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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from EFSA journal.

Data source

Reference
Reference Type:
secondary source
Title:
Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on the food colour Red 2G (E128) based on a request from the Commission related to the re-evaluation of all permitted food additives
Author:
European Food Safety Authority
Year:
2007
Bibliographic source:
The EFSA Journal (2007) 515, 1-28

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The subchronic repeated dose toxicity study of Red 2G (CAS No.- 3734-67-6) in mice was conducted to evaluate adverse effects by oral route.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Red 2G- Molecular formula (if other than submission substance): C18H15N3O8S2.2Na- Molecular weight (if other than submission substance): 509.426 g/mol- Substance type: Organic- Physical state: No data avaialble - Impurities (identity and concentrations): Purity: 85.9%Impurity: Water insoluble material 0.06%, Ether extractable material 0.01%, Subsidiary dye 1.0%, Arsenic, Lead <5ppm, Copper <5ppm

Test animals

Species:
mouse
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Three months.
Doses / concentrations
Remarks:
0, 0.01, 0.1, 1, or 2% Red 2G (equivalent to 14, 143, 1429, or 2858 mg/kg bw).
No. of animals per sex per dose:
Five groups of 15 male and 15 female mice were used.
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified
- Time schedule: Not specified
- Cage side observations checked in table [No.?] were included. Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: Not specified

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY: Not specified
- 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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined:Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 5 animals per group
- Parameters checked in table [No.?] were examined. Not specified

CLINICAL CHEMISTRY: Not specified
- Time schedule for collection of blood:Not specified
- Animals fasted: Not specified
- How many animals:Not specified
- Parameters checked in table [No.?] were examined.Not specified

URINALYSIS: Not specified
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined.Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations:Not specified
- Dose groups that were examined:Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other:Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations:Not specified
- How many animals:Not specified
- Dose groups that were examined:Not specified
- Parameters checked in table [No.?] were examined.Not specified

Sacrifice and pathology:
Five mice of each sex at each dose level were killed at 26, 55 and 96 days.

GROSS PATHOLOGY: Not specified

HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
At 0.1, 1.0 and 2.0% a dose-related decrease in Hb, RBC and PCV was seen, with some compensation for red cell loss at three months. A dose-related increase in reticulocytes, Heinz bodies, anisocytosis, polychromasia, poikilocytosis and marrow reaction was seen.
Splenomegaly was observed in both sexes at 2% and in females at 1%.
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:
effects observed, treatment-related
Description (incidence and severity):
A temporary effect on the relative spleen weight was seen at 0.1 and 1.0% in both sexes at 26 and 55 days.
Relative liver weights were increased in females at 1% and 2% at day 26, and at 2% at days 55 and 96.
Significant increases in kidney weight were also noted, being temporary at days 26 and 55 at the doses of 0.01, 0.1 and 1.0% but in females present at 2.0% at 96 days.
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Haemosiderin was increased in the liver (Kupffer cells) at 1% and 2%. In the spleen haemosiderin was increased at 2% at all test days, and at the other concentrations increased with treatment and duration.


Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
143 other: mg/kg bw
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
haematology
organ weights and organ / body weight ratios
histopathology: non-neoplastic
other: No adverse effects were evident.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the condition of the study,the no-observed adverse effect level (NOAEL) of Red 2G (CAS No.- 3734-67-6) in this subchronic study in mice was observed to be 143.0 mg/kg bw.
Executive summary:

The subchronic repeated dose toxicity study of Red 2G (CAS No.- 3734-67-6) in mice was conducted to evaluate the adverse effects by oral route. Five groups of 15 male and 15 female mice were given diets containing 0, 0.01, 0.1, 1, or 2% Red 2G (equivalent to 14, 143, 1429, or 2858 mg/kg bw) for three months. 5 animals per group were haematologically investigated and fully autopsied at days 26, 55, and 96. A dose- dependent increase in the incidence of Heinz bodies was observed. Splenomegaly was observed in both sexes at 2% and in females at 1%. Relative liver weig hts were increased in females at 1% and 2% at day 26, and at 2% at days 55 and 96. Haemosiderin was increased in the liver (Kupffer cells) at 1% and 2%. In the spleen haemosiderin was increased at 2% at all test days, and at the other concentrations increased with treatment and duration. No adverse effects on growth or food consumption were evident. Thus under the condition of the study, the no-observed adverse effect level (NOAEL) of Red 2G (CAS No.- 3734-67-6) in this subchronic study in mice was observed to be 143.0 mg/kg bw.