Safety evaluation of certain food additives - ipcs inchem

ALIPHATIC BRANCHED-CHAIN SATURATED AND UNSATURATED ALCOHOLS 309
(i) (E,Z)-Phytol (No. 1832)
Rats (number not specified) were fed diets containing 1% or 5% phytol for
3 weeks (equivalent to 500 and 1000 mg/kg bw per day). After 3 weeks, phytanic
acid accounted for 2.3% of the total liver fatty acids and 2.1% of the plasma fatty
acids in rats fed 1% phytol; and for 21.4% of the total liver fatty acids and 27% of
the plasma fatty acids in rats fed 5% phytol. In a subsequent experiment, two rats
were fed 5% phytol in the diet for 7 days, at which time phytanic acid accounted for
4.9% of the liver fatty acids in one of them. Phytol was then removed from the diet
of the other rat. Nine days later, this rat was sacrificed, and phytanic acid levels
were only 1.4% of total liver fatty acids (Steinberg et al., 1965). The observation in
this study that phytol is converted in rats into phytanic acid was confirmed in studies
by Klenk & Kremer (1965), Baxter et al. (1967) and Muralidharan & Muralidharan
(1985).
A series of experiments were conducted in mice and rats fed phytol and
phytanic acid in the diet (Mize et al., 1969). After feeding weanling mice for 3 weeks
with 2% phytol in the diet, significant levels of phytanic acid were present in the liver
(14% of total fatty acids) and skeletal muscle (11% of total fatty acids), with the
highest concentration shown in the heart (24% of total fatty acids). All tissues
showed an increase in branched-chain fatty acids progressively over the period of
the experimental diet. When mice were fed 2% phytanic acid for 10 days, branchedchain
fatty acids accounted for 25% of the total liver fatty acids. Compared with
controls, their total liver fatty acid content was 30% higher. Livers of rats and mice
sacrificed 2 min after intravenous injection with 14 C-labelled phytanic acid revealed
the rapid conversion of phytanic acid to pristanic acid. Pristanic acid represented
up to 41.5% of the total radioactivity in the liver (up to 10% of the dose administered),
with the level of radioactivity dropping significantly over time, presumably as a result
of -oxidation. 4,8,12-Trimethyltridecanoic acid was also present in the liver of rats
and mice injected with 14 C-labelled phytanic acid. In another experiment, one pair
of weanling rats and one pair of weanling mice were fed a diet containing 2% phytol
for 2 days, followed by intravenous injection with uniformly labelled [ 14 C]phytol. The
rats were sacrificed at 3 and 20 min post-injection, the mice after 2 and 10 min. More
than 40% of the dose was found in total liver lipids at 2 and 3 min, respectively.
Phytanic acid, pristanic acid and 4,8,12-trimethyltridecanoic acid were identified in
the total fatty acids (Mize et al., 1969).
Female Wistar rats were maintained on a phytol-free diet or on a diet
providing 1% phytol for 1 month (equivalent to 500 mg/kg bw per day). A third group
of female Wistar rats was first maintained on a control diet (duration not specified)
and then for 28 days on the 1% phytol diet. The animals maintained on the phytol
diet excreted 185–274 μmol 3-methyladipate/g creatinine in the urine as compared
with 9–27 μmol/g creatinine excretion by controls. Phytanic acid was detected in the
plasma of rats receiving phytol but not in the controls (Krywawych et al., 1985).
Figure 1 presents the proposed metabolism of phytol. Phytol undergoes
oxidation to phytanic acid, and thereafter it is metabolized via - and -oxidation
and cleavage to shorter-chain acids. Another possibility is that phytanic acid