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EC number: 225-533-8 | CAS number: 4904-61-4
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1986
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:CD (SD)IGS BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
- Age: males 59 days, females 52 days (approximately) - Route of administration:
- oral: gavage
- Details on exposure:
- ADMINISTRATION / EXPOSURE
- Vehicle: corn oil
- Concentration in vehicle: 6, 20, 60 mg/ml
- Total volume applied: 5 ml/kg bw/dose - Details on mating procedure:
- MATING PROCEDURES:
- mating period approximately 1-2 weeks, beginning after approximately four weeks of dosing. - Duration of treatment / exposure:
- Exposure period: males through test day 55; females 4 weeks premating through 4-day lactation period
Premating exposure period (males): approximately 4 weeks
Premating exposure period (females): approximately 4 weeks
Duration of test: approximately 60 days - Frequency of treatment:
- daily
- Dose / conc.:
- 30 mg/kg bw/day
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- No. of animals per sex per dose:
- Number of animals: 10 per sex and per dose group
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- - Clinical signs: at least once daily
- Mortality: at least twice daily
- Body weight: weekly, for females also on lactation days 0 and 4
- Food consumption: weekly
- Ophthalmoscopic examination: Both eyes of all rats prior to study and on test day 24, prior to clinical pathology evaluation (surviving rats).
- Clinical pathology evaluation on all rats after 4 weeks of dosing, and on male rats at the time of scheduled sacrifice:
- hematology / coagulation: erythrocyte count, total leukocyte count, platelet count, hemoglobin concentration, hematocrit, differential leukocyte count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, absolute reticulocyte counts, red cell distribution width, microscopic blood examination, activated partial thromoboplastin time, prothrombin time.
- clinical chemistry: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glucose, urea nitrogen, calcium, inorganic phosphorus, total bilirubin, cholesterol, triglyceride, creatinine, total protein, albumin, globulin, sodium, potassium, chloride.
- urine: volume, specific gravity, urobilinogen, blood, glucose, protein, appearance (quality, transparency, color), pH, bilirubin, ketones, sediment microscopy.
- Other: Neurobehavioral Functional Observational Battery (FOB) on all study rats prior to exposure and following approximately 4 weeks of test substance administration. - Litter observations:
- OFFSPRING: gestation length, mating index, gestation index, fecundity index, implantation site numbers, implantation efficiency, sex ratio, pups born alive, viability index
- Postmortem examinations (parental animals):
- ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Time: Sacrifice and necropsy of males on day 56 and of females on days 56-64.
- Organ weights P: liver, kidneys, adrenal glands, thymus, brain, spleen, heart, testes, epididymides. Calculation of ratios to final body and brain weights.
- Histopathology P: all high dose and control rats: testes, epididymides, ovaries, gross lesions; 5 high dose and 5 control rats per sex: additional 37 tissues 5 females from other groups with >= 1 offspring: liver - Postmortem examinations (offspring):
- Implantation site number and efficiency, sex ratio, mean pup weights, pups born alive, viability index
- Statistics:
- STATISTICAL METHODS:
- All weight parameters (P, not F), gestation length, clinical pathology, grip strength, foot splay: One-way analysis of variance followed with Dunnett's test or Kruskal-Wallis test; followed with Dunn's test.
- Incidence of clinical and FOB observations; mating, gestation, fecundity indexes: Sequential application of Cochran-Armitage test for trend
- Implantation site number and efficiency, sex ratio, pups born alive, viability index: Jonckheere's test
- Mean pup weights: Linear contrast of the least square means
- Motor activity: Levene's and Shapiro-Wilk tests followed by repeated measures analysis of variance followed by contrasts of Jonckheere's trend test. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no test substance-related effects on clinical observations
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One high-dose male was sacrificed in extremis due to a dosing-related injury. One high-dose female was found dead on day 57 from dystocia. No other deaths occured during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased body weight gain was observed and considered to be compound-related and of biological significance: 300 mg/kg males (-19 % for days 1-56, not statistically significant; weight -7%); 100 and 300 mg/kg females (only during gestation: gains -13% and -20%, weights -7% and -12%, respectively, statistically significant).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Increased food consumption was observed and considered to be compound-related and of biological significance: 300 mg/kg males (+19%) 100 mg/kg (+7%, not statistically significant) and 300 mg/kg females (+13%, statistically significant) during gestation.
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- As a consequence, food efficiency was significantly reduced: 300 mg/kg males (-33%) 100 and 300 mg/kg females during gestation (+14 and +29%, respectively, statistically significant).
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- no test substance-related effects
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- no test substance-related effects
- Clinical biochemistry findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- There were no test substance-related effects in neurobehavioral parameters or motor activity.
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- no test substance-related adverse effects
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- - Fertility index: no test substance-related effects
- Duration of gestation: no test substance-related effects
- Gestation index: no test substance-related effects
- Number of implantations: no test substance-related effects
- Mating index: no test substance-related effects;
- Implantation efficiency: no test substance-related effects - Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- other: no adverse effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- food efficiency
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- food efficiency
- Critical effects observed:
- no
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of pups in the 300 mg/kg group were significantly decreased (-17% on lactation day 4)
- Other effects:
- no effects observed
- Description (incidence and severity):
- - Sex and sex ratios: no test substance-related effects
- Pups born alive: no test substance-related effects - Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Critical effects observed:
- no
- Reproductive effects observed:
- no
- NOAEL 30 mg/kg for females, 100 mg/kg for males
- LOAEL 100 mg/kg for females, 300 mg/kg for males
- LOAEL 300 mg/kg for pups
Summary of reproductive outcomes:
- Dose (mg/kg) 0 30 100 300
- Mating Index(%): 80.0 90.0 100.0 100.0
- Fertility Index (%): 87.5 77.8 70.0 70.0
- Gestation Length (days): 22.0 22.0 22.0 22.0
- Implantations (mean/litter): 16.0 15.6 16.3 16.1
- Implantation efficiency (%): 92.1 96.2 92.0 89.5
- Gestation Index: 100.0 100.0 100.0 100.0
- Mean % Born Alive: 98.3 99.1 99.2 99.0
- 0-4 Day Viability (%): 98.0 99.0 98.2 98.3
- Sex Ratio (males): 0.45 0.50 0.49 0.45
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1986
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:CD (SD)IGS BR
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- ADMINISTRATION / EXPOSURE
- Vehicle: corn oil
- Concentration in vehicle: 6, 20, 60 mg/ml
- Total volume applied: 5 ml/kg bw/dose - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of the test substance indicated that the test substance was homogeneously distributed at all levels and that the concentrations were at the
targed level. Stability results indicated that the test substance was stable at all concentrations. - Duration of treatment / exposure:
- males through test day 55; females 4 weeks premating through 4-day lactation period
- Frequency of treatment:
- daily
- Dose / conc.:
- 30 other: mg/kg bw/day
- Dose / conc.:
- 100 other: mg/kg bw/day
- Dose / conc.:
- 300 other: mg/kg bw/day
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
MATING PROCEDURES: mating period approximately 1-2 weeks - Statistics:
- STATISTICAL METHODS:
- All weight parameters (P, not F), gestation length, clinical pathology, grip strength, foot splay: One-way analysis of variance followed with
Dunnett's test or Kruskal-Wallis test; followed with Dunn's test.
- Incidence of clinical and FOB observations; mating, gestation, fecundity indexes: Sequential application of Cochran-Armitage test for trend
- Implantation site number and efficiency, sex ratio, pups born alive, viability index: Jonckheere's test - Mean pup weights: Linear contrast of the least square means
- Motor activity: Levene's and Shapiro-Wilk tests followed by repeated measures analysis of variance followed by contrasts of Jonckheere's trend test - Clinical signs:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- A female in the 300 mg/kg bw/day group was found dead on test day 57 from dystocia. No other deaths occurred.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- During gestation, females administered 100 or 300mg/kg/day had test substance-related, significantly decreased body weight and body weight gain. On gestation day 21, body weights of females in the 100 and. 300mg/kg/day dosage groups were 7 and 12% (statistically significant) below the control mean, respectively .
Body weight gain values for females in the 100 or 300mg/kg/day groups were 13 and 20% below the control mean over the interval of gestation days 0-21, respectively . In addition, weight gain during the interval of gestation days 14-21 was significantly lower compared to the control mean . There were no test substance-related effects on body weight or weight gain for females in the 30 mg/kg/day group .
There were no test substance-related or statistically significant differences in body weight or weight gain during the premating phase for females administered 300 mg/kg/day or below. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- During premating, females in the 300 mg/kg/day group had slightly increased (11%) food consumption compared to the control me an over the interval of test days 1-29 (Table 1). During gestation, a test substance-related, statistically significant increase in food consumption occurred in females administered 300mg/kg/day . Food consumption was significantly increased in females administered 300 mg/kg/d ay during gestation days 7-14, and was increased 13% over the interval of gestation days 0-21 . Food consumption was also increased . 7% in females administered 100 mg/kg/day over the interval of gestation days 0-21.
There were no test substance-related effects or statistically significant differences in food consumption in the 30 mg/kg/day group . - Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Food efficiency was significantly decreased during gestation days 7-14 for both 100 and 300mg/kg/day females . Over the interval of gestation days 0-21, food efficiency was decreased 14 and 29% in 100 and 300 mg/kg/day females, respectively. The changes in food consumption and food efficiency were associated with changes in body weight during gestation, and were considered to be biologically significant.
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Changes in pregnancy duration:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- No effects on number of implantation sites
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- food efficiency
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of pups in the 300 mg/kg/day group were significantly reduced when compared to control pups on lactation days 0 and 4.
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- No effects on number of pups born
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1986
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Cyclododeca-1,5,9-triene
- EC Number:
- 225-533-8
- EC Name:
- Cyclododeca-1,5,9-triene
- Cas Number:
- 4904-61-4
- Molecular formula:
- C12 H18
- IUPAC Name:
- cyclododeca-1,5,9-triene
- Reference substance name:
- 1,5,9-Cyclododecatriene
- IUPAC Name:
- 1,5,9-Cyclododecatriene
- Details on test material:
- Test substance: 1,5,9-cyclododecatriene, purity 99.86%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD (SD)IGS BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
- Age: males 59 days, females 52 days (approximately)
- Number of animals: 10 per sex and per dose group
- Further information: see references
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- ADMINISTRATION / EXPOSURE
- Vehicle: corn oil
- Concentration in vehicle: 6, 20, 60 mg/ml
- Total volume applied: 5 ml/kg bw/dose - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of the test substance indicated that the test substance was homogeneously distributed at all levels and that the concentrations were at the
targed level. Stability results indicated that the test substance was stable at all concentrations. - Duration of treatment / exposure:
- males through test day 55; females 4 weeks premating through 4-day lactation period
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 30 other: mg/kg bw/day
- Dose / conc.:
- 100 other: mg/kg bw/day
- Dose / conc.:
- 300 other: mg/kg bw/day
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
MATING PROCEDURES: mating period approximately 1-2 weeks
Examinations
- Observations and examinations performed and frequency:
- PARAMETERS ASSESSED DURING STUDY P:
- Clinical signs: at least once daily
- Mortality: at least twice daily
- Body weight: weekly, for females also on lactation days 0 and 4
- Food consumption: weekly
- Ophthalmoscopic examination: Both eyes of all rats prior to study and on test day 24, prior to clinical pathology evaluation (surviving rats).
- Clinical pathology evaluation on all rats after 4 weeks of dosing, and on male rats at the time of scheduled sacrifice:
- hematology / coagulation: erythrocyte count, total leukocyte count, platelet count, hemoglobin concentration, hematocrit, differential
leukocyte count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, absolute reticulocyte counts, red cell distribution width, microscopic blood examination, activated partial thromoboplastin time, prothrombin time.
- clinical chemistry: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glucose, urea nitrogen, calcium, inorganic phosphorus, total bilirubin, cholesterol, triglyceride, creatinine, total protein, albumin, globulin, sodium, potassium, chloride.- urine: volume, specific gravity, urobilinogen, blood, glucose, protein, appearance (quality, transparency, color), pH, bilirubin, ketones, sediment microscopy.
- Other: Neurobehavioral Functional Observational Battery (FOB) on all study rats prior to exposure and following approximately 4 weeks of test
substance administration.
OFFSPRING: gestation length, mating index, gestation index, fecundity index, implantation site numbers, implantation efficiency, sex ratio, pups
born alive, viability index - Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Time: Sacrifice and necropsy of males on day 56 and of females on days 56-64.
- Organ weights P: liver, kidneys, adrenal glands, thymus, brain, spleen, heart, testes, epididymides. Calculation of ratios to final body and brain
weights.
- Histopathology P:
all high dose and control rats: testes, epididymides, ovaries, gross lesions;
5 high dose and 5 control rats per sex: additional 37 tissues 5 females from other groups with >= 1 offspring: liver - Other examinations:
- no other examinations
- Statistics:
- STATISTICAL METHODS:
- All weight parameters (P, not F), gestation length, clinical pathology, grip strength, foot splay: One-way analysis of variance followed with
Dunnett's test or Kruskal-Wallis test; followed with Dunn's test.
- Incidence of clinical and FOB observations; mating, gestation, fecundity indexes: Sequential application of Cochran-Armitage test for trend
- Implantation site number and efficiency, sex ratio, pups born alive, viability index: Jonckheere's test - Mean pup weights: Linear contrast of the least square means
- Motor activity: Levene's and Shapiro-Wilk tests followed by repeated measures analysis of variance followed by contrasts of Jonckheere's trend test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no test substance-related effects on clinical observations
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One high-dose male was sacrificed in extremis due to a dosing-related injury.
One high-dose female was found dead on day 57 from dystocia.
No other deaths occured during the study. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased body weight gain was observed and considered to be compound-related and of biological significance:
300 mg/kg males (-19 % for days 1-56, not statistically significant; weight -7%);
100 and 300 mg/kg females (only during gestation: gains -13% and -20%, weights -7% and -12%, respectively, statistically significant). - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Increased food consumption was observed and considered to be compound-related and of biological significance:
300 mg/kg males (+19%)
100 mg/kg (+7%, not statistically significant) and 300 mg/kg females (+13%, statistically significant) during gestation. - Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- 300 mg/kg males (-33%)
100 and 300 mg/kg females during gestation (+14 and +29%, respectively, statistically significant). - Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No test substance-related effects
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No test substance-related effects in neurobehavioral parameters and motor activity
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver weights were statistically significantly increased in several dosed groups:
Males: 30 mg/kg +10% relative; 100 mg/kg +14 % absolute, +21% relative; 300 mg/kg +34 % absolute, +45% relative.
Females: 100 mg/kg +15% relative; 300 mg/kg +36% absolute, +42% relative.
In females it was associated with microscopic centrilobular hepatocellular hypertrophy, which is indicative of a physiological response-induction of enzymes associated with metabolism, and is not considered biologically adverse.
In males, minimal diffuse hypertrophy may have occurred, which is hard to identify histologically.
- Kidney weights were statistically significantly increased in several dosed groups:
Males: 100 mg/kg +16% absolute, +21% relative; 300 mg/kg +22%, +37% relative
Females: 100 mg/kg +11% relative; 300 mg/kg +15% absolute, +17% relative
These findings were associated with some evidence of diuresis in high-dose males and females, but there were no compound-related changes in any other kidney parameter including histopathology. These weight changes may be an adaptive response to the physiological changes that occur following administration of large doses of a test material. They were not considered to be biologically adverse. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No test substance-related effects
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- - Fertility index: no test substance-related effects
- Duration of gestation: no test substance-related effects
- Gestation index: no test substance-related effects
- Number of implantations: no test substance-related effects
- Mating index: no test substance-related effects
- Implantation efficiency: no test substance-related effects
- Pups born alive: no test substance-related effects - Details on results:
- TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Body weights of pups in the 300 mg/kg group were significantly decreased (-17% on lactation day 4).
- Sex and sex ratios: no test substance-related effects
- Viability index: no test substance-related effects
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: associated with increased FC and decreased food efficiency
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- According to the outcome of the study it is concluded that the no-observed -adverse-effect level (NOAEL) was 100 mg/kg for male rats and 30 mg/kg/day for female rats.
- Executive summary:
Male and female rats were administered an oral, daily dose of 0, 30, 100 or 300 mg/kg/day 1,5,9 -cyclododecatriene.
According to the outcome of the study it is concluded that the no-observed -adverse-effect level (NOAEL) was 100 mg/kg for male rats and 30 mg/kg/day for female rats.
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