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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 264-780-6 | CAS number: 64338-16-5
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Sept 2008 - Jan 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Hostavin N 20
- IUPAC Name:
- Hostavin N 20
Constituent 1
- Specific details on test material used for the study:
- Batch No.: DEFD097971
Purity: > 99.9%
Expiry date: 26. July 2012
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Hsd: SD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Italy S.r.l, San Pietro al Natisone, Italy
- Age at study initiation: 27-29 days
- Weight at study initiation: 75-99 g
- Housing: up to 5 of one sex in clear polycarbonate cages with stainless steel mesh lid and floor
- Diet (e.g. ad libitum): laboratory rodent diet (4 RF 21, Mucedola S.r.l, Settimo Milanese, Italy), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 18 days
DETAILS OF FOOD AND WATER QUALITY:
Records of analyses of water and diet are kept on file at RTC
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°C
- Humidity (%): 55+/-15%
- Air changes (per hr): 15-25
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
From: 23. Sept. 2008 To: 26. Jan. 2009
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: sesame oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility
- Concentration in vehicle:
males: 2.5, 7.5 and 22.5 mg/mL
females: 1.0, 2.5 and 7.5 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Prior to commencement of treatment the proposed formulation procedure for the test item was checked in the range 1 - 22.5 mg/mL (concentration and homogeneity) and stability by chemical analysis.
Samples of the formulations prepared in weeks 1 and 13 of the study were analysed to check the homogeneity and concentration. - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 mg/kg bw/day (actual dose received)
- Remarks:
- males
- Dose / conc.:
- 75 mg/kg bw/day (actual dose received)
- Remarks:
- males
- Dose / conc.:
- 225 mg/kg bw/day (actual dose received)
- Remarks:
- males
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Remarks:
- females
- Dose / conc.:
- 25 mg/kg bw/day (actual dose received)
- Remarks:
- females
- Dose / conc.:
- 75 mg/kg bw/day (actual dose received)
- Remarks:
- females
- No. of animals per sex per dose:
- 10 + 5 animals/sex for 4 weeks recovery (control and high dose group)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
Based on the results of a 28 day dose range finder
- Post-exposure recovery period in satellite groups:
4 weeks - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily for clinical signs, twice daily for mortality
DETAILED CLINCAL EXAMINATION:
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
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:prior to treatment and suring week 13
- Dose groups that were examined: all groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: during week 13 and week 4 of recovery
- Anaesthetic used for blood collection: Yes (isofluorane)
anminals under food and water deprivation
- How many animals: all animals
- Parameters examined:
Haematocrit, haemoglobin, red blood cell count, reticulocyte count, reticulocyte maturation index, mean red blood cell volume, red cell volume distribution width, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, Haemoglobin concentration width, Heinz bodies, white blood cell count, differential leucocyte count, platelets, prothrombin time, activated partial thromboplastin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: during week 13 and week 4 of recovery
- How many animals: all animals
animals under food and water deprivation
- Parameters examined:
Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, lactate dehydrogenase, glutamat dehydrogenase, creatine kinase, urea, creatinine, glucose, triglycerides, phosphorus, total bilirubin, total cholesterol, total protein, albumin, globulin, A/G ratio, sodium, potassium, calcium, chloride
URINALYSIS: Yes
- Time schedule for collection of urine: during week 13 and week 4 of recovery (overnight)
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Yes
- Parameters examined:
Appearance, color, volume, specific gravity, pH, protein, total reducing substances, nitrite, glucose, ketones, bilirubin, urobilinogen, blood
Sediment examination:
epithelial cells, erythrocytes, leucocytes, crystals, spermatozoa and precursors, other abnormal components
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 12 and once during week 4 of recovery
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity
additionally (weekly):
handling reactivity, lachrymation, palperal closure, salivation, piloerection, rearing, spasms, myclonia, mobility impairment, arousal, vocalisation, stereotypies, unusual repsiratory pattern, bizarre behavior, urination, defecation, tremors, gait - Sacrifice and pathology:
- GROSS PATHOLOGY:
Yes, all animals
ORGAN WEIGHT:
From all animals completing the scheduled test period the following organs were weighed:
adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries, parathyroid glands,spleen, testes, thymus, thyroid, uterus
HISTOPATHOLOGY: Yes
from all main phase animals in the control and high dose groups, from all animals in low and medium dose groups died during the treatment and all abnormalities in all main phase animals.
Histopathologically examined organs/tissues:
adrenal glands, aorta, bone, boe marrow, brain, caecum, colon, duodenum, epididymides, heart, ileum, jejunum, kidneys, lungs, lymph nodes (mandibular and mesenteric), mammary gland, oesophagus, ovaries, oviducts, pancreas, prathyroid gland, pituitatry gland, prostate glandm rectum, salivary glands, sciatic nerve, skin, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea, urinary bladder, uterus/cervix, vagina - Statistics:
- For continuous variables the significance of the differences amongst groups was assessed by analysis of variance. Differences between each treated group and the control group were assessed by Dunnett’s test. The homogeneity of the data was verified by Bartlett’s test before Dunnett’s test. If data were found to be inhomogeneous a Modified t test (Cochran and Cox) was applied. The mean values, standard deviations and statistical analysis were calculated from the actual values in the computer without rounding off. Statistical analysis of histopathology findings was carried out by means of the non-parametric Kolmogorov-Smirnov
test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Hairloss was observed in some animals of both sexes of the high dose group. Other minor clinical signs, such as damaged eye, corneal opacity, broken/missing teeth, swollen head and skin/fur staining were observed in individual animals during the treatment period. These signs were not considered to be treatment-related.
No significant clinical signs were noted in recovery animals during the treatment-free period. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Very slight but statistically significant body weight reductions were observed in the high dose males from Day 15 (-4%) to Day 92 (-10%) of the treatment period. Very slight reductions were also observed in the high dose females, treated at 75 mg/kg/day, from Day 85 (-6% to -4%). Terminal body weight showed a statistically significant reduction (- 9%) in the high dose males, treated at 225 mg/kg/day.
Although all the above mentioned body weight reductions were treatment-related, they were considered to be of no toxicological importance as they were very slight (< 10%) and comparable to the historical control data. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Very slight decreases in food consumption (from -9% to -17%) were observed in the high dose males (225 mg/kg/day) from Day 8 to Day 43. Differences in food consumption disappeared by Day 50 and were no longer detected up to the end of the recovery period.
These changes were not considered of toxicological importance as they were slight and comparable to the historical control data.
No significant food consumption differences were observed in female animals at any stage of the study. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No changes of toxicological significance were observed.
Slight leucopenia was observed in all treated females and comprised almost all leukocyte cell types (approximately 30%-35% when compared with controls), whereas the decrement of white blood cells was not dose-related and the results obtained were within the range of historical data.
In addition, a slight increase in Heinz Bodies was observed in treated groups when compared to controls. However, due the lack of relation with the dose and of further related changes (anaemia, reticulocytosis) this change was considered to be of no toxicological significance.
The other statistically significant differences between control and treated animals (increase in haemoglobin in males treated with 25 mg/kg/day, haematocrit and mean corpuscular haemoglobin concentration in males receiving 25 and 225 mg/kg/day, 37% decrease in monocytes in males treated with 25 mg/kg/day and in mean corpuscular haemoglobin concentration) were of low severity (1-5%) and/or with no dose-relation, therefore they were considered to be incidental. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In general, minor fluctuations of some biochemical parameters were recorded in treated animals as showed below.
Males treated with 225 mg/kg/day showed a slight increase in alkaline phosphatase (+30%), alanine aminotransferase (+45%), urea (+23%), globulin (+10%) and chloride (+2%) and a decrease in bilirubin (-26%), cholesterol (-17%) and sodium (-2%). Cholesterol was also decreased in the other treated male groups and changes in globulin and sodium were observed even in those receiving 75 mg/kg/day. Females treated with 75 mg/kg/day showed an increase in alkaline phosphatase (+29%), cholesterol (+16%), chloride (+2%) and sodium (+2%) and a decrease in lactate dehydrogenase (-48%) and bilirubin (-23%).
Changes were considered to be of no toxicological importance, since they were of low magnitude and the direction of some of the alterations has no pathological importance. In addition, there were no histopathological findings which could be related with the liver and kidney marker changes. - Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight but statistically significant decrease in absolute and relative weight of the spleen (-23% and -16% respectively) was observed in the males dosed at 225 mg/kg/day. In addition, an increase in testes relative weight (+10%) was noted in the high dose males.
No other changes of toxicological significance were observed.
Partial or total recovery was observed at the end of the 4-week treatment-free period. As no correlated lesion was noted at histology, this change was not considered to be of toxicological importance. - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- The histopathological examination of the testes and epididymides did not reveal any evident differences between the findings observed in treated and control animals that could be considered treatment-related.
Seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and to the integrity of the various cell types within the different stages and no abnormalities were noted.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 225 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: no effects of toxicological relevance observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 75 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no effects of toxicological relevance observed
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
For clarification on the substance`s mode of action please refer to attached document "Assessment of toxicological mode of action_Hostavin N 20"
Applicant's summary and conclusion
- Conclusions:
- Based on the changes observed in the present 13 week oral toxicity study performed in Sprague Dawley rats the NOAEL was considered to be 225 mg/kg bw/d in males and 75 mg/kg bw/d in females (highest doses tested).
- Executive summary:
The oral toxicity of the test substancewhen given by daily administration to rats, has been investigated over a period of 13 consecutive weeks and recovery from any potential treatment-related effects over a period of 4 consecutive weeks.
No mortality occurred and no significant clinical signs were observed during the in vivo phase of the study. The slight reductions in body weight and food consumption observed in the high dose animals were not considered to be of toxicological importance due to the low magnitude (<20%).
The statistically significant changes observed in haematological parameters during dosing and/or recovery phase were considered to be of no toxicological significance, as they were of low severity and not dose-related. Minor fluctuations of some biochemical parameters were recorded in treated animals during the dosing and/or recovery phase. However, changes were of low magnitude and not in a direction to have pathological importance. In addition, there were no histopathological findings which could be related with the liver and kidney markers changes. Therefore they were considered to be of no toxicological importance. No changes of toxicological significance were observed in urine parameters. A slight but statistically significant decrease of the absolute and relative weight of the spleen was observed in the males dosed at 225 mg/kg/day. The toxicologically significance of this change was not supported by the microscopic examination of this organ. No changes of toxicological significance were found at post mortem macroscopic observation and microscopic examination performed at the end treatment and recovery periods. No abnormalities were noted at the evaluation in the seminiferous tubules of the stage in the spermatogenic cycle and in the integrity of the various cell types within the different stages.
On the basis of these results, some slight changes were seen at the high doses of 225 mg/kg/day for males and 75 mg/kg/day for females. However, these changes were of low magnitude and/or inconsistent between sexes. In addition, no lesions were observed at histopathological examination of tissues/organs.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)