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Toxicometrics is the scientific basis of hygienic regulation of toxic substances with which workers contact at the production or application.
A toxic substance
A toxic substance is a substance which at contact to an organism (at violation of safety rules) can cause poisoning, diseases or deviations in a state of health at contact period and in the remote terms of the life of the present and next generations and found out by modern methods.
Inhalation is the mainest way of penetration of chemical substances in to a working person organisme in ordinary conditions.
Other pathways may take place either at the accidental release of substances or violation of safety rules.
1. Penetration through a skin and mucous membrane is typical for unelectrolits, partially soluble in water (4,5 group by Lazarev`s coefficient) since penetration through bilipidic layer of cellular membranes and solubility in blood is necessary; contact duration and area, temperature. 2. Penetration through a stomach is defined by the character and the degree of stomach fullness, structure of the intestine`s microflora & its secretory function. Toxins come from the stomach into the liver where there its metabolism and detoxication take place (but not always).
Deposition of unelectrolits depends on blood supply of the body & sorbic capacity of tissues, physical and chemical properties of substance with a various degree of accumulation.
Second stage of biotransformation is realized by enzymes, for example, glucuronidase at reaction with the glucuronic acid.
Allocation of toxic substances The substances circulating in blood mainly are allocated through kidneys. The substances deposited in a liver (mercury, lead, manganese) get into an intestine with bile and are allocated with faeces. The substances with a low water solubility (benzene, toluene, chloroform, xylol) evaporate through lungs or with mother`s milk. Organic solvents are removed through lungs in an unchanged form. The chlorinated insecticides besides cumulate in a fatty tissue. They can be defined in a subcutaneous fat from a wall of a stomach. Alcohol and brominatad hydrocarbons can be found out in a saliva, benzene - in a bone brain, thiophose - in a secret of sweating glands. Mercury and CS4 are allocated with a secret of glands.
Toxic substances
Phosphorus organic insecticides (trichlorfon, nicotine, chemical war gases, etc.)
Dichloroethane, hexachloran, acetic inflammatory and necrotic changes in a essence, arsenic and its compounds, combination to the general toxic mercury (corrosive sublimate) resorptivic effect) General toxic effect (hypoxic spasms, a Hydrocyanic acid and its derivatives, coma, brain hypostasis, paralysis) carbonic oxide, alcohol and its substitutes, fighting poison gases Suffocating effect (toxic hypostasis of Nitrogen oxide, chemical war gases lungs) Tear gas and irritating effect (irritation A pair of strong acids and alkalis, of external mucous membranes) chloropicrin, fighting poison gases Effect on mentality (infringement of mental activity, consciousness) Chemical war gases, atropine
Neurotoxic substances
Those substances to which thresholds of sensitivity of nervous system are essentially below, than thresholds of sensitivity of other organs and systems, and infringements of motor and touch functions of nervous system and memory, thinking, emotions, behavior lay in a basis of their intoxication, are conditionally carried to neurotoxic substances even if mechanisms of their toxic action aren't known.
Selective toxicity
1. Cardiac with primary cardiotoxic action: many medical products, vegetative toxic substances, metal salts (salts of barium, potassium, cobalt, cadmium); 2. Nervous, causing mainly infringement of mental activity: carbonic oxide, organophosphorous compounds, alcohol and its substitutes, drugs, somnolent medical products, etc.; 3. Hepatic: first of all chlorinated hydrocarbons, phenols and aldehydes; 4. Nephritic: compounds of heavy metals, ethylene-glycol, oxalic acid; 5. Blood: aniline and its derivatives, nitrites, arsenous acid; 6. Pulmonary: oxides of nitrogen, ozone, phosgene, etc.
The force of narcotic action increases with increasing in number of carbon atoms in homological series of alyphatic hydrocarbons (unelectrolits, narcotic substances). The increasing of narcotic effect goes only up to a certain member and then decreases. That is connected with the sharp decreasing of the solubility. Exceptions: the first member of a homologous series (methane and its derivatives) as a role shows a specific effect (a methanol - defeat of an visual nerve).
Example 1. Narcotic effect amplifies in the series propane - butane pentane, then decreases down to absence of the effect owing to more intensive decreasing in solubility of the subsequent substances in comparison with increase in their toxicity. Example 2. Toxicity accrues in the series from methyl alcohol (3-) to pentyl alcohol (49-2-). If to accept force of narcotic action of ethyl alcohol for 1 unit, the other spirits are expressed as: methyl spirit (3) - 0,8; ethyl alcohol (25-) - 1; propyl alcohol (252-) - 2; butile alcohol(372-) - 3; pentyl alcohol (492-) - 4. Narcotic action of hydrocarbons is characterized by additivity of the effect. With strengthening narcotic action hemolytic action of the substances increases also.
CH3OH
177
C2H5OH
53.7
C3H7OH
18.2
C4H9OH
5.09
C5H11OH
2.09
C6H13OH
1.01
C8H17OH
0.53
7.43
4.11
0.80
0.44
0.18
0.06
0.02
3.6
3.47
2.36
1.95
1.33
The force of narcotic (toxic) effect is weakened at branching of carbon atoms chain. Example (alyphatic spirits). Propyl or butyl alcohol are stronger drugs than corresponding them iso-Propyl and isoButyl alcohols.
A Plenty of the chemical substances, differing by high toxicity, exists in the form of isomers which toxicity is various. Example 1. Para-isomers derivatives of benzene are more toxic, than meta-and rt-isomers: toxicity of isomers decreases in the series
para-> meta-> rt-.
Example 2. Among huge number of isomers of dioxins only 17 possess carcinogenicity (2,3,7,8).
Narcotic and irritating actions amplify at increase in number of multiple links in molecules.
The substances containing terminal halogen are more toxic, than the substances containing halogen, attached to a ring or the aromatic center. Example 3. Toxicity of chlorethylbenzene is expressed more, than ethylchlorobenzene. Cl-CH2-CH2-C6H5 > CH3-CH2-C6H4-Cl
Nitrogen-bearing substances acts just another than analogue without N-containing substances
Introduction in a molecule of benzene or toluene nitro groups -NO, -NO2 or amino -NH2 groups sharply changes character of action of the substances: Narcotic action of benzene and toluene containing NO, -NO2, -NH2 is not shown, It is shown specific action on blood (formation of methemoglobin), on the central nervous system, on parenchymatous organs (degenerate changes)
Example. For alkylethers of nitric and nitrogenous acids where groups -NO2 and -NO are connected with oxygen, there is typically vasodilating and vasohypotonic action (ethyl nitrite, amyl nitrite, ethyl nitrate, nitroglycerine).
Expansion of a molecule increases the probability of interaction of toxic substances with a biosubstratum (receptor) due to Van der Waals forces.
Endogenic bioregulators (neurotransmitters, hormones) cooperate with receptors basically due to weak Van der Waals forces. Then more a molecule volume of a toxic substance, then greater number of its atoms contacts to a receptor-target site at linkage. Flexibility of conformational structure of a toxic substance molecule promotes affine linkage. Those toxic substances, which molecular structure is similar to a structure of endogenic biologically active substances, enter interaction with receptors, simulating their effects and carrying out agonist function.
Example. This mechanism underlies toxic action of many alkaloids (nicotine, anabasine, etc.), glycosids, synthetic toxic substances, etc.
If a toxic substance has essentially greater volume, than natural agonist its strong fixing on a receptor is carried out due to Van der Waals forces. It leads to shielding of receptors from substances-agonists or to their block (antagonists).
Example. Atropine and curarin accordingly to -and - cholinergic receptors operate by this way.
Occupational aerozoles
Occupational aerosols dissolved in water (consequently in blood, lymph, extracellular and intracellular liquids) are considered as chemicals. Occupational aerosols undissolved in water are considered as fibrogenic dust causing fibrogenesis in lungs (occupational pneumoconiosis)
bad solubility in water; presence of an electric charge on dust particles; a crystal structure; the wrong (not spherical) form of particles; average dispersiveness (0,1 up to 10 microns) , the maintenance of a dioxide of silicon.
WHO carries a fine dust to very dangerous with stochastic effect. The CART denies presence of a threshold of action of an aerosol with the size of particles 10 microns and less.
The stochastic (unthreshold) effect is shown that already at very small concentration in air at a part of the exhibited persons probably development of pulmonary diseases
3. On way of formation: an aerosol of decomposition (at crushing, grinding, polishing, cotton fiber pulling in textile industry and other processing of firm materials) and an aerosol of condensation (at receipt of steams of fused metals or other firm substances in rather cold air).
Variants of pneumoconiosis
Silicosis is caused by a dust containing a dioxide of silicon SiO2 Silicatosis - silicate dust: asbestosis, kaolinosis, talcosis Antracosis, coal worker pneumoconiosis - coal (anthracite) dust Berylliosis metalloconiosis (berulium) Metalloconiosis: siderosis (iron oxide), berilliosis from a dust of a beryllium, aluminosis, stannosis (tin oxide), and baritosis (barium sulfate particles) Bissinosis - dust of a cotton, Bagassosis - dust of a sugar cane. Farmer's lung plant vegetable dust
Silicosis
The reason is the dust with the high maintenance of a dioxide of silicon (more than 70 %). 1 stage - poured fibrosis of lungs (on the roentgenogram blackout at roots of lungs) and dry cough, 2 - presence of the concentrated fibrous formations revealed only by means of a roentgenography (the roentgenogram as a snow storm ), strong cough with a sputum, 3 - global defeat of lungs with a massive fibrosis, the strongest cough with a sputum and blood (hemoptysis) (in 80 % the tuberculosis joins). Death rate is very high. The latent period - from 46 working days till 1 year.
Byssinosis - occupational lung disease caused by inhalation of dust from cotton, flax, hemp or sisal. The patient always feels a sense of tightness in the chest and stridor after the weekend, which takes place during the week. The cause of the disease has not been established.
Bagassosis (sugar cane waste) - allergic alveolitis caused by repeated inhalation of dust extraction product of sugar cane (bagasse) from the contained spores of fungi.
A 66 year old man had inhaled cotton fibre for 50 years at his workplace. He did not have any respiratory symptoms. Chest CT scans revealed diffuse centrilobular and peribronchovascular interstitial thickening. Lung biopsy specimens confirmed the presence of string-like foreign bodies as well as granulomas and fibrosis in the peribronchial region. Infrared spectrophotometry confirmed that the foreign bodies were composed of natural cellulose. This is the first study to show directly by examination of biopsy samples that cotton fibre inhalation can cause diffuse lung disease. The clinical features of the disease were entirely different from those of byssinosis [H Kobayashi, S Kanoh, K Motoyoshi, S Aida. Diffuse lung disease caused by cotton fibre inhalation but distinct from byssinosis// Thorax 2004;59:1095-1097].
MPC
3. establishment and sanitary observance of maximum permissible concentration of aerosols in air of a working zone:
>70 % of SiO2 in dust = 1 mg/m3, from 10-69 % SiO2 = 2 mg/m3, SiO2 <10 % = 4 mg/m3, Without SiO2 =10 mg/m3
asbestos and glass dust = 2 mg/m3, soot = 4 mg/m3, anthracene dust = 5 mg/m3. flour dust = 6 mg/m3 untoxic sugar and coal dust = 10 mg/m3 + many mixed dust on specific technology
Individual defence
- respirators of disposable use or with replaceable filters, antidust glasses and overalls from a dustrepulsive material (cotton impregnated by dustrepulsive chemical substances)