Registration Dossier

Diss Factsheets

Administrative data

Description of key information

oral:

Based on a weight of eveidence approach and based on the available read-across data, there is no evidence that Ammonium iron (3+) hexakis (cyano-C) ferrate (4- ) causes any adverse effects after repeated administration of doses up to 2500 mg/kg bw/d.

dermal:

no data are available for dermal repeated dose toxicity.

inhalation:

no data are available for repeated dose toxicity after inhalation.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Study data for subchronic repeated dose toxicity after oral administration are available from the read across substance Colloidal Prussian blue (Dvorak et al. 1971). The test material was administered at an estimated dose of ca. 2500 mg/kg bw/d to young male rats in the drinking water for a duration period of 12 weeks. Body weight was recorded during the administration period. Mortality, clinical signs of toxicity and cage side observations were checked. After the treatment period the animals were sacrificed and the gastrointestinal tract, kidneys, liver and spleen were removed and histopathologically analyzed. The body weight gain of all animals increased within the normal range. No clinical signs of toxicity or any other abnormalities in behaviour were observed during the dosing period in all animals. The histopathological examination of the gastroinestinal tract, kidneys, liver and spleen revealed no abnormalities in all animals. Based on this results the NOAEL was defined as ca. 2500 mg/kg bw/d.

Study data for subchronic repeated dose toxicity after oral administration are also available from the read across substance Berlin blue (Nigrovic et al. 1965). The test material was administered at an estimated dose of ca. 1000 mg/kg bw/d to rats in the food for a duration period of 120 days. The body weight was recorded during the administration period. According to the authors, the body weight of all animals increased within the normal range. Based on body weight gain data only the NOAEL was set at ca. 1000 mg/kg bw/d.

In a third subchronic oral repeated dose toxicity study which was conducted with the read across substance Prussian blue, rats were administered tap water containing Prussian blue at concentrations of 0.025 0.25 and 2.5 g/l for 60 days (equivalent to 0, 2.25, 21.25 and 210 mg/kg bw/d (based on an average body weight of 400 g and a daily fluid intake of ca. 33-37 ml/rat)) (Richmond and Bunde 1966). Each rat received approx. 0.84 µCi of carrier-free 137Cs via the lateral tail vein while under sodium pentobarbital anaesthesia (40 mg/kg bw i.p.); 100 µl of chloride solution (pH 3.5) were injected. About 30 min later, each animal was placed into a liquid scintillation counter and measured fo total 137Cs activity. The rats were then returned to their respective cages and for the following 60 days were allowed to ground food and tap water. The latter contained concentrations of 0, 0.025, 0.25 and 2.5 g/l Prussian blue. Fluid intakes were recorded daily, and the body weights were obtained at each of the 25 times on which the rats were whole body counted. Urinary and fecal samples were collected continuously for the first 30 days of the experiment. No significant differences for the daily fluid intake could be demonstrated. The daily fluid intake was 37.3 +/- 4.9 ml/rat in the control group, 37.2 +/- 5.5 ml/rat in the 0.025 g/l dose group, 34.0 +/- 5.0 ml/rat in the 0.25 g/l dose group and 33.5 +/- 4.2 ml/rat in the 2.5 g/l dose group. During the experiment the body weights increased at an average of 1.33 g/day. Based on this results, the NOAEL was defined as 210 mg/kg bw/d.

Another subacute repeated dose toxicity study is available which was conducted with the read across substance Prussian blue in dogs. After daily oral administration of 137Cs over a period of 10 days to six dogs (Alsatian, litter-mates, body weight 7 -8 kg, 3 months old) four dogs were treated daily with doses of 1.5 and 3.0 g PB, respectively (sub-divided into 3 or 6 fractions of 0.5 g) (equivalent to total daily doses of 0, 214.3 and 428.6 mg/kg bw/d). Two dogs served as controls. The 137Cs body burden was measured by whole-body counting over 11 days. In control dogs the biological half time was found to be 11 days, whereas in treated dogs it was reduced to 6.5 days. The well-being and body weight of the treated animals was not affected by Prussian blue. Based on the available results, the NOAEL was defined as 428.6 mg/kg bw/d.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

No individual study was selected as a weight of evidence approach with data from structurally-related substances was followed.

Justification for classification or non-classification

Taking the results together and based on a weight of evidence approach, no classification is warranted for Ammonium iron (3+) hexakis (cyano-C) ferrate (4- ) according to DSD (67/548/EEC) and CLP (1272/2008/EC) classification criteria for repeated dose toxicity, and the data is therefore conclusive but not sufficient for classification.

Categories Display