Registration Dossier
Registration Dossier
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EC number: 201-321-0 | CAS number: 81-07-2
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- 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:
- Tissue Levels of Saccharin in the Rat during Two-Generation Feeding Studies
- Author:
- T. W. SWEATMAN AND A. G. RENWICK
- Year:
- 1 982
- Bibliographic source:
- TOXICOLOGY AND APPLIED PHARMACOLOGY 62.465-473 (1982)
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: refer below principle
- Principles of method if other than guideline:
- Two-Generation reproduction toxicity study of Saccharin orally in Charles Rivers (CD)-derived Sprague-Dawley Rats
- 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:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles Rivers, Margate, Kent, United Kingdom.
- Age at study initiation: (P) x wks: No data available
(F1) x wks: 22 days old
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g: No data available
- Fasting period before study: No data available
- Housing: Animals were housed in groups of three to five per cage for a period of 4 weeks prior to mating, after mating female were housed singly in wire cages for the first 19 days of gestation and then transferred to Perspex boxes with wood shavings. Offspring were housed separately.
- Diet (e.g. ad libitum): Normal diet, ad libitum
- Water (e.g. ad libitum): No data available
- 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
Administration / exposure
- Route of administration:
- oral: feed
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: Normal diet
- Details on mating procedure:
- Details on study schedule:The offspring were sexed when 22 days old, and the males and females from each litter were housed in separate cages and fed the appropriate diet until killed.
- M/F ratio per cage:1: 1
- After successful mating each pregnant female was caged (how):Singly - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 or 5% (2500 mg/kg/day)
Basis:
no data
- No. of animals per sex per dose:
- No data available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Parental animals: Observations and examinations:
- No data available
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- No data available
- Postmortem examinations (parental animals):
- Tissue concentrations of saccharin were examined in liver, kidnye, bladder wall, plaema and amnoitic fluid.
- Postmortem examinations (offspring):
- Tissue concentrations of saccharin were examined in liver, kidney, bladder wall, plaema and amnoitic fluid.
- Statistics:
- Determined by unpaired Student’s t test
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 2 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No Effect on organ tissue concentration
Results: F1 generation
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 2 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No Effect on organ tissue concentration
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 5% (2500 mg/kg/day) in the F0 and F1 generation when male and female Sprague-Dawley rats were treated with saccharin.
- Executive summary:
In a two-generation repeated dose toxicity study, male and female Sprague-Dawley rats were treated orally in diet with saccharin in concentration of 0 or 5% (2500 mg/kg/day). In the F0 generation, tissue saccharin concentrations were decreased in female rats and no evidence of excessive accumulation were shown in the bladder wall or other tissues of female rats during in utero exposure or during lactation. The results showed decreased tissue saccharin concentrations in fetal liver, kidney and bladder wall when compared to maternal level.
Therefore, NOAEL was considered to be 2500 mg/kg/day (5%) in the F0 and F1 generation when male and female Sprague-Dawley rats were treated with saccharin
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