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Toxicological information

Basic toxicokinetics

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Administrative data

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 identical metal-cyanide complex species, the source substance sodium ferrocyanide and the target substance potassium ferrocyanide can be regarded as analogues, which implies that data from sodium ferrocyanide can be read-across to the target substance potassium ferrocyanide based on this information. The complete rationale can be found in the read-across report in section 13.
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Reason / purpose:
read-across source
Reference
Endpoint:
basic toxicokinetics
Type of information:
other: theoretical assessment based on physico-chemical properties
Adequacy of study:
key study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetic assessment based on the physico-chemical properties of sodium ferrocyanide and data available.
Principles of method if other than guideline:
Toxicokinetic assessment based on physico-chemical properties for the derivation of the percentage absorption after exposure by the oral, inhalation and dermal route for risk assessment purposes.
GLP compliance:
no
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. Therefore, the good water solubility 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 sodium ferrocyanide will show a high systemic exposure after oral administration. Based on the available physical/chemical properties of sodium ferrocyanide, 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 sodium ferrocyanide occurs mainly via urine through glomerular filtration. 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 particle size of sodium ferrocyanide, particles <100µm which have the potential to be inhaled, are not present.

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 sodium ferrocyanide 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.

Reason / purpose:
assessment report

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Physical appearance: (light) yellow crystals

Results and discussion

Main ADME results
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.

Any other information on results incl. tables

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. Therefore, the good water solubility 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 ferrocyanide will show a high systemic exposure after oral administration. Based on the available physical/chemical properties of potassium ferrocyanide, 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 ferrocyanide 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 ferrocyanide, 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 ferrocyanide 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.

Applicant's summary and conclusion