Sodium 1-amino-4-bromo-9,10-dioxoanthracene-2-sulphonate

Specific investigations: other studies

Administrative data

Endpoint:

nephrotoxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets basic scinetific principles.

Data source

Reference

Reference Type:

publication

Title:

Quantitation of a2-microglobulin after administration of structurally divergent chemical compounds

Author:

Hildebrand H, Hartmann E, Popp A, Bomhard E

Year:

1997

Bibliographic source:

Arch Toxicol 71: 351-359

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The potential of the test substance to induce alpha-2-microglobulin binding and subsequent hyaline droplet accumulation (HDA) potential was tested alongside other chemicals. HDA is a known precursor of necrosis and kidney tumours exclusively found in male rats.

Type of method:

in vivo

Endpoint addressed:

repeated dose toxicity: oral

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 1-amino-4-bromo-9,10-dioxoanthracene-2-sulphonate

EC Number:

228-391-5

EC Name:

Sodium 1-amino-4-bromo-9,10-dioxoanthracene-2-sulphonate

Cas Number:

6258-06-6

Molecular formula:

C14H8BrNO5S.Na

IUPAC Name:

sodium 1-amino-4-bromo-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Details on test material:

- Name of test material (as cited in study report): 2-Anthracenesulfonic acid, 1-amino-4-bromo-9,10-dioxo-, monosodium salt

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar (Hsd Cpb:WU)
- Source: Harlan-Winkelmann
- Age at study initiation: 12 - 14 weeks
- Housing: individually in Macrolon cages
- Diet (ad libitum): Altromin 1324
- Water (ad libitum): tap water

Administration / exposure

Route of administration:

other: no data

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

no data

Frequency of treatment:

no data

Post exposure period:

7 days

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:

3

Control animals:

yes

Results and discussion

Any other information on results incl. tables

Alpha2-Microglobulin-induced nephropathy is a phenomenon which is exclusively found in adult male rats. Various chemicals are able to bind to alpha2-microglobulin thus inhibiting its proteolytic degradation in lysosomes of the P2 segment of the rat nephron. The accumulation of this protein in 'protein droplets' or 'hyaline droplets' leads to necrosis, followed by regeneration which possibly later results in the formation of tumours. Reported was the development of a monoclonal antibody which is specific for alpha2-microglobulin. It was utilized to measure alpha2-microglobulin concentrations in plasma and tissues, and to stain alpha2 -microglobulin in fixed tissue slides. In two studies compounds were administered to adult male Wistar rats: (1) one group of structurally diverse compounds, which gave an overview of chemical entities capable of inducing the accumulation of alpha2-microglobulin (under these the test substance); and (2) another group of structurally closely related compounds (i.e. substituted benzene derivatives) for the purpose of elucidating possible structure-activity relationships. The degree of alpha2-microglobulin-induced nephropathy was determined by immunohistochemical staining of kidney sections (only Group (2)). In addition, liver and kidney tissue and plasma concentrations of alpha2-microglobulin were measured by competitive ELISA: Animals, that were treated with the test substance showed no elevated levels in plasma, but pronounced effects were observed in liver (137% increase: 1.46 +/- 0.48 versus 1.07 +/- 0.22 (control) mg/g tissue) and in kidney (184% increase: 2.10 +/- 0.38 versus 1.14 +/- 0.26 (control) mg/g tissue).

Comparing structurally related benzene derivatives, the hyaline droplet accumulating (HDA) potential was found to depend both on the type of substituent and its position at the aromatic ring. In general HDA activity increased in the order benzene=phenol=alkylated phenols < halogenated phenols < halogenated benzenes.