Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Based on the availability of a developmental toxicity study, no reproductive/developmental screening study is performed.

Effects on developmental toxicity

Description of key information

In an OECD 414 oral developmental toxicity study , rats were dosed up to 1000 mg/kg/ day of the target's analogue sodium ferrocyanide via gavage, resulting in no treatment related effects and thus an NOAEL of ≥ 1000 mg/kg/day could be derived (both maternal and developmental).

Link to relevant study records
Reference
Endpoint:
developmental toxicity
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.
Reason / purpose:
read-across source
Reason / purpose:
assessment report
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Number of pregnant rats/ group did not change with treatment:
Control: 21/25
100 mg/kg/day: 22/25
500 mg/kg/day: 21/25
1000 mg/kg/day: 23/25
One total resorption in control group.

Signs
No treatment-related signs, except treatment at 1000 mg/kg/day was associated with occasional instances of post dosing salivation in 12/23 pregnant rats with greatest incidence on day 9 of pregnancy. Salivation occasionally brown stained, ceased within half an hour of dosing. No differences between pregnant rats in different groups in bodyweight change. No mortalities occurred.

Water and food consumption
An increase in water consumption was noted for all treated groups (cumulative water consumption during treatment period showed dosage-related increase in all treated groups (p<0.05). No effect on food consumption was found.

Macroscopic examination
No adverse effects of treatment were revealed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No adverse effect of treatment was apparent, as assessed by embryofoetal loss, litter and mean foetal weight or sex ratio.
Incidence, type and distribution of malformation and skeletal anomalies and the percentage of foetuses with variant sternebrae were considered not to reflect any adverse effect of treatment.
In groups dosed with 500 or 1000 mg/kg/day a marginal but not statistically significant increase in the number of foetuses with increased dilation of the renal pelvis/ureter was found (4 and 5 foetuses from 4 and 4 litters resp.; in control group: 2 foetuses from 2 litters).
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Abnormalities:
not specified
Developmental effects observed:
not specified

The mean concentrations of sodium ferrocyanide in test solutions were all within 4% of nominal concentrations. The chemical stability of sodium ferrocyanide in aqueous solutions was confirmed during storage for 4 hours at ambient temperature and at +4 °C for 8 days. The method is confirmed to be precise and accurate.

Conclusions:
In an OECD 414 oral developmental toxicity study , rats were dosed up to 1000 mg/kg/ day of sodium ferrocyanide via gavage, resulting in no treatment related effects and thus an NOAEL of ≥ 1000 mg/kg/day could be derived (both maternal and developmental). This result can be read across to potassium ferrocyanide.

Executive summary:

In a prenatal developmental toxicity study, pregnant rats were orally exposed to different dosages of sodium ferrocyanide up to 1000 mg/kg/day. The animals were exposed daily, from day 6 to (and including) day 15 of the pregnancy. Rats were sacrificed at day 20. Treatment with sodium ferrocyanide at 1000 mg/kg/day elicited occasional instances of post-dosing salivation in about half of the animals with the greatest incidence occuring after 4 days of dosing. Over the dosing period as a whole, water intake of all three groups was significantly higher than of the control value, the greatest difference being recorded at 1000 mg/kg. This effect was not considered adverse. No other treatment or dosage-related responses were observed in the dams and litter parameters appeared to be unaffected at all of the dosages investigated, as judged by in utero survival, foetal growth and morphological development. Although a small number of foetuses from the two highest dosages showed increased dilation of the renal pelvis/ ureter, this increase was marginally and not statistically significant and thus not considered to be an effect of treatment. This results in a maternal NOAEL of ≥1000 mg/kg/day and a developmental NOAEL of ≥1000 mg/kg/day.

The results can be read across to the target substance, potassium ferrocyanide.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Performed according to GLP principles and OECD test guide line, although not according to current guideline. Some minor deviations are not expected to have influence on the study.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a prenatal developmental toxicity study, pregnant rats were orally exposed to different dosages of the target's analogue sodium ferrocyanide up to 1000 mg/kg/day. The animals were exposed daily, from day 6 to (and including) day 15 of the pregnancy. Rats were sacrificed at day 20. Treatment with sodium ferrocyanide at 1000 mg/kg/day elicited occasional instances of post-dosing salivation in about half of the animals with the greatest incidence occuring after 4 days of dosing. Over the dosing period as a whole, water intake of all three groups was significantly higher than of the control value, the greatest difference being recorded at 1000 mg/kg. This effect was not considered adverse. No other treatment or dosage-related responses were observed in the dams and litter parameters appeared to be unaffected at all of the dosages investigated, as judged by in utero survival, foetal growth and morphological development. Although a small number of foetuses from the two highest dosages showed increased dilation of the renal pelvis/ ureter, this increase was marginally and not statistically significant and thus not considered to be an effect of treatment. This results in a maternal NOAEL of ≥1000 mg/kg/day and a developmental NOAEL of ≥1000 mg/kg/day.

Justification for selection of Effect on developmental toxicity: via oral route:

One study available with Klimisch reliability 1.

Justification for classification or non-classification

Based on the available data, the target's analogue sodium ferrocyanide showed no reproduction toxicity. Therefore potassium ferrocyanide does not need to be classified for reproduction toxicity according to CLP Regulation (No) EC 1272/2008.