Safety evaluation of certain food additives - ipcs inchem

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 123
supplementation of their diet with 2% phytosterol esters for 6 months. In another
part of this study, treatment of C57/BL6 (wild-type) mice (10 males per group) for 4
weeks with 2% phytosterol esters added to the diet led to significantly reduced
endothelial-dependent vasorelaxation after induction with carbachol, but not after
induction with nitroglycerine. Cerebral lesions after experimental occlusion (30 min)
of the left filamentous middle cerebral artery were reported to be larger in the group
with phytosterol supplementation (results were presented graphically only)
(Weingärtner et al., 2008).
A cancer-protective effect has been claimed for phytosterols in humans
(Bradford & Awad, 2007). The review of data in support of this claim is beyond the
scope of this monograph.
2.2 Toxicological studies: Phytosterol esters
Data submitted to the Committee on the toxicity of phytosterol esters consist
of a series of publications (Ayesh et al., 1999; Baker et al., 1999; Hepburn et al.,
1999; Waalkens-Berendsen et al., 1999a; Weststrate et al., 1999; Sanders et al.,
2000; Wolfreys & Hepburn, 2002; Lea et al., 2004; Lea & Hepburn, 2006). These
data, in the form of original test reports, were evaluated previously by the SCF
(Scientific Committee on Food, 2000). A complete dossier containing the original
test reports was submitted by the same sponsor only very shortly before the meeting
of the Committee and could therefore not be considered exhaustively.
Phytosterol esters tested in this series were derived from vegetable oil
distillates (mainly soya bean). The main constituents were -sitosterol (45–51%),
stigmasterol (17– 23%) and campesterol (26–29%), esterified with fatty acids from
sunflower oil. If not indicated otherwise, studies discussed in this section were done
with this test material.
2.2.1 Short-term studies of toxicity
(a) Rats
In an oral toxicity study conducted in accordance with the United Kingdom
principles of Good Laboratory Practice (GLP) and the relevant Home Office
Guidelines (not specified), Alpk:APfSD (Wistar-derived) rats (20 males and
20 females per group) were fed diets containing phytosterol esters at 0, 0.16, 1.6,
3.2 or 8.1% by weight (w/w) for 90 days. These concentrations in feed equal 0, 0.08,
0.78, 1.6 and 3.9 g phytosterol/kg body weight (bw) per day for males and 0, 0.09,
0.87, 1.8 and 4.2 g phytosterol/kg bw per day for females (mean intakes over the
study period). During the study, clinical observations, body weights, and food
and water consumption were monitored. At the end of the application period, blood
was taken under anaesthesia to determine clinical chemistry and haematological
parameters. Plasma vitamin levels were not determined in this study. The rats
were killed, organ weights determined (adrenal glands, brain, epididymis, heart,
liver, kidneys, spleen, testes and thymus) and a broad range of tissues
histopathologically examined. No statistical differences in body weights or organ
weights were observed, and no clinical signs of toxicity were observed that were