Reaction products of 2-amino-4,6-dinitrophenol, 4-amino-5-hydroxy 2,7-naphthalenedisulfonic acid, 4-nitrobenzenamine and resorcinol, sodium salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From the 28th of November to the 6of December, 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Justification for Read Across is detailed in the endpoint summary and it is further detailed in the report attached to the IUCLID section 13.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Guideline:

other: no guideline available

Principles of method if other than guideline:

The porpouse of the study was to assess the toxicological profile of the test item when administered to rats by repeated oral gavage for a period of 5 days.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Similar substance 01 of Acid Brown 191

IUPAC Name:

Similar substance 01 of Acid Brown 191

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

TEST ARTICLE PREPARATION
The test item was weighted into a glass beaker on a tared Mettled PK 300 balance and the vehicle was added. The test article/vehicle mixture was prepared using a homogenizer

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

TEST ANIMALS
Source: Kleintierfarm Madoerin AG
Age at study initiation: (♂) 9 weeks; (♀) 10 weeks-
Weight at study initiation: (♂) 184 - 207 g; (♀) 178 - 209 g
Housing: The rats were housed in groups of three in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG)-
Diet (e.g. ad libitum): Pelleted standard Kliba 343, rat maintenance diet, Batch 34/88 ('Kliba', Klingentalmuehle AG),
ad libitum
Water (e.g. ad libitum): Community tap water from Itigen, ad libitm
Acclimation period: Two days under test conditions, after veterinary examination
ENVIRONMENTAL CONDITIONS
Temperature (°C): 22 ± 3 °C
Humidity (%): 40 - 70 %
Air changes (per hr): 10 - 15- Photoperiod (hrs dark / hrs light):
12 hours artificial fluorescent light/12 hours dark, music/light period

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
Concentration in vehicle: (Group 1) 0 mg/kg bw; (Group 2) 200 mg/kg bw; (Group 3) 2000 mg/ kg bw
Amount of vehicle (if gavage): 10 ml/kg bw

Duration of treatment / exposure:

5 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg diet

Doses / concentrations 2

Dose / conc.:

200 mg/kg diet

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg diet

No. of animals per sex per dose:

3 animals per sex per dose

Control animals:

yes

Details on study design:

Duration of treatment: 5 days
Duration of aclimatization period: 3 days
Frequency of observations and weighing: Observation for mortality and clinical signs were recorded daily, the food consumption and the body weight were recorded during the acclimatization period and on days 1, 3 and 5 of the treatment period using the on-line electronic recording system.
Necropsy of survivors performed: yes
Other. examinations performed: clinical signs, body weight,organ weights, histopathology, ophtalmoscopic examinations.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Treatment-related
No statistically significant differences were observed between the animals of the control and test article-treated groups which were related to treatment.
Treatment unrelataed
Statistically significant increased body weight were observed in male rats of group 2 (200 mg/kg bw) at day 1 of the acclimatization (pretest) period.Body weight gain.
No statistically significant differences in body weight gain were observed between the animals of the control and the test article-treated groups.

Ophthalmological findings:

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

A statistically significant decrease in absolte and relative adrenal weights of male rats of Group 3 (1000 mg/kg bw) as well as an increase of the relative kidneyweights of male rats of groups 2 and 3 was observed at terminal sacrifice when the results were compared to controls. No other statistically significant differences were observed.

Gross pathological findings:

no effects observed

Effect levels

1

Dose descriptor:

other: LD0

Effect level:

>= 1 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

2

Dose descriptor:

other: LD50

Effect level:

> 1 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

LD0 >= 1000 mg/kg bw
LD50 > 1000 mg/kg bw

Executive summary:

Method

The purpose of the study was to assess the toxicological profile of the test item when administered to rats by repeated oral gavage for a period of 5 days. During the test the substance has been administered to rats (9 males and 9 females) by repeated oral gavage, for a period of 5 days. The study was comprised of three groups, each containing three male and three female rats: one as control group and the ather associated to a 200 and 2000 mg/kg bw doses.

Observations

During the test no death occurred and no clinical signs were observed. A statistically significant decrease in absolte and relative adrenal weights of male rats of Group 3 (1000 mg/kg bw) as well as an increase of the relative kidneyweights of male rats of groups 2 and 3 was observed at terminal sacrifice when the results were compared to controls. In female animals of Group 3 (1000 mg/kg bw) a statistically significant decrease in food consumption was observed during days 2 to 4 of the treatment period when compared to that of the control. They are recovered at termination of the test. No other statistically significant differences were observed under the test condition.

Results

Under the test condition the substance is expected to have an LD0 >= 1000 mg/kg bw and an LD50 > 1000 mg/kg bw.