Occupational Diseases

Toxicology

The toxicity of a substance is its potential to cause harm by reaction with body tissues. Measures of toxicity include lethal dose (LD 50) and lethal concentration (LC 50). The LD 50 is the single dose of a substance which when administered to a batch of animals under test kills 50% of them. It is measured in terms of mg of a substance per kg of body weight. Typical degrees of LD toxicity are

  • Extremely toxic 1mg or less
  • Highly toxic 1-50 mg
  • Moderately toxic 50-500 mg
  • Slightly toxic 0.5-5 g
  • Practically non-toxic 5-15 g
  • Relatively harmless 15g or more

In a similar way, the LC 50 refers to an inhale substance and is the concentration which kills 50% in a stated time. The Ames test is a useful test for carcinogenic substances which measures the ability of a substance to damage genetic material (DNA) in special strains of bacteria.

The toxic response to a given substance depends on the dose, and this may be demonstrated in an animal's tissues, physiology, biochemistry and behaviour. However, with all animal testing there is difficulty in extrapolating these results to men, especially when the animals are tested in conditions to which man is not exposed.

Portals of entry

Occupational poisons gain entry to the body via the lungs, skin and sometimes the gut. Absorption of a poison depends on its physical state, particle size and solubility. Of the substances entering the lung some may be exhaled, coughed up and swallowed, attacked by scavenger cells and remain in the lung, or enter the lymphatics. Soluble particles may be absorbed into the blood stream. The skin is protective unless abraded when soluble substances can penetrate to the dermis, as they may also do via the hair follicles, sweat and sebaceous glands, and then be absorbed into the blood stream.

In pregnancy, harmful substances in the mother's body may cross the placenta to affect the unborn baby.

Effects

Effects may be acute, i.e. of rapid onset and short duration; or chronic, i.e. of gradual onset and prolonged. They may be local, occurring at the site of contact only, or general following absorption. Toxic substances may disturb normal cell function, damage cell membranes, interfere with enzyme and immune systems and RNA and DNA activity. Pathological response may be irritant, corrosive, toxic, fibrotic, allergic, asphyxiant, narcotic, anaesethetic, and neoplastic.

Metabolism

Most substances absorbed will be carried by the blood stream to the liver where they may be rendered less harmful by a change in their chemical composition. However, some may be made more toxic, e.g. naphthylamine which is responsible for bladder cancer and tetra-ethyl lead which is converted into tri-ethyl form and is toxic to the central nervous system.

Excretion

The body eliminates harmful substances in the urine, lungs and less commonly the skin. Some are also excreted in the faeces and milk. The time taken to reduce the concentration of a substance in the body to 50% is known as its biological half-life. A knowledge of bio-chemical changes and excretory routes of products is important in the design of screening tests.

Factors influencing toxicity

A number of factors are important when considering the toxic effect of a substance on the body. These include:

  • The inherent potential of a substance to cause harm.
  • Its ease of body contact and entry: particle size and solubility.
  • Dose received (concentration and time of exposure.
  • Metabolism in the body (biotransformation) and its half-life.
  • Susceptibility of the individual which depends on a number of factors:
  • Body weight; the same dose of substance is more damaging to the smaller person.
  • The extremes of age in the working population are more prone to skin damage.
  • Fair skinned persons are more liable than the dark skinned to chemically induced dermatitis, and to radiation induced skin cancer.
  • Physical and physiological differences between the sexes may cause a variation in toxic response.
  • Failure to reach a health standard set for a particular job may expose the individual to greater risk.
  • The level of training, information, supervision and protection provided.

A no-adverse-effect level

In the setting of Occupational Exposure Standards (OES), which are health based exposure concentration limits, it is necessary to establish, with reasonable certainty, the airborne concentrations which will not result in ill-health even if inhaled day after day. This concentration may be derived from the no-adverse-effect-level in animal species which is arrived at after careful epidemiological and toxicological tests. This level relates to the average work person but will not apply to individual who, under certain circumstances, are susceptible and, therefore, at special risk.

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