Types of Exposure -- Generally, exposure to toxicants may be either acute or chronic.

Acute exposure -- usually refers to a single exposure to a large dose of the toxicant.  The response, or evidence of toxicity, follows relatively rapidly.  However, in some cases the response to an acute exposure may not be evident for months or years, as with potential teratogens or carcinogens.

Chronic exposure -- usually refers to repeated exposure over time, often at a lower dose than acute exposure.  The toxicant may accumulate and eventually exert a toxic response or it may immediately begin to affect the body and exhibit a cumulative toxic effect over time.  Most cases of chronic exposure will not be fully manifest for weeks, months, or even years after the initial exposure.

Oral -- this route most often occurs at home and is usually accidental.  It most often involves either household cleaners or food contaminants, such as the methylmercury epidemic of Minamata Bay in Japan, when large quantities of contaminated fish were eaten.

Inhalation -- Most often occurs in industrial settings and may involve solvents, volatile compounds, or aerosolised toxicants such as pesticide spraying in agricultural settings.  Environmental disasters such as occurred in Bhopal, India or with train derailments of toxicants may also result in inhalational exposure at home.

Topical -- This type of exposure may occur either in the home, with cleaners or pesticides, the work place with solvents, or in agricultural settings.  These may be accidental or the result of some widespread exposure, again such as Bhopal or shipping accidents that may involve volatile compounds that may come in contact with the skin.

Direct Tissue Damage -- This response reflects some action of the toxicant that results in injury to a cell or tissue, most often involving structural damage.  On the cellular level, this may involve binding to and disruption of the cellular membrane, causing cell death.  Examples include 1) paracetamol toxicity (through its reactive metabolite) where hepatocytes undergo individual necrosis, resulting in organ failure; 2) hyper- or hypo-tonic solutions that will cause crenation or lysis of cells by osmotic diffusion leading to cell death; or 3) disruption of cellular channels resulting in electrolyte imbalance and cell death. Alternatively whole tissues may be damaged by direct exposure to corrosive chemicals such as acids, strong alkaline substances, or solvents.

Biochemical Lesions -- The toxicant may alter or interfere with a biochemical function of the cell leading to damage and/or death.  Mechanistically, cyanide reduces electron transport, effectively uncoupling oxidative phosphorylation (and consequently reducing cellular respiration)  that deprives the cell of required energy.  This leads to cell necrosis and, if enough cells are affected, organ failure and/or death.

Pharmacologic/Physiologic Responses -- These responses often present as a body-wide reaction to the effect of a toxicant.  An agent, for example, increases blood pressure.  The physiologic response to this could be MI, stroke, or aneurism.  Alternately, a toxicant that lowers blood pressure may reduce blood flow enough to cause local areas of ischaemia and necrosis (which could also occur with local areas of intense vasoconstriction!!!).

Allergic Reactions -- Many toxicants' effects may be mediated by the immune system in one of the four types of immune-mediated responses.

Note that Type I and IV are the most common responses to toxicants, however, a toxic compound may also cause a Type II or III response.

Teratogenicity -- This response results in birth defects by altering the development of the foetus.  It may often occur at levels that produce no response in the mother.  The mechanisms of teratogenicity will be covered later in the course.

Mutagenicity -- This response results in changes in the DNA or chromosomes of the cell of the organism.  These changes are then passed to the daughter cells, where the change is expressed.  If the mutagenic action takes place in germ cells, it may cause teratogenicity.  If somatic cells are affected, then altered function or cancerous growth may result.

Carcinogenicity -- This response is closely related to mutagenicity, but NOTE that not all mutagens are carcinogens and not all carcinogens are mutagens.  The mechanisms of carcinogenicity will also be covered later.

Gross changes in form may be examined either in the living animal or by necropsy.

Microscopic changes may be identified histologically.

Often, endogenous chemicals or biological activity are used to assess the response to a toxicant.  These are often referred to as BIOMARKERS.  Some biomarkers commonly used in human and/or environmental toxicology include the following:

Enzyme levels -- such as LDH, AST, ALT, CPK, to determine organ function or damage
Metabolites -- of the toxicant to assess its elimination from the organisms or environment
Vitellogenin -- is often used as a biomarker of reproductive response in environmental toxicology.
Bioluminescence -- is also used as a quick, efficient marker of potential toxicity of pesticides and other environmental pollutants.