Disposition of the flame retardant 1,2-bis(2,4,6-tribromophenoxy)ethane in rats following administration in the diet.
[14C]1,2-Bis(2,4,6-tribromophenoxy)ethane (FF-680) was administered at 0.05, 0.5, or 5% in the diet for 1 day to three groups (four rats per group) of rats, and daily at 0.05% in the diet for 10 days to another group of five rats. In addition, another group of four rats were given a single oral gavage dose of 200 mg/kg of [14C]FF-680 in corn oil and were used for bile collection. At all dose levels, [14C]FF-680-derived radioactivity was excreted almost totally via the fecal route (> 99% of the total excreted 14C), with < 1% recovered in the urine. No radioactivity was detected in the expired air, and very little radioactivity was excreted in the bile (ca. 0.04% of the dose). At 4 days after the start of administration of the dosed diet for 1 day, no radioactivity was detected in any tissue analyzed, except adipose tissue, skin, and thymus, in which trace concentrations of radioactivity were detected in some animals. At 10 days after the start of administration of dosed diet to rats dosed for 10 days, trace but detectable levels of radioactivity were observed in all tissues analyzed except the brain of some animals. Excluding the gastrointestinal tract, adipose tissue contained the highest concentration of 14C radioactivity, followed by kidney, skin, and thymus, whereas brain, testes, and spleen contained the lowest concentrations of radioactivity. No parent compound was detected in the urine, while fecal radioactivity was identified as the parent compound. Mean recovery of radioactivity ranged from ca. 86-101% of the [14C]FF-680 consumed. The data indicate that FF-680 was very poorly absorbed from the gastrointestinal tract. However, following daily administration for 10 days, trace amounts of radioactivity accumulated in tissues to provide detectable levels.
Nomeir
A A
AA
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.
Markham
P M
PM
Ghanayem
B I
BI
Chadwick
M
M
D000818:Animals; D001646:Bile / Q000378:metabolism; D001969:Bromobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D005243:Feces / Q000737:chemistry; D005411:Flame Retardants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D001969:Bromobenzenes; D005411:Flame Retardants; C081014:1,2-bis(2,4,6-tribromophenoxy)ethane