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Carcinogenicity

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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 Fe plasma concentrations were observed, and only a minor fraction (<0.003%) of the total administered dose of Fe 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 Fe 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 5.04 mg/L. The study has been performed according to OECD TG 436 and which shows no signs of acute toxicity after inhalation exposure to Pigment Fe-Si, indicating a LC50 > 5.04 mg/L. No mortality occurred.


No signs of mutagenic or clastogenic potential in three different genetic toxicity test systems could be observed.


 


(2) In in-vitro dissolution experiments in five different artificial physiological media, dissolved Fe concentrations from this pigment were very low, corresponding to a solubility of less than 0.45 %.


 


(3) In a 28-day oral toxicity study with 1,000 mg/kg pigment 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 < 0.003 % (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, 110.7% Fe of the dose were excreted via faeces within 3 days, with only <0.013% of the dose being excreted via urine at the same time.


 


(5)   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 soluble Fe3+compound (Fe(C6H5O7)*H2O)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 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 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 (<<0.005%) and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.016% for Fe).


 


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 Fe plasma concentrations were observed, and only a minor fraction (<0.003%) of the total administered dose of Fe 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.