Octanal, 2-(phenylmethylene)-, (2E)-

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1994; 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Hexylcinnamaldehyde is an alkyl-substituted cinnamaldehyde and therefore structurally similar enough to justify read-across. Cinnamic acid is the initial metabolite of cinnamaldehyde. Further justification included as attachement within endpoint summary. One of the studies is very old and probably less reliable. Nevertheless they are included here as supporting data to the metabolism of cinnamaldehyde provided as weight of evidence in this endpoint.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1994

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1961

Materials and methods

Test material

Test material information

Constituent 1

Test animals

Species:

other: rat; mouse; human

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Cinnamic acid is readily excreted in rat, mouse and human. The main urinary metabolite is hippuric acid.

Executive summary:

The effect of dose on the disposition of [3-14C]-cinnamic acid in F344 rats and CD1 mice has been studied [Nutley et al., 1994]. Five dose levels of cinnamic acid in the range from 0.0005 mmol/kg bw (0.072 mg/kg bw) to 2.5 mmol/kg bw (370 mg/kg bw) were given orally to groups of F344 rats (4/group) or by intraperitoneal injection to groups of CD1 mice (4/group). After 24 hours, 73-88% of the radioactivity was recovered in the urine of rats and 78-93% in the urine of mice. After 72 hours, 84¬97% of the radioactivity was recovered from rats mainly in the urine. In mice, the recovery was 89-100% within 72 hours. Only trace amounts of radioactivity were present in the carcasses, indicating that cinnamic acid was readily and quantitatively excreted at all dose levels. In both species the main urinary metabolite was hippuric acid although in the mouse, the excretion of cinnamoylglycine was significant at lower doses.

Eleven adult volunteers received single intravenous doses of cinnamic acid, equivalent to 5 mg/kg bw (Quarto di Palo et al, 1961). Analysis of the blood plasma revealed cinnamic acid at 100% of the total dose within 2.5 minutes declining to 0% after 20 minutes. Ninety minutes after dosing, urinalysis revealed mainly the glycine conjugate of benzoic acid (hippuric acid), cinnamoylglucuronide, and benzoylglucuronide present in a ratio of 74:24.5:1.5 (Quarto di Palo and Bertolini, 1961). These data demonstrate that cinnamic acid is rapidly oxidized to benzoic acid metabolites, and excreted in the urine of humans.