Toxicology is the key subject in the curriculum of Veterinary and Medical sciences. The fascinating science has several branches and its scope is been advocated since predated. Basic scientific acumen regarding concepts of general toxicology and mode of toxicity of different plants and mycotoxins is of utmost importance. Different sources of poisons also encompass the natural sources viz. plants and fungal toxins. Toxicodynamics, diagnosis and treatment of several plant toxins and mycotoxins is well narrated in this book. For the ease of understanding and easy comprehension this book is written in notes format and in simple language. Important points related to exam point of view have also being highlighted in bold letters. Pictorial depictions of plant plates are also mentioned in this book. This book contains 15 chapters encompassing detail concepts of General toxicology including history, source, factors affecting toxicity, toxicokinetic and basic principle of treatment of poisoning and toxicology of different plants and mycotoxins. All the chapters are covered as per the new academic regulations of VCI and ICAR - Broad Subject Matter Area (BSMA). This book will serve as a guide to deliver the ease learning material to the students of B.V.Sc. & A.H., M.V.Sc. and Ph.D. students for their excellence in the competitive exams viz. ICAR-SRF, JRF, NET, ARS, UGC-NET, CSIR-NET NIPER, IAS, PCS, IFS etc.

Definition Paracelsus saying– Nothing is devoid of poison it is the dose that differentiate between a drug and a poison. ? Poison- Any chemical substance either naturally present or Man made produces deleterious effect on the health of living organism are termed as Poisons. ? Toxicology term derived from Greek Word Toxicon which means Poison. Definitions ? Toxicology: It is the science or study of poisons on biologic systems, including their properties, actions and effects. Also their detection and identification, the treatment and prevention of the conditions produced by them. ? Toxicant: Any poisonous agent/ Professional Term used for Poison. ? Xenobiotic: Derived from Greek Word Xenos means – alien or foreign. ? Xenobiotics are those substances which are foreign to the body and are biologically active but do not take part in the process of energy production.

? Dioscorides- Classified Toxicants on the basis of their origin into Plant, Animal, and Mineral Sources. ? Ibn Hazer- Differentiated between a drug or a poison on the basis of matter of dose. ? Dementhes – died by swallowing an unknown poison in his pen. ? Socrates- was poisoned by a cup of Hemlock (Greek State Poison) obtained from Conium maculatum having active principle coniine causes paralysis, coma followed by death. ? Cleopatra- Egyptian lady use strychinine poisoning and she died of Egyptian Asp. ? Lady Toffana- Arsenic containing perfumes known as Aqua Toffana.

1. ABSORPTION Deals with the translocation of the xenobiotics. Passage of toxicant from site of adminstration to blood stream or systemic circulation. Translocation may occur by following processes a) Simple /Passive diffusion - most common route by which xenobiotic pass through the membranes: ? Down hill transport, No energy involvement ? It is not substrate specific. ? Small molecular weight (600) hydrophilic toxicants cross membranes by simple diffusion through aqueous pores. ? High molecular wt. hydrophobic molecules diffuse across the lipid domain of membranes. ? Follows Ficks Law of diffusion ? The rate of diffusion depends on their lipid: water partition coefficient value, Conc. Gradient, degree of ionization. ? Higher lipid: water partition coefficient and lower degree of ionization favours absorption of toxicants by this process.

Diagnosis of Poisoning     Three types of diagnosis  a) Tentative  b) Presumptive  c) Confirmative based on the following conditions  1. History  2. Physical examination and clinical evidences     Hyperthermia- Organochlorine;     Hypothermia- OP compunds     Miosis: Opium  Mydriasis- Belladona     Dryness of mouth (Xerostomia)- belladona;     Moist and Hypersalivation- OPC, Carbamates and synthetic pyrethroids  Bitter Almond    smell-Cyanide Garlic odor in expired air- Phosphorus, Arsenic     Mice smell- Hemlock     Rotten Garlic/Horse raddish smell- Selenium Poisoning

1. Acute    Toxicity      ? Duration-exposure of the toxicant for 24 hrs either single dose or  multiple doses  ? Species selection-Rat preferred rodent species  ? weight variation should not exceed ± 20% of mean weight  ? Number and sex -Atleast 5 rodents at each dose level of same sex  ? If female-nulliparous and non pregnant  Housing and feeding     ? Temperature of experimental room-22( ±3 °C)  ? Relative humidity (R.H.)-30-70%  ? Animals in cage should be properly spaced  ? Individual caging for morbid and excited animal  ? Artificial lightining-12 hrs light,12 hrs dark  ? Conventional laboratory diet & ad lib water

SOURCES OF POISON 1. Malicious poisoning Unlawful or criminal killing of the animals by certain toxicants as arsenic, Insecticide, datura etc.  2.Accidental    poisoning     A) Natural sources   ? Plants - e.g. Lantana, datura etc.  ? Animals - e.g. snake bite etc.  ? Microbes - fungi (aflatoxicoses etc.), bacteria (Botulinum toxin) etc.  ? Minerals - Se, As, fluoride etc.  B)  Man made sources  ? Agrochemicals - Insecticides, Herbicides etc.  ? Industrial wastes - Mercury, Copper, Lead etc.  ? Household products - disinfectants (phenol), Napthelene etc.  ? Therapeutic agents - paracetamol in cats be lethal  ? Food & feed - Genetically modified food (GM)  ? Environmental pollutants & managemental practices

BASIC PRINCIPLE FOR TREATMENT OF POISONING Introduction All the toxicants or poisons including various toxins causing various toxicoses or poisonings in animals comprise two major classes. Firstly, poisons having specific an tidotes and secondly, those having no specific antidotal therapy and require symptomatic and supportive therapy for the treatment of their poisonings. The adage "Treat the patient, not the poison" is the most basic principle of clini cal toxicology. Thus, in cases of both type of toxic conditions, an immediate attention is required for the maintenance of vital functions particularly cardiopulmonary function by providing supportive or therapeutic measures before institution of antidotal or symptomatic therapy. Vi tal signs and important reflexes should regularly be monitored to judge the response to therapy and progress of recovery. As per need of the situation, a flexile step wise practical approach may be opted by veterinarians for the diagnosis and treatment poisonings in animals.

? Cyanogenetic plants contain hydrocyanic acid or cyanogenic glycosides. ? Two forms of cyanide in plants- HCN( free form) and cyanogenic glycoside(bound form).HCN released from glycosides by physical disruption (mastication, trampling) , stress (drought, frost) or the action of an Hydrolyzing enzyme present in ruminal microflora beta glycosides and hydroxynitrile lyase. ? One of the most common plants poisoning among the grazing livestock. ? Cattle and buffaloes are most susceptible. Sheep and goats are less susceptible. ? Monogastric animals (pig, Horse) are relatively resistant due to destruction of the glycosides by the gastric activity. ? Poisoning occurs when HCN content in plants is high and ingestion of large amount of the plants in short period of time. ? Starved or underfed animal also ingest large amount of plants. Poisoning may also occur due to accidental ingestion of potassium cyanide.

INTRODUCTION ? Nitrate poisoning is generally caused when animals eat too much forage that is high in nitrates not changed to protein in the plant. ? Poisoning can also happen when animals eat too much urea or nitrogen fertilizer spilled in the field or left where the animals can find it. ? Nitrate fertilizer is palatable, especially to cattle. ? Nitrates are relatively non-toxic. ? Reduction of nitrates depends on the supply of fermentable energy as carbohydrates supply hydrogen ions for reduction of nitrates and production of nitrite in rumen.

1. Atropine Toxicity ? Toxicity of atropine depending upon the route of administration and the sp. of animal. ? Herbivores are more resis-tant than carnivores. Dogs, cats and birds are sensitive to its action. Rabbits are quite resistant to belladona leaves since an atropinase enzyme present in liver rapidly hydrolyses and inactivates atropine. ? Horse cattle and goats are relatively resistant to bellladona when administered orally, however poisoning on ingestion occurs more often in swine. Resistance in ruminants due to destructive maceration of atropine in rumen. ? All parts of plants are toxic as these contain atropine like alkaloids. Toxic dose of hyoscamine is 2.7 mg/kg for pigs.

? Lantana camara (lantana, wild sage, bunch berry) one of the ten most toxic weeds in the world. Brought to India in early part of the 19th century as an ornamental plant. ? Very hardy shrub grows very luxuriantly, capable of prospering in adverse soil. ? It has no. of adverse interactions with the biosphere. ? Causes hepatotoxicity, photosensitization in grazing livestock and growth inhibition of the neighboring vegetation due to allelopathic action which is rapidly changing the ecological balance. ? Reports of poisoning have been received form India, Australia, Cuba, Mexico, Kenya, Brazil and New Zealand. ? Very pungent plant. Cattle eat only in scarcity of other feed/fodder. ? Bos taurus more susceptible than Bos indicus.

Source ? Consumption of seeds (dog/cat), Baits containing strychinine kept for foxes, rats, mice ? Cattle are more susceptible to strychnine poisoning parenterally than orally because strychnine is destroyed in the rumen ? Ingestion of birds or rats poisoned with strychnine and ingestion of strychnine treated seeds of peanuts, wheat (in human). ? In Seeds, 1.53- 3.24% total alkaloids out of which 50% is strychnine. ? Loganin (glycoside), Vomicine, α-colubrine, betacolubrine, pseudo strychinine (alkaloid), Brucine, strychnine and strychnicine (leaves), Brucine and small amount of strychnine (bark) ? Average amount of strychnine and brucine in nuxvomica seeds is 1.23 and 1.55% respectively. ? Strychnine- an indole alkaloid found in seeds of Strychnos nuxvomica is extremely stable and can be detected in specimens many years even after the death of animals. ? It is rapidly absorbed from the GIT and parentrally significant amount found in liver and kidney while small amount reaches CNS. ? Metabolized by hepatic MFOs and primarily excreted in urine within 10 hrs.

Source ? Consumption of seeds (dog/cat), Baits containing strychinine kept for foxes, rats, mice ? Cattle are more susceptible to strychnine poisoning parenterally than orally because strychnine is destroyed in the rumen ? Ingestion of birds or rats poisoned with strychnine and ingestion of strychnine treated seeds of peanuts, wheat (in human). ? In Seeds, 1.53- 3.24% total alkaloids out of which 50% is strychnine. ? Loganin (glycoside), Vomicine, α-colubrine, betacolubrine, pseudo strychinine (alkaloid), Brucine, strychnine and strychnicine (leaves), Brucine and small amount of strychnine (bark) ? Average amount of strychnine and brucine in nuxvomica seeds is 1.23 and 1.55% respectively. ? Strychnine- an indole alkaloid found in seeds of Strychnos nuxvomica is extremely stable and can be detected in specimens many years even after the death of animals. ? It is rapidly absorbed from the GIT and parentrally significant amount found in liver and kidney while small amount reaches CNS. ? Metabolized by hepatic MFOs and primarily excreted in urine within 10 hrs.

Nerium oleander ? (Oleander, kaner, rose laurel) ? An ornamental plant and grown in lawns and gardens. ? Other species are Nerium indicum (kaner) & Thevetia peruviana (yellow oleander). Sources ? Almost all animal species are poisoned. ? Ingestion of branches, stem or leaves during drought or periods of food scarcity or consumption of contaminated water by ruminants or horses. ? Chewing of leaves may be responsible for toxicity in dogs. ? Ingestion of 30-60 gram fresh leaves of oleander is fatal for horses, cattle and sheep. ? All parts of plant are toxic, the leaves and flowers may be less toxic than the seeds.

? Oxalic acid is an organic dicarboxylic acid that readily forms insoluble salts with cations like calcium & magnesium. ? Sodium, potassium or ammonium salts are highly soluble and can induce toxicity in animals. Source ? Ingestion of large quantity of oxalate containing plants. ? For toxicity plant should contain > 10% oxalic acid on dry weight basis. ? The form in which oxalate is present in plant mainly as acid oxalate (Oxalis sp., Rumex sp.) or oxalate ions (chenopodiacae).

? Secondary metabolites of toxigenic fungi on animal food and food ingredients which causes adverse effects when consumed. ? 1942-44: Mycotoxicosis in man and animals was recognized in Russia. Fatal outbreaks of “toxic alimentary aleukia”.  ? 1955: “Hepatitis X” in dog and in cattle and swine in 1957. ? 1960: “Turkey- X disease” and 100,000 turkeys died in England due to Aspergillus flavus infested ground nut meal. ? 1962: Aflatoxin was first isolated. ? Favorable conditions for growth of fungi: Min. 15% moisture (10-13%), relative humidity: 90-95% (> 70%), ambient temp. of 24-25ºC (4-35ºC). ? Moulds infested feed along with nutritionally poor and inadequate diet makes animal more susceptible to mycotoxins induced harmful effects. ? More than 100 toxigenic fungi and mycotoxins have been identified during the last three decades.