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EC number: 203-692-4 | CAS number: 109-66-0
- 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
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Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996-05 to 1997-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This study is classified as reliable without restrictions because it is indicated in the study protocol that the study was conducted according to GLP or equivalent and the study appears to be well conducted and provides important information on the inhalation kinetics of cyclopentane.
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- basic toxicokinetics
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1996-05 to 1997-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This study is classified as reliable without restrictions because it is indicated in the study protocol that the study was conducted according to GLP or equivalent and the study appears to be well conducted and provides important information on the inhalation kinetics of cyclopentane.
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Preliminary studies:
- Metabolism of cyclopentane was found to be saturable with two different metabolic processes distinguished. The steady state curve was shaped like a hockey stick, reaching a maximum value of 0.36 µmol/mL of tissue at 1000 ppm. The alveolar retention of cyclopentane declined with increasing exposure. Steady-state concentrations of 0.0015, 0.0037, and 0.053 µmol/mL were determined in the mixed venous blood entering the right ventricle in rats exposed to 53, 111, or 1100 ppm, respectively. Based on the physiological toxicokinetic model performance, the authors concluded that the model predictions were in agreement with the experimental data.
- Details on absorption:
- Absorption was not measured.
- Details on distribution in tissues:
- Tissue distribution was not measured. However, partition coefficients of cyclopentane in the blood, muscle, liver, and fat were measured and results are provided in Table 1 below. A bioaccumulation factor of 2.5 was calculated for lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air.
- Details on excretion:
- Excretion was not measured.
- Metabolites identified:
- not specified
- Details on metabolites:
- As concentrations increased, greater amounts of cyclopentane were exhaled unmetabolized.
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results
A bioaccumulation factor of 2.5 was calculated for lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air. - Executive summary:
This data is being read across from the source study that tested cyclopentane based on analogue read across.
This study was conducted in two parts. The first study was conducted to quantify the toxicokinetic parameters of inhaled cyclopentane, while the second part of the study was conducted to develop a physiological toxicokinetic model that would enable the study of toxicokinetic process occurring in the rat when exposed to cyclopentane vapours. In the first study, two male rats were exposed to cyclopentane at concentrations of 10, 30, 100, 300, 1000, 3000, or 10,000 parts per million (ppm) via inhalation in a closed exposure system. Metabolism of cyclopentane was found to be saturable with two different metabolic processes distinguished. One metabolic process had low affinity and high capacity while the other had high affinity and low capacity. The authors’ assumption that cyclopentane metabolism was oxidative, was supported by the findings that biotransformation of cyclopentane was almost completely inhibited for the whole 6 hour exposure duration when the rats were administered dithiocarb, a P-450 inhibitor. The study authors reported that the rate of metabolism was dose related with a proportional increase in metabolism up to 100 ppm concentration following which metabolism became saturated at about 1000 ppm. The bioaccumulation factor was 2.5 at the lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air. The steady state in the rat was estimated by multiplying the bioaccumulation factor with the exposure concentration. The steady state curve was shaped like a hockey stick, which reached a value of 0.36 µmol/mL of tissue at 1000 ppm. The alveolar retention of cyclopentane declined from 35% (observed with concentrations <20 ppm) to 5.4% at 1000 ppm and was related to an exposure dependent increase in the exhalation of unmetabolized cyclopentane. At concentrations <20 ppm 20% of the cyclopentane was exhaled unmetabolized compared to 88% at 1000 ppm and 99% at 10,000 ppm. In the second part of the study, the authors used the results presented above to develop a physiological toxicokinetic model. This model permitted a better understanding of the toxicokinetic processes occurring in rats exposed to cyclopentane vapors. It enabled the prediction of not only the average cyclopentane concentration in the whole body, but also concentrations in select organs and tissues (lung, arterial and venous blood, live, muscle, fat and richly perfused tissues). According to the model demand, distribution coefficients of 2.6, 2.7, 2.3, and 63 were determined for the blood:air, muscle:air, liver:air, and fat:air, respectively. The model was validated by comparing simulated concentration-time curves of the test chemical in the atmosphere of closed exposure systems and of predicted cyclopentane concentrations in blood of exposed animals. Steady-state concentrations of 0.0015, 0.0037, and 0.053 µmol/mL were determined in the mixed venous blood entering the right ventricle in rats exposed to 53, 111, or 1100 ppm, respectively. Based on the physiological toxicokinetic model performance the authors concluded that the model predictions were in agreement with the experimental data.
This study received a Kilmisch score of 1 and is classified as reliable without restrictions because it is indicated in the study protocol that the study was conducted according to GLP or equivalent and the study appears to be well conducted and provides important information on the inhalation kinetics of cyclopentane.
Table 1. Partition coefficients of cyclopentane at 37 °C
Tissue:air; liquid:air |
Mean |
± Standard Deviation |
n |
Blood |
2.6 |
0.34 |
15 |
Muscle |
2.7 |
0.33 |
3 |
Liver |
2.06 and 2.55 |
|
2 |
Fat |
63 |
4.2 |
5 |
Water |
0.091 |
0.005 |
4 |
Olive oil |
156 |
3.81 |
4 |
Table 2 Measured and predicted steady-state concentrations of cyclopentane in mixed venous blood of male Chbb:THOM rats exposed to vapours of cyclopentane. The model predictions were calculated by the physiological toxicokinetic model.
Exposure concentration (ppm) |
Measured concentration in blood (mmol/liter) |
Predicted concentration in blood (mmol/liter) |
53 |
0.0015±0.0003 |
0.0018 |
111 |
0.0037±0.003 |
0.0046 |
1100 |
0.053±0.007 |
0.085 |
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- no
- Principles of method if other than guideline:
- The study was designed in order to develope a physiological toxicokinetic model and there were several parts conducted (both in vivo and in vitro) to determine the model.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Cyclopentane
- EC Number:
- 206-016-6
- EC Name:
- Cyclopentane
- Cas Number:
- 287-92-3
- Molecular formula:
- C5H10
- IUPAC Name:
- cyclopentane
- Details on test material:
- - Name of test material (as cited in study report): cyclopentane
- Substance type: C5 aliphatics
- Physical state: liquid
- Analytical purity: 95.6%
- Lot/batch No.: A
- Storage condition of test material: room temperature
Constituent 1
- Radiolabelling:
- not specified
Test animals
- Species:
- rat
- Strain:
- other: CHBB-THOM (SPF)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Provided by the sponsor
- Weight at study initiation: 200 to 250 grams
- Housing: During acclimation, rats were kept in Macrolon cages, type 3. During experiments, rats were kept in a special all-glass closed inhalation system.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not specified
Administration / exposure
- Route of administration:
- inhalation: vapour
- Vehicle:
- unchanged (no vehicle)
- Duration and frequency of treatment / exposure:
- 6 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
10, 30, 100, 300, 1000, 3000, or 10,000 ppm for determination of maximum enrichment of cyclopentane in the body
53, 111, or 1100 ppm for determination of blood levels of cyclopentane
- No. of animals per sex per dose / concentration:
- 2 male rats per dose
- Control animals:
- no
- Positive control reference chemical:
- None
- Details on study design:
- - Dose selection rationale: Dose was selected to gain sufficient data for calculation of kinetic parameters.
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, unclear if other measurements were made
METABOLITE CHARACTERISATION STUDIES
- From how many animals: 2
- Method type(s) for identification: GC
- Statistics:
- Atmosphere samples were taken and for the examined concentration range, calibration curves wr
Results and discussion
- Preliminary studies:
- Metabolism of cyclopentane was found to be saturable with two different metabolic processes distinguished. The steady state curve was shaped like a hockey stick, reaching a maximum value of 0.36 µmol/mL of tissue at 1000 ppm. The alveolar retention of cyclopentane declined with increasing exposure. Steady-state concentrations of 0.0015, 0.0037, and 0.053 µmol/mL were determined in the mixed venous blood entering the right ventricle in rats exposed to 53, 111, or 1100 ppm, respectively. Based on the physiological toxicokinetic model performance, the authors concluded that the model predictions were in agreement with the experimental data.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Absorption was not measured.
- Details on distribution in tissues:
- Tissue distribution was not measured. However, partition coefficients of cyclopentane in the blood, muscle, liver, and fat were measured and results are provided in Table 1 below. A bioaccumulation factor of 2.5 was calculated for lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air.
- Details on excretion:
- Excretion was not measured.
Metabolite characterisation studies
- Metabolites identified:
- not specified
- Details on metabolites:
- As concentrations increased, greater amounts of cyclopentane were exhaled unmetabolized.
Any other information on results incl. tables
Table 1. Partition coefficients of cyclopentane at 37 °C
Tissue:air; liquid:air |
Mean |
± Standard Deviation |
n |
Blood |
2.6 |
0.34 |
15 |
Muscle |
2.7 |
0.33 |
3 |
Liver |
2.06 and 2.55 |
|
2 |
Fat |
63 |
4.2 |
5 |
Water |
0.091 |
0.005 |
4 |
Olive oil |
156 |
3.81 |
4 |
Table 2 Measured and predicted steady-state concentrations of cyclopentane in mixed venous blood of male Chbb:THOM rats exposed to vapours of cyclopentane. The model predictions were calculated by the physiological toxicokinetic model.
Exposure concentration (ppm) |
Measured concentration in blood (mmol/liter) |
Predicted concentration in blood (mmol/liter) |
53 |
0.0015±0.0003 |
0.0018 |
111 |
0.0037±0.003 |
0.0046 |
1100 |
0.053±0.007 |
0.085 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results
A bioaccumulation factor of 2.5 was calculated for lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air. - Executive summary:
This study was conducted in two parts. The first study was conducted to quantify the toxicokinetic parameters of inhaled cyclopentane, while the second part of the study was conducted to develop a physiological toxicokinetic model that would enable the study of toxicokinetic process occurring in the rat when exposed to cyclopentane vapours. In the first study, two male rats were exposed to cyclopentane at concentrations of 10, 30, 100, 300, 1000, 3000, or 10,000 parts per million (ppm) via inhalation in a closed exposure system. Metabolism of cyclopentane was found to be saturable with two different metabolic processes distinguished. One metabolic process had low affinity and high capacity while the other had high affinity and low capacity. The authors’ assumption that cyclopentane metabolism was oxidative, was supported by the findings that biotransformation of cyclopentane was almost completely inhibited for the whole 6 hour exposure duration when the rats were administered dithiocarb, a P-450 inhibitor. The study authors reported that the rate of metabolism was dose related with a proportional increase in metabolism up to 100 ppm concentration following which metabolism became saturated at about 1000 ppm. The bioaccumulation factor was 2.5 at the lower concentrations and increased to about 9.1 at 1000 ppm with a maximum value of 11.5, which is the thermodynamic partition coefficient of whole body to air. The steady state in the rat was estimated by multiplying the bioaccumulation factor with the exposure concentration. The steady state curve was shaped like a hockey stick, which reached a value of 0.36 µmol/mL of tissue at 1000 ppm. The alveolar retention of cyclopentane declined from 35% (observed with concentrations <20 ppm) to 5.4% at 1000 ppm and was related to an exposure dependent increase in the exhalation of unmetabolized cyclopentane. At concentrations <20 ppm 20% of the cyclopentane was exhaled unmetabolized compared to 88% at 1000 ppm and 99% at 10,000 ppm. In the second part of the study, the authors used the results presented above to develop a physiological toxicokinetic model. This model permitted a better understanding of the toxicokinetic processes occurring in rats exposed to cyclopentane vapors. It enabled the prediction of not only the average cyclopentane concentration in the whole body, but also concentrations in select organs and tissues (lung, arterial and venous blood, live, muscle, fat and richly perfused tissues). According to the model demand, distribution coefficients of 2.6, 2.7, 2.3, and 63 were determined for the blood:air, muscle:air, liver:air, and fat:air, respectively. The model was validated by comparing simulated concentration-time curves of the test chemical in the atmosphere of closed exposure systems and of predicted cyclopentane concentrations in blood of exposed animals. Steady-state concentrations of 0.0015, 0.0037, and 0.053 µmol/mL were determined in the mixed venous blood entering the right ventricle in rats exposed to 53, 111, or 1100 ppm, respectively. Based on the physiological toxicokinetic model performance the authors concluded that the model predictions were in agreement with the experimental data.
This study received a Kilmisch score of 1 and is classified as reliable without restrictions because it is indicated in the study protocol that the study was conducted according to GLP or equivalent and the study appears to be well conducted and provides important information on the inhalation kinetics of cyclopentane.
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