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EC number: 233-566-4 | CAS number: 10236-47-2
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: ‘‘Technical Guideline for Acute Toxicity Test of chemical drugs’’ (SFDA, 2004 - PR China)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- GLP compliance:
- yes
- Remarks:
- All operations were carried out under the Good Laboratory Practice (GLP) Regulations of the State Food and Drug Administration of China.
- Test type:
- fixed dose procedure
- Limit test:
- yes
Test material
- Reference substance name:
- 7-(2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyloxy)-2,3-dihydro-4',5,7-trihydroxyflavone
- EC Number:
- 233-566-4
- EC Name:
- 7-(2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyloxy)-2,3-dihydro-4',5,7-trihydroxyflavone
- Cas Number:
- 10236-47-2
- Molecular formula:
- C27H32O14
- IUPAC Name:
- 7-(2-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyloxy)-2,3-dihydro-4',5,7-trihydroxyflavone
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- Naringin (batch No. 20080203) was extracted and purified in the laboratory.
Prepared from pulverized Citrus grandis 'Tormentosa' by the following procedures: extracted with water, precipitated by ethanol, and filtered; and then collected and further concentrated the filtrate; the filtrate, on standing, deposited crystals; the precipitate was separated and recrystallized from mixtures of ethanol and water at different ratios; the recrystallized precipitate was dried at 110 C.
Naringin was obtained, and identification was performed by ultraviolet–visible spectroscopy (UV/Vis), electron spray ionization–mass spectrometry, proton nuclear magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy. The purity analysis was performed on a Shimadzu (HPLC) LC-6A instrument (Shimadzu Corp., Kyoto, Japan) with a Dionex C18 column (5 µm, 4.6 mm 250 mm, USA) and a TL9000 Chromatographic Station. The mobile phase was prepared by a 45/55 (v/v) mixture of methanol/water and the pH was adjusted to 3.0 with acetic acid. The injection volume was 20 ll. The UV detector was set at a wavelength of 283 nm. The HPLC purity of naringin was determined to be >98.3% by external standard method.
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Male and female Sprague-Dawley (SD) rats, certified specific pathogen-free, were purchased from Slack Shanghai Laboratory Animal Co., Ltd. (Shanghai, China) under the license number SCXK(HU) 2007-0005.
- Weight at study initiation: 158.2 – 167.4 g for males and 138.4 – 156.4 g for females.
- Fasting period before study: overnight.
- Housing: three rats of the same gender from the same group were held in the same plastic cage.
- Diet ad libitum.
- Water ad libitum.
- Acclimation period: 1 week.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 55 ± 15
- Air changes (per hr): 12
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw.
- Doses:
- 16 g/kg bw
- No. of animals per sex per dose:
- 6
- Control animals:
- yes
- Remarks:
- intragastrical administration of sterile saline (10mL/kg).
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were thoroughly observed after test article administration immediately for the onset of any toxic signs and once daily thereafter for 14 days of observation period. Survival, feed intake (days 2 and 8), and body weight (days 0, 3, 7, 10, and 13) were monitored.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: hematology, biochemistry.
- Hematology: erythrocyte count (RBC), haemoglobin concentration (HGB), haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), reticulocyte count (RET), white blood cell count (WBC) and differential, platelet count (PLT), prothrombin time (PT) and activated partial thromboplastin time (APTT)
- Clinical biochemistry: biochemical indexes includes serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), creatine kinase (CK), alkaline phosphatase (ALP), urea nitrogen (UREA), total serum protein (TP), albumin (ALB), albumin/globulin ratio (A/G), blood glucose (GLU), total bilirubin (TBIL), creatinine (Crea), total cholesterol (CHOL), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), sodium (Na), potassium (K), and chloride (Cl). - Statistics:
- Body weight, organ weight (both absolute and relative weights), food consumption, hematology, serum biochemistry and serum sex hormone analyses were tested by conducting One-Way ANOVA using SPSS 13.0 statistical software. When statistically significant differences were indicated, the least significant difference (LSD) test was employed for comparisons between groups. Levene’s test was used to assess the homogeneity of variances in data. If the variance was not homogeneous, the Kruskal–Wallis test was applied.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 16 000 mg/kg bw
- Mortality:
- No death was recorded in any of the groups during 14 days of the study.
- Clinical signs:
- other: No clinical signs related to the administration of naringin at 16 g/kg dose were observed.
- Gross pathology:
- The macroscopic examination of the organs revealed no changes in the necropsies of any of the animals.
- Other findings:
- - The hematology assessments, including RBC, HGB, HCT, MCV, MCH, MCHC, RET, WBC, white blood cell differential count, PLT and PT for rats treated with naringin, were not remarkably different compared to control rats. APTT of naringin treatment group is significantly longer than that of control group (p < 0.05), but stayed within the normal reference range.
- The biochemical analyses indicated that no significant differences between the control and naringin treated groups were detected for any of the parameters.
Any other information on results incl. tables
Table 1. Hematology data for SD rats given a single oral dose (16 g/kg) of naringin.
Parameters |
Control group |
Treatment group |
|||||
WBC |
(109/L) |
3.616 |
± |
1.230 |
4.181 |
± |
1.061 |
NEU |
(%) |
10.538 |
± |
3.906 |
8.356 |
± |
2.685 |
LYM |
(%) |
85.15 |
± |
4.81 |
86.18 |
± |
2.96 |
MONO |
(%) |
2.384 |
± |
1.200 |
3.188 |
± |
0.829 |
EOS |
(%) |
1.500 |
± |
0.589 |
1.756 |
± |
0.715 |
BASO |
(%) |
0.4345 |
± |
0.3763 |
0.5299 |
± |
0.2767 |
RBC |
(1012/L) |
6.342 |
± |
0.285 |
6.446 |
± |
0.318 |
HGB |
(g/L) |
134.6 |
± |
6.2 |
137.6 |
± |
3.5 |
HCT |
(%) |
39.80 |
± |
1.64 |
40.73 |
± |
0.96 |
MCV |
(fL) |
62.79 |
± |
1.55 |
63.29 |
± |
2.31 |
MCH |
(pg) |
21.23 |
± |
0.59 |
21.37 |
± |
0.80 |
MCHC |
(g/L) |
338.0 |
± |
2.7 |
337.4 |
± |
4.7 |
RET |
(%) |
3.250 |
± |
1.023 |
3.403 |
± |
1.192 |
PLT |
(109/L) |
1014.8 |
± |
114.1 |
1078.7 |
± |
62.0 |
PT |
(s) |
7.75 |
± |
0.75 |
7.56 |
± |
0.51 |
APTT |
(s) |
14.58 |
± |
1.04 |
15.72 |
± |
0.81* |
Table 2. Serum biochemical data for rats given a single oral dose (16 g/kg) of naringin.
Parameters |
Control group |
Treatment group |
|||||
ALP |
(U/L) |
205.10 |
± |
59.71 |
182.04 |
± |
45.42 |
ALT |
(U/L) |
32.36 |
± |
3.80 |
31.53 |
± |
5.01 |
AST |
(U/L) |
111.14 |
± |
16.23 |
108.61 |
± |
18.58 |
CK |
(U/L) |
448.0 |
± |
117.2 |
406.8 |
± |
131.4 |
Urea |
(mmol/L) |
6.469 |
± |
1132 |
6.033 |
± |
1565 |
Crea |
(lmol/L) |
20.33 |
± |
2.31 |
18.27 |
± |
3.59 |
TP |
(g/L) |
52.33 |
± |
2.10 |
53.17 |
± |
1.47 |
ALB |
(g/L) |
38.57 |
± |
1.76 |
39.41 |
± |
1.48 |
A/G |
|
2.813 |
± |
0.171 |
2.880 |
± 0.26 |
|
GLU |
(mmol/L) |
6453 |
± |
0.953 |
6441 |
± |
0.640 |
TBIL |
(µmol/L) |
1.67 |
± |
0.61 |
1.94 |
± |
0.68 |
CHOL |
(mmol/L) |
1323 |
± |
0.367 |
1316 |
± |
0.316 |
TG |
(mmol/L) |
0.340 |
± |
0.182 |
0.438 |
± |
0.216 |
HDL-c |
(mmol/L) |
0.403 |
± |
0.089 |
0.409 |
± |
0.065 |
LDL-c |
(mmol/L) |
0.235 |
± |
0.098 |
0.219 |
± |
0.107 |
K+ |
(mmol/L) |
3873 |
± |
0.302 |
3880 |
± |
0.198 |
Na+ |
(mmol/L) |
144.59 |
± |
1.06 |
144.60 |
± |
2.04 |
Cl |
(mmol/L) |
105.72 |
± |
1.67 |
105.03 |
± |
1.44 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU criteria.
- Conclusions:
- The test item has an LD50 greater than 16g/kg in rats.
- Executive summary:
To determine the acute oral toxicity of the test item in rats, a limit test was performed, according to the ‘‘Technical Guideline for Acute Toxicity Test of chemical drugs’’(SFDA, 2004, China), similar to OECD 420 (GLP study). The test item was orally administered to 6 male and 6 female Sprague-Dawley rats, at a single bolus dose of 16 g/kg bw, by gavage. All animals were thoroughly observed immediately after administration for the onset of any toxic signs and once daily thereafter for 14 days. Survival, feed intake, and body weight were monitored. There were no mortality, adverse clinical signs, abnormal changes in body weights or food consumption, toxicologically relevant changes in hematology, clinical biochemistry and macroscopic findings during 14 days of the acute toxicity study. Under test conditions, the test item was found to be non-toxic by oral route, with an LD50 > 16g/kg in rats.
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