Safety evaluation of certain food additives - ipcs inchem

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 131
Table 2. Studies of genotoxicity with phytostanol/phytosterol mixtures
End-point Test system Material Concentration/
dose
In vitro
Reverse
mutation
Reverse
mutation
2.3.3 Reproductive toxicity
(a) Mice
S. typhimurium
TA98, TA100,
TA1535 and
TA1537, E. coli
WP2 uvrA
S. typhimurium
TA98, TA100,
TA1535 and
TA1537, E. coli
WP2 uvrA
Gene mutation Mouse
lymphoma
L5178Y cells,
Tk +/ locus
Chromosomal
aberration
Chromosomal
aberration
In vivo
Micronucleus
induction
Human
peripheral
blood
lymphocytes
Human
peripheral
blood
lymphocytes
Male and
female mice,
bone marrow
MPSS-SE 104–1667 μg/
plate
Result Reference
Negative a Pant (2000a)
MPSS-VD 16–1000 μg/plate Negative a Krul & van
Ommen
(2001)
MPSS-SE 5–167 μg/ml Negative a Pant (2000b)
MPSS-SE 100–1200 μg/ml Negative a Xu (2000b)
MPSS-VD 31.3–1000 μg/ml Negative a de Vogel
(2001)
MPSS-SE 50, 500 and 2000
mg/kg bw
Negative Xu (2000a)
a With and without metabolic activation (S9 mix from Aroclor 1254–induced rat liver).
No reproductive toxicity study was submitted for the mixtures of phytosterols
and phytostanols discussed above (MPSS-SE, MPSS-VD). The developmental
toxicity of a mixture of phytosterols and phytostanols was investigated in a limited,
non-guideline multigenerational study with mice at a single low dose. A mixture of
-sitosterol (75.7%), -sitostanol (13%), campesterol (9%) and artenols (0.9%) was
applied at a dose level of 0 or 5 mg/kg bw per day in the diet to 10 male and 10
female mice (F0) per group and, consecutively, to four generations of offspring
(similar group sizes). No information was given with respect to the length of the