Toxicology Flashcards
Poison Definition
A poison is a xenobiotic substance that after being contacted or entering the body by inhalation, ingestion, dermal contact or injection in sufficient quantity will cause a detrimental effect on the organism.
Venom Definition
A xenobiotic of biological origin that is inject via a bite or sharp body part to exert detrimental effects
Hazardous Definition
For a substance to be hazardous, it must be toxic and it must be likely to be encountered in a form that can be assimilated, likely to be eaten, inhaled or come into contact with integuement to cause sufficient harm, reach a sit in the body where it can do the harm, interact with crucial metabolic pathways.
The hazard is the potential of an agent under defined conditions of exposure to cause an adverse effect.
Toxic Definition
May not be likely to cause poisoning and may be non-hazardous.
So they might be unlikely to be encountered by animals, exist in a form that can be assimilated and may be needed in large volumes, highly unpalatable or emetic at sublethal doses.
Properties of Toxic Substances
Ionisable, fat soluble, diffusible gas, bind to body components
Absorption Mechanisms
Must cross natural barriers, absorption routes include GI tract (stomach and SI), lung-gases, skin barriers
May be absorbed by simple diffusion, passage through pores in plasma membrane, specialised transport systems
Volume Distribution
Into 3 major compartments - vascular, extracellular (must be lipid soluble to difuse through endothelium or fit into interendothelial pores), intracellular (enter through very small pores in plasma membrane).
Volume distribution can be complicated by continuous excretion, presnce of transport systems, extracellular storage sinks of fluoride, lead or strontium and barriers to distribution including blood-brain barrier, placental, blood-testes barrier.
Biotransformation
Conversion from lipophilic to hydrophilic form suitable for secretion. The liver is responsblie for this transformation but also occurs in lungs and kidneys.
Phase I - degradative reaction involving oxidation, reduction or hydrolysis, occurs in SER, requires cytochrome P450 and metabolites may become more or less toxic after this phase.
Phase II - synthetic reaction involving congugation with a hydrophilic molecule ready for excretion. Usually involves enzymes in the cytoplasm such as glucuronyl transferase.
Bioactivation
When a small number of compounds have low or no toxicity as ingested but after metabolic alteration, usually after Phase I, become toxic.
Induction
CYP are heterogenous groups of enzymes that have the capacity for up-regulation if increased amount of substrate is encountered, this is called induction. Allows organisms to adapt and become resistant to xenobiotic load. Can see SER hypertrophy and glassy hypertrophied cytoplasm.
Can be detrimental if a xenobiotic is so rapidly metabolised that it produces an excess of toxic metabolite in higher local concentrations or sometimes CYP induction to one compound impacts the toxicity of an incidental or unrelated compound. May increase metabolism of hormones or therapeutic agents.
Resistance and Tolerance
Ressitance is property developed by selection over many generations and possessed by all members of the species. Potential mechanisms include enhanced hepatic excretion, modification of ocmpounds by gut microflora, modification or circumvention of biochemical pathways vulnerable to the toxin. For example Koalas survive entirely off eucalyptus leaves.
Tolerance is an individuals acquired or conditioned resistance to normally toxic doses of the xenobiotic. Potential mechanisms for tolerance include ingestion of sub-lethal amounts altering absorption, storage or elimination rate, uo regulation (induction) of metabolic pathways which happens with many therapeutic agentsand partitioning of lipophilic substances into fat stores so that fat animals may tolerate higher doses of fat soluble substances because they partition into fat stores.
Mechanisms of Chronic Intoxication
Functional reserve of organs until significant amount of damage, high demand on organ
Intake versus utilisation for example in Vit D poisoning where adults acutely poisoned and young animals able to tolerate doses longer
Elimination which is exceeded by uptake, some compounds metabolised and excreted slowly, but exposure above elimination rate shows signs when uptake rates enhanced or storage capacity exceeded
