Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 700-515-7 | CAS number: 1236007-63-8
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented journal publication of a GLP study conducted at a respected contract laboratory.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 002
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- A subchronic toxicity test was conducted in which the substance was administered orally in the diet to male and female rats
- GLP compliance:
- yes
- Limit test:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- Isomaltulose (6-O-(alpha-D-glucopyranosyl)-D-fructofuranose), CAS No. 13718-94-0, is a reducing disaccharide that occurs natually in honey and sugar cane juice. Purity of the tested substance was 97.8%.
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Specific-pathogen-free-bred male and female Wistar rats (Crl:(WI)WU BR) were obtained by Charles River Deutschland (Sulzfeld, Germany) and acclimated to the laboratory conditions for nearly 2 weeks. At the start of the treatment period they were about 6 weeks old [mean body weights: males 176 g (range 157-204 g), females 141 g (range 125-156 g)]. They were housed in macrolon cages (one rat per cage) with stainless steel grid covers and wood shavings as bedding material, in a controlled environment (temperature 21-23 degrees C; humidity 30-60%; 12-h light/dark cycle; about 10 air changes per hour). The animals were housed individually to enable monitoring of individual food intake and food conversion efficiency in comparison with individual body weight development.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- A cereal-based, closed formula diet (Rat & Mouse No. 3 Breeding Diet, obtained from Special Diet Services, Witham, UK) was used as the basal diet. The experimental diets were prepared by supplementing the basal diet with isomaltulose and/or sucrose. Isomaltulose was incorporated at dietary levels of 2.5% (low-dose), 5% (mid-dose), and 10% (high-dose). The supplement in the low- and mid-dose diet was made up to 10% with sucrose. The control diet was made up of basal diet supplemented with 10% sucrose.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The diets were analyzed for isomaltulose using an HPLC method and found to be acceptable with respect to stability, homogeneity and achieved concentration of isomaltulose in the diet.
- Duration of treatment / exposure:
- The animals were fed the treatment diets daily for 13-weeks.
- Frequency of treatment:
- Daily in the diet
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 2.5, 5 or 10% isomaltulose
Basis:
nominal in diet
- No. of animals per sex per dose:
- Four groups of 20 rats per sex per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Four groups of 20 animals per sex were given the experimental diet at each dose from the start of the study until necropsy early in week 14.
Examinations
- Observations and examinations performed and frequency:
- The animals were observed daily for abnormal clinical signs. Body weights were recorded weekly from day 0 and on the day of necropsy. Food consumption was measured over successive 1-week periods, for each animal individually, by weighing the feeders. Food conversion efficiency in successive weeks was calculated as g weight gain per g food consumed. The intake of isomaltulose per kg body weight was calculated from the nominal dietary levels of isomaltulose, the food intake and the body weight. Water consumption was measured per animal by weighing the drinking bottles daily during 5-day periods in weeks 1, 6 and 12. Ophthalmoscopic observations were made before initiation of treatment in all rats and in week 13 in the control and high-dose group using an ophthalmoscope after induction of mydriasis by a solution of atropine sulphate.
- Sacrifice and pathology:
- At the end of the treatment period, the rats were sacrificed by exsanguination from the abdominal aorta under light ether anaesthesia, and a thorough necropsy was performed. The adrenals, brain , full and empty caecum, epididymides, heart, kidneys, liver, ovaries, spleen, testes, thymus and uterus of the rats were weighed (paired organs together). The relative organ weights were calculated on the basis of the terminal body weight of the rats. Samples of all organs and other tissues were examined for gross lesions and preserved in a neutral aqueous phosphate buffered at 4% solution of formaldehyde. Samples of the preserved organs from all rats of the control group and the high-dose group were processed and examined. The kidneys, liver and gross lesions were also examined in all rats of the intermediate dose groups.
- Other examinations:
- Examination of blood and urine was conducted on 10 rats per sex per group. Routine haematological examination was conducted in blood of non-fasted rats, collected from the abdominal aorta at necropsy early in week 14. The examination included haemoglobin, packed cell volume, red blood cell count, mean corpuscular volume, mean corpuscular concentration, total white blood cell count, thrombocyte count, differential white blood cell counts, and prothrombin time. Routine clinical chemistry was conducted in the same 10 rats per sex per group as used for haemotology. At necropsy, blood was collected from the abdominal aorta in heparinized tubes and plasma was prepared by centrifugation, then examined for alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total protein, albumin, albumin/globulin ratio, urea, creatinine, total bilirubin, total cholesterol, triglycerides, phospholipids, calcium, inorganic phosphate, sodium, potassium and chloride. Additional blood and glucose examinations were also measured. Neurobehavioral functioning was evaluated in week 13 in those 10 rats per sex per group that were not used for collection of blood and urine. The FOB consisted of non-invasive observational and interactive measures designed to assess the neurobehavioral and functional integrity of the rat, using measures taken from different functional domains including autonomic and neuromuscular function, sensorimotor reactivity, arousal and excitability.
- Statistics:
- Body weights were evaluated by a one-way analysis of covariance (covariate: body weight at initiation of treatment) followed by Dunnett's multiple comparison tests. Other parameters were evaluated by ANOVA follwed by Dunnett's. Other standard statistical methods were used as appropriate.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- All rats survived until scheduled necropsy and appeared healthy throughout the study. All parameters measured were normal throughout the study. No effects or signs of toxicity were observed in any animal in any dose. The test substance is not toxic to rats at doses up to 10% in the diet given daily for 13 weeks.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 8 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Equivalent to 10% in the diet
- Dose descriptor:
- NOAEL
- Effect level:
- > 7 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Equivalent to 10% in the diet
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The test substance is not toxic.
- Executive summary:
A subchronic toxicity test was conducted in which the substance was administered orally in the diet to male and female rats. Four groups of 20 rats per sex per dose were fed the treatment diets daily for 13-weeks at doses of 0, 2.5%, 5%, and 10%. All of the usual clinical parameters were measured. All rats survived until scheduled necropsy and appeared healthy throughout the study. All parameters measured were normal throughout the study. No effects or signs of toxicity were observed in any animal in any dose. The test substance is not toxic to rats at doses up to 10% in the diet given daily for 13 weeks.
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.