Exposure routes various toxic chemicals

Recognize what chemicals are toxic, using the categories in this section as a guide for analysis. Assess the level of risk based on likelihood of exposure by various routes. Be mindful of confined spaces (smaU labs) with regard to asphyxiants. 

Another difficulty comes from the consideration of the route of entry (sf the contaminant, as chemicals can enter the body by various routes and the human body responds to the action of a toxic agent primarily on the basis of the rate and route of exposure. Without any doubt, the most important route of exposure at the workplace is inhalation, and this should be the route used to set OELs. However, if there is a threat of significant exposure by other routes, such as cutaneously (including mucous membranes and the eyes), either by contact with vapors or by direct skin contact w ith the substance, additional recommendations may be necessary. 

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. ... 

The principal application of PBPK models is in the prediction of the target tissue dose of the toxic parent chemical or its reactive metabolite. Use of the target tissue dose of the toxic moiety of a chemical in risk assessment calculations provides a better basis of relating to the observed toxic effects than the external or exposure concentration of the parent chemical. Because PBPK models facilitate the prediction of target tissue dose for various exposure scenarios, routes, doses, and species, they can help reduce the uncertainty associated with the conventional extrapolation approaches. Direct application of modeling includes... 

The physico-chemical properties may provide indications about the absorption of the substance for various routes of exposure and may therefore be of importance in the evaluation whether an appropriate administration route has been applied in the available experimental toxicity studies. In order for a substance to be absorbed, it must cross biological membranes. Most substances cross biological membranes by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the logPoctanoi/water and the water solubility. 

Genetically caused polymorphisms are known for a number of enzymes, which metabolize chemicals, and are important for the interindividual variability to chemical exposures, especially if the polymorphic pathway represents the major route of elimination. Altered enzyme levels and activities may thus render some individuals more susceptible to exposure to chemicals than the general population. It could therefore be hypothesized that even a very low exposure to a chemical may be associated with various biological responses in such susceptible individuals as altered enzyme levels and activities may influence the individual s ability to detoxify a chemical or increase the conversion of a chemical to a toxic metabolite. 

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