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The following remarks on the toxicokinetics are based on physicochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

 

Statement from previous notification dossier, given by the notifier (1997)

"There is no clear indication of systemic effects following administration of the substance by ingestion or inhalation, other than an effect to alanine aminotransferase activity following oral administration daily over 28 days. The significance of this finding was itself debatable.

However, the results of the mouse micronucleus test indicates significant toxicity following intraperitoneal administration in a water suspension. Toxic effects were seen above 357 mg/kg with an estimated LD50 of 500 mg/kg.

This suggests poor absorption by the lungs and gastro-intestinal tract, although interspecies differences could account for some of this variance.

The particle size distribution indicates that the substance is potentially respirable and the low water solubility indicates the possibility of retention. However, it is not clear how the breakdown of the substance in aqueous environments would affect retention in the lung. Dermal absorption is predicted to be low.

In water the substance breaks down to form mainly zinc chloride, zinc hexacyanocobaltate and butylalcohol / polypropylene glycol. It is not clear how extensive this breakdown is in vivo, nor how much of these breakdown products could be absorbed. It is therefore not possible to make any clear statements about distribution, metabolism and potential routes of elimination."

 

Cited from Risk Assessment of Federal Institute for Risk Assessment (Germany) of previous notification (of 20.01.2004)

"The degree of purity of the substance is 99 to 100%. One chemically identified compound is given as impurity. By its chemical structure the main component is identified as complex compound of zinc hexacyanocobaltate with butylalcohol / polypropylene glycol.

From the physico-chemical data [water solubility (exact determination not possible due to rapid hydrolysis dependent on pH), partition coefficient log Pow revealing different values of the products of breakdown and molecular weight (983)] the substance can be assumed to have a probably moderate oral bioavailability. It seems likely that some products of hydrolysis reveal better bioavailability than the parent compound. This was partly confirmed by toxicological testing.

From the physico-chemical data [vapour pressure (1.1 x 10 (-5) Pa), particle size distribution (50% < 10.69 µm; 10% <3.16 µm) and molecular weight] the substance can be assumed to enter the body by the inhalation route, if dust exposure is given.

From the physico-chemical data (water solubility, partition coefficient and molecular weight) the substance can be assumed to enter poorly the body by the dermal route."

 

Deviating from the data above, more recent investigations indicate a mean molecular weight of 1125 g/mol.

 

A recently conducted reproduction/developmental screening study (OECD 421) gave also no indication for systemic availability after oral exposure, since no treatment related adverse effects were observed at all up to the highest dose of 1000 mg/kg bw.

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