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Diss Factsheets
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EC number: 224-809-5 | CAS number: 4500-29-2
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study according to GLP
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-(cyclohexylimino)bisethanol
- EC Number:
- 224-809-5
- EC Name:
- 2,2'-(cyclohexylimino)bisethanol
- Cas Number:
- 4500-29-2
- Molecular formula:
- C10H21NO2
- IUPAC Name:
- 2,2'-(cyclohexylimino)bisethanol
- Reference substance name:
- 2,2`-(cyclohexylomino)bisethanol
- IUPAC Name:
- 2,2`-(cyclohexylomino)bisethanol
- Test material form:
- other: liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Wistar rat, Crl: WI(Han) (SPF), Charles River, Germany
- Age at study initiation: 9-10 weeks old (males and females)
- Weight at study initiation: 249-288 g (males); 185-213 g (females)
- Fasting period before study: over night
- Housing: individual housing in IVC cages, type III H
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hourd light / dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on mating procedure:
- Animals were paired in the ratio 1:1 until evidence of copulation was observed. The females were removed and housed individually when:
- vaginal smear was sperm positive
- a copulation plug was observed
The day of vaginal plug and/or sperm was considered as day 0 of gestation.
All dams were allowed to give birth and rear their litter (F1 pubs) up to day 4 post partum. Day 0 was designated as the day on which a female had delivered all her pubs. - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- Males were dosed 28 days
Females were dosed 54 days - Frequency of treatment:
- once per day, 7 days per week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/kg
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
12 mg/kg
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
30 mg/kg
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
75 mg/kg
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on dose-range finder
- Rationale for animal assignment (if not random): random
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before assignment to groups; males weekly thereafter; females weekly during pre-mating period and on gestation day 0, 7, 14, 20 as well as on post-natal day 4 - Sperm parameters (parental animals):
- Detailed qualitative examination of the testes including the tubular stages of the spermatogenic cycle
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
- number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, survival
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals
- Maternal animals: All surviving animals
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY
- cervix, coagulating gland, epididymis, ovary, prostate, seminal vesicle, testis, uterus, vagina - Postmortem examinations (offspring):
- SACRIFICE
- on day 4 post natal
GROSS NECROPSY
- performed on all animals - Reproductive indices:
- copulation index, delivery index, fertility index, viability index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 75 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 75 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Based on the results of this study, the NOAEL for reproductive toxicity of the test item is equal or greater 75 mg/kg body weight per day.
- Executive summary:
Four groups comprised of 10 adult males and 10 non pregnant nulliparous female rats (Wistar Crl:WI) were dosed daily by oral gavage with 12, 30 and 75 mg/kg body weight per day of the test item at dose volume of 5 mL/kg body weight using sterile water as vehicle. Doses were selected based on a dose-range finder study. Control animals were treated identically with the vehicle alone. After 14 days of treatment to both male and female, animals were paired (1:1) till the evidence of mating in the form of sperm positive vaginal smears. Males and females were sacrificed on treatment day 29 and post natal day 4 respectively and subjected to necropsy.
No test item related clinical signs and mortalities were observed in both males and females. Body weight development and food consumption was not affected. Group mean litter weight, total litter weight as well as male and female litter weight on post natal day 0 and 4 was unaffected. No treatment related effect was observed on precoital interval and duration of gestation. Pre and post natal data like group mean number of corpora lutea, percent preimplantation loss and post implantation loss remained unaffected due to treatment when compared with controls. No treatment related effects were observed on reproductive indices like coagulation index, delivery index, fertility index and viability index and there were no effects on litter data like number of males and females, sex ratio and still birth. Survival of pubs from post natal day 0 to 4 remained unaffected and treatment related gross external findings were not observed.
With regard to organ weights, in males a statistical significant decrease in absolute right testes weight in LD group and a decrease in absolute epididymides (right, left and total weight) and relative total epididymides weight in LD and HD group when compared with the controls were revealed. However, since no dose relationship was established and no histopathological changes were observed, no toxicological significance is attributed to these findings. At necropsy of all male and female animals, no macroscopic changes were observed and no treatment-related histopathological findings of reproductive organs were revealed.
A detailed qualitative examination of the testes taking into account the tubular stages of the spermatogenic cycle, revealed no abnormal pathological findings.
In conclusion, the repeated administration of the test item to male animals for 28 days and female animals for a maximum of 54 days revealed no significant toxicological findings and mortalities. Reproductive toxic effects were not revealed. Based on the data, the no observed adverse effect level (NOAEL) for maternal toxicity was equal or greater 75 mg/kg body weight per day. The no observed effect level (NOEL) for reproductive toxicity was equal or greater 75 mg/kg body weight per day.
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