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Toxicology 



Introduction 

'All substances are poisons - the difference is in the dose' 

The above aphorism is attributed to Paracelsus. It illustrates that the potential for harm is widespread and all chemicals could be toxic but the degree of harm that a chemical can inflict on a human or any other living being depends on the dose or the degree of exposure as well as on other factors. 

In other words the risk (i.e. that product of the likelihood and the severity of harm) from a toxic hazard depends on the exposure

This account is intended for those with little or no background in toxicology. Toxicology is a complex and difficult science. In an attempt to make it more understandable, many broad generalisations are made, without detailing the mechanisms or addressing the exceptions. This page must therefore be interpreted cautiously.


Chemical hazards in the workplace and in the environment

People may be exposed to a range of toxic chemicals at work or in the general environment. Here are some examples:

Category

Examples

Metals, and metalloids  arsenic, cadmium, lead, mercury, nickel, tin, etc
Inorganics (other)  asbestos, carbon monoxide, hydrogen sulphide
Hydrocarbons - aliphatic  propane, butane, pentane, hexane
Aliphatic alcohols, ketones, ethers, aldehydes and acids  ethyl alcohol (ethanol), acetone, diethyl ether, formaldehyde, acetic acid
Hydrocarbons - aromatic  benzene, toluene, xylene, naphthalene
Phenols  phenol, pentachlorophenol
Chlorinated volatile organic compounds  perchlorethylene (tetrachloroethene), trichloroethylene (trichloroethene), vinyl chloride
Chlorinated non volatile organic compounds  chlorinated dioxins and dibenzofurans, polychlorinated biphenyls, pesticides such as chlordane and DDT
Miscellaneous organic compounds  acrylonitrile, benzidine, aniline, di-isocyanates, organophosphates
The exact chemical identity (the 'species') of a substance can make a very big difference as regards its toxicity. This concept is called 'speciation'. 

For example asbestos is a complex chemical compound containing atoms such as potassium, sodium, magnesium, aluminium, silicon and others which in a different context would have a much lower toxicity than they exhibit in the compound of asbestos. 

Chromium in the hexavalent state (Cr VI) is a human carcinogen (as in the orange coloured potassium dichromate or bichromate) while trivalent chromium (Cr III) (as in the green coloured chromium III chloride) appears not to be. If the chromium is in the Cr III form and oxidation to Cr VI is prevented, exposure should present no cancer risks. 

Nickel tetracarbonyl (Ni(CO)4) is a highly toxic gas inflicting severe damage to the lungs and heart, while nickel carbonate (NiCO3) is a solid which is much less hazardous. Metallic nickel probably poses no cancer risk at all while nickel subsulphide is almost certainly a very highly carcinogenic and dangerous compound which has been responsible for many sad deaths. 


Toxicokinetics

- or how the body handles poisons

Absorption into the body

  • As a general rule, fat soluble liquids are readily absorbed through the skin and fat soluble vapours are readily absorbed through the lungs. Notably these routes apply to organic solvents such as hexane, toluene, trichlorethylene and many others. 

Distribution within the body

  • Many factors affect the distribution of a toxic substance but water or fat solubility is very important. Thus for example water soluble compounds of lead are found (amongst other places) in the red blood cells, while fat soluble ones concentrate in the central nervous system (CNS).
  • The distribution of a toxic substance determines its concentration at a particular tissue and therefore the number and type of cells exposed to high concentrations of it. 

Metabolism/ biotransformation of toxic substances

  • Toxic substances may be converted into other substances (metabolites) by organs such as the liver and kidneys
  • Thus non-polar and therefore not water soluble organic compounds tend to be oxidised within the liver e.g.:
    • trichloroethane oxidised to trichloroethanol trichloroacetaldehyde and trichloroacetic acid
    • dichloromethane (methylene chloride CH2Cl2) oxidised to carbon monoxide (CO)
  • Water soluble metabolites are then more easily excreted by the kidney (see below)
  • Metabolism or biotransformation does not necessarily result in less toxic compunds. For example benzene may be oxidised to an expoxide which then inflicts damage on the DNA in genes, i.e. it is genotoxic and thence carcinogenic

Routes of elimination of toxic substances / or their metabolites

  • Kidneys - especially water soluble substances
  • Lungs - especially fat soluble vapours e.g. - alcohols, or gases such as carbon monoxide

Toxicodynamics

- or what poisons may do to the body

A note on terminology: 
  • Acute effects refer to the short term consequences of  exposure
  • Chronic effects relate to a much longer time scale, while  sub-acute are in between acute and chronic)
  • Some effects may be dose related - the higher the exposure the worse it gets e.g. irritant effects on the skin, asthma, asbestosis etc
  • Other effects are 'all or none' and for a given exposure there is an element of chance (stochastic) as to whether or not the disease develops e.g.the development of cancer (carcinogenesis) or some forms of developmental damage to the foetus (teratogenesis)

Irritant effects:

  • detergents may remove fat from the skin and cause dermatitis 
  • cement dust being alkaline may irritate the skin, or cause more severe damage (chromates within cement may also cause sensitisation and allergic dermatitis).
  • respiratory irritation may be caused by low concentrations of formaldehyde vapour

More serious inflammation:

  • more toxic agnets and/or higher exposures may be associated with damage resulting in inflammation for example of terminal bronchioles and alveoli leading to a chemical pneumonitis and pulmonary oedema (e.g. from nitrogen dioxide NO2)

Corrosive effects: 

  • severe local effects by contact e.g. caustics such as sodium hydroxide, or acids such as sulphuric, nitric or hydrochloric acid. 

Narcotic and anesthetic effects: 

  • fat soluble solvents will behave as anaesthetics and cause drowsiness, nausea, headache, unconsciousness and death e.g. vapours from organic solvents such as ether or trichlorethylene

Asphyxiation: 

    Various gases can cause asphyxia by interfering with oxygen transport. Examples: Carbon monoxide, Hydrogen cyanide, Hydrogen sulphide. Carbon monoxide is present wherever there is incomplete combustion of carbon compounds. It is odourless, and will react with haemoglobin (Hb) to form COHb which cannot carry oxygen.. Hydrogen sulphide might initially be detected by its smell at low concentrations but it paralyses the sense of smell and can effectively become odourless. Hydrogen cyanide: in the form of its salts sodium and potassium cyanide is used in many industries and the organic cyaniden acrylonitrile (vinyl cyanide) is used in the rubber industry. Absorption can also occur through the skin. At low concentrations these gases poison cytochromes and cause the rapid onset of headache, dizziness, vomiting and confusion.  At high concentrations they are very rapidly lethal. 

Other effects  on specific organs:

You may wish to refer to another resource on specific organ damage, but here are some other points: 
  • 'Heavy' metals e.g. Pb (lead) Cd (Cadmium) and Hg (mercury) have a propensity to bind sulphur and indeed in nature in the earth's crust are often found as sulphides. they tend to bind to sulphydryl groups -SH in enzymes and other proteins and cause damage in various parts of the body
  • The lungs are often the subject of damage e.g paraquat poisoning
  • Cardiovascular effects include arrhythmias e.g. caused by trichloroethane or by carbon disulphide
  • A very specific effect of exposure to some poisons such as the organophosphate insecticides (e.g. malathion, parathion) relates to their anticholinesterase effect. Synaptic transmission from a nerve cell to another cell such as a muscle cell in many situations relies on acetyl choline. The enzyme  acetylcholinesterase in nerve endings catalyses the hydrolysis of acetylcholine to choline and acetylCoA, thus determining a very short action of acetylcholine. Organophosphate and carbamate pesticides inhibit acetylcholinesterase and lead to accumulation of acetylcholine at sites of  neuromuscular transmission causing weakness of muscles, and paralysis including of respiration.
  • Endocrine mimicking agents can act as endocrine disrupters

Sensitisers: 

These provoke an immune response (sensitisation) resulting in asthma, rhinitis, allergic dermatitis e.g. diisocyanates, glutaraldehyde, nickel

Carcinogens:

e.g. vinyl chloride causes hepatic haemangiosarcomas, benzene is a genotoxic carcinogen. Occupational exposures to high concentrations of benzene have shown to increase the likelihood of an individual developing leukaemia; the added risk incurred as a result of being exposed to 1 ug/m3 of benzene for a lifetime is about 4 X 10-6. 

Other effects on DNA:

  • Mutagenic effects: inherited defects by DNA damage e.g. alkylating agents such as mechlorethamine

  • Teratogenic: Damage to foetus, not necessarily damaging the mother e.g methyl nitro nitroso-guanidine (MNNG). 

Prevention and treatment

Preventing exposure: 

Through the practice of good occupational hygiene

Treatment: 

  • Decontamination e.g. eye washes, showers, etc 
  • Antidotes e.g. methylene blue for treating methaemoglobinaemisa caused by aniline
  • Other treatment e.g. oxygen for asphyxia

Note:

    For a more detailed account of occupational and environmental toxicology, another resource comes strongly recommended.