Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate

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:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1962

Materials and methods

Objective of study:

excretion

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other: Excretion and Metabolism study of the test chemical

Principles of method if other than guideline:

The present investigation deals with the metabolism and excretion of the test chemical

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate

EC Number:

240-474-8

EC Name:

Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate

Cas Number:

16423-68-0

Molecular formula:

C20H8I4O5.2Na

IUPAC Name:

disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate

Details on test material:

- Name of test material (as cited in study report):
D&C Red 3
- Molecular formula (if other than submission substance): C20-H6-I4-O5.2Na
- Molecular weight (if other than submission substance): 879.8424 g/mol
- Substance type: Organic
- Physical state: Solid

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: Young Adult
- Weight at study initiation: 200 g
- Housing: After dosing, the animals were placed in individual metabolism cages and urine collected free from feces in a glass separator (Gage, 1961)
- Diet (e.g. ad libitum): The animals were maintained on Diet 86 (North-Eastern Agricultural Cooperative).
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: 0.5 g/kg of the test chemical was administered in aqueous suspension to rats

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

Duration and frequency of treatment / exposure:

3 days

Doses / concentrations

Remarks:

64, 108, 156, 100 mg

No. of animals per sex per dose / concentration:

64, 108, 156 - number of animals - 4
100 - number of animals - 2

Control animals:

not specified

Positive control reference chemical:

Details not available

Details on study design:

no data available

Details on dosing and sampling:

TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, blood, plasma, serum or other tissues, cage washes, bile ): urine
- Time and frequency of sampling:
- Other: To minimize oxidation of am!nophenols, the urine collectors were immersed in solid carbon dioxide. Urine was analyzed daily for at least 3 days after dosing
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile ) urine
- Time and frequency of sampling: Urine was analyzed daily for at least 3 days after dosing
- From how many animals: (samples pooled or not) : 4
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC) : Glucuronic acid and ethereal sulfate were determined
as described by Mead et al., 1958. Ultraviolet absorption measurements were made on a Unicam SPSOO spectrophotometer in silica cells with a 10-mm optical path. Measurements in the visible range were made on a Unicam SP600 spectrophotometer. Infrared spectra were determined in Nujol mull on a Grub-Parsons G62 spectrophotometer.
- Limits of detection and quantification:
- Other: Isolation and identification of metabolites was estimated fluorimetrically in bile using an Aminco-Bowman spectrophotofluorimeter. Various dilutions of bile were made in 0.1 M Na2HP04 (pH 9.1) and the test chemical was estimated at 550 rnp after activation at 528 mu. The instrument was set at zero absorbance against a solution of the test chemical (1 ug/ml) in 0.1 M Na2HP04.

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Statistics:

Details not available

Results and discussion

Main ADME results

Main ADME results 1

Type:

metabolism

Results:

It appeared that the test chemical was metabolized to some extent in the tissues

Main ADME results 2

Type:

excretion

Results:

The test chemcial was found to be largely excreted in the feces and no color could be identified in the urine. A small amount of the color is excreted in the bile, and, on the basis of the amount of color recovered (50-70%).

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Details not available

Details on distribution in tissues:

Details not available

Details on excretion:

The test chemcial was found to be largely excreted in the feces and no color could be identified in the urine. A small amount of the color is excreted in the bile, and, on the basis of the amount of color recovered (50-70%).

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

Details not available

Any other information on results incl. tables

THE EXCRETION, IN RATS, OF THE TEST CHEMICAL IN THE BILE AND FECES

Total amount fed (mg)	Number of animals	Excreted in feces (%)	Excreted in bile (%)
64	4	60	-
108	4	72	-
156	4	55	-
100	1	-	0.44
100	1	-	1.67

Applicant's summary and conclusion

Conclusions:

The test chemical was found to be largely excreted in the feces and, despite the presence of two groups capable of undergoing conjugation, no color could be identified in the urine. A small amount of the color is excreted in the bile, and, on the basis of the amount of color recovered (50-70% ),it appeared that the test chemical was metabolized to some extent in the tissues.

Executive summary:

A study has been performed to assess the metabolic behavior of the test chemical. 0.5 g/kg of the test chemical was administered in aqueous suspension to rats. The animals were maintained on Diet 86 (North-Eastern Agricultural Cooperative). After dosing, the animals were placed in individual metabolism cages and urine collected free from feces in a glass separator (Gage, 1961). To minimize oxidation of aminophenols, the urine collectors were immersed in solid carbon dioxide. Urine was analyzed daily for at least 3 days after dosing. All animals used were males. Glucuronic acid and ethereal sulfate were determined as described by Mead et al., 1958. Ultraviolet absorption measurements were made on a Unicam SP500 spectrophotometer in silica cells with a 10-mm optical path. Measurements in the visible range were made on a Unicam SP600 spectrophotometer. Infrared spectra were determined in Nujol mull on a Grub-Parsons G62 spectrophotometer. Isolation and identification of metabolites was estimated fluorimetrically in bile using an Aminco-Bowman spectrophotofluorimeter. Various dilutions of bile were made in 0.1 M Na₂HP0₄(pH 9.1) and the test chemical was estimated at 550 mµ after activation at 528 mµ. The instrument was set at zero absorbance against a solution of the test chemical (1 µg/ml) in 0.1 M Na₂HP0₄.The test chemical was found to be largely excreted in the feces and, despite the presence of two groups capable of undergoing conjugation, no color could be identified in the urine. A small amount of the color is excreted in the bile, and, on the basis of the amount of color recovered (50-70% ),it appeared that the test chemical was metabolized to some extent in the tissues