Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate

Endpoint summary

Link to relevant study record(s)

Reference

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The aim of this study is to describe the absorption, distribution and excretion of ~4C-labelled Brown HT in the rat, mouse and guinea-pig following oral administration at low (50-70mg/kg) and high (250 mg/kg) dose levels.

GLP compliance:

not specified

Radiolabelling:

yes

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

The labelled colouring, diluted with unlabelled colouring, was administered as an aqueous solution at a volume (5 ml/kg body weight) that provided a dose level of 50-70 or 250mg Brown HT/kg body weight

Duration and frequency of treatment / exposure:

single dose of 14C-labelled Brown HT
Study duration 3 days

Remarks:

Doses / Concentrations:
50-70 (low dose) or 250mg Brown HT/kg body weight (high dose)

No. of animals per sex per dose / concentration:

3 animals (male)

Control animals:

not specified

Positive control reference chemical:

Not Available

Details on study design:

Not Available

Details on dosing and sampling:

Not Available

Statistics:

Not Available

Type:

absorption

Results:

There is no direct evidence for absorption of unchanged Brown HT from the gastro-intestinal tract.

Type:

distribution

Results:

Major part of the distribution is in the gastro-intestinal tract, liver and kidneys.

Type:

metabolism

Results:

Naphthionic acid was the major urinary metabolite, whereas in the faeces naphthionic acid, trace quantities of unchanged dye and at least two unidentified metabolites were found.

Type:

metabolism

Results:

Recovery of administered radioactivity (%) in Guinea pig in the low dose (50 mg/kg bw and high dose 250 mg/kg bw was found to be 99.3 and 95.7 respectively. Guinea-pigs excreted a greater proportion of the higher dose in the urine

Details on absorption:

Not applicable

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolites identified:

yes

Details on metabolites:

Naphthionic acid & two unidentified metabolites

Organs exhibiting radioactivity

·         Liver

·         Kidney

Conclusions:

In vivo study upon oral administration of the chemical Brown HT [IUPAC name: disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate] to male guinea pig indicates that the chemical is expected to have low bio-accumulation potential since most of the administered radioactivity was eliminated in the faeces after 72 hours.

Executive summary:

From the available data on absorption, distribution, metabolism and excretion in an in vivo study upon oral administration of the chemicalBrown HT [IUPAC name: disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate] to male guinea pig there are indications that the chemical is expected to have low bio-accumulation potential since most of the administered radioactivity was eliminated in the faeces after 72 hours.

Description of key information

Basic toxicokinetics:

In vivo study upon oral administration of the chemical Brown HT [IUPAC name: disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate] to male guinea pig indicates that the chemical is expected to have low bio-accumulation potential since most of the administered radioactivity was eliminated in the faeces after 72 hours.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Basic toxicokinetics:

Based on the available data of basic toxicokinetics for the target substance disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate following result is summarized:

The absorption, metabolism, tissue distribution and excretion of 14C-labelled Brown HT has been studied in the rat, mouse and guinea-pig. Following administration of a single oral dose of either 50 or 250 mg Brown HT/kg, substantially all of the dose was excreted in the urine and faeces within 72 hr, with the majority (more than 80%) being accounted for in the faeces. A significant difference in urinary excretion of radioactivity was seen between male and female rats, as well as clear species differences at the two dose levels used. In all species studied, naphthionic acid was the major urinary metabolite, whereas in the faeces, naphthionic acid, trace quantities of unchanged dye and at least two unidentified metabolites were found. The accumulated radioactivity is cleared rapidly from most tissues on cessation of treatment.

Upon oral administration by gavage of the chemical of14C-labelled Brown HT to guinea pigs and rats, from the information available pertaining to absorption, distribution, metabolism and excretion, it can be concluded that the most of the administered chemical which is metabolized as well as the unchanged dye are excreted out of the living system within 72 hours. Thus, the chemical is expected to have low bio-accumulation potential based on study results and weight of evidence approach.