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EC number: 247-952-5 | CAS number: 26741-53-7
- 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
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity of the test item was examined in several subchronic and chronic studies in rats and dogs (most of them prior GLP, equivalent to OECD guideline 408, 452 or 409). In addition, a study on delayed neurotoxicity was performed (OECD guideline 418). In the majority of the studies all animals survived, adverse effects or signs of toxicity were not observed. In one dog study, myelin lesions and behavioural changes were observed. However, the test on neurotoxicity as well as the outcome of the other studies in rats and dogs gave no hint for a neurotoxic potential. The NOAEL after repeated dose administration is therefore considered to be 78 mg/kg bw in males and 91 mg/kg bw in females.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1978 - 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- no analytical verification of test material, age of animals not mentioned, no description of environmental conditions and diet, no analysis of platlet count and quick time, no measurement of albumin and protein, no measurement of electrolytes
- GLP compliance:
- no
- Remarks:
- prior inition of GLP-guidelines
- Limit test:
- no
- Specific details on test material used for the study:
- - test item: Weston XR-1532
- hand written note: contains 1% xxxpropanolamine - Species:
- rat
- Strain:
- other: Charles River CD@ rats
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Age at study initiation: /
- Weight at study initiation: male 80 - 107g, females 77 - 98g
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: /
ENVIRONMENTAL CONDITIONS
animals were housed individually in hanging wire-mesh cages and maintained in a temperature-, humidity- and light-controlled room
IN-LIFE DATES
07.11.1978 - 5./6.02.1979 - Route of administration:
- oral: feed
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): daily
- Mixing appropriate amounts with (Type of food): first making a p remix of appropriate amounts of the test material and Rodent Laboratory Chow, premix was then added to additional amounts of Rodent Laboratory Chow@ and mixed
- Storage temperature of food: - 200°C liquid nitrogen (prevent hydrolysis) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Recovery determinations, Homeogeneitiy determinations, test diet analysis,
- Duration of treatment / exposure:
- 90d
- Frequency of treatment:
- daily
- Dose / conc.:
- 100 ppm
- Remarks:
- corresponding to 7.6 mg/kg bw in males and 8.7 mg/kg bw in females
- Dose / conc.:
- 300 ppm
- Remarks:
- corresponding to 22 mg/kg bw in males and 26 mg/kg bw in females
- Dose / conc.:
- 1 000 ppm
- Remarks:
- corresponding to 78 mg/kg bw in males and 91 mg/kg bw in females
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: not given
- Rationale for animal assignment (if not random): on the basis of general good health
- Rationale for selecting satellite groups: no satellite group
- Post-exposure recovery period in satellite groups: no post observation period - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- daily
OPHTHALMOSCOPIC EXAMINATION: Yes
- Dose groups that were examined: all
HAEMATOLOGY: Yes
- Time schedule for collection of blood: month 1 and 3 of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10/group
- Parameters checked: hematocrit, hemoglobin concentration, erythrocyte count and total and differential leucocyte counts
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: month 1 and 3 of the study
- Animals fasted: Yes
- How many animals: 10/group
- Parameters checked: blood glucose levels, blood urea nitrogen levels, serum alkaline phosphatase, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), Cholinesterase activities in plasma, red blood cells and brain (termination only), Brain cholinesterase was determined at termination only
URINALYSIS: Yes
- Time schedule for collection of urine: month 1 and 3 of the study
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked: appearance, pH, volume and specific gravity; qualitative measurements for albmin,glucose, bilirubin, occult blood, microscopic examination of the spun deposit
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
At the termination of the study period all the rats were sacrificed using carbon dioxide gas and necropsied. Select organ weights were from all rats were recorded.
HISTOPATHOLOGY: Yes
The following tissues from 10 male and 10 female rats from the control group and the 1000-ppm group were paraffin embedded, sectioned, stained with hematoxylin and eosin and examined microscopically: adrenals, aorta, eye and optic nerve, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, liver, trachea, spleen, pancreas, urinary bladder, bone marrow (sternum), prostateluterus, seminal vesicles, testes/ovaries, brain, heart, lung and bronchi, sciatic nerve, pituitary, thyroid and parathyroid, mesenteric lymph node, mandibular lymph node, spinal cord, salivary gland, (submaxillary), skeletal muscle (thigh), skin, mammary gland, thymus, kidneys, any other tissue with gross lesions
Additionally livers and spleens from 10 male and 10 female rats from the 100-ppm and 300-ppm groups were similarly processed and examined. - Other examinations:
- Bone marrow smears from all rats were made at the time of necropsy, fixed in methyl alcohol, stained by Giemsa's method and examined microscopically.
- Statistics:
- All statistical analyses compared the treatment groups with the control group by sex. Body weights (week 13 ), food consumption (weeks 1-13), absolute and relative organ weights (terminal sacrifice), and hematology, biochemistry and urinalysis parameters (1 and 3 months) were compared by analysis of variance (one-way classification), Bartlett's test for homogeneity of variances and the appropriate t-test (for equal or unequal variances) as described by Steel and Torrie using Dunnett's multiple comparison tables to judge significance of differences.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No signs of overt toxicity were observed among the treated rats. Incidental signs observed for a few control and/or treated rats included hair loss, missing or malalinged upper incisor, excessive lacrimation, red material around eyes, leaning to left, red or swollen eyes, rales, corneal opacity, swollen ventral neck, swollen conjunctiva and dilated pupil.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- All animals survived until scheduled day of necropsy with exeption of one female animal of the high dose group. It is not documented whether this female died by accident or not.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The group mean body weights of both the low- and mid-dose male and female rats were greater than control values, and both groups of high-dose males and females had group mean body weights lower than
controls. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Low- and mid-dose male rats consumed slightly more food than did controls, while high-dose males ate slightly less than control. All of the groups of female consumed approximately equivalent amounts of food.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- There were no compound-related effects noted during the 3-month ophthalmic examinations.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No compound-related effects on the results of the hematologic tests.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No compound-related effects on the results of the biochemical tests.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No compound-related effects on the results of the urinalysis tests.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No compound-related organ weight variations were seen in any of the rats fron treatment groups.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No compound-related gross lesions were seen in any of the rats fron treatment groups.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic lesions considered probably compound-related were seen in livers and spleens of the female rats from the 1000-ppm group. This consisted of very slight to slight extramedullary hematopoiesis in these organs. This lesion was not present in rats from the control and the 300-ppm groups, but was seen in one rat from the 100-ppm group. However, in as much as a mild degree of extramedullary hematopoiesis in liver and spleen could occasionally occur in normal young rats, occurrence of this lesion in one rat from the 100-ppm group, was not considered in any way related to the compound administration.
- Histopathological findings: neoplastic:
- not examined
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 ppm
- Sex:
- male/female
- Remarks on result:
- other: corresponding to 78 mg/kg bw in males and 91 mg/kg bw in females
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 55 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Several studies (prior GLP, similar to concurrent OECD guideline) were conducted to examine toxicity after repeated dose application to rats. The test material was administered in diet to male and female rats at dose levels from 100 - 3000 ppm for 90 days, 6 months or 2 years, respectively. Treatment related death were not recorded. In the key study, one female animal was found dead with an unknown cause of death. Except for the key study, clinical signs of toxicity, changes in hematology clinical chemistry or urinalysis as well as changes in body weight and food consumption were not observed in any of the studies. In the course of the key study, slightly lower body weight and slight extramedullary hematopoisis in animals of the high dose group were recorded. The 90d rat study performed by IBT was disregarded considering the history of IBT of falsifying study reports.
In the 4-month study performed with dogs, the test item was applied unchanged in capsules to beagle dogs (4/sex/dose) at concentrations of 4, 12 and 40 mg/kg bw. One female was sacrificed in moribund due to strong decrease in food consumption and subsequent body weight loss starting from week 9. At this female, signs of uncoordinated behaviour were observed; histopathology revealed abnormalities of axonal fibers and myelin. Moreover, 7/8 high dose animals showed degenerative myelin lesions. Beside this finding, animals from all treatment groups suffered from an eosinophilic pneumonia. This effect is not regarded as treatment related but may origin from parasite infestation. A second study with dogs is available by IBT. Similar to the rat study mentioned above, this study report was also disregarded.
To further investigate the neurotoxicity findings a test on delayed neurotoxicity in hens was performed. The animals (4 female hens/dose) received a single dose of 800, 1200, 1800, 2700, 4050 or 6080 mg/kg bw of the substance by gavage. The hens were observed for 14 days, group 1 and 2 was then necropsied. Animals of the other groups were redosed and observed for further 21 days. Check for neurotoxicity was performed three times a week. None of the hens died; sings of (neuro)toxicity or any changes in histopathology were not observed.
Discussion:
Subchronic or chronic administration of the test material did not induce mortalities (except for the dog study) or any sign of toxicity in rats and dogs. Also behaviour and reactions were considered to be normal. At the end of the dog study degenerative myelin lesions were observed in the top dose group. A test on delayed neurotoxicity performed in hens was also without findings. All animals appeared to be normal referring to gait, motoractivity, balance or leg weakness. Histhopathological examination of the nervous system gave no hint on myelin lesions. Thus, it is questionable if the effects observed in the second dog study result from the test item or from an impurity. On the other hand, test substance purity was given as 100%. Another finding of the dog study was pneumonia in animals of all treatment groups. With regard to this health status, an additional disease, i.e. virus infection, leading to neurotoxicity is thinkable.
In conclusion, the substance is not considered to be neurotoxic and the NOAEL after repeated dose administration is 1000 ppm or 78 mg/kg bw in males and 91 mg/kg bw in females.
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.
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