Nutritional Toxicology- What is toxicologyo Very similar to farmicology o Mainly concerned with the toxic part of our nutrition Poisons o Occurrence- where are they producedo Detection- o Regulation- what does the government do with it How do we keep it out of our food chain o Effects- can it kill you What does it do to you What does it do to our animals o Properties- are they fat/water soluble Where are they found Can they be destroyed - Nutrient Reponse vs. toxic response (*Chart on slides*) o Really only looking at the right side o No effect doesn’t really cause any effect to the animal or human o Threshold does- tip the animal or human into toxicities- We have hit where it is dangerous the animal o So what makes something toxic is the dose So even water can be toxic o- What defines a toxicant (poison)o Central concept in oxicology Dose response concept It is the lethal dose that makes it a toxicanto “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.”- Paracelsus (1493-1541)- Dose response concept o Two types of dose responses: Graded (individual) dose response – characterized by dose related changes in severity of the toxic response.- The time, the circumstances etc. it is on a personal level Quantal (population-all or none) Dose Response- Characterized by dose related changes in the number of individuals of a population responding- LD50- the lethal dose for a rat or mouse. (graph on slideso Potency vs. efficacy Potency – the dose at which you are first effected by More effective because your response goes to a higher levelo So what must happen for a chemical to elicit a toxicosis in an individual? Exposure- how much can you come into contact before all goes to hell in a hand basket Disposition - Absorption- Disruption- Elimination- excreting it from the body and metabolism Toxicodynamics – the mode of action (how does it elicit it’s effect) - Goals of Toxicology o We study these effects to help with prevention and to more manage what is in our food supplyo Toxicant identification Need to know what it is before we protect the animal from it- Toxicants- fall into 3 broad categorieso Manmade Organophosphates- VX gas- Sarin Dioxinso Natural plant toxicants Ricin (caster oil plant, lectin- carbohydrate binding protein) Gossypol (cottonseed-reproductive toxicant) o Fungal toxicants Mycotoxins- Swainsonine- Ergot alkaloids- Mycotoxinso Produced by fungio Often associated with foods/feedso General types Field (fungi)- During growth of the plant (environment and/or damage to plant) o Swainsonine (Rhizoctonia spp., Embellisia spp.) –a neurotoxino Ergot alkaloids (Neotuphodium coenophialum) o Alfatoxinso Storage (fungi) During storage of product (improper storage)- Aspergillus (aflatoxin), Fusarium spp. (fumonisins, tricothecenes) - Swainsonineo Indolizidine Alkaloid 8aB-indolizidine-1a,2a,8B-triol Present in:- Swainsona, astragalus, oxytropis spp.- Rhizoctonia leguminicola N-oxide exists in at least Astagalus spp. o Mode of action Inhibition of a-mannosidase enzymes- Lysosomal form (i.e., acid a-mannosidase)o Result-lysosomal storage disease- Golgi form (i.e., a-mannosidase II)o Result- high mannose type glycoproteins- The lysosome swells - With out that golgi we cant get the high mannose typeo Relevance to animal health Natural exposure via locoweed consumption- ~$330 million loss/ye Locoism - Related to genetic mannosidosis- Depression - Ataxia- Infertility - Cardiovascular disease (high mountain disease)- Impaired immune function- Emaciation- Tremors- Abortion o Disposition-
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