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EC number: 441-420-8 | CAS number: 113889-23-9
- 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
Endpoint summary
Administrative data
Description of key information
NOAEL Cyclobutanate >= 1000 mg/kg bw (OECD TG 407)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Species:
- rat
- Quality of whole database:
- Three repeated dose toxicity studies are available. One for the substance as such and two of a close analogue (90-day study and Reproscreen). The latter information is used to support the reproductive read across.
Additional information
The key study present for Cyclobutanate is a 28-day repeated dose toxicity study. For a closely related analogue, Cyclacet, a 90 days subchronic repeated dose toxicity study is available, which is used to support the read across to Cyclobutanate from Cyclacet for the reproductive toxicity endpoint, where a full read across justification is presented. After the summary of the Cyclobutanate 28-day study a summary will be presented on the repeated dose toxicity of Cyclacet (OECD TG 408) and the systemic toxicity of Cyclacet in the Reproscreen study (OECD TG 421).
Cyclobutanate 28 -day study
This oral repeated dose toxicity study conducted according to OECD guideline 407, which was performed to determine the toxicity of Cyclobutanate in rats after repeated exposure. Male and female rats were exposed to 0, 15, 150 or 1000 mg/kg bw/day of Cyclobutanate for 28-days. Also two satellite groups were included that were allowed to recover for 14 days. Mortality, clinical signs, body weight, food consumption and organ weights were recorded. Hematology, clinical chemistry and urinanalysis, gross pathology and histopathology were performed.
An increase in salivation from day 6 onwards was observed in the high-dose group animals, recovery was apparent in the 14 day period after treatment. This effect is usually considered attributable to an unpleasant tasting or locally irritant formulation rather than an indication of systemic toxicity. In the mid-dose group females a significant reduction of body weight was observed in the last week of treatment. As no dose-relationship was observed, this finding was not considered of toxicological importance. A higher incidence of globular accumulations of eosinophilic material in the tubular epithelium was observed in male rats of the high and mid-dose group (hydrocarbon nephropathy). Regression of this condition was seen in the 14 days of recovery. All remaining morphological changes were commonly observed in laboratory rats and therefore not considered to be of toxicological importance.
Results: Under the conditions of this study, no adverse effects were observed in female and male rats up to the highest dose group. For males, non-adverse hydrocarbon nephropathy was observed histopathologically in the 150 and 1000 mg/kg bw/day dose groups, which is an effect not relevant for humans. Therefore, a NOAEL of >=1000 mg/kg bw/day was set for risk assessment.
Cyclacet - 90 -day study
In a sub-chronic repeated dose toxicity study performed according to OECD 408 and under GLP conditions, rats were orally exposed to Cyclacet for 90 days via the food. The dose levels were 0, 200, 2000, 6000, and 20000 ppm, corresponding to 0, 15.3, 154.9, 464.1, and 1504.6 mg/kg bw/day, respectively. Clinical signs, functional observations, body weight change, dietary intake, and water consumption were monitored during the study. During week 7 and at the end of the study, haematology, blood chemistry and urinalysis were evaluated. Furthermore, oestrus cycle assessment was performed on female animals between week 6 and 7 and week 12 and 13. Opthalmoscopic examination was performed at the start and end of the study in control and high-dose animals. At the end of the study, all animals were subjected to gross necropsy examination and histopathological examination of tissues was performed on animals from control and high-dose. Furthermore, sperm assessment was performed on males at necropsy.
Results: Reduced overall body weight was observed in male and female animals in the highest dose group, correlated with reduced food consumption and adverse effects on food efficiency, indicating decreased food palatability. At the highest dose level, reduced chloride concentration, sodium concentration, aspartate aminotransferase levels, alanine aminotransferase levels, bile acid levels, and increased cholesterol levels were observed in male animals. The observed changes in aminotransferases, bile acid and cholesterol can be explained by the reduced food consumption. Changes in chloride and sodium concentrations may be explained by the observed kidney effects in males. Increased kidney weights were also observed in males, as well as hyalin droplet nephropathy, which is a rat-specific effect that is not relevant for humans. In females, no toxicologically significant effects were observed in clinical chemistry, organ weights or histopathology. Therefore the NOAEL could be established as the highest dose tested, 20000 ppm or 1500 mg/kg bw/day, under the conditions of this test.
Cyclacet systemic effects in the ReproScreen test (OECD TG 421)
In addition to this key study absence of systemic effects was confirmed in the oral gavage reproductive toxicity screening study (OECD TG 421) of the structurally related substance Cyclacet.
Based on these results, the NOAEL for Cyclobutanate for humans is established to be ≥1500 mg/kg bw/day based on the subchronic information from Cyclacet and sub-acute information from Cyclobutanate.
Justification for classification or non-classification
Based on the NOAEL of >=1000 mg/kg bw/day (highest dose tested) observed in a 28 day study of Cyclobutanate, therefore the substance does not need to be classified for (oral) repeated dose toxicity according to EU CLP (EC 1272/2008 and its amendments).
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