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EC number: 204-886-1 | CAS number: 128-44-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- SODIUM SACCHARIN: REPRODUCTION AND FERTILITY ASSESSMENT IN CD-1 MICE WHEN ADMINISTERED IN DRINKING WATER
- Author:
- JUGUSLAVA PECEVSKI, LJILJANA VUKSSANOVIC, NADA SAVKOVIE, DRAGAN ALAVANTIC AND DLJSANKA RADIVOJEVIC
- Year:
- 1 985
- Bibliographic source:
- NTIS PB REPORT (PB 85-188258,NTP 85-078):197 PP,1985
Materials and methods
- Principles of method if other than guideline:
- Reproductive and fertility effect of the test chemical was asessed in CD-1 mice.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt
- EC Number:
- 204-886-1
- EC Name:
- 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt
- Cas Number:
- 128-44-9
- Molecular formula:
- C7H5NO3S.Na
- IUPAC Name:
- sodium 1,1,3-trioxo-2,3-dihydro-1H-1λ⁶,2-benzothiazol-2-ide
- Reference substance name:
- Sodium Saccharine
- IUPAC Name:
- Sodium Saccharine
- Test material form:
- solid: crystalline
- Details on test material:
- - Name of test material: Sodium Saccharine
- Molecular formula:C7H5NO3S•Na
- Molecular weight : 205.2 g/mol
- Substance type: Organic
- Physical state: Solid
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- - Molecular formula:C7H5NO3S•Na
- Molecular weight : 205.2 g/mol
- Substance type: Organic
- Physical state: Solid
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on species / strain selection:
- No Data Available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- Source: Charles River Breeding Laboratory Inc
- Weight at study initiation: 25 to 32 g
- Housing: Cage: Polycarbonate shoebox type cages (5" xII" x 7") with stainless steel wire bar lids
Bedding: Ab-Sorb-Dri
-Age at study initiation: Eleven-week old
- Diet (e.g. ad libitum): Purina certified Rodent Chow animal diet 5002 (ad libitum)
- Water (e.g. ad libitum): Distilled water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25 deg C
- Humidity (%): 20 to 70%.
- Air changes (per hr): 10 or more air changes per hour
- Photoperiod (hrs dark / hrs light): 14 hour light cycle
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Treatment solutions will be prepared in quantities adequate for two weeks of treatment period.The test chemical stock solution will be prepared by dissolving the test article in distilled water. The remaining dose levels will be prepared by appropriate dilutions or independently formulated. An aliquot of
each formulation will be sent to Midwest Research Institute (Kansas City, MO) prior to onset of exposure at week 1, 5, 11, and 17 to confirm dose levels and certify stability of the test article. - Details on mating procedure:
- - M/F ratio per cage : 1:1 ratio
- Length of cohabitation : 14 weeks (100 days)
- Proof of pregnancy : Vaginal plug
- After successful mating each pregnant female was caged : individually - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No Data Available
- Duration of treatment / exposure:
- No Data Available
- Frequency of treatment:
- Daily
- Details on study schedule:
- The study was performed in 4 stages
Task 1: Dose finding study:
In dose range-finding study, sodium saccharin was tested at the following dose levels: 0, 0.25, 0.50, 1.0, 2.5, and 5.0% (w/v)
Task 2: Reproduction and fertility study:
Based on dose finding study this task 2 was performed, male and female CD-1 mice exposed to sodium saccharine at dose level 0, 0.25, 2.5, and 5.0% (w/v) during a 7 day premating period, after which they were randomly paired (one male: one female) within each dose group and cohabited for approximately 14 weeks (100 days). Newborn litters were evaluated and immediately sacrificed.
Task 3: Determination of affected sex:
Based on the results obtained from Task 2, the experimental animals will be assigned to Task 3 which will determine which sex is affected
Task 4: Offspring assessment:
Based on the results obtained from Task 2, the experimental animals will be assigned to Task 4 which will determine the reproductive capacity of the ,1st generation offspring.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 1.25%, 2.5%, 5% (0, 12.5, 25, 50 mg/ml)
Basis:
nominal in water
- No. of animals per sex per dose:
- Treatment group: 20 males and 20 females
Control group: 40 male and 40 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No Data Available
- Positive control:
- No Data Available
Examinations
- Parental animals: Observations and examinations:
- Task 2: Body Weight, Number of litters produced, Number and percent of live pups per litter, Mean body weight of live offspring, Percent of infertile pairs were observed
Task 3: For males: Body weight, Liver weight, Fixed Brain Weight, Right Testicular Weight, Ventral Prostate Weight (pair), Seminal vesicle weight, Right epididymal weight, Left testis with attached epididymis weight.
For females: Body weight, Liver weight, Fixed brain weight, Fixed pituitary weight,Weights of complete reproductive tract (ovaries,
oviducts, uterus, and vagina). - Oestrous cyclicity (parental animals):
- Task 4: Vaginal smears were prepared for 7 consecutive days from 5 second generation female mice
which failed to deliver any pups at the end of Task 4. These slides were evaluated for the relative frequency of estrous stages and approximate estrous cycle length - Sperm parameters (parental animals):
- Task 4: Sperm morphology studies were also conducted at necropsy. Sperm motility, sperm density, and the incidence of abnormal sperm were counted
- Litter observations:
- Task 4:
Second generation pups will be examined on postnatal day 0, humanely sacrificed, and the following parameters evaluated: Number and percent fertile pairs, Litter sizes, Litter weight, males and females weighed separated, Number and percent of live pups per litter - Postmortem examinations (parental animals):
- No Data Available
- Postmortem examinations (offspring):
- No Data Available
- Statistics:
- The Kruskal-Wallis test is the nonparametric analysis of the parametric one-way analysis of variance. Pairwise comparisons of sroup medians are performed usins the Mann Whitney U test. Pairwise comparisons of proportionsare performed using Fisher's exact test.
- Reproductive indices:
- The fertility index in the control and various treatment groups varied between 97 to 100%: all breeding pairs except one in the control group delivered at least one litter
- Offspring viability indices:
- No Data Available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- There was no mortality in the low dose (1.25%) group and only 1 animal died in the 2.5% dose group. Eight out of 40 animals died in the 5.0% dose group.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant decrease in body weight observed in females of highest dose group significant increase in food consumption observed in dose group (1.25% and 2.5%)
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Significant decrease in body weight observed in females of highest dose group significant increase in food consumption observed in dose group (1.25% and 2.5%)
- 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:
- not specified
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- Two out of 5 animals (one from each group) were in diestrus phase during all 7 days of smearing.
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- Sperm motility, sperm density, and the incidence of abnormal sperm were not affected by the test chemical treatment.
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Reproductive performance
Number of litters per fertile pair in the control and three treatment groups was essentially the same live offspring in the 5.0% dose group was significantly lower (p<0.05) than the control group. Proportion of pups born alive, and sex ratio values were not affected
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 25 other: mg/ml
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: mortality, body weight , food consumption, water consumption, no. of litters, pups born alive, and sex ratio
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When the live pup weight was adjusted for the total number of live and dead pups per litter, the average male and the combined pup weight values in the 5.0% dose group were significantly decreased
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not examined
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 25 other: mg/ml
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: no adverse effects observed
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Based, on all of the above observesations, the No Observed Adverse Effect Level of the test chemical on male and female CD-1 mice was found at dose concentration of 25 mg/ml.
- Executive summary:
The purpose of this study was to evaluate the toxicity of the test chemical on reproductive performance of CD-1 mice. CD-1 mice were exposed to the test chemical in drinking water at dose concentration of 0, 0.25, 2.5, and 5.0% (w/v) during a 7 day premating period, after which they were randomly paired (one male: one female) within each dose group and cohabited for approximately 14 weeks (100 days). Newborn litters were evaluated and immediately sacrificed. Exposure to the test chemical in the drinkinq water did not appear to seriously affect the reproductive performance of CD-l mice. No siqnificant differences in fertility, averaqe number of litters, proportion of pups born alive or proportion of male pups were observed in Task 2. Averaqe litter size and averaqe adjusted pup weight in the high dose group was significantly decreased. Although the decrease in overall pup weiqht was statistically siqnificant, it represented only a 5% decrease, relative to controls. An assessment of the effects of the test chemical on mid dose offsprinq relative to control offsprinq was performed in Task '4. No siqnificant differences were observed in fertility, proportion of pups born alive or proportion of male pups. Mid dose pairs were found to have sliqhtly smaller litters and decreased pup weiqhts, but the differences were not statistically siqnificant. Based, on all of the above observesations, the No Observed Adverse Effect Level of the test chemical on male and female CD-1 mice was found at dose concentration of 25 mg/ml.
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