Cinnamaldehyde

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

other: Authoritative data base

Title:

HSDB Number 209

Year:

2011

Bibliographic source:

HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC

Reference 2

Reference Type:

other: Authoritative data base

Title:

No information

Year:

2012

Bibliographic source:

NTP (National Toxicological Program)by Agency for Toxic Substances and Disease Registry; Division of Toxicology/Toxicology Information Branch, 1600 Clifton Road NE, E-29, Atlanta, Georgia 30333

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from HSDB & NTP

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Cinnamaldehyde

EC Number:

203-213-9

EC Name:

Cinnamaldehyde

Cas Number:

104-55-2

Molecular formula:

C9H8O

IUPAC Name:

3-phenylacrylaldehyde

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): cinnamaldehyde
- Substance type: Organic
- Physical state: Liquid

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

7 days

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 50, or 500 mg/kg bw

No. of animals per sex per dose / concentration:

8/group

Details on dosing and sampling:

Twenty-four hours later, animals in each group received a single oral dose of [3-(14)C]cinnamaldehyde equivalent to the pretreatment level. At 50 and 500 mg/kg bw, radioactivity could be measured in animals terminated 3 days after dosing.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Cinnamaldehyde is easy absored within the body rapidly and further distributed in various organs

Main ADME results 2

Type:

distribution

Results:

Radioactivity is distributed primarily to the gastrointestinal tract, kidneys, and liver, after single- or multiple-dose oral administration. At all dose levels, a small amount of the dose is distributed to the fat.

Main ADME results 3

Type:

metabolism

Results:

In the high dose pretreatment group, benzoic acid is the major metabolite, suggesting that saturation of the glycine conjugation pathway occurs at repeated high dose levels of cinnamaldehyde.

Main ADME results 4

Type:

excretion

Results:

After 24 hr, >80% of the radioactivity is recovered in the urine and <7% in the feces from all groups of rats, regardless of dose level.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

Radioactivity is distributed primarily to the gastrointestinal tract, kidneys, and liver, after single- or multiple-dose oral administration. At all dose levels, a small amount of the dose is distributed to the fat.

Details on excretion:

After 24 hr, >80% of the radioactivity is recovered in the urine and <7% in the feces from all groups of rats, regardless of dose level.

Metabolite characterisation studies

Details on metabolites:

Except for the high dose pretreatment group, the major urinary metabolite is hippuric acid, accompanied by small amounts of cinnamic and benzoic acid. In the high dose pretreatment group, benzoic acid is the major metabolite, suggesting that saturation of the glycine conjugation pathway occurs at repeated high dose levels of cinnamaldehyde.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Based on the study conducted on male rat on cinnamaldehyde by oral route the toxicokinetcs are found be as follows

Absorption:
Cinnamaldehyde is easy absored within the body rapidly and further distributed in various organs

Dirtibution:
Radioactivity is distributed primarily to the gastrointestinal tract, kidneys, and liver, after single- or multiple-dose oral administration. At all dose levels, a small amount of the dose is distributed to the fat.

Metabolism:
In the high dose pretreatment group, benzoic acid is the major metabolite, suggesting that saturation of the glycine conjugation pathway occurs at repeated high dose levels of cinnamaldehyde.

Execrition
After 24 hr, >80% of the radioactivity is recovered in the urine and <7% in the feces from all groups of rats, regardless of dose level.

Executive summary:

Based on the study conducted on male rat on cinnamaldehyde by oral route the toxicokinetcs are found be as follows

Absorption:

Cinnamaldehyde is easy absored within the body rapidly and further distributed in various organs

Dirtibution:

Radioactivity is distributed primarily to the gastrointestinal tract, kidneys, and liver, after single- or multiple-dose oral administration. At all dose levels, a small amount of the dose is distributed to the fat.

Metabolism:

In the high dose pretreatment group, benzoic acid is the major metabolite, suggesting that saturation of the glycine conjugation pathway occurs at repeated high dose levels of cinnamaldehyde.

Execrition

After 24 hr, >80% of the radioactivity is recovered in the urine and <7% in the feces from all groups of rats, regardless of dose level.