Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

The Metabolic Disposition of 14C-Labelled Carmoisine in the Rat after Oral and Intravenous Administration

Author:

C. L. Galli, M. Marinovich and L. G. Costa

Year:

1982

Bibliographic source:

Fd Chem. Toxic. Vol. 20. pp. 351 to 356, 1982

Materials and methods

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate

EC Number:

222-657-4

EC Name:

Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate

Cas Number:

3567-69-9

Molecular formula:

C20H12N2Na2O7S2

IUPAC Name:

disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate

Details on test material:

SOURCE OF TEST MATERIAL
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Lot/batch No.of test material: 0015
- Expiration date of the lot/batch: 13 Feb.; 2021
- Purity test date: No data

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: No data
- Specific activity: No data
- Locations of the label: No data
- Expiration date of radiochemical substance: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient Temperature
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: No data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was moistened with distilled water before application.
- Preliminary purification step (if any):No data
- Final dilution of a dissolved solid, stock liquid or gel: No data
- Final preparation of a solid: No data

FORM AS APPLIED IN THE TEST (if different from that of starting material) No data

OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Inc., Calco, Como
- Age at study initiation: No data available
- Weight at study initiation: 150-200 g
- Fasting period before study: 12 hrs
- Housing: The animals were housed individually in metabolic cages
- Diet (e.g. ad libitum): free access to a standard diet (4 RF 21, from Charles River Inc.)
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

other: Drinking water

Details on exposure:

Each rat was dosed with [14C]carmoisine either orally (200 mg/kg body weight; 25 µCi), the dye being dissolved in distilled water to a final volume of 0.3mL

Duration and frequency of treatment / exposure:

5 min

Doses / concentrations

Remarks:

Doses / Concentrations:
200 mg/Kg bw

No. of animals per sex per dose / concentration:

No data available

Control animals:

not specified

Results and discussion

Preliminary studies:

Levels of 14C activity in the samples were determined with a Packard Tri-Carb 3255 scintillation counter.

Main ADME results

Main ADME results 1

Type:

absorption

Main ADME results 2

Type:

distribution

Main ADME results 3

Type:

excretion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Within 5 min of oral administration of the dye, the
blood levels of radioactivity were significantly higher than the blank values, indicating a rapid absorption of carmoisine. The highest level of radioactivity, corresponding to 0.01 % of the orally administered dose per ml of blood, was reached within 10 min and then slowly declined, no 14C activity being detected at 32hr.

Details on distribution in tissues:

Radioactivity was not detected in the brain after any interval, indicating that neither the azo dye nor its metabolites crossed the blood-brain barrier. Among the other tissues analysed, the lungs, testes, spleen, epididymal adipose tissue and muscle showed no levels of radioactivity significantly above the blank values. In the gastro-intestinal tract and liver, radioactivity levels were very well correlated
with the blood values at all times after oral administration. The rate of disappearance from tissues and blood suggests that no accumulation of the dye and/or its metabolites occurs.

Recovery in the urine and faeces accounted for 50% of the oral dose of ~4C activity in the first 16 hr after dosing and for as much as 90% over a 32-hr period.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

No data available

Any other information on results incl. tables

Gastrointestinal tract, liver, kidneys, lungs, spleen, brain, testes, muscles, adipose tissues are the organs exhibiting radioactivity

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
The chemical Carmoisine is expected to have “low bio-accumulation potential” within the body of rats.

Executive summary:

The absorption, distribution and excretion of the red azo dye carmoisine (Ext. D & C No. 10) was studied in male rats. [¹⁴C]Carmoisine was administered in a dose of 200 mg/kg (25/~Ci) by gavage. Radioactivity was measured in blood, tissue, faeces and urine at different times after dosing.

 

After oral administration of the dye, no radioactivity was detected in the brain, adipose tissue, muscle, testes, spleen or lung, and recovery of the administered activity in faeces and urine was almost complete by 32 hr. The radioactivity profile of the blood indicated rapid but poor absorption of [¹⁴C]carmoisine, a maximum radioactivity content corresponding to 0.01% of the dose per ml of blood being reached within 10 min.

 

The highest levels of radioactivity occurred in the gastro-intestinal tract and liver after the injection but after 24hr no radioactivity was detectable in these or other tissues.

 

The bioavailability of [¹⁴C]carmoisine, calculated from the blood-radioactivity curves after oral was less than 10%.

 

Thus, from the above, it can be concluded that the chemical Carmoisine is expected to have “low bio-accumulation potential” within the body of rats.