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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
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Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: Oral
The purpose of this study was to evaluate the toxicity of the test chemical in Sprague-Dawley Rats. Sprague-Dawley Rats were given the test chemical in diet at dose of 20000 ppm (1000 mg/Kg). Body weight, food consumption, Haematology, Clinical chemistry, Urinalysis, gross and histopathology were examined in the treated animals. No Statistically significant difference were observed in body weight, Organ weight, food consumption, Haematology, Clinical chemistry, Urinalysis in treated as compared to control. No test material related lesions were observed during gross and microscopic studies. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) of the test chemical on Sprague-Dawley Rats in 13 weeks study was considered to be at a dose concentration of 20000 ppm (1000 mg/kg bw/day).
Repeated dose toxicity: Inhalation
The particle size distribution of the test substance was found to vary in the size of 53-500 µm, so the potential for the generation of inhalable forms is low. Moreover the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and therefore repeated dose toxicity by inhalation route was considered to be waived.
Repeated dose toxicity: Dermal
Since the substance is used in solid form there is very low probability of the substance penerating the skin. Further the results are negative for skin sensatization and skin irritation. Therefore this end point for repeated dose toxicity by dermal route of exposure was considered for waiver.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- 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 reviewed publication
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Effect of the test chemical was assessed in CD-COBS rats in a 25- to 54-day study.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CD-COBS
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Calco, Italy
- Weight at study initiation: 150 ± 10 g
- Diet (e.g. ad libitum): standard open formula diet
- Water (e.g. ad libitum): ad libitum - Route of administration:
- oral: feed
- Vehicle:
- other: standard open formula diet
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: A standard open formula diet containing the test chemical was prepared by Dottori Piccioni, Brescia, Italy, and consisted of 28.7% corn, 10% wheat, 13% barley, 7.3% corn germ, 4% fish meal, 5.5% meat meal, 10% soya flour extract, 11% carob pulp, 2% dry yeast, 2% hydrogenated coconut oil, 1% calcium carbonate, 1% salt mixture, 1% bone phosphate, plus vitamin mixture.
DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data
VEHICLE
- Justification for use and choice of vehicle (if other than water): standard open formula diet
- Concentration in vehicle: 0, 1, 2.5 and 5% (0, 1666.66, 4166.66, 8333.33 mg/kg bw/day)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 25 to 54 days
- Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:
0, 1, 2.5 and 5% (0, 1666.66, 4166.66, 8333.33 mg/kg bw/day)
Basis:
nominal in diet - No. of animals per sex per dose:
- EFFECT ON PRIMARY HUMORAL ANTIBODY PRODUCTION
3-6 animals per experimental group (3 in total) for 25, 30 or 54 days of exposure.
EFFECT ON PHA RESPONSIVENESS
3-6 animals per experimental group (3 in total) for 30 or 54 days of exposure - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
- Observations and examinations performed and frequency:
- BODY WEIGHT
Animals were weighed in the beginning of the experiment and then on day 30 and 54.
HAEMATOLOGY
The number of spleen plaque-forming (PFC) cells and phytohemagglutinin (PHA) responsiveness were evaluated.
Plaque forming cells:
The rats were immunized in the morning by i.p. injection of 4.108 SRBC. 4 days later they were killed between 9 and 11 a.m. and the number of spleen PFC was evaluated by localized hemolysis in gel
PHA (phytohemagglutinin) responsiveness
Spleens were minced with scissors in BME. The cells were washed with 50 ml of BME and resuspended in RPM1 1640 medium supplemented with 10% fetal bovine serum and 50 ug/ml gentamycin. One vial of PHA was dissolved in 5 ml BME and used as 100% PHA solution. Lymphocytes (4 x 105/0.2 ml) were cultured for 72 h in the round-bottomed wells of micro titer plates, 20 h before the end of the experiment cultures were pulsed with 0.5 uCi [methy13H]thymidine The cultures were harvested on filters Harvester. Radioactivity was measured using a Nuclear Chicago liquid scintillation spectrometer. - Sacrifice and pathology:
- GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes
PHA (phytohemagglutinin) responsiveness
Spleens were minced with scissors in BME. The cells were washed with 50 ml of BME and resuspended in RPM1 1640 medium supplemented with 10% fetal bovine serum and 50 ug/ml gentamycin. One vial of PHA was dissolved in 5 ml BME and used as 100% PHA solution. Lymphocytes (4 x 105/0.2 ml) were cultured for 72 h in the round-bottomed wells of micro titer plates, 20 h before the end of the experiment cultures were pulsed with 0.5 uCi [methy13H]thymidine The cultures were harvested on filters Harvester. Radioactivity was measured using a Nuclear Chicago liquid scintillation spectrometer. - Other examinations:
- No data
- Statistics:
- Results are mean +S.D. and significance was assessed by Duncan’s new multiple range test. PFC values were evaluated after logarithmic transformation of the data
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Increase in body weight observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- dose dependent suppression of primary humoral antibody production was observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Details on results:
- Body weight and weight gain
Increase in body weight after day 30 of treatment (346±11, 348±16, 346±23 and 341±65 g) was observed for rats fed diets containing 0, 1, 2.5 and 5% saccharin per day, respectively. After 54 days of treatment body weights were 415±16, 407±19, 396±24 and 408±9 for controls and rats given 1, 2.5 and 5% saccharin per day.
Hematology
Rats fed for 54 days with diets containing 1 to 5% saccharin per day showed marked, dose dependent suppression of primary humoral antibody production against SRBC. At a 5% saccharin per day concentration, inhibition of direct PFC/spleen ranged from 80 to 98%.
There is borderline inhibition of PHA responsiveness observed only at one mitogen concentration (0.1% per day) was not detectable after 54 days of exposure to saccharin in the same experiment or after 30 or 25 days of treatment in subsequent experiments. - Dose descriptor:
- LOAEL
- Effect level:
- 1 666.66 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Body weight, hematology
- Critical effects observed:
- not specified
- Conclusions:
- The Low Observed Adverse Effect Level (LOAEL) of the test chemical in CD-COBS rats for the period of 25 to 54 days was considered at dose concentration of 1666.66 mg/kg bw/day
- Executive summary:
The purpose of this study to evaluate the immune competence of rats fed diets containing high concentrations of the test chemical. The test chemical was administered in feed to male CD-COBS rats for the period of 25 to 54 days at dose concentration of 0, 1, 2.5 or 5% (0, 1666.66, 4166.66, 8333.33 mg/kg bw/day) saccharin per day. The test chemical showed marked, dose-dependent suppression of primary humoral antibody production against SRBC. In contrast to this PFC response, PHA blastogenesis was relatively unaffected, borderline suppression being observed only in one experiment at one PHA concentration. Increase in body weight was also observed in treated group as compared to control group. Therefore, Low Observed Adverse Effect Level (LOAEL) of the test chemical in CD-COBS rats for the period of 25 to 54 days was considered at dose concentration of 1666.66 mg/kg bw/day
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Experimental exposure time per week (hours/week):
- 1
- Species:
- rat
- Quality of whole database:
- The data is K2 peer reviewed publication
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Waiver
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Waiver
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Data available for the target chemical was reviewed to determine the mutagenic nature of the test chemical. The studies are as mentioned below:
Repeated dose toxicity: Oral
The purpose of this study was to evaluate the toxicity of the test chemical in Sprague-Dawley Rats. Sprague-Dawley Rats were given the test chemical in diet at dose of 20000 ppm (1000 mg/Kg). Body weight, food consumption, Haematology, Clinical chemistry, Urinalysis, gross and histopathology were examined in the treated animals. No Statistically significant difference were observed in body weight, Organ weight, food consumption, Haematology, Clinical chemistry, Urinalysis in treated as compared to control. No test material related lesions were observed during gross and microscopic studies. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) of the test chemical on Sprague-Dawley Rats in 13 weeks study was considered to be at a dose concentration of 20000 ppm (1000 mg/kg bw/day).
Another study was performed to evaluate the repeated dose oral toxicity of the test chemical in Beagle dogs. Beagle dogs were given the test chemical alone at dose of 20000 ppm alone 20000 ppm (500 mg/Kg/day) for 16 weeks. Body weight, food consumption, Haematology, Clinical chemistry, Urinalysis, gross and histopathology were examined. No Statistically significant difference were observed in body weight, Organ weignt, food consumption, Haematology, Clinical chemistry, Urinalysis in treated as compared to control. No test material related lesions were observed during gross and microscopic studies. Based on the observations made, the no Observed Adverse Effect Level (NOAEL) of the test chemical on Beagle dogs in 16 weeks study was observed at dose concentration of 20000 ppm (500 mg/kg bw/day).
Yet another study was performed to evaluate the immune competence of rats fed diets containing high concentrations of the test chemical. The test chemical was administered in feed to male CD-COBS rats for the period of 25 to 54 days at dose concentration of 0, 1, 2.5 or 5% (0, 1666.66, 4166.66, 8333.33 mg/kg bw/day) saccharin per day. The test chemical showed marked, dose-dependent suppression of primary humoral antibody production against SRBC. In contrast to this PFC response, PHA blastogenesis was relatively unaffected, borderline suppression being observed only in one experiment at one PHA concentration. Increase in body weight was also observed in treated group as compared to control group. Therefore, Low Observed Adverse Effect Level (LOAEL) of the test chemical in CD-COBS rats for the period of 25 to 54 days was considered at dose concentration of 1666.66 mg/kg bw/day
In another study, combined repeated dose & carcinogenicity was performed to determine the toxic nature of the test chemical upon repeated exposure by oral route. Spargue dawley rats were fed the test chemical in the diet at dose level of 0 or 5% (0 or 2500 mg/Kg/day) for 80 weeks. During the study period, the test animals were observed for general condition, mortality, body weight changes, food consumption and the animals were subjected to gross and histopathology. The general condition of rats was not altered and no mortality was observed during the study. There was no difference in the weight gain in treated and control rats. The consumption of feed was higher in SD rats during the initial 8 wk, but was slightly lower in the following period. At the beginning of the study, relative urinary volume was also significantly higher in SD rats given the test chemical in comparison with rats fed the control diet. Urinary excretion of sodium was approximately twice as high in the test chemical treated groups, but urinary pH was not affected by rat strain or treatment. All of the bladders appeared to be normal with no evidence of bladder stones, enlargement, or detectable lesions. Histological examination revealed simple hyperplasia in two rats amongst the treated animals, but no carcinomas or precancerous lesions were observed. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical is considered to be 2500 mg/Kg/day when male rats were exposed to the test chemical for 80 weeks.
Repeated dose toxicity: Inhalation
The particle size distribution of the test substance was found to vary in the size of 53-500 µm, so the potential for the generation of inhalable forms is low. Moreover the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and therefore repeated dose toxicity by inhalation route was considered to be waived.
Repeated dose toxicity: Dermal
Since the substance is used in solid form there is very low probability of the substance penerating the skin. Further the results are negative for skin sensatization and skin irritation. Therefore this end point for repeated dose toxicity by dermal route of exposure was considered for waiver.
Based on the data available for the target chemical, the test chemical is not likely to be toxic upon repeated exposure by oral route. Hence the test chemical is likely to be "not classified" for repeated exposure by oral, inhalation and dermal route as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical, the test chemical is not likely to be toxic upon repeated exposure by oral route. Hence the test chemical is likely to be "not classified" for repeated exposure by oral, inhalation and dermal route as per the criteria mentioned in CLP regulation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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