows (determination of Zr and Cd):

Solubility of Cd from the pigment Zircon, cadmium yellow in physiological media was in a range of 0.180 µg/L (PBS) and 0.398 µg/L (ALF) after 2 hours. After 24 hours a dissolution range from 0.140 µg/L (GMB) - 0.722 µg/L (GST) was measured.

Solubility of Zr from the pigment Zircon, cadmium yellow in physiological media was in a range of below LOD and 0.812 µg/L (ALF) after 2 hours. After 24 hours a dissolution range from below LOD (ASW) - 1.44 µg/L (ALF) was measured.

The read-across substance Silicic acid, zirconium salt, cadmium pigment encapsulated afforded after 2 hours a solubility for the element Cd in range of 0.07 µg/L (GMB) 2.58 µg/L (GST) and after 24 hours a solubility of 0.07 µg/L (GMB) to 6.13 µg/L (GST).

Solubility of Zr from the pigment Silicic acid, zirconium salt, cadmium pigment encapsulated in physiological media was in a range of below LOD and 0.52 µg/L (ALF) after 2 hours. After 24 hours a dissolution range from below LOD - 1.25 µg/L (ALF) was measured.

T/D testing of the pigment Zircon, cadmium yellow afforded the following solubility at 1mg loading after 28 days:
Cadmium: below LOD (<0.0048) and 0.2077 ± 0.0993μg/L at pH 8 and pH 6, respectively
Zirconium:
T/D testing of the read-across substance Silicic acid, zirconium salt, cadmium pigment encapsulated afforded the following solubility at 1mg loading after 28 days:
Cadmium: 0.34 ± 0.09 μg/L and 0.86 ± 0.39 μg/L at pH 8 and pH 6, respectively
Zirconium:
In sum, the two zircon type pigments are structurally identical with very similar composition and both show a very low solubility in different artificial and aqueous media. In fact, the read-across substance Silicic acid, zirconium salt, cadmium pigment encapsulated shows slightly higher dissolution and bioaccessibility without showing any signs of systemic or local toxicity in various studies (acute inhalation, skin/eye irritation, sensitisation). No toxicity on algae, fish and invertebrates could be observed in respective studies.
Hence, read-across to Silicic acid, zirconium salt, cadmium pigment encapsulated is fully justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2010-07-22
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: ECVAM international validation study on in vitro tests for acute skin irritation (Altern Lab Anim. 2007 Dec; 35 (6):559-601)
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-03-30

Test material