Safety evaluation of certain food additives - ipcs inchem

136 PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS
Table 4. In vitro studies of genotoxicity with phytostanol esters
End-point Test system Material Concentration Result Reference
Reverse
mutation
Reverse
mutation
S. typhimurium
TA98, TA100,
TA1535 and
TA1537
S. typhimurium
TA98, TA100,
TA1535 and
TA1537
Gene mutation Mouse
lymphoma
L5178Y cells,
Tk +/ locus
Gene mutation Mouse
lymphoma
L5178Y cells,
Tk +/ locus
Chromosomal
aberration
Chromosomal
aberration
Chinese
hamster ovary
cells
Chinese
hamster ovary
cells
WDPSE 62–5000 μg/plate Negative a van Delft
(1997a)
VODPSE 62–5000 μg/plate Negative a van Delft
(1997b)
WDPSE 20–500 μg/ml Negative a van Delft
(1997c)
VODPSE 125–3000 μg/ml Negative a van Delft
(1997d)
WDPSE Up to 500 μg/ml Negative a van Delft
(1997f)
VODPSE Up to 2000 μg/ml Negative a van Delft
(1997e)
a With and without metabolic activation (S9 mix from Aroclor 1254–induced rat liver).
2.4.4 Reproductive toxicity
(a) Rats
In a two-generation reproductive toxicity study performed according to
OECD Test Guideline 416, groups of 28 Wistar rats (Crl:(WI)WU BR) per dose and
sex were administered diets containing 0, 1.75, 4.38 or 8.76% VODPSE
(corresponding to 0, 1, 2.5 or 5% phytostanols). Intakes of phytostanols in F0 and
F1 were 0.6–1.3, 0.4–0.7 and 1.0–2.1 g/kg bw per day for the low dose group
females during premating, gestation and lactation, respectively (ranges of weekly
averages). For the middle-dose females, intake levels were 1.5–3.4, 1.0–1.7 and
2.5–5.6 g/kg bw per day during premating, gestation and lactation, respectively. For
high-dose females, intake levels were 3.2–7.3, 2.1–3.6 and 5.2–11.1 g/kg bw per
day during premating, gestation and lactation, respectively. Intakes by F0 and F1
males during premating were 0.5–1.4, 1.3–3.5 and 2.8–7.7 g/kg bw per day for low-,
middle- and high-dose animals, respectively. Females of the parent generation were
exposed 10 weeks prior to mating, during mating and gestation up to weaning (PND
21). Males were exposed during the premating (10 weeks) and mating period (up
to 3 weeks) and then sacrificed. To form the F1 generation, on day 21, 28 animals