Tripotassium hexacyanoferrate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Based on the presence of identical metal-cyanide complex species, the source substance sodium ferrocyanide and the target substance potassium ferricyanide can be regarded as analogues. This implies that data from sodium ferrocyanide can be read across to the target substance potassium ferricyanide. The complete rationale can be found in the read-across report attached in 'Attached justification'.

Reason / purpose for cross-reference:

read-across source

Type:

absorption

Results:

For risk assessment purposes 10% oral and 10% dermal absorption is taken into account. The potential inhalation exposure is negligible and thus no absorption derived.

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. The good water solubility of Sodium ferrocyanidef avors the uptake from the gastro-intestinal tract. However, the presence of ionisable groups and the moderate high molecular weight are indicative for impaired absorption, as ionized substances do not easily pass the gastro-intestinal wall. It is therefore unlikely that potassium ferricyanide will show a high systemic exposure after oral administration. Based on the available physical/chemical properties of potassium ferricyanide, for risk assessment purposes the oral absorption is set at 10%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Excretion of the target's analogue ,sodium ferrocyanide, occurs mainly via urine through glomerular filtration ands is assumed too for potassium ferricyanide based on the similar physcial and chemical properties. Bioaccumulation is not expected for this substance, as during metabolism cyanide will be transformed to thiocyanide, which has a plasma half-life of less than 1 hour.

In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled. Based on the high particle size, physical state and vapour pressure of potassium ferricyanide, The potential for inhalation is negligble. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW>500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of potassium ferricyanide do not meet the criteria for limited dermal absorption, for risk assessment purposes 100% dermal absorption needs to be considered. It is, however, generally accepted that dermal absorption is lower compared to oral absorption. The 100% dermal absorption derived from the physical/chemical properties of the substance should therefore be considered as unrealistic worst case assumption. For risk assessment purposes a lower dermal absorption value of 10% is considered more appropriate. This result is read across to Potassium ferricyanide.

Description of key information

 According to the REACH Guidance IR CSA R.7c, an assessment on the toxicokinetic properties of a substance analogue has been performed, resulting in low absorption via de oral and dermal route, while via the inhalation route no significant inhalable fraction is present due to the high particle size. This conclusion is read across to Potassium ferricyanide (the rationale is attached in section 13).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

10

Additional information

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. The good water solubility of Sodium ferrocyanide favors the uptake from the gastro-intestinal tract. However, the presence of ionisable groups and the moderate high molecular weight are indicative for impaired absorption, as ionized substances do not easily pass the gastro-intestinal wall. It is therefore unlikely that potassium ferricyanide will show a high systemic exposure after oral administration. Based on the available physical/chemical properties of potassium ferricyanide, for risk assessment purposes the oral absorption is set at 10%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Excretion of the target's analogue, sodium ferrocyanide, occurs mainly via urine through glomerular filtration and is assumed too for potassium ferricyanide based on the similar physcial and chemical properties. Bioaccumulation is not expected for this substance, as during metabolism cyanide will be transformed to thiocyanide, which has a plasma half-life of less than 1 hour.

In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled. Based on the high particle size, physical state and vapour pressure of potassium ferricyanide, the potential for inhalation is negligble. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW>500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of potassium ferricyanide do not meet the criteria for limited dermal absorption, for risk assessment purposes 100% dermal absorption needs to be considered. It is, however, generally accepted that dermal absorption is lower compared to oral absorption. The 100% dermal absorption derived from the physical/chemical properties of the substance should therefore be considered as unrealistic worst case assumption. For risk assessment purposes a lower dermal absorption value of 10% is considered more appropriate. This conclusion is read across to Potassium ferricyanide (the rationale is attached in section 13).