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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, the highest dissolved Zr, Si and Pr concentrations were below 2.4 µg/L (24h, ALF), 62.7 µg/L (24h, ALF) and 574 µg/L (24h, GST), respectively, even at the highest loading of 0.1 g/L, referring to a solubility of 0.0024 %, 0.063 % and 0.574 %, respectively. Thus, the pigment is considered biologically inert. The dissolved Zr, Pr and Si concentrations from this pigment in GST, after 2h hours (2-hour gastric passage) were below LoD, 350 μg/L and 30 μg/L, respectively, 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, the highest dissolved Zr, Si and Pr concentrations were below 2.4 µg/L (24h, ALF), 62.7 µg/L (24h, ALF) and 574 µg/L (24h, GST), respectively, even at the highest loading of 0.1 g/L, referring to a solubility of 0.0024 %, 0.063 % and 0.574 %, respectively. Thus, the pigment is considered biologically inert. The dissolved Zr, Pr and Si concentrations from this pigment in GST, after 2h hours (2-hour gastric passage) were below LoD, 350 μg/L and 30 μg/L, respectively, 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 of in-vitro dissolution testing (1) with in-vivo results (2-4), 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 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 an in-vitro dissolution 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).

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