2. WHAT IS TOXICOLOGY
The work is carried out in two phases: first by collecting data on the properties of chemicals, results of studies and accidental misuse of chemicals, second by predicting the effects of chemicals in different situations.
To make relevant predictions there must be information available on:
Large amounts of toxicological information are collected into data bases and data banks.
For many substances the greatest effects and the most rapid responses occurs when the substance is inserted directly into the blood circulation. In toxicological animal experiments the routes of exposure may be:
Classification may be based on the LD50 and LC50 values (see Annex 8A in 'Identification, Classification and Labelling of Chemicals' and 'Major Hazard Chemicals'). The assessment of the effects is tested in laboratories using animals, mainly rats, mice and rabbits.
The test substance or preparation may be applied to the animal orally, under the skin, by inhalation, into the abdomen or into the vein. LD50 and LC50 are the parameters used to quantify the results of different tests so that they may be compared.
LD50 is the abbreviation used for the dose which kills 50% of the test population.
LC50 is the abbreviation used for the exposure concentration of a toxic substance lethal to half of the test animals.
LD50 is expressed in milligrams per kilogram of body weight of the test animal (which must be mentioned).
LC50 is expressed in millilitres per kilogram of body weight of the test animal (which must be mentioned), exposed to the substance by inhalation during a specified period. The variation in the numerical values of LD50 and LC50 is wide.
The following list describes the variation in LD50 values measured in ingestion studies on the rat:
________________________________________ Substance LD50 (mg/kg, oral, rat) ________________________________________ Vitamin C 11 900 Ethyl alcohol ('alcohol') 7 060 Citric acid 5 040 Sodium chloride (table 3 000 salt) Ferrous sulphate 320 Dieldrin 38 Parathion 2 Dioxin (contaminant in 0.02 herbicide) ________________________________________It is important to mention the species on which the test was conducted because the numerical values of LD50 and LC50 depend on several factors, such as the biological system or animal, strain, sex, age and diet. The LD50 of DDT insecticide administered orally is 87 mg/kg of body weight for a rat but 150 mg/kg of body weight for a dog. The LD50 for dioxin is 0.02 mg/kg of body weight for a rat and 0.001 mg/kg of body weight for a dog, i.e. the rat is twenty times more tolerant than the dog.
The assessment of how a human system would react is not straightforward estimation from the animal tests. However, the animal test gives an idea of the level of the toxic effects.
There are different kinds of limit values. The TLVs (Threshold Limit Values) are published by the American Conference of Governmental Industrial Hygienists (ACGIH) and concern the airborne concentrations of hazardous substances. They set a limit concentration below which it is believed that nearly all workers can be repeatedly exposed day after day without adverse effect. The TLVs are regularly reviewed and corrected when new information becomes available.
There are two main ways in which chemicals may exert their effects. Local effects occur at the area of the body which has been in contact with the chemical. Examples are injuries from acids or lung injuries from inhaled reactive gases. Systemic effects occur after the chemical has been absorbed and distributed from the entry point to other parts of the body. Most substances produce systemic effects, but some substances may cause both types of effects. An example is tetraethyl lead, which is a gasoline additive and produces skin effects at the contact site. It is absorbed and transported into the body causing typical effects on the central nervous system and on other organs.
The degree of the toxic effect is not the same in all organs. Usually there are one or two organs which show the major toxic effect. These are referred as target organs of toxicity of the particular substance. The central nervous system is the target organ of toxicity most frequently involved in systemic effects. The blood circulation system, liver, kidneys, lungs and skin follow in frequency of systemic effects. Muscle and bones are the target organs for a few substances. The male and female reproduction systems are vulnerable to many substances.
An allergic reaction, or sensitization as it is also called, may appear after repeated contact to a substance. Once the sensitization has bee produced, even very low doses can provoke a reaction. The different allergies are numerous, varying from minor skin irritation to very severe or even fatal reactions.
The pattern of sensitization varies according to the species. In humans, the skin and the eyes are the most common areas of allergic response, whereas, for example, in the guinea pigs reactions are more common in the respiratory system.
The effect of simultaneous exposure to two or more substances may differ from a simple additive effect (1+1=2). Organophosphate pesticides, such as dialiphos, naled and parathion, are examples of chemicals where the combined effect is the sum of the effects observed when the chemicals act individually.
The effect can be more than the sum of the individual effects of two chemicals (e.g., 1+1=4). An example of an increase in risk is with asbestos fibres and cigarette smoking. They act together: the risk of developing lung cancer after exposure to asbestos fibres is forty times greater for a smoker than for a non-smoker. Another pair of the chemicals where the combined risk is greater than a mere additive effect are the solvents, trichloroethylene and styrene.
The adverse effects of two substances may counteract one another (1+1=0). This effect is used to find an antidote to a poison.
In other cases, a substance may not cause harm on its own but may make the effect of another chemical much worse (0+1=3). For example, two commonly used solvents isopropanol and carbon tetrachloride have this kind of joint effect. Isopropanol, at concentrations which are not harmful to the liver, increases the liver damage caused by carbon tetrachloride.
In some cases, when the exposure to a substance is repeated the body may decrease its sensitivity to the substance, i.e. it increases its tolerance to it.
In the natural environment, large numbers of potentially toxic substances are present. In some cases, when the substance is on its own it would cause no harm but it may interact with other toxic substances or under specific conditions it may be concentrated or transformed to a more dangerous compound.
An example of an air pollution reaction is the production of photochemical smog. Chlorinated hydrocarbons such as DDT and dieldrin have similar chemical and biological effects. When present together they lead to more serious effects than when acting separately.
To assess the effects of toxic substances in the environment some indicators of ecotoxicity are used.
In laboratory, fish and insects called Daphnia (water-flea) are used to test acute toxic effects in the aquatic environment. Green algal species are also used in the assessment of water pollution.
ANNEX 1. Factors that may influence the human
reproduction system and the effects
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