Safety evaluation of certain food additives - ipcs inchem

POLYDIMETHYLSILOXANE (addendum) 169
considered to be 50 000 mg/kg diet, equivalent to 2500 mg/kg bw (United States
Environmental Protection Agency, 1995a). When 350 cSt PDMS was administered,
yellow matting at the base of the tail was noted in the 2500 mg/kg group during
weeks 8–13 at the weekly physical examinations. Corneal opacities were first noted
in the diet-treated groups, followed by the gavage-treated groups, then the control
groups. After 3 weeks of dosing, all animals in all groups had corneal opacities. The
severity of the corneal opacities (noted as corneal crystals by the veterinary
ophthalmologist) was increased in a dose-related manner in all treated groups when
compared with the control groups. At the microscopic examination, suppurative
inflammation of the corneal epithelium occurred at a dose-related increased incidence
in all treated groups when compared with the control groups. Food consumption
was increased in males and females at a dietary concentration of 50 000 mg/
kg (essentially throughout the study). These increases were presumably due to
the high concentration of non-nutritive test article in the diet (5% of the diet at
50 000 mg/kg). Lethalities and slight clinical signs (yellow matting at the base of the
tail) were observed at 2500 mg/kg. In general, dose-related increases in the severity
of corneal crystals (observed grossly as corneal opacities) were observed in all
treated groups (diet and gavage). Microscopically, suppurative inflammation of the
corneal epithelium was noted in all treated groups; the number of animals affected
was dose related. The NOAEL for 350 cSt PDMS was considered by the study
laboratory to be greater than 50 000 mg/kg diet (equivalent to 2500 mg/kg bw)
(United States Environmental Protection Agency, 1995d).
The oral toxicity of 35 cSt PDMS fluid was evaluated in relation to its potential
use as a fat substitute in certain foods. Three groups of 15 male and 15 female
CD-1 mice were given 0, 5 or 10% 35 cSt PDMS fluid in the diet (0, 50 000 and
100 000 mg/kg diet) for 90 days. Most animals in the 10% dietary group exhibited
oily fur, and most anal leakage was seen in females in this dietary group. There
were significant increases in food consumption in treated groups compared with
controls, with the greatest consumption seen in the 10% dietary group. No noted
changes in stool consistency or coating were observed in any treated animals. No
deaths or behavioural abnormalities were observed, and there were no significant
differences in body weights or organ weights. No significant treatment-related
effects were observed during necropsy or histopathological examination (United
States Environmental Protection Agency, 1994a).
PDMS fluids at viscosities of 35, 350 and 1000 cSt were evaluated to
determine their subchronic oral toxicity. Five groups of 100 male rats each received
0 (two control groups) or 10% PDMS fluids of each viscosity in their feed (0 and
100 000 mg/kg diet) for 90 days. The animals were observed twice daily for signs
of toxicity, appearance, behaviour and mortality. Body weights were recorded at the
initiation of the study and weekly thereafter, whereas food consumption was
determined weekly. Haematological parameters were measured prior to the
termination of the study. All surviving animals were sacrificed and examined by
gross necropsy and histopathologically. No statistically significant differences
between treated and control rats were reported in any end-point examined with any
of the three viscosities of the test material (United States Environmental Protection
Agency, 1994b).