Safety evaluation of certain food additives - ipcs inchem

170 POLYDIMETHYLSILOXANE (addendum)
2.2.3 Long-term studies of toxicity and carcinogenicity
In order to evaluate possible long-term toxic and oncogenic effects, 10 cSt
PDMS fluid was administered orally in the diet to F344 rats for 12 and 24 months.
PDMS fluid with a viscosity of 10 cSt was administered on a continuous basis in the
diet at dose levels of 100, 300 or 1000 mg/kg bw per day. Each group consisted of
90 male and 90 female F344 rats. At the outset, the males were 38 days old and
the females were 37 days old. The animals were observed twice daily for mortality
and morbidity. Clinical observations were recorded daily, and detailed physical
examinations, palpable masses, body weight and food consumption were recorded
weekly. Clinical pathology parameters (haematology, serum chemistry and
urinalysis) were evaluated for 20 animals per sex per group at approximately 3, 6
and 12 months of the study. In addition, blood smears were prepared from all
animals that were euthanized in extremis and from the animals from the oncogenicity
study (24 months) at the study week 104 primary necropsy. Ophthalmic
examinations were conducted prior to test article administration (study week –1)
and during study weeks 12, 51 and 103. Necropsies were performed on all animals,
and selected organs were weighed. Selected tissues were examined
microscopically from all animals.
Survival was unaffected by test article administration. Survival in the animals
from the chronic toxicity study (12 months), the animals from the chronic recovery
study (24 months) and the animals from the oncogenicity study (24 months) was
70% or greater in all groups. There were no toxicologically significant test article–
related effects on body weight, food consumption or clinical pathology parameters.
There were no test article–related macroscopic or microscopic (neoplastic or nonneoplastic)
findings for the animals from the chronic toxicity study (study week 52
interim necropsy). There were no test article–related proliferative changes observed
in the animals from the chronic recovery study (study week 104). Test article–related
clinical findings consisted of slightly increased incidences of corneal opacities in
males at 300 mg/kg bw per day and in males and females at 1000 mg/kg bw per
day. Possible test article–related macroscopic findings were limited to increased
incidences of corneal opacity for the animals from the oncogenicity and chronic
recovery studies. In the 24-month study with 10 cSt PDMS in F344 rats, corneal
opacity was observed at slightly increased incidences in males at 1000 mg/kg bw
per day and in females at 100 and 1000 mg/kg bw per day. In the animals from the
chronic recovery study, the incidence of eye opacity was slightly increased in all test
article–treated male groups (not dose related). Corneal opacity was usually correlated
with the microscopic finding of keratitis or the incidental microscopic finding
of corneal dystrophy. Microscopically, exposure to the test article for 2 years did not
result in any evidence of systemic toxicity. Inflammation of the nasolachrymal duct
was observed with slightly increased incidence and severity in males at 1000 mg/kg
bw per day. An increased incidence of primarily minimal to mild keratitis was
observed in all test article–related males and females in the oncogenicity group.
The test article–treated animals from the oncogenicity study also had a higher
incidence of bilateral keratitis compared with the control group animals, in which
keratitis was usually unilateral. The increased inflammation in the duct at this level
was considered secondary to test article draining from the eye into the duct and