Registration Dossier

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test procedures cannot be subsumed under testing guideline, nevertheless are well documented and scientifically acceptable. Justification for Read Across is reported in the endpoint summary and in the Category Justification Report attached to the Section 13 of this dossier.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1967
Report date:
1967

Materials and methods

Principles of method if other than guideline:
Groups of 6 male and 6 female rats were given during 10 weeks (5 doses/week) 30, 60, 120, 250 or 500 mg of the test substance/kg as a solution in oil administered by gavage. A further group of 12 male and 12 female rats received daily 5.0 ml of oil/kg (control). During the experimental period, the condition of the animals, the body weight, the blood and Harnstatus, the prothrombin time, the SGPT and SGOT Transaminases and SDH were determined. 24 hours after the last administration, the animals were sacrificed with ether and the internal organs (liver, kidneys, adrenals, thyroid, spleen, ovary, testis, lung) macroscopically examined and weighed.
GLP compliance:
no
Remarks:
Pre GLP.
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrasodium 4,4'-bis[[4-[bis(2-hydroxyethyl)amino]-6-(4-sulphonatoanilino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate]
EC Number:
240-521-2
EC Name:
Tetrasodium 4,4'-bis[[4-[bis(2-hydroxyethyl)amino]-6-(4-sulphonatoanilino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate]
Cas Number:
16470-24-9
Molecular formula:
C40H44N12Na4O16S4
IUPAC Name:
tetrasodium 2,2'-ethene-1,2-diylbis[5-({4-[bis(2-hydroxyethyl)amino]-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate]

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: in the male rat groups the average body weight at start of the experiment was 165 g, in the females was 147 g .

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: oil
Duration of treatment / exposure:
10 weeks.
Frequency of treatment:
5 doses/week.
Doses / concentrations
Remarks:
Doses / Concentrations:
30, 60, 120, 250 or 500 mg/Kg bw
Basis:
actual ingested
No. of animals per sex per dose:
6 males and 6 females per dose
12 male and 12 female for the control group.
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS
The condition of the animals was observed daily.

BODY WEIGHT
The body weights of all the animals were weekly recorded.

HAEMATOLOGY
The blood and Harnstatus were analysed in 3 males and 3 females per dose, at 14 -days.
At the end of the experiment the prothrombin time was recorded in 3 males and 3 females per group

CLINICAL CHEMISTRY
At the end of the experiment the SGPT and SGOT Transaminases and the SDH were determined in all animals.
Sacrifice and pathology:
24 hours after the last administration, the animals were sacrificed with ether.
Liver, kidneys, adrenals, thyroid, spleen,ovary,testis and lung were macroscopically examined and weighed.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
The animals of the experimental groups showed no apparent symptoms of poisoning and behaved similarly to the control animals.

BODY WEIGHT AND WEIGHT GAIN
The bodyweight is not significantly altered in the female and male experimental groups compared with the control groups (P > O.1).

HAEMATOLOGY
In both sexes, no dose-dependent changes in the complete blood count was recorded.

CLINICAL CHEMISTRY
The checks of all animals liver function tests (SDH, SGPT, SGOT) showed no evidence of damage to the liver function.

URINALYSIS
The urine tests (protein, sugar, sediment) revealed no pathological findings.

ORGAN WEIGHTS
A significant dose-dependent change in the absolute and relative organ weights could not be determined (P > 0.1) in the experimental groups compared with the control groups.

GROSS PATHOLOGY
After killing the rats, the internal organs in the experimental groups compared with the control groups did not appear changed.

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The active ingredient used in these experiments was at the beginning, during and at the completion of the half of the experiment was tested for acute toxicity. This always resulted in a same normal oral toxicity.

Applicant's summary and conclusion

Conclusions:
NOAEL: 500 mg/kg bw/day
Executive summary:

Method

Groups of 6 male and 6 female rats were given during 10 weeks (5 doses/week) 30, 60, 120, 250 or 500 mg of the test substance/kg as a solution in oil administered by gavage. A further group of 12 male and 12 female rats received daily 5.0 ml of oil/kg (control). During the experimental period, the condition of the animals was observed daily, body weights (all animals) were weekly recorded; blood and Harnstatus (3 males and 3 females per dose) were analysed at 14 -days, and at the end of the test, the prothrombin time (3 males and 3 female sper group) and in all animals the SGPT and SGOT Transaminases and SDH were determined

24 hours after the last administration, the animals were sacrificed with ether and the internal organs (liver, kidneys, adrenals, thyroid, spleen, ovary, testis, lung) macroscopically examined and weighed.

Results

No adverse effetcts were recorded: the animals of the experimental groups showed no apparent symptoms of poisoning and behaved similarly to the control animals.

The bodyweight is not significantly altered in the experimental groups compared with the control groups. The complete blood count, the checks of liver function tests and the urine tests did revealed no pathological findings.

After killing the rats, the internal organs in the experimental groups compared with the control groups did not appear changed and a significant dose-dependent change in the absolute and relative organ weights could not be determined (P > 0.1) in the experimental groups compared with the control group.