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EC number: 236-216-9 | CAS number: 13241-33-3
- 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
Oral route: Weight of evidence:
- Read-across from analogue substance. Source: Method similar to OECD 420. Based on read-across approach, the oral LD50 in rats for the target substance was determined to be >= 4984 mg/kg bw.
- Read-across from analogue substance. Source: Method similar to OECD 420. Based on read-across approach, the oral LD50 in rats for the target substance was determined to be >= 4984 mg/kg bw.
- Read-across from analogue substance. Source: Method similar to OECD 474. Based on read-across approach, the oral LD50 in rats for the target substance was determined to be >= 4984 mg/kg bw.
Dermal route:
- Key study. Method according to OECD 402 (limit test), GLP study. No mortality or systemic clinical signs related to the administration of the test item were observed throughout the study. The test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.
Inhalation route:
- Data waiving (other justification): According to Regulation (EC) No. 1907/2006, Annex VIII, 8.5.3, column 2, the acute toxicity by inhalation route is not required, as both oral and dermal studies are available.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From April 19th to May 3rd, 1973.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Principles of method if other than guideline:
- - Procedure found in Section 191.1 (f)(1) of the Federal Hazardous Substance Act; NPI Standard Test No.6.
- GLP compliance:
- no
- Test type:
- fixed dose procedure
- Limit test:
- yes
- Specific details on test material used for the study:
- TEST MATERIAL
- Lot No. 6-RS-7, received April 5, 1973.
- Purity (HPLC): 98.5%
- Impurities: Arsenic < 3ppm, Heavy metals < 15ppm.
- Loss on drying: 10.0%
- Residue on ignition: 1.0%
- Name of test material (as cited in study report): neohesperidin dihydrochalcone (Neo-DHC)
- Molecular formula (if other than submission substance): C28H36O15
- Molecular weight (if other than submission substance): 612.5764
- Smiles notation (if other than submission s.): CC1C(O)C(O)C(O)C(OC2C(O)C(O)C(CO)OC2Oc2cc(O)c(C(=O)CCc3ccc(OC)c(O)c3)c(O)c2)O1
- InChl (if other than submission substance): InChI=1/C28H36O15/c1-11-21(34)23(36)25(38)27(40-11)43-26-24(37)22(35)19(10-29)42-28(26)41-13-8-16(32)20(17(33)9-13)14(30)5-3-12-4-6-18(39-2)15(31)7-12/h4,6-9,11,19,21-29,31-38H,3,5,10H2,1-2H3 - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 234g (females) and 290g (males).
- Fasting period before study: overnight
- Diet: commercial laboratory animal feed ad libitum.
- Water: bottled spring water ad libitum.
- Acclimation period: 6d.
IN-LIFE DATES: From: April 19, 1973 To: May 3, 1973. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: The test material was used in a 12.5% gravimetric suspension in water.
- Amount of vehicle (if gavage):
MAXIMUM DOSE VOLUME APPLIED:
DOSAGE PREPARATION: the powdered neohesperidin dihydrochalcone was mixed with 8cc of distilled water and allowed to stand 15min prior to being administered to animals. Females received 1.2g and males 1.5g test item each. - Doses:
- 5000 mg/kg bw.
- No. of animals per sex per dose:
- 5 per sex per dose
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6 and 24h post-dosage. Observations were made daily thereafter to a total of 14d.
- Necropsy of survivors performed: yes. Animals sacrificed at the end of the 14-day observation period were subjected to complete gross necropsy.
- Other examinations performed: clinical signs, body weight, histopathology. - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 5 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Mortality:
- All animals were alive at the completion of the test.
- Clinical signs:
- other: No effects observed.
- Gross pathology:
- No gross changes observed.
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU criteria
- Conclusions:
- Based on read-across approach, the target substance was found to be non toxic, LD50 ≥ 5000mg/kg.
- Executive summary:
The acute oral toxicity of neohesperidin dihydrochalcone on rats was studied by a method similar to OECD TG 420. A limit test was performed by administering a single dose of 5g/kg bw test item to 10 (5M/5F) Wistar rats, and observing the effects for 14 days (clinical signs, body weights). No effects were observed in any animal. Therefore, the test item was found to be non toxic, with an LD50 > 5000 mg/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 4 984 mg/kg bw
- Quality of whole database:
- The two studies used for read-across have a Klimisch score of 2.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From November 15th to November 29th, 2016.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- (SPF Caw)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: the males were 7 weeks old and the females 8 weeks old.
- Weight at study initiation: the mean weight of male rats was 267.6 g, and the mean weight of female rats 222.0 g
- Housing: during the treatment, animals were kept in individual cages. They were solid-bottomed clear polycarbonate cages with a stainless steel mesh lid, containing dust free weed shavings (changed at least 2 times per week).
- Diet (e.g. ad libitum): foodstuff (ENVIGO 2016) ad libitum.
- Water (e.g. ad libitum): tap-water from public distribution system ad libitum.
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12 - Type of coverage:
- semiocclusive
- Vehicle:
- DMSO
- Details on dermal exposure:
- TEST SITE
- % coverage: at least 10%
- Type of wrap if used: non occlusive porous gauze dressing (50 mm x 50 mm non woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic microporeTM adhesive tape from 3M)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with distilled water.
- Time after start of exposure: 24h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 0.2 g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no
VEHICLE
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw. - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg bw.
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- yes
- Remarks:
- historical control.
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out daily to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. The animals were weighed on day 0 (just before administering the test item) then on day 2, day 7, and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (only if organs presenting abnormalities). - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred during the study.
- Clinical signs:
- other: No systemic clinical signs related to the administration of the test item were observed.
- Gross pathology:
- The macroscopic examinations of the animals at the end of the study did not reveal treatment-related changes.
- Other findings:
- - Other observations: Erythema was noted in all animals (10/10) at 24 hours post dose. This reaction was totally reversible at day 3. Dryness of the skin was noted in females at day 2 and in all animals at day 3. The skin recovered a normal aspect on day 4. A yellow coloration was noted in all animals at 24 hours post-dose.
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU criteria.
- Conclusions:
- The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.
- Executive summary:
The acute dermal toxicity of the test item was studied according to OECD 402 (GLP study). A limit test was performed by dermal administration of the test item at a dose of 2000 mg/kg bw to 5 male and 5 female Wistar (SPF:Caw) rats. After 24 h of exposure, the area was rinsed with water, and the animals were observed daily for 14 days. Observations included clinical signs, mortality, body weights, gross pathology and, if any abnormality was observed, histopathology of the affected tissues. No mortality or systemic clinical signs related to the administration of the test item were observed throughout the study. Erythema was noted in all animals (10/10) at 24 hours post dose. This reaction was totally reversible at day 3. Based on the results of the study, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.
Reference
Table 1. Body weight evolution
Males |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
Rm 0689 |
266 |
268 |
2 |
317 |
51 |
401 |
135 |
Rm 0690 |
271 |
273 |
2 |
317 |
46 |
381 |
110 |
Rm 0691 |
271 |
271 |
0 |
327 |
56 |
379 |
108 |
Rm 0692 |
258 |
265 |
7 |
315 |
57 |
384 |
126 |
Rm 0693 |
272 |
276 |
4 |
333 |
61 |
379 |
107 |
Mean |
267.6 |
270.6 |
3.0 |
321.8 |
54.2 |
384.8 |
117.2 |
SD |
5.9 |
4.3 |
2.6 |
7.8 |
5.8 |
9.3 |
12.6 |
Females |
|||||||
Rm 0694 |
217 |
213 |
-4 |
242 |
25 |
259 |
42 |
Rm 0695 |
229 |
224 |
-5 |
258 |
29 |
274 |
45 |
Rm 0696 |
226 |
222 |
-4 |
253 |
27 |
270 |
44 |
Rm 0697 |
222 |
221 |
-1 |
247 |
25 |
279 |
57 |
Rm 0698 |
216 |
213 |
-3 |
239 |
23 |
283 |
67 |
Mean |
222.0 |
218.6 |
-3.4 |
247.8 |
25.8 |
273.0 |
51.0 |
SD |
5.6 |
5.2 |
1.5 |
7.8 |
2.3 |
9.2 |
10.7 |
Table 2. Necropsy data sheet.
Observations |
Males Rm0689 to Rm0693 |
Females Rf0694 to Rf0698 |
General appearance |
Normal |
Normal |
Oesophagus |
NTR |
NTR |
Stomach |
NTR |
NTR |
Duodenum |
NTR |
NTR |
Jejunum |
NTR |
NTR |
Ileon |
NTR |
NTR |
Caecum |
NTR |
NTR |
Colon |
NTR |
NTR |
Rectum |
NTR |
NTR |
Spleen |
NTR |
NTR |
Liver |
NTR |
NTR |
Thymus |
NTR |
NTR |
Trachea |
NTR |
NTR |
Lungs |
NTR |
NTR |
Heart |
NTR |
NTR |
Kidneys |
NTR |
NTR |
Urinary bladder |
NTR |
NTR |
Ovaries |
- |
NTR |
Uterus |
- |
NTR |
Testicles |
NTR |
- |
Treatment area (skin) |
NTR |
NTR |
Adrenals |
NTR |
NTR |
Pancreas |
NTR |
NTR |
Particulars |
None |
none |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- The study has a Klimisch score of 1.
Additional information
Oral route: Weight of evidence:
- Read-across from analogue substance. The acute oral toxicity of neohesperidin dihydrochalcone on rats was studied by a method similar to OECD TG 420. A limit test was performed by administering a single dose of 5g/kg bw test item to 10 (5M/5F) Wistar rats, and observing the effects for 14 days (clinical signs, body weights). No effects were observed in any animal. Therefore, the analogue substance was found to be non toxic, with an LD50 > 5000 mg/kg bw. Based on read-across approach, the oral LD50 in rats for the target substance was determined to be >= 4984 mg/kg bw.
- Read-across from analogue substance. The study of the acute oral toxicity of neohesperidin dihydrochalcone on rats was performed by a method similar to OECD TG 420. A limit test was performed by administering a single dose of 5g/kg bw test item to 10 (5M/5F) Wistar rats, and observing the effects for 14 days (clinical signs, body weights). One male died on day 9, but no gross changes were observed, and no effects were noted on any other animal. Therefore, the analogue substance was found to be non toxic, with an LD50 > 5000 mg/kg bw. Based on read-across approach, the oral LD50 in rats for the target substance was determined to be >= 4984 mg/kg bw.
- Read-across from analogue substance. During an in vivo micronucleus assay on the analogue substance neohesperidin dihydrochalcone, male and female Swiss-Webster mice were treated with the test substance over the range of 200-5000mg/kg, and observed for 48h. Under test conditions, no toxicity signs were observed on mice treated with the test substance. Therefore, the analogue substance is considered to be non-toxic, with an LD50 > 5000 mg/kg bw. Based on the read-across approach, the target substance is non toxic, with an LD50 > 4984 mg/kg bw.
Dermal route:
- Key study. The acute dermal toxicity of the test item was studied according to OECD 402 (GLP study). A limit test was performed by dermal administration of the test item at a dose of 2000 mg/kg bw to 5 male and 5 female Wistar (SPF:Caw) rats. After 24 h of exposure, the area was rinsed with water, and the animals were observed daily for 14 days. Observations included clinical signs, mortality, body weights, gross pathology and, if any abnormality was observed, histopathology of the affected tissues. No mortality or systemic clinical signs related to the administration of the test item were observed throughout the study. Erythema was noted in all animals (10/10) at 24 hours post dose. This reaction was totally reversible at day 3. Based on the results of the study, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.
Justification for classification or non-classification
Based on available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) No. 1272/2008.
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