Him him him him him him what you will instruct the scores in today's lecture adsorption intoxicants will do is try to talk about this progression of toxicology sources pathways receptors and controls I like to talk about this in terms of the sequence in fact the Fed's absorption of toxic and Susan that first stage will we have a source of intoxicant and we actually have a initiation of a path when we cross that fundamental threshold from chemistry to biology as we do this cross will have to know about some of the structures of routes are example of inbox and that's perhaps the major point of today's lecture are learning objectives what women do is try to describe some of the ways in which toxicants interact with selves what are we but sales and collections of cells which are in fact collections of chemicals and biochemicals so if we have a chemical toxicants actually going to interact how does this interact with these fundamental structures and substructures and recognize how the molecular characteristics of intoxicant affect its entrance so horrified explains human anatomy this is not anatomy course but I want to give you some briefing here in lecture and also in our textbooks of how toxicology is related to the integumentary respiratory and digestive systems of three major modes of intoxication or pathways of intoxication when is try to summarize these routes of intoxicant absorption as well wealth easy for us to come understand the organization of the body because insurance and suspicion the macro sense it's a part of us at we are but what we like to do is look at it in terms of the different levels of organization of the body and so in terms of toxicology we are very interested in the chemical level because toxicants are are are just that their chemicals and so they interact in a very direct basis with the chemicals and biochemicals bitter in our life system within advanced of the cellular system and then to the tissue level only organ level in the organ system level okay finally that will maybe have a disease manifestation that effects the entire individual but we start off small we start off in terms of our interactions at the molecular level so we would like to understand how this organism organizes from the molecular level on throughout because if we have an effect that the smallest level that can affect the demonstration of organization up through the whole lifecycle it's important for us to understand metabolism biosynthesis as well as catabolism is associated with the development of molecules of life it's important that we understand that these molecules of life start out as subunits and that are typically monomers and develop into polymers since the subunits are the raw chemicals and sometimes we can have some substitutions are some impacts were toxicants actually impacts of the subject unit level but then we have macromolecules in some examples of those are saccharides polysaccharides glucose to glycogen amino acids to proteins and nucleotides to DNA and RNA and so interrupting this assembly of the bio synthesis of these polymers these macromolecules is a potential source of toxic host we can look into the relative importance of some of these monomers in the polymers if we examine the composition of bacteria in this table gives us than the makeup of E. coli in terms of some of these endpoints of biosynthesis will know that the percent of water seminary percent in both most light forms is only counselor one molecule is in contrast to proteins which amount to about 10 to 15% inverse lifeforms that actually give us as much as 3000 individual types of molecules great diversity and proteins that should be a clue that in fact in terms of the mechanism of body and all of the life systems that we support proteins have a Pacific because of the diversity have very specific roles and the potential to disrupt is very high because are so many of them in terms of molecules of life nucleic acids DNA and
RNA we have one DNA obviously but in terms of RNA RNA codes for specific proteins and so we need at least as many RNAs as we have discrete proteins and so will have more than 3000 RNAs polysaccharides set in terms of percent of total weight about 3% and there's about five or so different types of molecules

lipids about 20 different types of molecules various building block molecules sulfate phosphates of those type about 500 and the various ions about 20 different modules and so all of these tell us that in fact to terms of the consequences of intoxication impacting proteins released from a numerical point of view we have a high probability of potentially disrupting life processes to understand the toxicology adsorption we need to have the basics in in biology and cell structure and I'll take you back to your freshman sophomore biology classes printing high school biology on reorient shoe lift to the basic processes we of the cell nucleus cell membrane for important terms of transport of chemicals into a place within the cell that they are perhaps these chemicals can do some damage we had ribosomes that connect to the protein RNA coding with the cytoplasm of the internal cellular fluids the mitochondria which developed the energy for cellular processes but these are important things you don't understand so a quick review of your biology is probably going to helpful in terms of understanding toxicology refresher here memories as well about the basic reproductive functions of the self in DNA we have the in the nucleus we have DNA that is performing replication that replications allowing transcription of RNA that actually leaves the nucleus and allows for translocation process in the ribosomes to actually make these proteins to the many different biological processes these proteins into the cytoplasm and sometimes are released from cell studies proteins are typically synthesized through a process called translation is actually these perform building brought are actually built from the building blocks called amino acids these proteins are long chains of amino acids they are made up of peptide bonds and disulfide bonds it's very important because all the time we have an accumulation of structures or build up the structure metabolism if you will we have a potential for toxic interaction and so in the building up of proteins whether it be by toxic peptides or by compounds and interfere with the disulfide bonds in the protein confirmation these are potential aspects of consequences on the molecular basis if we look at the role of proteins and we will hear a moment on we can see that we can have dramatic effects from this coating proteins the primary structure of our proteins referred to the sequence sometimes these proteins were modified by various groups in group sugar groups phosphates and they give us the diversity that is terms of amino acids from your biology remember that these are small molecules and give me a couple of them here just to give you an idea of what the Sistine alanine look like they give us an idea of what the subunits of protein look like as we collect those together they spontaneously form these peptide bonds and amino acid chains this particular chain I develop with support for modeling software is based in terms of thermodynamics pretty much or just added one amino acid after another income chaotic array which you notice is that they form long chains and they also have a substructure in the substructure is identifiable little bit with a provenfilling model the protein as these amino acid change develop you start seeing what amounts to helical coil and I feel coil is a secondary structure in a protein will also get some folding and some pleated sheets will also get some random coiling going on but this gives us the dimensionality of proteins that is very important in terms of their presentation of receptors and active sites for various things like enzyme function receptor function is very very important that as we understand toxicology we understand the chemical molecular basis of toxicology and we tried it would least imagine this in three dimensions even though our textbooks are slides are two dimensional on the websites we have some links to some structural programs that allow you to go in with certain macromolecules and actually grab them and rotate them I invite you in terms of resources and some challenges with this particular module to go in and play with that structural software that is available over the Internet to look at some of these databases of biological molecules to

get a sense for this third dimension depths of her speak so that you kind of understand how chemicals relate to biochemical for you back your hemoglobin protein structure begins as a two-dimensional representation you can see the alpha coils here comes the proteins substructure but you can see that within this hemoglobin protein structure we have between groups and hear the white dots in both of these cases the oxygen that the in group is is using as to transport and so this is important in terms of understanding the roles and relationships of intoxicating chemicals to the biochemicals that make us now terms of protein functions we need to understand that there is a potential for disruption once we have adsorption of a chemical in terms of the primary phase of toxic roses protein functions are wide ranging or go to a list here just to give you an idea of the laxity of these 3000 or so chemicals that make up lifeforms antibodies so these are proteins that recognize molecules of invading organisms are very important terms of function receptors are part of the cell membrane are typically will respond recognizable proteins are chemicals and somehow through some chemotaxis informed cell to start a cascade of effects if we look at things like a endocrine disruption terms of the picture toxicological fact there's a receptor disruption we have a set proteins it function as enzymes that will assemble or digest the other chemicals we have five neurotransmitters are hormones that trigger receptors we have structural proteins that form channels and pores within cells and support tissues in terms of cellular absorption there are many different functions that happen in terms of a chemical crossing a cellular membrane typically with the ways that chemicals Ross saw that membrane will result from diffusion that requires a concentration gradient that we have a high concentration on one side of the membrane and a low concentration on the other sometimes will have a facilitated diffusion will be some membrane surface carrier proteins actually facilitate the transport of these chemicals across membrane's these for instance an example of this is glucose transport and then we have active transport where we actually use cellular energy the ATP to help actually transport or change chemical some examples of these are and/or exocytosis or visual pizza ptosis the swallowing up that souls do in terms of their particular metabolism and one of things we need to cut of have a good recognition of this would undertake an analysis of adsorption of toxicants is so the structure and form of the cell membrane and this is fundamentally as you recall your biology chemistry and biochemistry classes made up of the phospholipids in a bilayer that forms the so micellar membranes is very important that we understand that these in fact are chemicals that can have chemical reactions. Even though they are structural they still can be interacted so for example when we talk about oxidative stress free radicals and free radical damage this lipid bilayer can be attacked could happen oxidative attack was free radicals which cause and effect of the layer perhaps rupture of the cell membrane antigen can potentially release those of some obstructive contents or disrupt critical resources within itself that are required for life now we need to understand that if absorption that there are four basic types of cells in the human body of the epithelial cells in the particular makeup things like covers windings and secretions fervor important barrier first layer barrier there are convective cells they give us support and energy their muscle cells so they allow us to move in and the nervous cells the new cells will yield electrical impulses transmit information or conduit so to speak of are neurological system to types that are most important in toxicology or the epithelia and nervous system cells the epithelial we have a classification for breakdown on this graphic of what these cells look like in terms of their their structures squamous shells are cells are flat simple squamous tend to actually run in and rose and stratified squamous 10 run in sheets will have cuboidal and simple cuboidal and clung our type self shapes in the epithelial and these are specific

for different types of tissue throughout the body they help us manage particular processes that occur in that organ or organ system in terms of nerve cells you'll find that there made up primarily of neurons of various kinds that allow for the development of a neurological response the connect to each other via dendrites in these dendrites have a synaptic cleft across which each cell can communicate to one another and typically in neurotoxicity we impact either the delicate balance of chemicals that allows the development of charger polarization of the self or in within an individual cell or we disrupt some of the tissues about that make up the cell cell membrane or we upset the balance of the enzymes in the critical neurotransmitters that allow the cells neurons communicate with each other and will talk about neural toxicology lectures in terms of the human body we have 11 organ systems the integument earlier this skin the largest organ in our body and skeletal muscular nervous system the endocrine system the cardiovascular system the lymphatic system the digestive system respiratory urinary and reproductive systems each one of these can be the target of intoxication in terms of adsorption this is the process by which toxicants across this epithelial cell barrier and so this is the critical first transmembrane movement terms of the cascade of effects of toxic roses and so what affects absorption will affect toxic roses we talked about and introduce the concept in terms of the initial concepts in toxicology lecture about all the different chemical manifestations of toxicants and how those manifestations physical state like a gas or liquid its polarity it's PK in terms of its ionization is KO'd W its optimal water partition coefficient all of these chemical phenomenon can affect absorption and absorption therefore affects them sort the exposure the exposure will affect those ghosts will affect size of the toxic response and so now you have the connectivity between the chemical and that is manifestation routes of adsorption is our primarily a integument earlier percutaneous thermal with you will respiratory and digestive these are the three routes and absorption or we are primarily concerned with in toxicology and so we have to have a good understanding of the physical structures and also the cellular makeup of those physical structures in terms of understanding routes of adsorption the integumentary system route is our skin or hair nails memory landslides largest organ in the body as I said it's made up of the epidermis dermis in the hypo dermis the epidermis is a vascular it's the outer one means it's doesn't have blood supply is made up of the characterized as stratum corneum that's about 215 or 20 cells that it actually provides maximum toxicant protection if you work around chemicals it's a good idea to keep the skin especially of your hands in good shape cracks in your epidermis of cracks you'll allow more potential absorption via more potential exposure the next layer down was the dermis this is highly vascular rises is where we have our nerve endings so we have a lot of the hands but in our skin general's the touch that we have the hair follicles of sweat glands or in the dermis in the hypo dermis we have the connectivity adipose tissue the support tissue that gives us are good looks this gives you out of a graphical representation of what skin looks like in two-dimensional here we have the stratum corneum the dead cells of Wilber are out there and we should these on regular basis that's a part of the epidermis followed by the dermis this vascularized area and the subcutaneous hypo dermis tissue that actually has a lot of the support structures and major bloodflow capillary systems that provide the nutrients for cell replication and skin growth but also provide a mechanism for transport of toxicants away from this barrier into other areas of the body in a systemic intoxication this gives you an idea of a quick case study in terms of skin lesion and how chemicals can have dermal toxicity of some variety another this is an unfortunate Kenyan child that found a pretty beautiful unfortunately this very attractive people was of the genus brachial's break in a style that is the bombardier beetles bombardier beetles have a defensive mechanism that they have

the mixing chambers in their body actually varies good at chemical warfare in terms of a creditor relationships this these two mixing chambers they have if they feel threatened though they actually squirt out this particular toxin itself a very high temperature exothermic reactions with the hot fluid it's a quinone based toxin and you can see from this young child it's not a nice wound happens is shooting the insect venom or the major routes in terms of rapid intoxication is the respiratory system route is rapid because we got that system of air we grieve the fairly rapidly and we have extremely high efficient exchange of atmospheric chemicals primarily oxygen and CO2 across our respiratory membranes it's made up of the stratified squamous epithelial tissues of the skin but in the respiratory system it's a squamous epithelium ciliated lumbar and cuboidal epithelium this allows for the development of noncharacterize her soft tissues but it ciliated Nick gives us what's referred to as a musical ciliary escalator if you've ever been in a dusty environment for extended period time and find yourself coughing for the rest of the day and your coughing up one of what looks like dusty material sputum is start it actually is the inhale dust that has risen up with these silly little microscopic hairs that is clear over period of time all have experienced that at one point in time the respiratory system is made up the nasopharyngeal associate the first part in the trachea bronchial and finally the pulmonary system in terms of its relationship with exchange with your vascular system this is a diagram of cartoon of the respiratory tract. See the nasopharyngeal aspect of the system the trachea bronchial's essentially hardware types going down into the pulmonary region of the we have these going off into the primary bronchus distribution tubes into the from the major freeways and the minor back Rosa bronchioles the bronchioles will feed the alveoli high surface area tissues that allow for this membrane transport membrane transport is actually through the arterioles Or function change gaseous exchange back and forth in terms of carbon dioxide and oxygen from rest ration you can respect that so there are many other chemicals that have high enough vapor pressure whether it is on inhalation or exhalation that are high enough vapor pressure to cross those membrane thresholds as well you can respect that the respiratory tract using fact one of the routes of elimination potential elimination of toxicants and hot sufficiently high vapor pressure in terms of the respiratory system route the nasopharyngeal it's our nostrils or nasopharynx (X and laryngeal fairness there's hair and mucus in there that allow for trapping of greater than 5 µ particulates it's really important in terms of risk assessment that we protect ourselves from particulates that are smaller than that because there is not a good mechanism to remove those they actually get traps down the trachea bronchial area of the trachea the bronchi the bronchioles in the Silvio action down there the luminal mucus can trap those 25 µ particulates and water-soluble aerosols and gases and so that particularly can have an effect because it doesn't necessarily reverse it doesn't climb that nuchal ciliary escalator and in fact some of those small micron sized particles are actually the ones it can do a tremendous amount of damage in terms of manifestation of diseases such as silicosis and asbestosis these are small solid particles will get trapped in silicosis because of size and asbestosis because of the confirmation of the particle is busters is a needlelike particle it's very hard for needles to actually be resolved via the nuchal ciliary escalator and sellers a tissue damage phenomenon in terms of asbestos exposure in the pulmonary exchange area we have the alveoli these are extremely high surface area maximize for gas exchange with the cardiovascular system in terms of the membrane if we were to actually take this strong early high servicer in lung tissue any in an adult human and laid out flat in terms of its surface area it would cover the estimated size about half the size of a volleyball court this is very large-scale service to allow membrane transport of volatile because of the rapid influx

of respiratory chemicals it is a potential rapid route of intoxication because it is highly managed in terms of allowing for membrane transport this gives you an idea from a dissection point of view of what lung tissue looks like this is a dissection I did on the bovine lung lobe the idea was to do just dissect this laterally in terms of the these feel of this particular tissue the bronchus bronchioles this is a very
Cartledge type material very hard structural material typing is probably the best way to describe it it takes a lot of heft on your sharp scissors to actually cut through this material whereas the pulmonary regions of the longer gas exchange happens is a very soft and almost gelatinous type of material so you get structure in terms of this sort of material and then the softer parts in terms of the other parts of the lung material this gives you an idea terms of the substructure of close up here where we got the bronchus leading off to the bronchial bronchial bronchioles of these little portals here in terms of the substructure that how allow for transport of gases and exchange of gases throughout the whole mass of the lung tissue inside fusion idea that it's a very efficient gas transport system high surface area high connectivity with all the area the ability for us to sustain toxic damage if we are exposed to significant toxicants is is pretty significant myself and my own experience as a scientist during my PhD studies I was exposed to fluorine gas by another student to left the gas tank open the only reason I knew that I was being exposed as I started tasting the metal fillings in my mouth what effect was happening not little to my knowledge at that point in time was that the fluorine gas of two was actually reacting with the water in my lung tissue. HCl and had I not gotten out of there because I started feeling quite ill quite sick… I would sustained a significant amount of tissue damage lung damage it was met with a full hazmat team and gives you the idea that when you were working on chemicals you should be very cautious and careful perhaps in recent history when the largest impacts of four respiratory toxicology happened in
Bhopal India were as many as 10 and some estimates 20,000 people suffered in respiratory illness from a plasticizer chemical put out from and Union Carbide plant as a result of human error at the plant at the factory couple valves worship the reader should be around a huge amount of mortality and morbidity in that particular case I believe it was 1980 another case study more recently and this happened in May
2000 was a fixed obstructive lung disease and workers in a microwave popcorn factory and you may have read about this or heard about this in the news these reports come to us not only for the news that this is the CDC publication mortality and morbidity weekly reports on clinical manifestations of disease and quite often that stops processes and so what this is is site given a few case studies here of the semester that are reports out of the CDC mortality morbidity weekly in this particular case studies is in
Missouri my point popcorn factory for those you with a background food science know about food additives food flavors in fact in my quick popcorn to try to give it the butter flavor as it turns out to in this time. There was a occupational medical medicine physician that actually made report to the CDC to about the cases of the fixed obstructive lung disease essentially these individuals had been an exceptional levels of scarring on the lung tissue and four of these particular workers were actually on a lung transplant list they did some background investigation found that these individuals had all worked at this one factory between the years of 1992 and 2000 this initiated and occupational health investigation was causing the the potential disease and how much diseases because the workers when they did their epidemiological assessments they found that the workers not figure factory are about 10 or 11 times more likely to have lung disease then the standard populations is an indicator of a problem in terms of analysis the problem and follow-up the assume because it was respiratory that it was associated with chemicals or particulates that were in the plant of the Atlas of the answer plant the

reduced it down in terms of the hundred or so volatile organic compounds when the plant here to compounds such as guy acids heal which is a compound flavoring that is used to flavor butter together butter flavor in my quirk, this is a key tone they found the near concentration about the 18 ppm where it was actively being used and lesser concentrations throughout the plant is it turns out there is no PEL or permitted exposure level for this particular chemical compound the suggestion was elbow that was not dose response that these chemical compounds in the flavoring will causing this very high level scarring in this and in fact to the change in terms of Plant operations included enhanced protection of workers from volatile species and that was done by personal respirators and also by increasing their exchange throughout the plant and air exchange or those particular processes for transition off to the digestive system group in food toxicology this is obviously one of the most important routes if we talk about the interaction of food and potential for toxic causes this route involves the mouth the wall cavity the esophagus stomach small intestine the rectum and anus as it turns out the residence time can determine the cytotoxic and injury of the mouth we have a relatively short amount of time small intestine is a relatively long time and so if this is a material that is going to have a require a fair amount of time have toxic interaction it may impact the intestinal linings and certainly your mouth in terms of a incidental injury in search of toxicants can take place anywhere but much over the whole structure in the digestion system is actually designed for work nutrients and all those molecules that are required for metabolism of those molecules wife so that happens and got in so this is a system that has highly facilitated transport for some chemicals opportunities for recirculation in terms of control adequate circulation so this is a system that set up for absorption and therefore has a potential in terms of intoxication there was a clinical case reports a couple years ago about an individual that was so depressed had the suicidal inclinations when Elton drank a bottle of liquor and chased it with essentially what amounted to kitchen cleaner that was a lie-based materials strong base potassium hydroxide potassium hydroxide actually will break down cell membranes for rapidly or had these on your hand in the laboratory noticed a slippery feeling kind of feels like soap because in fact it's making soap out of the facts that are in your skin membranes also is dissolving your skin so this caustic actually had a dramatic impact on the sport individual he actually was rescued after he attempted suicide unfortunately it was a little bit too late in terms of some of the tissues especially the esophageal lining and his stomach and at that time in terms of bringing this unfortunate for the recovery about all he could do would do was to remove his esophagus remove his stomach and actually take the undamaged part small intestine and actually connected externally to his rib cage underneath the skin and so he eats in small amounts actually has to work this particular part of his body to to affect absorption of nutrients required for life fairly dramatic demonstration of intoxication with caustic material to gastrointestinal tract as we know no one understand terms of introductory anatomy we got the mouse and the esophagus essentially some piping to allow us to connect to the stomach where we first have the primary digestion systems are digestive systems are involved with liver liver enzymes and drop adequate circulation via the gallbladder and discharge will learn more about that but then we enter the intestinal tract the large intestine and small intestine finally throughout fecal elimination the digestive system route to terms of differentiation of tissues we have mucosa because it is the outer lining this is a vascular's typically squamous cell or columnar cell epithelium in some cases the structures are villi and microvilli of the microvilli and though I actually aid in absorption or high surface area subscriptions will micrograph moment we also have a submucosal layer below that mucous membrane in the digestive system and

that's where a lot of the exchange starts happening we have high blood flow have lived system interface there outside of that we have been muscular artists which allows for her stall took movement that allows for the passage materials through the digestive system outside of that we have been the casing of the sub rosa that contains all of this organ substructure in the gastrointestinal tract in terms of the intestine and its structures and substructures to see from the sun cartoon here the small intestine is made up of some substructures will we have the will of the mucosa on the surface of submucosa villi themselves these high surface area structures are highly vascularized again optimized for nutrient absorption they are vascularized not only with the blood system but also with the lymph system because we have a tremendous amount of immune function it's happening in terms of responding from immune point of view to pathogens that might be in the food system to immune system there has to be very good at recognizing chemicals toxicants even potential allergens or pathogens good ones from bad ones obviously we want to absorb nutrients we absorbed protein so we won't be able to absorb all those molecules required for metabolic resources so this is particularly well orchestrated symphony of absorption if the small intestine mucosa actually this is a microscopic histology slides us as I think this is my first introduction for you on histology these are two dimensional representations of threedimensional cells and organs so I always tell students next time you're cutting up a cucumber pricing experiments on cutting it in different directions and seeing what it looks like if you cut it long ways it has a dramatically different representation than if you cut it in small thin chips crosswise which will give a round representation so this is the lengthwise representation of these villi and it gives you some indication of the cellular structure on the periphery that aids in membrane transport and absorption of nutrients as well as toxicants old finish up today with a case study in this particular case study this is an herbal supplements. This is a case study associated with June you long toxicity in children this is an incident report in Colorado 1993 these three incidents am going to report came for mortality and morbidity weekly on these unrelated instances in terms of they all had different aspects but they all were similar in that contain young children develop them children and exposure to this particular
Chinese herb that traditional Chinese herbal products are widely available in the United States since a greater than $1 billion market because these are marketed as herbs and not as drugs they do not have
FDA oversight there is some concern because people actually do take these as drugs for therapeutic value they have sometimes very highly potent natural products in this case on me times their alkaloids jingle long is manufactured in China and the state of ingredients are polyglot chain esses L alkaloid at
30% and starch at 70% is an analgesic is used as a pain reliever as's known from morphine type responses as well as a known how to talk some people have taken as part of river basins and come down with the acute and chronic hepatitis and so this is something that should be well out of the hands of children one of the problems associated these types of products is the variability in terms of what's in it not in terms of just the active ingredient that is labeled for but other plant or verbs that might be cool administered to be on what's on the label in this particular case representation patient one this is a 13month-old boy Tara actually was lethargic and breathing abnormally when found about 20 minutes after ingesting about 60 of these tablets reticular child presented with the CNS central nervous system depression and was responsible only to painful stimuli other words didn't really have the normal responses that we should have in terms of stimuli he was lethargic he had the very relaxed muscles so no muscle tone and he had the transit bradycardia written rapid heart he actually was treated with activated charcoal he was integrated in the actually survive the episode and had no real follow-up

problems in terms of the short-term Mr. Quesada patient number two to a half-year-old girl was lethargic and breathing abnormally she was found about an hour after ingesting about 17 of those tablets she was unresponsive and respiratory depression rapid heartbeats was treated with atropine she had the CNS depression symptoms diminish respiratory weight she required intubation her condition improved and she actually vomited out the tube that was a sexy place to help her in her respiration she had gastric lavage also known as getting your stomach pump to recover the tablets that were in their about eight hours urine serum were negative for other typical compounds associated with drug intoxication no permanent conditions terms of short-term follow-up of this page the third patient in this particular case study of 23 Mayor-month-old girl was lethargic parents founder about our after she had about seven of these tablets she was transported to emergency room she had her stomach pumped as well the administered charcoal and cathartic economy vomit out as much of this material is she could she was observed in and discharged opinion no permanent impact to turn the case follow-up this is as important to anomalies to track the individuals associated with these cases but also the toxic agent in this particular series of cases and analysis of the products identified that it was 36% concentrated by weight level tetrahydro throw Palm Latino THP witches saw the active alkaloids not in the species identified in this particular model verbs by a other plant species it has morphine like properties each tablet contained about 28 mg of this particular material but no other alkali was was identified plants so what I does is give you some background as we tie up the end of the absorption election because you some background on absorption of chemicals as we start this progression of events which versus pathways receptors and is well controls within the body allows to get out of a full-scale's representation of toxicology the next time my next lecture will do his will try to discover what happens next in terms of routes of toxicology was his crosses membranes it is going to be transported and distributed throughout the organism and perhaps stored or metabolized in flex time we'll see you then and the humor