hi everyone welcome back to public health 462 we are going to go over topic 6 toxic effects of pesticides and pesticide residues this is part 1 of the lecture today we'll talk about different types of pesticides which includes herbicides insecticides fungicides rodenticides we will mainly focus on herbicides and insecticides we will go over particularly three different herbicides glyphosate - 4d and paraquat and then we'll spend just a few minutes talking about rodenticides and fungicides and in the second part of the lecture we'll talk about insecticides there are three different kinds of insecticides pyrethroids organochlorines and organophosphates and carbamates and lastly we'll talk about pesticide residues we'll go over the pesticide data program by USDA a past can be any species of plant animal fungi or microorganism that threatens human health and well-being of course sometimes we inappropriately blame others as pests like our little brothers and sisters but in fact when we talk about pests these are the things that harm humans and our health these are disease-causing organisms not just on human health but also in our ecosystem in our crops and etc even paga and zebra mussels are pests you probably have never imagined these muscles being pests but in fact this is a big problem in California especially in clora River aqueduct where these mussels are growing in our reservoirs and in our aqueducts unfortunately they grow on top of one another if they just grew flat on the surface next to each other then this won't be a problem but the fact is these mussels they grow on top of as you can see in these pictures now they inhibit the pathway of the water and it can actually slow down the movement of water that delivers this precious water to Southern California pesticides are materials that are used to kill repel or change the behavior of unwanted organisms and this has been a backbone of pest control in the last half a century when we say pesticides we are really referring to mostly chemical pesticides here there are over 900 active ingredients that are commercially used today the EPA estimates that in 2012 over 1.1 billion pounds of pesticides were applied in the United States and in fact that number has slightly decreased since 2012 unfortunately with herbicides we have been applying more worldwide the majority of pesticide applications were in fact herbicides perhaps this is somewhat surprising to you because when you think of pesticides maybe you probably thought of insecticides first here in this graph the black represents world grey or presents United States herbicide has highest use among all the pesticides and then it's the insecticides fungicides and other fumigants in terms of who actually uses pesticides gray represents the home and garden black represents agriculture and the white represents commercial use and governmental use so with herbicides it's mostly used in agriculture some is are used in residential applications insecticides interest in E there are more domestic applications compared to agriculture ideally toxic effects of pesticides will be highly specific for undesirable targets meaning that when you apply pesticide you want to just kill the pests not the other organisms that in that environment unfortunately most pesticides are not that specific and are generally toxic to many non-target species as well and that includes humans too so it's very important for us when we apply pesticides that we minimize the possibility of exposure to non-target organisms as with all of the other chemicals that we use in our society we have to think about the benefits and risk especially with pesticides and often people think of pesticides and they already have negative predisposition towards pesticide use but in fact there are important benefits we have to balance the benefits in the wrist first pesticides allow us to control vector borne diseases I don't like mosquitoes not only do they cause itching once I'm bitten but also they carry diseases and the best way as far as the technology we have today the best way to control the vector borne diseases is using pesticides particularly it's the insecticides right also there is excessive loss of food crops because of insects and other kinds of pests and it's important for us to harvest and keep as much of the crops as possible so that we can deliver the food for consumption so this table tells us the damage of crops that's caused by pests if we didn't use pesticides for avocado we'll lose about 43 percent banana 33% we lose about 25% of grain we lose about 70% of pineapple who lose 95% of sweet potato and we would lose 62% of lettuce if we didn't use any pesticides so pesticides the benefits obviously is that it saves the food that we grow let's compare the pesticides use between 2000 and 2012 this is a data for 2000 here's a data for 12 if you look at the world market in fact by 2012 we have used more pesticides however here in the United States our pesticide use has gone down unfortunately we have been using more herbicides here in the United States in 2012 compared to 2000 this table shows us EPA's classification of different toxic chemicals they divide toxic chemicals into different categories 1 2 3 & 4 1 being most toxic in order to be considered category 1 toxic chemical if any of these facts apply to the pesticide or the chemical it will be considered category 1 if ld50 of acute or exposure is equal to or less than 50 milligrams per kilogram it will be considered category 1 Chemical regardless of what acute dermal acute interrelation my irritation levels are so if any one of these fit into the chemical it will be considered category 1 category 2 acute oral exposure ld50 is between 50 and 500 milligrams per kilogram and you can see that in category 3 that number increases in category 4 is much much greater so category 4 is least toxic category 1 is most toxic for eye rotation one of the things that EPA looks for is the damage to the cornea cornea is the transparent tissue that's in your eye and if it gets burned or it is inflamed it can become cloudy and when it becomes cloudy obviously you will not be able to see through the cornea very those people who were content lenses scratching your cornea is not very good you don't want to cause inflammation in the cornea because continual irritation and inflammation can lead to cloudy cornea if the chemical is category 1 it will need to have danger label in the product if it's category 2 it should have warning category 3 caution and for category for labeling is not required so you can see here an example here's a product a cute or oh is category 3 oq dermal is category 4 and you can see although acute normal is 4 and primary skin is 4 because there are category 3 component it will get caution label here's another example acute product see acute oral exposure is category 1 and regardless of what the other ones are it will get the danger label if the chemical is toxic through oral dermal or inhalation pathways then it will also get this poison label as well now if you look at product D it is a primary eye toxin so you will get danger but it is not one of those oral dermal or inhalation exposures so you will not get poison there's no poison for this and I want to talk about special inert it's the inert chemical that's in the product itself it's not an active ingredient that may also be toxic wheeze cause about 11 billion dollars of loss annually and thankfully most of herbicides are not very persistent and they tend to break down rather quickly and for consumers it's good because by the time it comes to was most of the herbicides have been broken down to safe chemicals these are the most commonly used pesticides the most used pesticides is glyphosate it gets ranked one we'll talk about this and then it's atrazine will briefly talk about atrazine H stands for herbicides fum stands for female guns we'll also talk about two for D it's a fifth most used pesticide and etc although I will go over the mechanism of toxicity for these herbicides but here is a quick summary of mechanism of toxicity we'll talk about atrazine atrazine inhibits photosynthesis we'll talk about phenoxy acids an example of phenoxy acids is 2 4 D and it is an oxen growth regulator it acts like a growth hormone and that becomes toxic for plants we'll talk about glyphosate glyphosate is enol pyruvate aqui mazda3 phosphate synthase inhibitor and by inhibiting the process it prevents the plants from growing and living and lastly we're going to talk about paraquat it causes disruption in cell membranes so these are the four herbicides that we are going to talk about today as mentioned glyphosate it's also known as Rhonda it's the trademark name well briefly talk about genetically engineered crops and then we'll talk about 2 for dichloro phenoxy acidic acid or known as 2 4 d paraquat and atrazine you've probably heard of roundup roundup is a trademarked name for glyphosate it used to be owned by Monsanto and Monsanto is now currently bought out by Bayer glyphosate is a non-selective systemic herbicide it kills most of broadleaf plants and grass if it has broad leaves it will kill them it interferes with the synthesis of essential amino acids such as phenylalanine tyrosine and tryptophan in plants I'll actually talk about the pathway it's acute oral ld50 in rats is about 5600 milligrams per kilogram which puts it in category four Noel and oal is about 10 milligrams per kilogram per day it causes renal tubular dilation in this slide we're going to talk about how glyphosate works and how it causes plants to die as a result of exposure now you know that there are 20 amino acids and about ten of them are essential in order for plants or living organisms to survive they need to have all of these twenty different amino acids whether they're able to make it innately or have to absorb it from the environment the way glyphosate works is that it inhibits an important enzyme in the pathway of producing these important amino acids aromatic amino acids such as tryptophan tyrosine and phenylalanine are synthesized in plants by a pathway called shakeela a pathway glyphosate is a competitive inhibitor of this enzyme call epsp synthase it's enol pyruvate cobalt III phosphate synthetase which I briefly mentioned in one of the previous slides so glyphosate inhibits this enzyme it prevents it from working so here in order to produce tryptophan tyrosine phenylalanine he needs to go through this pathway but this chemical glyphosate inhibits the process by preventing the enzyme from working now since animals do not have the Shikata pathway enzymes roundup is considered to be animal safe herbicide you private her to Roundup Ready crops it's genetically modified crops that resists the toxicity of glyphosate and we have been using a lot of genetically modified soybeans that was was as well as corn the way the Roundup Ready works is that Roundup Ready crops have modified genetic makeup by introducing a new gene this is bacterial gene into the plant into the soybean or corn by introducing this new gene it allows this Roundup Ready genetically modified soy bean to bypass the toxicity of glyphosate even if epsp synthase is inhibited for these genetically modified plants it's okay because they have a different pathway in which they can produce tryptophan phenylalanine and etc insertion of the bacterial gene that allows these genetically modified Roundup Ready plants to survive the toxicity of glyphosate so for farmers it's really easy if you have Roundup Ready plants what you have to do you just plant them and even if there are other kinds of wheat growing at the same time you don't have to specifically spray glyphosate just on wheat plants if you just spray all of it weeds which do not have this genetically modified enzyme will die but Roundup Ready crops will survive that's the idea behind this gently modify soybean or corn the way these genetically modified plants work is you are isolating a gene that's of an interest and this can come from bacteria it can come from animal cells or can come from other plant cells once you have isolated it you want to insert that gene and you have a carrier gene that allows you to insert it and you've looked for a trait that you want in these inserted plants once you plant them and you grow them and if these new plants have or expresses this new in trista gene then voila you have it you have this genetically modified organism or in this case a plant in humans glyphosate that's not easily passed through the skin and as I mentioned because the pathway in which glyphosate inhibits is specific to plants not in animals so it is less likely to be toxic to humans studies with rats showed that about one third of a dose of glyphosate was absorbed by the rat's intestine and glyphosate is eliminated in urine and in feces without being bio transformed given its widespread use glyphosate if you remember is the number one sold pesticides it's used not only in agriculture but also at home also in government properties in forests etc etc the exposure to glyphosate is inevitable because they are really widely used mild intoxication results mainly in transient gastrointestinal symptoms some moderate severe poisoning presents with GI tract bleeding hypotension pulmonary dysfunction and renal damage it's not teratogenic meaning that it does not cause birth defects or cause developmental problems or reproductive toxic effects the second herbicide that we're going to talk about is two for dichloro phenoxy acetic acid or known as 242 for D is one of the most commonly used herbicide in the world as well not as frequently as glyphosate but it is still widely used in farming clora phenoxy herbicides are what we call chemical analogues of oxen oxen is a plant growth hormone imagine if you were given too much growth hormones something is going to grow out of control and that's exactly what happens to plants when plants are exposed to 2 4 D there's just too many growth hormones in its tissue and this causes the plants to have this uncontrolled unsustainable growth and causing these stems to curl over and leaves start whither and eventually the plant itself will die and this really targets specifically the broad-leaved plants 240 has been used in the United States since the 1940s here's a picture of leaf here is a normal leaf now when is exposed to 240 it grows very quickly and then it curls over and eventually the leaves fall and die and which will result in plant dying in Yemen sue for tea is not absorbed well through the skin or lungs however sunscreen in seg repellents that can aid the absorption of these type of pesticides 240 is uniformly distributed and there is no bioaccumulation 240 is eliminated in Europe without biotransformation more than 75% of the absorptive OD leaves the body in the first four days after exposure meaning that it has very short half-life and shorter the half-life tends to be that the chemical is less toxic the oral ld50 of t4d is in the range of between 639 to 1646 now this is more toxic than glyphosate as you can tell while the ld50 of 2 4 d suggests that it is only moderately toxic the product carries the danger signal and the reason it is not because of the acute toxicity due to dermal exposure or or exposure it is because t4d causes serious eye and skin irritation to 4 D was evaluated for re-registration in 2005 and it is eligible for rear education ingestion of 2 4 D has caused acute poisoning in humans anything that's really concentrated and pure and if you have too much of it you know it's not going to be good for you right rats given moderate amounts of 240 in the diet for 2 years did not cause chronic adverse effects in humans prolonged reading or 2 4 D causes coughing burning dizziness and perhaps it can even cause loss of muscle coordination term exposure is major root of unintentional exposure to 40 in humans no human data were found on chronic effects of 242 for D is somewhat relatively known because of the fact that it's tied to Agent Orange many herbicides were used during the Vietnam War and depending on the type of herbicide they were put in different color drums 240 were placed in orange barrels unfortunately although 240 itself is moderately toxic during the production of 2 for D at the time there was a very toxic contaminant that was found in these orange barrels that contain 2 for D it's known as TCDD it's very very toxic synthetic human may compound and TCDD is known as a human carcinogen and also it's teratogen teratogen means that it can cause birth defects paraquat is a court nari nitrogen herbicide that was widely used in the past to control proudly f-- plants or weeds is very quick acting and the way it causes toxicity to plants is that it disrupts the cell membrane it can also inhibit the photosynthesis as well on the contact paraquat is a restricted use pesticides meaning that you need to have a license to use it particularly because it is more toxic than the other herbicides we just talked about if you want to buy glyphosate you can just order it on Amazon but paraquat you need to have a license to buy it the oral ld50 of paraquad in its various forms ranges from 20 milligrams per kilogram to about 150 milligrams per kilogram of body weight which will put it in danger category class one chemical paraquat is highly toxic to animals by all routes of exposure it has very low no absorbable effect level a large majority of fatalities from paraquad is not from exposure in spraying the pesticides in the agricultural field the fact that paraquat is so toxic and it was readily available to farmers that it was often used as intentional self administration to commit suicide some of the chronic effects for humans have been inferred from animal studies that can lead to Parkinson's disease and also irreversible lung damage when people die people often die because of the lung damage and they cannot breathe only small amount is absorbed from the gut however it accumulates in the lungs where it forms free radicals we talked about free radicals in reference to metals free radicals are very very toxic because they will react with almost anything and when there is accumulation of paraquad and they release these free radicals it starts to damage the lungs very very quickly lastly atrazine is used in crops such as sugar cane corn pineapples and macadamia nuts and etc etc it is the second highest use herbicide in the world it dissolves in water and enters plants through their roots and atrazine has been shown to cause changes in blood hormone levels in animals and this herbicide can perhaps be a potential endocrine disruptor so he was banned in EU in 2003 because of the groundwater contamination and they were concerned about the fact that it may act as an endocrine disruptor here you can see the various use of atrazine in the United States rodenticides kill primarily rats mice and moles rodents caused about four billion dollars in Los Angeles one of the often used rodenticide is called warfarin you might be familiar with this chemical because it is also used as a medication for people who have risk for heart disease warfarin causes internal bleeding it supposedly is safe for children and most pets because the bait contains chemical that causes vomiting however rodents cannot vomit so it will cause internal bleeding and they'll die warfarin is an anticoagulant meaning that warfarin causes blood to seep out of capillaries coagulants prevent the blood from seeping out now because warfarin is an anticoagulant it prevents the blood from sticking together and coagulate and individually they'll start leaking out of capillaries and this causes internal bleeding it is commonly prescribed as oral anticoagulant for people with increased tendency for thrombosis blood clot inside blood vessels the problem with warfarin used as medication is that it is difficult to determine the effective dose it has very narrow therapeutic range the acute or ld50 for warfarin in rats is variously reported to be three milligrams per kilogram to as high as 58 milligrams per kilogram in female rats it has very low noël value 0.02 9 milligrams per kilogram per day and warfarin has been established as a human teratogen that can cause birth defects so when I said that warfarin has a very narrow therapeutic range what it means is that the difference between being beneficial and toxic is very very small the black line here represents the beneficial use of warfarin efficacy the red line represents the toxicity so really the effective dose the safe dose is around here and this those is very narrow so if you don't use enough it's not going to be very effective if you use slightly too much it can kill a person major bleeding episodes in 1 to 2 percent of all patients that have initially use warfarin and it does sometimes cause deaths if you are accidentally given too high of dose but it does prevent 20 strokes for each bleeding event so it is underused because of the fear of bleeding people have this innate fear when they see this internal bleeding that's seen as bruise in hands or arms and etc so it is less utilized fungicides kill fungi fungal disease are virtually impossible to control without chemical applications there aren't too many things we can do to kill fungi most fungicides are surface or plant protectants and they are usually applied before the infection by fungal spores so by the time the spores are there it's probably too late with a few exceptions fungicides have very low acute toxicity in mammals here's an example of a fungus I captain is a broad-spectrum protectant of fungicides it is a potent irritant but it is only mildly skin irritant dermal absorption is very slow it is mutagenic in individual tests meaning that in the laboratory however in vivo tests have shown to be mostly negative it is known to induce the development of tumors in mice so captain is classified by the EPA as a probable human carcinogen ld50 for rat is about eight thousand four hundred to about fifteen thousand milligrams per kilogram of body weight there are other kinds of fungicides and some are quite natural just because it's natural does not mean it's not toxic copper sulfate is known to be a fungicide it has overall low toxicity and remains one of the most widely used fungicides triphenyl tin acetate is also used as a fungicide it has moderate to high acute toxicity but may also cause reproductive toxicity organic mercury such as methyl mercury was used as fungicide in the past and we know that this is very toxic not just to fungi but to bacteria as well as animals like humans so we don't really use it anymore in the past the way the organic mercury was used is to prevent fungi from growing in the seeds that will be planted in next season