Effects of Chemical Exposure on Organisms | Toxicology

In this article we will discuss about the acute and chronic toxic effects of chemical exposure on organisms.

Acute Toxic Effects:

Acute toxic effects are those that occur shortly after expo­sure to a relatively high dose of a toxicant. These effects occur rapidly as a result of short term exposure of a few hours, days or weeks to a chemical.

Asphyxiants, explosives, pyrophorics, organic peroxides, water reac­tive and unstable/reactive chemicals, corro­sives and poisons, typically produce acute effects. Generally, acute effects are severe causing lethality or mortality.

Acute Toxicity Tests:

Acute toxicity tests are designed to determine the dose or con­centration of a particular test chemical or effluent that will produce a specific response/ effect on a group of test organisms, under controlled conditions. The common tests are lethality, irritation studies and potentiation or sensitizing agents.

(a) Lethality (LC₅₀, LD₅₀) tests:

This is one of the most widely used tests to express acute toxicity. LC₅₀ is used to denote the lethal concentration necessary to kill 50% of a large population of test species under stated conditions. This is done experimentally by administering a chemical at a particular graded dose, to a group of organisms and then observing the resultant effect (mortality) at a set time period, say 96 hours or so. The test species are rats, mice, rabbits, guinea pigs, hamsters etc.

To calculate LC₅₀ a number of methods can be used of which three independent approaches are:

(i) Parametric method,

(ii) Moving average method, and

(iii) Non-parametric method.

The most frequently used LC₅₀ value calculation are parametric methods. If an asymptote has been reached in the toxicity curve (such as acute lethality has ceased), then the final value should be called incipient LC₅₀ on threshold lethal con­centration.

Test methods for acute toxicity are done in accordance to length of exposure, test situa­tion, criteria of effects and test organisms. In earlier acute toxicity tests, data were expressed as the median tolerance limit (TLm or TL₅₀).

It is expressed as the test material concentration at which 50% of the test organisms survive for a specific exposure time (usually 24-96 hours). This term has now been replaced by median lethal concen­tration (LC₅₀) and median effective concen­tration (EC₅₀).

There are several methods by which test organisms may be exposed to test materials. These methods, for example, in aquatic sys­tems, are static, recirculation, renewal or flow-through methods. Thus, a common acute testing approach is to design a test so that a quantal response (an all-or-none response that is dead or alive) is elicited. Then a concentration mortality curve can be plotted depending on the relation between test material concentration and the percen­tage of exposed organisms affected.

Such short term tests can be expressed as:

(i) The percentage of organisms killed or immobilised in each concentration, and

(ii) The LC₅₀ or EC₅₀ derived by observation, interpo­lation or calculation.

Test data on acute toxi­city tests conducted on sheepshead minnows are given in the Table 4.32:

LD₅₀ (Lethal median dose) toxicity test is the measure of the dose at which 50% of the test organisms (of the same species) are killed within a specified period. It essentially means that any one organism exposed to that close has a 50/50 chance of dying. If other than lethality, the effect of exposure to some toxic is of interest (example: loss of hair etc.), then ED₅₀ (effective dose) can be determined.

LD₅₀ (also ED₅₀) data are based on experi­ments or epidemiological studies, where the chemical is introduced into the organism through inhalation, injection etc. Fig. 4.69 illustrates the basic principles of an LD₅₀ test. A number of animals are exposed to the pollutant over a range of concentrations.

For convenience it is usually expressed as log dose. If this range is properly selected, a more or less normal distribution of responses will occur (Fig. 4.69A). This means that a small number of individuals will die at very low concentrations and only a few will sur­vive at very high concentrations, while majo­rity will die at over a range of intermediate doses.

If this data is redrawn by plotting the proportion of individuals at each dose (that is, the percentage response at each dose), then a sigmoidal dose-response curve will result (Fig. 4.69B). The final step is to straighten this line. Several methods are available enabling its slope (the rate of response to increasing dose) to be easily calculated.

This can be done by expressing the deviation from the mean as a probability unit or profit (Fig. 4.69C). The dose at which 50% of the population is killed can easily be read off the line. An environmental standard is based on the LD₅₀ by applying a safety margin by simply multiplying the value with some factor, say 0.1.

The concentration of the toxic chemical in the atmosphere or water, where the test organism lives is known in many cases but the amount actually taken into the organism is unknown. In such instances, LC₅₀ and EC₅₀ are used. Values of LD₅₀ and LC₅₀ are useful for defining relative toxicities. Evaluation of LD₅₀ in several animal species is a fair guide to the acute lethal toxicity of the same compound in man.

LD₅₀ values and commonly used categories of relative toxicity are given in Table 4.33. LD₅₀ is a calculated value and is accompanied by a statement of the error of the estimated value. The smaller the LD₅₀ values, the more toxic a chemical is and thus, the toxicants can be graded according to their LD₅₀ values (as given in Table 4.33).

LD₅₀ values are also useful in making an objective comparison of inherent toxicity of different compounds. The dose-effect curves for two different chemicals are shown in Fig. 4.70. Here, although both the chemicals A and B have equal LD₅₀s, incremental increase in dose results in greater increases in per­centage of population affected for chemical A than for chemical B.

The LD₅₀ method was originally devised to measure the toxicity of a range of drugs for human consumption at a time when no effec­tive method was available. Although LD₅₀ is widely used to assess the environmental toxicity of many pollutants it has a number of limitations, which are listed:

1. It is based upon a limited period of expo­sure.

2. It is based upon a single species.

3. A single test can only measure the impact on one sex or one stage of the life cycle.

4. It makes no allowance for the effect of a toxic burden on interactions with other species.

5. It makes no allowance for synergistic interactions with other pollutants.

6. The test is unable to measure the impact on the reproductive potential of a species.

7. The LD₅₀ toxicity test is insensitive to chronic toxic effects that may in the long term effect survival.

8. To assess the ecological impact of a pol­lutant, the effectiveness of the test relies upon the correct choice of a sensitive species.

9. The test organism has to be standar­dised for size, sex and health. It also has to be acclimatized to the test conditions before exposure to the pollutant.

In practice the LD₅₀ test conditions are a compromise between what is desirable and what is actually feasible. As for example, LD₅₀ tests are generally conducted on easily handled adult animals. However, the younger forms of these animals are more sensitive. Another example, is the larval crabs, the growth rate of these are most sen­sitive indicators of zinc and copper toxicity, but the rates are not easily or rapidly mea­sured.

(b) Skin and eye tests:

Skin and eye tests are conducted with chemicals that act as primary irritants. These when applied to the skin or mucous membranes lead to various types of tissue alternatives. These tests are conducted generally on rabbits, mice, guinea pigs etc. and the tissue damage is recorded subjectively.

For example, when these chemi­cals are applied to the eye of the test animals, the tissue response may lead to toxic mani­festations such as corneal damage and blind­ness. When inhaled it may destroy tissues in the respiratory tract. Awareness of such effects on primary tissues, for a specific chemical could alert individuals to handle the chemical with proper care.

(c) Potentiation:

Potentiation or sensi­tization means that when two chemicals are acting on the same or different organs or sys­tems, one chemical acts more effectively in the presence of the other. This potential sensitisation effect of chemical agents is a major problem to toxicologists. To distinguish between a substance acting as a primary irri­tant and one acting as a sensitizing agent, is another problem.

The primary irritant elicits its effects immediately on application, while the sensitizing agent may show no primary irritation. Sensitizing agent when applied or injected may combine with a protein molecule and act as an antigenic agent, which, in turn, produces antibodies. The tests are generally conducted on guinea pigs. In man, patch testing is often used, but only after preliminary animal sensitizing tests have been conducted.

Sub-acute Toxicity:

Sub-acute exposures comprise of instances where a population is exposed repeatedly to a toxicant over a period of several days or months. It gene­rally involves more than 21 days exposure. Such studies are carried out at three or more dose levels, in two or more species. One of the major objectives of such tests is to esta­blish a dose which could be classified as no effect dose. Anything above this dose would be considered as harmful to man.

Sub-acute toxicity tests also provide information on the major toxic effects of a chemical pollutant and the target organ affected (as given below):

Chronic Toxic Effects:

Chronic toxi­city effects are those that occur over long periods of time exposures (for decades on years), including effect of sensitizers and car­cinogens. For example, many lung cancers related to exposure to asbestos and cigarette smokes develop only after a long period of 40 years. As chronic effects become apparent only after a long period of exposure, they are particularly difficult to relate to a specific exposure of a particular toxicant.

Thus, our current state of knowledge regarding the potential effects of the more than 60,000 chemicals in daily commerce is more exten­sive in case of their acute effects than in their chronic effects. This is mainly due to the methodological difficulties involved in the scientific investigation of chronic effects, which, however, does not imply that chronic effects are of less concern.