Basic concepts in hazardous chemicals: Toxic effects of chemicals

By Dr Mohamed Isa Abdul Majid
The Sun, March 26, 1996

What do Bhopal and Seveso have in common? These two places have experienced the devastating effects of toxic chemicals due to the close proximity of chemical production areas and disposal sites to residential areas.

Such unfortunate incidents reflect how chemicals can act on humans whenever there is a complete disregard to its potential toxic effects. In general, these effects can be divided into local and systemic.

Certain chemicals can cause injuries at the site of first contact with the host. These local effects can be induced by caustic substances on the gastro-intestinal tract, by corrosive materials on the skin and by irritant gases and vapours on the respiratory tract.

One example of a class of chemicals with local effects are irritants. Such chemicals causes inflammation of mucous membranes when in concentrations below those needed to cause corrosion. In addition, irritants can cause changes in the mechanics of respiration and lung function. Of such chemicals, sulphur dioxide, acetic acid, formaldehyde, formic acid, sulphuric acid, acrolein and iodine have been identified to induce these changes. In some instances, irritants have also been further classified into primary and secondary irritants based on the extent of the effects caused by these agents. A primary irritant such as hydrogen chloride exerts no systemic toxic action either because the products formed on the tissue of the respiratory tract are non-toxic or the irritant action is far in excess of any systemic toxic action.

A secondary irritant's effect on mucous membranes is overshadowed by a systemis effect resulting from absorption. Examples include hydrogen sulphide and aromatic hydrocarbons. Exposure to a secondary irritant can result in pulmonary oedema, haemorrhage and tissue necrosis. Long term exposure to irritants is manifested by increased mucous secretions and chronic bronchitis.

Another group of irritant chemicals are described as corrosives. They are chemicals that may cause visible destruction or irreversible alteration in living tissue by chemical action at the site of action. Some examples of corrosive chemicals include sulphuric acid, potassium hydroxide, chronic acid and sodium hydroxide.

Another group of chemicals, asphyxiants, have the ability to deprive tissue of oxygen. Generally, asphyxiants can be categorised as simple and chemical asphyxiants. Simple asphyxiants are physiologically inert and will displace oxygen at high concentrations. Nitrogen, nitrous oxide, carbon dioxide and hydrogen are some examples.

Chemical asphyxiants render the body incapable of utilising an adequate oxygen supply. They are toxic at very low concentrations (few ppm). Some chemicals which possess this property include carbon monoxide, cyanide and hydrogen sulphide.

Finally, there are the primary anaesthetics which have a depressant effect on the central nervous system. Some examples of primary anaesthetics include halogenated hydrocarbons and alcohols. The above four classes of toxic chemicals described normally contribute towards acute poisoning.

In addition to the above class of chemicals, there are also agents which tend to require long periods of exposure before their effects are seen. Such chemicals could be hepatotoxic, nephrotoxic, neurotoxic, teratogenic and mutagenic.

Hepatotoxic chemicals cause damage to the liver. Some examples include carbon tetrachloride, nitrosamines and tetrachloroethane.

Nephrotoxic agents cause damage to the kidneys. Halogenated hydrocarbons and uranium compounds are known to exert this effect. Neurotoxic agents damage the nervous system. The nervous system is especially sensitive to organometallic compounds and certain sulphide compounds. Examples are trialkyl tin compounds, methyl mercury, organic phosphorus insecticides, manganese, tetraethyl lead, carbon disulphide and thallium.

Some chemicals can affect blood cells or bone marrow. Examples include nitrites, aniline, toluidine, nitrobenzene and benzene. A teratogen is an agent which interferes with normal embryonic development without damage to the mother or exert lethal effect on the foetus. The effects of a teratogen usually occurs during embryonic development and is subsequently magnified by the growth of the organ involved or of the surrounding tissue. These effects are not hereditary which indicate that the effects are seen only in one generation of the offspring. Examples of known teratogens are lead and dibromo/dichloropropane.

A mutagen is a chemical agent which may be able to react with nucleophilic structures such as DNA. Mutations can occur on the gene level (gene mutations) when, for example, one nucleotide basepair is changed to another. Mutations can also occur on the chromosomal level (chromosomal mutations) when the number of chromosomal units or their morphological structure is altered. Examples of mutagens include most radioisotopes, barium permanganate and methyl isocyanate. A similar effect that is synonymous to mutation is carcinogenesis which also involves changes in the DNA.

However, carcinogenesis, especially those induced by chemicals, refer to the multi-stage processes which begin with the initiation of certain genetic changes in acell, thereby promoting the formation of abnormal cells (or neoplasm). Examples of known chemical carcinogens include 4-aminobiphenyl, arsenic, asbestos, auramine, benzene, benzidine, chlorambucil, chlornaphazine, chromium, diethylstilbestrol and treosulphan.

A sentitiser causes a substantial proportion of exposed people to develop an allergic reaction in normal tissue after repeated exposure to the chemical. The reaction may be as mild as a rash (contact dermatitis) or as serious as anaphylactic shock. Epoxides, nickel compounds, poison ivy, chromium compounds, chlorinated hydrocarbons, formaldehyde, amines and toluene diisocyanate are known to cause sensitising effects.

To conclude, many chemicals exhibit a multiplicity of biological effects. Some of these are beneficial, others may be inconsequential to the well-being of the organism and others are harmful and may even be lethal. These effects are normally determined from studies on the interaction of these chemicals with living cells to assess the health hazards associated with exposures to such chemicals.

Besides determining the effects of chemicals on cells and tissues, health effects monitoring is also done from continuous human epidemiology studies and case reports. By having these studies, the detection of possible unwanted effects can be done at the earliest possible stage so that intervention programmes can be initiated before an injury has taken place.

Before extensive data could be accumulated for an unknown chemical, the best policy to adopt when handling chemicals would be to incorporate personal protective equipment, engineering controls as well as environmental and biological monitoring techniques to minimise or eliminate human exposure.

The writer is a pharmacist and Head of Toxicology Laboratory at the National Poison Centre, Univesiti Sains Malaysia.

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