Human Physiological Responses to Toxic Substances

The human body needs very small quantities of chemicals that are poisonous in large doses. This applies, for example, to some heavy metals, such as copper, magnesium and manganese. The adverse effect is strongly related to the dose. The effects may be immediate or delayed, and they may be reversible or irreversible toxic effects [Ref. 1, 2, 5; and]. The worst possible effect is fatality.

  • Local/systemic toxicity: There are two main ways in which chemicals may exert their effects. Local effects occur at the area of the body which has been in contact with the chemical. Examples include external tissue injuries from acids or lung injuries from inhaled reactive gases. Systemic effects occur after the chemical has been absorbed and distributed from the entry point to other parts of the body. Most substances produce systemic effects, but some substances may cause both types of effects. An example is tetraethyl lead, which is a gasoline additive and produces skin effects at the contact site.It may also be absorbed and transported into the body causing adverse effects on the central nervous system and on other organs.
  • Target organs: The degree of the toxic effect is not the same in all organs. Usually there are one or two organs which show the major toxic effect. These are referred as target organs of toxicity of the particular substance. The central nervous system is the target organ of toxicity most frequently involved in systemic effects. The blood circulation system, liver, kidneys, lungs and skin follow in frequency of systemic effects. Some substances attack muscle and bones. Both the male and female reproductive systems are susceptible to adverse and often debilitating impacts from many substances.

Skin. The largest organ in the human body (~1.5-2 m 2 in area) provides a protective cover to the body organs but can allow permeation of chemicals if the load is excessive. Many substances can infiltrate through the skin and find its way to the hematological system, for example phenol, which may even lead to fatality in the event of heavy exposure. Most common forms of skin disorders that may occur due to chemical contact are: eczemas, irritation and local inflammation.This condition can be either a non-allergic or allergic reaction to exposure to chemical substances.Examples of common contact allergens are several colorants and dyes, nickel, chromium, cobalt and their salts, organomercuric compounds, acrylate and methacrylate monomers, rubber additives and pesticides. Chemical skin injury may also be influenced by extreme levels of humidity and heat.

Lung. The lung is the major route through which toxic substances in the workplace enter the body. It is also the first organ to be affected by dusts, metal fumes, solvent vapours and corrosive gases. Allergic reactions may be caused by substances such as cotton dust, toluene diisocyanate (TDI, used in the manufacture of polyurethane plastics), and methylisocyanate (MIC, used in production of carbaryl insecticide). Allergic reactions may result from exposure to bacteria or fungi. When dust particles of size lower than 0.1µm are inhaled the lungs are unable to exhale them. They become embedded in the lung leading to a condition called pneumoconiosis. Pneumoconiosis is mainly a problem for human beings exposed to the dust of silica (quartz) and asbestos, and is the commonest non-malignant occupational lung disease throughout the world.Other substances, such as formaldehyde, sulphur dioxide, nitrogen oxides and acid mists may cause irritation and reduce the breathing capacity [Refs. 2, 5].

Nervous System. Several types of substances act as neurotoxins. The nervous system is sensitive to the hazardous effects of organic solvents, such as carbon disulphide. Some heavy metals also affect the nervous system; examples include lead, mercury and manganese. Several organophosphate insecticides (malathion, parathion) and other chemicals such as acrylamide hinder chemical neurotransmitter function in the nervous system, leading to weakness, paralysis and sometimes death [Ref. 2].

Blood. The blood circulation system may also be adversely affected by solvents. For example,benzene affects the bone marrow; the first sign is mutation in the lymphocytes. Pure as well as compounds of lead, carbon monoxide, and cyanides, may overcome enzyme activities involved in the production of hemoglobin in red blood cells. Chronic lead poisoning, for example, may result in anaemia, a condition in which the ability of the blood to distribute oxygen through the body is impaired.

Liver. The main function of liver is to break down unwanted substances in the blood. Solvents such as carbon tetrachloride, chloroform, nitrosamines and vinyl chloride, as well as alcohol, are hazardous to the liver. Such substances are termed hepatotoxins.

Kidneys. Kidneys help excrete waste substances that the blood transports from various organs of the body. This helps: (i) ensure that the body fluids contain an adequate blend of various necessary salts; (ii) maintain the blood pH constant. Solvents such as carbon tetrachloride, other halogenated hydrocarbons, may irritate and can severely damage kidney function. Turpentine in large quantities is also harmful to the kidneys: `painter's kidney' is a known condition related to occupational exposure. Other well-known kidney- damaging substances (otherwise termed nephrotoxins) are lead and cadmium [].

Reproductive system. Several classes of compounds are also known to produce disorders of the reproductive system and impair birth functions. Examples include thalidomide, formamide, tetracycline, etc.

Allergic reactions. An allergic reaction (or sensitization) may appear after repetitive contact with a substance. Once the sensitization has been produced, even very low doses can provoke a reaction. Allergies can range from minor skin irritation to very severe or even fatal reactions. The pattern of sensitization varies according to the organism exposed to an allergen. In humans, the skin and the eyes are the most common areas of allergic response.

Interactive effects of chemicals on human body. The effect manifested by combination of chemicals (and mixtures) is known to be varied []. In some cases the effect may be additive (1+1=2). Organophosphate pesticides (for example, dialiphos, naled and parathion) exhibit such additivity of effects.
In other cases the combined effect of chemicals may exceed that of the individual ones (e.g.,1+1=4).It has been found that the risk of developing lung cancer after exposure to asbestos fibres is forty times greater for a smoker than for a non-smoker. In the domain of solvents, trichloroethylene and styrene manifest similar behaviour.
When two substances negate each other’s effect (1+1=0), it may provide an indication as to an antidote (as say for a poison).
In still other instances, a relatively risk-free substance may aggravate the effect of another (e.g., 0+1=3). Isopropanol and carbon tetrachloride have this kind of mutual effect. Isopropanol, at
concentrations which are not harmful to the liver, increases the liver damage caused by carbon tetrachloride.