Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The in-vitro and in-vivo experiments described above are in very good agreement with regards to the negligible level of bioavailability of the elements Zr and Pr contained in the pigment.

(1)   In in-vitro dissolution experiments in five different artificial physiological media, dissolved Zr and Pr concentrations from this pigment were below 2.4 μg/L, 350 μg/L even at the highest loading of 0.1g/L, corresponding to a solubility of less than 0.4%,

(2)   In a 28-day oral toxicity study with 1,000 mg/kg pigment no increase in Zr and 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 << 0.001 % (m/f) were found in the terminal 24-h urine collection period.

(3)   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.

(4)   In a bioavailability study, the absolute (0.000055% (Pr)) and relative (0.000011% (Pr)) bioavailability of orally administered pigment was calculated in relation to a soluble Pr3+compound (PrCl3), injected i.v..

Comparing the findings ofin-vitrodissolution testing (1) within-vivoresults (2-4), thein-vivodata consistently demonstrates slightly lower bioavailability. This is in agreement with the general understanding thatin-vitroexperiments in simulated gastric juice provide a conservative estimate of actual (in-vivo) bioavailability.

In conclusion, the oral 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 comparably results supported by anin-vitrodissolution experiment 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 (<<0.001% for Pr) 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).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The in-vitro and in-vivo experiments described above are in very good agreement with regards to the negligible level of bioavailability of the elements Zr and Pr contained in the pigment.

(1)   In in-vitro dissolution experiments in five different artificial physiological media, dissolved Zr and Pr concentrations from this pigment were below 2.4 μg/L, 350 μg/L even at the highest loading of 0.1g/L, corresponding to a solubility of less than 0.4%,

(2)   In a 28-day oral toxicity study with 1,000 mg/kg pigment no increase in Zr and 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 << 0.001 % (m/f) were found in the terminal 24-h urine collection period.

(3)   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.

(4)   In a bioavailability study, the absolute (0.000055% (Pr)) and relative (0.000011% (Pr)) bioavailability of orally administered pigment was calculated in relation to a soluble Pr3+compound (PrCl3), injected i.v..

Comparing the findings ofin-vitrodissolution testing (1) within-vivoresults (2-4), thein-vivodata consistently demonstrates slightly lower bioavailability. This is in agreement with the general understanding thatin-vitroexperiments in simulated gastric juice provide a conservative estimate of actual (in-vivo) bioavailability.

In conclusion, the oral 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 comparably results supported by anin-vitrodissolution experiment 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 (<<0.001% for Pr) 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).