Toxi part 1 Flashcards

Question

Horsetail (Equisetum palustre) | Alkaloids

Answer 1

- Contains alkaloids palustrin and nicotine, thiaminidase. - Poisonings mainly in cattle, usually after chronic intake. - Signs: decrease of body weight, decrease of milk yield, diarrhoea, paralysis of muscles. - Treatment: change of the diet and a supplement of vitamin B1 (thiamine)

Answer 2

- Contains alkaloid coniin– influences Ach receptors. - Coniin irritates GIT, and then causes paralysis of motoric and bulbar centers in brain. - It is an up-going poisoning => first a paralysis of legs, then of a neck, head and finally trunk and chest. =>Death comes due to the paralysis of respiratory muscles and it is in full consciousness. - Coniin is a volatile substance, so beware of smelling it, => can cause a mild poisoning – headaches, vomiting – even while smelling it. - Treatment is only symptomatic and usually unsuccessful

Answer 3

- Contains alkaloid aconitine, most potent plant toxic substance in Europe => the lethal dose is 2 mg of aconitine for the death of an adult man. - It blocks neuronal transmission especially in nervus vagus - influences Na ions on synapses and in heart and causes death by => respiration collapse in the full consciousness.

Answer 4

- Contains pyrrolizidine alkaloids – senecin, senecionin. - Most common is spring poisoning. It follows chronic or long – term exposure. * In spring, alkaloids are bound in a plant to sugars and other chemicals=>don’t change its taste. -Young and inexperienced animals - especially horses - are the main victims. - In late summer and autumn, pyrrolizidine alkaloids release from their bonds and cause a very bitter taste of plants, so there aren’t any poisonings in this period of year. - Signs: weakness, inappetence, icterus, increased neuronal irritability, blindness. -Treatment is only symptomatic.

Answer 5

- Contains alkaloids atropine, solanine and nicotine. Some animals are resistant to atropine, have enzyme in blood which deactivates it => singing birds, pheasants, guinea pigs, sheep, rabbits, horses. - Nicotine stimulates and irritates ganglias - solanine was mentioned in food toxins – its effect is similar to organophosphates - atropine is a parasympatolytic agent. - Treatment of the poisoning is only symptomatic.

Answer 6

- Contain lactone called protoanemonin, which is found in all the Ranunculaceae family - The alkaloid is highly toxic for water organisms, especially for fish and young frogs. - It affects mainly kidneys, treatment is symptomatic. - The poison is destroyed by drying – hay is not toxic.

Answer 7

- Contains furanocoumarins, which are highly locally irritating – cause strong inflammation of the skin and subcutaneous tissues which is compared to yperit (an agent used in wars). - Treatment is very difficult, a necrosis occurs very often, a secondary bacterial infection of the place is also typical, a strong hyperpigmentation of the scar remains for months or years.

Answer 8

- Take approximately 500 pieces of bees = 60 g - Withdraw also 200 g of plants on which pesticides were applied (pesticides are the source of death in 99 %) - It is necessary to send them to lab within 72 hours after pesticide application – after that time the breakdown may start – no detection - The examination is conducted by State veterinary administration; State phytosanitary administration, the owner of the bees and the person who applied the pesticide are also present *Poisons are usually insecticides

Answer 9

Ammonia autointoxication - Very often - Aquarium or pond - especially when immediately stocked to full capacity - Nitrification bacteria is not able to convert all ammonia to nitrates - Treatment impossible, prevention very easy – small number of fish, increase aeration - Lethal dose is 0,5 mg/l for Salmonids 1,0 mg/l for Cyprinids -According to a table in which temperature and pH are involved=> we count the amount of toxic NH3

Answer 10

Pure chlorine – Cl2 -Free chlorine is used especially as an industrial chemical -disinfection of drinking water. -In water it is quickly dissolved while forming hydrochloric acid according to following scheme: Cl2 + H2O = HCl + HClO. -HClO is very unstable and almost immediately is decomposed onto HCl and atomic oxygen=> which kills microorganisms. -Atomic oxygen released by this mechanism severely destroys tissues of water organisms. Especially susceptible to this damage are gills of fish, which are then unable to transport oxygen to blood. -Also pure chlorine when absorbed to blood damages organism – especially CNS.

Answer 11

- LD50 for fish is lower than 1 mg/l., - concentrations higher than 0,05 mg/l can be lethal for more susceptible fish. - Acceptable concentration of free chlorine in water is said to be Cl2 < 0,1 mg/l. - Chlorine is more toxic in higher temperatures. - Clinical signs of intoxication => - seizures of fins and mouth - increased amount of mucus on gills and skin - patechias and haemorrhages may be observed. Fish are trying to escape, - start to move quickly and cumulate under the water surface, where they often lay on their side. - die because of corrosive effect or because of suffocation.

Answer 12

- Oxygen – in mg/l or % - we measure it with oximeter IN THE PLACE of poisoning! - Salmonids - need between 8-12 mg/l of oxygen in water - Cyprinids – need between 6 - 8 mg/l of oxygen in water

Answer 13

- Assessed by MnO4- or Cr2O7- - Non-direct method of assessing oxygen in water - We detect the value of organic compounds in water - these are reduced by above mention ions and for this reduction they need oxygen which they take from water - Measured both substances biologically degradable and non-degradable - Optimum is - less than 10 mg/l in Salmonids - less than 20 – 30 mg/l in Cyprinids

Answer 14

- Only biologically degradable organic substances are measured - Oxygen amount is assessed in time 0 and then we put it into thermoregulator for 5 days keeping it at dark in 20°C - After that we measure oxygen again - The concentration of used oxygen shouldn’t be more than - 5 mg/l in Salmonids -8-15 mg/l in Cyprinids - Biochemical demand is always lower than chemical demand

Answer 15

- Take whole bodies -best if fish are still living with signs of damage. - If there is only one species in the water source – take 5-20 pieces - if there are more species take 3-5 pieces from each one -- Withdraw also samples of water – ABOVE, IN and UNDER the place of contamination – 2-4 l; and sediments in the same places – 2 kg

Answer 16

Intoxication: all species Infection: one species immediate fish kill gradual fish kill full stomach (not in winter) empty stomach

Answer 17

- Every time we must do! : - Examination of the place of poisoning - Examination of water - Biological test of water toxicity - Examination of dead fish - Also we can do, but it is not obligatory: - Hydrobiological examination - Sediment examination (in pesticide, PAH, metal contamination) - Examination of food, if it is a fishing pond and we feed the fish

Answer 18

• Important!!!! – Clinical signs in damaged fish => especially color of gills (it changes quickly on the air), dissection right in the place - Temperature and concentration of oxygen in water => must be measured immediately and in the place – we cannot do it lately in lab! - Draw a plan of place – factories nearby, estuaries, tributaries, houses or villages (towns)

Answer 19

-Color – we assess it according to Setchi desk -Turbidity -Odor -Temperature (important in ammonia intoxication) - Content of nitrates and nitrites - pH - optimum lies between 6,5 and 8,5 Salmonidae - death - lower than 4,2 and higher than 9,2 Cyprinidae - death - lower than 5,0 and higher than 10,8 -Alcality = acid neutralization capacity -> how much of strong acid you need to change pH to certain pH value (usually to 4,5). *depends on an ability of H2CO3 - HCO3- buffer system to work. Optimum is to 3,0 mmol/l (ANC or KNK)

Answer 20

- typical for veterinary practice, doesn’t occur in people -Salt is toxic in high levels -Livestock is human-dependent => most of the poisonings because of bad treatment or because of the exchange of feed -An animal eats a lot of NaCl and usually lacks water -The intake of salt as mash or liquid is much worse - intoxication is worse in young animals - taste not developed yet - lower content of blood proteins – lower oncotic pressure, bigger oedemas limits value for manufactured feed mixtures and for water established in law: -Limit for feed: max. 1 % of NaCl in feed mixture -Limit for water: must be of the same quality as drinking water for people Cl- limit value => 100 mg/l -maximum limit value (Hygiene committee must give the licence) 250 mg/l

Answer 21

-NaCl is absorbed completely from guts => excess irritates GIT and causes liquefaction of its content -Na and Cl are extracelular ions( important for osmotic balance in an organism ) -↑ ions in interstitium => passage of water from cells to interstitium => inner dehydration -NaCl in excessive amount destroys endothelium of capillaries => ↑ permeability of vessels -These mechanisms lead to accumulation of water in intercellular tissues => cause oedemas which oppress organs (brain is the most sensitive one ) -Increased content of Cl- ions leads to metabolic acidosis

Answer 22

-Increased salivation, thirst -Vomiting, diarrhoea, colic pains -Oedemas, coordination disturbances, epileptic attacks, paresis and paralysis – paralysis of back legs in pigs - they sit like dogs – typical sign !!! -If we don't treat the animal – death in coma within 2-3 days *Temperature, breathing and heart rate are not affected Na: K rate=> in feed is an important factor in intoxication development: - ruminants 1:40 – it is much more difficult to change the rate to the situation when there is more Na than K ions - carnivores, omnivores 1:1 – higher risk for intoxication

Answer 23

- Congestion to inflammation of GIT tissues - Petechias in brain, meningoencefalitis - Oedemas - Typical histopathological sign in pigs – infiltration of eosinophils in brain tissue

Answer 24

-withdraw liver sample for NaCl content => in poisoning approx. 3000 – 3500 mg/kg of liver tissue (normal level is 1500 – 2000 mg/kg according to animal species ) -also it is possible to measure concentration of chloride ions in blood plasma

Answer 25

Change of feed and drinking water Administration of water, but never ad libitum !!! => could deteriorate oedemas and cause death =>Recommended dosage is 0,5 % of body weight every hour ``` Table: Lethal doses of NaCl in different animal species Animal species g NaCl (pro toto) Cattle 1500 – 3000 Sheep, goat 100 – 200 Horse 900 – 1000 Pig 50 – 200 Poultry 2 - 4,5 Dog 20 – 60 Cat 5 – 20 ```

Answer 26

-Nitrates are industrial fertilizers -Poisoning most often due to exchange of salt and these fertilizers =>appropriate storage of them is very important !!! -Fertilizing can cause increased levels of nitrates in feed=> especially in fodder crops and vegetables -These agents can also contaminate drinking water -Limits for drinking water is : -50 mg/l in adults -15 mg/l in infants

Answer 27

-same course of poisoning as in salt intoxication : – nitrates are osmoticaly active substances => only in massive intoxication by nitrates - signs occur in 3- 7 hours after ingestion – thirst, diarrhoea, colic, excitation, convulsions - treatment similar to that described in salt intoxication – emetics, adsorbents, pure water administered gradually -In GIT, a big part of nitrates is converted into nitrites => reduction process mediated by bacterial microflora =>Non-resorbed nitrates and nitrites are converted to ammonia, which is a source of nitrogen for the production of nitrosamines in guts =>CARCINOGENS !!!

Answer 28

- Technical and industrial chemicals - used in food industry for preservation of meat (cause the rich pink colour of products) - Quickly absorbed from GIT - Act as poisons with effect on blood and vessels - Limits for drinking water: - 0,1 mg/l - outlet of water source - 0,5 mg/l - water tap - 0 mg/l for infants

Answer 29

- in massive intake of pure nitrites => direct effect on vessels causes => paralysis of vascular tissue, vasodilatation, collapse - treatment: -inactivation + elimination of non-resorbed substance from GIT, -administration of analeptics (reinforce circulatory system) -adrenalin in collapse

Answer 30

- most common -nitrites convert haemoglobin into methaemoglobin (iron 2+ => tiron 3+ ) => leads to insufficient oxygen transport to tissues => later to hypoxia + asphyxia ->Physiological value of MetHb < 5 % ->Mild intoxication 10 – 15 % Light cyanosis, respiration with mouth open, dyspnoea ->Medium intoxication 15 – 20 % Significant cyanosis, dyspnoea, apathy, fatigue, decreased mobility -> Severe intoxication 20 – 30 % Whole body cyanosis, dyspnoea, often convulsions of legs, immobility, abortions in pregnant animals -> Critical status, death > 50 % Unconsciousness, convulsions, great hypoxia, death

Answer 31

Erythrocytes -have methaemoglobin-reductase=> w reduces iron in haem back to Fe2+. -This enzyme is of limited capacity => after depletion, signs of intoxication occur - Fish have very high level of enzyme=> they bear higher doses of nitrites. =>Moreover, they have chloride cells on gills, where chloride + nitrite ions are absorbed. =>In sufficient concentration of chloride ions in water, the poisoning doesn't develop => (they have higher affinity to receptors on these cells than nitrites have) - almost never found in sea water - young animals have a very low activity of methaemoglobin-reductase => common intoxications => mainly in young cattle => when change the diet from milk to grass (higher content of nitrogen compounds in green feed)

Answer 32

Pathological – anatomical examination: - congestion of organs, dilatation of vessels, gastritis, enteritis - non-coagulable blood of brown colour, serosa and mucosa of the same colour Diagnostics: - clinical signs - pathology - examination of blood – determination of methaemoglobin spectrofotometrically

Answer 33

-adsorbents and emetics in first, resorption stage -antidote is methylene blue, which reduces Fe3+ back to Fe2+, administered i.v. in the concentration of 1-4 mg/kg.w. in the form of solution in physiological solution -small animals we may also administer: - vitamin C -oxygen by inhalation route - make blood transfusion -necessary to keep animals absolutely calm - animals that will be slaughtered=> we never administer methylene blue (would cause the degradation of meat quality)

Answer 34

Drugs: - benzocain, lidocain and other local anaesthetics - paracetamol, phenacetin – analgesics - amylnitrite – an antidote in cyanide poisoning - sulphonamides – antibiotics Chemicals: - fertilizers, chlorates, aniline, toluene, benzene, carbamates

Answer 35

- colourless and odourless gas - lighter than air - product of the incomplete combustion of carbon-containing compounds * notably in internal-combustion engines - Dangerous in spaces with bad ventilation => gas flow-heaters, gas heating, gas oven

Answer 36

- binds to haemoglobin => carbonylhaemoglobin (or carboxyhaemoglobin) - very stable => affinity of CO to haemoglobin is approx. 240x higher than the affinity of O2, - in fetal haemoglobin it is even higher -The bond is reversible -Also the exchange of CO2 is disrupted and is the source of alkalosis -CO binds also to myoglobin (can cause rabdomyolysis and renal failure) =>oxidative phosphorylation in muscle – deterioration of myocardial contractility =>blocks mitochondrial enzymes (cytochrome P450) => inhibit cellular breathing

Answer 37

-according to stage of poisoning => weakness, vertigo, fast breathing, headache, coma, convulsions of skeletal muscles, tachycardia, slow pupillary reaction to light, deep coma, death - chronic intoxications described – tiredness, vertigo, problems with vision, stomach aches, parestezia in almost 1/3 of affected animals => late complications develop. -deterioration of memory, changes in behaviour, deterioration of hearing, damage of cerebellum functions, parkinsonism

Answer 38

- typical sign is cherry-red colour of blood and mucosas - blood remains non-coagulable - petechias in CNS - lung oedema

Answer 39

- transfer the affected animal into fresh air + inhalation of oxygen in overpressure - if there is a problem with heart action => administer analeptics - at risk of lung oedema=> administer hypertonic solution of glucose (40 %) or NaCl (10 %)

Answer 40

- Preparations used against insect pests in all developmental forms and stages - Used in agriculture, medicine (as antiparasitics), industry and the household - Division: according many criteria - route of application: fumigation; spray – effective after contact, feed; with local or systemic effect - type of effect: immediately effective, after chronic/repetitive intake or with residual activity - chemical structure: chlorinated insecticides, organophosphates and carbamates, pyrethrins and pyrethroids, phenylpyrazoles, neonicotinoids

Answer 41

- To this group belong DDT, HCH, aldrin, endrin, heptachlor, toxafen etc. - very stable and accumulate in the environment - Nowadays( beside a few exceptions) => not used. - Most of them banned. But there are still old resources, residues in water, soil, food chain

Answer 42

-3 types of alteration in animals: -acute poisoning: the animal is timid, hypersensitive, nystagmus, clonus of mimic muscles, seizures, salivation, gnashing !, collapse of breathing, death -chronic poisoning: same signs, longer and gradual coming - deposition in fatty tissues, elimination to milk => alteration of next food chain links

Answer 43

Pathological findings - non-specific - may find oedemas of parenchymatic organs, petechias, degenerative changes on liver and kidneys, slight inflammation of stomach and guts Treatment - Symptomatic - forbidden to use oil laxatives – faster absorption, these agents are very lipophilic!!!!

Answer 44

- Several forms=> γ isomer called lindan is the most toxic - Used as an ectoparasitic agent against scabies - Inhibits GABA system and Na/K ATPase - signs: diarrhoea, vomiting, hyperactivity of muscles, convulsions - Treatment => symptomatic - Probably doesn't cumulate in the environment

Answer 45

- In Czech republic banned in 1974, manufactured till 1983 for foreign countries -Still persists in food chain => Accumulation in fat - Slow conversion: DDT=> DDE => DDD (DDE metabolite has xenoestrogennic effect) -Acts both after contact and ingestion - Affects nervous system => destroys Na+ channels=> leads to repolarisation of neurons. - chronic intake => alters calcium metabolism and causes malacia (softening) of eggshells in birds and reptiles -Pathology examination doesn't show any specific damage, only typical mousy smell from GIT

Answer 46

- insecticides/ antiparasitics - have systemic effect => applied on plant, absorbed to its tissues, act for days to weeks, it is necessary to keep the protection period - enter in the organism very easily and in every route => inhalation, ingestion, skin contact

Answer 47

– irreversible inhibition of enzymes, particularly of acetylcholinesterase (by phosphorylation of hydroxyl group of serine bound in the active centre of ACHE). -In blood we find butyrylcholinesterase – we can measure it, but it may be decreased also during pregnancy, acute infection or kidney diseases =>this can influence the interpretation of results

Answer 48

- fluorophosphates: (sarin, soman, tabun) =>war gases in World war I => all strictly banned - pyrophosphoric acid derivates (trichlorfon, dichlorvos) => pesticides, insecticides=> rarely used nowadays - thiophosphoric acid derivates (parathion, metathion, diazinon) => selective toxicity to insects=> relatively less toxic to mammals

Answer 49

Mechanism action - reversible inhibition of acetylcholinesterase ( carboxylation of hydroxyl group of serine bound in the active centre of ACHE). LD 50: < 100mg/kg: oxamyl, carbofuran 100-200 mg/kg: propoxur, pirimicarb > 200 mg/kg: carbaryl

Answer 50

1. stage: PRODROMAL - non-specific signs: fear, headache, anxiety, dysopsia 2. stage: MUSCARINIC - fluently follows and blend together with the first stage - activation of parasympaticus=> - increased activity on muscarinic receptors in GIT and glands => hypersalivation, lacrymation, sweating, nausea, vomiting, colic, spontanneous defecation and emiction, miosis !!! 3. stage: NICOTINIC - Again follows and blends with the two previous stages. - hyperactivity of muscles, begins on head and neck, pure clonic seizures, exitus due to respiration centre paralysis often delayed-onset neurological aftermath !!!

Answer 51

Pathological examination: - No significant signs - Characteristic smell of cadaver Treatment: - reactivators of acetylcholinesterase – oxims – eg. pralidoxim. - when administered in first or beginning of second stage=> bind organophosphates. - When covalent bond between enzyme and OP already made => ineffective. - We don't administer them in carbamate intoxication – pointless, no covalent bond!

Answer 52

Antidote for Organophosphates -as soon as possible, 25 % of dose i.v. (if a dryness of mucosas and immediate mydriasis occur – it is not an OP intoxication!). =>Then administer atropine i.m., gradually and for a long time. -When miosis starts to occur again, we give another dose of atropine. - recommend oxygen inhalation - treat convulsions with diazepam (never barbiturates – inhibition of respiratory centre!)

Answer 53

- insecticides/ antiparasitics -Pyrethrins => isolated from a plant Pyrethrum cinerariaefolium -Pyrethroids => synthetic derivates -Used alone or in combination => most often with organophosphates or carbamates -relatively less toxic to mammals, exceptions are young animals, *cats most sensitive => of glucuronyl transferase (conjugation) => low in cat -Highly toxic for fish and bees!!! fish (LC50 below 0,1 mg/l) bees (LD50 2 – 11 µg/bee) - contact and feed poisons - act immediately - knock down effect

Answer 54

- influence mainly Na+ channels => cause their hyperexcitability - also Ca2+ channels and GABA receptors * pyrethroids T (tremor) => contain no α-cyano group - cause reversible block of sodium channels (e.g. permethrin) * pyrethroids CS (choreoatetosis, salivation) => contain α-cyano group - cause reversible block of sodium channels and inhibition of GABA (e.g. deltamethrin)

Answer 55

Clinical signs: - within 1-3 hours - hypersalivation, nausea, vomiting, muscle trembling, ataxia, dyspnoe. - If the poisoning is via inhalation route => course of poisoning is much faster Pathological examination: nothing specific death because of pyrethrin intoxication rarely Treatment: emetics, absorbents, atropine, symptomatic treatment - insecticides - antiparasitics

Answer 56

- the mainly used substance from this group is fipronil - it is already banned in agriculture due to residual activity and toxicity for bees and fish, and also banned in food producing animals - fipronil is used as an ectoparasitic agent in companion animals (Frontline) - phenylpyrazoles block GABA receptors – in overdose increased irritability, problems with coordination, tremor, convulsions - Fatal for rabbits, higher risk of poisoning is described in guinea pigs

Answer 57

- many substances used in agriculture - problems mainly with substance called imidacloprid - imidacloprid is highly toxic to bees - poisonings in mammals are rare with non-specific signs - mechanism of action is either activation or inhibition of nicotinic receptors on muscles which leads to hyperexcitation or paralysis respectively

Answer 58

- Bioracional insecticides – synthetic analogues of insect hormones – juvenile or feromones - not toxic, but some signs of usually GIT irritation or skin damage occur due to solvents and additives in the products

Answer 59

- International convention on termination or restriction of use of these chemicals (POPs), which accumulate in the environment and are badly degradable - all POPs are lipophilic and spread on long distances in form of vapours or solid particles - originally 12 substances or their mixtures (called Dirty dozen), divided into Annexes - right now 28 substances classified in this convention

Answer 60

- > Annex A: aldrin, dieldrin, chlordan, endrin, heptachlor, HCH, mirex, toxafen (all pesticides), but also PCBs, pentachlorbenzene etc. (industrial chemicals) – req. termination and prohibition of production and use - > Annex B: DDT – req. of max. restriction of production and use. Eliminate its use at the moment in some countries of Africa and Asia – agent effective on Anopheles mosquito, a vector of malaria. Very cheap, must ask for exception. - > Annex C: polychlorinated dibenzodioxins and dibenzofurans (PCDDs and PCDFs), not substances manufactured intentionally, but produced as non-purpose by-products in industry or during burning of waste. Req. of new technologies, which will restrict their production and release.

Answer 61

• Rodenticides are a group of pesticides which is primarily established for rodent control • There are strict rules how, when and where to use them. In spite of this they are common source of both wild and domestic animals ́ poisoning and are also used for malicious intentions to harm • Poisoning is quite easy when baits with rodenticides are placed inconveniently at locations easily accessible for domestic animals esp. dogs and cats • In these animals is also possible to poison themselves by eating a dead rodent which died of rodenticide poisoning – so called secondary poisoning

Answer 62

according to chemical character: - inorganic – zinc phosphide (and other phosphides), formerly arsenic or thallium - organic – natural (strychnine, scilliroside, vitamin D), synthetic (anticoagulants) according to the route of administration: for eating, for drinking, for dusting, for fumigation according to the type of action: one dose, cumulative/repetitive intake

Answer 63

- The only inorganic and single-shot used agent nowadays - very potent and non-selective => causes many unwitting poisonings - used as bait for eating or fumigated in closed spaces (stocks, stores). - Baits are made of grains impregnated by zinc phosphide or granules with active substance. - Usually are not colourful! - Often causes poisonings of wild animals (pheasants, eagles, hares etc.) because used on fields

Answer 64

-In acid environment of stomach easily and quickly hydrolysed => releases gas phosphan, *which is the real toxic agent -The gas affects stomach mucosa at first => causes its irritation, inflammation and necrosis -Then goes to blood and damages veins and all organs. -When inhaled causes lung oedema -Intoxication is always acute or peracute -prognosis is always malignant because of irreversibility of damage

Answer 65

Clinical signs: nausea, vomiting, severe colic with bloody excrements, animal is rapidly weakening and dies within a few hours Pathological examination: gastritis and enteritis with haemorhagia and necrosis, GIT content smells like garlic. Petechias on serosas, brain, endocardium, parenchymatic organs are dystrophic -For laboratory examination is used GIT content immediately store in a closed glass bottle !!!

Answer 66

First aid and treatment are usually ineffective. Only if you see an animal eating a bait, immediately, administer a solution -of blue vitriol (CuSO4) – but keepers usually don’t have it

Answer 67

• Cholecalciferol is so called antirachitic vitamin • It increases intestinal absorption of calcium, decreases it excretion, and mobilises it from bones (osteolysis) which results in hypercalcaemia • Hypercalcaemia lasting for more then a few minutes is dangerous, so the body tries to quickly store calcium elsewhere. In overdose the re-deposition into bones is a too slow process, so calcium from blood is then deposited in other organs and structures, especially in vein walls and kidneys. The results are fragility of veins and kidney failure. • Rodents and cats are mainly susceptible to this poisoning. Damage in other animals is not so quick, but juvenile dogs and horses are also quite sensitive to it • Even if therapy of poisoning is successful, damage of kidneys can cause problems for many months and sometimes it lasts for the rest of the animal’s life • Often chronic poisoning not from a rat bait, but as an overdose of food supplements

Answer 68

Clinical signs: - anorexia, haematemesis, diarrhoea with signs of blood in excrements, ataxia, lethargy, bradycardia; hematuria, anaemia, polyuria and polydypsia due to kidney damage, in final stages neurological symptoms from uraemia Pathological examination: - Calcification and damage of kidneys, veins, eventually other organs, exostosis

Answer 69

- If found early - emetics or gastric lavage, activated charcoal - For a quite long period (three - four weeks) we must increase calcium elimination by administration of fluids, diuretics and in cats sometimes also corticosteroids - Animals must be kept in calm and in shadowy place to avoid exposition to sunlight (activates cholecalciferol formation in skin of mammals and birds)

Answer 70

• It is a cardiotoxic glucoside found in a plant called Scilla maritima (sea onion) • Cardioactive glucosides have enterohepatic cycling • It has been used since ancient times as a powder made from bulbs • For animals with vomiting reflex this natural product is quite safe due to content of emetin, which causes tenacious vomiting and prevents absorption of higher doses of scilliroside to the organism • In USA and some countries pure scilliroside is used, so no protection of emetin presence and toxicity to all species of animals must be expected

Answer 71

Mechanism of action: - all cardioactive glucosides inhibit myocardial form of the enzyme Na/K ATPase, which leads to the cummulation of Na+ inside of muscle cells and their stimulation to prolonged contraction Clinical signs: - changes of heart rhythm, which are serious and can lead to death - nausea, diarrhoea, ataxia, fainting, bradycardia, cyanosis Treatment: - emesis, gastric lavage, repetitive doses of activated charcoal, administration of antiarrythmic agents, fluid therapy, oxygen inhalation

Answer 72

- the Most often used rodenticides - Divided into 3groups: - coumarine derivates => first generation => cumulative principle - coumarine derivates => second generation => often single-shot agents - indandione derivates=> often single-shot agents

Answer 73

Coumarines -similar to vitamin K -compete with it on hepatocyte receptors -Several factors of blood coagulation produced in liver in an inactive form => activation is done by carboxylation in the presence of vitamin K as a co-factor -Vitamin K must be in active quinone form. - After carboxylation changes to inactive epoxide form *To transform it back, we need an enzyme epoxide-reductase -Coumarines bind to this enzyme and block the cycle of vitamin K - increasing amount of inactive clotting factors in blood=> haemostasis worsens -Chronic exposition - direct damage of veins - increased fragility

Answer 74

-first phase - spontaneous bleeding from nose (epistaxis), mouth, anus; -weakness, sleepiness, apathy, hematuria and melena (black excrements with digested blood) long bleeding after the slightest injury second phase – spontaneous subcutaneous bleeding, bleeding to muscles, body cavities – haemorrhagic diatesis. Animals die due to hypovolaemia and anaemia Factors that worsen intoxication: => physical activity, hard and rough diet Pathological examination: multiple haematomas, hemothorax, hemoperitoneum, anaemia of body organs; blood not coagulated, of red colour even after death

Answer 75

- Intravital or post mortem samples of tissues, GIT content, blood, urine +rests of food or bait: -Quick test.=> measures prothrombine time in blood plasma (citrates – block coagulation – coagulate after addition of calcium and tromboplastine ) -Physiological time for dogs /cats is about 10 sec, pathological 100 sec -PIVKA test => measures the concentration of inactive clotting factors in blood Inorganic rodenticides (Zn3P2)

Answer 76

- Keepers often come quite late => first signs of poisoning are mild and non-specific - Administer vitamin K as a direct antidote for at least 5 weeks ! - Administer it s.c. to avoid another massive bleeding - In critical cases, blood transfusion is also possible - Keep animal in calm, give fluid diet (in ruminants grains, not hay)

Answer 77

-Micromycetas => microscopic fungi which are saprophytes -They are heterotrophic=> don’t use photosynthesis - Most of them produce toxic => mycotoxins -products of secondary metabolism and their production depends on many factors as temperature, humidity, substrate etc. -Very stable in many conditions, esp. termostable - We know quite well what are the signs of acute exposition to mycotoxins -But there are also chronic expositions and not only by alimentary route, but also by inhalation. We don’t know much about that, but we predict their harmful effect (for example aflatoxins are surely carcinogenic)

Answer 78

-Mycotoxicosis has been known since ancient times -There were a lot of poisonings from ergot alkaloids -Ergot (cockle) is a parasite on rye. - Main signs were convulsions, abortions, hallucinations, maniacal depression, etc. -Since 18th century, wheat and potatoes are a significant part of diet instead of rye=> these poisoning are rare

Answer 79

- There are more than 300 mycotoxins - only 20 of them are toxicologically important - Laboratory diagnosis of mycotoxins is not very easy - there are a lot of them - methods are rather expensive and difficult - mycotoxins are not homogenously distributed in the substrate -Decontamination of affected food is very expensive and usually impracticable,=> food must be destroyed

Answer 80

-Aflatoxins are the most known and spread mycotoxins in middle Europe - Discovered in 1960 in the Great Britain => Turkey X disease was examined an found that it was not an infectious disease but poisoning by mycotoxins from contaminated food -Produced by Aspergillus flavus, A. nomius, A. parasiticus -4 aflatoxins - B1, B2, G1, G2 -In an organism=> changed by hydroxylation to aflatoxins M1, M2, GM1, GM2 - The best substrates for their production are cereals, oily crops -termostable, they bear up temperatures above 250 °C -Toxicity of aflatoxins: B1 > G1 > B2 > G2, others less toxic -B1 is a potent hepatotoxic agent +carcinogenic and mutagenic effect, forms adducts with DNA -There are international limits on aflatoxin content in food (FAO/WHO) -To aflatoxins closely belongs sterigmatocystin, also produced by Aspergillus - Its structure is similar to aflatoxins - It is genotoxic and is suspected from carcinogenity

Answer 81

-Produced by microscopic fungi families of Penicilium and Aspergillus - The most potent ochratoxin A -Optimal temperature for growth is 25-30 °C for Penicilium *but grows also in 6 °C in a fridge if there is enough humidity 30-40 °C for Aspergillus -There is a great distribution to all organs in organisms -Only in ruminants are small doses destroyed by bacterial microflora in paunch - Block proteosyntesis – molecule contains phenylalanin – exchange with it -Destination organs of ochratoxin are liver and kidneys - Ochratoxins are primarily nephrotoxic - chronic exposition act as immunosuppressive, teratogenic and potentially carcinogenic agents -Ochratoxin A causes pig disease called => Porcine mycotoxic nephropathy and on cause Balkan peninsula human disease called=> Balkan endemic nephropathy

Answer 82

-Fusarium produces a lot of different mycotoxins -The substrates are usually cereals and potatoes -We distinguish 3 main groups of Fusarium mycotoxins: trichotecens, zearalenon, fumonisines -In contaminated food, there are often many of them together. =>Their combination is worse than effect of each one separate

Answer 83

-148 agents most common are: deoxynivalenol, nivalenol and T2 toxin -Absorbed very well and fast - metabolised and quickly excreted by urine and excrements -Don’t stay as a residue in tissues -Gastrotoxic, cause vomiting and inappetence; - haematotoxic – damage haematopoetic and lymphatic tissues - cause immunosuppression

Answer 84

- Also called F2 toxin - Significant estrogenic effect - Causes vulvovaginitis, disturbs sexual hormones - problems with reproduction in animals, especially in swine - Its typical substrate is maize (corn – Zea mays)

Answer 85

• Produced also by Penicilium and Aspergillus, most common is Penicilium expansum • Substrates - apples and less often other fruits (soft rottening of fruits) • Spores of P. expansum live naturaly on the surface of fruit and don’t cause any harm • But after the damage of the fruit (mechanical or by insects) they get to the flesh of the fruit, germinate, start to grow inside and produce patulin • The content of patulin is measured especially in food for children (fruit snacks etc.) • It is destroyed in temperatures above 80 °C (pure patulin, but in fruits it needs approx. 120 °C for 20 minutes, as it is stabilised by vitamin C) and during alcohol fermentation

Answer 86

* Patulin binds to –SH groups of proteins and changes functions of enzymes and proteins, increases permeability of cell membranes * Acute poisoning is seen in farm animals fed with waste from cider houses etc. and include GIT and neurological signs. * In humans and some herbivorous pet animals chronic poisoning is more possible and involves teratogenic and immunosuppresive effects

Answer 87

Produced also by Penicilium and Aspergillus, most common is Penicilium roqueforti Substrates are cereals, nuts, fruits, but mainly spoiled food like bakery, pasta, cheese, meat products, silage etc. Toxins produces are penitrem, paspalinin and most often roquefortin Poisoning is typical in dogs and is sometimes called garbage poisoning

Answer 88

Inhibition of inhibitory neurotransmitters GABA and glycine, or stimulation of receptors for excitatory neurotransmitter glutamate. All mechanisms lead to hyperexcitation ``` Clinical signs may involve GIT signs like vomiting and diarrhoea, but are typical with long lasting (hours to days) and hard to treat tremors and convulsions ```

Answer 89

- Mainly on maize in Mediterranean area and USA | - All species can be affected, but fatal outcome is typical for horses and pigs

Answer 90

- Interference with sphingolipid metabolism. Lacking sphingolipids are problem for membrane function of all cells - In all species liver damage, where sphingolipids are synthesized, appears - Horses are sensitive to lack of sphingolipids in myelin sheaths in neurons and suffer from a disease called ELEM (Equine leucoencephalomalacia) which results in paralysis of muscles and failure of vital centres in brain - Pigs suffer from lack of sphingolipids in myocardial cells and develop cardiac failure with lung oedema (PPE – porcine pulmonary oedema) and die from suffocation - Fumonisines are also promoters of carcinogenesis and tumours of oesophagus and liver were observed after chronic intake of minimal doses

Answer 91

- Date, when it was found out - All present people, including their addresses and phones - Locality - Owner if it is a pond - Length or area of affected place - Kinds, age and numbers of dead fishes - Behaviour and clinical signs in living fish - Possible sources of contamination - Samples – what was taken, how much, where it was sent - Measures in place – temperature and oxygen !!! - Conclusion of present people what kind of toxin could be a source of poisoning - Plan of the place - Signatures of all present people

Answer 92

Poisons in honey bees cumulate in a venom sack. Honey is absolutely necessary source of nutrition for bees, moreover in winter they can’t remove their faeces from hives, so poisons can’t be excreted these ways. Almost everything goes to venom, differences in honey quality (means honey produced directly by bees, not mentioning treatment of bees or changes and contamination added later during the processing of honey) are thus quite low.

Answer 93

a) plant toxins  Many plant toxins are safe for honey bees, because bees lack the function which is influenced by toxin, or have specific detoxifying enzymes.  Toxic are colchicine (Colchicum autumnale) and anemonine (Ranunculaceae family plants) - not massive intoxications, appear only in locations where there is huge amount of this plant. Bee is not dying after visiting one flower like this.  Probably toxic are oligosacharides in lime tree (Tilia sp.) and sunflower. We found a lot of dead bees under these plants. Might be also amplified by other conditions, because so called “summer” honey bees, which live only a few weeks, are during the flowering of these plants at around the end of their life, so are old and thus maybe more susceptible.

Answer 94

b) NaCl  solution of concentration more than 1 % is toxic to honey bees c) Metals  arsenic – released mainly form fossil fuels like coal. With decrease in using coal, the number of such poisonings decreases too.  Also lead and copper poisoning in honey bees were described in industrial areas. d) Gases  chlorine, fluorine – bees are a sensitive indicator of it

Answer 95

Hydroxymethylfurfural  HMF – its content allows control honey quality easily. It increases if the honey is old, in case it was processed under higher temperatures, or sucrose solution was added to adulterate it  produced from sugars during caramelization of sugar  inedible for bees – they suffer from hunger and it causes them GIT problems, in higher concentrations the poisoning might be quick.  in humans it is classified as a possible carcinogen. Quality limit for HMF – Czech Republic only 20 mg/kg of honey, EU 40 mg/kg of honey. Toxic concentration for honey bees is 200 mg/kg.

Answer 96

 nowadays most common source of poisonings in honey bees  very dangerous are bipyridil herbicides (desiccants) paraquat and diquat – death comes after longer time, bees bring the contamination to hive where they affect other bees. After some time they loose the ability to fly, so they walk and “paths” of walking honey bees are seen around hives.  most dangerous and causing most of the poisonings are insecticides:  fipronil from phenylpyrazole group (LD50 = 6 nanograms/bee) - inhibition of GABA, death after approx. 4 hours – they return back to hive and contaminate also other bees.  imidacloprid from group of neonicotinoids – influence nicotinic receptors  both fipronil and imidacloprid have residual activity (stay in plant tissues but also in contaminated bees for weeks and by contact can still cause poisoning)  organophosphates and carbamates

Answer 97

1) Based on cases of poisoning, cases studies (case histories) It is not possible to perform toxicity tests/ monitor effects of chemical on people and most species of animals. =>important to learn as much as possible from individual cases of poisoning =>that’s why we so often return to the history of toxicology

Answer 98

2) Methods for toxicity prediction -the relation between the chemical structure of substances <=> their biological characteristics. *the knowledge of molecule structure of a new xenobiotic alone will not be suffice for a definite evaluation of biological properties. -chemical structure will allow for a group classification. Toxicity prediction => can use successfully in case of series substances exhibiting chemical similarities. -relationship between the chemical structure and biological activity expressed as: Quantitative Structure – Activity Relationship (QSAR). -Computer programmes are developed for => toxicity predictions. But predictions may differ from reality => tests on experimental animals are necessary before a final decision can be taken. Thanks to prediction processes, however, the tests can be minimized (low number of animals)

Answer 99

performed at the level of: - cells and tissues (in vitro tests) - organisms - Biocenoses (all organisms interacting in the same biotope)

Answer 100

- 2 type of cells can be used: - primary cell cultures (higher sensitivity, lower reproducibility) - stable cell cultures (lower sensitivity, higher reproducibility) - 2 types of evaluation - direct evaluation - numbers of dead cells - cytopathic effects - indirectly evaluation (evaluations based on physiological reactions of the cells). - example :

Answer 101

- example : Neutral Red Test (NRT). - undamaged lysosomes => bind neutral red. - After a 20-hour period of exposure to the test substance => neutral red solution is added (wating) => then it is drained off =>lysing solution is added. Undamaged cells are lysed,=> neutral red released ( measured by photocolorimetric)

Answer 102

- vitro test advantage: - speed - reproducibility - low financial and time demands. Vitro test disadvantage: -not substitute for the enzymatic - immune system of the living organism.

Answer 103

- most frequently performed . -include all trophic levels, i.e. bacterias, invertebrates and vertebrates - Methods used in such experiments => are unified world-wide by the : Organisation for Economic Cooperation and Development (OECD) International Organization for Standardization (ISO).

Answer 104

- very expensive and time consuming - used in special cases only. => preparation applied over a defined area of land => its effects are monitored on: soil microorganisms, earthworms, game, birds etc., * and its residual concentrations are studied. Similar methods are used for experiments in the aqueous environment.

Answer 105

- Chemicals play an important role in daily life. Therefore, their safety for man and the environment has to be considered carefully. OECD works on the development and co- ordination of environment health and safety activities internationally. - The OECD Guidelines for the Testing of Chemicals are a collection of the most relevant internationally agreed testing methods used by government, industry and independent laboratories to assess the safety of chemical products.

Answer 106

Reduction (less laboratory animals) Replacement (replace with evolutionary lower organisms and if possible, by tissue cultures, cells, computer modelling) Refinement (the animal should be stressed and harmed as little as possible, welfare of laboratory animal is absolutely necessary)

Answer 107

Testing is divided into several parts: Section 1: Physical Chemical Properties Section 2: Effects on Biotic Systems Section 3: Degradation and Accumulation Section 4: Health Effects Section 5: Other Test Guidelines

Answer 108

LD50 (lethal dose which causes death of 50 % of tested animals) LC50 (lethal concentration which causes death of 50 % of tested animals) NOEC (no observed effect concentration – the highest concentration tested in which no adverse effect was detected) LOEC (lowest observed effect concentration – the lowest concentration tested in which an adverse effect was detected)

Answer 109

Based on the value of LD/LC/LOEC assessed, chemical is classified and described by Risk and Safety Statements, also known as R/S statements or R/S sentences, a system of hazard codes and phrases. - In 2015, the risk and safety statements will be replaced by Hazard statements and Precautionary statements in the course of harmonizing classification, labelling and packaging of chemicals by introduction of the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Answer 110

- acute and chronic tests - tests on lethality, carcinogenicity, genotoxicity, reproduction, mutagenicity, dermal and eye toxicity, inhalation toxicity etc. - for the treatment of poisonings, the most important is acute toxicity

Answer 111

Acute toxicity: If we do not know approximate toxicity from testing on other animals, we start testing with so called limit dose, which is 2000 mg/kg of body weight. If the result is negative (no toxic effect on the organism), we do not continue with further testing.

Answer 112

- OECD 401 – Acute oral toxicity: - not used since 2002, but all the substances which were approved for the use before this date were tested by this method - 10 animals for each dose (usually 3-5) had to be used - the result of the test is value LD50 - according to LD50, we divide chemicals into several categories, they are described by so called R (risk) sentences – these are always mentioned on the label of the product: R 28 – very toxic if swallowed, LD50 is less than 25 mg/kg R 25 – toxic if swallowed, LD50 is between 25 - 200 mg/kg R 22 – harmful if swallowed – LD 200 – 2000 mg/kg

Answer 113

- OECD 423 - Acute Toxic Class Method: - only 3 animals used (usually females) - only fixed doses tested: 5, 50, 300 and 2000 mg/kg - the experiment goes in several steps - one of the fixed doses is chosen (based on information from previous tests, or limit dose), first experiment is done. According to the result, test is repeated with the same dose in males, dose might be increased or decreased. - according to the results in last step, substance is put into one of the 5 categories (0-5, 5-50, 50-300, 300-2000 and 2000-5000 mg/kg) according to Globally Harmonized System (GHS)

Answer 114

- Fish used in the tests: e.g. zebrafish (Danio rerio), common carp (Cyprinus carpio), medaka (Oryzias latipes), guppy (Poecillia reticulata), rainbow trout (Onchorhynchus mykiss) - Limit test is done with the concentration 100 mg/l of water - Types of test based on testing solution changes:  Static test (only one solution during whole 96 hours) - usually impossible to perform it due to cummulation of metabolism products and due to decrease in tested substance concentration  Semistatic test (change of solution every 48, 24, 12 or less hours according to the situation and stability of the substance) – fish are moved to other aquariums with newly prepared tested solutions  Flow through test – continuous change of tested solution - Test with standard (K2Cr2O7) together with test with the substance itself is necessary to check sensitivity of tested fish and avoid using more or less sensitive fish than is average

Answer 115

- 10 fish into each concentration - Result is LC50 value - Validation of the test:  Mortality of fish in control tank should not exceed 10 %  Oxygen saturation in water has to be higher than 60 %  Concentration of tested substance should not decrease under 80 % of original concentration

Answer 116

OECD 204 - Fish, Prolonged Toxicity Test: 14-Day Study - Results are values of LC50(14d), NOEC and LOEC OECD 210 - Fish, Early-Life Stage Toxicity Test + OECD 212 - Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages - Fertilised embryos are used - Lasts:  31 days for carp – OECD 210, so called embryolarval test  6-7 days for carp – OECD 212, so called embryonal test - Results are NOEC and LOEC

Answer 117

OECD 215 - Fish, Juvenile Growth Test - weight gain is evaluated - we use mainly rainbow trout - results are NOEC and LOEC values

Answer 118

 R50: LC50 is less than 1 mg/l - Very toxic to aquatic organisms  R51: LC50 is between 1-10 mg/l - Toxic to aquatic organisms  R52: LC50 is between 10-100 mg/l - Harmful to aquatic organisms  R53: May cause long-term adverse effects in the aquatic environment

Answer 119

``` OECD 205 - Avian Dietary Toxicity Test: - oral toxicity - LC50 in mg/kg of feed OECD 206 – Avian Reproduction Test: - NOEC and LOEC Classification: - no R sentences for birds ```

Answer 120

- Testing of pesticides mainly OECD 213 - Honeybees, Acute Oral Toxicity Test: - oral LD50 in micrograms/1 bee OECD 214 Honeybees, Acute Contact Toxicity Test: - dermal LD50 in micrograms/1 bee

Answer 121

Classification: LD50 < 2 micrograms/bee – very toxic R57 (others do not have R sentence 2-11 micrograms/bee slightly toxic > 11 micrograms/bee relatively non-toxic) Better classification is based on hectare dose of pesticide: calculation of so called Risk factor. RF=hectare dose in grams/ LD50 in micrograms per bee

Toxi part 1 Flashcards

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