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EC number: 947-965-2 | 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- (2-carboxyethyl)({2-[(2-carboxyethyl)(2-hydroxyethyl)amino]ethyl})azanium; [({2-[(2-carboxyethyl)(2-hydroxyethyl)amino]ethyl}carbamoyl)methyl](dodecyl)dimethylazanium; ethanol
- IUPAC Name:
- (2-carboxyethyl)({2-[(2-carboxyethyl)(2-hydroxyethyl)amino]ethyl})azanium; [({2-[(2-carboxyethyl)(2-hydroxyethyl)amino]ethyl}carbamoyl)methyl](dodecyl)dimethylazanium; ethanol
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld
- Age at study initiation: approx. 6 weeks at start of treatment
- Weight at study initiation:-
- Fasting period before study:-
- Housing: 5 animals per sex per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +- 3°C
- Humidity (%):30 - 70 %
- Air changes (per hr):-
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Duplo samples of formulations prepared during week 2, 8 and 13 were taken for analysis of accuracy and homogeneity (16 samples in total).
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Once daily for at least 90 days, 7 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
50 mg/kg/day, 150 mg/kg/day, 450 mg/kg/day
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 a 14-day range finding study
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
DETAILED CLINICAL OBSERVATIONS:
- Time schedule: once daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION :Yes
- Time schedule for examinations: weekly
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at pretest all animals
- Dose groups that were examined: groups 1 and 4 at week 13
HAEMATOLOGY: Yes
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination
- Anaesthetic used for blood collection: Yes (iso-flurane)
- Animals fasted: Yes (overnight)
- How many animals: all animals
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination
- Animals fasted: Yes (overnight)
- How many animals: all animals
- Parameters checked in table [No.1] were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 12-13
- Dose groups that were examined: all animals
- Battery of functions tested: sensory activity / grip strength / motor activity /
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 2)
ORGAN WEIGHTS: Yes (see table 3)
HISTOPATHOLOGY: Yes (see table 4) - Statistics:
- - Univariate one-way analysis of variance was used to assess the significance of intergroup differences.
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
- The Steel-test (many-to-one rank test) was applied when the data could not be assumed to follow a normal distribution.
- The Fisher-Exact test was applied to frequency data.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables. No statistical analysis was performed on motor activity data. Test statistics were calculated on the basis of exact values for means and pooled variances. Individual values, means and standard deviations may have been rounded off before printing. Therefore, two groups may display the same printed means for a given parameter, yet display different test statistics values.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- ALAT and ASAT increased in high dose males
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- spleen and liver weight affeted
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- effects in stomach, lungs and kidneys
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No mortality occurred during the study period which could be attributed to treatment with the test substance. No clinical signs of toxicity were observed.
BODY WEIGHT AND WEIGHT GAIN: Body weights and body weight gain of treated animals did not show changes that were considered to have arisen as a result of treatment.
FOOD CONSUMPTION AND COMPOUND INTAKE : There were no differences in food consumption between treated and control animals, which were considered to be related to treatment with the test substance.
OPHTHALMOSCOPIC EXAMINATION: There were no ophthalmoscopic findings at pre-dose and in week 13 among the treated animals.
HAEMATOLOGY: There were no changes of haematology parameters that were considered to represent a sign of direct toxicity.
CLINICAL CHEMISTRY: Alanine aminotransferase and aspartate aminotransferase activity values were increased among high dose males. In addition, cholesterol values were reduced among these males.
NEUROBEHAVIOUR: No changes were observed in hearing ability, pupillary reflex, static righting reflex and grip strength in the treated animals, when compared to control animals. The variation in motor activity did not indicate a relation with treatment.
ORGAN WEIGHTS: Spleen and spleen to body weight ratios were reduced among high dose males. In addition, liver to body weight ratios of group 3 and 4 males were lower than controls. Liver weights uncorrected for body weights were reduced in group 3 only, while mean liver weights of group 4
showed no statistically significant reduction. Among high dose females, increased kidney and kidney to body weight ratios were observed.
GROSS PATHOLOGY: Macroscopic findings recorded in this study were considered to be comparable in incidence and severity with the control animals or within the normal range of background alterations that may be seen in untreated animals of this age and strain.
HISTOPATHOLOGY: NON-NEOPLASTIC: An increased incidence of minimal to moderate accumulations of foam cells in the lungs of group 4 males and group 4 females was noted. The forestomach of males and females of group 4 showed minimal to marked squamous hyperplasia (with accompanying
inflammatory changes). These lesions affected the main body of the forestomach. Additionally, minimal to slight cortical tubular basophilia of the kidneys was noted in group 4 females.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOAEL
- Effect level:
- 75 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- From the results presented in this report a No Observed Adverse Effect Level (NOAEL) for the substance of 50 mg/kg/day was established. Based on the absence of functional or morphological disturbances supporting the liver weight changes noted for group 3 males, a NOAEL of 150 mg/kg/day is considered.
- Executive summary:
A 90 -day oral toxicity study with the substance by daily gavage in the rat was performed. The study was based on the following guidelines: - EEC Directive 87/302/EEC, B Repeated Dose (90 days) Toxicity (orat), 1988.
- OECD 408, Repeated Dose go-day Oral Toxicity Study in Rodents, 1998.
Based on a 16 day range finding study the dose levels were selected to be 0, 50, 150 and 450 mg/kg/day.
The test substance was administered daily for at least 90 days by oral gavage to Wistar rats. One control group and three treated groups were tested, each consisting of 10 males and 10 females.
The following parameters were evaluated:
Clinical signs, functional observations, body weight, food consumption and ophthalmoscopy. At termination: clinical pathology, macroscopy, organ weights and histopathology on a selection of tissues.
RESULTS: Accuracy and homogeneity of formulations of test substance in milli-U water were demonstrated by analyses.
Treatment related findings observed were as follows:
50 mg/kg/day:- No treatment-related findings noted.
150 mglkg/day:- Liver weight reduced (males).
450 mglkg/day:- Alanine and aspartate aminotransferase activity values increased and cholesterol values reduced (males).
- Irregular surface of the forestomach (males and females), with dark red foci or thickening (males); thickened limiting ridge and/or dark red contents of the stomach (females); gray-white foci on the lungs (females).
- Spleen and liver weight reduced (males); kidney weights increased (females).
- Pulmonary foam cell accumulations and squamous hyperplasia of the forestomach (with accompanying inflammatory changes) (males and females); cortical tubular basophilia of the kidneys (females).
CONCLUSION: From the results presented in this report a No Observed Adverse Effect Level (NOAEL) for
the substance of 50 mg/kg/day was established. Based on the absence of functional or morphological disturbances supporting the reduction of liver weights of group 3 males, a NOAEL of 150 mg/kg/day was considered.
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