Routes of Absorption

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

As stated earlier, inhalation is the main route of absorption for occupational exposure to chemicals. Absorption of gaseous substances depends on solubility ifi blood and tissues (as presented in Sections 2.3.3-2.3.5), blood flow, and pulmonary ventilation. Particle size has an important influence on the absorption of aerosols (see Sections 2.3.7 and 3.1.1). 

Absorption across biological membranes is often necessary for a chemical to manifest toxicity. In many cases several membranes need to be crossed and the structure of both the chemical and the membrane need to be evaluated in the process. The major routes of absorption are ingestion, inhalation, dermal and, in the case of exposures in aquatic systems, gills. Factors that influence absorption have been reviewed recently. Methods to assess absorption include in vivo, in vitro, various cellular cultures as well as modelling approaches. Solubility and permeability are barriers to absorption and guidelines have been developed to estimate the likelihood of candidate molecules being absorbed after oral administration. ... 

Inorganic Lead. Once absorbed, inorganic lead appears to be distributed in essentially the same manner regardless of the route of absorption (Kehoe 1987). This implies that a common lead transport... 

Molecules with a large molecular weight or size are confined to the transcellular route and its requirements related to the hydrophobicity of the molecule. The transcellular pathway has been evaluated for many years and is thought to be the main route of absorption of many drugs, both with respect to carrier-mediated transport and passive diffusion. The most well-known requirement for the passive part of this route is hydrophobicity, and a relationship between permeability coefficients across cell monolayers such as the Caco-2 versus log P and log D 7.4 or 6.5 have been established [102, 117]. However, this relationship appears to be nonlinear and reaches a plateau at around log P of 2, while higher lipophilicities result in reduced permeability [102, 117, 118]. Because of this, much more attention has recently been paid towards molecular descriptors other than lipophilicity [86, 119-125] (see section 5.5.6.). The relative contribution between the para-cellular and transcellular components has also been evaluated using Caco-2 cells, and for a variety of compounds with different charges [110, 112] and sizes [112] (see Section 5.4.5). 

Types of Effects Route of Absorption Mild Exposure Severe Exposure... 

Lukas, G., Brindle, S.D. and Greengard, P. (1971). The route of absorption of intraperitoneally administered compounds. J. Pharmacol. Exptl. Ther. 178 562-566. 

Toxicology. Acrylic acid is a severe irritant of the eyes, nose, and skin. The major route of absorption is ingestion of inhaled vapors. 

Most compounds are designed for single (acute) or regular (chronic) oral application with a well defined route of absorption within the GI tract and with a consideration of... 

In humans, the predominant route of absorption of fluoride is via the gastrointestinal tract. Airborne fluoride may also be inhaled. Dermal absorption is negligible except in cases of hydrofluoric acid burns [42]. 

With regard to worker exposure to nitrosamines present in agricultural chemicals, the volatile nature of these materials suggests inhalation and dermal contact as the major routes of absorption. There is a potential hazard of exposure to field applicators, especially commercial farmers and growers who regularly spray their crops and land. Manufacturers of the formulations may have workers who are exposed to unusually... 

Figure 5.1 Pharmacokinetics and pharmacodynamics of the psychotropic drugs in the body. Pharmacokinetic routes of absorption, cSstribution, metabolism and excretion are represented by single lines. Pharmacodynamic effects such as biological and neurobio logical effects, receptoi binding, modulation of signal transudation, etc. are represented by double-dotted lines...

C. Consideration of routes of absorption by man, animals, or aquatic life... 

Form Entering Body Major Route of Absorption Distribution Major Clinical Effects Key Aspects of Mechanism Metabolism and Elimination... 

The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses of 200-500 pg produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity. Traditionally the herb is consumed either by chewing the fresh leaves or by drinking the juices of freshly crushed leaves. The effects of the herb when consumed this way depend on absorption of salvinorin A through the oral mucosa before the herb is swallowed. 

The oral mucosa apparently acts as a time release buffer, slowly diffusing salvinorin A into the blood stream hence when consumed orally, the effects begin more gradually, last longer and subside over a longer period of time than when the material is vaporized and inhaled. Although variable in duration, the effects experienced have the same overall characteristics regardless of the route of absorption used. 

Many foreign substances are ingested orally, either in the diet or as drugs, and poisonous substances taken either accidentally or intentionally. Most suicidal poisonings involve oral intake of the toxic agent. Consequently, the gastrointestinal tract is a very important site and perhaps the major route of absorption for foreign compounds. 

Oral Exposure Animals and humans are exposed to chemicals through different routes. Chemical toxicity differs depending on the route of absorption.52,64 Entry... 

The noncorneal route of absorption involves penetration across the conjunctiva and sclera into the intraocular tissues. There are three pathways for drug penetration across the sclera ... 

It is interesting that the noncorneal route of absorption may be important for hydrophilic compounds with large molecular weights such as timolol maleate and gentamicin. This route may also be attractive in... 

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