How Do Reachers Introduce Toxicant To Lab Animals

2. Exposure

To have an adverse effect a substance must be able to enter the organisation. The exposure depends of the amount of substance and the period during which information technology affects the target, east.k. humans, animals or bacteria.

two.i Routes

The major routes through which the toxic substances may enter the body, under normal working condition, are: inhalation, through the skin and ingestion.

For many substances the greatest effects and the most rapid responses occurs when the substance is inserted direct into the claret circulation. In toxicological animal experiments the routes of exposure may be:

• Inhalation (animate in)
• Assimilation (through the pare or eyes)
• Ingestion, oral (eating, swallowing)
• Transfer beyond the placenta to the unborn baby
• Intravenous (injection into the vein)
• Intramuscular (injection into the muscle)
• Subcutaneous (injection under the skin)
• Intraperitoneal (injection within the membrane that lines the interior wall of the abdomen)

two.2 LD50 and LC50

For different substances the doses needed to produce an agin effect varies widely. LD50 values are used to compare astute toxicity.

Classification may exist based on the LD50 and LC50 values (run into 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 exam animate being (which must be mentioned).

LC50 is expressed in millilitres per kilogram of body weight of the examination creature (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 listing describes the variation in LD50 values measured in ingestion studies on the rat:

________________________________________ Substance                  LD50 (mg/kg,                            oral, rat) ________________________________________ Vitamin C                  xi 900 Ethyl booze ('booze')  7 060 Citric acrid                5 040 Sodium chloride (table     three 000 salt) Ferrous sulphate           320 Dieldrin                   38 Parathion                  2 Dioxin (contaminant in     0.02 herbicide) ________________________________________

Information technology is of import 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 arrangement or animal, strain, sex, age and diet. The LD50 of DDT insecticide administered orally is 87 mg/kg of body weight for a rat simply 150 mg/kg of trunk 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 torso 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. Nevertheless, the fauna test gives an idea of the level of the toxic effects.

2.three Limit values

In guild to control toxic effects, there is a need to prepare priorities, goals and strategies. In places of work one way is to gear up limit values to guide the users. Occupational limit values are based on the best available information from industrial experience, from experimental laboratory studies and from accidents. They are informed and negotiated compromises, not stock-still safety standards.

In that location are dissimilar 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 gear up a limit concentration below which it is believed that nearly all workers tin can exist repeatedly exposed twenty-four hour period after day without adverse effect. The TLVs are regularly reviewed and corrected when new information becomes available.

TLV-TWA (Threshold Limit Value - Time Weighted Average) is a time-weighted average concentration for an eight hr working day or 40 hours a week to which almost all workers may be repeatedly exposed without adverse result.

TLV-STEL (Threshold Limit Value - Curt Term Exposure Limit) is the concentration to which workers may be exposed for a curt fourth dimension (usually 15 minutes) without suffering from irritation, long-term or irreversible tissue impairment or damage likely to increase accidental injury, affect self-rescue or reduce work efficiency. Daily TLV-TWA values should not exist exceeded.

TLV-C (Threshold Limit Value - Ceiling) is a concentration that should non be exceeded at all during work exposure.

iii. What are the responses of a system when exposed to poisons?

The human torso needs very pocket-sized quantities of some chemicals that are poisonous in large doses. This applies, for example, to some metals, such every bit copper, magnesium and manganese, which pose a problem in places of piece of work. The adverse effect is strongly related to the dose. The ultimate upshot is death. Commonly the effects of toxic chemicals are less astringent, from altered food consumption to serious wellness issues.

3.1 Human torso

The effects may exist immediate or delayed, and they may be reversible or irreversible toxic furnishings (see Part ane., Introduction to Rubber in the Use of Chemicals).

Local/systemic toxicity

There are two main ways in which chemicals may exert their furnishings. Local furnishings 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 furnishings occur after the chemic has been absorbed and distributed from the entry point to other parts of the body. Most substances produce systemic effects, simply some substances may cause both types of furnishings. An example is tetraethyl lead, which is a gasoline condiment and produces skin effects at the contact site. Information technology is absorbed and transported into the body causing typical effects on the central nervous system and on other organs.

Target organs

The degree of the toxic effect is not the same in all organs. Usually there are one or 2 organs which show the major toxic effect. These are referred as target organs of toxicity of the particular substance. The cardinal nervous system is the target organ of toxicity almost frequently involved in systemic effects. The claret circulation organization, liver, kidneys, lungs and skin follow in frequency of systemic effects. Musculus and bones are the target organs for a few substances. The male person and female reproduction systems are vulnerable to many substances.

• Skin is the largest organ in the human body, 1.5-2 thou² in area. It provides a protective cover to the body just tin fail if the load is overwhelming. A number of substances can penetrate healthy intact peel and enter the claret circulation. Phenol is a substance that may fifty-fifty result in death later exposure and penetration through the skin. The vast bulk of piece of work-related skin diseases are contact eczemas, irritation and inflammation of the pare. This condition tin can be either a non-allergic or allergic reaction to exposure to chemic substances. Examples of common contact sensitizers are several colorants and dyes, metals such equally nickel and its salts, chromium and cobalt salts and organomercuric compounds, monomers of a number of acrylates and methacrylates, safety additives and pesticides. In exercise chemical skin injury is too influenced past ecology conditions such as humidity and heat.
• The lung is the major route through which toxic substances in the workplace enter the body. It is also the first organ to be afflicted past dusts, metal fumes, solvent vapours and corrosive gases. Allergic reactions may be caused by substances such as cotton wool dust, TDI (toluene diisocyanate, used in the manufacture of polyurethane plastics), and MIC (methylisocyanate, used in production of carbaryl insecticide). In a catastrophic chemical accident in Bhopal, India, in 1984, more than 2000 people died from exposure to MIC. Allergic reactions may outcome from exposure to bacteria or fungi: this is the example in allergies from handling stocked hay (`farmer's lung') or dried sugar pikestaff. When grit particles of a sure size of some substances are inhaled the lungs are unable to remove them. They become embedded in the lung causing a condition chosen pneumoconiosis. Pneumoconiosis is mainly a problem for workers exposed to the dust of silica (quartz) and asbestos, and is the commonest non-malignant occupational lung disease throughout the world. Other substances, such as formaldehyde, sulphur dioxide, nitrogen oxides and acrid mists may cause irritation and reduce the animate capacity.
• The nervous organisation, the `mystery of matter and mind', is sensitive to the hazardous furnishings of organic solvents. Some metals affect the nervous system, especially heavy metals such as pb, mercury and manganese. Organophosphate insecticides such as malathion and parathion interfere severely with information transmission (chemical neurotransmitter role) in the nervous system, leading to weakness, paralysis and sometimes death.
• The blood apportionment is a target for the adverse effects of solvents. Blood cells are mainly produced in the bone marrow. Benzene affects the bone marrow; the beginning sign is mutation in the blood cells called lymphocytes. To study mutation, lymphocytes are cultured in the laboratory to notice specific types of cellular changes. Lead, in the grade of the metal or its compounds, is another archetype example of a chemical that may cause blood problems. Atomic number 82 in the blood may inhibit certain enzyme activities involved in the product of hemoglobin in cherry-red claret cells. Chronic lead poisoning may consequence in a reduced ability of the blood to distribute oxygen through the body, a condition known as anaemia.
• The liver is the largest of the internal organs in the body and has several of import functions. It is a purification plant which breaks down unwanted substances in the blood. The liver has a considerable reserve capacity; symptoms of liver disorder announced only in serious diseases. Solvents such as carbon tetrachloride, chloroform and vinyl chloride, equally well as alcohol, are hazardous to the liver.
• The kidneys are role of the body's urinary organization. They have the task of excreting the waste products that the blood has transported from various organs of the body, of keeping the fluids in residue and of ensuring that they comprise an adequate blend of diverse necessary salts. They also maintain the acidity of the claret at a constant level. Solvents may irritate and impair kidney role. The most hazardous to the kidneys is carbon tetrachloride. Turpentine in large quantities is also harmful to the kidneys: `painter'south kidney' is a known condition related to occupational exposure. Other well-known kidney- damaging substances are pb and cadmium.

Allergic reactions

An allergic reaction, or sensitization as information technology is too chosen, may announced 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 pocket-sized skin irritation to very severe or fifty-fifty fatal reactions.

The design 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.

Interactions

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 result tin be more than the sum of the individual effects of ii chemicals (e.g., i+i=iv). An example of an increment in risk is with asbestos fibres and cigarette smoking. They act together: the chance of developing lung cancer after exposure to asbestos fibres is forty times greater for a smoker than for a non-smoker. Some other pair of the chemicals where the combined take a chance is greater than a mere additive effect are the solvents, trichloroethylene and styrene.

The adverse furnishings of two substances may counteract one some other (ane+i=0). This result is used to find an antidote to a poisonous substance.

In other cases, a substance may not cause impairment on its own but may make the effect of some other chemical much worse (0+1=3). For case, two usually used solvents isopropanol and carbon tetrachloride accept this kind of joint effect. Isopropanol, at concentrations which are not harmful to the liver, increases the liver harm 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.due east. it increases its tolerance to information technology.

3.2 The surroundings

The surroundings has a certain capacity to biodegrade toxic substances. Even so, some substances are resistant to decomposing processes. The agin effects increase with the concentration of these substances and their accumulation in foodchains.

In the natural surround, large numbers of potentially toxic substances are present. In some cases, when the substance is on its own it would crusade no harm but information technology may interact with other toxic substances or nether specific weather it may be concentrated or transformed to a more dangerous compound.

An instance 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 nowadays together they lead to more serious effects than when acting separately.

To assess the furnishings of toxic substances in the environment some indicators of ecotoxicity are used.

In laboratory, fish and insects called Daphnia (h2o-flea) are used to test acute toxic effects in the aquatic environment. Green algal species are also used in the cess of water pollution.

ANNEX 1. Factors that may influence the human reproduction organization and the effects
ANNEX 2. Substances able to produce occupational lung diseases
ANNEX 3. Route of assimilation, distribution and excretion of potentially toxic substances
ANNEX 4. Pregnant woman at work

BIBLIOGRAPHY

ARBETSMILJÖ (Working Environment/ The Piece of work Environment Association), Your trunk at work, 2nd Ed., Stockholm 1987

CLAYTON Chiliad.D. and CLAYTON F.E., ed., Patty's Industrial Hygiene and Toxicology, third Revised Ed., John Wiley & Sons Inc., Us 1978

Eastward African Newsletter on Occupational Wellness and Condom, Supplement 2/ 1989, Institute of Occupational Health, Republic of finland 1989

ILO, International Labour System, Encyclopedia of Occupational Wellness and Safety, Vol I - Iii, Geneva 1983

IPCS, International Programme on Chemical Safety, Chemical Condom, Fundamentals of Applied Toxicology, Training Module No one, Geneva 1992

IPCS, International Plan on Chemical Safety, How to use the IPCS Health and Safety Guides

KLAASSEN C.D., AMDUR M.O. and DOULL J., ed., Casarett and Doull's Toxicology, The Basic Science of Poisons, 3rd Ed., Macmillan Publishing Visitor, New York 1986

NIOSH, RTECS Database, CCINFO Disc, Canadian Heart for Occupational Health and Safety, Hamilton 1993

SAX Northward.I. and LEWIS R.J.Sr, Unsafe Backdrop of Industrial Materials, 7 ed., Nostrand Reinhold Co., New York 1988

SEILER H.G. and SIGEL H., Handbook of Toxicity of Inorganic Compounds, Marcel Dekker, Inc., New York 1988

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Updated by AS. Approved by EC. Last update: 30.eleven.2004.

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