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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 283-640-5 | CAS number: 84696-21-9 Extractives and their physically modified derivatives such as tinctures, concretes, absolutes, essential oils, oleoresins, terpenes, terpene-free fractions, distillates, residues, etc., obtained from Hydrocotyle asiatica, Umbelliferae.
- 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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Hydrocotyle asiatica, ext.
- EC Number:
- 283-640-5
- EC Name:
- Hydrocotyle asiatica, ext.
- Cas Number:
- 84696-21-9
- Molecular formula:
- not applicable
- IUPAC Name:
- Hydrocotyle asiatica, ext.
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 28-day
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Control (conr oil)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- The wet weight of a subset of tissues was taken and a set of organs/tissues was preserved.
A full histopathological evaluation of the tissues was performed on high dose and control animals. Any gross lesion macroscopically identified was examined microscopically in all animals.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No clinical signs were observed in all animals of the male and female control and LD group. All animals of the female MD group were seen without clinical findings during the treatment period. For two males in the MD group and all males and females in the HD group polydipsia/polyuria was recorded directly after test item application on several days in the first half of the treatment period. As no other clinical findings were noted and clinical biochemistry, haematology or histopathological evaluation showed no test item-related findings, the transiently observation polydipsia/polyuria was not considered to be an adverse systemic toxicological finding and might be a local reaction on test item treatment.
Weekly detailed clinical observation showed a statistical significant decrease of 100% below control for animal sleeps and an increase of animal moving in cage (400 % above control) in the male HD group in week 3. In females, a statistical significant decrease was found for animal sleeps (60 % below control) and presence of grooming in the MD group in treatment week 1.
Furthermore, the parameter animal sleeps was statistically significantly decreased in the MD group (100 % below control) and the HD group (80 % below control) and for the presence of animal moving in cage in the MD and HD group in week 2. The findings were seen transiently in single weeks and without dose relation. Considering the absence of systemic clinical findings the statistical significances are considered to be without toxicological relevance.
In males and females, no toxicological relevant effects were observed in any of the parameters of the functional observation battery before and at the end of the treatment period when compared with the controls.
Statistical significances were seen in in the week before the administration period (in males for the absence of animal sleeps and the presence of moving in cage in the HD group, an increase of response to handling in the MD group (25 % above control), a decrease of 30 % below control for head touch in the LD group and rearing supported in the MD group (75.76 % below control), an increase of equilibrium reflex in the male LD and MD group (40 % above control), in females for the response to handling in the LD group (19.05 % above control)) and in the last week of treatment in females for the absence of animal sleeps in the LD, MD and HD group, in all dose groups for animal moving in cage (400 % above control), response to handling in all dose groups (16.67% below control in all dose groups), rearing supported (113.33 % above control in the LD group) and in the female MD group for the absence of urination.
As the statistical significances were found in the week before the first administration but not in the last treatment week or were found without dose dependency and additionally, clinical observation showed no systemic findings, the differences were not considered to be of toxicological relevance. There were no biologically relevant differences in body temperature between the groups.
With exception of a moderate decrease in body weight change in all female dose groups in week 3 of the treatment period (LD 61.17 %, MD 76.47 % and HD 67.06 % below control), no statistical significant changes were found for mean body weight and mean body weight gain in all male and female dose groups. Mean body weight increased during the entire treatment period in all male and female dose and control groups. There was no test item-related effect on body weight development in this study. - Mortality:
- no mortality observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was no test item-related effect on food consumption observed. No statistical significances were seen in all male and female dose groups.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The test item had no effect on haematological parameters and coagulation parameters determined at the end of the treatment period.
In males, statistical significant differences compared to the control group were seen for the slight increases of mean WBC count (63.36 % above control), mean HGB (9.11% above control) and mean HCT (7.89 % above control) in the MD group. A slight decrease of mean monocytes was found with statistical significance in the LD and MD group (LD: 31.77 % and MD 34.12 % below control). Mean MCHC was slightly and statistically significantly increased in the female MD and HD group (MD 4.11 % and HD 4.36 % above control).
No dose dependency was noted for the statistical significant parameters in males, the differences were seen in one gender and histopathological evaluation showed no test item-related effects on the examined organs. Therefore, a toxicological effect of the test item was not considered.
There was no test item-related effect on the coagulation parameters considered. No statistical significant changes were found for coagulation parameters in all male and female dose groups and mean values were comparable to the corresponding control groups. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The test item had no effect on parameters of clinical biochemistry determined at the end of the treatment period.
Mean ASAT was slightly and statistically significantly decreased in the female HD group when compared to control (30.67 % below control). A decrease between 26.33 % (male LD) and 35.88 % (male MD) was found in male groups but without dose dependency and statistical significance. In the female HD group, a slight statistical significant decrease was noted for Urea. The mean value was found with a decrease of 23.78% below control. In males, a decrease of urea was found with 11.29 % below control and without dose dependency or statistical significance. The statistical significant changes were found in one gender and as no toxicological effect was found at microscopic evaluation, a toxicological effect of the test item was not considered. - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No test item-related effect on urinary parameters was found.
Macroscopically, a cyst at the greater curvature of the stomach was seen in one male control animal and a bladder stone was found in the urinary bladder of one HD male animal. No other macroscopic findings were noted for all other animals in the study. As the findings were seen in one control animal or in one single HD animal and under consideration of histopathological assessment, the gross lesions were considered to be incidental and not induced by the treatment with the test item. - Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Absolute weight of pituitary gland was slightly and statistically significantly increased in the female MD group (19.66 % above control), but no dose dependent increase was seen for absolute and relative organ weight. Under consideration of the absence of microscopic test item-related findings, the increase is not considered to be of toxicological relevance. No adverse effects of the test item on organ weights were found.
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No changes related to the test item administration were observed at histopathological evaluation. The histopathological NOEL (no observed effect level) may be established at 1000 mg/kg bw.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The test item Centella asiatica dry ext. did not cause indicators of toxicity under the conditions of this study. No adverse effects of the test item were found at all tested dose levels. The NOAEL may be established at 1000 mg/kg bw.
- Executive summary:
On the basis of this 28-day Repeated Dose Oral Toxicity study with Centella asiatica dry ext. in male and female Wistar rats with dose levels of 100, 300, and 1000 mg/kg body weight day the following conclusions can be made.
The test item Centella asiatica dry ext. did not cause indicators of toxicity under the conditions of this study. No adverse effects of the test item were found at all tested dose levels. The NOAEL may be established at 1000 mg/kg bw.
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.