Toxicology WHAT IS TOXICOLOGY Toxicology is the study

Toxicology

WHAT IS TOXICOLOGY? Toxicology is the study of how natural and man made poisons cause undesirable effects in living organisms. Harmful Effects of Toxicology It may damage the survival or normal functions of an individual.

What is Toxicity? The degree to which a substance is poisonous or can cause injury. The toxicity depends on a variety of factors. 1. Dose 2. Duration 3. Route of Exposure 4. Shape and structure of the chemical itself

What is Toxicant? A toxicant is any chemical that can injure or kill humans, animals or plants. Toxicant is the term used when talking about toxic substances that are produced by or are a by product of man-made activities. What is a Toxin? The term toxin is used when a toxic substance is produced naturally(phytotoxin, zootoxin or bacteriotoxin) OR synthetic chemicals that alter the growth, development or kill the organism

Toxic Symptom Any sign or feeling that represents or indicates the presence of a poison in the system Toxic Effect/Poisonous Effect Health effects that occur due to exposure to a toxic substance Selective Toxicity Means that a chemical/toxin will produce injury to one kind of living matter without harming another form of life, even though the two may exist close together

TYPES OF TOXIC EFFECT Death - arsenic, cyanide Organ Damage - ozone, lead Mutagenesis UV light Carcinogenesis - benzene, asbestos Teratogenesis – thalidomide

How Does Toxicity Develop? Before toxicity can develop a substance must come in contact with the body surface or respiratory tract. The dose or amount of a toxin also matters a lot in this case Dose Actual amount of a chemical that enters the body Dose received may be due to either Acute Exposure or Chronic Exposure �Acute Exposure(occurs over a short period of time, usually 24 hours) �Chronic Exposure(occurs over long period of time such as weeks, months or years) The amount of exposure and the type of toxin will determine the toxic effect.

Dose–Response Curve Direct relationship between exposure and health effect. Greater is the exposure worst is the effect on human/living things

Threshold Dose The lowest amount of exposure or dose at which no adverse effects can be seen in population

FIELD OF TOXICOLOGY Sub disciplines of toxicology �Environmental Toxicology (study of effects of pollutants on living organisms, populations, ecosystem and the biosphere) �Regulatory Toxicology (use of scientific data to decide how to protect humans and environment from excessive risks) �Clinical Toxicology (deals with the prevention, diagnosis and treatment of different poisoning cases)

• Food Toxicology (study of the nature, properties, effects, and detection of toxic substances in food, and their disease manifestation in humans) • Forensic Toxicology (deals with the study of chemical analysis to determine the cause and circumstances of death and postmortem investigations)

NATURAL TOXINS: Naturally Usually, present in plants & animals natural toxins are not acutely toxic, except in a few cases in animals.

Endogenous toxins of plant origin § § § Toxic phenolic substances: flavonoids, tannins, coumarin, safrole, and myristicin Cyanogenic glycosides Glucosinolates Acetylcholinesterase inhibitors Biogenic amines Central stimulants Natural contaminants § § § Mixing of edible plants with toxic plants Contamination resulting from intake of toxic substances by animals Microbial toxins

ENDOGENOUS TOXINS OF PLANT ORIGIN 1. Flavonoids: � � � A class of plant pigments that are widely present in human food. These pigments are polyhydroxy-2 -phenylbenzo-γ-pyrone derivatives, occurring as aglycones, glycosides and methyl ethers. A group of yellow pigments that occurs abundantly is the flavones. Examples nobiletin, tangeretin (in citrus fruits) and 3, 3′, 4′, 5 , 6 , 7, 8 -heptamethoxyflavone (in grapefruit). The flavones are generally located in the oil vesicles of the fruit peel. Flavones are non-polar, and therefore readily soluble in the oil. They can be found in the juice after pressing the peel.

2. Tannins: v v 1. 2. v v v Tannins are a heterogeneous group of broadly distributed substances of plant origin. Two types of tannins can be distinguished on the basis of degradation behaviour and botanical distribution: hydrolysable tannins and condensed tannins. The hydrolysable tannins are Gallic, digallic, and ellagic acid esters of glucose or quinic acid. Example: tannic acid, also known as Gallo tannic acid, Gallo tannin, or simply tannin. Tannic acid has been reported to cause acute liver injury, i. e. , liver necrosis and fatty liver.

3. Goitergens: Glucosinolates are a particular group of substances, occurring in cruciferous plants, such as cabbage and turnips. They can be considered as natural toxins, but also as antinutritives. Presents in many commonly consumed plants, such as cabbage, cauliflower, Brussels sprouts, broccoli, turnip, radish, oil seed meals. Inhibit the uptake of iodine by the thyroid iodine deficiency. Concerning toxicity and antinutritive activity, the hydrolysis products are the active agents, not the glucosinolates themselves. Hydrolysis of glucosinolates results in the formation of isothiocyanates and nitriles. The enzyme becomes available for catalysis when cells are damaged on cutting or chewing. Several isothiocyanates have been shown to be embryotoxic in rats, while in vitro studies have proved a number of them to be cytotoxic and mutagenic.

4. Safrole, coumarin, myristicin 5. Mushroom Toxins Some other natural toxins: Biogenic amines, Acetyl cholinesterase inhibitors, Cyanogenic glycosides,

NATURAL CONTAMINANTS: Natural contaminants can also originate from biological systems different from those in which they occur. There are three important sources: § Raw materials of plant origin can become contaminated if they are mixed with toxic non-nutritive plant species. § Raw materials of animal origin, mainly fish and milk, can also become contaminated if the animal has ingested toxic substances of natural origin. § Contaminants of natural origin can be the products of microorganisms.

NATURAL TOXINS IN AQUATIC ORGANISMS Paralytic shellfish poisoning (PSP) is attributed to the consumption of shellfish that have become contaminated with a toxin or group of toxins from the ingestion of toxic plankton, in particular toxic dinoflagellates. The shellfish involved are pelecypods, a family of mollusks, including mussels and clams. The dinoflagellates produce a complex mixture of toxins. One of the components has been identified as saxitoxin. Shellfish poisoning symptoms: tingling and burning in face, lips, tongue, and ultimately the whole body, and parathesia followed by numbness, general motor incoordination, confusion, and headache � These symptoms develop within 30 minutes after ingestion. Death, preceded by respiratory paralysis, occurs within 12 hours. �

MYCOTOXIN Mycotoxins are secondary metabolites of fungi which can induce acute as well as chronic toxic effects (i. e. , carcinogenicity, mutagenicity, teratogenicity, and estrogenic effects) in animals and man. Currently, a few hundred mycotoxins are known, often produced by the genera Aspergillus, Penicillium, and Fusarium. Toxic syndromes resulting from the intake of mycotoxins by man and animals are known as mycotoxicoses. Because of their chemical stability, several mycotoxins persist during food processing, while the molds are killed.

AFLATOXINS Aflatoxins are the most important mycotoxins, which is produced by certain species of Aspergillus (A. flavus and A. parasiticus), which develop at high temperatures and humidity levels. Aflatoxins are carcinogenic substances and may be present in a large number of foods. This toxin cause cancer, cirrhosis of the liver. For substances of this type there is no threshold below which no harmful effect is observed. The most common commodities contaminated are tree nuts, peanuts, and corn and cottonseed oil. The major aflatoxins of concern are B 1, B 2, G 1, and G 2 �usually found together in various proportions. Aflatoxin B is usually predominant, and it is the most toxic and carcinogenic. TLC method can detect aflatoxins.

PROCESS-INDUCED FOOD TOXINS: Modern processing techniques: � Heat treatments (preservation) � Flavour enhancing � Texture or appearance enhancing � Shelf-life Changes in food Chemical reactions between food components Desirable and Undesirable (toxins) generate potentially harmful compounds. Examples: Partially hydrogenated oils, Sodium nitrate/nitrite levels, MSG, Pesticides, artificial sweeteners

It Involves: � naturally-occurring components in the food � food additives, ingredients, � food packaging materials that were intentionally used. Examples of such Food process induced chemicals: � Acrylamide � Benzene � Chloropropanols � Ethyl carbamate � Furan � Heterocyclic aromatic hydrocarbons � Nitrosamines � Polycyclic aromatic hydrocarbons (PAH's) � Semicarbazide

MEASUREMENT OF TOXICITY

WHAT IS TOXICITY? The toxicity of a substance is its capacity to cause injury to a living system. Toxicity represents the kind and extent of damage that can be done by a chemical or how poisonous something is.

KINDS OF TOXICITY: Acute toxicity: � Acute toxicity is used to describe effects which appear promptly, or within 24 hours of exposure. � The acute toxicity of a pesticide is used as the basis for the warning statements on the label. � Acute toxicity may be measured as acute oral toxicity, acute dermal toxicity, and acute inhalation toxicity.

Chronic toxicity: � It is the delayed poisonous effect from exposure from a substance. � It is measured in experimental conditions after three months of either continuous or occasional exposure. � The effects of both acute toxicity and chronic toxicity are dose-related; the greater the dose, the greater the effect.

RISK = TOXICITY X EXPOSURE The risk of harm from a toxicant exposure is equal to how poisonous the toxicant is, multiplied by the amount and route of exposure to the toxicant

MEASUREMENT OF ACUTE TOXICITY: Lethal � This dose (LD 50): is defined as the dose required to kill half the members of a specific animal population when entering the animal’s body. � LD 50 is stated in milligrams per kilogram (mg/kg): milligram of chemical per kilogram of body weight The lower the LD 50 --the lower the lethal dose-the more toxic the substance. The term LC 50 -Lethal Concentration is used to measure the toxicity of gases. The LC 50 is stated in milligram of chemical per liter (or cubic meter) of air.

Fixed � In dose procedure: 1992, the fixed-dose procedure (FDP) was proposed as an alternative test to LD 50. � Fewer animals used, less pain and suffering. � Here the test substance is given at one of four fixed-dose levels (5, 500 and 2000 milligrams per kilogram) to five male and five female rats. � When a dose produces clear signs of toxicity but no death is identified, the chemical is then classified at that level.

Parts �To per million: compare chemicals causing toxicity at very low levels. �Parts per million (ppm), parts per billion (ppb) and parts per trillion (ppt) are the most commonly used terms. �They are measures of concentration – the amount of one substance in a larger amount of another substance. �Scientists often use these measurements when measuring a toxic chemical in a lake or toxins in the air such as greenhouse gases.

MEASUREMENT OF CHRONIC TOXICITY: Carcinogenic toxicity: � Carcinogenesis bioassay: Utilizes high-dose studies on laboratory animals to look for even the rare case of cancer for 24 -30 months It may not be the best scientific approach but is an effective way to address to public concerns by generating carcinogenic risk values. For carcinogenic toxicity, scientists try to find even the rare cases of cancer.

Non-carcinogenic toxicity: �Lowest Observable Effect Level (LOEL) Looking for the smallest dose of the substance that cause a detectable change. For dose-response studies: administering small doses to substances to several groups of test animals everyday over a lifetime. Periodically observing animals and final autopsy to determine the effect. LOEL is measured in milligrams (mg) of substance per kilogram (kg) of body weight, or in parts per million (ppm) of substance in food.

Determining Safe Levels: �To protect the public, scientists also determine the highest dose at which no effects occur, known as No Observable Effect Level (NOEL). �The NOEL is considered the "safe level" for that chemical in the species studied. �The NOEL is not necessarily the "safe level" for humans, because: humans may be more/less sensitive to the substance than the animals studied. humans have more genetic, health, age, and other variability's, which may affect individual human reactions.

NOAL: NO OBSERVABLE ADVERSE EFFECT LEVEL LOAEL: LOW OBSERVABLE ADVERSE EFFECT LEVEL

HUMAN SENSITIVITY &VARIABILITY: The "safe level" calculation for humans assumes that humans are more sensitive than animals, but humans are not more sensitive in all cases. This variation is usually due to the different degrees and rates of absorption, metabolism, and/or excretion of the substance by the different species.

Mathematical models vary: �A mathematical model is a set of equations that mimic a real situation and predict what will happen under different circumstances. � For toxicity assessments, models are made to apply the values obtained from the animal studies to human conditions. � The choice of model strongly affects the outcome of the toxicity assessment.

Non-Threshold �Non-Threshold Model: It is based on the assumption that even one molecule of a cancer-causing agent can lead to the disease. This type of model is also referred to as a "one-hit" model. � Threshold vs. Threshold Models: Model: It is based on the premise that repeated exposures to a chemical are needed before a threshold of exposure is reached and cancer follows.

RISK ASSESSMENT: The risk assessor estimates ‘real world’ risk by combining information on toxicity and exposure. • • A toxicity assessment provides information on how much of a chemical causes what kind of harm. Toxicity assessment provides only an estimate of the harm to humans.

TOXICOKINETICS &TOXICODYNAMICS Toxicokinetics (Determines the no. molecules that can reach the receptors) Uptake Transport Metabolism & transformation Sequestration Excretion Toxicodynamics (Determines the no. of receptors that can interact with toxicants) Binding Interaction Induction of toxic effects

IMPORTANT PRINCIPLES - The effect which a drug produces is dependent on: 1. 2. The dose The concentration in the target organ - The kinetics of a drug may differ from therapeutic dose to its toxic dose - Toxicokinetics is important in predicting the plasma concentration of a drug

UPTAKE AND ELIMINATION Uptake K 1 Biological System K 2 Elimination K 1 > K 2 : Accumulation & Toxic effect

Slowing of absorption (A B) - prolonged Tp - lower Cmax In instances when the absorption rate is slower than elimination rate, the rate of washout of toxicant becomes rate-limited by absorption rather than by elimination (i. e. , a depot effect).

TOXICOKINETICS 1. 2. 3. 4. 5. Uptake Transport Metabolism & Transformation Sequestration Excretion

ABSORPTION - UPTAKE ROUTES 1. 2. 3. Ingestion (toxicity may be modified by enzymes, p. H and microbes) Respiration (Air borne toxicants) Body surface (Lipid soluble toxicants such as carbon tetra chloride and organophosphate)

UPTAKE BARRIERS 1. 2. 3. 4. 5. Cell membrane Cell wall/cuticles/stomata Epithelial cells of GI tract Respiratory surface (lung, gill tracheae) Body surface

UPTAKE OF TOXICANTS 1. 2. 3. 4. Passive diffusion Facilitated transport Active transport Pinocytosis

UPTAKE BY PASSIVE DIFFUSION Uncharged molecules may diffuse along conc. gradient until equilibrium is reached Not substrate specific Small molecules of < 0. 4 nm (e. g. CO, N 20, HCN) can move through cell pores Lipophilic chemicals may diffuse through the lipid bilayer

UPTAKE BY PASSIVE DIFFUSION First order rate process, depends on: � Concentration gradient � Surface area (aveoli = 25 x body surface) � Thickness (fluid mosaic phospholipid bi-layer ca. 7 nm) � Lipid solubility & ionization(dissolved before transport, polar chemicals have limited diffusion rate) � Molecular size (membrane pore size = 4 -40 A, allowing MW of 10070, 000 to pass through)

UPTAKE BY FACILITATED TRANSPORT Carried by trans-membrane carrier along concentration gradient Energy independent May enhance transport up to 50, 000 folds Example: Calmodulin for facilitated transport of Ca

UPTAKE BY ACTIVE TRANSPORT Independent of or against conc. gradient Require energy Substrate –specific Rate limited by no. of carriers Example: � P-glycoprotein pump for xenobiotics (e. g. OC) � Ca-pump (Ca 2+ -ATPase)

UPTAKE BY PINOCYTOSIS For large molecules ( ca 1 um) Outside: Infolding of cell membrane Inside: release of molecules Example: �Airborne toxicants across alveoli cells �Carrageenan accross intestine

TRANSPORT &DEPOSITION Transport Blood Lymph, haemolymph Water stream in xylem Cytoplamic strands in phloem Deposition Toxicant Pb Cd OC, PCB OP Aflatoxin Target organs Bone, teeth, brain Kidney, bone, gonad Adipose tissue, milk Nervous tissue Liver

DISPOSITION OF XENOBIOTICS

METABOLISM &TRANSFORMATION Evolved to deal with metabolites and naturally occurring toxicants Principle of detoxification: Convert toxicants into more water soluble form (more polar & hydrophilic) 2. Dissolve in aqueous/gas phases and eliminate by excretion (urine/sweat) of exhalation 3. Sequestrate in inactive tissues (e. g bone, fat) 1.

P 450 SYSTEM A heme-containing cytochrome protein located in ER, and is involved in electron transport. Highly conservative, occur in most plants & animals Two phases of transformation May increase or decrease toxicity of toxicants after transformation (e. g turn Benzo[a]pyrene into benzo[a]pyrene diol epoxide, and nitroamines into methyl radicals) Inducible by toxicants

INDUCTION OF P 450 Toxicant Aryl Hydrocarbon Receptor Toxicant-Receptor Complex Bind at Specific site hours Translocating protein m-RNA for CYP 1 A

PHASE I TRANSFORMATION

EXAMPLES OF PHASE I TRANSFORMATION Hydrolysis RCOO-R’ + H 2 O -----> RCOO-H + R’-OH Hydroxylation NADP+ R-H -------------> R-OH + H 2 O

EXAMPLES OF PHASE I TRANSFORMATION Epoxidation O R-CH==CH-R’ ------> R---CH ----CH-R’

PHASE II TRANSFORMATION

IMPORTANT PHASE II ENZYMES Glutathion S-transferases (GST) Epoxide Hydrolase (EH) UDP-glucuronosyltransferase (UDP-GTS) Sulfotransferase (ST).

EXAMPLES OF PHASE II TRANSFORMATION Deamination R-NH 2 --------------> R=O + NH 3

EXAMPLES OF PHASE II TRANSFORMATION Dealkylation R-CH 2 -CH 3 -----------> R + CH 3 -CH 2 O Dehalogenation: R-Cl -----------------> R-H + Cl+

GLUTATHIONE-S-TRANSFERASE GST) ( O R------R’ -----------> HO-R-SG GST R-Cl ---------------> R-SG + Cl GST

SEQUESTRATION Animals may store toxicants in inert tissues (e. g. bone, fat, hair, nail) to reduce toxicity Plants may store toxicants in bark, leaves, vacuoles for shedding later on Lipophilic toxicants (e. g. DDT, PCBs) may be stored in milk at high conc and pass to the young Metallothionein (MT) or phytochelatin may be used to bind metals

EXCRETION Gas (e. g. ammonia) and volatile (e. g. alcohol) toxicants may be excreted from the gill or lung by simple diffusion Water soluble toxicants (molecular wt. < 70, 000) may be excreted through the kidney by active or passive transport Conjugates with high molecular wt. (>300) may be excreted into bile through active transport Lipid soluble and non-ionised toxicants may be reabsorbed (systematic toxicity)

THE TOXICOLOGICAL PROCESS

Reaction Types; Non Covalent Binding Electron Transfer Enzymatic Reaction Molecular Targets Concept Outcomes; Dysfunction Destruction Neoantigen Formation

CARCINOGENESIS The process in which a normal cell converted to a cancerous cell. The cell have no. of genes in it – that decides its destination

CARCINOGENESIS This tumor formed due to carcinogenesis Tumor is of two types: Malignant Benign: remain in localized area While malignant: invade near cells and spread in whole body

CARCINOGENESIS Carcinogenesis is a multistep process at both the phenotypic and the genetic levels. It starts with a genetic damage: �Environmental Chemical (toxin substances) Radiation (ionizing and non-ionizing) Viral �Inherited (egg and sperm- carrying mutated gene)

FACTORS CAUSING CANCER During division the chances of cancer occurring is higher than at rest These are following factors that cause cancer: primary determining factors; secondary determining factors (inheritance) favoring factors (sex, age, nutrition)

PRIMARY FACTORS This is of our interest Physical and chemical factors Physical one involve ionizing and non-ionizing radiations : mineral substances, organic substances and mixed substances (tobacco, food carcinogens, etc. ). Chemical carcinogens act either directly, causing mutations, or indirectly, reactivating repressed carcinogens.

TOXINS Toxin not man made only but also present naturally in food. Some of these are neutralized while processing such as soaking, fermenting or cooking the food substance, others are poisonous in any form: Aflotoxin, hydrazine, lectin, goiterogen

EXAMPLES Aflatoxin- fungal source- legumes Goitrogens- suppress the function of the thyroid gland by interfering with iodine uptake Hydrazines: volatile carcinogens found in many raw mushrooms, Mice display a significant increase in the incidence of several types of tumors after they are fed uncooked mushrooms.

CONTI Cooking the mushrooms destroys a third of the hydrazine compound Lectins: toxic protein compounds found in most foods, but in heavy amounts in many seeds, grains and legumes damage the heart, kidneys and liver, lower blood clotting ability, destroy the lining of the intestines, and inhibit cell division Cooking – neutralize and then gastric juice (some extend)

TUMOR ARE DIVIDED IN 3 GROUPS: : which include approximately 90% of human cancers, are malignancies of epithelial cells. Sarcomas: which are rare in humans, are solid tumors of connective tissues, such as muscle, bone, cartilage, and fibrous tissue Leukemia and lymphomas: cancer of precursor of blood cells and lymph cells Carcinoma

AFLOTOXIN MODE OF ACTION Hepatocellular carcinoma (HCC) -primary liver malignancy worldwide . Its incidence is rising at alarming rates and has become a public concern globally. Dietary exposure to aflatoxins -major HCC risk factors. Aflatoxin B 1, which is a genotoxic hepatocarcinogen, which presumptively causes cancer by inducing DNA adducts leading to genetic changes in target liver cells.

MECHANISMS OF ACTION LEAD TUMOR . AFB 1 is metabolized by cytochrome-P 450 enzymes to the reactive intermediate AFB 1 -8, 9 epoxide (AFBO) which binds to liver cell DNA, resulting in DNA adducts interact with the guanine bases of liver cell DNA and cause a mutational effect in the P 53 tumor suppressor gene at the codon 249 hotspot in exon 7, which may lead to HCC.

PREVENTION AND CURE OF TOXICANTS

PURPOSE OF PREVENTION Prevention is defined as the promotion of health by the individual and the community. Prevention of toxic exposures is concerned with preventing chemicals of synthetic or natural origin from reaching people in amounts or at rates that exceed human tolerance to them. Types of Prevention A toxic exposure occurs when a susceptible individual or population comes into contact with a chemical/toxin in a particular environment.

Primary • Primary poisons prevention activities intervene before the event. • Active strategies seek to change attitudes, lifestyles and behaviors of individuals • Passive strategies automatically protect people, by improving the safety of products and the environment where they are used. Secondary • Secondary poisons prevention is the action taken after an exposure has occurred, to prevent the poisoning from progressing to chronic stage and to restore the victim to his/her former state of health. • It includes the initial steps to minimize the effects of the toxic agent, the diagnosis, decontamination and first aid treatment, and specific antidote therapy. Tertiary • Tertiary poisons prevention deals with the diagnosis and treatment of poisoning victims who cannot be treated to full recovery, to prevent death or permanent disability.

MECHANISMS FOR MINIMIZING TOXIC EFFECTS Every material can be poisonous under certain conditions. Metabolic Degradation In mammals, the liver is the primary site of detoxification of both natural and introduced poisons. Harmful products converted to harmless products Excretion And Repair Effects of waste products and environmental toxins reduced by eliminating via excretion. Tissues and organs often have mechanisms for damage repair by cellular reproduction.

GUIDELINES TO PREVENT FOOD TOXICITY Wash hands, utensils and food surfaces often. Keep raw foods separate from ready-to-eat foods. When shopping, preparing food or storing food, keep raw meat, poultry, fish and shellfish away from other foods. This prevents cross-contamination. Cook foods to a safe temperature. Refrigerate or freeze perishable foods promptly Defrost food safely. Throw it out when in doubt.

Food poisoning is especially serious and potentially life-threatening for young children, pregnant women and their fetuses, older adults, and people with weakened immune systems. Following food items are harmful: Raw or rare meat and poultry Raw or undercooked fish or shellfish, including oysters, clams, mussels and scallops Raw sprouts, such as alfalfa, bean, clover and radish sprouts Unpasteurized juices and ciders Unpasteurized milk and milk products Soft cheeses, such as feta, Brie and Camembert; blue-veined cheese; and unpasteurized chees

PURCHASE AND STORAGE Keep packages of raw meat and poultry separate from other foods, particularly foods to be eaten without further cooking. Buy products labeled “keep refrigerated” only if they are stored in a refrigerated case. Buy dated products mentioning expiry date of product. Use an appliance thermometer to make sure refrigerator is between 35 and 40 F and freezer is 0 F or below.

PREPARATION When using slow cookers or smokers, start with fresh rather than frozen. Avoid interrupted cooking. Never partially cook products, to refrigerate and finish later. If microwave cooking instructions on the product label are not appropriate for your microwave, increase microwave time to reach a safe internal temperature. Before tasting, boil all home-canned vegetables and meats 10 minutes plus one minute per 1, 000 feet.

DRUG THERAPIES Oral rehydration therapy Antibiotics Antitoxin to neutralize toxins from C. botulinum (only given within the first 72 hours) Amitriptyline to control the numbness and tingling from ciguatera poisoning Apomorphine or ipecac syrup to cause vomiting and help rid the body of toxins Atropine for mushroom poisoning Diphenhydramine and cimetidine for fish poisoning Mannitol for nerve-related symptoms of ciguatera poisoning

COMPLEMENTARY AND ALTERNATIVE THERAPIES Complementary and alternative therapies are best used to strengthen the body and aid in the prevention of food poisoning. Nutrition Herbs Homeopathy

NUTRITION Drink plenty of fluids (to prevent dehydration). Drink barley or rice water (to soothe inflamed stomach or intestine). Taking probiotics, (Lactobacillus and acidophilus), can help restore the balance of good bacteria in the intestine. Apple cider vinegar is a traditional remedy Cooking herbs, like thyme, rosemary, basil, coriander, sage, and fennel have strong antimicrobial effects against food borne pathogens.

NUTRITION Specific Food poisoning Alpha-lipoic acid Vitamin A Calcium phosphate Supplements to avoid Fish oil

HERBS Milk thistle (Silybum marianum) is often used for liver disorders and is widely used in Europe to treat Amanita mushroom poisoning. Chinese and Japanese combination herbal remedies used for Listeria. Asian ginseng (Panax ginseng) Astragalus root (Astragalus membranaceus) Chinese cinnamon bark (Cinnamomum aromaticum) Ginger root (Zingiber officinale) Licorice ( Glycyrrhiza glabra) Peony root (Paeonia officinalis) Skullcap (Scutellaria lateriflora) v v v v

HERBS Herbs have antibacterial or antimicrobial properties that are effective for treating food poisoning in humans. Barberry (Berberis vulgaris) has also been used traditionally to treat diarrhea from infectious causes such as E. coli and V. cholera.

HOMEOPATHY Arsenicum album Chamomilla Podophyllum Sulphur

HUMAN DISEASES CAUSED BY MOLDY FOODS Disease Molds Involved Toxins Implicated Aflatoxicosis Aspergillus flavus, A parasiticus Aflatoxins Ergotism Claviceps purpurea, C. paspali, C. fusiformis Ergot Alkaloids Alimentary toxic aleukia Fusarium sporotrichiodes T-2 toxin Yellow rice (cardiac beri) Penicillium citreoviride Luteoskrin, Islanditoxin

AFLATOXICOSES Acute lethal toxicity Immune suppression Hemorrhagic anemia syndrome Hepatotoxicity Teratogenicity Carcinogenicity

EFFECTS OF AFLATOXINS ON IMMUNITY Effects on cellular responses, Phagocytosis by macrophages reduced Delayed cutaneous hypersensitivity reduced Lymphoblastogenesis reduced (response to mitogens) Effects on humoral factors Immunoglobins (Ig. G and Ig. A) concentrations in serum may be reduced Complement activity reduced

AFLATOXIN—A HUMAN CARCINOGEN Incidence of Liver Cancer (HCC) 589, 000 deaths in 1999 (WHO) HCC is the third leading cause of cancer death worldwide >80% of HCC occurs in the developing world >400 million HBV carriers worldwide

GOITER TREATMENT Observation: If goiter is small and doesn't cause problems, and thyroid is functioning normally. Medications: In hypothyroidism, thyroid hormone replacement with levothyroxine will resolve the symptoms of hypothyroidism as well as slow the release of thyroid-stimulating hormone from pituitary gland, often decreasing the size of the goiter. For inflammation of thyroid gland, your doctor may suggest aspirin or a corticosteroid medication to treat the inflammation.

GOITER Surgery: Removing all or part of your thyroid gland (total or partial thyroidectomy). Surgery is also the treatment for thyroid cancer Radioactive iodine: radioactive iodine is used to treat an overactive thyroid gland. The radioactive iodine is taken orally and reaches thyroid gland through bloodstream, destroying thyroid cells. The treatment results in diminished size of the goiter, but eventually may also cause an underactive thyroid gland.