Biology Reference
In-Depth Information
placenta is a typical plasma membrane barrier that is permeable to lipophilic and non-
ionized molecules that readily cross plasma membranes, thereby exposing the fetus to
toxicants. 1,1-Dichloro-2,2-bis( p -chlorophenyl)ethylene (DDE) and 2,4-D have been
demonstrated to cross the placenta in rats, rabbits, and bats ( Kim et al., 1996; Sandberg
et al., 1996; Thies and McBee, 1994 ), and prenatal human exposure to 2,4-D has been
associated with mental retardation in offspring ( Casey and Collie, 1984 ).
Storage and Redistribution
Chemicals may accumulate in body compartments because of protein binding, active
transport processes, or high solubility in (i.e., affinity for) a particular tissue. These sites
of accumulation can be considered storage depots. Because a chemical in any tissue
compartment is in equilibrium with its free concentration in blood, storage is dynamic.
Removal of free chemical from the body by metabolism or excretion shifts the equi-
librium such that stored chemical is released.
Plasma Proteins
Plasma protein binding plays a very important role in chemical-induced toxicity.
Displacement of one chemical by another from plasma proteins can have severe con-
sequences. If the bound chemical is very toxic, its displacement results in a higher free
concentration in plasma, which results in greater availability for distribution to its site
of toxic action.
Fat
Adipose tissue is a storage depot for a number of highly lipophilic chemicals, including
pesticides. Storage in adipose tissue may be considered a protective mechanism, in that
the pesticide is stored in a nontarget tissue, thereby lowering its concentration at the site
of toxic action. For example, the chlorinated insecticides DDT ( Dale et al., 1962; Hayes
et al., 1958 ), chlordane ( Ambrose et al., 1953 ), hexachlorobenzene isomers ( Davidow
and Frawley, 1951 ), lindane ( Ludwig et al., 1964 ), aldrin, and dieldrin ( Robinson et al.,
1969 ) are lipophilic and accumulate in fat. Upon dieting and starvation, fat is mobilized
and the stored chemical is released, which results in a sudden increase in the blood
concentration and availability of the pesticide for redistribution. As was described for
plasma proteins, chemicals stored in adipose tissue may be displaced by other chemicals.
Street (1964) demonstrated that DDT displaces dieldrin from its storage sites in rat adi-
pose, yet methoxychlor does not affect dieldrin storage. Toxicity may be observed if the
released chemical is redistributed to the target organ.
Other Tissues and Tissue Components
Sequestration in tissues (e.g., kidney and liver) may be due to interaction of chemicals
with tissue macromolecules such as proteins and nucleic acids, which influences the
Search WWH ::




Custom Search