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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline assay, but acceptable well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Suppressive effect of cocoa powder on atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic rabbits
Author:
Kurosawa T et al.
Year:
2005
Bibliographic source:
J Atheroscler Thromb. 12, 20-28

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
A six-month dietary study was performed on a hypercholesterolemic rabbit strain to investigate the suppressive effect of cocoa powder on atherosclerosis. Rabbits were assessed for clinical signs of toxicity, food consumption, growth, haematology, blood chemistry, blood lipid profile, and a number of effects on the aorta related to the development of atherosclerosis.

GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Cocoa powder
IUPAC Name:
Cocoa powder
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): As cited in study report: Cocoa powder
- Substance type: Natural product (UVCB)
- Physical state: Solid
- Analytical purity: Not applicable
- Impurities (identity and concentrations): Not applicable
- Composition of test material, percentage of components: Composition of test material, percentage of components: 16% carbohydrate, 14.7% fat, 21.1% protein, 25.8% fibre, 8.1% minerals, 0.34% caffeine, 2.5% theobromine, 0.0002 % α-tocopherol, 0.003%γ-tocopherol, 7.8% total polyphenol.
- Isomers composition: not applicable
- Purity test date: Not applicable
- Lot/batch No.: No data available
- Expiration date of the lot/batch: No data available
- Stability under test conditions: No data available
- Storage condition of test material: as mixed diet, at -20 ºC until immediately before feeding
- Other: cocoa powder was prepared in-house by roasting, grinding and compressing cocoa beans

Test animals

Species:
rabbit
Strain:
other: Kurosawa and Kusanagi-hypercholesterolemic (KHC)
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Six months
Frequency of treatment:
Daily
No. of animals per sex per dose:
3

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 3 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: No adverse effects (on clinical signs; mortality; body weight; food consumption and haematology) were seen over the course of the study. his was the only tested dose.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a non-guideline study, no treatment-related adverse effects were seen in hypercholesterolemic rabbits fed cocoa powder at 10% in the diet for six months. The no-observed-adverse-effect level (NOAEL) was approximately 3000 mg/kg bw/day (the only tested dose).

Executive summary:

The subchronic toxicity of cocoa powder has been assessed in a non-guideline study on a hypercholesterolemic strain of rabbits. This study is well-documented and meets basic scientific principles.

 

Groups of Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits (3/sex) were given either a standard (control) diet, or a standard diet containing 10% cocoa powder [approx. 3000 mg/kg bw/day] for six months. Daily observations for clinical signs of toxicity, and measurements of food consumption, were conducted. Measurements of body weight, haematology, blood chemistry and low density lipoprotein (LDL) oxidation were performed each month. After the six-month treatment period, animals were sacrificed and the aorta was excised to detect atherosclerotic lesions, to measure its lipid content and to examine its static rheological properties.

 

No treatment-related adverse effects were seen over the course of the study. Cocoa powder was seen to have a protective effect against the oxidation of LDL cholesterol in the second and third month of administration, and suppressed the development of atherosclerosis. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw/day (since this was the only tested dose).

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