Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complex

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

The Metabolism and Excretion of Tartrazine in Rat, Rabbit and Man

Author:

R. Jones, A. J. Ryan and S. E. Wright

Year:

1964

Bibliographic source:

Food & Cosmetic Toxicology. Vol. 2, pp. 447-452, 1964

Materials and methods

Objective of study:

other: To study the metabolism and excretion of Tartrazine in Rat, Rabbit & Man

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Tartrazine was given to rats by intraperitoneal injection or by stomach tube in aqueous solution. Intraperitoneal doses were at the rate of 2.4 mg/kg and the amount of tartrazine excreted in urine was determined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

EC Number:

217-699-5

EC Name:

Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Cas Number:

1934-21-0

Molecular formula:

C16-H12-N4-O9-S2.3Na

IUPAC Name:

trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Details on test material:

- Name of test material (IUPAC name): Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- Name of test material :Tartrazine
- Molecular formula:C16H12N4O9S2.3Na
- Molecular weight :534.3681 g/mol
- Smiles notation: n1(c2ccc(cc2)S(=O)(=O)[O-])c(c(c(n1)C(=O)[O-])/N=N/c1ccc(cc1)S(=O)(=O)[O-])O.[Na+].[Na+].[Na+]
-InChl:1S/C16H12N4O9S2.3Na/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;;;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);;;/q;3*+1/p-3/b18-17+;;;
- Substance type:Organic

Radiolabelling:

yes

Remarks:

[14C]tartrazine

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Tartrazine was given to rats by intraperitoneal injection or by stomach tube in aqueous solution. Intraperitoneal doses were at the rate of 2.4 mg/kg; oral doses were 5 mg/rat.

Administration / exposure

Route of administration:

other: intraperitoneal injection or by stomach tube in aqueous solution

Vehicle:

water

Details on exposure:

[14C]Tartrazine was administered to rats by intraperitoneal injection at 2.4 mg/kg. Urine was collected for 48 hr and assayed for radioactivity. The acid-hydrolysed urine was examined for labelled sulphanilic acid by the addition of a known amount of unlabelled material, equilibration and isolation, followed by purification to constant specific activity.

Duration and frequency of treatment / exposure:

Urine was collected for 48 hr and assayed for radioactivity

Doses / concentrations

Remarks:

Doses / Concentrations:
intraperitoneal injection was given at 2.4 mg/kg & oral dosage was given at 5 mg/rat.

No. of animals per sex per dose / concentration:

Not specified

Control animals:

not specified

Details on study design:

Measurement of radioactivity: This was estimated using a gas flow Geiger-Muller counter. Pure compounds were counted at infinite thickness. Urine samples were counted as agar discs according to the method of McCready (1958).
Estimation of sulphanilic acid in urine: Sulphanilic acid was estimated before and after acid hydrolysis of the urine using the method described by Bratton & Marshall (1939) for sulphanilamide.
Paper chromatography of urinary metabolites: This was carried out in three solvent systems: butan-1-ol-2N-acetic acid-water (4:1:5, by vol.); butan-1-ol-2N-NH3 (1:1, by vol.); butan-1-ol-ethanol-water (7:1:2, by vol.). Amines were detected with Erhlich's reagent.

Details on dosing and sampling:

[~4C]Tartrazine was administered to rats by intraperitoneal injection at 2.4 mg/kg & oral dosage was given at 5 mg/rat. Urine was collected for 48 hr and assayed for radioactivity.

Results and discussion

Main ADME results

Type:

excretion

Results:

After intraperitoneal injection, radioactivity was quantitatively recovered in the rat urine (Table 1) but no labelled sulphanilic acid could be found.

Toxicokinetic / pharmacokinetic studies

Details on excretion:

Paper chromatography of the urine from rats dosed intraperitoneally with tartrazine showed only unchanged colouring present. No evidence was found for the presence of conjugated colouring. No amines derived from the reduction of the colouring in vivo could be found either before or after acid hydrolysis of the urine. In contrast to these results the urine of rats given oral doses of tartrazine contained no colouring, but sulphanilic acid was detected

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

sulphanilic acid was the metabolite identified by the oral route

Any other information on results incl. tables

Table 1.Excretion of radioactivity by rats after intraperitoneal dosage with[¹⁴C]tartrazine

Experiment no.	Intraperitoneal dosage		Percentage of administered radioactivity excreted during
	Weight (mg)	Activity (cpm × 10^-8)	0-24 hr	24-48 hr
1	0.78	5.73	100.8	0
2	0.72	5.28	73.8	0
3	0.65	4.77	92.8	0
4	0.57	4.19	91.5	0

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
Since majority (almost 92%) of the administered tartrazine is metabolized and excreted out of the Rat, it cn be concluded that the chemical shall have low bio-accumulation potential.

Executive summary:

The results obtained in these experiments show that tartrazine can be reduced in vivo when given orally but not when given by intraperitoneal injection. It must be concluded, therefore, that reduction of this compound is carried out by the gastro-intestinal flora.