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EC number: 240-347-7 | CAS number: 16219-75-3
- 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:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP test according to guideline. The test report from the Japanese Ministry of Health & Welfare is not available, but all the data were validated by the Japanese authorities within the OECD SIDS program Information in this record is from therefore from the SIDS dossier, a reliable secondary source, and used as supportive information. Reliability assessment based on that given in SIDS dossier.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 000
- Reference Type:
- publication
- Title:
- SIDS Initial Assessment Report for SIAM 14, Paris 26-28 March 2002.
- Author:
- Japan Ministry of Foreign Affairs, Economic Affairs Bureau, Second International Organizations division
- Year:
- 2 002
- Bibliographic source:
- OECD, Paris. http://www.chem.unep.ch/irptc/sids/OECDSIDS/16219753.pdf
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- No further information available.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 5-ethylidene-8,9,10-trinorborn-2-ene
- EC Number:
- 240-347-7
- EC Name:
- 5-ethylidene-8,9,10-trinorborn-2-ene
- Cas Number:
- 16219-75-3
- Molecular formula:
- C9H12
- IUPAC Name:
- 5-ethylidenebicyclo[2.2.1]hept-2-ene
- Details on test material:
- - Test substance: 5-Ethylidene-2-norbornene (CAS No. 16219-75-3)
- Source: Nippon Petrochemicals Co., Ltd, Lot No.6J01
- Purity: 99.4%
- Stability during use confirmed by gas chromatography.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CrjCD (SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Individual rats were identified by ear tattoo and cage cards.
- Age at study initiation: 5 weeks
- Diet (e.g. ad libitum): rat chow diet was provided ad libitum.
- Water (e.g. ad libitum): Water was provided ad libitum
- Housing: Rats were housed individually in suspended wire mesh metallic cages
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24 0C
- Humidity (%): 31-79%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light-dark cycle.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Doses of test article were administered by gavage in corn oil once/day at 5.0 ml/kg.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 14 M, 14 F control and high dose, 7 M, 7 F mid and low dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: 14 days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Observations for mortality, morbidity and clinical signs were made at least once a day.
BODY WEIGHT: Yes
- Time schedule for examinations: Body wt was determined at initiation and on dosing days 2, 5, 7, 10, 14, 21, and 28 and recovery days 2, 5, 7, 14 and at necropsy.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption was determined at initiation and on dosing days 2, 5, 7, 10, 14, 21, and 28 and recovery days 2, 5, 7, 14 and at necropsy.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Water consumption was determined and unfasted urines were collected during dosing days 25-26 and recovery days 11-12.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Hematological analysis was conducted on day 29 and on day 15 of recovery.
- Parameters checked: Parameters examined were RBC, Hct, Hb, MCV, MCH, MCHC, platelets, reticulocytes, three coagulation factors, WBC and differential counts.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Hematological analysis and clinical chemistries were conducted on day 29 and on day 15 of recovery.
- Parameters checked: GOT, GPT, Al-P, LDH, gamma-GTP, glucose, total cholesterol, triglycerides, bilirubin, BUN, creatinine, sodium, potassium, chloride, calcium, inorganic phosphate, total protein, albumin, and protein fractionation.
URINALYSIS: Yes
- Parameters checked: Urine was analyzed for pH, protein, glucose, ketones, urobilinogen, bilirubin, occult blood, color, sediment, volume, specific gravity, sodium, potassium, chloride, calcium, and inorganic phosphates. - Sacrifice and pathology:
- At end of dosing and on day 15 of recovery, rats were sacrificed
GROSS PATHOLOGY: Yes, Brain, pituitary, thymus, thyroid, parathyroid, lung, heart, liver, kidneys, spleen, adrenal glands, testes and ovaries were weighed before fixation.
HISTOPATHOLOGY: Yes, 46 tissues/organs were fixed and prepared for histopathologic examination: liver, kidneys, spleen, heart, lung, brain, pituitary, adrenal glands, thyroid, parathyroid, thymus, mesenteric lymph nodes, pancreas, tongue, mandibular lymph nodes, submandibular gland, sublingual gland, parotid gland, zymbal gland, skin, sternum, femur, spine, skeletal muscle, thoracic aorta, pharynx, trachea, bronchi, esophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, bladder, seminal vesicle, prostate, ovary, uterus, vagina, ischiatic nerve, testes, epididymides, eye and Hardarian gland. - Statistics:
- Bartlett's test and analysis of variance as necessary and Dunnett's test. Kruskal-Wallis and Mann-Whitney U-test for histopathology.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At dosage termination, mean body wt was significantly reduced in high dose males but not in the recovery group;
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose males water consumption was decreased, however this changes were not seen after the recovery period.
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical chemistry showed a significant increase in albumin in both sexes at the highest dose that was not present after recovery. Males showed a decrease in alpha-1-globulin at the 20 and 100 mg/kg dose levels that was not present in recovery animals.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis revealed an increase in the number of animals with protein-positive urine and a decrease in water consumption in males given 100 mg/kg. These changes were not found at the end of recovery period.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose males there was increased brain/body wt ratio and increased kidney/body wt ratio; both effects were absent in recovery males
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose males there was increased brain/body wt ratio and increased kidney/body wt ratio; both effects were absent in recovery males. Pale discoloration of the kidneys was observed in males given 100 mg/kg,
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathology showed increased hyaline droplets in renal tubule epithelium of all male rats in the 20 and 100 mg/kg groups. Thyroid effects were hypertrophy of follicular cells, decreased colloid and irregular follicular shape in 6 males, 1 female in 100 mg/kg group, 1 male each in 20 and 4 mg/kg groups. These thyroid effects were not seen in any recovery animals. There were no effects on the testes.
- Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Dose descriptor:
- NOAEL
- Effect level:
- < 4 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- histopathology: non-neoplastic
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
open allclose all
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 4 mg/kg bw/day (nominal)
- System:
- endocrine system
- Organ:
- thyroid gland
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 20 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
Applicant's summary and conclusion
- Conclusions:
- Hyaline droplets in the renal tubular epithelium, hypertrophy and irregular shape of follicular cells and decreased colloid in the thyroid, were observed in male rats at doses of 4 mg/kg/day and higher. The kidney effects are likely due to the male-rat-specific alpha 2u globulin accumulation. Increa ed albumin, and hypertrophy of follicular cells and decreased colloid in thyroid were found in the female 100 mg/kg/day group. Thyroid effects are reversible in both sexes. Therefore, the oral NOAEL for systemic effects other than thyroid and kidney is 20 mg/kg/day, based on reduced body we ght of females in the 100 mg/kg/day group.
- Executive summary:
A rat 28-day repeated oral dose toxicity test was conducted under the guidelines of the Japanese government (MHLW, Japan, 2000). Sprague-Dawley rats (7 animals/sex/dose with recovery groups of 7 additional animals/sex for the control and high dose groups held an additional 14-d) received doses of 0, 4, 20 and 100 mg/kg/day for 28-d by oral gavage.
In the 100 mg/kg group females the mean body weight was significantly reduced at dosage termination but not in the recovery group. Food consumption was not affected. Urinalysis revealed an increase in the number of animals with protein-positive urine and a decrease in water consumption in males given 100 mg/kg. These changes were not found at the end of recovery period. In the hematological examination, no effect was observed after administration of ENB. In the blood biochemical examination, 20 and 100 mg/kg group males showed a decrease in alpha-1 globulin level. However, these changes were not found at the end of the recovery period. In high dose males there was increased brain/body wt ratio and increased kidney/body wt ratio; both effects were absent in recovery males. At autopsy, pale discoloration of the kidneys was observed in males given 100 mg/kg, and histopathology showed increased hyaline droplets in renal tubule epithelium of all male rats in the 20 and 100 mg/kg groups. Histopathological examination of the thyroid indicated hypertrophy of follicular epithelium, as well as decrease in colloid or irregular shape of follicles in males given 4 mg/kg or more. Hypertrophy of follicular epithelium and decrease in colloid were also observed in females given 100 mg/kg. There were no effects on the testes. The NOAEL of ENB for repeated dose toxicity was reported to be less than 4 mg/kg/day for males (based on thyroid effects at 4 mg/kg and kidney effects at 20 mg/kg) and 20 mg/kg/day for females (based on thyroid effects at 100 mg/kg). However, the male rat kidney effects are consistent with alpha-2u-globulin nephropathy and are not considered to be relevant to humans (IARC, 1998). The thyroid effects are also likely to be a species specific effect not relevant to humans (IARC, 1998). For these reasons, the oral NOAEL based on systemic effects other than thyroid and kidney is 20 mg/kg/d, based on reduced body weight of females in the 100 mg/kg/d group.
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