Prussian blue

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Studies of Any Toxicological Effects of Prussian Blue Compounds in Mammals—A Review

Author:

J. Pearce

Year:

1994

Bibliographic source:

Food and chemical toxicology, Vol. 32, no. 6, pp. 577-582, 1994

Reference 2

Reference Type:

publication

Title:

Diminution of radiocaesium body-hurden in dogs an human beings by Prussian Blue

Author:

F. Bohne, V. Nigrovic, K. Madshus, A. Strömme

Year:

1966

Bibliographic source:

Strahlentherapie 130, 413-419

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Subchronic toxicity study was performed to determine the toxic nature of Berlin Blue

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Prussian blue

EC Number:

237-875-5

EC Name:

Prussian blue

Cas Number:

14038-43-8

Molecular formula:

C6FeN6.4/3Fe

IUPAC Name:

iron(2+);iron(3+);octadecacyanide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: Prussian blue
- IUPAC name: C.I. Pigment Blue 27
- Molecular formula: C6FeN6.4/3Fe
- Molecular weight: 859.23 g/mol
- Smiles : [CH-](#N)[Fe+2]([CH-]#N)([CH-]#N)([CH-]#N)([CH-]#N)[CH-]#N.[CH-](#N)[Fe+2]([CH-]#N)([CH-]#N)([CH-]#N)([CH-]#N)[CH-]#N.[CH-] (#N)[Fe+2]([CH-]#N)([CH-]#N)([CH-]#N)([CH-]#N)[CH-]#N.[Fe+3].[Fe+3].[Fe+3].[Fe+3]
- InChI : 1S/18CN.7Fe/c18*1-2;;;;;;;/q18*-1;3*+2;4*+3
- Substance type: Inorganic
- Physical state: Solid powder (dark blue)

Specific details on test material used for the study:

- Name of test material: Prussian Blue
- Molecular formula: C6FeN6.4/3Fe
- Molecular weight: 877.3812 g/mol
- Substance type: Inorganic
- Physical state: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

other: Albino (Heiligenberg strain)

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

not specified

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed to give dose level of 0 or 1% (500 mg/kg/day)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0 or 500 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required):
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

120 days

Frequency of treatment:

Twice daily

Doses / concentrations

Remarks:

0 or 500 mg/Kg/day

No. of animals per sex per dose:

No data

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Yes, the animals were observed for toxic side effects
- Time schedule: No data

BODY WEIGHT: Yes, body weight changes were noted
- Time schedule for examinations: During the study period

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

No data

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No treatment related toxic side effects were noted

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

A slight increase in the weight gain of treated rats was noted but it did not show any statistical significance (P: 0.2) and hence there was no impairment of growth

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No data

Effect levels

Dose descriptor:

NOAEL

Effect level:

500 other: mg/Kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No statistically significant increase in the weight gain of growing rats was noted

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No observed adverse effect level (NOAEL) for Berlin blue is considered to be 500 mg/Kg/day.

Executive summary:

Repeated dose oral toxicity study was performed to determine the toxic nature of Prussian blue. The test chemical was mixed with feed and was tested at dose levels of 0 or 500 mg/Kg/day for 120 days. The test chemical was given by the oral (feed) route of exposure. During the study period, Berlin blue caused a slight increase in the weight gain of treated rats but it did not show any statistical significance (P: 0.2). Based on these considerations, the No observed adverse effect level (NOAEL) for Berlin blue is considered to be 500 mg/Kg/day.