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Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

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 elements Al and Mn contained in the pigment, indicating a lack of any concern for genetic toxicity properties.

(1) no signs of local toxicity in an acute inhalation toxicity test at the limit dose of 6.2mg/L. The study has been performed according to OECD TG 403 and which shows no signs of acute toxicity after inhalation exposure to Pigment Mn-Al, indicating a LC50 > 6.2 mg/L. No mortality occurred.

No signs of mutagenic potential in an in-vitro test system that was performed according to OECD 471, could be observed.

(2) In in-vitro dissolution experiments in five different artificial physiological media, dissolved Mn and Al concentrations from this pigment were very low, corresponding to a solubility of less than 1.1 %.

(3) In a 28-day oral toxicity study with 1,000 mg/kg pigment no increase in Al and Mn 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 < 0.002 % (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, 95.5% Al, and 144% Mn of the dose were excreted via faeces within 3 days, with only <0.005% 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 0.09% (Al) and 0.07% (Mn) in relation to a mixture of soluble Al3+and Mn2+compounds (Al2(SO4)3, MnSO4)injected i.v..

Comparing the findings ofin-vitrodissolution testing (2) within-vivoresults (1,3-5), 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 "Manganese alumina pink corundum" 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 (<<0.002% for both metals) and (ii) a mass balance study involving a single dose of 1,000 mg pigment/kg bw (0.004% for Mn and 0.0002% for Al).

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 Al and Mn plasma concentrations were observed, and only a minor fraction (<0.002%) of the total administered dose of Al and Mn 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.

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 Al and Mn plasma concentrations were observed, and only a minor fraction (<0.002%) of the total administered dose of Al and Mn 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 genetic toxicity according to EC Regulation No. 1272/2008 is anticipated.