Registration Dossier

Diss Factsheets

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 in this dataset are in very good agreement with regards to the negligible level of bioavailability of the element Fe contained in the pigment.

(1)  In in-vitro dissolution experiments in five different artificial physiological media after 24h, dissolved Fe and Si concentrations from this pigment were below 63 μg/L and 413 μg/L, respectively, even at the highest loading of 0.1 g/L, corresponding to a solubility of less than 0.5 %,

(2)  In a 28-day oral toxicity study with 1,000 mg/kg pigment minimal or no increase in Fe 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 << 0.005 % (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, 110.7 % Fe, were excreted via faeces within 3 days, with only <0.016 % of the dose being excreted via urine at the same time.

(4)  In a relative bioavailability study, the relative bioavailability of orally administered pigment was calculated 0.95/0.58 % Fe (m/f) in relation to a mixture of soluble Fe3+compound (Fe(C6H5O7)*H2O)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 “High-temperature calcination products of diiron trioxide and amorphous silica resulting in a glassy silica matrix” 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 and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.016 % for Fe).

 

Absorption rate - oral: 0.01 %

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 in this dataset are in very good agreement with regards to the negligible level of bioavailability of the element Fe contained in the pigment.

(1)  In in-vitro dissolution experiments in five different artificial physiological media after 24h, dissolved Fe and Si concentrations from this pigment were below 63 μg/L and 413μg/L, respectively, even at the highest loading of 0.1g/L, corresponding to a solubility of less than 0.5 %,

(2)  In a 28-day oral toxicity study with 1,000 mg/kg pigment minimal or no increase in Fe 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 << 0.005 % (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, 110.7% Fe, were excreted via faeces within 3 days, with only <0.016 % of the dose being excreted via urine at the same time.

(4)  In a relative bioavailability study, the relative bioavailability of orally administered pigment was calculated 0.95/0.58 % Fe (m/f) in relation to a mixture of soluble Fe3+compound (Fe(C6H5O7)*H2O)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 “High-temperature calcination products of diiron trioxide and amorphous silica resulting in a glassy silica matrix” 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 and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.016 % for Fe).

 

Absorption rate - oral: 0.01 %