Registration Dossier
Registration Dossier
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EC number: 269-075-7 | CAS number: 68187-15-5 An inorganic pigment that is the reaction product of high temperature calcination in which praseodymium (III) oxide, praseodymium (IV) oxide, silicon oxide, and zirconium (IV) oxide in varying amounts are homogeneously and ionically interdiffused to form a crystalline matrix of zircon. Its composition may include any one or a combination of the modifiers alkali or alkaline earth halides.
Carcinogenicity
Administrative data
Description of key information
Key value for chemical safety assessment
Carcinogenicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
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. Either no or only marginal increases in Pr plasma concentrations were observed, and only a minor fraction (<<0.001%) of the total administered dose of Pr was collected via urine, documenting the lack of bioavailability of this pigment. The no observed adverse effect level (NOAEL) in rats is 1000 mg/kg/day.
No classification for carcinogenicity according toEC Regulation No. 1272/2008 is anticipated.
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 element Pr contained in the pigment, indicating a lack of any concern for carcinogenic properties.
(1) no signs of local toxicity in an acute inhalation toxicity test at the limit dose of 5.5 mg/L. The study has been performed according to OECD TG 403 and which shows no signs of acute toxicity after inhalation exposure to the pigment, indicating a LC50 > 5.5 mg/L. No mortality occurred. An acute oral toxicity test according to OECD 401 afforded a LD50 value of >2200 mg/kg.bw.
No signs of mutagenic or clastogenic potential in three different genetic toxicity test systemscould be observed.
(2) In in-vitro dissolution experiments in five different artificial physiological media, dissolved Zr, Si and Pr concentrations from this pigment were very low, corresponding to a solubility of less than 0.4% (GST, 2h)
(3) In a 28-day oral toxicity study with 1,000 mg/kg pigment no increase in Pr plasma and urine concentrations were observed when sampled at the end of the 28-day exposure period. From a final dose of 1,000 mg/kg of the pigment that the animals received on the last day of the study, only cumulated relative amounts of < 0.00001 % (m/f) were found in the terminal 24-h urine collection period.
(4) In a mass balance study with a single oral dose of 1,000 mg/kg of the pigment, 102% Pr of the dose and 74.3% Zr were excreted via faeces within 3 days, with only <0.00001% Pr and < 0.002% Zr of the dose being excreted via urine at the same time.
(5) In a bioavailability study, the absolute and relative bioavailability of orally administered pigment was calculated 0.00005/0.000007% Pr (m/f) in relation to a soluble Pr3+compound (PrCl3)injected i.v..
Comparing the findings of in-vitro dissolution testing (2) with in-vivo results (1,3-5), the in-vivo data consistently demonstrates slightly lower bioavailability. This is in agreement with the general understanding that in-vitro experiments in simulated gastric juice provide a conservative estimate of actual (in-vivo) bioavailability.
In conclusion, the oral absolute and relative bioavailability of the pigment "Zirconium praseodymium yellow zircon" 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 <<0.01% 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 (<<0.00001%)and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.00003% for Pr and <<0.00001% for Zr).
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. Either no or only marginal increases in Pr plasma concentrations were observed, and only a minor fraction (<<0.001%) of the total administered dose of Pr was collected via urine, documenting the lack of bioavailability of this pigment. The no observed adverse effect level (NOAEL) in rats is 1000 mg/kg/day.
Overall conclusions
Considering the well-documented poor bioavailability, the absence of any indication of genotoxicity and the lack of any adverse findings in a 28d oral toxicity study, there is no concern for carcinogenicity to be anticipated.
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