Registration Dossier
Registration Dossier
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: 224-809-5 | CAS number: 4500-29-2
- 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 oral administration of the submission substance at doses of 0, 12, 30 and 75 mg/kg body weight per day for 28 consecutive days to groups of 5 male and 5 female Wistar rats revealed no mortality and no clinical signs of intoxication. Additionally, no adverse effects were noted in functional observation battery, ophthalmoscopic, haematological or blood coagulation parameters. Body weight development was not impaired. Gross macroscopy and histopathology revealed no adverse effects. However, a preceding 14-day dose-range-finder study in rats revealed clinical effects, reduction in food intake and tendencies of reduced body weight gain as well as indications of altered organ weights and secondary inflammatory changes as evidenced by white blood cell counts at doses slightly above the highest dose tested in the main study. Based on all available data, the no-observed-adverse-effect level (NOAEL) of the test item with regard to repeated dose toxicity is considered to be equal or greater 75 mg/kg body weight per day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February - July 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study according to GLP
- 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:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Wistar rat, Crl: WI(Han) (SPF), Charles River, Germany
- Age at study initiation: 7-8 weeks (males); 7-8 weeks (females)
- Weight at study initiation: 132-178 g (males); 123-138 g (females)
- Fasting period before study: over night
- Housing: individual housing in IVC cages, type III H
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hourd light / dark - Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 7 days/week, for 28 days
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
0 mg/kg
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
12 mg/kg
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
30 mg/kg
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
75 mg/kg
Basis:
actual ingested - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on 14 day dose-range finder
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: n.a.
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): random - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: at beginning of treatment and weekly thereafter
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:before tretament, last week of treatments, end of recovery period
- Dose groups that were examined: all animals
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after last administration
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: all surviving animals
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after last administration
- Animals fasted: No
- How many animals: all surviving animls
URINALYSIS: Yes
- Time schedule for collection of urine: prior to sacrifice
- Metabolism cages used for collection of urine: No
- Animals fasted: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: once before first exposure and in forth week of exposure
- Dose groups that were examined: all animals
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Functional observation battery - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - 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):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No mortality and no clinically signs
BODY WEIGHT AND WEIGHT GAIN
no effects on body weight development
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
no effect on food consumption and/or water intake
FOOD EFFICIENCY
n.a.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
n.a.
OPHTHALMOSCOPIC EXAMINATION
no ophthalmoscopic findings
HAEMATOLOGY
no changes in haematological parameters
CLINICAL CHEMISTRY
all changes noted within range of historical controls
URINALYSIS
no changes in urinary parameters
NEUROBEHAVIOUR
no effects in FOB parameters noted
ORGAN WEIGHTS
no treatment related changes in organ weights
GROSS PATHOLOGY
no macroscopic findings
HISTOPATHOLOGY: NON-NEOPLASTIC
no treatment or test substance related histopathological changes
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
n.a.
HISTORICAL CONTROL DATA (if applicable)
n.a. - Dose descriptor:
- NOAEL
- Effect level:
- >= 75 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- Based on the data of the present study, the no observed adverse effect level (NOAEL) of the test substance is equal or greater 75 mg/kg body weight per day.
- Executive summary:
The test item was orally administered in graduated doses of 0, 12, 30 and 75 mg/kg body weight per day to 3 groups of male and female Wistar rats by oral gavage. One group receiving the vehicle sterile water served as control. The volume of application was 5 mL/kg body weight and the animals were dosed 7 days per week for a period of 28 days. No mortality and no clinical signs were recorded in any of the dose groups during the treatment period of this study. Additionally, no effects with clinical relevance were observed in any of the parameters of the functional battery testing and no ophthalmoscopic findings were noted. Body weight development and food intake were not affected. No relevant differences were found for haematological and blood coagulation parameters. Slight deviations in the clinical biochemistry parameters glucose, total protein, cholesterol and sodium in male or female treatment groups were within the range of historical controls. Additionally, deviation observed for relative weight (to terminal body weight) of kidney in female high dose group animals were not associated with histopathological findings and hence, were unlikely to be related to treatment. Based on the data generated the no observed adverse effect level (NOAEL) of Genamin CH 020 is considered to be equal or greater 75 mg/kg body weight per day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 75 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Guideline study according to GLP available. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information valid and meets data requirements with regard to hazard identification and classification.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Available data allows for route-to-route extrapolation.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Available data allows for expert judgement concerning this endpoint.
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Available data allows for route-to-route extrapolation.
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- Available data allows for expert judgement concerning this endpoint.
Additional information
There are no human data available on repeated dose toxicity of the test item. Likewise no data from repeated dose studies are available for the inhalatory or dermal route of exposure. For the oral route of exposure information from a 14 -day dose-range-finder study as well as from a guideline compliant subacute 28 -day study is available.
In the 14 -day DRF mortality occurred at the high dose of 500 mg/kg body weight per day. Clinical signs of intoxication, tendencies of reduced food intake and body weight gain, and slightly altered organ weights were observed at the mid-dose of 125 mg/kg body weight. With regard to the corrosive nature of the test material, these effects may be regarded to be secondary due to irritative stress mediated by inflammatory changes as substantiated by differential blood cell count data.
In the 28-day oral toxicity study, doses up to 75 mg/kg body weight per day were devoid of any distinct adverse effect attributable to the treatment. There were no mortalities, no influence on food intake or body weight development and no clinical signs of intoxication. No relevant effetcs were observed in any parameter from the functional observation battery before and at the end of the treatment period. There were also no relevant differences in body temperature between the groups. Haematology, urinalysis and clinical chemistry revealed no statistical significant differences between treated and control animals. With regard to organ weights, there were slight deviations in the relative kidney weight in females from the high dose group. However, these were not considered to be treatment related since there were no structural and/or functional histopathological findings neither in the kidneys nor in any other organ evaluated. The no-observed-adverse-effect level (NOAEL) from this 28 -day oral toxicity study was considered to be 75 mg/kg body weight per day.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Guideline study according to GLP with a Klimisch rating of 1. Study design allows for endpoint related classification of substance
Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: other; digestive: stomach; digestive: other
Justification for classification or non-classification
The results from the available studies with repeated exposure of the submission substance indicate that the test material is systemically available following oral administration. Mortalities in male and female animals were observed at doses of 500 mg/kg body weight per day after approximately 6 - 8 days of dosing. Decrease in food intake was observed in male and female animals of the 500 mg/kg and 125 mg/kg dose groups in the first week of treatment. Haematological findings revealed increases in white blood cell count in male and females from these two higher dose groups as well as increased neutrophil counts in males and increased monocyte, eosinophil and baophil counts in females. These haematological findings are interpreted to be associated with inflammatory changes related to treatment. A possible explanation may be seen in the strong irritative / corrosive properties of the test material which may excert a cytotoxic potential at any site of contact, e.g. the mucosa of the gastrointestinal tract. The no-observed-adverse-effect level (NOAEL) from the subsequent 28 -day subacute oral toxicity study was established at 75 mg/kg body weight per day.
Based on ECHA guidance on the application of the CLP criteria (version 3.0), substances are classified as specific target organ toxicants following repeated exposure by the use of expert judgement on the basis of the weight of all evidence available, including the use of recommended guidance values. In this respect, the evidence from studies with repeated dose toxicity studies indicate that the submission substance has the potential to be harmful to human health following repeated exposure. Taking into account the guidance values as provided in annex 3.9.2.9.7 to Regulation (EC) No 1272/2008 (CLP), the respective dose range showing adverse health effects is indicative of a category 2 classification for the test item. Based on the extrapolated "equivalent" guidance values from 28 -day oral toxicity studies, the relevant dose range where adverse effects have to be seen is between 30 and 300 mg/kg body weight per day. The NOAEL for the test item identified in the 28 -day study is 75 mg/kg body weight per day.Taking into account that mortality was observed at 500 mg/kg body weight per day and at 125 mg/kg body weight per day significant changes in body weight development, organ weights and haematologial parameters occurred, the submission substance should be classified as
Xn; R48/22 Harmful: Danger of serious damage to health by prolonged exposure if swallowed (according to DSD)
Warning; STOT-RE Category 2 - H373: May cause damage to the gastrointestinal tract through prolonged or repeated
exposure via the oral route (according to CLP)
Inclusion of the inhalation route of exposure in the hazard statement according to CLP is not considered necessary, because of the very low vapour pressure of the submission substance and because the material is not a solid and thus exposure to dusts will not occur. In the unlikely event that the substance becomes airborne as an inhalable aerosol, the strong irritative properties of the submission substance will exhibite self-warning effects in the respiratory tract.
Inclusion of the dermal route of exposure in the hazard statement according to CLP is not considered necessary, because any dermal exposure has to be minimized due to strong irritative / corrosive properties of the submission substance and because the gastrointestinal tract is the primary target organ.
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.
