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EC number: 441-100-8 | CAS number: 351197-46-1
- 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:
- other: Part of the SNIF file, which was accepted by the Belgian national authority for NONS.
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: EEC Directive 96/54, B.7
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 441-100-8
- EC Name:
- -
- Cas Number:
- 351197-46-1
- Molecular formula:
- Hill formula: C24 H48 N4 O6 CAS formula: C24 H48 O6 N4
- IUPAC Name:
- 2-[2-(dimethylamino)ethoxy]ethyl N-{[1,3,3-trimethyl-5-(9-methyl-2-oxo-3,6-dioxa-1,9-diazadecan-1-yl)cyclohexyl]methyl}carbamate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Wistar (SPF)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: bidistilled water
- Details on oral exposure:
- Method of administration:
gavage - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Test duration: 28 days
- Frequency of treatment:
- Dosing regime: 7 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 30, 150, 450 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 30 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 10 animals at 450 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 30 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 10 animals at 450 mg/kg bw/day - Control animals:
- yes
Results and discussion
Results of examinations
- Details on results:
- Clinical observations:
MORTALITY / VIABILITY
One male treated with 450 mg/kg/day died at treatment day 23 and one male of the same dose group at day 26. Four females treated with 450 mg/kg/day died on treatment days 5, 10 and 19. The cause of the deaths was not evident at microscopic level. However, a relation to the treatment with the test item cannot be excluded. All other animals survived until scheduled necropsy.
CLINICAL SIGNS
No test item related clinical signs were evident in animals treated with 30 or 150 mg/kg/day. The following signs were observed in animals treated with 450 mg/kg/day. Slight piloerection was seen in two males and three females in treatment week three and in one female in treatment week four. This finidngs may be test item related. Slight ataxia was observed in two males and three females in treatment week three and in one female in treatment week two. Slight tremor was observed in two males and five females in treatment week three and in one female in treatment week two. It could not be excluded that these findings were test item related. Slight spasm was noted in two females in treatment week one. It could not be excluded that this was test item related. Slight sedation was noted in two males and seven females in treatment week three and one female in treatment week two. It could not be excluded that this was test item related. Slight dyspnea was noted in four females in treatment week one. Slight bradypnea was noted in one male in treatment week one. Breathing noise was evident in two males and in four females in treatment week three. It could not be excluded that these findings are due to test item treatment. No other clinical signs were evident in males or females (week 1-3).
FUNCTIONAL OBSERVATIONAL BATTERY
Grip Strength
No test item related changes in fore- or hind limb grip strength were evident in males or females when compared with controls.
Locomotor Activity
Significantly decreased (p<0.01) locomotor activity was observed in males treated with 450 mg/kg/day during the whole observation period of 60 minutes when compared with controls. In females of the same dose group this activity was significantly decreased in the first 30 minutes (p<0.01), and between 45 and 60 minutes (p<0.05) of observation. Between 30 and 45 minutes this decrease was not significant. Significantly decreased locomotor activity was also observed in males treated with 150 mg/kg/day in the first 30 minutes of observation (p<0.01), and between 45 and 60 minutes (p<0.05). Between 30 and 45 minutes this decrease was not significant. These differences in locomotor activity were considered to be test item related.
No further changes in locomotor activity were noted when compared with controls.
FOOD CONSUMPTION
No changes in mean daily or relative food consumption were observed in males or females after four or six weeks when compared with control animals.
BODY WEIGHT
Significantly decreased (p<0.05) mean body weight was noted in males treated with 450 mg/kg/day in treatment week four when compared with the controls. Significantly decreased (p<0.05) mean body weight gain was observed in males treated with 450 mg/kg/day in treatment weeks three and four when compared with the controls. Significantly (p<0.01) decreased mean body weight gain was noted in females treated with 450 mg/kg/day on days 22 (week four) and 28 (week four) and in females treated with 150 mg/kg/day on day 28 (week four). Significantly decreased (p<0.05) mean body weight gain was noted in females treated with 450 mg/kg/day within week two of the recovery period when compared with controls. These effects were considered to be test item related. No other significant changes were observed in males or females after four or six weeks.
Laboratory findings:
Hematology
Significantly decreased relative and absolute reticulocytes were noted in males treated with 450 mg/kg/day after four weeks when compared with controls. A dose response relationship could be observed within the absolute values. The decrease was also observed in females of this dose group but without statistical significance after four or six weeks when compared with controls. It can not be excluded that this effect is test item related. No other test item related changes in parameters of hematology were seen in test item treated animals after four or six weeks when compared with controls.
Clinical Biochemistry
Significantly increased activity of Aspartate aminotransferase was measured in males treated with 150 and 450 mg/kg/day after four and six weeks when compared with controls. This increase was also observed in females but was only significant at 450 mg/kg/day. Due to this and due to dose response relationship the increase was considered to be test item related.
The activity of Lactate dehydrogenase was significantly increased in males treated with 150 or 450 mg/kg/day after four weeks when compared with controls. This was considered to be test item related because it was also seen in males treated with 450 mg/kg/day after six weeks and in females treated with 450 mg/kg/day after four weeks when compared with controls.
Urinalysis
No test item related changes in parameters of urinalysis were evident in males or females after four or six weeks when compared with control animals
Effects in organs:
ORGAN WEIGHTS
No changes in mean organ weights, organ to body- or organ to brain weight ratios were noted in test item treated males after four weeks when compared with controls.
Significantly increased (p<0.01) mean liver to body weight ratios were noted in females treated with 150 or 450 mg/kg/day after four weeks when compared with controls. This was considered to be test item related because a dose response relationship was observed.
No test item related changes in mean organ weights, organ to body- or organ to brain weight ratios were noted in males and females treated with 450 mg/kg/day after six weeks when compared with controls.
MACROSCOPIC / MICROSCOPIC FINDINGS
A number of gross findings distinguished some treated decedents from rats at terminal sacrifice:
Lung, pancreas, mandibular lymph node, salivary glands:
Reddish to dark red discoloration in a few males of group 04 and dark red discoloration of lung in 1 female of group 04; Lung, stomach, thymus, ovaries: Dark red foci in a few males or females of group 04;
Intestinal tract: Distended with gas in 1 female of group 04
A number of findings were noted at the end of the treatment period. From these findings, the following ones distinguished decedent rats from rats at terminal sacrifice (K0):
Lung, adrenal glands, stomach, liver, kidneys, thymus, mesenteric and mandibular lymph nodes, ovaries, brain, pancreas, salivary glands:
A congestion was present in some males and/or females of group 04.
Lung, thymus:
A hemorrhage occurred each in 1 high-dose female.
Lung:
An alveolar edema was noted in 1 high-dose female.
All other findings noted in this study at the end of treatment (K0) were considered to be incidental findings commonly occurring in rats of this strain and age.
None of the microscopic findings present after an additional recovery period (R1) were considered to distinguish treated group 04 rats from the control rats.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Basis for effect level:
- other: original NCD unit is mg/kg/day.
- Dose descriptor:
- NOEL
- Effect level:
- 30 mg/kg bw/day (nominal)
- Basis for effect level:
- other: original NCD unit is mg/kg/day.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Classified as: Not classified
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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