Safety evaluation of certain food additives - ipcs inchem

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 133
Guidelines 401 and 423 (Acute Toxic Class Method) in a limit test with three male
and three female rats at 2000 mg/kg bw. None of the stanol ester mixtures caused
lethal effects, and no clinical signs were observed (with the exception of one male
rat dosed with WDPSE that showed diarrhoea). Based on these results, the median
lethal dose (LD50) was concluded to exceed 2000 mg/kg bw for both mixtures (Appel,
1998a, 1998e).
The dermal toxicity of both mixtures was investigated in rat studies in compliance
with OECD Test Guideline 402. A dose of 2000 mg test substance/kg bw in
maize oil was applied dermally to five male and five female rats for 24 h. No deaths
or clinical signs of toxicity were observed after application of WDPSE. After
VODPSE application, one male rat died during the 14-day observation period.
Dermal LD50 values were considered to exceed 2000 mg/kg bw for both mixtures
(Appel, 1998b, 1998f).
(b) Skin irritation and corrosion
Skin irritation/corrosion was tested in studies with male albino rabbits in
compliance with OECD Test Guideline 404. A dose of 2000 mg/kg bw was applied
to the clipped skin of three rabbits for 4 h under semi-occlusive conditions. WDPSE
did not cause any skin effects and was considered non-irritating to skin. VODPSE
caused very slight erythema after 1 h of treatment, which was completely reversible
within 24 h after treatment (Appel, 1998c, 1998g).
(c) Eye irritation
Prior to in vivo eye irritation testing in compliance with OECD Test Guideline
405 (Draize test) with albino rabbits, a screening was performed using a non-GLP
(ex vivo) chicken enucleated eye test. Both mixtures did not reveal irritating potential
in the chicken enucleated eye test. In the rabbit eye in vivo, WDPSE and VODPSE
caused slight and slight or moderate discharge, respectively, which was reversible
within 24 h after treatment. Both mixtures were considered minimally irritating to
rabbit eyes (Appel, 1998d, 1998h).
(d) Skin sensitization
Possible skin sensitizing properties were investigated in maximization tests
in guinea-pigs in compliance with OECD Test Guideline 406. Neither WDPSE nor
VODPSE caused signs of skin sensitization after application (in induction and
challenge phase) to 10 male guinea-pigs (Prinsen, 1998a, 1998b).
2.4.2 Short-term studies of toxicity
(a) Rats
In a 90-day oral toxicity study performed according to OECD Test Guideline
408 and in compliance with OECD GLP principles, Wistar rats (20 animals per group
and sex) received 0, 0.34, 1.7 or 8.4% (w/w) of WDPSE in the feed (corresponding
to 0, 0.2, 1 and 5% of phytostanols in the feed) for a period of 13 weeks. Three other