Registration Dossier
Registration Dossier
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EC number: 701-413-5 | CAS number: -
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Additional information
The in-vitro and in-vivo experiments described in the dataset are in very good agreement with regards to the negligible level of bioavailability of the elements Zr, Cd and Se contained in the pigment, indicating a lack of any concern for toxicity to reproduction properties.
(1) No signs of local toxicity in an acute inhalation toxicity test at the limit dose of 5.07 mg/L and no signs of mutagenic or clastogenic potential in different genetic toxicity test systems could be observed.
The inhalation study has been performed according to OECD TG 436 and which shows no signs of acute toxicity after inhalation exposure to the pigment, indicating a LC50 > 5.07 mg/L. No mortality occurred.
(2) In in-vitro dissolution experiments in five different artificial physiological media, dissolved Zr, Cd and Se concentrations from this pigment were very low, corresponding to a solubility of about 0.001%, 0.006% and 0.0008%, respectively.
(3) In a 28-day oral toxicity study with 1,000 mg/kg pigment the uptake of Sn and Cr during 24 hour urine and plasma sampling period was demonstrated to be negligible considering that <<0.05 % of the dose was excreted via urine for both metals, mirrored by either minimal or no increase in blood plasma concentrations. This supports the assumption that all three elements are not biologically available upon ingestion of the pigment Zirconium zircon with encapsulated cadmium selenium sulphide.
(4) In a mass balance study with a single oral dose of 1,000 mg/kg of the pigment, 86.3 % cadmium (Cd) of the dose was excreted via urine and faeces during the first three days after exposure (mean for 10 animals), with only <0.000001 % of the dose being excreted via urine.
(5) In a relative bioavailability study, a relative bioavailability of approx. 0.032/0.033 % (males/females) was calculated for cadmium, following treatment with the pigment.
In conclusion, the oral absolute and relative bioavailability of the pigment "Zirconium zircon with encapsulated cadmium selenium sulphide" can be assumed to be negligible, as demonstrated in three independent in-vivo studies in rats yielding very comparable results, supported by in-vitro dissolution experiments in five different artificial physiological media.
A rounded value of <<0.05% for oral absorption can be taken forward from (i) terminal urine/plasma sampling in a study involving 28 repeated oral doses of 1,000 mg pigment/kg bw/d (<<0.05% for Cd, Zr and Se) and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.000001 % for Cd).
It is concluded that the pigment was well tolerated and that no signs of systemic toxicity whatsoever were observed in rats when administered at a dose of 1000 mg/kg bw/day for up to 28 days. The analysis of cadmium, zirconium, and selenium concentrations of 24h-urine sampled after the last dosing demonstrated the negligible bioavailability of the test substance, with <<0.05% of the dose being
excreted via urine for all three metals. The no observed adverse effect level (NOAEL) in rats is 1000 mg/kg/day.
Effects on developmental toxicity
Additional information
The in-vitro and in-vivo experiments described in the dataset are in very good agreement with regards to the negligible level of bioavailability of the elements Zr, Cd and Se contained in the pigment, indicating a lack of any concern for toxicity to reproduction properties.
(1) No signs of local toxicity in an acute inhalation toxicity test at the limit dose of 5.07 mg/L and no signs of mutagenic or clastogenic potential in different genetic toxicity test systems could be observed.
The inhalation study has been performed according to OECD TG 436 and which shows no signs of acute toxicity after inhalation exposure to the pigment, indicating a LC50 > 5.07 mg/L. No mortality occurred.
(2) In in-vitro dissolution experiments in five different artificial physiological media, dissolved Zr, Cd and Se concentrations from this pigment were very low, corresponding to a solubility of about 0.001%, 0.006% and 0.0008%, respectively.
(3) In a 28-day oral toxicity study with 1,000 mg/kg pigment the uptake of Sn and Cr during 24 hour urine and plasma sampling period was demonstrated to be negligible considering that <<0.05 % of the dose was excreted via urine for both metals, mirrored by either minimal or no increase in blood plasma concentrations. This supports the assumption that all three elements are not biologically available upon ingestion of the pigment Zirconium zircon with encapsulated cadmium selenium sulphide.
(4) In a mass balance study with a single oral dose of 1,000 mg/kg of the pigment, 86.3 % cadmium (Cd) of the dose was excreted via urine and faeces during the first three days after exposure (mean for 10 animals), with only <0.000001 % of the dose being excreted via urine.
(5) In a relative bioavailability study, a relative bioavailability of approx. 0.032/0.033 % (males/females) was calculated for cadmium, following treatment with the pigment.
In conclusion, the oral absolute and relative bioavailability of the pigment "Zirconium zircon with encapsulated cadmium selenium sulphide" can be assumed to be negligible, as demonstrated in three independent in-vivo studies in rats yielding very comparable results, supported by in-vitro dissolution experiments in five different artificial physiological media.
A rounded value of <<0.05% for oral absorption can be taken forward from (i) terminal urine/plasma sampling in a study involving 28 repeated oral doses of 1,000 mg pigment/kg bw/d (<<0.05% for Cd, Zr and Se) and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.000001 % for Cd).
It is concluded that the pigment was well tolerated and that no signs of systemic toxicity whatsoever were observed in rats when administered at a dose of 1000 mg/kg bw/day for up to 28 days. The analysis of cadmium, zirconium, and selenium concentrations of 24h-urine sampled after the last dosing demonstrated the negligible bioavailability of the test substance, with <<0.05% of the dose being
excreted via urine for all three metals. The no observed adverse effect level (NOAEL) in rats is 1000 mg/kg/day.
Justification for classification or non-classification
It is concluded that the pigment was well tolerated and that no signs of systemic toxicity whatsoever were observed in rats when administered at a dose of 1000 mg/kg bw/day for up to 28 days. The analysis of cadmium, zirconium, and selenium concentrations of 24h-urine sampled after the last dosing demonstrated the negligible bioavailability of the test substance, with <<0.05% of the dose being excreted via urine for all three metals. The no observed adverse effect level (NOAEL) in rats is 1000 mg/kg/day.
No classification for toxicity to reproduction according to EC Regulation No. 1272/2008 is anticipated.
Additional information
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