Basic concepts in hazardous chemicals: Understanding toxicity

We have been regularly "educated" of the effects of toxic chemicals through various sources and would probably be aware of the term "toxic waste".

Despite numerous attempts to highlight safe handling and awareness of toxic chemicals, recent experience on the interaction between toxic chemicals and humans through inadequate handling procedures and sheer negligence is still resulting in the loss of life or permanent disability.

One such incident is the exposure of workers to toxic fumes (believed to be hydrogen sulphide) in a drilling barge in West Port, Klang. The toxic exposure resulted in the death of four workers while 14 others were hospitalised.

On the international front, the contamination of food with a class of toxic chemical known as polychlorinated biphenyls (PCBs) resulted in several hundred people in Japan becoming ill while pregnant mothers gave birth to infants with symptoms of a disease called Yusho disease.

This incident has led to the development of a standard for the permissible exposure of PCBs in the workplace and resulted in close monitoring of PCB levels in the environment, withe the aim of reducing its toxic effect on humans. PCBs are suspected to have carcinogenic effects and this problem is compounded by its persistent presence in the environment.

The study of toxicology deals with the nature and action of chemical poisons. The term toxicity refers to the ability of a chemical molecule or compoundto produce injuryonce it reaches a susceptible site in or on the body while toxicity hazard is the probability that injury will occur considering the manner in which the substance is used.

Besides these basic terms, a number of established terminology has been used to describe the toxic nature of chemicals. This include among others, the toxic potency of a chemical which is defined as the response that is produced in a biological system. The potential toxicity (harmful action) inherent in a substance is exhibited only when that substance comes in contact with a biological system.

All effects of chemicals, be it beneficial, indifferent or toxic, are dependent on a number of factors. The most important is known as the dose-time relationship, which measures how much of a chemical is involved (dose) and how often during a specified period of time the exposure occurs (time). The dose is the amount of chemical a person is exposed to.

In the workplace, there are certain guidelines or regulations which try and limit exposure to hazardous substances. These guidelines, which are set by various regulatory and professional organisations, are referred to as workplace exposure limits.

It sets the parameters for which airborne concentrations of a hazardous material cannot exceed so that a worker can be exposed without any adverse effect.

Among the standard limits are Time Weighted Average (TWA), which is the average concentration of a substance integrated over a period of time (example a normal eight-hour workday) and Short Term Exposure Limit (STEL) which is the maximum concentration limit for continuous 15 minutes exposure provided that the daily TWA is not exceeded.

It is important to note that all these measurements, though often based on data from animal research, refer to the exposure and resistance of a healthy adult. Most exposure standards are based on the inhalation route.

They are normally expressed in terms of parts per million (ppm) or miligrams per cubic metre (mg/m) concentration in air.

In addition, the American Occupational Safety and Health Administration (OSHA) has established Permissible Exposure Limits (PELs) and the American Conference of Governmental Industrial Hygienists (ACGIH) has established Threshold Limit Values (TLVs) for employee exposure limits.

In many instances, the PEL and TLV are represented as the same number. In the instances where one is lower than the other, it is a prudent safety practice to maintain exposures at the lowest level achievable. If a significant route of exposure for a substance is through skin contact, the TLV or PEL will have a skin notation.

However, it should always be remembered that these levels do not necessarily apply to pregnant women, their unborn foetuses or adults who are ill or under special stress. In such situations, the organisation must carefully consider all pertinent information.

Besides the dose-time relationship, the degree of toxicity of a chemical is also dependent on its route of exposure.

There are four main routes by which hazardous chemicals enter the body: inhalation (absorption through the respiratory tract), dermal absorption or absorption through the mucous membranes, ingestion or absorption through the digestive tract which occur through eating or smoking with contaminated hands or in contaminated work areas.

The least common route of toxicity, which is injection, involves introducing the toxin into the bloodstream by accidental needle-stick injury or puncture of the skin with a sharp object. In general, this route of poisoning is of little practical importance to the average person. In addition, there are a number of other factors which can modify the toxicity effect, namely: age, sex, nutrition, state of health, individual sensitivity and the presence of other chemicals.

As an example, age does exert an influence on the acute toxicity of some chemicals. A typical case to indicate this effect is boric acid, which is much more acutely toxic orally to infants and toddlers than to adults as seen from the Ipoh "loh see fun" poisoning case which happened in 1988.

The differences between the age groups can be considered to be due in part to differences in the activity of the enzyme systems that metabolise foreign chemicals. These systems, which are underdeveloped in infants, would not be able to reduce the concentrations of the toxic chemical in the body, thereby exerting a larger toxic effect.

Besides age, the toxicity of a chemical can also be modified by the presence of other chemicals, extensive studies of asbestos workers have shown that the risk of lung cancer in a smoker exposed to asbestos is 20 to 30 times greater than a non-smoker exposed to the same asbestos concentrations.

The dose-time relationship gives rise to two different tyoes of toxicity that must be distinguished form one another: acute toxicity and chronic toxicity. Acute toxicity is characterised by rapid absorption of the substance when the exposure is sudden and severe.

Normally, a single large exposure is involved. Examples of toxic chemicals that cause this include carbon monoxide and cyanide.

On the opposite and, chronic toxicity refers to the ability of a chemical to do systemic damage as a result of many repeated exposures during a prolonged period of time. If chronic exposure to a chemical is of sufficient magnitude to produce adverse effects, such effects are usually not detected until the exposure has continued for some period of time.

Normally, chronic toxicity effects are characterised by prolonged or repeated exposures of a duration measured in days, months or years. Under such circumtances, symptoms may not be immediately apparent. Examples of some chronic toxic chemicals are lead, mercury and pesticides.

Besides the classification of such chemicals based on the onset of toxic effects, other classifications being used to describe toxic chemicals include:

This refers to the site of action of an agent. The site may be skin, mucous membranes, the respiratory tract, gastrointestinal system, eyes, etc. Absorption does not necessarily occur. Examples are strong acids or alkalis.

This refers to a site of action other than the point of contact and pre-supposes absorption has taken place. For example, inhaled benzene affects the bone marrow.

Some poisons are characterised by materials that tend to build up in the body as a result of chronic exposure. The effects are not seen until a critical body burden is reached. Examples are heavy metals.

This occurs when two or more hazardous materials present at the same time have a resulting action greater than the effect predicted based on the individual substances. For example, workers exposed to benzene may experience toxic effects in their haematopoietic tissues and therefore be more susceptible to oxygen-displacing agents such as carbon monoxide.

A toxic chemical can be an aerosol, gas, liquid or a solid. The effects that can be seen from each substance varies, depending on the physical form of the chemical. When considering the toxicity of gases and vapours, the solubility of the substance is a key factor.

Highly soluble materials like ammonia irritate the upper respiratory tract. On the other hand, relatively insoluble materials like nitrogen dioxide penetrate deep into the lungs. Fat soluble materials, like pesticides, tend to have longer lingering times in the body. An aerosol is composed of solid or liquid particles of microscopic size dispersed in a gaseous medium. The toxic potential of an aerosol is only partially described by its concentration in miligrams per cubic metre (mg/m3).

To conclude, the mechanisms by which a chemical exerts a toxic action are many and varied. Some chemicals are in themselves toxic.

Others must be converted metabolically to other forms before they become toxic. In other instances, there are chemicals which act indirectly in some manner such as by destroying an essential nutrient which in turn is the damaging event. A point to note is that some chemicals may result in only one harmful effect whereas others can produce damage by several means.

For example, hydrochloric acid and sodium hydroxide are corrosive in concentrated form and irritant in dilute solution.

Neither is classified as toxic but both can cause death by destroying tissues which it comes into contact with. In such cases, death is the result of the body's inability to survive the harm caused by tissue destruction.

In coming issues, the effect of toxic chemicals on health will be further discused with the hope that individuals constantly exposed to these chemicals would be able to recognise their harmful effects and appreciate the strict implementation of safety procedures to reduce such exposures.

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