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Diss Factsheets
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EC number: 201-142-8 | CAS number: 78-78-4
- 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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Developmental toxicity / teratogenicity
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: no restrictions, fully adequate for assessment
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: no restrictions, fully adequate for assessment
- Reason / purpose for cross-reference:
- read-across source
- Species:
- rat
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
There were no unscheduled deaths. Rats exposed to 2000 or 7000ppm exhibited a transient diminished or absent alerting response during each exposure session; this effect was not seen in rats exposed to 500ppm. Overall mean body weight gain for the exposure period (days 6-16) was statistically significantly reduced for rats exposed to 7000 ppm (69% of control) and mean daily food consumption was 89% of control. Mean body weight gain for the exposure and post-exposure period (Days 6-21) calculated using the final body weight minus the gravid uterine weight) was also statistically significantly reduced (75% of control). There was judged to be no effect of exposure to 2000 or 500ppm on maternal bodyweight.
A similar reduction in weight gain was seen in the pair-fed animals. There were no post-mortem findings that were considered indicative of a treatment-related effect - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 500 - 2 000 ppm
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
There were no treatment-related differences in pregancy rate, early delivery rate, abortion rate, total resoption rate, mean number of implantations per litter, the mean number of live foetuses per litter or sex ratio. There were no dead foetuses, nor was there any difference in the incidence of early, late or total resorptions. Foetal weight was unaffected by treatment. There were no effects on the incidence of foetal malformations or variations. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 7 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Cyclohexane was not a developmental toxin in female rats exposed during pregnancy. The foetal NOAEC was 7000 ppm, and the maternal NOAEC was 500 ppm (based upon transient sedation) or 2000 ppm (based upon significant reductions in absolute and adjusted body weight gain).
- Executive summary:
This data is being read across from the source study that tested cyclohexane based on analogue read across.
The developmental toxicity of cyclohexane was assessed in Crl:CD BR rats. The animals were exposed whole-body to nominal atmospheric concentrations of 0, 500, 2000, or 7000 ppm cyclohexane vapour. For rats in the 7000 ppm group, statistically significant reductions were observed in overall and adjusted maternal body weight gain while a transient diminished or absent response to a sound stimulus was apparent at 2000 ppm. Therefore the maternal no-observed-adverse-effect concentration (NOAEC) was 500ppm (1,720 mg/m3) (based upon transient sedation) or 2000 ppm (6,880 mg/m3) (based upon significant reductions in overall and adjusted body weight gain). No compound-related evidence of developmental toxicity was observed at any test concentration, equivalent to a NOAEC of 7000 ppm (24,080 mg/m3).
Mean maternal bodyweight gain (g) selected timepoints
0 |
0# |
500 |
2000 |
7000 |
|
0 to 6 |
18.7 |
22.4 |
22.3 |
24.6 |
22.1 |
6 to 16 |
64.2 |
32.1† |
60.1 |
57.2* |
44.2* |
6 to 21 (b) |
49.6 |
12.5† |
43.0* |
43.0* |
37.1* |
# - pair fed control b- ANOVA and Dunnets test
†- Significant difference from control (ANOVA and Dunnetts test); p< 0.05
* significant trend (linear contrast of means from ANOVA); p< 0.05
b- bwt gain on GD6-21 after correction for gravid uterus weight
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 000
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- Because the study examined the inhalation affects related to exposure of cyclohexane, test animals received whole body exposure to the cyclohexane vapour. Test animals failed to be weighed daily but rather were weighed weekly.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Cyclohexane
- EC Number:
- 203-806-2
- EC Name:
- Cyclohexane
- Cas Number:
- 110-82-7
- IUPAC Name:
- cyclohexane
- Details on test material:
- This substance is very similar in structure to the substance being registered.
Purity: 99.99%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD BR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Approximately 11 weeks
- Housing: Animals were housed individually in suspended, wire-mesh, stainless steel cages.
- Diet: Purina "Certified Rodent Checkers" was available ad libitum, except during exposures to all rats other than those in the pair-fed control group of the developmental toxicity study. Beginning with exposure, each animal in the pair-fed control group received an amount of Purina Certified Rodent Checkers approximately equal to the cumulative average amount of food consumed by the high-concentration group (7000 ppm) animals on the corresponding gestation day
- Water: tap water ad libitumexcept during exposures
ENVIRONMENTAL CONDITIONS
- Temperature: 23±2°C
- Humidity: 50±10%
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: All exposure chambers were constructed of stainless steel and glass and had a nominal internal volume of 1.4 m3. The chamber volume was chosen so that the total body volume of the test animals did not exceed 5% of the chamber volume. A tangential feed at the chamber inlet promoted gas mixing and uniform chamber distribution of vapour.
- Atmospheres of cyclohexane were generated by metering the liquid test substance into a heated glass Instatherm flask with a Fluid Metering Inc. pump. Nitrogen, introduced into the flask, swept the cyclohexane vapour into the inhalation chamber air supply. The chamber concentration of cyclohexane was controlled by varying the amount of the metered liquid evaporated in the chamber air stream. Nitrogen and air were passed through the control chamber at approximately the same flow rates as those used in the exposure chambers.
TEST ATMOSPHERE-The atmospheric concentration of cyclohexane was determined by gas chromatography at approximately 15-minute intervals during each 6-hour exposure. Chamber-atmosphere samples were drawn by vacuum pump from representative areas of the chamber where animals were exposed and were directly injected into a Hewlett Packard model 5880 Gas Chromatograph equipped with a flame ionization. All samples were chromatographed isothermally at 70°C on an HP-20M Carbowax column. The chamber distribution of cyclohexane vapour was determined prior to animal exposures in the high-concentration exposure chamber and while the study was underway with animals in the low- and high-concentration chambers. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The atmospheric concentration of cyclohexane was determined by gas chromatography at approximately 15 minute intervals during each 6-hour exposure. The results of these determinations indicated the distribution of cyclohexane vapour was sufficiently homogeneous (less than 2% difference in chamber concentration from position to position).
- Duration of treatment / exposure:
- Assumed-pregnant rats (25/concentration level) were exposed on days 6-15 of gestation (6-15G). The day that copulation was confirmed was designated as day 0.
- Frequency of treatment:
- 5 d/wk
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 (air), 500, 2000 or 7000 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0 (air), 500, 2000 or 7000 ppm
Basis:
other: overall mean measured
- No. of animals per sex per dose:
- 25 per concentration level
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- A pair-fed control group was established for the 7000 ppm treatment group. Beginning with exposure, each animal in the pair-fed control group received an amount of Purina Certified Rodent Checkers approximately equal to the cumulative average amount of food consumed by the high-concentration group (7000 ppm) animals on the corresponding gestation day. Each rat received approximately 150 grams per day of Purina Certified Rat Diet HF #5325; feed was not available during exposure.
Examinations
- Maternal examinations:
- During the exposure period, the animals were weighed daily and clinical signs were recorded before and after exposure. During the pre- and post- exposure periods, rats were weighed weekly and clinical signs were recorded once per day. Near the end of gestation (21 days), the maternal animals were sacrificed and the organs of the thoracic and abdominal cavities were examined grossly. The method of euthanasia was carbon dioxide asphyxiation.
- Ovaries and uterine content:
- The uterus of each animal was removed and opened. The types of implants (live and dead foetuses, and resorptions) were counted and their relative positions were recorded.
- Fetal examinations:
- The foetuses were euthanatized by decapitation or by intraperitoneal injection of sodium pentobarbital. They were weighed, sexed, and examined for external, visceral and skeletal alterations.
- Statistics:
- Sequential trend testing was applied to the data of each parameter. Adult body weight and food consumption data were analyzed by pair-wise comparisons. Parametric analyses were used to compare continuous data. Linear contrast of means from One-way Analysis of Variance (ANOVA) was the method of analysis followed by Dunnett's test. Litter-related continuous data were analyzed by a nonparametric method Jonckheere's trend test. For litter parameters, the litter mean was used as the experimental unit for statistical evaluation. Where the data were tied, exact p values were calculated using permutation methodology. Pup weight data were analyzed by an Analysis of Covariance (covariates: litter size, sex ratio) followed with a linear contrast of the least square means. Discrete data were evaluated by the Cochran-Armitage test for trend. Microscopic observations were analyzed by the Fisher's exact test.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
There were no unscheduled deaths. Rats exposed to 2000 or 7000ppm exhibited a transient diminished or absent alerting response during each exposure session; this effect was not seen in rats exposed to 500ppm. Overall mean body weight gain for the exposure period (days 6-16) was statistically significantly reduced for rats exposed to 7000 ppm (69% of control) and mean daily food consumption was 89% of control. Mean body weight gain for the exposure and post-exposure period (Days 6-21) calculated using the final body weight minus the gravid uterine weight) was also statistically significantly reduced (75% of control). There was judged to be no effect of exposure to 2000 or 500ppm on maternal bodyweight.
A similar reduction in weight gain was seen in the pair-fed animals. There were no post-mortem findings that were considered indicative of a treatment-related effect
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 500 - 2 000 ppm
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
There were no treatment-related differences in pregancy rate, early delivery rate, abortion rate, total resoption rate, mean number of implantations per litter, the mean number of live foetuses per litter or sex ratio. There were no dead foetuses, nor was there any difference in the incidence of early, late or total resorptions. Foetal weight was unaffected by treatment. There were no effects on the incidence of foetal malformations or variations.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 7 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Mean maternal bodyweight gain (g) selected timepoints
0 |
0# |
500 |
2000 |
7000 |
|
0 to 6 |
18.7 |
22.4 |
22.3 |
24.6 |
22.1 |
6 to 16 |
64.2 |
32.1† |
60.1 |
57.2* |
44.2* |
6 to 21 (b) |
49.6 |
12.5† |
43.0* |
43.0* |
37.1* |
# - pair fed control b- ANOVA and Dunnets test
†- Significant difference from control (ANOVA and Dunnetts test); p< 0.05
* significant trend (linear contrast of means from ANOVA); p< 0.05
b- bwt gain on GD6-21 after correction for gravid uterus weight
Applicant's summary and conclusion
- Conclusions:
- Cyclohexane was not a developmental toxin in female rats exposed during pregnancy. The foetal NOAEC was 7000 ppm, and the maternal NOAEC was 500 ppm (based upon transient sedation) or 2000 ppm (based upon significant reductions in absolute and adjusted body weight gain).
- Executive summary:
The developmental toxicity of cyclohexane was assessed in Crl:CD BR rats. The animals were exposed whole-body to nominal atmospheric concentrations of 0, 500, 2000, or 7000 ppm cyclohexane vapour. For rats in the 7000 ppm group, statistically significant reductions were observed in overall and adjusted maternal body weight gain while a transient diminished or absent response to a sound stimulus was apparent at 2000 ppm. Therefore the maternal no-observed-adverse-effect concentration (NOAEC) was 500ppm (1,720 mg/m3) (based upon transient sedation) or 2000 ppm (6,880 mg/m3) (based upon significant reductions in overall and adjusted body weight gain). No compound-related evidence of developmental toxicity was observed at any test concentration, equivalent to a NOAEC of 7000 ppm (24,080 mg/m3).
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.
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