TYPES OF HEALTH EFFECTS.docx

**TYPES OF HEALTH EFFECTS** **3.1 ASPHYXIATION** An asphyxiant is a substance that can reduce the level of oxygen in the body to dangerous levels. Asphyxiants can be divided into two general types. 1. Simple asphyxiants (e.g. nitrogen, argon) - they are chemically inert but prevent normal re...

**TYPES OF HEALTH EFFECTS** **3.1 ASPHYXIATION** An asphyxiant is a substance that can reduce the level of oxygen in the body to dangerous levels. Asphyxiants can be divided into two general types. 1. Simple asphyxiants (e.g. nitrogen, argon) - they are chemically inert but prevent normal respiration by reducing the oxygen level in the air. This may occur by the asphyxiant simply displacing oxygen in an enclosed environment. Air normally contains about 21% oxygen. If this is reduced below about 16% it can result in unconsciousness and at lower levels can lead to death. 1. Chemical asphyxiants prevent the body utilising oxygen for normal cellular metabolic processes. The amount of oxygen in the air being breathed in is normal but the body cannot use it. Haemoglobin, found in red blood cells, transports oxygen around the body as a complex called oxyhaemoglobin. Carbon monoxide will displace the oxygen and bind more tightly to the haemoglobin to form the very stable carboxyhaemoglobin. This reduces the amount of haemoglobin available to transport oxygen, possibly to dangerous levels and the body effectively suffocates Hydrogen cyanide is an extremely potent and fast-acting asphyxiant which acts by preventing the biochemical process that converts sugars to energy Many other substances can cause asphyxiation either directly by chemical action, or indirectly by displacing oxygen from the air. People at particular 12 risk are those who work in confined spaces e.g. fuel tanks, compartments on ships, sewers and pits. **3.2 IRRITATION** An irritant is a substance that can cause reversible inflammation on contact with a body tissue such as the skin or mucous membranes. The body's response to an irritant may manifest in a number of ways including the following: - Skin -- red or blotchy at point of contact - Eyes -- itchy, painful, red or watery - Nose -- itchy or runny - Upper respiratory tract -- coughing, sneezing -- in severe cases the lungs may produce excess fluid causing breathing difficulties Examples of irritants include gases such as ammonia, chlorine, and oxides of nitrogen. Vapours from liquids such as formaldehyde can also cause irritation. Dermal exposure to solvents may also play a role in irritation due to the de-fatting of skin. In addition to the acute effects of irritants outlined above chronic exposure can lead to other health effects. Chronic exposure to a respiratory irritant can lead to bronchitis and chronic exposure to a skin irritant may lead to dermatitis. The symptoms of dermatitis include dry, flaking skin as well as itching, redness and inflammation. It is important not to confuse irritant contact dermatitis with allergic contact dermatitis which is a type of skin hypersensitivity. The latter involves an autoimmune response typical of those agents that cause sensitisation. An extreme form of irritation is from contact with corrosive substances that can cause tissue damage, similar to burns, from which the tissues do not 13 generally recover. Examples of corrosive substances include concentrated hydrochloric acid, sodium hydroxide, and chromic acid. It should be noted that a corrosive substance at lower concentrations, may only cause irritation. **3.3 NARCOSIS** A narcotic substance is one that depresses the normal function of the central nervous system (CNS). Initially exposure to narcotic substances may lead to symptoms of fatigue and headache as well as feelings of light headedness and euphoria. At higher exposures, effects may include dizziness, nausea, unconsciousness and death. A very common group of substances that can cause narcosis are organic solvents. Alcoholic drinks, which contain ethanol, can produce narcotic effects. **3.4 SYSTEMIC TOXICITY** Toxicity is the degree to which a substance is able to damage an exposed organism. Systemic toxicity describes the adverse effects caused by a substance that affects the body at organs remote from the point of contact with the body. These effects may be caused by the substance itself or by a metabolite or breakdown product of the substance. Due to the metabolic processes within the body the liver and kidney are particularly susceptible to damage by toxic substances. Examples include the damage caused by cadmium in the kidney and organic solvents such as carbon tetrachloride that cause liver damage because of the way they are broken down by this organ. Other examples include the neurological deterioration caused by accumulation of lead in the central nervous system. 14 **3.5 GENOTOXICITY AND CARCINOGENICITY** **3.5.1 Genotoxicity** Genotoxicity is a term used to describe the ability of a chemical to induce damage to the genetic material in a cell. Such substances are termed genotoxic or mutagenic. These are important effects since damage to genetic material can disrupt the normal function of a cell and can lead to irreversible changes called mutations. A mutation is a permanent change to the genetic material that can lead to changes in the functioning of a cell or tissue because it alters the genetic message being carried. If mutations occur in germ cells they can be passed on to the offspring where the effects may then be seen. In non-germ (somatic) cells, mutation may result in changes to the way that normal cell division is regulated so that it becomes uncontrolled and can lead to the development of cancer. **3.5.2 Carcinogenicity** Carcinogenicity is the ability of a substance to induce cancer. A substance that can cause cancer is termed a carcinogen. Cancer is a disorder of cells in the body which is characterised by abnormal cell division and growth. It begins when one or more cells fail to respond to the normal control mechanism and continue to divide in an uncontrolled manner. As ultimately the induction of cancer is believed to be a consequence of mutations; then substances that are genotoxic are often considered to be likely to possess carcinogenic activity. However, not all carcinogens are necessarily genotoxic themselves (or through metabolites). An example of this is asbestos. There must therefore be a non-genotoxic mechanism. It is thought that repeated damage to tissues may stimulate an increased rate of cell division. As background agents such as radiation are continually 15 causing background damage to genetic material (which is also being constantly repaired by cells) any increase in cell division may help to make this "background" damage become permanent as mutations rather than be repaired. Thus stimulation of cell division may itself lead to induction of cancer although the substance inducing the stimulation may not itself possess genotoxic activity. A non-genotoxic mechanism such as repeated damage to tissues may explain why some substances appear to cause cancer at high doses in animal tests but do not appear to cause cancer in humans at lower exposure levels. **3.5.3 Benign and malignant tumours** The new growths whether caused by mutagens or any other mechanism are called tumours or neoplasms and may be either \"benign\" or \"malignant\". - Benign tumours include warts, polyps and fibroids. A benign tumour can grow large enough to cause pain and may damage nearby organs, however, these tumours do not invade surrounding tissues and do not spread to other sites in the body. They can usually be removed surgically without likelihood of recurrence. They are usually not life threatening (unless they are growing near a key internal organ). - Malignant tumours can spread (or *metastasise*) throughout the body by invading neighbouring tissues, entering blood vessels, lymphatic vessels and other spaces with development of secondary tumours. They tend to be aggressive, respond poorly to surgery and / or chemotherapy and radiotherapy, and are usually life threatening. 16 **3.5.4 Difficulties in identifying carcinogens** There are many potential causes of cancer and it is often difficult to prove a causal link between exposure to a certain chemical and subsequent cancer. A particular problem in establishing causes of cancer is that in many cases there is a long latent period between exposure and development of cancer. This may be many years or even many decades. However, there is significant evidence that tumours may develop after occupational exposure to a number of different chemicals. Cancer caused by industrial exposure may occur in many different organs, some examples are listed below: Site of cancer Substance Lung Asbestos, chromium, nickel carbonyl, rubber fume Nasal sinuses Wood dust Liver Vinyl chloride monomer Kidney Cadmium Bone marrow Benzene Skin Mineral oils, tar **3.5.5 Classifications of carcinogens** Several organisations and bodies provide lists of known or \"suspect\" carcinogens, classified into different categories. It is important to note that the classification is complicated and is not universally agreed upon. Some of these are given below. Two non-regulatory schemes in common use are those of the International Agency for Research on Cancer (IARC) and the American Conference of Governmental and Industrial Hygienists (ACGIH). The IARC Monographs on the Evaluation of Carcinogenic Risks to Humans have been evaluated for more than 900 environmental agents and 17 exposures. Each exposure is classified into one of five groups according to the strength of the published evidence for carcinogenicity. Group 1 Carcinogenic to humans Group 2A Probably carcinogenic to humans Group 2B Possibly carcinogenic to humans Group 3 Not classifiable as to carcinogenicity to humans Group 4 Probably not carcinogenic to humans The complete list of the evaluations can be found at http://monographs.iarc.fr (accessed May 2009) The ACGIH system uses the following notations: 1. A1 Confirmed Human Carcinogen: The agent is carcinogenic to humans based on the weight of evidence from epidemiologic studies. 1. A2 Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s) or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans. 1. A3 Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at relatively high dose, by route(s) of administration, at site(s), of histologic 18 1. levant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure. 1. A4 Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not produce indications of carcinogenicity which are sufficient to classify the agent into one of the other categories. 1. A5 Not Suspected as a Human Carcinogen: The agent is not suspected to be a human carcinogen on the basis of properly conducted epidemiologic studies in humans. These studies have sufficiently long follow-up, reliable exposure histories, sufficiently high dose, and adequate statistical power to conclude that exposure to the agent does not convey a significant risk of cancer to humans, OR, the evidence suggesting a lack of carcinogenicity in experimental animals is supported by mechanistic data. Under the Globally Harmonised System of Classification of Labelling of Chemicals (see Section 11) which is now beginning to be implemented in many countries, there are regulatory requirements to identify carcinogens on labels. **3.6 SENSITISATION - (ALLERGIC REACTION)** Sensitisation is a term used to denote a process by which the body's immune system, carrying out what are its normal functions, produces an adverse reaction that can in some cases be of a serious nature. In effect the body treats a substance as if it was an invading micro-organism, against 19 which it is defending itself. Hay fever induced by exposure to pollen is a typical example of a sensitisation response (in this case of the respiratory tract). There are a number of different white blood cells and associated antibodies within the body that play a part in the body's defence and immune systems. One particular type of antibody, Immunoglobulin E (IgE) plays an important role in many allergic responses, and is particularly associated with the most severe hypersensitivities. The first time an allergy prone person comes into contact with an allergen they make large amounts of specific IgE antibodies. After the first exposure the specific IgE antibodies remain attached to other cells within the blood serum for many years, ready to respond rapidly to subsequent exposure to that particular substance. In industrial hygiene, the two main categories of sensitisers are respiratory sensitisers and skin sensitisers. Sensitisation normally develops over a period of time following repeated exposure of an individual to a chemical substance. Once someone becomes "sensitised" then they are always likely to respond adversely if they subsequently come into contact with the substance. As described earlier, the substance interacts with the individual's immune system cells with the result that the substance is eventually "seen" as an invading foreign body that needs to be isolated through a typical immune reaction. For the skin this results in the release of histamine locally which can cause an inflammation of the skin (allergic contact dermatitis). This usually manifests as a red, itchy, scaly rash, often localised to the area of contact. It is a delayed hypersensitivity reaction which usually occurs between 6 and 48 hours after exposure. Less critical reactions include urticaria -- an itchy 20 rash on the skin consisting of a number of raised pale bumpy wheals surrounded by red skin (similar to nettle rash). For the respiratory tract the release of histamine causes a range of effects including narrowing and inflammation of the airways, difficult in breathing and rhinitis (inflammation of the nose -- e.g. hay fever like symptoms). In many cases the respiratory symptoms collectively are characteristic of asthma (which is a condition that can be induced by a number of factors including chemicals, cold air, exercise) and in fact the term "occupational asthma" is often used as an alternative to respiratory sensitisation. In extreme cases, if an individual is particularly sensitised then the reaction can be very severe leading to arrest of the heart (anaphylactic shock). As stated earlier, the two main categories of sensitisers in the workplace are respiratory sensitisers and skin sensitisers. Examples of skin sensitisers include chromium, nickel, latex and epoxy resin adhesives that can cause contact dermatitis. A number of substances are known to be respiratory sensitisers. Some of the more common examples are given below: - Isocyanates - Grain and flour dusts - Rosin-cored solder fume (colophony) - Animal proteins - Dusts of some woods - Detergent and bakery enzymes - Antibiotics There are a number of different assessment methods that are available for determining whether or not a person is allergic to a particular substance. These include lung function tests (or spirometry), challenge testing, skin 21 prick testing and blood IgE testing. These are examined in more detail in Section 6.3 **3.7 REPRODUCTIVE EFFECTS** A substance may affect an individual by reducing their fertility, thereby making it more difficult, or impossible, to have offspring. These are reproductive toxicants and examples include some glycol ethers, lead, and some pesticides. Another category is developmental toxicants (often referred to as teratogens) that can cause damage to a developing foetus. While these substances may not harm the mother they may result in physical abnormalities of the child, or affect its development after birth. Examples of these include lead, methyl mercury and thalidomide.