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EC number: 946-937-7 | CAS number: -
- 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:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Section 4 of the Guidelines for the Testing of Chemicals: Health Effects (ministry of environmental protection of People's Republic of China).
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- Not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2,2-bis[(allyloxy)methyl]butyl (3-{[({2,2-bis[(allyloxy)methyl]butoxy}carbonyl)amino]methyl}-3,5,5-trimethylcyclohexyl)carbamate
- EC Number:
- 946-937-7
- Molecular formula:
- C36H62N2O8
- IUPAC Name:
- 2,2-bis[(allyloxy)methyl]butyl (3-{[({2,2-bis[(allyloxy)methyl]butoxy}carbonyl)amino]methyl}-3,5,5-trimethylcyclohexyl)carbamate
- Test material form:
- liquid
- Details on test material:
- - Storage: cool and dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- clean grade
- Details on species / strain selection:
- The rat was the preferred rodent species for this study and the Sprague-Dawley strain was chosen due to its sensitivity against the known chemicals and uniformity in genetic properties.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 133 to 161 g
- Housing: There were two animals in one polycarbonate box, and the boxes were changed twice every week. The boxes were disinfected with an autoclave.
- Diet: powdered diet
- Water: The drinking water was sterilised, and rats were allowed to drink freely for drinking water during the experimental period.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 25°C
- Humidity: 40 to 70%
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- other: metallic stomach catheter
- Details on route of administration:
- The test substance was administered orally to animals once daily by a metallic stomach catheter.
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
A prescribed amount of the test material was weighed and then diluted with corn oil to designed concentrations. - 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.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Dose / conc.:
- 62.5 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: Groups of 1000, 250, 62.5 and 0 mg/kg-bw (high, middle, low and control group) were set up according to the result of the acute oral toxicity study.
- Animal assignment: Before the test, animals were assigned to 6 groups randomly, 10 rats per sex in each group.
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
Toxicological signs were recorded including the time of onset, degree and duration. Abnormalities were recorded in detail.
BODY WEIGHT: Yes
- The body weight of the rats were recorded weekly
FOOD EFFICIENCY: Yes
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- At the end of experiment, blood samples from all animals were collected for analysis of red blood cell (RBC), white blood cell (WBC), leukocyte differential count (the rate of neutrocyte (NEU%), the rate of lymphocyte (LYM%), the rate of monocyte (MONO%), the rate of basophils (BASO%), the rate of eosinophil (EOS%), platelet (PLT) counts, plasma prothrombin time (PT(INR)), activated partial thromboplatin (APTT) and hemoglobin (Hb) content.
CLINICAL CHEMISTRY: Yes
- At the end of experiment, blood samples were collected to analyse alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin total (TBIL), protein total (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CREA), cholesterol total (CHOL), glucose (GLU), cholinesterase (CHE), Na, K, Cl, Ca and P.
URINALYSIS: Yes
- At the end of experiment, urine samples from all of the animals were collected to analyse the specific gravity, colour, pH, protein contents, crypt-blood and sugar concentrations.
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No
OTHER:
Brain, heart, lung, liver, spleen, kidney, adrenal gland, testis or ovary and thymus were weighed immediately after collection. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- All the animals were subjected to a full gross necropsy and macroscopically observed in detail at the end of experiment. All tissues collected were fixed with 10% formaldehyde for histological examination.
HISTOPATHOLOGY: Yes
- The following tissues were collected for histological examination in control and high groups: brain, heart, lung, liver, spleen, kidney, adrenal gland, testis or ovary, nervus ischiadicus, cervical, spinal cord, thymus, thyroid, pancreas, stomach, duodenum, jejunum, ileum, colon, rectum, mesenteric lymph node, prostate, epididymis, urinary bladder and uterus. - Statistics:
- Data was analysed by ANOVA, and the additional high and control dosage group were analysed by t-test using SPSS10.0.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No abnormalities were observed.
- Mortality:
- no mortality observed
- Description (incidence):
- There was no mortality during the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No obvious effects were observed.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- No obvious effects were observed.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For females, the rate of BASO was increasing in both high and middle groups (p<0.05), but it had no clinical meaning.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For females, ALT was decreasing in the high group (p<0.05) and for males CREA was descending in the high group compared with the control group (p<0.05). The results had no clinical meanings.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- There was no abnormality of the specific gravity, colour, sugar, pH, crypt-blood and protein.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For females, the weight of the thymus in the additional high group was decreasing (p<0.05) compared to the additional control group, but it had no clinical meaning.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Gross necropsy showed that there was no overt abnormality.
In the female control group, no abnormality was found in any of the organs.
In the male control group, light-grade fatty degeneration of liver cells was observed in one animal, middle-grade infiltration of inflammatory cell around pulmonary vascular was observed in one animal, light-grade infiltration of inflammatory cell in-between the prostate was observed in two animals and middle-grade infiltration was observed in one animal.
In the female, high dose group, light-grade infiltration of inflammatory cell in-between the portal area of liver was observed in one animal, local cerebral lung consolidation and middle-grade infiltration of inflammatory cell was observed in one animal, local cerebral light-grade hyperaemia in alveolar wall was observed in one animal, light-grade infiltration of inflammatory cell in-between interstitial of the urinary bladder was observed in one animal and middle-grade infiltration was observed in one animal
In the male high dose group, light-grade infiltration of inflammatory cell in-between the portal area of liver was observed in one animal, light fatty degeneration of liver cells was observed in three animals, light-grade degeneration of bladder epithelium was observed in one animal, light-grade infiltration of inflammatory cell in-between the epididymis was observed in two animals, light-grade infiltration of inflammatory cell in-between the prostate was observed in one animal and light infiltration of inflammatory cell in-between the prostate, accompanied with middle epithelial degeneration, necrosis and light-grade fibrous connective tissue hyperplasia was observed in one animal.
In the additional female control group, no abnormality was found in any of the organs.
In the additional male control group, light fatty degeneration of liver cells was observed in one animal, local cerebral alveolar filled with inflammatory and red cells found was observed in one animal, light-grade infiltration of inflammatory cell in-between the prostate was observed in one animal and middle-grade infiltration of inflammatory cell in-between the prostate was observed in two animals.
In the additional female high dose group, light-grade infiltration of inflammatory cell in-between the portal area of liver was observed in one animal and light-grade infiltration of inflammatory cell in-between lamina porpria mucosae of ladder was observed in one animal.
In the additional, male high dose group, light fatty degeneration of liver cells was observed in two animals, light-grade infiltration of inflammatory cell in-between the portal area of liver was observed in one animal, middle-grade hyperaemia and thickening of alveolar wall was observed in one animal, middle-grade infiltration of inflammatory cell in-between the prostate was observed in one animal and light-grade infiltration of inflammatory cell in-between the prostate was observed in four animals. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food efficiency
- gross pathology
- haematology
- mortality
- organ weights and organ / body weight ratios
- urinalysis
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the study, the NOAEL for the test material has been determined to be greater than 1000 mg/kg bw.
- Executive summary:
The repeat dose oral toxicity of the test material to rats was determined in accordance with Section 4 of the Guidelines for the Testing of Chemicals: Health Effects (ministry of environmental protection of People's Republic of China), in a 28 day oral study. Ten animals per sex were dosed with test material (1000, 250, 62.5 and 0 mg/kg bw) once daily for 28 days via a stomach catheter. Concentrations were selected according to the results of the acute oral toxicity study. To observe the reversibility and delayed effects, an additional high dosage group (1000 mg/kg bw) and an additional control group (0 mg/kg bw) were applied and observed for another 14 days. During the study, body weight and food consumption were recorded weekly and overt signs of toxicity (including quality of hair, general condition of eyes, mouth, teeth, nose and ears, posture, gait, behaviour or activity, character of excreta, etc.) were observed daily. At the end of the study, urine and blood samples were collected before the rats were sacrificed and organs were subsequently taken for pathological examination. The data were statistically analysed by ANOVA between groups and the t-test was used for the additional groups respectively using SPSS 10.0.
No abnormal clinical signs and no mortality was observed during treatment. No significant changes was exhibited in body weight and total food efficiency. Compared with the control group, no significant difference was observed in organ to body weight ratios, haematology analysis and routine urinary analysis. Gross necropsy and pathological detection indicated that no significant changes were exhibited in any of the groups. Compared with the additional control group, no significant difference was observed in the additional high groups for every index measured. Under the conditions of the study, the NOAEL was determined to be greater than 1000 mg/kg bw.
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