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EC number: 201-788-0 | CAS number: 87-99-0
- 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
Endpoint summary
Administrative data
Description of key information
3-Week feeding study; rat; NOAEL: 20000 mg/kg (highest dose tested). Reliability = 2
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- 106-week oral diet study in mice
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- other: CFLP
- Sex:
- male/female
- Route of administration:
- oral: feed
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 106 weeks or when 20% survival was reached
- Frequency of treatment:
- daily
- Dose / conc.:
- 2 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 10 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 20 other: %
- Remarks:
- nominal in diet
- No. of animals per sex per dose:
- 100/sex/dose level
- Control animals:
- yes, plain diet
- other: 20% sucrose in the diet
- Dose descriptor:
- NOAEL
- Effect level:
- 2 other: % in diet
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- other: see "Remarks'
- Remarks:
- Macroscopic examination indicated a large increase in the incidence of urinary bladder calculi, urinary bladder nodules and masses, and urinary bladder distention for the 10 and 20% test substance males. Histological examination of the 10 and 20% test substance males revealed hyperplasia, metaplasia, and neoplasia of the transitional epithelium of the urinary bladder in male mice associated with the macroscopically observed calculi. No metastasis was observed in the bladder tumours.
- Dose descriptor:
- NOAEL
- Effect level:
- 20 other: % in diet
- Based on:
- test mat.
- Sex:
- female
- Remarks on result:
- other: highest dose tested
- Critical effects observed:
- not specified
- Executive summary:
Groups each of 100 male and 100 female CFLP mice per group were fed diets containing levels of 0, 2, 10, or 20% xylitol or 20% sucrose. The diet of all groups was maintained at 20% carbohydrate supplementation through the use of rice starch. Protein was maintained constant in all groups through the addition of casein. A group was terminated when 20% survival was reached. Initially the highest level of carbohydrate in any of the diets was 10%. Subsequently, desired levels of carbohydrate were obtained by increasing the amount in the diets by 5% each week.
No diarrhoea was observed with up to 10% xylitol or sucrose during the first three weeks. During the fourth week, mice receiving 15% xylitol (male and female) exhibited diarrhoea. The males also had associated inflammation of the anogenital region. The 15% sucrose group also showed some evidence of diarrhoea. These mice were returned to 10% xylitol and sucrose until week seven when they again received 15% xylitol and sucrose. The same signs as above were again seen. By week 11 the mice seemed normal and the 20% xylitol and sucrose levels were achieved by week 14. It therefore took as long as 16 weeks to achieve dietary accommodation to 20% xylitol and sucrose.
An overall significant increase in mortality was seen for 20% xylitol males during the first year. Some increases in food intake was seen for males in the 10 and 20% xylitol groups between weeks one and 106 and for females in these groups between weeks one and 80. The 20% sucrose group showed increased food intake for the first year of the study. Males in the 10 and 20% xylitol groups as well as 20% xylitol females had decreased body weight gains. Water intake was increased for the 20% xylitol males.
Macroscopic examination indicated a large increase in the incidence of urinary bladder calculi, urinary bladder nodules and masses, and urinary bladder distention for the 10 and 20% xylitol males. No similar effects were seen in the 2, 10, and 20% females, 2% xylitol males, or the 20% sucrose group. Histological examination of the 10 and 20% xylitol males revealed hyperplasia, metaplasia, and neoplasia of the transitional epithelium of the urinary bladder in male mice, associated with the macroscopically observed calculi. No metastasis was observed in the bladder tumours. The incidence of treatment-related tumours, metaplasia or neoplasia was not increased for the 2% xylitol males nor the 2, 10, and 20% xylitol females. Analysis of the bladder calculi indicate they are composed of calcium, phosphate, and oxalate. In the 20% sucrose-fed males there was an increase in kidney lesions described as cellular infiltration. Macroscopic examination of mice dying during the study revealed a statistically significant, dose-related reduction in the number of male mice bearing liver masses treated with xylitol, as compared to controls. Among mice killed at termination a lower prevalence of liver masses was recorded for males treated with 10 or 20% xylitol and attained a level of statistical significance (P 0.05) when compared to controls. Histologically, the liver masses were mainly benign adenomas, a small proportion had a structure suggestive of carcinoma. The prevalence in the sucrose group was similar to controls. The differences were statistically significant when 10 and 20% xylitol males were compared to controls and when 2, 10 or 20% levels of xylitol compared to 20% sucrose group.
The incidence of hepatocellular tumours (benign) was increased for the 20% sucrose females. Male 20% sucrose mice also showed an increase in fatty degeneration of hepatocytes No diarrhoea was observed with up to 10% xylitol or sucrose during the first three weeks. During the fourth week, mice receiving 15% xylitol (male and female) exhibited diarrhoea. The males also had associated inflammation of the anogenital region. The 15% sucrose group also showed some evidence of diarrhoea. These mice were returned to 10% xylitol and sucrose until week seven when they again received 15% xylitol and sucrose. The same signs as above were again seen. By week 11 the mice seemed normal and the 20% xylitol and sucrose levels were achieved by week 14. It therefore took as long as 16 weeks to achieve dietary accommodation to 20% xylitol and sucrose.
An overall significant increase in mortality was seen for 20% xylitol males during the first year. Some increases in food intake was seen for males in the 10 and 20% xylitol groups between weeks one and 106 and for females in these groups between weeks one and 80. The 20% sucrose group showed increased food intake for the first year of the study. Males in the 10 and 20% xylitol groups as well as 20% xylitol females had decreased body weight gains. Water intake was increased for the 20% xylitol males.
Macroscopic examination indicated a large increase in the incidence of urinary bladder calculi, urinary bladder nodules and masses, and urinary bladder distention for the 10 and 20% xylitol males. No similar effects were seen in the 2, 10, and 20% females, 2% xylitol males, or the 20% sucrose group. Histological examination of the 10 and 20% xylitol males revealed hyperplasia, metaplasia, and neoplasia of the transitional epithelium of the urinary bladder in male mice, associated with the macroscopically observed calculi. No metastasis was observed in the bladder tumours. The incidence of treatment-related tumours, metaplasia or neoplasia was not increased for the 2% xylitol males nor the 2, 10, and 20% xylitol females. Analysis of the bladder calculi indicate they are composed of calcium, phosphate, and oxalate. In the 20% sucrose-fed males there was an increase in kidney lesions described as cellular infiltration. Macroscopic examination of mice dying during the study revealed a statistically significant, dose-related reduction in the number of male mice bearing liver masses treated with xylitol, as compared to controls. Among mice killed at termination a lower prevalence of liver masses was recorded for males treated with 10 or 20% xylitol and attained a level of statistical significance (P 0.05) when compared to controls. Histologically, the liver masses were mainly benign adenomas, a small proportion had a structure suggestive of carcinoma. The prevalence in the sucrose group was similar to controls. The differences were statistically significant when 10 and 20% xylitol males were compared to controls and when 2, 10 or 20% levels of xylitol compared to 20% sucrose group.
The incidence of hepatocellular tumours (benign) was increased for the 20% sucrose females. Male 20% sucrose mice also showed an increase in fatty degeneration of hepatocytes.
Reference
No diarrhoea was observed with up
to 10% xylitol or sucrose during the first three weeks. During the
fourth week, mice receiving 15% xylitol (male and female) exhibited
diarrhoea. The males also had associated inflammation of the anogenital
region. The 15% sucrose group also showed some evidence of diarrhoea.
These mice were returned to 10% xylitol and sucrose until week seven
when they again received 15% xylitol and sucrose. The same signs as
above were again seen but were less severe. By week 11 the mice seemed
normal and the 20% xylitol and sucrose levels were achieved by week 14.
It therefore, took as long as 16 weeks to achieve dietary accommodation
to 20% xylitol and sucrose.
An overall significant increase in mortality was seen for 20% xylitol
males during the first year; however. Some increases in food intake was
seen for males in the 10 and 20% xylitol groups between weeks one and
106 and for females in these groups between weeks one and 80. The 20%
sucrose group showed increased food intake for the first year of the
study. Males in the 10 and 20% xylitol groups as well as 20% xylitol
females had decreased body weight gains. Water intake was increased for
the 20% xylitol males.
Macroscopic examination indicated a large increase in the incidence of
urinary bladder calculi, urinary bladder nodules and masses, and urinary
bladder distention for the 10 and 20% xylitol males. No similar effects
were seen in the 2, 10, and 20% females, 2% xylitol males, or the 20%
sucrose group. Histological examination of the 10 and 20% xylitol males
revealed hyperplasia, metaplasia, and neoplasia of the transitional
epithelium of the urinary bladder in male mice, associated with the
macroscopically observed calculi. No metastasis was observed in the
bladder tumours. The incidence of treatment-related tumours, metaplasia
or neoplasia was not increased for the 2% xylitol males nor the 2, 10,
and 20% xylitol females. Analysis of the bladder calculi indicate they
are composed of calcium, phosphate, and oxalate. In the 20% sucrose-fed
males there was an increase in kidney lesions described as cellular
infiltration. Macroscopic examination of mice dying during the study
revealed a statistically significant, dose-related reduction in the
number of male mice bearing liver masses treated with xylitol, as
compared to controls. Among mice killed at termination a lower
prevalence of liver masses was recorded for males treated with 10 or 20%
xylitol and attained a level of statistical significance (P 0.05) when
compared to controls. Histologically, the liver masses were mainly
benign adenomas, a small proportion had a structure suggestive of
carcinoma. The prevalence in the sucrose group was similar to controls.
The differences were statistically significant when 10 and 20% xylitol
males were compared to controls and when 2, 10 or 20% levels of xylitol
compared to 20% sucrose group.
The incidence of hepatocellular tumours (benign) was increased for the
20% sucrose females. Male 20% sucrose mice also showed an increase in
fatty degeneration of hepatocytes.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 20 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose studies with xylitol have been completed in several species of experimental animals. The subchronic toxicity of xylitol was examined in Wistar rats receiving either 20% xylitol in their diet or receiving the control diet. In a short-term (13 weeks) study four groups of eight female and eight male Charles River CD rats weighing 120-150 g, were fed 0, 5, 10 and 20 g dietary xylitol/kg/day. Groups of Wistar rats (70 rats/group) were allocated to diets of either 20% xylitol (two groups, one group was gradually adapted beginning with a 5% diet to prevent diarrhoea) or control diet (one group). In summary, except for transient diarrhoea in a number of treated animals in these studies, no other significant changes were observed and no significant histopathological lesions related to the xylitol administered were noted. In addition, xylitol has a long-standing history of daily consumption by the human population with no reports of systemic toxicity.
Justification for classification or non-classification
No effects were observed in repeated dose toxicity studies in multiple species. Therefore, the substance does not need to be classified for repeated dose toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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