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BIOL272 Investigative Methods
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Toxicity 

Toxicity is a measure of how poisonous a substance is, or how large a dose is required to kill or damage an organism; the more toxic a substance, the smaller the lethal dose. Although the concept of toxicity appears to be straightforward, measuring it is subject to many complicating factors.

Toxicity Testing

There are many different ways in which toxicity can be measured. Most commonly, the measure (‘end-point’) is death, although there is growing interest in the use of more sophisticated indices. The desire to minimise lethal toxicity testing with vertebrate animals is a significant driving force here. Biochemical, physiological, reproductive and behavioural effects can all provide measures of toxicity. Many toxicity tests provide estimates of the dose (or the concentration in food or water) which will cause a toxic response at the 50% level, eg the median lethal dose is the dose that will kill 50% of a population. It is also possible – and this approach is gaining in popularity – to establish the highest concentration or dose that will not cause an effect.

Several terms used in relation to toxicity testing require definition. First, in lethal toxicity testing, LD50 represents the median lethal dose, whereas LC50 represents the median lethal concentration. In toxicity tests which determine these values, it is also possible to determine the highest doses or concentrations which cause no toxicity – the no observed effect dose (NOED) and no observed effect concentration (NOEC) respectively. These values can only be determined in situations where a higher dose or concentration has produced an effect in the same toxicity test. These points are illustrated in the Fig ??, which refers to the determination of an LC50 after 96 hour exposure. If a test is carried out where the end-point is an adverse response other than death, then an EC50  or ED50 is determined. Here the concentration or the dose producing the effect in 50% of the population is determined. As with lethal toxicity testing it is possible to determine NOEC or NOED following this approach. However, values for NOED or NOEC are only meaningful in a test in which a higher dose has been shown to produce an effect.

Laboratory testing

Laboratory ecological tests are designed to evaluate both acute and chronic effects. Laboratory acute tests are designed to evaluate effects resulting from short-term (a few days) exposure to relatively high concentrations of a test substance. Typically, the end-point of the test is mortality. Chronic tests are designed to evaluate effects from longer-term (several weeks) exposure to relatively low concentrations of a test substance. End points of the test are usually mortality, reduction of gropwth or reproductive performance or both.

Similar principles apply to tests with both terrestrial and aquatic organisms. Groups of the test organism are exposed to a range of concentrations of the test substance (often arranged in a geometric series of concentrations) for a pre-determined period. At intervals and at termination of the exposure period, the groups are scored for effects.

The results of the scoring exercise are analysed statistically to determine the concentrations which, it is predicted, would result in a given magnitude of effect over a particular exposure period. In acute toxicity tests, LC50 or EC50 values are determined. These values represent the concentration which it is calculated that 50% of the exposed animals would die (LC50) or otherwise being affected if a different end-point criterion is being used (EC50). These values are usually prefixed by the duration of the exposure period (often 48hrs).

Thus the results from a series of tests could be used to predict that exposure to a solution of a toxic substance (eg a solution of copper) at a concentration of 5 mg l-1 would resulted in the death of 50% of the test organisms (eg Daphnia) after 48 hrs exposure. Statistical procedures for calculating the value from acute toxicity test data include probit analysis (REF).

Ecotoxicological studies are designed to form part of the process for predicting the likely hazard associated with the manufacture, transport, use or disposal of a substance. It contributes to environmental exposure assessment through the determination of concentrations re3sulting from chemical application in field experiments that are designed to represent either realistic application conditions or ‘worst-cases’.

Assessing toxicity of a substance can be achieved using one of two approaches:

1                    Prediction on the basis of its molecular structure using Quantitative Structure Activity  Relationships (QSARs)

2                    Measurement using model test systems

Test systems used to measure the toxicity of a substance range from relatively simple laboratory tests to more complex field tests involving natural or semi-natural communities.

Laboratory tests are designed to evaluate both chronic and acute tests. Chronic tests are designed to effects resulting from longer-term (usually several weeks)