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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
A SHORT-TERM STUDY IN THE PIG OF THE EFFECTS ON THE LIVER AND ON THE BLOOD OF EIGHT AZO DYES
Author:
D. SONDERGAARD, E.V. HANSEN G. WIJRTZEN
Year:
1977
Bibliographic source:
Toxicology, 8 (1977) 381--386

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Sub chronic repeated dose toxicity test was carried out with 2 male and 2 female SPF pigs of Danish Landrace to determine the toxic nature of the test compound disodium 2-amino-5-[(4-sulphonatophenyl)azo]benzenesulphonate.
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report):Fast Yellow AB- Molecular formula (if other than submission substance):Not applicable- Molecular weight (if other than submission substance):Not applicable - Substance type:Organic- Physical state:solid- Impurities (identity and concentrations):Purity: 87.4%

Test animals

Species:
pig
Strain:
other: SPF pigs of Danish Landrace
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: No data available- Age at study initiation: No data available- Weight at study initiation: No data available- Fasting period before study: No data available- Housing: No data available - Diet (e.g. ad libitum): No data available- Water (e.g. ad libitum): No data available- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%): No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data available IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Details on oral exposurePREPARATION OF DOSING SOLUTIONS: No data available DIET PREPARATION- Rate of preparation of diet (frequency): No data available- Mixing appropriate amounts with (Type of food): No data available- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): No data available- Concentration in vehicle: No data available- Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
77 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:1000 & 1500mg/kgBasis:actual ingested
No. of animals per sex per dose:
2 male and female
Control animals:
yes
Details on study design:
Details on study design- Dose selection rationale: No data available- Rationale for animal assignment (if not random): No data available- Rationale for selecting satellite groups: No data available- Post-exposure recovery period in satellite groups: No data available- Section schedule rationale (if not random): No data available

Examinations

Observations and examinations performed and frequency:
Observations and examinations performed & frequencyCAGE SIDE OBSERVATIONS: No data- Time schedule: No data- Cage side observations checked in table [No.?] were included.DETAILED CLINICAL OBSERVATIONS: No data- Time schedule: No dataBODY WEIGHT: Yes - Time schedule for examinations: weeklyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes- daily- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD EFFICIENCY:- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations: No data- Dose groups that were examined:HAEMATOLOGY: Yes - Time schedule for collection of blood: From truncus jugularis 2 days prior to and 5, 19 and 68 days following the start of the dosing period.- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals: No data- Parameters checked in table [No.?] were examined. No dataCLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: No data- Animals fasted: No data- How many animals: No data- Parameters checked in table [No.?] were examined. No dataURINALYSIS: No data- Time schedule for collection of urine: No data- Metabolism cages used for collection of urine: No data- Animals fasted: No data- Parameters checked in table [No.?] were examined.NEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined:- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
no effects observed
Description (incidence and severity):
No significant effect observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No significant effect observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No any significant toxic effects on the examined liver and blood parameters.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In conclusion, there is no any significant toxic effects on the examined liver and blood parameters were observed at dose level. Therefore the NOAEL value is 1500mg/kg/day.
Executive summary:

Sub chronic repeated dose toxicity test was carried out with 2 male and 2 female SPF pigs of Danish Landrace. All pigs are dosed with 1000mg/kg and 1500mg/kg by gavage for total 77 days. Hematological examinations were performed at intervals and organ histopathology was performed at necropsy. No effects were detected and no Heinz bodies were found in the red blood cells. There is no significant toxic effect on the clinical & hematological parameters and on the examined liver and blood parameters. Therefore the NOAEL value is reported to be 1500mg/kg/day.