Toxicokinetics - trdoer40189

structural malformation, organ system dysfunction, and ectodermal dysplasia

syndrome. Dioxin-like compounds have also been found to be genotoxic by

activating gene transcription through aryl hydroxylase activity (AHA). TCDD,

the most potent of all the dioxin congeners has been shown to be a multisite

carcinogen in both sexes of mice and in hamsters. It is believed that there are

multiple mechanisms for TCDD's "tumor promoting" activity. The carcinogenic

effects of TCDD are hepatocellular carcinomas and hepatocellular hyperplastic

nodules.

Toxicokinetics

Following oral exposure, gastrointestinal absorption of TCDD in animal

studies is nonlinear, with the greatest absorption occurring at < 0.01 u mol/kg.

Gastrointestinal absorption of TCDF in animals is almost complete (90 percent

or greater). In humans, absorption via oral exposure is variable, incomplete, and

congener- and vehicle-specific. Transpulmonary absorption is similar to that

observed after oral exposure, however, the rate of absorption via dermal routes is

slower. Dioxin-like compounds are often associated with lipoprotein in the blood

and in lymph, thus they may be distributed to organs of the body in proportion to

the amount of blood flow to each organ and organ size. The adrenal glands and

muscle are the first organs to which dioxins and furans are distributed, followed

by the liver, adipose tissue and skin. The highest concentrations of dioxin-like

compounds have been found in the liver and adipose tissue. Dioxins and furans

are metabolized by the body to polar compounds and excreted as urine, bile, and

feces.

Ecological effects

Early life stages of animals have been more sensitive to TCDD than adult

animals. Studies have shown that TCDD is directly toxic to pike, rainbow trout,

lake trout, and Japanese medaka. The toxic effects on young fry of these fish

species are edema, hemorrhage, arrested growth and development, and death.

TCDD has been extremely toxic to bird eggs. Signs of toxicity are species-

specific; however, embryo mortality is common to all species.

D37

Appendix D Toxicological Profiles