Toxicology and Environmental Aspects

Iron blue pigment compounds show no toxicity in animal studies, therefore they are not expected to cause any adverse effects on human health. No toxic effects were reported in humans when iron blue pigment compounds were used experimentally or therapeutically.

Toxico-kinetic studies showed, that the adsorption of iron blue pigments is very low. Following intravenous injection of a 59Fe radio-labeled iron blue pigment, the 59Fe(CN)6- ion was rapidly and virtually completely excreted with the urine. After oral administration of ferric hexacyanoferrate (59Fe) approx. 2% of the labeled hexacyano — ferrate ion was adsorbed by the gastro-intestinal tract [3.199]. Most of the substance is excreted with the feces [3.200] and there was no evidence of its decomposition.

The decomposition of iron blue to toxic cyanide in aqueous systems is very low. The HCN release of KFe[Fe(CN)6] in artificial gastric or intestinal juice was 141 or 26 pg g-1 per 5 h respectively and in water 37 pg g-1 per 5 h. The corresponding figures of Fe4[Fe(CN)6]3 were 64, 15 and 22 pg g-1 per 5 h [3.201].

In the breath of rats after intraperitoneal injection of 14C-labeled KFe[Fe(CN)6], less than 0.01% (detection limit) was found, whereas in another study 0.04-0.08% of the orally administered dose was found in the exhaled air [3.202]. It can be concluded, that the hexacyanoferrate(II) complex disintegrates only to a small extent in the intestinal tract after oral administration. This is confirmed by the results of acute oral toxicity studies which show in high doses no clinical symptoms or lethality. The LD50 values are above 5000-15,000 mg kg-1 (limit tests) [3.203-3.205].

In primary irritation tests no or only slight effects were seen at the skin or in the eyes of the treated rabbits respectively [3.205, 3.206]. No skin sensitization occurred in a Guinea pig maximization test [3.203].

The subchronic (90-120 days) consumption of iron blue at concentrations of 1-2% in the food or drinking water influenced slightly the body weight gain, but no other clinical signs or histopathological changes were observed [3.207-3.210]. After the administration of daily doses of 200 or 400 mg kg-1 for ten days to dogs their body weight gained and the general condition remained unaffected [3.211].

In a bacterial test system (Ames test) no increase of mutagenicity was detected without or in the presence of a metabolic system [3.205].

In human volunteers who received 1.5 or 3.0 g ferric hexacyanoferrate(II) for up to 22 days apart from a slight obstipation no effects were reported [3.211, 3.212].

Prussian blue Fe4[Fe(CN)6]3 can bind cesium; therefore it is used in clinical practice as an antidote for the treatment of humans contaminated with radioactive cesium (see also Section 3.6.4). Clinical use of ferric ferrocyanide in doses up to 20 g d-1 for decontaminations of persons exposed to radiocesium has not been associated with any reported toxicity [3.201].

Prussian blue is also used as an effective antidote for thallium intoxication. Fer­ric ferrocyanide interferes with the enterosystemic circulation of thallium ions and enhances their fecal excretion [3.213].

In a semistatic acute fish toxicity test (Leuciscus idus. melanotus, fresh water fish) a saturated solution with different iron blue compounds (with undissolved material on the bottom or filtered solution) no deaths occurred within 96 h. Based on the quantity weighed, the No Observed Effect Level (NOEL) is greater than 1000 mg L-1 (nominal concentrations) [3.214].

The bacterial toxicity was measured according DEV, DIN 38412, L3 [TTC(2,3,5- triphenyl-2H-tetrazoliumchloride) test]. The result gives an EC50 (effective concen­tration) varying between 2290 and 14,700 mg L-1, and estimated NOEL values in the range of <10 to 100 mg L-1 [3.215].

There are no harmful effects on fish, but the toxic effects on bacteria constitute a slight hazard when iron blue is present in water.

References

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