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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 203-013-1 | CAS number: 102-20-5
- 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 Oral Toxicity:
Repeated dose oral study for test chemical was assessed for its possible toxic potential. Groups of 10 male and 10 female Osbourne-Mendel rats were provided test chemical mixed in the diet at concentrations of 0, 1000, 2500 or 10,000 ppm which corresponding to an average daily intakes of 0, 50, 250, or 500 mg/kg bw per for 17 weeks. At termination, hematological examinations revealed no effects due to administration of the test chemical. At necropsy, no differences were reported in major organ weights between test and control animals. Gross examination of tissue of all animals was unremarkable and histopathological examination of six-eight animals, equally represented by gender, for the high-dose group and the control group revealed no treatment-related lesions. Hence, the highest dose tested i.e 500 mg/kg/day can be considered as the NOAEL.
Repeated dose toxicity: Inhalation
The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical. The experimental vapour pressure was 0.0248Pa at 20 deg C. Also, the LC50 was considered to be >5500 mg/m3, when rats were exposed to the test chemical by inhalation route for 4 hours. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore, this study is considered for waiver
Repeated dose toxicity: dermal
A short-term repeated dose dermal toxicity study need not be conducted because exposure of humans via dermal route in production and/or in use is highly unlikely based on the thorough and rigorous risk assessment provided. Also, the acute dermal toxicity LD50 value for the test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. The test chemical was also found to be not sensitizing to the skin. Considering this, the end point for repeated dermal toxicity is considered as waiver.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from publication.
- Qualifier:
- according to guideline
- Guideline:
- other: As mention below
- Principles of method if other than guideline:
- To evaluate the toxic potential of test chemical in male and female rats by oral feed for 17 weeks.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Osborne-Mendel
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: The animals were housed individually in wire cages
- Diet (e.g. ad libitum): Rodent diet ad libitum
- Water (e.g. ad libitum): water ad libitum - Route of administration:
- oral: feed
- Vehicle:
- other: Rodent diet
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency):The test chemical was fed in the diet and fresh diets were made and distributed weekly.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Not specified.
- Duration of treatment / exposure:
- 17 weeks
- Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:
1000, 2500 and 10000 ppm, corresponding to an average daily intake of 0, 50, 250 or 500 mg/kg bw
Basis:
no data - No. of animals per sex per dose:
- Total number of animals 80
0 mg/kg/day-10 male and 10 female
50 mg/kg/day-10 male and 10 female
250 mg/kg/day-10 male and 10 female
500 mg/kg/day-10 male and 10 female - Control animals:
- yes, plain diet
- Details on study design:
- no data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: 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: Not specified
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Haematological examinations were made at termination of the subacute studies
- Parameters checked in table [No.?] were examined. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits
CLINICAL CHEMISTRY: Not specified
URINALYSIS: Not specified
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified
OTHER: The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes , At the termination of the experiments the rats were sacrificed and exsanguinated.
HISTOPATHOLOGY: Yes , The tissues of all the rats were examined macroscopically at the time of sacrifice. These organs, the remaining abdominal and
thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological
examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. - Other examinations:
- Tissues from rats dying during the experiment were examined for gross changes and were preserved if autolysis was not advanced. Organs were not weighed but abnormalities and the suspected reason for death were noted
- Statistics:
- Not specified
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Weekly measurement of body weight showed no significant difference between test and control animals.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Weekly measurement of food intake showed no significant difference between test and control animals.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- At termination, haematological examination revealed no effects due to treatment. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- At necropsy, no difference between test and control animals in the weights of major organs was reported.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Gross examination of tissues from all animals revealed no remarkable changes, and histological examination of three to four animals of each sex at the high dose and from the control group revealed no treatment-related lesions.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- Critical effects observed:
- no
- Conclusions:
- At termination, hematological examinations revealed no effects due to administration of the test chemical. At necropsy, no differences were reported in major organ weights between test and control animals. Gross examination of tissue of all animals was unremarkable and histopathological examination of six-eight animals, equally represented by gender, for the high-dose group and the control group revealed no treatment-related lesions. Hence, the highest dose tested i.e 500 mg/kg/day can be considered as the NOAEL.
- Executive summary:
Repeated dose oral study for test chemical was assessed for its possible toxic potential. Groups of 10 male and 10 female Osbourne-Mendel rats were provided test chemical mixed in the diet at concentrations of 0, 1000, 2500 or 10,000 ppm which corresponding to an average daily intakes of 0, 50, 250, or 500 mg/kg bw per for 17 weeks. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. Measurement of body weight and food intake recorded weekly showed no significant difference between test and control animals at any intake level. At termination, hematological examinations revealed no effects due to administration of the test chemical. At necropsy, no differences were reported in major organ weights between test and control animals. Gross examination of tissue of all animals was unremarkable and histopathological examination of six-eight animals, equally represented by gender, for the high-dose group and the control group revealed no treatment-related lesions. Hence, the highest dose tested i.e 500 mg/kg/day can be considered as the NOAEL.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated Dose Oral Toxicity:
Various studies have been reviewed to determine the toxic effect of the test chemical when exposed repeatedly via oral route. These include in vivo experimental studies performed on rats for the test chemical. The results are mentioned below:
Repeated dose oral study for test chemical was assessed for its possible toxic potential. Groups of 10 male and 10 female Osbourne-Mendel rats were provided test chemical mixed in the diet at concentrations of 0, 1000, 2500 or 10,000 ppm which corresponding to an average daily intakes of 0, 50, 250, or 500 mg/kg bw per for 17 weeks. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. Measurement of body weight and food intake recorded weekly showed no significant difference between test and control animals at any intake level. At termination, hematological examinations revealed no effects due to administration of the test chemical. At necropsy, no differences were reported in major organ weights between test and control animals. Gross examination of tissue of all animals was unremarkable and histopathological examination of six-eight animals, equally represented by gender, for the high-dose group and the control group revealed no treatment-related lesions. Hence, the highest dose tested i.e 500 mg/kg/day can be considered as the NOAEL.
This result is supported by a Combined repeated dose repro-developmental toxicity study performed to provide evaluations of general and reproduction/ developmental toxicity endpoints associated with administration of repeated doses of test substance in Wistar rats. The animals were randomly allocated to the four main groups (13/sex/group) and two recovery groups (5/sex/group). The doses selected for main groups were; 0 (G1-control),308 mg/kg body weight (G2), 556 mg/kg body weight (G3) and 1000 mg/kg body weight (G4) daily for 64 days. The recovery groups G1-R and G4-R were dosed with similar doses of respective main groups. Vehicle corn oil to G1 and G1-R and test item to G2, G3, G4 and G4-R animals were administered by oral gavage route each day during the dosing period. No mortality and morbidity were observed any of the groups of animals throughout the study period. Animals of all dose groups were observed for Clinical signs/ symptoms daily once during the experimental period. No apparent treatment related clinical signs were observed in any of the animals throughout the treatment and recovery period. All hematological and clinical chemistry parameters in animals of different treated groups of both the sexes were comparable to their respective control groups. No treatment related changes were observed in any of the treatment groups. At the end of treatment and recovery period, absolute and relative weight of organs of treated group rats of either sex did not differ significantly when compared to the respective control group rats. External and visceral examination of all male and female rats of control and all treated groups including recovery groups did not reveal any abnormality of pathological significance. Terminally sacrificed pups of all treated groups did not reveal any lesion of pathological significance in any of the group when compared with control group. Pups that died among the control and treated groups during the course of study, revealed various lesions when examined externally and internally but the observations were not considered treatment related. From the patho-morphological results presented, it was concluded that, the treatment of test chemical at 308, 556 and 1000 mg/kg body weight in male and female rats did not affect adversely and no alteration of pathological significance was observed in any of the organs and reproductive organs of high dose treated group rats are well comparable with respective control group rats and exhibited no dose relationship. Further these observed lesions are common in occurrence in rodents during toxicological studies. Hence, occurrence of these lesions could be considered as spontaneous or incidental in nature and not to be attributed to the administration of the test chemical. Based on the findings of Repeated Dose Oral Toxicity Study in combination with Reproduction/ Developmental Toxicity of test chemical in Wistar Rats with 14 days recovery, where in 0, 308, 556 and 1000 mg/kg body weight, doses were tested; no test item related changes were observed at any of the dose level, hence the general No Observed Adverse Effect Level (NOAEL) of test chemical was considered to be more than 1000 mg / kg body weight.
These results are further supported by a Repeated Dose 28-day Oral Toxicity study designed and conducted to determine the toxicity profile of the test chemical when administered daily for 28 days to the Sprague Dawley rats. The study was performed according to OECD 407 Guidelines.A total of 48 animals (24 males + 24 females) were selected and randomly distributed into four groups with 6 animals/sex/group and 3/sex/cage. The test chemical was administered to animals at the dose levels of 250 mg/kg,500 mg/kg and 1000 mg/kg body weight. The control animals were administered with corn oil only. Rats were observed daily for Viability, Behavior, Alterations, Vocalizations, Respiration and Palpebral closure. The rats were observed for reaction to removal, reaction to handling, urination, defecation, prominence of eye, lacrimation, salivation, piloerection, examination of mucous membrane, examination of skin / fur, examination of natural orifices and animal appearance. The animals were also placed in the open field and its appearance and behavior were observed. The quantity of feed consumed by control and different treatment groups was recorded weekly until scheduled sacrifice. All the rats survived through the dosing period of 28 days and were sacrificed and gross lesions were noted. The rats were sacrificed by CO2 asphyxiation and Gross necropsy was conducted. All the animals of 0 mg/kg, 250 mg/kg, 500 mg/kg and 1000 mg/kg/bw/day group were sacrificed and gross lesions were noted. Liver, Kidneys, Adrenals, Epididymides, Prostate + Seminal Vesicle with Coagulation gland as whole, Thymus, Spleen, Brain, Heart, Lungs, Uterus, Testes/Ovaries were dissected free of fat and weighed. The paired organs were weighed together.Following tissue samples of organs from control and animals treated at different dose groups were preserved and those from control and treated at the highest dose level of 1000 mg/kg were subjected to histopathological examination.Adrenals, Aorta, Brain (cerebrum, cerebellum and pons), Caecum, Cervix, Colon, Duodenum, Epididymides, Eyes, Heart, Ileum, Jejunum, Kidneys, Liver, Lungs, Mesenteric Lymphnodes, Oesophagus, Ovaries, Pancreas, Pituitary gland, Pharyngeal Lymphnodes, Prostate, Rectum, Skeletal Muscles, Skin with Mammary Gland, Spleen, Sternum with bone marrow, Sciatic Nerve, Spinal Cord (Cervical, mid thoracic and lumbar), Stomach, Seminal Vesicles with Coagulation Gland, Testes, Thymus, Thyroid, Trachea, Vagina, Urinary Bladder, Uterus. All the male and female animals from control and all the treateddose groups up to 1000 mg/kg survived throughout the dosing period of 28 daysMale and female animals from control and all the treated dose groups exhibited normal body weight gain at the end of the dosing period of 28 days.Male and female animals from control and all the treated dose groups exhibited normal body weight gain at the end of the dosing period of 28 days.Daily clinical observations did not reveal any signs of toxicity in male and female animals from different dose groups during the dosing period of 28 days.Towards the end of the exposure period in week 4, functional observation battery such as sensory reactivity to stimuli of different types (e.g. auditory, visual and proprioceptive stimuli) revealed no abnormalities attributable to the treatment.Grip strength values observed in male and female animals for control and different dose groups were comparable.Higher values for motor activity were observed in male animals from 500 mg/kg dose group for first interval. Lower values for motor activity were observed in female animals from 500 mg/kg dose group for first and second interval.These changes were within laboratory range and were considered to be of no toxicological importance. Haematological analysis performed on 29thday revealed statistically significant increase in the values of Hb of male rats dosed at 500 mg/kg and 1000 mg/kg, MCHC of male rats dosed at 500 mg/kg, Total WBC of male rats dosed at 1000 mg/kg and Platelets of female rats dosed at 1000 mg/kg.Organ weight data of male animals sacrificed on day 29, was found to be comparable with that of controls.Organ weight data of female animals sacrificed on day 29, revealed increased relative weights of liver, ovaries and lungs of animals from 1000 mg/kg dose group.Although significant changes in organ weights were observed in female animals from high dose group, no related gross pathological or histological changes were seen and hence considered to be of no toxicological importance.Gross pathological examination conducted in rats of all dose groups during necropsy did not reveal any abnormality attributable to the treatment. Histopathological examination conducted in rats of control and high dose groups did not reveal any abnormality attributable to the treatment. Based on these findings the No Observed Adverse Effect Level (NOAEL) of the test chemical in the Sprague Dawley rat via oral route, was considered to be 1000 mg/kg body weight in male and female animals.
Based on the available results, the NOAEL value for the test chemical can be considered to be >500 mg/kg/day when exposed for longer duration to test animals orally. Hence, the test chemical can be considered to be comparatively non-toxic via oral route of administration and can be classified under the category “Not Classified” as per CLP Regulation.
Repeated dose toxicity: Inhalation
The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical. The experimental vapour pressure was 0.0248Pa at 20 deg C. Also, the LC50 was considered to be >5500 mg/m3, when rats were exposed to the test chemical by inhalation route for 4 hours. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore, this study is considered for waiver
Repeated dose toxicity: dermal
A short-term repeated dose dermal toxicity study need not be conducted because exposure of humans via dermal route in production and/or in use is highly unlikely based on the thorough and rigorous risk assessment provided. Also, the acute dermal toxicity LD50 value for the test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. The test chemical was also found to be not sensitizing to the skin. Considering this, the end point for repeated dermal toxicity is considered as waiver.
Justification for classification or non-classification
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.