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Administrative data

Description of key information

Oral route:

- Key study. Method similar to OECD 420 (non-GLP). The oral LD50 in rats for the substance was found to be ≥ 5000 mg/kg bw.

- Key study. Method similar to OECD 420 (non-GLP). The oral LD50 in rats for the substance was found to be ≥ 5000 mg/kg bw.

- Supporting study: Method similar to OECD 474 (non-GLP). During an in vivo micronucleus assay, the acute oral LD50 in rats for the substance was found to be ≥ 5000 mg/kg bw.

Based on the available data, the substance is considered to be non-toxic, with an LD50 ≥ 5000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1983.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 474
Principles of method if other than guideline:
Acute exposure during in vivo micronucleus assay: single administration of 4 doses up to 5000 mg/kg bw, 6 animals per dose, observation time 48h.
GLP compliance:
no
Test type:
other: in vivo micronucleus assay.
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
TEST MATERIAL
- Source: Synthesized by Nutrilite Products, Buena Park, CA. The NMR spectrum was consistent with a purity of ca. 99%.
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, CA.
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 16-32 g
- Diet (e.g. ad libitum): commercial rodent diet (Purina Rodent Chow, Ralston Purina Co., St. Louis, MO).
- Water ad libitum.
Route of administration:
oral: gavage
Vehicle:
other: 2% acacia (gum arabic) in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Oral dosing was by gavage in 2% acacia (gum arabic) in water at 10ml/kg bw.
Doses:
200, 500, 1000, and 5000 mg/kg bw.
No. of animals per sex per dose:
6 animals of either sex (12 in negative and positive controls).
Control animals:
yes
Details on study design:
- Duration of observation period following administration: Single dose administration, observation period of 48h after treatment.
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:
No mortality was observed after 48h.
Clinical signs:
No effects.
Body weight:
No data.
Gross pathology:
No data.
Interpretation of results:
GHS criteria not met
Remarks:
EU criteria.
Conclusions:
The test item was found to be non toxic, with an LD50 > 5000 mg/kg bw.
Executive summary:

During an in vivo micronucleus assay of the test substance, male and female Swiss-Webster mice were treated with the test substance over the range of 200-5000mg/kg. Under test conditions, no toxicity signs were observed on mice treated with the test substance. Therefore, the test item is considered to be non-toxic, with an LD50 > 5000 mg/kg bw.

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
Reference:
Composition 0
Qualifier:
equivalent or similar to
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
Test material information:
Composition 1
Specific details on test material used for the study:
TEST MATERIAL
- Lot No. 6-RS-7, received April 5, 1973.
- Purity (HPLC): 98.5%
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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:
No effects observed.
Body weight:
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.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Agust 11th to September 24th, 1978.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Principles of method if other than guideline:
- Procedure by Hagan, E.C. (1959). Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp. 17-25. (see 'Attached background material').
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
TEST MATERIAL
- Lot No. 26-RS-17, received 11/8/1978.
- Purity (HPLC): 98.5%
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 176-210 g.
- Fasting period before study: overnight
- Diet: commercial laboratory animal feed ad libitum.
- Water: bottled spring water ad libitum.
- Acclimation period: 6d.
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.
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.
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:
1/5 males died at day 9, 0/5 females died.
Clinical signs:
No effects observed.
Body weight:
No effects observed (see table 1).
Gross pathology:
No gross changes observed.

Table 1. Acute Oral Toxicity for neohesperidin dihydrochalcone.

Animal Number

Sex

Body weight (g)

Hours

Days

Body weight (final, g)

1

3

6

24

2

3

4

5

6

7

14

1

M

204

N

N

N

N

N

N

N

N

N

N

N

358

2

208

N

N

N

N

N

N

N

N

N

N

N

348

3

210

N

N

N

N

N

N

N

N

N

N

N

382

4

176

N

N

N

N

N

N

N

N

N

N

N

308

5

206

N

N

N

N

N

N

N

N

N

N

+

160

6

F

196

N

N

N

N

N

N

N

N

N

N

N

230

7

202

N

N

N

N

N

N

N

N

N

N

N

254

8

188

N

N

N

N

N

N

N

N

N

N

N

244

9

196

N

N

N

N

N

N

N

N

N

N

N

254

10

188

N

N

N

N

N

N

N

N

N

N

N

228

N: normal, D: depression, SD: slight depression, D: severe depression, +: animal death.

Remarks: Animal #1 - #4, #6 - #10: no gross changes observed. Animal #5: No gross changes observed (died on day 9).

Interpretation of results:
GHS criteria not met
Remarks:
EU criteria.
Conclusions:
The test item was found to be non toxic, LD50 ≥ 5000 mg/kg bw.
Executive summary:

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 test item was found to be non toxic, with an LD50 > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 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

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral route.

- Key study. The acute oral toxicity of the test item on rats was studied by a method similar to OECD TG 420. A limit test was performed by administering a single dose of 5 g/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.

- Key study. The study of the acute oral toxicity of the test item on rats was performed by a method similar to OECD TG 420. A limit test was performed by administering a single dose of 5 g/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 test item was found to be non toxic, with an LD50 > 5000 mg/kg bw.

- Supporting study. During an in vivo micronucleus assay on the test item, male and female Swiss-Webster mice were treated with the test item over the range of 200-5000mg/kg, and observed for 48h. Under test conditions, no toxicity signs were observed on any of the treated mice. Therefore, the test item is considered to be non-toxic, with an LD50 > 5000 mg/kg bw.

Justification for classification or non-classification

Based on available data (oral LD50 > 5000 mg/kg bw in rats), the substance is not classified for acute toxity according to CLP Regulation (EC) No. 1272/2008.