introduction to toxicology and toxin 2024.pptx

The ppt presents an introduction to the interaction between toxins and the environment

1. Introduction to Toxicology Toxicology is a field of science that helps us understand the harmful effects that chemicals, substances, or situations, can have on people, animals, and the environment. Toxicology uses the power of science to predict what, and how chemicals may cause harm and then shares that information to protect public health and for sustainable development. Toxicology —the science that deals with the study of the adverse effects (toxicities) chemicals or physical agents may produce in living organisms under specific conditions of exposure. It is a science that attempts to qualitatively identify all the hazards (i.e., organ toxicities) associated with a substance, as well as to quantitatively determine the exposure conditions under which those hazards/toxicities are induced. Toxicology is the science that experimentally investigates the occurrence, nature, incidence, mechanism, and risk factors for the adverse effects of toxic substances

2. Introduction cont,----- Toxic —having the characteristic of producing an undesirable or adverse health effect. Toxicity —any toxic (adverse) effect that a chemical or physical agent might produce within a living organism. Exposure—to cause an adverse effect, a toxicant must first come in contact with an organism. The means by which an organism comes in contact with the substance is the route of exposure (e.g., in the air, water, soil, food, medication) for that chemical. Dose—the total amount of a toxicant administered to an organism at specific time intervals. The quantity can be further defined in terms of quantity per unit body weight or per body surface area. Lethal dose- is the amount of material per unit of body weight of the test animals that kills all of test population in a certain time. Median dose, etc

3. Acute toxicity —an adverse or undesirable effect that is manifested within a relatively short time interval ranging from almost immediately to within several days following exposure (or dosing). An example would be chemical asphyxiation from exposure to a high concentration of carbon monoxide (CO). Chronic toxicity —a permanent or lasting adverse effect that is manifested after exposure to a toxicant. An example would be the development of silicosis following a long-term exposure to silica in workplaces such as foundries.  

4. Introduction cont,---- Hazard – it is a substance or an action that can cause injury, disease or economic loss or environmental damage, most hazards come from exposure to various factors in the environment ‘The hazards can be physical hazards (1) physical hazard -ionizing radiations, (ii) chemical hazards-harmful chemicals in the air (iii) biological- disease causing bacteria and viruses, pollen and parasites Toxicity thresholds- -- refer to the exposure level or dose of an agent above which toxicity or adverse health effects can occur, and below which toxicity or adverse health effects are unlikely. This situation can be portrayed graphically by means of dose-response curves.

5. The region of the dose response curve that marks the transition from “no-toxicity” to “toxicity” corresponds to the toxicity threshold – the dose immediately above which responses caused by the chemical begin to manifest themselves and below which no effect occurs. Thresholds for toxicity exist because, up to a certain point, the body can repair damage and detoxify chemicals to which it is exposed. If the exposures get too high, however, the detoxification and repair mechanisms are overwhelmed and toxicity starts to occur.

6. TYPES OF TOXIC SUBSTANCES There are several types of toxicants 1. Natural toxicants - and examples are the polycyclic aromatic hydrocarbons which are mainly from bushfires fuel emissions, their mode of action is carcinogen they are DNA adduct formation 2 Biological toxins- Microorganisms (bacteria, Fungi and dinoflagellate green algae) commons source is Gastrointestinal and are Necrotic and Neurotoxic Inorganic (SO 2 , CO, CO 2 NO 2 SH 2 and NH 2 ) source is from volcanic eruption, coal and vehicle emissions, fertilizers. Their mode of action is that it blocks biochemical pathways 4. Metallic (As, Ag, Cd, Cr, Cu, Pb, Sn, Sb, Zn) sources Mining, Smelting, Metallurgic and industries, electronics, batteries, paints, and herbicides They are neurotoxic and block respiration and biosynthesis, 5. Phenolic compounds-from plant waste and disinfectant their mode of action is Antioxidant and cell inhibitors

7. Artifical 6 .Anilines- source is dyes (textile paints) rubber and pharmaceuticals industries and their mode of action is oxidation and dehydration 7. Antibiotics, sulfonamides and sulfonylurens sources are biocides, herbicides and pharmaceuticals, they are amino acids and proteins inhibitors 8. Benzoylureas - source is insecticides and mode of action is chitin synthesis inhibitors Carboxamides, phthalimides, pyroles and strobilurins, source is biocides and mode of action is respiration inhibitors Chlorofluorocarbons from coolants, propellants, solvents fire suppressants affect greenhouse gases and ozone depletion

8. 10.DDT and synthetic pyrethroids-- source is insecticides and the effect is neurotoxic 11. Dibenzodioxins and dibenzofurans ---source is pesticides, industry and waste burning emissions 12. Imidazoles, Morphines and triazoles --source is fungicides, it is a Ergosterol biosynthesis inhibitors 13. Nacrotics- from pharmaceutical industries 14. Neonicotinoids --from insecticides-neurotoxic nicotinic receptors inhibitor 15. Nonylphenols, nonylphenol ethoxylates and steroids, source is Detergents and pharmaceutical industries

9. 16 Organochlorides sources is insecticides/fungicides they are neurotoxic, 17. organometallic compounds source is biocides, antifoulants-chelating oxidants, respiration inhibitors 18. Organophosphate and Carbamate pesticides-- source is insecticides, herbicides, neurotoxic-acetyl cholinesterase inhibitor 19. Perfluorinated compounds source is semi-conductors, oil/water proof materials

10. Routes of Entry of Chemicals into the Body Human body is exposed to the outside world through the skin, lungs, nose, mouth and the digestive, urinary, and genital tracts. Hazardous agents (e.g., chemicals and micro-organisms such as bacteria and viruses) can get into the body through any of these surfaces. The most common routes of entry are: through the lungs (inhalation), the skin (absorption) mouth (ingestion) More hazardous agents get into your body by inhalation (by being breathed in) than by any other route. The body respiratory system has effective mechanism to filter out normal pollutants from the air. the hair in the nose and mucus in the mouth and lungs prevent large particles from getting into the body

11. Large dust particles (including fibres ) can be filtered out of the respiratory system. But small dust particles are difficult to eliminate and can reach the deepest parts of the lungs where they can cause serious local respiratory problems When the lungs are exposed to high concentrations of dust, toxic vapours, cigarette smoke, etc. (high amounts of the pollutant in the air), the filtering mechanisms can become overloaded and damaged. Once they are damaged, various bacteria, viruses, etc. are more likely to grow in the lungs, causing infections such as pneumonia. Many workers in dusty occupations are susceptible (open) to tuberculosis, bronchitis and other respiratory diseases than workers in non-dusty occupations.

12. Chemicals can be in form of vapours, solids, liquids, dusts and gases, you can inhale almost all of these. Some will affect the lungs, while others will be absorbed into the bloodstream and have potentially damaging effects on various target organs. Guidelines/concentration for domestic waste water, drinking water and for irrigatio n

13. TOXINS A toxin is a harmful substance produced within living cells or organisms. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor such as a bee sting to almost immediately deadly such as botulinum toxin from bacteria Clostridium botulium.

14. Types of toxins Endogenous toxins are those produced by the body as a by-product of biochemical processes, and may tend to accumulate in the joins or various muscle groups. Exogenous toxins are toxins ingested or absorbed by a person into the body from external sources, including food, water, air, contact. Autogenous toxins that one is born with, in the form of pathogens or toxic compounds, generally from environmental/dietary exposure over multiple generations. These are usually passed down from the maternal line, from the mother to the baby in the womb. . However, these are in a sense just exogenous toxins that happen to be absorbed from the mother rather than from the environment.

15. Other toxins Organic chemical compounds include certain petroleum and petrochemical/synthetic chemical derivatives and plastics, tar from cigarettes and other smoked herbs, inhaling smoke from joysticks lit by misguided massage practitioners. Inorganic chemical toxins include: toxic elements, e.g. heavy metals - mercury, arsenic, cadmium; toxic element salts, mercuric sulphate, mercuric oxide; ammonia, e.g. cigarette smoke; preservatives, e.g. nitrites.  examples of common natural toxins

16. aquatic biotoxins Toxins formed by algae in the ocean and fresh water are called algal toxins. Algal toxins are generated during blooms of particular naturally occurring algal species. Shellfish such as mussels, scallops and oysters are more likely to contain these toxins than fish. Algal toxins can cause diarrhea, vomiting, tingling, paralysis and other effects in humans, other mammals or fish. The algal toxins can be retained in shellfish and fish or contaminate drinking water. They have no taste or smell, and are not eliminated by cooking or freezing. Another example is ciguatera fish poisoning (CFP) which is caused by consuming fish contaminated with dinoflagellates that produce ciguatoxins. Some fish known to harbour ciguatoxins include barracuda, black grouper, dog snapper, and king mackerel. Symptoms of ciguatera poisoning include nausea, vomiting, and neurologic symptoms, such as tingling sensation on fingers and toes. 

17. Cyanogenic glycosides Cyanogenic glycosides are phytotoxins (toxic chemicals produced by plants) plant species used as food. Cassava, sorghum, stone fruits, bamboo roots and almonds. The potential toxicity of a cyanogenic plant depends primarily on the potential that its consumption will produce a concentration of cyanide that is toxic to exposed humans. In humans, the clinical signs of acute cyanide intoxication can include: rapid respiration, drop in blood pressure, dizziness, headache, stomach pains, vomiting, diarrhoea, mental confusion, cyanosis with twitching and convulsions followed by terminal coma. Death due to cyanide poisoning can occur when the cyanide level exceeds the limit an individual is able to detoxify. There is currently no specific treatment for ciguatera poisoning

18. Furocoumarins. These toxins are present plants such as parsnips, celery roots, citrus plants (lemon, lime, grapefruit, bergamot) and some medicinal plants. Furocoumarins are stress toxins and are released in response to stress, such as physical damage to the plant Some of these toxins can cause gastrointestinal problems in susceptible people. Furocoumarins are phototoxic, they can cause severe skin reactions under sunlight (UVA exposure). While mainly occurring after dermal exposure, such reactions have also been reported after consumption of large quantities of certain vegetables containing high levels of furocoumarins. 

19. Lectins Many types of beans contain toxins called lectins, and kidney beans have the highest concentrations – especially red kidney beans. As few as 4 or 5 raw beans can cause severe stomachache, vomiting and diarrhoea. Lectins are destroyed when the dried beans are soaked for at least 12 hours and then boiled vigorously for at least 10 minutes in water. Tinned kidney beans have already had this process applied and so can be used without further treatment.

20. Mycotoxins Mycotoxins are toxic compounds produced by certain types of moulds . Moulds that can produce mycotoxins grow on numerous foodstuffs such as cereals, dried fruits, nuts and spices Mould growth can occur before harvest or after harvest, during storage, on/in the food itself often under warm, damp and humid conditions. Most mycotoxins are chemically stable and survive food processing. The effects of food-borne mycotoxins can be acute with symptoms of severe illness and even death appearing quickly after consumption of highly contaminated food products. Long term effects on health of chronic mycotoxin exposure include the induction of cancers and immune deficiency.

21. Solanines and chaconine All solanacea plants, tomatoes, potatoes, and eggplants, contain natural toxins called solanines and chaconine (which are glycoalkaloids). While levels are generally low, higher concentrations are found in potato sprouts and bitter-tasting peel and green parts, as well as in green tomatoes. The plants produce the toxins in response to stresses like bruising, UV light, microorganisms and attacks from insect pests and herbivores. To reduce the production of solanines and chaconine it is important to store potatoes in a dark, cool and dry place, and not to eat green or sprouting parts.

22. Poisonous mushrooms Wild mushrooms contain several toxins, such as muscimol and muscarine, which can cause vomiting, diarrhoea, confusion, visual disturbances, salivation, and hallucinations. Onset of symptoms occurs 6–24 hours or more after ingestion of mushrooms. Fatal poisoning is usually associated with delayed onset of symptoms which are very severe, with toxic effect on the liver, kidney and nervous systems. Cooking or peeling does not inactivate the toxins. It is recommended to avoid any wild mushrooms, unless definitively identified as non-poisonous.

23. How to minimize health risk from toxins In a usual balanced, healthy diet, the levels of natural toxins are well below the threshold for acute and chronic toxicity. To minimize the health risk from natural toxins in food, people are advised to: Not assume that if something is 'natural' it is automatically safe; Throw away bruised, damaged or discoloured food, and in particular mouldy foods; Throw away any food that does not smell or taste fresh, or has an unusual taste; and only eat mushrooms or other wild plants that have definitively been identified as nonpoisonous

24. WHO RESPONSES WHO, in collaboration with FAO, is responsible for assessing the risks to humans of natural toxins – through contamination in food – and for recommending adequate protections. Risk assessments of natural toxins in food done by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) are used by governments and by the Codex Alimentarius Commission (the intergovernmental standards-setting body for food) to establish maximum levels in food or provide other risk management advice to control or prevent contamination. Codex standards are the international reference for national food supplies and for trade in food, so that people everywhere can be confident that the food they buy meets the agreed standards for safety and quality, no matter where it was produced.

25. JECFA sets the tolerable intake level for natural toxins JECFA or ad hoc FAO/WHO scientific expert groups consist of independent, international experts who conduct scientific reviews of all available studies and other relevant data on specific natural toxins. The outcome of such health risk assessments can either be a maximum tolerable intake (exposure) level, or other guidance to indicate the level of health concern (such as the Margin of Exposure), including advice on risk management measures to prevent and control contamination, and on the analytical methods and monitoring and control activities. Exposure to natural toxins needs to be kept as low as possible to protect people. Natural toxins not only pose a risk to both human and animal health, but also impact food security and nutrition by reducing people’s access to healthy food. WHO encourages national authorities to monitor and ensure that levels of the most relevant natural toxins in their food supply are as low as possible and comply with both national and international maximum levels, conditions

26. Toxins synthesized by venomous animals from both terrestrial animals and marine animals, such as scorpions, snakes, spiders, bees, cone snails, and sea anemones, Animal venom, Snake venom --The neurotoxins in snake venom affect the neuromuscular transmission at pre-or post-synaptic levels. Pre-synaptic neurotoxins inhibit release of acetylcholine while post synaptic acting neurotoxins cause a reversible blockage of acetylcholine receptors Treatment: Mixture of antibodies that neutralize venoms Scorpion venom has -neurotoxicity Symptoms-local pain, restlessness ,roving eye movement

27. Treatment-antivenom Centipede scolopendra subspinipes Symptoms-localized pain, erythema, induration and tissue necrosis. Mortality is uncommon and may result from secondary infection or anaphylaxis Bee and wasp sting Symptoms, allergic reactions Venom immunotherapy is used to prevent further allergic reactions to insect sting

28. Key things of venom Modern Clinical Drugs- The potency, specificity and stability of toxins have made them valuable sources of natural pro dugs for drug discovery e.g. antihypertensive drug, neurogenic diseases, metabolic diseases Snake venom has specificity to platelet surface proteins(it has c-type lectin) this has made great contribution in understanding of thrombosis and hemostasis Venom is used to establish basic concept in blood coagulation system, venom protease was used to classy basic concepts in blood coagulation Neurodegenerative diseases such as Parkinson Alzheimers , Huntington, epilepsy multiple sclerosis which are incurable. Venoms are rich in neuroactive molecules which can be pharmacological drugs tools to analyze the pathological progress of neurodegenerative disorders and provide good products for new drug development. Antitumor drug from animal venom. Toxins from snake venom show potent cytotoxic activity to cancerous cells through modulation of the apoptosis response pathway, impairment of cancer proliferation, inhibition of enzymatic activities or alternation of cell cycle,

29. Inorganic toxic substances Heavy metals in surface water create acute or chronic effect in fish and other aquatic organisms. Ionic forms produce immediate fish kills while complexed compounds tend to accumulate in body tissues over a long period of time. Inorganic forms of heavy metals are known to create irritation of fish kills resulting in the secretion of mucus, the deterioration of the internal laminas of the gills and hence eventual suffocation. Aquatic organisms accumulate high and ultimately lethal concentrations of heavy metals over long periods from low water concentration, for example in USA the brown bullheads has been shown to accumulate chromium to Conc. more than 2600 times that found in stream water. The Response of a living organism exposed to a chemical or toxic pollutant depends upon the chemical dose, exposure time and the higher the dose the more significant the effect. and this is called dose response relationship

30. Inorganic toxic substances Alu minium: Agent used in water treatment where it acts as a coagulant to assist in removal of particulate matter. EC recommended limits is 0.2mgl -1 and above this, there are disastrous effects, Acute - headache , nausea ,vomiting , diahorrea ,fever , cold ,excessive tiredness ,blurred vision ,painful mouth/tongue ,bad breath , ear ache ,difficulty in passing urine, chest pain ,stomach ache ,painful joints ,pain in muscles and skin rashes after bathing in affected water. Chronic: Loss of concentration,poor short term memory , muschlo -skeletal pains , Alzueimer’s disease , dermentia mental imparement . It affects phosphorus absorbtion .

31. Arsenic It is extremely toxic but in small concentration, It is used as ant poison, insecticide and weed killer. The pathogenicity is due to the binding of sulfhydryl enzymes which disrupts cellular metabolism. Current EC limits in drinking water is 0.05mgl -1 . Acute: Vomiting and copious water diarrhoea which may be bloody three-four hours after taking water with Arsenic . Gastro-Intestinal pains, dehydration develop quickly leading to death from circulatory collapse. If death does not occur, Jaundice and renal failure may develop after a couple of days. Fatal dose may be as low as 100mg. Chronic: Chronic cough, lip herpes, abdominal pains, chronic diarrhoea in children loss of weight, typical skin changes such as bronzing and hyperkeratosis of palms and soles. Peripheral neuritis cardiac, renal and liver changes , skin cancer ,vascular disturbances, Blackfoot and Raymond syndrome.

32. Copper It is widely used in metal plumbing in domestic pipes . European limit of copper in drinking water is 3.0mgl-1. Outbreaks of illness linked to excess copper in water is there and it 10 to 20 minutes after drinking water that has a blue tint, and the illness stops as soon as you stop drinking that water. Although copper is non –toxic high concentration in drinking water has both acute and chronic effects. Acute: Vomiting and abdominal pains, nausea, severe diahorrea , hypertension, epigastric burning and coma. Chronic: Renal failure , severe liver disease(cirrhosis) in children , demyelination and brain damage.

33. Lead Used extensively in water distribution pipes. WHO standards in drinking water is 50mgL -1 . Lead is high in soft water and acidic water. Acute: Irritation of gastro-intestinal tract, metallic taste, vomiting , abdominal pains and diarrhoea, constipation ,abdominal pain and peripheral nerve palsies, children present encephalopathy leading to coma convulsions. Chronic effects Interferes with bio-synthesis of haem which is essential for the production of haemoglobin. It does so by interfering with the insertion of iron into protoporphyrins . Lead binds to amino acids, RNA and DNA

34. CADNIUM The WHO recommends 0.4-0.5mg l -1 in drinking water Acute: Increased salivation,choking sensationAbdominal painDiarrhoea Loss of consciousness and persistent vomiting begins 15-30 minutes after ingestion. Chronic: Impairment of kidney functionsHypertension ,Anaemia Osteomalia (softening of bone , poor reproductive capacity. WHO recommends 0.3mgL-1 in drinking water per person per week of which no more than 0.2mgL -1 should be methyl mercury. Chronic: Disrupts functions of the kidney and the liver and brain damage .In Mina Mata in Japan 22 infants with serious brain damage were born to mothers with no symptoms of mercury poisoning.

35. Mercury Mercury binds strong with sulphur groups in proteins and enzymes and disrupts enzymatic system and synthetic mechanism Methyl Mercury – Includes adverse effects in the central nervous system resulting in changes in the sensory and co-ordination functions. Parental exposure may lead to development retardation . The present concern about Mercury is focussed on parental exposure as a result of fish consumption by the mother. Though the risk is not there, It may be aggregated in the future by increasing reliance on sea-food and by acidification which enhances the availability of Mercury from soil and sediments. Mercuric salts are absorbed in soluble form from water, by organisms and retain in the tissue. Plants are insensitive to toxic effects of Mercury compound.

36. Bariun It is an alkaline earth metal very reactive with water it is used as a contrast medium for x-ray examinations of gastro-Intestinal tract. Limit in drinking water is 1.0 mgl -1 . Acute; gastroenteritis, weakness paralysis, convulsions and myocarditis it affects muscle cell membranes so that muscle fibres

37. Pesticides They are chemicals toxic to living orgnism ( bacteria and higher plants)and man. They do not occur naturally in the environment and their detectable concentrations indicate pollution. Chlorinated hydrocarbons They are long lived chemicals e.g. pesticides like DDT alderin , Dieldrin,Heptachor Lindane,mirex and all have been burned in USA) but are still used in the less developed countries they are found in high concentration in the environment than any other pesticides because of their widespread use. Persistent 2-5 years.Most living pests have developed resistant

38. Organophosphate They are esters of phosphorus, more toxic than hydro-chlorinated insecticides- melathion (used widely at home and on crops)parathion 2-12 weeks ) Carbamates –carbonyl maneb , priopoxor , mexicabate , aldicarb, aminocarb, they have low persistent (days to weeks). Pyrethroids; chemicals that repel insects widely used in homes and crops as insect ides, they cause little harm to birds and animals including man.

39. Herbicides They are contact herbicides, systematic and soil sterilants . The contact are atrazine and parquet kill foliage by interfering with photosynthesis Systematic= they are substituted urea, and examples are diuron, norea and fenuron, they create excessive growth but plants die due to lack of nutrients to sustain growth. Soil sterilents , they are Triflurain , dalapon , butylate, diphenamid kills soil microorganisms essential to plant growth.

40. PROOBLEMS They are long-lived their metabolites have human and animal health effects DDT interferes with the animal reproduction by altering the egg shell thickness. it affects enzymatic activity of the liver, thus reducing one of the body’s defence against ingested poison. DDT is transferred across the placental barrier from human mothers to their unborn children ,

41. Synthetic detergents They are present in low concentrations in water but even in low concentration they; Retard rate of reabsorption of atmospheric oxygen into partially de-oxygenated stream. A source of phosphate and assist in the eutrophication of a lake resulting in heavy and unwanted blooms of algae. Reduces the effectiveness of primary treatment ,prevent sedimentation by emulsifying oils and grease, thus prevent their removal, e.g. they interfere with the normal settling out of suspended solids.

42. Oil and petroleum products Present in surface water in many forms as dissolved film and emulsion, interactions between the fractions is complex and depends on specific gravity, boiling point, surface tension solubility of the compounds present. The permissible cons. in water depends on the intended use of water. Drinking water supplies and fisheries production is between 0.01 and 0.1 mgl-1 and more than 0.3mgl-1 can cause toxic effects in freshwater fish. They are carcinogenic and accumulate in the fatty parts of marine food chains sources., oil extraction, transportation and refining.

43. Phenols Important group of pollutants that enter water through wastes discharge from industries. Formed under natural conditions due to the metabolism of aquatic organism, biochemical decay and transportation of organic matter in water and in bottom sediments. They cause a marked deterioration in the organic characteristics of water. The WHO guideline level for phenol in drinking water is 0.0001mgl-1 conc. Phenol but in unpolluted water, it is less than 0.02mgl-1 but it is toxic.

44. Nitrates/phosphorus compounds NITRITES As such has no health effect but are converted by bacteria within tissues to nitrites. Nitrites react with haemoglobin in the red blood cells and this causes the cells to loss their ability to carry oxygen and threaten the body with (asphyxiation)unable to breathe. Infants suffer from methemoglobinemia this is because their gastric juice have a low PH which creates a suitable environment for the bacteria that convert their nitrates to nitrites. Children receive nitrates from cow's milk that drank water high in nitrates.

45. Phosphorus They are important in Agricultural productivity but interfere with the action of enzymes. It converts Serine to phosphorus ester and also affects the transmission of impulse. Pathways of chemicals in the environment