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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviwed journal

Data source

Reference
Reference Type:
publication
Title:
Chronic Toxicity of the given test chemical to Rats
Author:
K. J. DAVIS ET AL.
Year:
1966
Bibliographic source:
TOXICOLOGY AND APPLIED PHARAMACOLOGY

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Combined Repeated Dose and Carcinogenicity
Principles of method if other than guideline:
Combined Repeated Dose and Carcinogenicity was performed to determine the toxic nature of the test chemical in Sprague Dawley rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate
EC Number:
224-909-9
EC Name:
Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate
Cas Number:
4548-53-2
Molecular formula:
C18H16N2O7S2.2Na
IUPAC Name:
Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Ponceau SX
- Molecular formula : C18H16N2O7S2.2Na
- Molecular weight : 480.4276 g/mol
- Smiles notation: [Na+].[Na+].Cc1cc(C)c(cc1N=Nc2cc(c3ccccc3c2O)S(=O)(=O)[O-])S(=O)(=O)[O-]
- InChl :1S/C18H16N2O7S2.2Na/c1-10-7-11(2)16(28(22,23)24)8-14(10)19-20-15-9-17(29(25,26)27)12-5-3-4-6-13(12)18(15)21;;/h3-9,21H,1-2H3,(H,22,23,24)(H,25,26,27);;/q;2*+1/p-2/b20-19+;;
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Rats were caged individually.

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
The test chemical was mixed into a commercial laboratory chow diet for each feeding study.
Vehicle:
other: commercial laboratory chow diet
Details on oral exposure:
The test chemical was mixed into a commercial laboratory chow diet for each feeding study.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2yrs
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
0, 500, 1000 mg/kg bw
No. of animals per sex per dose:
control - 200(100/ sex)
500 mg/kgbw/day - 100 (50/sex)
1000 mg/kgbw/day - 100 (50/sex)
Control animals:
yes, concurrent vehicle
Details on study design:
Two-year tests were run in which 400 rats were distributed into various treatment groups. The test chemical was mixed into a commercial laboratory chow diet for each feeding study.Rats were individually caged. Each animal received in the Pathology Laboratory was given a careful gross examination, and all lesions were recorded. Of those not received, most were discarded because of advanced postmortem autolysis. So far as can be determined, none of the discarded animals had tumors. Lesions which could not clearly be identified as neoplastic or non-neoplastic, and tumors, the type of which was uncertain or uncommon, were also sectioned and examined microscopically. Tissues sectioned include the following: liver, lung, heart, spleen, pancreas, stomach, small in testine, colon, kidney, adrenal, thyroid, testis (or ovary and uterus), leg muscles, leg bones with included marrow, and any tumor or other unusual condition.Sections of the mammary glands were also observed for tumours.

Examinations

Observations and examinations performed and frequency:
The animals were observed for survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
No data available
Statistics:
No data available

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals
Mortality:
no mortality observed
Description (incidence):
The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals
Body weight and weight changes:
no effects observed
Description (incidence and severity):
The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
No effect due to ingestion of the test chemical on either tumor incidence or tumor type was noted in Sprague Dawley strain on this two-year experiment.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
No effect due to ingestion of the test chemical on either tumor incidence or tumor type was noted in Sprague Dawley strain on this two-year experiment.
Histopathological findings: neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
No effect due to ingestion of the test chemical on either tumor incidence or tumor type was noted in Sprague Dawley strain on this two-year experiment.
Other effects:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical signs
histopathology: neoplastic
histopathology: non-neoplastic
mortality
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Lesions observed in the 2 year feeding study

Parameter

Control

1%

2%

Number of rats started

200

100

100

Number of survivors at 80 weeks

122

66

54

Number received by pathology

147

83

74

Number of males with tumors

14

5

4

Number of females with tumors

24

11

10

Total number of rats with tumors

38

16

14

Tumor type in each rat

 

 

 

Fibroadenoma, mammary                          

21

9

9

Adenocarcinoma

1

1

0

Lymphosarcoma

5

4

4

Lymphoblastoma

4

0

0

Fibrosacroma

3

0

0

Interstitial cell tumor

0

0

0

Endometrial sarcoma

0

0

0

Other tumors

5

2

4

Other pathology

 

 

 

Chronic pneumonia

30

13

13

Granular kidneys

31

9

18

Splenic enlargement

12

9

8

Splenic atrophy

12

3

4

Testicular atrophy

13

4

4

Adrenal enlargement

7

2

7

Chronic arteritis

9

2

5

Applicant's summary and conclusion

Conclusions:
The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals. No effect due to ingestion of the test chemical on either tumor incidence or tumor type was noted in Sprague Dawley strain on this two-year experiment. Hence, the No Observed Adverse Effect level was considered to be 1000 mg/kgbw/day in both male and female Sprague Dawley rats.
Executive summary:

Combined Repeated Dose and Carcinogenicity was performed to determine the toxic nature of the test chemical in Sprague Dawley rats. Two-year tests were run in which 400 male and female Sprague Dawley rats were distributed into various treatment groups. The treatment groups were - 100 rats/dose (50/sex) and 100 rats/sex for controls. The test chemical (500 mg/kg bw/day, 1000 mg/kg bw/day) was mixed into a commercial laboratory chow diet for each feeding study. Rats were individually caged. Each animal received in the Pathology Laboratory was given a careful gross examination, and all lesions were recorded. Of those not received, most were discarded because of advanced postmortem autolysis. So far as can be determined, none of the discarded animals had tumors. Lesions which could not clearly be identified as neoplastic or non-neoplastic, and tumors, the type of which was uncertain or uncommon, were also sectioned and examined microscopically. Tissues sectioned include the following: liver, lung, heart, spleen, pancreas, stomach, small intestine, colon, kidney, adrenal, thyroid, testis (or ovary and uterus), leg muscles, leg bones with included marrow, and any tumor or other unusual condition. Sections of the mammary glands were also observed for tumors. The ingestion of the test chemical had no effect on survival, growth, or weights at autopsy of heart, liver, kidney, spleen, or testes in the test animals. No effect due to ingestion of the test chemical on either tumor incidence or tumor type was noted in Sprague Dawley strain on this two-year experiment. Hence, the No Observed Adverse Effect level was considered to be 1000 mg/kg bw/day in both male and female Sprague Dawley rats.