Disposition of radioactivity in fischer 344 rats after single and multiple inhalation exposure to [(14)C]Octamethylcyclotetrasiloxane ([(14)C]D(4)).
The retention, distribution, metabolism, and excretion of [(14)C]octamethylcyclotetrasiloxane (D(4)) were studied in Fischer 344 rats after single and multiple exposures to 7, 70, or 700 ppm [(14)C]D(4). Subset groups were established for body burden, distribution, and elimination. Retention of inhaled D(4) was relatively low (5-6% of inhaled D(4)). Radioactivity derived from [(14)C]D(4) inhalation was widely distributed to tissues of the rat. Maximum concentrations of radioactivity in plasma and tissues (except fat) occurred at the end of exposure and up to 3 h postexposure. Maximum concentrations of radioactivity in fat occurred as late as 24 h postexposure. Fat was a depot, elimination of radioactivity from this tissue was much slower than from plasma and other tissues. With minor exceptions, there were no consistent gender effects on the distribution of radioactivity and the concentrations of radioactivity were nearly proportional to exposure concentration over the exposure range. Excretion of radioactivity was via exhaled breath and urine, and, to a much lesser extent, feces. Urinary metabolites included dimethylsilanediol and methylsilanetriol plus five minor metabolites. Relative abundance of these metabolites was the same from every test group. Elimination was rapid during the first 24 h after exposure and was slower thereafter (measured up to 168 h postexposure). In singly-exposed female (but not male) rats, small dose-dependent shifts in elimination pathways were seen. After multiple exposures, the elimination pathways were dose- and gender-independent. These data define possible pathways for metabolism of D(4) and allow estimation of the persistence of D(4) and/or its metabolites in rats.
Plotzke
K P
KP
Toxicology, Health, and Environmental Sciences, Dow Corning Corporation, Midland, Michigan 48686, USA. kathy.plotzke@dowcorning.com
Crofoot
S D
SD
Ferdinandi
E S
ES
Beattie
J G
JG
Reitz
R H
RH
McNett
D A
DA
Meeks
R G
RG
D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D001273:Atmosphere Exposure Chambers; D001822:Body Burden; D005260:Female; D006207:Half-Life; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012129:Respiratory Function Tests; D012727:Sex Characteristics; D012833:Siloxanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D012833:Siloxanes; C024064:octamethylcyclotetrasiloxane