Safety evaluation of certain food additives - ipcs inchem

168 POLYDIMETHYLSILOXANE (addendum)
and females at 50 000 and 100 000 mg/kg diet and lower mean triglycerides
and low density plus very low density lipoprotein cholesterol (LDL + VLDL Chol)
levels in males at 25 000 and 50 000 mg/kg diet and in males and females at
100 000 mg/kg diet when 10 cSt PDMS was administered. In the case of 350 cSt
PDMS, the only other test article–related effect was yellow matting of the fur,
primarily at a dietary concentration of 100 000 mg/kg. If the ocular lesions are
considered to be the result of a topical effect and not a systemic effect, the lower
triglycerides and lipoprotein cholesterol (LDL + VLDL Chol) levels were not
considered by the study laboratory to be an adverse effect, and the matting of the
fur is due to anal leakage. For 350 cSt PDMS, the no-observed-adverse-effect level
(NOAEL) for systemic toxicity was considered by the study laboratory to be greater
than 100 000 mg/kg diet (equivalent to 5000 mg/kg bw) (United States
Environmental Protection Agency, 1995b, 1995c).
Potential toxic effects of the test article, 10 cSt and 350 cSt PDMS, were
evaluated in a 13-week study in rats at dietary concentrations of 5000, 10 000,
25 000 and 50 000 mg/kg. The test article was administered to four groups, each
consisting of 15 male and 15 female CDF (F-344) CrlBr rats 25 days of age for
350 cSt PDMS and 28 days of age for 10 cSt PDMS. In the case of the 10 cSt PDMS,
all animals survived to the scheduled necropsy. Test article–related clinical signs
consisted of a dose-related increase of matting at the base of the tail and the
anogenital region (wet and dried yellow) in males and females at 50 000 mg/kg
and an increase in severity of corneal opacities in males and females at 25 000
and 50 000 mg/kg. Ophthalmological examination revealed an increase in severity
of corneal crystals in males and females at 25 000 and 50 000 mg/kg diet.
Vascularization of the corneal stroma was also observed in males at dietary concentrations
of 25 000 mg/kg and in males and females at 50 000 mg/kg. Suppurative
inflammation and neovascularization of the corneal stroma were observed in the
same groups at the histopathological evaluation. No test article–related effect on
body weight was observed. Treatment-related increases in mean food consumption
were apparent at 10 000 (males only), 25 000 and 50 000 mg/kg diet and were
presumably related to the nutritive balance at the high concentration of the test
article in the diet (5% of test article in the diet at 50 000 mg/kg). Haematological and
urinalysis parameters were unaffected by dietary intake of 10 cSt PDMS. Mean
total cholesterol, high-density lipoprotein (HDL) cholesterol and phospholipid
levels were reduced in all treated groups of males and were statistically significant
(P < 0.05 or P < 0.01) except for the cholesterol and phospholipid means in males
at 5000 mg/kg. Aside from corneal changes, no test article–related histomorphological
changes were observed. Dietary administration of 10 cSt PDMS at 25 000
and 50 000 mg/kg diet produced an increase in severity of corneal crystals
(observed grossly as opacities) and corneal vascularization. Microscopic
suppurative inflammation and neovascularization of the corneal stroma were also
observed at these dosage levels. Other test article–related effects included base of
tail/anogenital matting in males and females at 50 000 mg/kg, increased mean food
consumption in males at 10 000 mg/kg and in males and females at 25 000
and 50 000 mg/kg diet (presumably due to the high concentration of the non-nutritive
test article in the diet) and reduced mean total cholesterol, HDL cholesterol and
phospholipid for all treated groups of males. The NOAEL for 10 cSt PDMS was