Absorption - Pesticide Biotransformation and Disposition - page 45

that would cause irritation by other routes. As will be discussed in the pharmacokinet-
ics section of this topic, the plasma concentration-time data obtained from iv admin-
istration are necessary for estimating the absolute bioavailability of a substance given
by an extravascular route. The major disadvantages of iv administration are that the
administered dose cannot be removed, systemic toxicity may occur with some pesti-
cides because of the transiently high concentration achieved, sterile pesticide prepa-
rations are required, and pesticides that are insoluble in plasma may precipitate and
cause embolus formation. For experimental pharmacokinetic studies, pesticides can be
administered intravenously by bolus injection or infusion or added to fluid drip bags.
Intra-arterial injection is very similar to iv administration, but more hazardous since
the pesticide is delivered directly to the arterial circulation. This mode is often used in
pharmacology to treat localized tumors that have accessible arteries for injection.
Other routes of exposure that are used in the laboratory include intraperitoneal
(ip) injection, where chemicals are absorbed primarily through the portal circulation,
and intramuscular or subcutaneous injection. Chemicals administered intramuscularly
(im) or subcutaneously (sc) are absorbed more slowly than by ip injection. Injection
is into the muscle mass, which is well perfused by the vascular system, and can result
in usually rapid absorption. Lipid solubility of the administered drug is not impor-
tant as both hydrophilic and charged chemicals are easily absorbed in the rich capillary
networks of muscle tissue. Absorption may be modulated by the vehicle used to inject
the drug into the muscle. In this case, release of drug from the vehicle becomes the
rate-limiting step. The sc mode of administration is very similar to im injection except
that the drug is deposited into the rich capillary beds perfusing the skin and absorption
is (in general) slower than via the im route and can be very erratic. Injection of tis-
sue-irritating substances may cause local reactions and even skin sloughing, which alter
absorption. Other routes of administration are intradermal, intramammary, and subcon-
junctival, which are not often associated with animal testing or human routes of expo-
sure for pesticides.
SUMMARY AND FUTURE DIRECTIONS
Human exposure to pesticides can result in absorption by passive diffusion across the
epithelial layers of the skin and/or the gastrointestinal tract. As occupational exposure
via the skin is the most likely source and route for human exposure, this chapter has
focused on the main physicochemical, biological, and environmental factors that could
significantly influence systemic absorption following dermal exposure to examples
of pesticides with diverse physicochemical properties. There are several in vitro and
inert membrane models (Bronaugh and Stewart, 1984; Carver et al., 1989 ) that can be
used experimentally to evaluate membrane transport, and there has been some suc-
cess in comparing absorption across in vitro and in vivo systems ( Wester et al., 1998 ).