Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: - | 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:
- other: read across from supporting substance
- Adequacy of study:
- key study
- Study period:
- From September 23,1985 to October 23,1985
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant with international guideline
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- yes
Test material
- Reference substance name:
- Similar substance 1
- IUPAC Name:
- Similar substance 1
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hoechst A.G
- Age at study initiation: 6 weeks
- Housing: in fully air-conditioned rooms in Makrolon cages (type 4) on softwood granules (lignocellulose) into groups of 5 animals
- Diet: Altromin 1323, ad libitum, no food consumption between 9.30 to 12 (administered test item dose by gavage)
- Water: tap water in plastic water bottles ad libitum, no drink consumption between 9.30 to 12 (administered test item dose by gavage)
- Acclimation period: 5 days
- Health check: The behavior and general health of all animals used during the experiment was 2 x daily, checked on weekends and holidays, 1 x daily. Every week the rats to neurological disorders, clouding of the eye media, adverse effects on oral mucosa and disorders of tooth development were examined.
ENVIRONMENTAL CONDITIONS
- Temperature:22 ± 3° C
- Humidity: 50 ± 20 %
- Air changes (per hr):romm fully air conditioned
- Photoperiod: 12 hours cycle dark/light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
dose mg/kg bw day concentration %(w/v) appl. Volume ml/kg vehicle
0 0 5 water
62.5 1.25 5 water daily
250 5 5 water daily
1000 20 5 water daily - Duration of treatment / exposure:
- 30 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 62.5 , 250, 1000 mg/kg bw day
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 animals x sex x 4 doses
- Control animals:
- yes
Examinations
- Observations and examinations performed and frequency:
- The behavior and general health of all animals used during the experiment was checked twice a day, on weekends and holidays, once a day. Every week the rats were examined for neurological disorders, clouding of the eye, adverse effects on oral mucosa and disorders on teeth development .
CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
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: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
CLINICAL CHEMISTRY: Yes
sodium
potassium
inorg. phosphorus
uric acid
total bilirubin
creatinine
Glucose in serum
Urea-N (BUN)
calcium
chloride
ASAT (G0T)
ALT (GPT)
alkaline phosphatase (AP)
y-glutamyl
Total protein
Electrophoresis
URINALYSIS: Yes
The urine production was carried out overnight on 29-30. The experiment (16 hours) to non-fed animals and not soaked in metabolic cages (single urine). The urine analyzes were performed on all males and females performed and extended to the following parameters:
Parameters. method
appearance
color
pH hemoglobin
protein
glucose
ketone bodies
bilirubin
urobilinogen
density
sediment
NEUROBEHAVIOURAL EXAMINATION: Yes
HAEMATOLOGY: Yes
The following haematological parameters were determined:
parameter method
hemoglobin
Erythrocyte count
Leucozytenzahl
hematocrit
reticulocyte*
Differential blood count
Platelet count
* Was performed only on the control group and the 1000 ppm group Furthermore, the calculated values for MCV, MCH and MCHC were determined. - Sacrifice and pathology:
- Sacrifice:
After the retro-orbital blood sampling for hematological tests, the animals were killed in nembutal narcosis (injection of approximately 50 mg / kg ip) by transection of the vena cava cranialis and exsanguination.
GROSS PATHOLOGY: Yes
After killing and bleeding, the animals were dissected in accordance with Section I Procedure (Prof. K / G of 02.04.1982). Sections have been taken from skin, body orifices, eyes, teeth, oral mucosa and the inner.
Organs were assessed macroscopically. Abnormal findings were recorded.
HISTOPATHOLOGY: Yes
In accordance with Section I Procedure (Prof. K / G of 04.02.1982), from the animals of the main groups 1 - 4 fragments of the following organs were fixed and delivered for histological examination:
heart
lung
liver
kidneys
spleen
stomach
jejunum
Colon
bladder
testicle
epididymis
prostate
seminal vesicle
ovaries
uterus
thyroid
pancreas
adrenal
thymus
pituitary
brain
Eye with N. optic
Bone marrow (femur) - Statistics:
- The following measurements were evaluated statistically at a significance level of p = 0.05:
Body weights on the individual time points
Body weight during the first interval
1- 15 experiment
15 - 29 experiment
29 - 31 experiment
Hematological parameters (except for differential blood count)
Clinical-chemical parameters
Absolute and relative organ weights
Urine analysis (pH and specific gravity)
The evaluation was carried out with the aid of a program package for evaluating toxicological tests, according to the Standard Operating Procedure
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- at 1000 mg/kg bw day
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- red urines
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
The behavior and general health of the animals in Groups 1, 2 and 3 (0, 62.5 and 250 mg / kg bw. / Day) were not mentioned during the study period. Only a male of 62.5 mg / kg bw. / Day group was injured in the nek. For this reason, the animal was kept individually.
Two females and one male of the 1000 mg / kg bw. / Day group showed the following symptoms: ruffled fur, crouching position, long-legged speed, tumbling and passivity. One of the two females died on 29° day of test, may be by cannibalism.
Neurological disorders, eye opacity, disorders of tooth development and oral lesions, which could be attributed to the administration of the test substance were noted in any dose group.
BODY WEIGHT AND WEIGHT GAIN
The statistical analysis of body weight gain in males was observed that in the highest dose group (1000 mg / kg bw. / Day) was a statistically significant delay of body weight. All other treated groups showed no statistically significant differences compared to control.
WATER CONSUMPTION
The relative water consumption was after administration of 1000 mg / kg bw. / Day significantly increased.
In the other dose groups, the relative water consumption by Council abreichung the test substance was unaffected.
HAEMATOLOGY
All parameters are normal.
CLINICAL CHEMISTRY
All tested parameters showed no significant deviations from the normal, except inorganic phosphorous (both male and female), sodium (female), chloride (female), bilirubin (female), urea (female), Alanine transaminase (female).
These deviations are still all within the normal range of biological rat strain used.
The differences are therefore particularly suitable for the animals in groups 2 and 3 (62.5 and 250 mg / kg bw); therefore it is not of toxicological relevance.
The serum electrophoresis showed no evidence of compound-related changes.
The only result is a decrease in the α-globulins in the animals of the 1000 mg / kg bw. Group.
URINALYSIS
Changes in the urinalysis were not observed. The sediments content were normal. It was only a statistically significant increase in specific gravity in females of the 250 mg / kg bw. Group. The urine samples of 250 and 1000 mg / kg bw. Group were found in red colour.
ORGAN WEIGHTS
In the 62.5 ppm group, there were no statistically significant changes in absolute and relative organ weights.
In the 250 mg/kg bw. Group, the absolute kidney weights of males were increased, but not statistically significant. This differences are very minimal and there isn't a dose-dependence of histologically detectable changes, then no toxicological significance can be derived.
MACRO AND MICROSCOPICAL ANALYSIS
The macroscopic studies in animals showed the highest dose (1000 mg / kg bw. / Day) a pink discoloration of the gastro-intestinal tract. The sex organs of male animals (seminal vesicle, testis) of 1000 mg / kg bw. Group were partially reduced.
Microscopically resulted in male and female rats, no compound-related organ damage morphologically tangible.
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- ca. 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: clinical signs; mortality; body weight; food consumption; food efficiency; water consumption ; ophthalmoscopic examination; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology
- Dose descriptor:
- NOEL
- Effect level:
- ca. 214.5 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: clinical signs; mortality; body weight; food consumption; food efficiency; water consumption ; ophthalmoscopic examination; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Neurological disorders, eye opacity, disorders of tooth development and oral lesions, which could be attributed to the administration of the test substance were noted in any dose group.
The behavior and general health of the animals of 62.5 mg / kg and 250 mg were / kg bw / Day group during the study period without special features. Only a male of 62.5 mg / kg bw. / Day group was from 15 Experiment to test the end of an injury in the neck.
Two female and one male of the 1000 mg / kg bw. / Day group hava had , from day 22 of experiment to the end, the following symptoms: ruffled fur, crouching position, long-legged speed, tumbling and passivity.
One of the two females died on day 29 of the experiment.
The statistical analysis of body weight gain in males was the highest dose group (1000 mg / kg bw. / Day) from 15 The experiment, a statistically significant retardation of body weight. All other treated
deltas groups showed no statistically significant differences compared to control.
The relative water consumption was after administration of 1000 mg / kg bw. / Day significantly increased.
In the other dose groups, the relative water consumption was unaffected by the administration of the test substance.
The haematological and clinical chemistry tests did not reveal any clues about toxicological changes.
The urinalysis was normal and also showed 'no evidence of toxic damage to the animals. It was only in the 250 and 1000 mg / kg bw. Group in both sexes to a reddish to red discoloration of urine.
Applicant's summary and conclusion
- Conclusions:
- In a 30-day test by daily gavage administration, the similar substance 1 showed significative adverse effects at the dose of 1000 mg / kg body weight on rat. These symptoms are presented in the form of impairment of body weight and development of drinking water consumption. Two female and one male showed the following symptoms: ruffled fur, crouching position, long-legged speed, tumbling and passivity. A female died on 29° day of the experiment. The hematology, clinical chemistry, and macroscopic and histological studies revealed no evidence of specific toxicity. A NOEL of 250 mg/kg bw was determined.
- Executive summary:
The test substance was administered orally by gavage (total 30 applications, 7 x per week) in a 30-day study on SPF-Wistar rats at doses of 0 / 62.5 / 250/ 1000 mg / kg body weight per day. In all experimental groups the daily behaviorwas assessed and the general state of health tested. The body weight gain and food consumption were assessed twice a week, the water consumption determined weekly.
Hematological, clinical chemistry and urinalysis tests were performed on the study. At necropsy, the animals were examined macroscopically for gross pathology, the major organs weighed and calculated the relative organ weights. of a large number of tissues of these animals were made histological preparations and examined. The body weights, haematological and clinical chemistry parameters and urinalysis (specific gravity, pH) and the absolute and the relative weights were statistically tested and the differences are compared to the control groups.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.