let's talk about arsenic arsenic is a very toxic metalloid or semi-metal it's been actually used as poison to kill people husbands wives etc arsenic is also known as the poison of kings and the king of poisons so it's been used as poison for many years and one of the consequences of acute exposure is death as we talk about arsenic the diseases that we're going to talk about are more of chronic exposure that leads to problchromated copper arsenate or cca and you'll find that cca has a lot of toxic stuff and these are all different kinds of metals or metalloids it has hexavalent chromium right and that's pretty toxic so by weight 47.5 percent of cca is hexavalent chromium about 18.5 percent is copper and about 34 is arsenic so you can see ccatissue kidney and even the nervous system and what's so unfortunate about arsenic is that we don't have a lot of uses for arsenic there are cases when we can use arsenic for medicinal purposes but it's vchromated copper arsenate or cca found naturally in the environment it's found in rocks soil water air and even in plants and animals as i mentioned arsenic is a metalloid so it's not really metal nor is it non-metal it has characteristics of both metals and non-metals and of course arsenic has different species and we'll find that the two most stable species of arsenic is plus three and plus five sometimes plus three is known as arsenic trioxide and plus five is sometimes known as arsenic pentoxide and arsenic trioxide tends to be more toxic than arsenic pentoxide we can also categorize arsenic into inorganic arsenic as well as organic arsenic so when we say inorganic arsenic we're referring to the fact that arsenic is bound to elements besides carbon organic arsenic means that arsenic is bound to some form of carbon in this case unlike mercury inorganic arsenic tends to be more toxic than organic arsenic organic arsenic tends to be less toxic it's often found in shellfish and fish but it's less toxic than inorganic an example of organic acid is arsenic acid where arsenic is actually bound to once again this is carbon right okay so the fact that arsenic is bound to carbon makes this arsenic molecule an organic arsenic whereas an example of inorganic arsenic includes arsenic trioxide where arsenic is really bound to hydroxide once again arsenic in this case in the inorganic form it is not bound to carbon it's only bound to hydroxyl group particularly it's the oxygen atom and this makes this form an inorganic arsenic and makes this organic arsenic once again if arsenic is bound to a carbon atom then it is organic most common oxidation states for arsenic as i mentioned is plus three and plus five and plus three is also known as arsenites and it tends to be much more toxic than arsenates which is plus five so this is an example of arsenic plus five and here's an example of arsenite which is arsenic plus three so arsenate is an example of arsenic three plus and arsenite is an example of five plus and toxicologically speaking it's the arsenic trioxide or the arsenite that is much more toxic than arsenate and both arsenic trioxide and arsenic pentoxide are usually found in nature as salt with cation like sodium so here is arsenic 5 plus in the form of sodium arsenate here's sodium three plus in the form of sodium arsenite although i didn't mention this in the lecture slide here but there's also a gaseous form of arsenic an example of that is called arsine and our scene has molecular structure of this this is gaseous form so you can get arsine in the air and if you're exposed to arsine and you inhale it it can also cause toxicity so mostly arsenic exposure comes from occupational setting occupational exposure to arsenic usually occurs in the manufacturing or the use of pesticides which includes herbicides and other kinds of agriculture products even arsenic is used in taxidermy to preserve the tissue of dead animals and arsenic is also used in the preservation of wood it prevents insects microorganisms other things from eating away the wood an example of wood preservative that uses arsenic is known as chromated copper arsenate or cca and you'll find that cca has a lot of toxic stuff and these are all different kinds of metals or metalloids it has hexavalent chromium right and that's pretty toxic so by weight 47.5 percent of cca is hexavalent chromium about 18.5 percent is copper and about 34 is arsenic so you can see cca is pretty toxic and therefore it is a good industrial chemical that can be used as a preservative as long as people are not going to be inhaling or being exposed to this preservative in this next graph it shows the amount of arsenic used in different products yellow represents the use of arsenic as wood preservatives and red color represents the use of arsenic in agricultural chemicals and blue is other so you can see over the years the increased use of arsenic in wood preservatives especially in chromated copper arsenate or cca one of the very first generation of pesticides that were developed used these toxic metals and these include things like lead arsenate calcium arsenide and they were used as insecticides you can kind of see how toxic this probably is right lead arsenate but back then we didn't have as good of understanding of toxicity of metals so lead arsenate was used because it was really good at killing insects but unfortunately lead arsenate is very toxic to animals including humans so it is now bad arsenic has been used as red poison and also in the form of chemical weapon what are some ways in which humans are exposed to arsenic ingestion eating meat poultry fish and also from water fish contains actually relatively high amounts of arsenic but it's in the form of organic arsenic so organic arsenic is less toxic than inorganic arsenic water is an important pathway in which people are exposed to arsenic and in fact long-term exposure of arsenic through drinking water can lead to chronic arsenic poisoning which can lead to arsenicosis of course you can also inhale arsenic from smeltering processes mining process even burning coal because arsenic is a contaminant in these processing of ores therefore people who work in smelting and mining processes can have exposure to arsenic by inhalation and interestingly one of the minor exposure route of arsenic is dermal arsenic can actually be absorbed by putting your hand in water that contains arsenic compounds or even handling wood products that contain arsenic such as cca so arsenate and arsonites actually do get biotransformed but this biotransformation process is somewhat unique because it's something that we didn't really talk about when we went over biotransformation it's the methylation methylation is one of the processes in conjugation however because of the fact that it is not as often used and also because it doesn't really increase the water solubility i decided not to spend too much time on it so if you're exposed to arsenite or arsenic trioxide it can in fact be metabolized to arsenic 5 or arsenic pentoxide and once arsenic pentoxide is formed it can go through methylation and add one methyl group and in fact it can add additional methyl group and then become dimethyl arsine as you can see this really doesn't increase the water solubility in fact some of the studies recent studies have shown that dimethyl arsine and methyl arsenic are still relatively toxic as i go over some of the attributes of toxicokinetics not just for arsenic but also for chromium lead and mercury i'm not going to spend a lot of time explaining things these are just really factual information okay inorganic arsenic is well absorbed so either from eating food or drinking water that's contaminated with arsenic but thankfully some of these inorganic arson compounds have low water solubility so they don't tend to solubilize in water very well and that leads to less absorption most arsenic is promptly excreted in the urine as a mixture of arsenite arsenate and organic arsenic compounds dimethyl arsenic is usually the primary form in urine and of course through bile some of that can also be excreted in feces as well biological half-life of ingested arsenic is only about 10 hours it doesn't spend a lot of time in the body however arsing tends to accumulate in skin which can cause toxicity in the skin cells and arcing can also be excreted by discrimination or the peeling of the skin as well but by that time that happens arsenic already has caused damage to the skin cells and arsenic is known to cause skin cancer so there are a few important mechanisms of toxicity as a result of artistic exposure first acute poisoning or ingesting large doses of arsenic in a very short period of time we mentioned it's within 24 hours and this can lead to all kinds of problems and death can actually result symptoms may include things like fever liver damage cardiac arrest damage to the gi tract causing irritation and the sloughing of the gi tract epithelial tissue and also damage to the nervous system and when a pregnant mother has exposure to arsenic arsenic can also travel into the fetal tissue and they also cause damage as i mentioned skin is one of the major target organ in chronic exposure to inorganic arsenic and this can lead to hyperpigmentation so there's darkening of the skin and eventually can lead to hypopigmentation as well whitening of skin and then it can kill off so as i mentioned it can lead to cancer as well exposure to arsenic for over long periods of time can also damage the nerve cells and people have used the term pins and needles to describe the painful sensation as a result of the exposure to arsenic and the damage that happens to nerve cells so there are two important mechanisms of toxicity first it's the disruption of enzyme activity it's the first general mechanism of toxicities that we already discussed inorganic arsenic has a positive charge because it has a positive charge it tends to be attracted to negative charge so thiol is an example of part of the molecule that may have negative charge and this can inhibit enzymes so that's one mechanism in which arsenic can cause damage the second mechanism is that it can also do mimicry arsenic can pretend to be phosphate so here's an example of phosphate this is atp atp is a cache for energy atp is created in mitochondria through the oxidative phosphorylation unfortunately when you have exposure to arsenide arsenic can displace phosphate and instead of having the three phosphate groups you may end up getting three arsenic groups and this of course is not going to function as atp so it's going to decouple the oxidative phosphorylation and the mitochondria will no longer produce atp and this is very toxic to cells also arsenic and its metabolites have been shown to produce oxidants and oxidative dna damage so this is causing oxidative damage whether it's through the production of free radicals or other kinds of oxidants that can damage the dna proteins enzymes and etc in this experiment this shows how arsenic can actually kill cells three doses are used to determine the toxicity of arsenic trioxide here is a control and each of these represent cells in the second picture here five micromolars of arsenic trioxide was added and in the last picture 10 micromolar we've doubled the amount of arsenic trioxide and you can see there is a lot of damage and and a lot of cells have actually died right it causes both apoptosis or known as cellular suicide or necrosis or just sort of bursting of these cells as they die you probably heard of how people in bangladesh have high exposure to arsenic because of the groundwater bangladesh is a very poor and high density population and although it has a lot of water children especially would have high increase of child mortality because of the fact that they were drinking water that was contaminated with microorganisms because they're drinking water straight from river and so on so recognizing this unicef actually went in in 1970s and started drilling these two wells because they actually had groundwater and this represents the water table so two wells are these very small tubes they're not like wells where if you dig below the water table you can start pumping right and you actually use a pump handle to pump out the water so this really reduce the child mortality in that country as children start drinking safe water so millions of these two whales were duck in bangladesh here's what two wheels actually look like and you can see that these aren't like wells right these are relatively small tubes and use a handle to pump up the water unfortunately people didn't realize or at least they didn't test for arsenic in the groundwater people in unicef they assume that the groundwater is safe and they've tested for many other kinds of contaminants but they never tested for arsenic and people have been drinking this groundwater and for many years they had this chronic exposure to arsenic millions of people drink from the whales and after 10 15 20 years later people started having these latent arsenic poisoning symptoms and sometimes it would occur in the skin first who an epa limit for arsenic is about 10 parts per billion however bangladesh they decided to have that limit to be much higher knowing that their groundwater has high levels of arsenic otherwise they won't be able to use the groundwater at all 35 percent of tested wells had arsenic level above 50 parts per billion and unfortunately 61 percent of the population lived in areas that had whales contaminated with arsenic and estimated over 20 million people were poisoned by ours and you can kind of see the areas where our sink level is very high so chronic exposure can lead to arsenicosis it may start with the damage to skin and also the lining of gut as well as even the epithelial tissues of lungs and heart blood vessels and other epithelial tissues first people are seeing changes in the pigmentation of skin as i mentioned first there's a discoloration there's a hyperpigmentation and then it becomes white and it peels off an arsenic was being accumulated in the skin and was causing damage it was causing oxidative damage to these skin cells and it was also causing mutation hence chronic exposure to arsenic led to skin cancer bladder cancer where the epithelial tissue of bladder was actually becoming mutated and the permutation eventually stood bladder cancer same thing with lungs skin kidney and etc so we know that arsenic is a human carcinogen you can see the pictures here of you can see the hyperpigmentation also you can see the hypo pigmentation as well from the white parts unfortunately cleaning up arsenic from groundwater is quite expensive if this happened in the united states we have money our economy is big enough to really clean up the water we can use reverse osmosis to remove arsenic from the groundwater but unfortunately in bangladesh because the country itself is so poor cleaning up the groundwater was a task that the country could not commit to instead they devised this filtration system known as sonofilter which basically uses sediments that's found in bangladesh and having these two bucket system eventually can remove arsenic from the water and what happens to our thing is that it actually gets bound to the soil that's found in the sonofilter and what comes out of these two bucket system is water that is free of arsenic chromium is used in various industrial products we already talked about the use of chromium in wood preservatives chromium copper arsenide chromium is also used in chrome plating it's used to make refractory bricks that are used for industrial ovens basically and also chromium is used in the manufacturing of dyes and pigments and also used in tanning processes all of these industrial use of chromium eventually gets into our environment for example groundwater and surface water chromium can have different species of course there's a chrome metal there's a chrome 3 and chrome 6. in nature chromium is mostly found in the form of chrome 3. and chrome 6 is really the byproduct of industrial processes unlike other metals chromium is different because one of the species is essential for cellular processes but the other specie hexavalent chromium in this case or chrome 6 plus is very toxic and has no use in the cellular processes the trivalent chromium or chrome 3 plus is essential but hexavalent chromium or chrome 6 plus is very toxic and besides the fact that hexavalent chromium is toxic to cellular processes it is also much more soluble than chrome 3. because it's more soluble in water than chrome 3 it's more mobile meaning that it can migrate in the environment much more quickly compared to chrome 3 plus and it's also as i mentioned is very toxic although trivalent chromium or chrome 3 plus is essential it is less soluble less mobile and less toxic than hexavalent chromium of course when i say less toxic anything can be toxic right so just like any other essential metals if you have too much chromium three it can be toxic but in comparison to chrome 6 it's less toxic there are many different products that use chrome 6 and our focus is really on hexavalent chromium or chrome 6 because it's the more toxic specie of the chromium chrome 6 is found in sometimes groundwater surface water as well as in many different kinds of products it's used in as i mentioned pigments in paints inks and plastics it's used as anti-corrosion coating such as chrome plating it's also used in stainless steel people who actually will steal as they weld them as you cut through the steel some of the hexavalent chromium can actually evaporate and welders can actually breathe in hexavalent chromium it's also used in textile dyes as we mentioned in wood preservation and leather tanning as well these are some common jobs where workers may have potential for hexavalent chromium exposure first it's people who work in chrome plating or electroplating here's an interesting video that kind of shows how chrome plating is done you can actually chrome plate on top of the plastic as well so it involves the etching process of plastic so you can actually put metals on top of the plastic very interesting but in the process of trying to put a very thin layer of chromium workers can be exposed to hexavalent chromium you can see a welder here cutting through the steel obviously it's very hot and it can actually cause chromium to evaporate and a person can breathe this in one of the most important hexavalent chromium root of exposure is inhalation especially in workplaces inhalation of dust mist fumes that may contain hexavalent chromium so in the occupational setting you may have eye or skin contact with powdered dust or liquids that contain chrome 6. mentioned hexavalent chromium have higher absorption as compared to chrome 3 but relative to other kinds of chemicals absorption rate is pretty low it's just that hexavalent chromium has higher absorption rate compared to chromium 3. interestingly hexavalent chromium can enter into cells using sulfate and phosphate carriers or transporters so not only is chrome 6 more readily absorbed and soluble in water it can also hijack a carrier process to get itself into the cells so it's much more mobile within a living organism as compared to chromium 3. dermal absorption is minimal but depends on the chemical form and of course the integrity of the skin and the half-life of for example potassium chromate is about 35 to 40 hours what's interesting about chrome 6 is the fact that it's reduction process that changes chrome 6 into chrome 3 is the reason for its toxicity so as chrome 6 plus becomes chrome 3 plus it causes oxidative damage and it produces free radicals reactive oxygen species that can damage proteins and dna hence hexavalent chromium is a probable carcinogen dna damage involves the formation of addicts or sort of a bond or link between the chrome 3 plus and the dna and this causes mutations here's a description of the toxicity of hexavalent chromium as i mentioned hexavalent chromium can use sulfate and phosphate transporter and hijack the system and get into a cell whereas in chrome 3 plus has difficult time getting into different kinds of cells yes chrome 3 plus is an essential metal so they'll be shuttled by proteins that binds to metals but unfortunately chrome 6 plus is much more mobile within the living organism because they can hijack sulfate and phosphate channels so once hexavalent chromium enters into the cell process begins where hexavalent chromium is reduced to chromium three plus in the process of reduction this reduction means that chromium is accepting more electrons so it's going from 6 plus to 3 plus how does that happen when it accepts three electrons right and this process of accepting electrons is called reduction in the process of reducing hexavalent chromium into chrome 3 plus it produces oxidative damage and this is result of formation of free radicals once that reactive oxygen species or free radicals are formed it can damage the lipids the proteins also interact with the dna it can also cause dna damage and mutation and etc then eventually can lead to cancer as well now once chrome 3 plus is inside the cell and this chrome 3 is in a place where it is not essential anymore the essentiality of chrome 3 plus is in the process of glucose metabolism but in a cell when hexavalent chrome reduces chrome 3 plus now there's a potential for the chrome 3 plus to enter into the nucleus and also form an adduct with the dna which can cause mutations and this can lead to genomic instability or damage or mutation to the cells and if there is enough damage within the cell it can go through cellular suicide known as apoptosis so in reality it's the reduction of hexavalent chromium into chrome 3 plus is causing cellular damage what are some of the health effects of exposure to hexavalent chromium lung cancer when a person inhales chromium vapor chromium vapor itself will be absorbed in the epithelial tissue of the respiratory system and chromium will start causing damage and can eventually lead to lung cancer as people breathe in if you breathe in through your nose and there's enough deposition in the nasal cavity it can actually cause a puncture in the nasal cavity we call this nasal septum ulcers it's a perforation in the skin because chrome 6 is very corrosive and also can lead to bronchitis and asthma for a person who has dermal exposure hexavalent chromium can cause skin ulcers and also allergic reaction as well and may cause inflammation in the epithelial tissue of the skin known as dermatitis one of the most talked about heavy metal is mercury i think one of the reasons for that is because we have determined that mercury can bioaccumulate in fish and that a lot of us do eat fish now especially for pregnant mothers eating fish that may contain high levels of methyl mercury could be very toxic to the fetus in fact in fact organic mercury is able to pass through the placental barrier and bioaccumulate in fetus so how does mercury get into the environment well mercury just like any other metals is found naturally in the environment mercury can vaporize into the atmosphere from volcanic activities however the majority of mercury in the atmosphere is from industrial processes such as burning coal mining processes all of them will evaporate mercury into the atmosphere and this is in the form of elemental mercury right so that stands for the elemental mercury elemental mercury is also known as quicksilver elemental symbol for mercury is hg it's not mc this comes from latinized greek hydroardurum basically means water or means silver water mercury being liquid state at room temperature makes this very unique metal so hence it's hg so hg0 represents elemental mercury or the quicksilver it's the vaporized form of the elemental mercury it gets into the atmosphere of course in the atmosphere it can be distributed so even places that don't have sources of mercury can have mercury in the environment once it's in the air it's going to react in the atmosphere with water and eventually becomes inorganic mercury in the form of mercury two plus well eventually because mercury two plus can dissolve in water will come down to the surface of the earth in the form of inorganic mercury and then it will reside in the environment such as lakes ocean rivers and etc in the soil as well from different kinds of process including microorganisms some of that inorganic mercury can actually go back to its elemental form once it's in the elemental form elemental mercury tends to vaporize very quickly into the atmosphere and then we'll go back to atmospheric mercury and some of that mercury can stay as inorganic mercury and can in fact cause exposure to humans at the same time some of that inorganic mercury can become methyl mercury through an aerobic bacteria and because methylmercury is very lipophilic it tends to bioaccumulate in the food chain and that's how humans can be exposed of course this kind of leaves out occupational exposure right people who work in places where mercury is used it may involve medical instrumentation or scientific instrumentation they could have increased exposure to mercury as i mentioned there are different types of mercury there's the elemental mercury and it's liquid at room temperature it's also known as quicksilver and because it's liquid at room temperature it also volatizes evaporates much readily compared to other kinds of metals so if you let that quicksilver sit around for a while slowly it will evaporate when i was doing my phd i once broke a mercury thermometer and i really thought about cleaning up the mercury spill by myself then i said no i should just call the environmental safety office and they in fact came and spent the whole day cleaning up the mercury spill it was just one thermometer but it's really important to make sure that we get all of the quicksilver because any that's left over can slowly evaporate and people who spend time in that room will inhale that volatized elemental mercury and inhalation of elemental mercury is very very toxic inorganic mercury includes mercurous and mercuric salts this we can sort of write it as hg plus the reason why i don't have it hg plus is because hg plus really doesn't exist it exists in the form of two mercury linked together bound together that has two plus charge so this is mercurus and this is mercuric salt lastly organic as i mentioned an example of organic mercury includes methylmercury you can also have things like dimethylmercury so this would be a dimethylmercury you can also have diethyl mercury diaphyl mercury have also been used in vaccines as preservatives some of you may have heard of the marisol so thimerosal is a preservative that's used in vaccines and it has diethyl mercury it's kind of scary right putting mercury in vaccines thankfully all of the new vaccines really don't contain the marisol anymore you'll find them so in vaccines where it's not a one-time use you have a bottle of vaccine you keep it in a refrigerator and use it over and over they need preservatives you want to make sure that there aren't any microorganisms growing there however one-time use single-dose vaccines usually don't contain the merosa what are some of the sources of exposure elemental mercury comes from coal burning plants dental amalgam vapor that is if you have silver amalgam in your mouth then it has a little bit of mercury and this is concerning right however all the recent data shows that the exposure of mercury from amalgam is very very low electronics have mercury in them some pesticides which includes fungicides may have mercury in the mercury is very toxic to not just animals but also the fungi as well some of you still may use compact fluorescent light bulbs like this and compact fluorescent light bulbs contain mercury paper inside the lamp so if you break it some of the mercury is going to get out so i'll briefly talk about how you should clean up a broken cfl light bulb and we did have little mercury in interior latex paint which was banned in 1990. organic mercury yes it's fish a certain type of fish that's very fatty because organic mercury tends to bioaccumulate and be stored in fat portion of the tissue and as i mentioned sometimes organic mercury is used in vaccines so if you do have a broken cfl light bulb according to epa in fact they have like two page instruction of how you should clean that up one of the things that they tell you is not to vacuum you don't want all of that elemental mercury vapor to disperse everywhere okay the best thing is just to use a stiff paper or cardboard or even sticky tape to collect all of the broken pieces of the bulb and you really want to ventilate so if you're interested you can just search for epa's instruction on broken cfl bulb cleanup people really don't know about this because they don't know that the cfl light bulbs contain mercury about 80 of inhaled mercury will be absorbed into through the respiratory system 80 that's really high and this is one of the reasons why vaporized elemental mercury or quicksilver is very very toxic because it has such a high absorption rate but if you were to eat the elemental mercury it has relatively poor absorption rate however in organic mercury whether it's in mercurous or mercuric form it doesn't have very high absorption rate compared to vaporized elemental mercury but it still has relatively high levels we're talking about 10 to 15 percent of exposure on the other hand organic mercury just like the elemental mercury has relatively high absorption whether it's inhalation or through the gi tract because it's very lipophilic elemental mercury is found in blood as soon as it is absorbed and then over time elemental mercury becomes oxidized to inorganic mercury but it doesn't happen instantaneously it's done by enzyme known as catalase in the erythrocytes in the red blood cells however it takes time unfortunately because the elemental mercury is not oxidized to inorganic mercury very quickly some of that elemental mercury will actually get into the brain will pass through the blood-brain barrier get into the brain and then inside the brain it will be oxidized to inorganic mercury which will eventually cause damage to the nervous system so one of the effects of elemental mercury absorption is the fact that it causes it causes nervous system damage so some of the main storage for elemental mercury is the brain and the kidney why kidney because once elemental mercury is oxidized to inorganic mercury then it gets stored in the kidney and inside the brain because after it gets into the brain eventually it will be oxidized to inorganic mercury so it will be stuck in the brain and will continue to cause damage on the other hand inorganic mercury will be distributed especially in the kidneys and will cause damage to the kidneys thankfully inorganic mercury does not cross the blood-brain barrier or the placental barriers but organic mercury is able to readily cross the blood-brain barrier and the placental barriers yes organic mercury is much more lipophilic the way that organic mercury for example methylmercury gets into the brain is not through passive diffusion through the blood-brain barrier instead it actually binds to the thio group of certain amino acids that contain the sulfur and then it actually attaches itself to the amino acids and then it enters into the brain and once methylmercury gets into the fetus and passes the placental barrier methylmercury accumulates and concentrates in the brain of the fetus and causes developmental damage so organic mercury can really get to many different places you know brain fetus as well as it can also concentrate in kidneys as well elemental mercury after a short-term exposure to mercury vapor about one-third of the absorbed mercury will be eliminated in unchanged form through exhalation but approximately 10 percent of the murky vapor is exhaled within a week but ultimately about a third will be exhaled out the rest of the absorbed elemental mercury will be oxidized into inorganic mercury and then will be eliminated in feces mostly and and this goes through through a different process where it spends a lot of time in the liver and then it uses the bio duct and is eliminated as a bile so it actually is eliminated in feces inorganic mercury of course is also eliminated in feces so it's a little bit urine as well organic mercury mostly in the feces and a little bit in urine inorganic mercury binds to the thio group so this is one of the general mechanisms of toxicity that we talked about and then it inactivates some of these important enzymes and this can lead to cellular damage for example inorganic mercury can inactivate certain enzymes such as superoxide dismutase and catalase methylmercury penetrates all cells in the body but particularly as i mentioned in the central nervous system and then once it's in the brain it can cause damage to the nerve cells other general mechanism toxicity have also been proposed and that it interrupts the microtubule formation inhibition of certain enzymes which talked about oxidative stress and interruption of protein and dna synthesis so they're still a little bit unknown but we know that mercury can cause multiple pathways of destruction and damage in the cellular system exposure to high concentrations of vaporized elemental mercury can cause acute necrotizing bronchitis pneumonia and even death long-term exposure is going to impact and damage the central nervous system exposure to inorganic mercury can cause damage to the mucosal lining of the intestine and also it can cause kidney damage exposure to organic mercury can cause vision damage optic nerve damage depression irritability tremors insomnia and also organic mercury is a teratogen which means that it can cause birth defects so some of the neurobehavioral effects of mercury includes blindness deafness cerebral palsy seizures abnormal reflexes and muscle tone motor development visual and auditory deficits and delay motor development so all of these are just very problematic if you have read the book alice's adventure in wonderland there is a character named matt hatter and matt header came from a real life character and that's because hatter back in those days used mercury compounds to help cure the felt that's used in making these hats so every day they come to work they use this mercury solution that has mercuric nitrate and they are slowly poisoning themselves and this chronic exposure eventually leads to damage to the brain and all of those neural behavioral toxic effects we just talked about are actually shown in these mad hatters you know they have slur speech and they lose the ability to see things they have something called tunnel vision tunnel vision is when you lose the peripheral optic nerve cells so that only optic nerve cells that actually works are the ones right in the center so you lose that peripheral vision known as tunnel vision so these coal power plants release elemental mercury into the environment so does the volcanic activities inorganic mercury that's found in soil and water can revert back to its elemental state and vaporize into the atmosphere however once that elemental mercury is in the atmosphere eventually as i mentioned it's turned into inorganic mercury it comes down in the form of rain and once it's in the water and aerobic bacteria can convert that inorganic mercury into organic mercury such as methylmercury and the methyl mercury bioaccumulates in the food chain and people will be exposed to methylmercury some of the fish that have high levels of methyl mercury include shark swordfish king mackerel and tilefish humans have used lead for at least the last 7000 years lead is really easy to extract and work with and is very highly malleable and ductile so that it was used in many different kinds of metal alloys the elemental symbol for lead is pb and this comes from latin word plumbum and plumbum is lead so hence the symbol is pb of course we have the elemental lead we also use inorganic lead plumbing two plus and we also have organic lead which tends to be four plus we have used organic lead in gasoline before of course now that is banned inorganic lead is often used in pigments paint that has very bright color it's very resistant to deterioration so we have used lead in paint however that also was bad because lead itself is toxic elemental mercury and mercury alloys are also used in batteries car batteries contain lots of lead and also in ammunitions as well and if you are an avid fisher we know that some of the weights that are used in fishing weights are made of lead the use of lead in residential paint was banned in 1977 after determining that lead is very toxic unfortunately some countries still use toxic lead as additives in gasoline of course a number of these countries are actually very few some of the sources of lead exposure includes old leather paint especially in government housing that were built before the ban of the leaded paint some toys may in fact contain a little bit of lead especially very bright color now this was unintentional use of lead in paint sometimes high concentration of lead is found in candies that are produced in mexico for many years mexico used leaded gasoline and all that lead eventually came down and all that led then is hyper accumulated by certain type of plants and these plants like chili was used to make spicy candies and these candies would have high levels of lead some artificial turf have lead in it the seam that's used to hold the fake grass actually had a little bit of lead so some of that lead will actually evaporate people could be exposed to lead by using lead crystals now these shouldn't be really used for consumption but sometimes people don't know especially children it's got this beautiful very sparkly glass and sometimes they want to drink like oranges or lemonade now especially with acidic drinks it can leech lead from these crystals folk medicine that uses herbs and these herbs just like in lead candy can hyper accumulate some of that lead and people could be exposed to lead by consuming folk medicine and even soldering as you can see in this picture if you use less solder you see all of that fume and you could actually expose yourself to lead fumes if you don't wear a mask solid line represents a production of lead and the dotted line represents emission of lead lead had a lot of uses if you were to go to dental office or if you go to a medical office and you get an x-ray well you wear that very thick and heavy vest and that heavy vest is really mostly made of lead alloy and it's designed to block the x-ray so the production of lead increased but there was a dramatic emission increase now this is when we started using leaded gasoline in car engines now that we've banned the use of leaded paint and leather gasoline the emission of lead into the environment has dropped significantly if one inhales vaporized lead as i mentioned if you actually use lead in the soldering process it can vaporize that lid and you can inhale if you do inhale the vaporized lead all of it will pretty much be absorbed if you consume lead about 10 to 30 percent will be absorbed if you are an adult however if you are a child you can absorb as much as 50 of the dietary lead in the food why is that the case well there's higher need for children to increase the uptake of calcium and unfortunately lead is mimicking calcium and is going to be hyper accumulated in the body especially in children so they have higher uptake of lead if you have inadequate intake of iron and calcium then if you are exposed to lead if you were to consume lead in food or water your uptake of lead will increase because your body needs more of the calcium and iron and your body thinks lead is either calcium or iron so if you have dietary deficiency of iron and calcium your absorption of lead could actually increase inorganic lead obviously is not going to be absorbed however organic lead which is very lipophilic can be absorbed via dermalee and most of the lead complexes are not biotransformed lead is carry bound to the red blood cells most of the lead is actually bound to hemoglobin or myoglobin they are distributed extensively throughout the tissue bone teeth liver lung kidney brain and spleen and unfortunately lead can also cross the blood brain barrier and can concentrate in the grain matter as well as the placenta so lead is really toxic it gets into the brain it gets into the fetus and it goes into the kidney it goes into in fact causing problems in the cardiovascular system lead can really impact many different organs in the body one of the lead storage sites in the body are the bones and for much of the older females the stored lead can mobilize again during the osteoporosis as they lose some of that bone density the lead that was stored in the bones can actually get back into the blood and also cause toxicity approximately forty to seventy percent of the blood lead in adults comes from bone lead now especially in pregnant mothers if the pregnant mother had high exposure to lead when she was a child and there was storage of lead in the bones during her pregnancy mothers lose bone mass calcium to support the growth of the fetus so if the mother had high exposure to lead when she was a child and there's high levels of lead in the bones well it can become mobilized and then it will accumulate in fetus and this could be very dangerous to fetus bloodlight levels in mothers and fetus are usually identical because lead passes across a placenta without really much hindrance most of the lead is excreted in the kidneys as well as in feces lead half-life in adults in blood is about 25 days soft tissue is 40 days boom is about 25 years hence when people go through osteoporosis because of the older age this can mobilize the store led back into the blood now this diagram shows an example of how toxic lead can be to nerve cells led slows down the nerve activity in the next topic when we talk about pesticides especially insecticides we'll talk about how these nerve systems communicate and how they send information from one cell to other cells this communication process involves many different processes and imagine signal coming in this way and eventually many things need to happen where these vesicles these are neurotransmitters that are released into this synaptic cleft well in order to do that there has to be several things that happen before those vesicles are released well lead can actually disrupt many of these processes particularly lead can actually bind to protein kinase c ed50 represents effective concentration 50 means it's a concentration that's needed to cause a 50 change in function now if there's 50 change in function it may not work very well right so for this protein kinase c process it only takes one pickle molar of lead in the nerve cell to disrupt the function of that enzyme by 50 that picomolar is smaller than micromolar it's smaller than nanomolar so after nano it's pickle we're talking about really really small concentration to disrupt this nerve activity so if this step in this communication pathway is disrupted will everything get slowed down right hence lead can slow down the nerve activity lead has many different effects in animals with normal cell function and various physiological processes exposure to lead can cause damage to peripheral and central nervous systems as i mentioned it can also cause blood cell production problems it prevents the bone marrow from producing the red blood cells also disrupts the metabolism of vitamin d and calcium it also damages the kidneys it can also cause reproductive system damage meaning that it can cause a problem with the sperms it can actually damage the sperms and slow them down it can also cause damage in the female reproductive system not only that as i mentioned it can get into the fetus so it can also cause birth defects it's a developmental toxin as well and it is a probable human carcinogen really nasty nasty toxin if you were to ask toxicologists what would be one of the most toxic substances toxicologists will say bacterian toxin is probably the most acutely toxic but if you think about toxins that has highest impact to general population a lot of people will agree it's the lead not only is lead ubiquitous in the environment it's also used in the industrial processes but also lead can cause so many different toxic effects and we're talking about toxicity to fetus toxicity in the nerve system kidneys reproductive system and etc some of the early symptoms of that poisoning includes vomiting abdominal pain constipation loss of appetite irritability lethargy and you may in fact have loss of muscular coronation eventually can lead to seizures and even death so this table shows the different blood lead levels and the different outcomes as a result among adults and children and what i'm trying to show you is that the children are much more sensitive to the toxic effects of lead in the blood at 10 micrograms per deciliter in the blood in adults it may cause hypertension because it impacts the cardiovascular system but in children it can cause impairment in iq it can also partially inhibit the heme synthesis so there will be less red blood cells you know how much children need more of these red blood cells at 20 micrograms per deciliter in adults there's inhibition of heme synthesis and in children there's a beginning of impairment of nerve conduction velocity and this can lead to further impairment in iq at 40 micrograms per deciliter it may cause infertility in males and there's going to be hemoglobin synthesis inhibition in children so children are much more sensitive to the toxic effects of lead in the blood the average lead levels american children is about 2 micrograms per deciliter and about 8.9 of american children have lead poisoning which is just too high right thankfully within the last few decades the percentage of children that have lead poisoning has declined and lead intoxication is much more prevalent in minority groups and among those who live in the northeast as well children tends to have highest exposure of lead from old house the paint that was used in these old houses and lead in them so as these paint chip away children can actually suck the chipped paint or the dust from the paint itself can be inhaled by children with severe lead intoxication mental retardation in children can happen there's about drop of five points of iq for every micrograms per deciliter in the blood other adverse developmental outcomes as a result of light exposure in children they may have aggressive behaviors they're hyperactive they may have anti-social behaviors and they will have learning disability so it's really important for the public health professionals to prevent childhood lead exposure as much as possible it's just really toxic chemical all right that's about it for this topic we went over four different important toxic metals arsenic chromium mercury and lead we also talked about the three general mechanisms of metal toxicity and the speciation of metals all of these are very important concepts if you have not really understood all of it make sure to go back and re-watch the video also you'll need to read the required textbook reading for this topic and once you feel like you're ready you may take them in a quiz and that's about it for this lecture okay take care bye