Tissue distribution and excretion of 14C-labelled cinnamic aldehyde following single and multiple oral administration in male Fischer 344 rats.
14C-labelled cinnamic aldehyde (CNMA) was given as a single oral dose, or 24 hr after multiple oral administration of non-radioactive CNMA for 7 days at 24-hr intervals, to male Fischer 344 rats at dose levels of 5, 50 or 500 mg/kg body weight. Residues of radioactive CNMA were measured. After the single dose radioactivity was distributed primarily in the gastro-intestinal tract, the kidneys and the liver of the rats. The radiolabel was excreted mainly in the urine, and at 24 hr 85.1, 84.2 and 81.2% of the administered radiolabel was recovered in the urine at the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel at 24 hr for the 5, 50 and 500 mg/kg doses was 5.1, 4.0 and 3.2% of the administered dose, respectively. At all dose levels, a small amount of the dose was distributed to the fat and was easily measured in animals killed 3 days after dosing at the 50 or 500 mg/kg dose levels. Following multiple oral administration, similar tissue distribution and excretion patterns of radiolabel were found at the three dose levels. After 24 hr the administered radiolabel was distributed mainly to the fat, liver and gastro-intestinal tract. At 24 hr, recoveries of the radiolabel in the urine were 80.4, 80.6 and 81.9% of the dose for the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel after multiple dosing at 24 hr accounted for 6.3, 6.9 and 4.5% of the administered radioactivity at the 5, 50 and 500 mg/kg dose levels, respectively. The major metabolic pathway of CNMA for all single and the 5 and 50 mg/kg multiple dose levels in this species of rat was found to be degradation to benzoic acid through beta-oxidation and excretion in the urine mainly as hippuric acid, with much smaller amounts of benzoic and cinnamic acids. At the multiple dose level of 500 mg/kg, benzoic acid was the major urinary metabolite, indicating that in the Fischer 344 male rat at this relatively high oral dose level the detoxification of CNMA proceeds differently and an alternative metabolic pathway is proposed.
Sapienza
P P
PP
Division of Toxicological Studies, Food and Drug Administration, Washington, DC 20204.
Ikeda
G J
GJ
Warr
P I
PI
Plummer
S L
SL
Dailey
R E
RE
Lin
C S
CS
D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D006868:Hydrolysis; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D000171:Acrolein; C012843:cinnamaldehyde