Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Data is from opinion document of European Food Safety Authority

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

Author:

European Food Safety Authority

Year:

2007

Bibliographic source:

The EFSA Journal (2007) 515, 1-28

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Details of the guidelines are not mentioned in the publication

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

EC Number:

223-098-9

EC Name:

Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Cas Number:

3734-67-6

Molecular formula:

C18H15N3O8S2.2Na

IUPAC Name:

disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate

Constituent 2

Reference substance name:

Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate

IUPAC Name:

Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Cas No: 3734-67-6Chemical Name: Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate (Synonym: Red 2G)Nature of the chemical: Organic

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

250 mg/kg bw Red 2G was administered to male and female rats by gastric intubation

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

250 mg/kg bw Red 2G was administered to male and female rats by gastric intubation

Duration and frequency of treatment / exposure:

48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:250 mg/kg bw

No. of animals per sex per dose / concentration:

No data

Control animals:

not specified

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Absorption is expected to take place in the gastro-intestinal tract

Main ADME results 2

Type:

distribution

Results:

No data

Main ADME results 3

Type:

metabolism

Results:

Pre-systemic and systemic azo-reduction yields 2-amino-8-acetamido-1-naphto-3,6- disulphonic acid and aniline. Aniline is further oxidized to p-aminophenol and o-aminophenol.

Main ADME results 4

Type:

excretion

Results:

Based on excretion of Red 2G metabolites in bile and urine, at least 50-70% of the dose is reduced at the azo-bridge. In urine and faeces of rats less than 5% of unchanged Red 2G could be detected.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

2-amino-8-acetamido-1-naphto-3,6- disulphonic acid & aniline. Aniline is further oxidized to p-aminophenol and o-aminophenol

Any other information on results incl. tables

Metabolism: Pre-systemic and systemic azo-reduction yields 2-amino-8-acetamido-1-naphto-3,6-disulphonic acid and aniline. Aniline is further oxidized to p-aminophenol and o-aminophenol. p-Aminophenol (free and conjugated) was quantitatively the most important metabolite in urine following administration of Red 2G

Excretion: Based on excretion of Red 2G metabolites in bile and urine, at least 50-70% of the dose is reduced at the azo-bridge. In urine and faeces of rats less than 5% of unchanged Red 2G could be detected. Urinary excretion of the aniline moiety takes place mainly in the form of aminophenols (in total 42-56% of the dose). Faecal excretion of these products was also observed although to a lesser degree than in urine.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study resultsDisodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate (Synonym: Red 2G) is known to be metabolized in male and female rats which were administered the chemical by gavage and excreted out of the living system through the urine and a minor amount in feaces. Urinary excretion of the aniline moiety takes place mainly in the form of aminophenols (in total 42-56% of the dose). Faecal excretion of these products was also observed although to a lesser degree than in urine. Thus, considering the quick time (48 hours) in which more than half of the administered dose of the chemical is excreted out of the body of rats, bio-accumulation potential is expected to be low.

Executive summary:

Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate (Synonym: Red 2G) is known to be metabolized in male and female rats and excreted out of the living system through the urine and a minor amount in feaces. In 48 hours in males and females 42.2% and 56.4% of the dose was excreted as p-aminophenol. In 24 hours in males and females 3% and 2.6% of the dose was excreted as unreduced dye. Thus, considering the quick time in which more than half of the administered dose of the chemical is excreted out of the body of rats, bio-accumulation potential is expected to be low. However, the EFSA panel concluded that it would be prudent to regard Red 2G as being of safety concern since it is extensively metabolized to aniline.