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EC number: 445-090-6 | CAS number: 5614-37-9
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 2012-11-16 to 2014-08-25
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study, non GLP, but in compliance with China National Metrology Accreditation, in which the test parameters documented are based on testing guideline.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- no
- GLP compliance:
- no
- Remarks:
- non GLP, but in compliance with China National Metrology Accreditation
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 445-090-6
- EC Name:
- -
- Cas Number:
- 5614-37-9
- Molecular formula:
- C6 H12 O
- IUPAC Name:
- Cyclopentyl methyl ether
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Batch No.: 2820246
Purity: 99.9%
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Zhejiang Center of Laboratory Animals, Hangzhou, Zhejiang
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: males 4-5 weeks, females 8-9 weeks
- Weight at study initiation: Males: 177-211g; Females: 99-132g
- Fasting period before study:
- Housing: Polycarbonate cages, stainless steel racks, two rats per cage
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): tap water by aseptic filtration, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 12 air changes/hours
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
According to set doses, emulsified test substance in the plant oil, tween-80 and water, then dissolved well in drinking water, makes different concentrations of test substance to achieve the designed doses. - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 3 weeks
- Proof of pregnancy: presence of sperm or vaginal plugs, set as day 0 of gestation - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Exposure for P generation:
Male rats were exposed for a period of 10 weeks pre-mating and continued to be exposed until successful mating, female rats were exposed for a period of 2 weeks pre-mating and continued to be exposed during the period of mating, pregnancy and lactation.
For F1 generation:
Male and female rats for mating were exposed after weaning, the male rats were exposed for a period of 10 weeks and continued to be exposed until mating was finished, the female rats were exposed for a period for 10 weeks and continued to be exposed during the period of mating, pregnancy and lactation. - Details on study schedule:
- One male and one female of the F1 generation were selected randomly for mating after weaning from different litters in the same group to produce the F2 generation.
F1 generation offspring not utilized for mating were humanely sacrificed after weaning.
There should be about 20 pregnant rats in each group.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/L drinking water
- Dose / conc.:
- 313 mg/L drinking water
- Dose / conc.:
- 1 250 mg/L drinking water
- Dose / conc.:
- 5 000 mg/L drinking water
- No. of animals per sex per dose:
- 48 animals with 24 per sex
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: Based upon available information that acute oral LD50 values of the test substance were 3160 mg/kg in male and 2330 mg/kg in female rats.
- Rationale for animal assignment (if not random):
- Other:
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: each day
A general clinical observation was made each day to each animal such as behavior change, abnormality of excretion, death and other toxic clinical signs.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: each day
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, weekly
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (4/sex/litter as nearly as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities
GROSS EXAMINATION OF DEAD PUPS:
Yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead.
- Postmortem examinations (parental animals):
- Gross necropsy:
At the time of termination or death during the study, all parental animals with external abnormalities or clinical signs, were examined macroscopically for any structural abnormalities or pathological changes. Special attention was paid to the organs of the reproductive system. Dead pups or pups in a moribund condition were examined for possible defects of appearance and organs.
Histopathological examination:
At the time of termination, body weight and the weight of ovaries, testicle, and epididymis of P and F1 parental animals were determined. Uterus, ovaries, cervix, testicle, epididymis, seminal vesicle, prostate, penis, pituitary, brain and target organs were preserved for histopathological examination. - Postmortem examinations (offspring):
- Gross necropsy:
At the time of termination or death during the study, all parental animals with external abnormalities or clinical signs, were examined macroscopically for any structural abnormalities or pathological changes. Special attention was paid to the organs of the reproductive system. Dead pups or pups in a moribund condition were examined for possible defects of appearance and organs.
Histopathological examination:
At the time of termination, body weight and the weight of ovaries, testicle, and epididymis of P and F1 parental animals were determined. Uterus, ovaries, cervix, testicle, epididymis, seminal vesicle, prostate, penis, pituitary, brain and target organs were preserved for histopathological examination. - Statistics:
- A parameter or non-parameter test was selected based on the results of normality test and homogeneity of variance test. One-way analysis of variance and Dunnett's t test were used in parameter test, Kruskal-Wallis rank sum test and Wilcoxon-Wilcox rank sum test were used in non-parameter test, the test level of a was 0.05. Chi-square test and Fisher exact probability test were used in enumeration data, the test level of a was 0.05, corrected a' was 0.0170.
- Reproductive indices:
- rate of mating success (%) = (number of successful mating animals / number of female animal be mated) * 100%
pregnancy rate (%) = (number of pregnant animals / number of female animals be mated) * 100%
live birth rate (%) = (number of female animals producing live offspring / number of pregnant animals) * 100%
rate of birth livability (%) = (number of offspring survived on day 4 / number of offspring survived on birth day) * 100%
survival rate after weaning (%) = (number of offspring survived on 21 d after weaning / number of offspring survived on day 4) * 100%
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- During the total test period, eating and behavior of animals were normal and no clinical signs of toxicity were observed.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Before mating, for P generation of intermediate and high dose level groups, the body weight gain of male rats were lower than the control group, the body weight gain of female rats of high dose level group was lower than control group, there were statistically significant differences.
The body weights of pregnant rats at high dose level on gestation day 0, 7, 14, 20 were lower than control group, there were statistically significant differences.
The body weight of maternal rats at high dose level on day 0, 4, 7, 14, 21 and total body weight gain during lactation period were lower than control group, there were statistically significant differences. - Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- The average drinking water consumption of parental rats of intermediate and high dose groups were lower than control group, there were statistically significant differences.
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
Reproductive function / performance (P0)
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences in rate of mating success, pregnancy rat, live birth rate, rate of birth livability and survival rate after weaning in each dose level group compared with control group.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 169.18 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Dose descriptor:
- NOAEL
- Effect level:
- 193.45 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
Target system / organ toxicity (P0)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 5 000 mg/L drinking water
- System:
- male reproductive system
- Organ:
- other: testicle
- Treatment related:
- yes
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- In the total test period, there was one pregnant rat that died in childbirth in high dose level group of F1 generation.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Before mating, for F1 generation, in high dose level groups, the total body weight gain of male and female rats were lower than the control group, there were statistically significant differences.
The body weights of pregnant rats at high dose level on gestation day 0, 7, 14, 20 were lower than control group, there were statistically significant differences.
The body weight of maternal rats at high dose level on day 0, 4, 7, 14, 21 were lower than control group, there were statistically significant differences.
The average litter weight on day 14, 21 and the average body weights of pups on day 7, 14, 21 of high dose level group were lower than control group, there were statistically significant differences. - Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- The average drinking water consumption of parental rats of intermediate and high dose groups were lower than control group, there were statistically significant differences.
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- The organ coefficient of testicle in high dose group of male rats was higher than control group, there were statistically significant differences.
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 250 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
- body weight and weight gain
- organ weights and organ / body weight ratios
Target system / organ toxicity (F1)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 250 mg/L drinking water
- System:
- male reproductive system
- Organ:
- other: testicle
- Treatment related:
- yes
- Relevant for humans:
- not specified
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The average litter weight on day 14, 21 and the average body weights of pups on day 14, 21 of high dose level group were lower than control group, there were statistically significant differences.
Overall reproductive toxicity
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In summary, the main reproductive toxicity of test sample was shown below:
in high dose level group, weight of pups of F1 generation and F2 generation decreased; organ coefficient of testicle in high dose level group of paternal rats of P generation and F1 generation were higher than control group; in intermediate dose level group and low dose level group, no reproduction toxicity was observed.
Under this study condition, the no observed adverse effect concentration for two-generation reproduction toxicity study was estimated to be 1250 mg/L in drinking water for male and female rats, converted into average intake of sample, the NOAELs were 193.45 mg/kg/day for female rats and 169.18 mg/kg/day for male rats.
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