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EC number: 205-737-3 | CAS number: 149-32-6
- 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
- Study period:
- 10/1990-12/11/1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Erythritol
- EC Number:
- 205-737-3
- EC Name:
- Erythritol
- Cas Number:
- 149-32-6
- Molecular formula:
- C4H10O4
- IUPAC Name:
- butane-1,2,3,4-tetrol
- Reference substance name:
- unknown impurities
- IUPAC Name:
- unknown impurities
Constituent 1
impurity 1
- Specific details on test material used for the study:
- Erythritol, Lot number 90006-138
Upon arrival, the test substance was stored in the dark, at room temperature, in the original plastic bottles
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- outbred (Hsd/Cpb:WU) rats, derived from a specific-pathogen free (SPF) colony
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Initial body weights: males: 91.4-92.2 g; females: 81.5-82.3 g
diet: CIVO cereal-based stock : (75% are defatted soybean meal, whole ground wheat, and whole ground corn. The diet contained balanced amounts of vitamins and minerals.)
From their arrival until the end of the study he rats were housed in groups of five in suspended stainless steel cages, fitted with wire-screen bottoms and fronts.
Animals were acclimatized for 6 days
Temperature room : 22.5°C-26°C
Relative humidity : 50-75%
Ventilation rate : 15 air changes per hour
Light : artificial, 12h per day
Administration / exposure
- Route of administration:
- oral: feed
- Details on route of administration:
- Erythritol mixed into the diet
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- Erythritol mixed into the diet at 0 (control), 5, or 10% at the expense of dietary starch; food and water available ad libitum; homogeneity, stability, and nominal concentrations over test period confirmed -28 days
Food intake was estimated by weighing the feeders twice weekly. Fresh food was supplied twice weekly. Tap water was supplied in glass bottles, which were refilled daily with fresh water. Weekly water consumption was estimated by daily weighing of the bottles. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- At each meal, food and water available ad libitum
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- 0% in the publication
- Dose / conc.:
- 1 700 mg/kg bw/day (nominal)
- Remarks:
- 5% at the expense of dietary starch in the publication (corresponding to 1.7 g/kg bw in a similar diet study in rats referenced in SCF, 2003)
- Dose / conc.:
- 3 800 mg/kg bw/day (nominal)
- Remarks:
- 10% at the expense of dietary starch in the publication (corresponding to 3.8 g/kg bw in a similar diet study in rats referenced in SCF, 2003)
- No. of animals per sex per dose:
- 10 rats/sex/dose then 60 rats
- Control animals:
- yes
- Details on study design:
- Not specified
- Positive control:
- Not specified
Examinations
- Observations and examinations performed and frequency:
- signs for ill health : twice daily observation, once daily on weekends
body weights : recorded 3 days prior to and at study initiation and weekly there after food/water consumption, food utilization efficiency, and test substance intake determined weekly - Sacrifice and pathology:
- - haematology. blood samples collected on day 25 and included PCV, Hb, RBC, red blood tell distribution width (RDW-SD), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood tell count (WBC), dilferential white blood tell count, prothrombin time (PII), thrombocyte count, activated partial thromboplastin time (APTT), mean platelet volume (MPV) and platelet distribution width (PDW)
- clinicat chemistry. samples collected on days 27 and 28 (except glucose: day 25) and included: glucose, alkaline phosphatase (ALP), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma glutamyl transferase (GGT), total protein, albumin, globulin, protein electrophoresis, ratio of albumin to globulin, urea, creatinine, total bilirubin, Na, K, Ca, Cl, inorganic phosphate, cholesterol, triglycerides, and phospholipids
- urinalysis: samples collected on day 25 and included: appearance, pH, glucose, occult blood, ketones, protein, bilirubin, urobilinogen, sediment, volume, density, Na, K, Cl, Ca, and citrate
- organ weight determinations were made at terminal necropsy for the adrenals, brain, caecum (full and empty) heart, kidneys, liver, lungs, ovaries, pituitary, prostate, seminal vesicles, spleen, sublingual salivary glands, submaxillary salivary glands, testes, thymus, thyroid, and uterus
- pathology : gross examinations and histopathology performed on the adrenals, aorta, axillary lymph nodes, brain, caecum, colon, exorbital lachrymal glands, eyes, femur, Harderian glands, heart, kidneys, liver, lungs, mammary gland, mesenteric lymph node, esophagus, ovaries, pancreas, pituitary, prostate, rectum, sciatic nerve, seminal vesicles, skin, smalt intestine, spinal cord, sternum, stomach, sublingual salivary glands, submaxillary salivary glands, testes, thymus, thvroid with parathyroids, trachea and bronchi, uterus, vagina, and any other gross lesions. - Other examinations:
- - ophthalmology. examinations of all rats prior to treatment and at the end of the study
- Statistics:
- body weight data analysed using one way analysis of co-variance and Dunnett's multiple comparison tests; haematological, clinical chemistry, volume and density of urine, electrolytes in the urine and organ weights analysed using ANOVA and Dunnett's multiple comparison tests. Food and water intake and food efficiency were evaluated by analysis of variance followed by least significant difference tests. Histopathologicat findings were evaluated by the Fischer exact test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Early in the study, soft stools and diarrhoea were observed in rats fed digits containing 10% erythritol and in some of the 5% dose level females. These effects disappeared as the study progressed, indicating adaptation.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Females: no change;
Males fed the 10% level showed a significant reduction in mean body weight. Coincident with decreased body weights were decreased food intake in high-dose males during the first 2 weeks and relatively lower food efficiency in these animais. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Females: no change;
Males fed the 10% level showed a significant reduction in mean body weight. Coincident with decreased body weights were decreased food intake in high-dose males during the first 2 weeks and relatively lower food efficiency in these animais. - Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Male : Coincident with decreased body weights were decreased food intake in high-dose males during the first 2 weeks and relatively lower food efficiency in these animais.
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Water intake was statistically increased in both sexes at the high-dose, with lesser increases noted in the low-dose males.
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No changes
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related changes in red blood tell variables. Prothrombin lime was slighlly increased and neutrophil count slightty decreased in the high-dose females.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- ALP activity increased in high dose animais; slightly decreased plasma albumin and ASAT activity in treated females; decreased plasma globulin 5-1 in treated males; decreased plasma globulin a-2 in low dose females; decreased plasma creatinine level in males and chloride levels in high-dose females.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No indication of impaired renal function. Urine density was slightly increased in high-dose males. Na and K concentrations in females treated at both dose levels were slightly lower than controls, but total urinary excretion of these electrolytes was not significantly different over a 16-hour period.
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No changes in appearance or behaviour reported.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- lncreased absolute and relative weights of the caecum, both full and empty, in both test groups of both sexes. This effect did not always reach the point of statistical significance. Absolute and relative weights of the kidneys were increased in males al both dose levels. In treated males, absolute heart weights were decreased white in low-dose females absolute heart weights were slightly increased. Also in treated females, both absolute and relative spleen weights were slightly increased compared to the controls.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- The only grossly visible change in the treated animais was an enlarged caecum in one of the top dose males. No histopathological changes, including in the caecum, were found which could be attributed to erythritol treatment.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- Not specified
Effect levels
- Key result
- Dose descriptor:
- conc. level:
- Remarks:
- 10% in diet
- Effect level:
- >= 3 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- food efficiency
- gross pathology
- urinalysis
- water consumption and compound intake
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- several adaptative changes observed but no signs of toxicity
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 3 800 mg/kg bw/day (nominal)
- System:
- gastrointestinal tract
- Organ:
- heart
- kidney
- spleen
- other: caecum
Applicant's summary and conclusion
- Conclusions:
- - Increased caecal weights, both full and empty, were generally ascribed to the presence of increased amounts of osmotically active substances (Le., erythritol and short-chain fatty acids resulting from microbial fermentation of any erythritol which was not absorbed in the small intestine) in the large intestine. This finding was considered an adaptive effect as no histopathological correlates were found.
- The increased ALP activity also was ascribed to changes associated with caecal enlargement as the intestine is considered to be the main source of this enzyme in non-fasting rats. Also, other substances which produce an increased osmotic load in the large intestine, including other polyols and slowly digested carbohydrates, have been shown to increase ALP in association with caecal enlargement.
- The increase in kidney weights in the males was not accompanied by impaired renal function as measured by urinalysis parameters or by gross and histopathological examinatns. The rapid absorption and excretion of erythritol is known to induce a diuretic effect, resulting in an increased workload on the kidneys. The increased kidney weights were therefore considered to be an adaptive rather than a toxicological effect. This also is evidenced by the increased water consumption in high-dose animais.
- Changes in absolute and//or relative heart and spleen weights in some of the erythritol-treated animais were of a minor nature and were not accompanied by any histopathological changes. As a result, these changes were not considered to be of toxicological significance.
Based on an analysis of the results obtained, the study authors concluded that the feeding of erythritol at a dietary levet of 10% did not result in overt signs of toxicity, although several adaptive changes were observed - Executive summary:
In a diet study in 60 rats (protocol equivalent to OECD 407), the authors concluded that the feeding of erythritol at a dietary levet of 10% did not result in overt signs of toxicity, although several adaptive changes were observed
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