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Flashcards in Toxicology Deck (44):

Define toxicant

A poison that is made by humans or put into the environemtn by human activities. Many pesticides are toxicants


Define venome

A type of toxin, a poisonous substance secreted by some animals and typically injected into aggressors by biting or stinging


Define a toxin

A poison of biological origin


Define toxicity

The dose required of a toxicant to produce a detrimental effect (the degree to which a toxin can harm an organism)


Define xenobiotic

"Stranger to life", a chemical that is not usually sound at significant concentrations or expecteed to reside for long periods in organisms (a substance that is foreginto the body or to an ecological system, typically synthetic)


Define toxicosis

A pathological conditions caused by the action of a toxin


What is LD50?

The dose required to kill 50% of the population


What is EC?

The effective concentration


Describe toxicant accumulation

- Xenobiotic compound enters body
- Absorption exceeds elimination
- Xenobiotic compound enters the ecosystem and accumulation exceeds destruction or removal


Describe how tolerance may occur

- The ability to show less response to a specific dose with repeat exposure
- Acquired, not innate, resistance
- As exposure to a toxin increases, so does the ability's body to remove it (think light-weight vs regular drinker)
- Metabolism is not as used to dealing with the toxin when there is infrequent exposure


What is the chronicity factor of a toxin?

- The ratio of a the acute to chronic LD50 dose
- (1 dose LD50)/(90 dose LD50)= chronicity factor
- A value over 2 indicates a compound is relatively cumulative (effect builds up as time goes on)
- An increasing chronicity factor suggests that the compound is accumulate and signs are more significant


How does tolerance affect chronicity factor?

- Toleracne icnreases the 90 dose LD50
- This in turn decreases the chronicity factor
- The body is more able to remove the toxin


Where can toxicants be absorbed?

- Alimentary tract
- Skin
- Mucous membranes
- Lungs
- Uterus
- Injection


What can affect absorption of a toxicant?

- Solubility
- Formulation
- Ionisation


Explain how solublity affets absorption

- E.g. barium vs barium sulphate
- Barium highly toxic, barium sulphate not easily absorbed


Explain how ionisation leads to varying degrees of absorption and trapping

- E.g. antibiotics can be ionised depending on pHof an organ/tissue
- When ionised are trapped
- Certain antibiotics may be trapped in certain organs


Describe the distribution of toxicants

- Local
- In blood stream to site of toxicity
- Storage deposits (fat vs water soluble, things in water usually excreted, things in fat usually stored)


Describe the storage of toxicants

- Not necessarily at site of toxicity (target)
- e.g. lead concentrates in bone/teeth but causes neuropathy/blood disorders
- Where is put in or accumulates may not impact where teh toxicity occurs


Describe the metabolism/elimination of toxicants

- Drugs may be metabolised to a less or more toxic state
- Drastically affects rate of clearance of compounds
- Can occur at any point during compound's journey from absorption to excretion


Describe thr excretion of toxicants

- Metabolites excreted in bile
- Some specific active secretion in bile (lead, arsenic, mercury)
- Enterohepatic recycling can occur
- Toxicants in faeces may enter food chain if faemes remain unchanged and are ingested by another organism


Describe enterohepatic recycling

- Bile salts recycled
- If compunds are bound to bile salts, can be taken up and recycled leading to repeated exposure to toxicant


Define an acute intoxication

Effects during a 24 hour period


Define a subacute intoxication

Effects of daily exposure within 1-30 days


Define a subchronic intoxication

Effects of daily exposure within 30-90 days


Define a chronic intoxication

Effects during a period longer than 3 months


List ways in which toxicantsmay produce toxicosis

- Metabolism form a harmless substance to a harmful one
- Toxicity can result from adverse cellular, biochemical or macromolecular changes
- Toxicants may be specific to a tissue or system
- May cause generalised damage
- carcinogenicity
- Developmental toxicity


What may affect the toxicity of a toxicant?

- Exposure factors (dose, frequency, time or year, concurrent factors -ingestion)
- Biological factors (species differences in kinetics, inability to vomit, health status, age, gender)
- Chemical factors (isomers)


Explain how toxicants can be carcinogenic

- Complex multistage process of abnormal cell growth and differentiation
- Initial neoplastic transformations result from mutaiton of cellular genes that control normal cell functions
- May lead to abnormal cell growth
- May involve loss of suppressor genes that would usually restric abnormal cell growth
- Benign tumours grow at site of origin, do not invade adjacent tissues or metastasis, generally treatable
- Malignant invade adjacent tissues or migrate to distant site, metastasise, more difficult to treat


Describe developmental toxicity

- Adverse effects in developing embryo or foetus
- Toxicant exposure can be to either parent before conception or to mother and her developing embryo/foetus
- 3 basic types: embryolethality, embryotoxicty, teratogenic
- Can either act directly on cells of embryo causing cell death or damage, leading to abnormal organ development
- May induce mutation in parent's germ cell, transmitted to fertilised ovum
- Different effects at different stages of pregnancy


Define embryolethality

Embryotoxicity that causes the death of the embryo


Define embryotoxicity

Toxic effects on the embryo by a substance that crosses the placenta


Define a teratogen

An agent that can disturb the development of an embryo or foetus


List the key information in the investigation of a suspected case of intoxication

- Number of animals exposed/sick/dead
- Age, weight
- Chronology of morbidity and mortality
- Clinical signs and course of disease
- Any prior disease conditions
- Lesions obserbed at necropsy, careful examination of ingesta
- Response to treatment
- Related events e.g. feed change, water source, other medications, feed additives, pesticide applications
- Description of facilities, acces to refuse, machinery etc
- Recent/past locations and when moved


Outline the therapeutic options for the management of toxicosis in veterinary species

- Reduce furher absorption
- Support
- Specific antidotes


How can absorption of a toxinbe reduced?

- Emetics
- Decontamination (skin, administration of activated charcoal, vacuum, vegetable oil for oil based toxins)
- Adsorbents (coating action, binds bacteria and toxins)


List some common examples of poisons

- Pharmaceutical products
- Pesticides
- Household products
- Toxins
- Industrial chemicals


List some hepatotoxins of veterinary importance

- Paracetamol
- Copper, iron dextran
- Vitamin A
- Mebendazole
- Carbon tetrachloride
- Coal tar/pitch
- Phenols
- Aflatoxin
- Fumonisin
- Amanita mushroom
- Blue-green algae
- Pyrrolizidine alkaloids


List some important toxins of the CRS

- Paraquat
- Digoxin
- Cytotoxic mixture of enzymes from adder bite


List some importnat GIL toxins

- Ragwort (pyrrolizidine alkaloid)
- Ibuprofen
- Rhododendron (andromedotoxins)


List some important URI toxins

- Antifreeze (ethylene glycol)
- Grapes/raisins (mechanisms of toxicity unknown)
- Acorns (pyrogallol, gallotannins, polyhydroxyphenolic compounds or their metabolites)


List some important LCB toxins

- Bracken (norsequiterpene glycosides, thiaminases, ptaquiloside)
- Onion (N-propyl disulphide)
- Anticoagulant rodenticides (warfarin, diphacinone, bromadiolone, brodifacoum)


List some important NEU toxins

- Slug or snail bait (metaldehyde)
- Chocolate (theobromine)


Give an important MSK toxins

Sycamore (hypoglycin A)


Give an important ECN toxin

Artificial sweetener (xylitol)