39 mercury, and aniline. Absorption of phenol through just a few square inches of
intact skin can be lethal. Impervious protective clothing like gloves will increase the rate of absorption if accidental contamination occurs on the
inside. Damaged skin also facilitates absorption of toxins.
Distribution: Once substances have entered the body they can distributed
around the body through the blood supply bound to plasma proteins or to red cells. They may concentrate differentially in the organs. Other toxic materials
may be in solution or bound to lipids. Only lipid-soluble substances can pass the blood-brain barrier.
3.3.4 Metabolism
Substances which are distributed through the body then tend to be metabolised. The main site of metabolism is the liver, although the kidneys,
lungs and skin can metabolise some chemicals. Metabolism can convert a toxic substance to a non-toxic one and vice versa e.g. n-hexane is
metabolised in the liver to another compound which causes damage to the nervous system. Most detoxification is, however, beneficial. A typical
detoxification process involves oxygenation stages followed by conjugation with glucuronic acid. The rate of metabolism depends on the rate of
absorption water-soluble compounds are less well-absorbed than fat soluble and the extent of protein-binding this reduces the concentration at sites of
metabolism. Enzyme systems are poorly developed in the very young who thus metabolise more slowly. The liver renders hydrophobic substances i.e.
not soluble in water to hydrophilic water-soluble forms so that they can be excreted by the kidney or into bile.
3.3.5 Excretion
This takes place mainly through the kidneys via the urine, but also via bile high molecular weight compounds, lungs volatile hydrocarbons excreted
unchanged, gastric juices nicotine, breast milk pesticides and skin iron. The more rapidly excretion takes place the less likely is a toxin to damage the
body. Excretion products are often used to monitor work exposure.
40
3.3.6 Response to toxins
The bodys response to toxins depends on several variables: Age
The elderly and very young tend not to cope well as their metabolic pathways are less efficient than average.
Sex Women are more vulnerable to fat-soluble toxins because of
their greater percentage of fat to lean body mass. Underlying
Illness Some conditions, for example diarrhoea or reduced lung
function will limit toxic effects by reducing absorption. Others, for example anaemia, would compromise even further the
bodys response to lead or carbon monoxide.
Medication Drugs can affect enzyme systems, increasing or decreasing
the effects of toxic substances. Alcohol
May compromise liver function and thus detoxification processes.
Smoking Smoking potentiates the action of some substances like
asbestos. Individual
People vary enormously in their responses to external agents, from noise to coal dust, and allergens to chemicals.
This is probably a genetic effect.
Type of response Local effects at the point of entry e.g. irritation, burns.
Allergic reactions e.g. dermatitis, asthma. Effects on target organs.
Cancer. Reproductive effects e.g. sterility, abortions.
Teratogenesis - congenital birth defects. Childhood tumours in offspring of those exposed.
3.4 Stages of toxicological Evaluation
