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Administrative data

Description of key information

Repeated dose toxicity: Oral

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.

Repeated dose toxicity: Inhalation

The melting point C.I.Pigment Blue 27 is >300 C. This suggests that Prussian violet insoluble decomposes between 210°C -360 °C without melting and does not exhibit very high vapour pressure. Inhalation is therefore not the likely route of exposure and hence this end point for repeated dose toxicity be inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The Prussian blue insoluble (14038-43-8) has high molecular weight i.e 877.381 g/mol. This suggests that Prussian violet insoluble has no potential for significant rate of absorption through the skin and hence this end point for repeated dose toxicity dermal is considered for waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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
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
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
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
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
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
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
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
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
Critical effects observed:
not specified
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is from peer reviewed publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver

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
Quality of whole database:
Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data available for the target chemical has been reviewed to determine the toxic nature of Prussian blue (insoluble) (C.I.Pigment Blue 27) upon repeated exposure by oral, dermal or inhalation route of exposure. The summary is as mentioned below:

Repeated dose toxicity: Oral

Repeated dose oral toxicity study was performed by V. Pearce (Food anc chemical toxicology, 1994) and Bohne et al (Strahlentherapie, 1966) to determine the toxic nature of Prussian blue (CAS no 14038 -43 -8; IUPAC name: C.I.Pigment Blue 27). 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.

In another study mentioned by V. Pearce (Food and chemical toxicology, 1994) and Nigrovic (Physics in medicine and biology, 1965), Repeated dose oral toxicity study was performed to determine the toxic nature of Prussian blue (CAS no 14038 -43 -8; IUPAC name: C.I.Pigment Blue 27). The test chemical was tested at dose levels of 0 or 100 mg/Kg/day for 11 days. The test chemical was given by gastric tube to group of 6-10 Albino rats for 11 days. During the study period, Prussian blue did not affect the body weight of the animals and no treatment related toxic side effects were noted. Based on the observations made, the No observed adverse effect level (NOAEL) for Prussian blue is considered to be 100 mg/Kg/day.

Repeated dose toxicity: Inhalation

The melting point C.I.Pigment Blue 27 is >300 C. This suggests that Prussian violet insoluble (C.I.Pigment Blue 27) decomposes between 210°C -360 °C without melting and does not exhibit very high vapour pressure. Inhalation is therefore not the likely route of exposure and hence this end point for repeated dose toxicity be inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The Prussian blue insoluble (CAS no.: 14038-43-8; IUPAC name: C.I.Pigment Blue 27) has high molecular weight i.e 877.381 g/mol. This suggests that Prussian violet insoluble has no potential for significant rate of absorption through the skin and hence this end point for repeated dose toxicity dermal is considered for waiver.

Based on the data available for the target chemical and its read across, Prussian blue (insoluble) (C.I.Pigment Blue 27) is not likely to be toxic upon repeated exposure by oral, dermal and inhalation route as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, Prussian blue (insoluble) (CAS no 14038 -43 -8) is not likely to be toxic upon repeated exposure by oral, dermal and inhalation route as per the criteria mentioned in CLP regulation.