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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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
Key value for chemical safety assessment
Effects on fertility
Description of key information
The NOAEL is based on read across from Cyclacet which was tested in an OECD 421, GLP, oral gavage. The systemic NOAEL was determined to be 1000 mg/kg bw/day based on the absence of treatment-related toxicologically relevant effects. The fertility NOAEL is considered to be >= 1000 mg/kg bw/day based on the absence of treatment-related reproductive effects
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The fertility information is retreived from an OECD TG 421 of an analogue and from repeated dose toxicity information of the same analogue. This information is considered to be sufficiently adequate to cover this endpoint.
Additional information
No study was available with test substance Cyclobutanate, however, a reproscreening study (OECD TG 421) with structural similar substance Cyclacet can be used for read across. Cyclobutanate has a similar tricyclodecenyl fused ring-backbone compared to Cyclacet. Cyclobutanate, however, has a butyl ester attached to this backbone, while Cyclacet has an acetic (ethyl) ester here (see for a documentation of the read across document the end of this section). The additional propyl group in Cyclobutanate is considered minimally relevant for the toxicity to reproduction/developmental toxicity. In addition, no effects on gonads were seen in the repeated dose toxicity study of 90 days with Cyclacet and the 28 day study with Cyclobutanate further supporting the absence of fertility effects.
The study with Cyclacet complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 “Reproduction/Developmental Toxicity Screening Test” (adopted 27 July 1995), and potential adverse effects of Cyclacet on reproduction including offspring development were assessed.
The test material was administered by gavage to three groups, each of ten male and ten female Wistar rats, for up to forty-six consecutive days (including a two week maturation phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg/day. A control group of ten males and ten females was dosed with vehicle alone (Arachis oil BP).
Clinical signs, bodyweight change, dietary intake and water consumption were monitored during the study. Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation. During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of surface righting reflex.
Adult males were terminated on Day 43, and all females and surviving offspring on Day 5post partum. All animals were subjected to a gross necropsy examination and histopathological evaluation of reproductive tissues was performed.
The oral administration of Cyclacet to rats by gavage, for a period of up to forty six consecutive days at dose levels of 100, 300 and 1000 mg/kg/day did not result in any treatment-related reproductive effects. The ‘No Observed Adverse Effect Level’ (NOAEL) for reproductive toxicity was therefore considered to be >=1000 mg/kg/day. Based on this result, the read-across NOAEL for Cyclobutanate was also established to be >=1000 mg/kg bw/day.
Effects on developmental toxicity
Description of key information
The NOAEL is based on read across from Cyclacet which was tested in an OECD 421, GLP, oral gavage. The systemic NOAEL was determined to be 1000 mg/kg bw/day based on the absence of treatment-related toxicologically relevant effects. The developmental NOAEL is considered to be >= 1000 mg/kg bw/day based on the absence of treatment-related developmental effects.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
Additional information
For Cyclobutanate fertility information is available from the OECD TG 407 subacute study but fertility information on other than gonads and developmental toxicity is missing. For the assessing these endpoints an OECD TG 421 study from the structurally, kinetically and toxicologically related Cyclacet is used. The read across justification is presented below after presenting the summary of the Cyclacet OECD TG 421 study.
Cyclacet – OECD TG 421 Reproductive toxicity screening test
The study complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 “Reproduction/Developmental Toxicity Screening Test” (adopted 27 July 1995), and potential adverse effects of Cyclacet on reproduction including offspring development were assessed.
The test material was administered by gavage to three groups, each of ten male and ten female Wistar rats, for up to forty-six consecutive days (including a two week maturation phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg/day. A control group of ten males and ten females was dosed with vehicle alone (Arachis oil BP).
Clinical signs, bodyweight change, dietary intake and water consumption were monitored during the study. Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation. During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of surface righting reflex. Adult males were terminated on Day 43, and all females and surviving offspring on Day 5 post partum. All animals were subjected to a gross necropsy examination and histopathological evaluation of reproductive tissues was performed.
The oral administration of Cyclacet to rats by gavage, for a period of up to forty six consecutive days at dose levels of 100, 300 and 1000 mg/kg/day did not result in any treatment-related developmental effects. The ‘No Observed Adverse Effect Level’ (NOAEL) for developmental toxicity was therefore considered to be 1000 mg/kg/day.
The assessment of reproductive toxicity (including fertility and developmental toxicity of Cyclobutanate using read across from Cyclacet
Introduction and hypothesis for the analogue approach
Cyclobutanate is a butylester attached to a tricyclodecenyl fused ring structure. For this substance no reproductive toxicity (i.e. fertility and developmental toxicity) data are available. In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the fertility and developmental toxicity of Cyclobutanate the analogue approach is selected because for one closely related analogue reliable fertility and developmental toxicity information is available from a Reproscreen OECD 421 study.
Hypothesis: Cyclobutanate has similar reproductive toxicity compared to Cyclacet resulting in a similar NOAEL because the analogue Cyclacet based on structure, kinetic and toxicological similarity.
Available experimental information: For Cyclobutanate a 28-day repeated dosed toxicity study (OECD TG 407 under GLP) is available in which no effects were seen on male and female reproductive organs up to 1000 mg/kg bw with a reliability of 1. The source substance Cyclacet has been tested in a well conducted Reproscreen study (OECD TG 421 under GLP) up to 1000 mg/kg bw and the test result receives a reliability of 1.
Target chemical and source chemical(s)
Chemical structures of the target chemical and the source chemical are shown below. These two Cycla-esters have a tricyclodecenyl fused ring structure with on the left ring an ester bond with an alkyl chain an unsaturated bond in the right ring. Physico-chemical properties and toxicological information, thought relevant for reproductive and developmental toxicity of the two substances, are listed in the data matrix below.
Purity / Impurities
The constituents and impurities of the source and target chemicals indicate a similar reproductive toxic potential. The impurities are all below < 10%.
Analogue approach justification
According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. This read across is presented with reliable and adequate documentation and can be applied for C&L and/or risk assessment.
Structural similarities and differences: The target and the source chemical, have a tricyclodecenyl fused ring structure with an unsaturated bond in the right ring. The alkyl chain attached to the ester of Cyclobutanate (C4) is two methyl groups longer than of Cyclacet (C2). These differences between the target and source chemical are not expected to behave differently compared to the target organs because the alkyl side chains (butyl versus acetyl) are not expected to influence significantly the reproductive toxicity of these chemicals.
Toxico-kinetic considering absorption, distribution and excretion via all exposure routes Cyclobutanate (target) and Cyclacet (source) have similar toxico-kinetic behaviour: the molecular weights are 220 and 198, respectively; both are both liquids and; vapour pressures are similar. The t the water solubility and log Kow are somewhat lower and higher for Cyclobutanate and Cyclacet respectively because of the longer alkyl chain of Cyclobutanate.
For metabolisation the target and the source chemical will both be metabolised into the Cycla-alcohol (3385-61-3) by carboxylesterases and butyl and acetic acid for Cyclobutanate and Cyclacet, respectively. This metabolisation of the Cycla-ester is further outlined and illustrated in the toxico-kinetic section.
Similarities in results for toxicological endpoints between the target and the source chemical(s):
In the data matrix a summary of the other toxicological data is presented to show that there are hardly toxicological differences between the target and the source chemical and a similar C&L is derived. The acute oral and dermal toxicity data show limited acute toxicity for the source and the target chemical. The repeated dose toxicity in both are >=1000 mg/kg bw. Cyclobutanate and Cyclacet also show negative results in the available genotoxicity tests (e.g. Ames) and therefore reproductive toxicity resulting from genotoxicity is not expected.
Uncertainty of the prediction: The prediction of the NOAEL of >=1000 mg/kg bw for the target chemical for reproductive toxicity (both fertility and developmental toxicity) has a high certainty because of close similarity between the target and the source chemical. The two methyl groups difference in the alkyl chain will not have an impact on the reproductive toxicity. The available information from the source chemical is a high quality Reproscreen test (Reliability 1). Furthermore, for the target chemical itself no effects up to the limit dose of 1000 mg/kg bw on gonads were found in a 28 day repeated dose toxicity study.
Data matrix
The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix.
Conclusions on reproductive toxicity
For Cyclobutanate limited effects on fertility and no information on developmental toxicity is available, while such information is present on a closely related analogue Cyclacet, which can be used for read across. When using read across the result derived should be applicable for C&L and/or risk assessment and is presented with adequate and reliable documentation.
For Cyclacet (acetyl side chain) a well conducted Reproscreen test is available (Reliability 1) with a NOAEL of >=1000 mg/kg bw for fertility, developmental toxicity and systemic toxicity. Based on the read-across applied it can be concluded that Cyclobutanate also has a NOAEL of >=1000 mg/kg bw for reproductive toxicity.
Final conclusion: Cyclobutanate has a NOAEL of >=1000 mg/kg bw for fertility and developmental toxicity.
Data matrix for the read across to Cyclobutanate from Cyclacet for reproductive toxicity
Common names | Cyclobutanate Target | Cyclacet Source |
Chemical structures |
|
|
CAS no | 113889-23-9 (generic) | 54830-99-8 (generic) |
Empirical formula | C14H20O2 | C12H16O2 |
441-420-8 | 441-420-8 | 911-369-0 |
REACH registered | Yes | Yes |
Molecular weight | 220 | 192 |
Physico-chemical data |
|
|
Physical state | liquid | liquid |
Melting point oC | < -20 | < -20 |
Boiling point oC | 275 | 249 |
Vapour pressure Pa | 11.2 | 2.1 |
Water solubility mg/l | 11.5 | 186 |
Log Kow | 4.48 | 3.9 |
Human health endpoints |
|
|
Acute oral tox in mg/kg bw | >5000 (OECD TG 423) | 2750 (OECD TG 401) |
Acute dermal tox in mg/kg bw | >2000 (OECD TG 402) | >5000 (OECD TG 402) |
Genotoxicity – Ames test | Negative (OECD TG 471) | Negative (OECD TG 471) |
Repeated dose toxicity (mg/kg bw/day) | NOAEL >=1000 (OECD TG 407) | NOAEL >=1000 in 90-day study (OECD TG 408) and in a Reproscreen (OECD TG 421) |
Reproductive toxicity Fertility
Developmental toxicity
| In repeated dose no effects on gonads were seen in 28-day study up to 1000 mg/kg bw Read across | NOAEL >=1000 for fertility in a 90-day study (OECD TG 408) and in a Reproscreen study (OECD TG 421)
No developmental toxicity effects seen in the Reproscreen study. |
Justification for classification or non-classification
Based on the results of the available Repeated dose and Reproductive toxicity studies the substance does not have to be classified for reproductive toxicity (fertility and developmental toxicity) according to EU CLP (EC 1272/2008 and its amendments).
Additional information
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.