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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
in vivo (LLNA) study
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2012-03-28 to 2012-04-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline 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 guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
2010-07-22
Deviations:
yes
Remarks:
modified OECD 429 ,method according to Ehlings et al. 2005
Principles of method if other than guideline:
The test was performed in accordance with the method according to Ehling et al (2005): An european inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round, Toxicology 212 (2005) 60-68 and Ehling et al (2005): An european inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round, Toxicology 212 (2005) 69-79.

Threshold values of the stimulation indices of lymph node cell count (i.e. sensitising properties) and ear weight (i.e. irritating properties) were calculated by dividing the average values per group of the test item treated animals by the vehicle treated ones. Values above 1.4 (cell count) or 1.1 (ear weight) are considered positive
(these values were fixed empirically during the inter-laboratory validation of this method). In addition, the lymph node weights were determined for concentration related properties.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Type of study:
mouse local lymph node assay (LLNA)

Test material