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Toxicological information

Repeated dose toxicity: oral

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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

Referenceopen allclose all

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 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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.