Registration Dossier
Registration Dossier
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EC number: 201-321-0 | CAS number: 81-07-2
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Distension of the urinary bladder in rats fed Saccharin containing diet
- Author:
- A.G. RENWICK and J. SIMS
- Year:
- 1 983
- Bibliographic source:
- Cancer Letters, 18 (1983) 63-68
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: refer below principle
- Principles of method if other than guideline:
- Subacute repeated dose toxicity study of orally administered saccharin in male rat.
- GLP compliance:
- not specified
- Limit test:
- yes
Test material
- Reference substance name:
- Saccharin
- IUPAC Name:
- Saccharin
- Reference substance name:
- 1,2-benzisothiazol-3(2H)-one 1,1-dioxide
- EC Number:
- 201-321-0
- EC Name:
- 1,2-benzisothiazol-3(2H)-one 1,1-dioxide
- Cas Number:
- 81-07-2
- Molecular formula:
- C7H5NO3S
- IUPAC Name:
- 1,2-benzisothiazol-3(2H)-one 1,1-dioxide
- Details on test material:
- - Name of test material (as cited in study report):Saccharin
- Molecular formula (if other than submission substance):C7-H5-N-O3-S
- Molecular weight (if other than submission substance): 183.186 g/mole
- Substance type:Organic
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Charles Rivers CD
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles Rivers (Margate, Kent, U.K.)
- Age at study initiation: No data available
- Weight at study initiation: 250 g
- Fasting period before study: No data available
- Housing: Housing: After 1 month of treatment, animals were transferred for 24 h to individual plastic metabolism cages prior to collection of urine and faeces.
- Diet (e.g. ad libitum): CRMX Expanded Feed, ad libitum
- Water (e.g. ad libitum): Water, ad libitum
- Acclimation period: No data available
ENVIRONMENTAL 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: feed
- Vehicle:
- other: CRMX Expanded Feed
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Saccharin incorporated in CRMX Expanded Feed giving of 7.5 % in diet.
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): CRMX Expanded Feed
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): CRMX Expanded Feed
- Concentration in vehicle: 0 and 7.5 % (0 and 7500 mg/kg/day)
- 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:
- 1 month i.e. 30 days
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 and 7.5 % (0 and 7500 mg/kg/day)
Basis:
no data
- No. of animals per sex per dose:
- Total: 10 males
Control (0%; 0 mg/kg/day): 5 males
7.5% (7500 mg/kg/day): 5 males - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked included. No data available
DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: No data available
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY: No data available
- 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 data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked: No data available
CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked . No data available
URINALYSIS: Yes
- Time schedule for collection of urine: At the end of 1 month treatment
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No
- Parameters checked in table examined: Parameters examined: Total urine volume, average volume per 15 min, number of fractions containing >0.1, >0.5 or >1.0 ml, and maximum volume in 15 min were examined.
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER: No data available - Sacrifice and pathology:
- GROSS PATHOLOGY: No data available
HISTOPATHOLOGY: No data available - Statistics:
- Statistical analysis was performed by used Student’s t-teat for unpaired data.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant decrease in body weight was observed in treated rats as compared to control.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in food consumption was observed in treated rats as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in water consumption was observed in treated rats as compared to control.
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in total urine volume, Average volume per 15 min, Number of fractions containing and Maximum volume in 15 min were observed in treated rats as compared to control.
- 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
- Details on results:
- The increased urine volume was associated with both an increased average volume per fraction and also an increased frequency of urination.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 7 500 other: mg/kg/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Effect on body weight, food consumption, water consumption and urination
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 7.5 % (7500 mg/kg/day) when male CD rats were treated with saccharin.
- Executive summary:
In a subacute repeated dose toxicity study, male CD rats were orally exposed to saccharin in diet in the concentration of 0 or 7500 mg/kg/day (7.5 %). A significant decrease in body weight and increase in food consumption were observed in treated rats as compared to control. In addition, significant increase in water consumption and increase in total urine volume, average volume per 15 min, number of fractions containing and maximum volume in 15 min were observed in the saccharin-treated rats. Therefore, NOAEL was considered to be 7500 mg/kg/day (7.5 %) when male CD rats were treated with saccharin orally in diet for one month prior to urinanalysis.
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