Repeated inhalation exposure to octamethylcyclotetrasiloxane produces hepatomegaly, transient hepatic hyperplasia, and sustained hypertrophy in female Fischer 344 rats in a manner similar to phenobarbital

Octamethylcyclotetrasiloxane (D4) has been described as a phenobarbital-lik e inducer of hepatic enzymes. Phenobarbital (PB) and phenobarbital-like che micals induce transient hepatic and thyroid hyperplasia and sustained hyper trophy in rats and mice. The extent to which these processes are involved w ith D4-induced hepatomegaly is not known. The present study has evaluated t he effects of repeated inhalation exposure to D4 vapors on hepatic and thyr oid cell proliferation and hypertrophy with respect to time and exposure co ncentration. Female Fischer 344 rats were exposed via whole body inhalation to 0 ppm D4, 700 ppm D4 vapors (6 h/day; 5 days/week), or 0.05% PB in drin king water over a 4-week period. Incorporation of 5 ' -bromo-2-deoxyuridine (BrdU) and the abundance of proliferating cell nuclear antigen were used a s indicators of cell proliferation. Designated animals from each treatment group were euthanized on study days 6, 13, and 27. The effect of D4 exposur e concentration on hepatic cell proliferation was evaluated at 0, 7, 30, 70 , 150, 300, or 700 ppm. Liver-to-body weight ratios in animals exposed to 7 00 ppm D4 were increased 18, 20, and 22% over controls while PB-treated ani mals showed increases of 33, 27, and 27% over controls on days 6, 13, and 2 7 respectively. Hepatic incorporation of BrdU following exposure to D4 was highest on day 6 (labeling index = 15-22%) and was at or below control valu es by day 27. This pattern of transient hyperplasia was observed in all hep atic lobes examined and was similar to the pattern observed following treat ment with PB. (C) 2001 Academic Press.