Open Integrated Pest Management Education Resource

Roundup as a Probable Carcinogen: What Does It All Mean? 07/02/2015




Dr. Susan: I'll talk really loud. How about that? It's a pleasure to be here, and I know there's a lot of interest with what’s going on with Glyphosate. What I’ll try to do is put together some information on what the studies are, what I think they are basing the rating on, and a little bit more in depth about how IARC goes about determining rating. I'll start by telling you a little bit about pesticides usages. We provide resources and tools for risk assessment and for understating more about how you might be exposed to pesticides, what happens if you are and what effects pesticides may have on humans, fish, birds, bees.

I want to start by providing a little bit more detail about GIR process. That video was great. I'm going to dive in just a little bit deeper, and then we're going to take a look at the studies on which the rating is based, at least, the ones we know about it. And then what does this really mean for people using that pesticide or thinking about using it or thinking about getting rid of it.

Next slide. IARC is an international body, The International Agency for Research on Cancer, and they are overseen by the World Health Organization. Many governments use their expertise to understand more about the risks associated with exposures, not just chemicals, but as Chris mentioned, occupational exposures. The process is that Working Group of scientists gets together and looks at all of the data. What are people exposed to, how are they exposed, what do we know about the mechanism of carcinogenesis, and then animal studies, human studies, cell-culture studies that will actually help us figure out what is going on.

Female voice: Are companies’ representatives allowed to be in that Working Group? The representatives of companies for manufactured products?

Dr. Susan: I know that for the Glyphosate one for sure, they were not. But JMPR, the joint -- I can’t remember what that stands for, but there is another group that looks at Pesticide Residues, GMPR. That group does have chemical company representatives, and they're planning on taking a second load.

Next slide. These are the categories that the Working Group uses to weigh the evidence. Is the evidence taken on balance sufficient to show that there's a definite positive relationship between exposure and an outcome of cancer. There's a lot of things that can go wrong in these kinds of studies. Not wrong, but that make it very difficult to pin something down with precision. There’s multiple exposures, people smoke, people have jobs that may expose them to other carcinogens besides the one that you are looking at. There’s a lot of things that might make it difficult. Many of these studies are done retrospectively, which means they ask people what kind of chemicals or pesticides did you use in the last 10 years. Are you going to remember that? Are you going to remember how many times per year what was your exposure? There are issues like that that make studies like that. The second category down is, is there limited evidence. Maybe there's some associations between cancer and the agent, but you can’t really definitively say that it’s true.

Inadequate evidence: You don’t have enough, you can’t really say for sure but there's a hint of something going on.

Then the converse, is there strong evidence that the agent is not necessarily involved. This is for humans, and then the same assessment is for animals. Humans and animals are different, laboratory animals. There are different mechanisms by which we metabolize chemicals in our bodies between rats and humans, and there are different organs that take care of doing this kind of processing. Rats have a forestomach that does a lot of processing of what goes in, we don’t. You have to take into account the physiology of the animal that we are talking about.

Sufficient evidence here, for animals, you’ve got some kind of causal relationship that shows up. You dose the animals with the chemical, you get X number of tumors or animals with tumors. Then you would see that it is proportional to the dose. This needs to be true in two species of animals. It's usually mice and rats that are tested. Or you could have two or more independence studies in different labs that get the same kind of result that’s sufficient.

So, limited evidence, again, the experimental design might not be quite right or the results, the interpretation of results that you've got, you often don't have the actual raw data. You are looking at results that someone else has written up, and that might be confusing or not clear. Or you may be only seeing benign tumors, not malignant tumors. They are adenomas instead of carcinomas.

I'm not sure about this last one. Tumors are observed only in a narrow range of tissues or organs. If you’ve got one cancer, you’ve got one cancer. Anyway, that’s the criteria. Inadequate evidence, you don’t get enough, you cannot say anything definitively, and of course, evidence are not carcinogenic.

The third thing that they look at, this Working Group, is Mechanistic Data. There are tests that you can do, you may heard of the AIMS test, which looks at immunogenicity of a chemical, it doesn’t alter your DNA. There are a lot of cell-culture tests like that that will tell you something about whether the agent damages your DNA, messes up the chromosome, basically scrambles things so that you do get cancer effects. You also can look at the tumors themselves, the histology, the pathology, the tumor itself. There may be genetic effects that go across from mother to child. You are altering DNA when you are making cancer cells. For example, you can also look at what the molecule looks like, the agent that may be your carcinogen and say, well, is it mechanistically possible from the chemical perspective to say forget the biological organism, if you could put these two molecules together, will they react to alter the DNA. Knowing whether there are other compounds out there that will do all kinds of things, are they similar in structure, those kinds of analysis also.

Next slide. The questions about mixtures, I would say that's a huge gap. There are a lot of issues. Some chemicals actually take out your body’s system for detoxifying things. If any of you is taking statins, you know that you shouldn’t be drinking grapefruit juice because grapefruit juice basically shuts down the production of the enzyme that metabolizes the statin. You have to worry about mixtures. It's a very difficult thing to do technically, and so our whole system is not quite geared up to handle it in terms of assessing risk for mixtures.

They weigh all the evidence and they come up with a rating.

Group 1. Carcinogenic to humans.

Group 2A: Probably carcinogenic to humans

Group 2B: Possibly carcinogenic to humans

Group 3: Unclassifiable as to carcinogenity to humans

Group 4: Probably not carcinogenic to humans. Then they developed a monograph. What’s not done yet for Glyphosate is they haven’t yet published the monograph. All they published is a two-page document or a two-page paper in Lancet, a medical journal. Teaser, exactly.

Next slide, please. I wanted to give you some examples, so that you can kind of put things in context with what you know, what you work with or you are exposed or you think about it. Group 1 chemicals have sufficient evidence of carcinogenicity in humans. For all of these, this is interesting, there are known human exposures. There's disease, there's drugs that you know what the dose is that the person is getting, occupational exposures and then lifestyle exposures such as drinking and smoking. These are few, contraceptives, alcohol, smoking, working in petroleum facilities and Hepatitis C virus.

The next slide shows you a longer list. These are things that you probably already know cause cancer: Arsenic, bad stuff; Hexavalent chromium, we all saw Erin Brokovich, Cadmium, Beryllium, Radionuclides, radioactivity, we all know that that is trouble. Benzene is a solvent and is used in many industrial processes; Benzidine is a precursor for a dye production. Formaldehye shows up in trailers they used to house the Katrina victims and a lot of building materials. Dioxins, coal tar, solar radiation. On that side is a kind of chemical things. Here, it’s sun, exposure, wood dust. If you're in furniture making or cabinet making, it’s a numb risk. Alcoholic beverages, smoking, etoposide in combination with Cisplatin and Bleomycin. Some of these anti-cancer drugs or treatment chemotherapy drugs are actually alkaloid agents that modify the DNA of tumor cells, and you just hope you don’t get a second round of cancer from being exposed to these drugs. Biological agent Hepatitis, Human Papillomavirus. Aflatoxin mold is a liver carcinogen that is fairly prevalent in the developing world, often in peanuts which is a staple crop in Africa. It gets moldy, and there is a lot of incidents of liver tumors that related there. Epstein-Barr virus.

Next slide. 2A, this is the group that Glyphosate is in. Limited evidence of carcinogenicity in human but sufficient evidence in animals, strong mechanistic -- this is general, this is not for Glyphosate inseparable. In general, this is what you need to have a rating. Diesel exhaust, tanning beds and certain pesticides.

Next slide. Petroleum refining, Creosote, PCBs that are used as insulators for electrical transformers. Tetrachloroethylene or perchloroethylene used as a dry-cleaning solvent. There’s a lot of waste still in the ground water. Malathion, which is insecticide, it’s widely used. Glyphosate. Ethylene dibromide is a fumigant used to be used for fumigating flowerbeds. Lead compounds fall into this category. Androgenic anabolic steroids that weightlifters use. Hairdresser or barber occupational exposures, UV radiation, sunlamps, tanning beds. Adriamycin, another chemotherapy agent, Phenacetin drug and Acrylamide in French fries.

Male voice: It seems like solar radiation is in two places. UV on 2A and then you get solar radiation on 1.

Dr. Susan: Yes, I know. Solar radiation is kind of in there twice.

Next slide. Group 2B Chemicals. These are the possible human carcinogens. Limited evidence of humans and not quite sufficient evidence in animals, but pretty good mechanistic evidence that there's probably a connection between the cancer that you see and the agent. Chlorinated Phenols fall in this category. Triclosan is a hand sanitizer that’s widely used. Orange soaps that are frequently used everywhere. Butylated hydroxyanisole, which is used as an antioxidant in cereals and crackers and things like that.

Next slide. Chlorophenoxy herbicides like 2, 4 –D, and 2, 4, 5 –T. They just reevaluated 2, 4 –D and it ended up as the same, as possible. Carbon tetrachloride used to be used as a dry-cleaning solvent, which no longer is. Chlorothalonil is a fungicide that’s widely used on fruits and vegetables and golf course turf. Pentachlorophenol is a wood preserver that is probably painted on many of your houses. Other poly-chlorophenols for occupations, carpentry and joinery, welding fumes, gasoline engines as opposed to diesel engines exhaust which were 2A, glass wool like insulation, BHA preservative and Phenobarbital, which is a drug widely used for treatment of atrial fibrillation.

Next slide. I gave you some context for the kinds of chemicals that have these ratings. Glyphosate, the committee, the Working Group decided that there was sufficient evidence of cancer in mice and rats that were fed Glyphosate over several years, and this is where I'm not exactly sure what studies they are looking at. We are going to talk about those studies and we’ll see. There’s strong evidence of carcinogenicity from mechanistic studies that explain how Glyphosate may cause cancer, and then there's limited evidence of cancer in humans for epidemiologic studies of people, and most of these studies have been done on pesticide applicators or farmers.

Next slide. We're going to start by looking at the human epidemiological studies. In 1999, two Swedish scientists (Hardell and Eriksson) published a paper that showed the correlation of exposure -- that was not statistically significant but yet significant enough to publish -- of exposure to Glyphosate with the non-Hodgkin’s lymphoma. To put this in context, people who work with pesticides a lot, like farmers and pesticide applicators, tend to have a higher incidence of non-Hodgkin’s lymphoma. What you've got going on there is a huge picture of exposures, the farmers are using a herbicide one week and then an insecticide the next week and a fungicide and a herbicide next week. So, a lot of mixtures, a lot of potential for confounding, where we can't tell where the effect is from. Is it from one chemical, the other, or the mixture.

A little bit about this, the odds ratio tells you how much more likely you are to have gotten cancer if you were exposed versus not exposed. This was a retrospective study. This required people to remember well what they were exposed to. The point that was just made is that if your confidence interval (CI) is below 1, it's not statistically significant. That's why it's not significant, but it's a trend. You can see that the odds ratio or range goes up to 13, which is pretty high. The problem with this is that there was a very small number of cases and controls. Four cases, three controls, not enough to raise a flag.

Next slide. In 2002, Hardell and Eriksson, these guys went back. The hairy cell leukemia is another type of non-Hodgkin’s lypmphoma, they are related. They pooled that data and said, okay, well, let's look at those types of cancers together. They actually got more cases that way, and they found statistical significance. One confidence interval 3.04(95% CI 1.08-8.52), and risk increased with increased exposure. That's kind of an important observation. It's still confounded by multiple exposures.

Next slide. In 2008, they included additional data after 1998, also still pooling data, still retrospective, and they found again statistically significant association. Odds ratio 2.02. Confidence interval 910/1. The statistical significance is good. If you had more than 10 days of exposure to Glyphosate in a year, maybe that's throughout the period we are looking at, the Odds ratio goes up high into the confidence ratio or the confidence interval. They have 910 cases and 1016 controls. They're starting to put some significance to the IP of it, non-Hodgkin’s lymphoma and Glyphosate. They are associated. There’s still potential confounding for exposure.

Next slide. McDuffie. This is a Canadian study. They also found a correlation between the non-Hodgkin’s lymphoma and Glyphosate exposure for people exposed at least 10 days per year. Their Odds ratio was about the same as with the other ones. So, it’s starting to be consistent. If they put all of the subjects, including the ones that only used it once a year or twice a year, whatever, you will lose the significance. That is actually starting to be a reproducible observation. They had 23 cases and 36 controls.

Female voice: What constitutes exposure?

Dr. Susan: That’s a really good question. That's very difficult to measure. When you're doing epidemiological work, that's the very difficult thing. Because what you're assuming is that when someone uses the pesticide, they are exposed to a certain level, and some people wear gloves, some people don’t, so that's going to be variable. There are ways to make estimates of that exposure. They have done that.

Next slide. This particular research is part of the Agricultural Health's Study. The National Cancer Institute, the National Institute of Health has this giant study going on that's looking at a lot of farmers. When they were doing their preliminary research, they started looking at other studies that they can start to get hypothesis from them. They put together three case control studies of farmers in Iowa, Kansas, Minnesota and Nebraska from 1980s. They were kind of going backwards to see hopefully if they can come up with some hypothesis. And they found a statistically significant association of Glyphosate exposure with non-Hodgkin’s lymphoma. Again, very similar Odds ratio 2.1, range, confidence interval is similar, good number of cases and controls, 650 and 1933. They actually were able to control for exposure to other pesticides with using statistical techniques.

Next slide. Same researchers and this is in their own study. The Agricultural Health Study looked at 50,000 farmers and their spouses from Iowa and North Carolina. It's a prospective study. They are surveying people every year, and they are asking them what are you going to use, what did you use, and they're asking them often enough so that they don't have that recall problem where they can’t remember what they did 10 years ago. This is a much better study design and they found no correlation between Glyphosate exposure and non-Hodgkin’s lymphoma in their first paper. But, they did find a statistically significant association with multiple myeloma, another form of cancer. Non-statistical significance, confidence interval CI 0.7-9.4, but for the highest exposure group, it is statistically significant. Huge number of people in this study, so there's no problem with having the statistics. The authors also say, well, there are still limitations in the data for pinning down something as a definitive cause. The limitations are there. There are multiple exposures, these are farmers and they are using lots of different pesticides. They’ve got ridden of the recall bias or the recall problem but you still have the issue that they are using a lot of different pesticides, and sometimes together.

Female voice: Did they include spouses, is that for control or is that for effective results?

Dr. Susan: Well, spouses handle the clothes. Say it's a classic traditional marriage where the woman does the laundry. They are exposed too. The person comes in from the field, hugging them or touching them and people don't wash up right away. When did they start the agricultural studies? I don't know the exact dates. They are still collecting data, so they're going to redo this analysis. I think they started it not that long ago, in 2000 or something. I don't know. But it's been going for about 15 years now. Alright, that was human studies. Now, there are maybe other studies that the committee, the Working Group looked at. These are studies that I found in the literature, and that's why I can't wait until that monograph comes out so that we can actually see what they're talking about.

Now, we are going to look at animal studies. These also are the only animal studies that I had access to. They may have had access to others. Rats - study lasts for 24 months, two years, the lifetime of a rat. Whenever you do a cancer assessment, you basically give your test animals a series of different doses over a lifetime for the animal, and normally for cancer studies, you actually do kind of bump it up to pretty high doses, the maximum tolerated dose that will still provide animals to survive for the experiment. HDT is highest dose tested, for the top one, 31.5 mg per kilogram per day was highest dose tested. That's kind of mid range for a lot of toxicity tests, something like a second study where the highest those tested was over a 1000mg per kilogram per day - that's a lot. That’s really high. Rats, 26 months, they didn’t report the highest dose tested. We saw some tumors and all of this, even at a low and mid range ones. Testicle tumors in high-dosed males, increased in pancreatic range islet cell adenomas benign and adrenal cortical carcinomas at the HDT. Thyroid tumors, the toxicologists were evaluating the study, they dismissed these as just normal incidents. You do have background levels of cancer. I wonder these days with all the Roundup Ready corn and soybeans, what are they feeding the rats? The problem in these last studies is they didn’t dose the rats high enough.

Next slide. Mice. Remember if you want sufficient evidence in animals, you need two species. So, mice, two years, lifetime of a mouse, they didn’t get the highest dose tested but basically they saw lots of different tumors. Lung tumors, liver tumors, tumors of a lymphoreticular system. There's no clear dose-response relationships which is something that you look forward. If you dosed animals higher, you should see more tumors if it’s not the agent that’s causing the tumor. It wasn't statistically significant compared to historical controls. All of these animal studies, by the way, were done by the manufacturers of the pesticides, Preparation for a Chemical Register. There are guidelines for doing those tests, so EPA lays out how the tests should be done. Hopefully, in accordance with the guidelines. Second one, pancreatic islet cell adenomas, increase in adrenal cortical carcinoma and renal tubule adenomas was higher than that of controls. Two of the toxicologists said, well, they are not treatment-related, something else is causing them.

Next slide. Those were the animal studies, and again, there's probably more but I don't have access to them. Mechanistic studies are usually done in cell culture. These are things like the AIMS tests. It's mostly negative for gene mutation and DNA. It doesn’t seem to alter their structure. Chromosomal aberration, mostly negative and DNA damage mostly negative. EPA’s final assessment and Cal EPA’s final assessment is that it’s not genotoxic or mutagenic, nor clastogenic, which is causing or inducing breaking of the chromosomes. But recent studies are showing some evidence that Glyphosate in formulation, which means the product with all of its “inert ingredients”. There is some evidence that there is some clastogenetic activity that the chromosomes are being disrupted.

Again, there may be more studies that we were going to find out.

Female voice: Isn’t it assumed that that inerts are gases?

Male voice: From the ‘70s to now, they changed the definition of inert, no. Inert, it means just as inert as anything else.

Female voice: Are the studies reflecting that yet?

Dr. Susan: They are doing studies on pure active ingredient. They do these huge toxicity tests on the soup. There’s what’s called a six pack.

Female voice: Is there a movement to try to get them to be required on a list of inerts?

Dr: Susan: Yes, someone just filed a lawsuit last week, maybe earlier this week. Here’s what the Working Group said about Glyphosate: there's sufficient evidence of cancer in mice and rats that were fed Glyphosate over several years. With all these results, there's definitely some tumors in there. There's strong evidence of carcinogenicity from mechanistic or cellular studies. I didn't see that in those studies that I looked at. Then there’s this what they call limited evidence of cancer in humans from those epidemiological studies, probably because of all of the confounding because of multiple exposures.

Next slide. A lot of people disagree with this ranking. Glyphosate manufacturer, Monsanto: IARC did not base its decision on all this evidence. Instead, IARC disregarded dozens of scientific studies and relied heavily on papers that created false associations. Crop Life America, which is the chemical manufacturer published an article in which it said: EPA reviewed over 55 epidemiological studies conducted on the possible cancer and non-cancer effects of Glyphosate. Our review concluded that this body of research does not provide evidence to show that Glyphosate causes cancer, and it does not warrant any change in EPA's cancer classifications for Glyphosate. So, looking back at the history of the cancer rating at EPA for Glyphosate, if you look at the IRIS, the Integrated Information System, it was rated initially as a group C. It’s the EPA’s categorization. Possible carcinogen, that was in 1993. A current IRIS category is a D-class, not classifiable as to human carcinogenicity. But OPP, the Office of Pesticide Programs, a different branch of EPA, says it's group E. There's evidence of non-carcinogenicity for humans.

Female voice: Do you have confidence in the IRIS system?

Dr. Susan: No. The older ones maybe. I wasn’t paying attention back then but right now they have enough data after so many years and it’s all tied up in politics. Do I trust IRIS? They're so far behind and outdated in their assessments. EPA has Glyphosate in what they call Registration Review. Every 15 years, EPA re-evaluates every pesticide. They promised careful look at what IARC put together, so, hope to see that in the next six months or so.

Next slide. The German Federal Institute for Risk Assessment basically said: “It's not possible to fully comprehend indications for a genotoxic potential of Glyphosate based on the short report published by IARC.” I actually agree. “In particular also due to the fact that the assessment included studies using different Glyphosate containing plant protection products that are not specified in any detail.” This gets back to the issue of the inerts, the formulative products. “The BfR will perform a thorough review of the classification.”

The Netherlands Board of Authorization of Plant Protection products: “There's no reason to suspect that Glyphosate causes cancer and changes to the classification of Glyphosate. Based on the large number of genotoxicity and carcinogenicity studies, the EU, U.S. EPA Residues and the WHO panel of the Joint FAO/WHO meeting concluded that Glyphosate is not carcinogenic.” JNPR committee, one that does have pesticide company representatives or equal associated with them on it. NRDC is working to make sure that WHO excludes people of conflicts of interest from that. I don’t know if they’ve succeeded. They say, “It’s not clear on what basis and in what manner IARC established the carcinogenicity of Glyphosate.”

Next slide. Health Canada basically reviewed Glyphosate for re-registration in 2015. Their conclusion was, “Hazard identification, including carcinogenic potential is an important component in the determination of the potential human risk of a pesticide. The determination of such risk, however, not solely driven by the hazard profile but is also a function of the potential exposure to the pesticide. For this reason, both the hazard and potential exposure must be considered together when performing a human health risk assessment for a pesticide, since an identified hazard may be offset by the fact that the potential for human exposure is considered to be sufficiently low so as not to pose a risk of concern to human health.” There's a low level of concern for Glyphosate due to benign nature of tumors observed at the limit dose, the highest dose tested, and lack of oncogenicity in other studies. So that's Health Canada, that's the equivalent of EPA. They kind of agree that there's some tumor risk, but at high doses.

Male voice: I have a question in regards to high doses for what we use. I’m using 1 to 3 ounces per gallon, so, I use it twice a year. I’m not poring the concentrate on my hands, I’m not inhaling the fumes, so what is my potential risk? I’m 62 years old, I’ve got maybe 10 years of life left, what the hell do I care? I just want to spray my Roundup and simplify my life. I can’t do a damn thing. My life is crumbling with leaves, and I am tired of it. I want you to make it easier for me to spray NOW. I’ve been cut out, I don’t know about these other guys. I had 7 gardeners, now I’ve got only three. I’m overwhelmed with a lot of work that I’ve got to do.

Dr. Susan: That's a harder problem that I'm going to talk about right now. Next slide. It’s pretty clear that we really need to see what those guys do to know what’s going on. What human studies evaluate, what animal studies evaluate, what mechanistic information was considered, I’m quite sure I don’t have all of that.

Female voice: Did they already disclosure rules about the public rights?

Dr. Susan: The committee will get to see some of the raw data that is never accessible to public.

Male voice: Actually, Susan, I read the opposite on the IARC, they claimed that they were only using public available data. That's what they said on one of the pages. I want to figure that out. I was surprised to see that.

Dr. Susan: For this one?

Male voice: For this one.

Dr. Susan: I know that they’ve had access to confidential business reports. Now, there’s one thing that we haven't really talked about in detail and that is how potent the carcinogens are. That matters because if it's something that is superpotent then you only need to be exposed for a little tiny bit, and you make a cancer. You can be exposed to 4,000mg per kilogram for a whole lifetime, you’ll get a cancer. Maybe it's not something that you should worry so much. You might not be getting that kind of exposure. Cancer potency is our term or saying how much the cancer rate in a population, how many people parts per million population, how does that increase with an increase in exposure. This is an example, you’ve got a dose, parts per million per year food if you are a rat. And this is generic.

Next slide. Cancer potency and cancer ratings don't match necessarily. So, some things that are known carcinogens may be less potent than things that are probable or possible carcinogens. Let’s look at the few of these. Potency is what we call Q*. The lower the number the less potent it is in causing cancer. Methylene chloride is a solvent, that’s the lowest on this list. It’s got a possible rating from IARC. We also have 1, 3-Dichloropropene, it’s also possible, it’s got 0.04 value of order magnitude, factor 10 higher. There’s Toxaphene, 2B, possible with 1.1 potency. So, you get exposed to Toxaphene, and even they are calling it possible carcinogen, it’s actually quite potent in causing cancer. The point is the system that they use for rating these things is based on what we know about people that are exposed to. The known carcinogens are the things that have been used in industries, for solvents, things that we’ve been using for a long time. Heavy metals, things like drugs where you are taking a particular dose. If you know how much you are taking, you can track the result.

The fact that it's known doesn't necessarily mean it’s potent conversely. If it's possible or probable it can still be quite potent, and we don’t have enough data to say known.

There's all kinds of reasons why they might be more potent. Does that make sense?

Male voice: So, it's about how sure we are about the evidence versus what the evidence would say if it's true in terms of its potency.

Dr. Susan: That one study had been evaluated by IARC, and it was the EPA basically in one sentence of risk assessment saying, well, we didn’t look at the cancer data.

Female voice: Which chemical are you talking about?

Dr. Susan: Chloropicrin, the second one from the bottom.

Male voice: Which is widely used.

Dr. Susan: As a fumigant gas insecticide for strawberries.

Male voice: Tear gas.

Dr: Susan: DPR, Department Pesticide Regulation did do a careful evaluation. They gave a cancer-causing factor 2.2, which is high, very high. You can see that sometimes these listings are whatever they get around to or whatever they are told not to look at. You see a lot of that. So, there are issues there.

Male voice: So, this tells me that focusing on the dying industry and other dye industry in other countries might be a really important thing for public health, Benzidine.

Dr. Susan: Yes, Benzidine.

We don't know what the cancer potency of Glyphosate is. You have to do some special studies to get that number, but the fact that you're getting tumors only in the individuals exposed to the highest dose suggests that potency is low. You can be exposed to a lot before you get cancer. This just suggests this. This is where we are a kind of pointed to that direction. The implications are that people who are exposed to a lot of Glyphosate, they have reason to be concerned much more than people who might apply it twice a year. Children are typically more susceptible to both EPA and more carefully OEHHA have put together guidelines for assessing risks to children and also for less than lifetime exposure, because the way things change and stay with chemicals, you are not necessarily exposed to a chemical for a whole lifetime, this can change, unless it’s gasoline. So, for children potency it is assumed to be a factor 10 higher. That’s default.

In pursuit of larger markets, Glyphosate products are now being marketed to farmers as “burndown” herbicides. As you get close to harvest, they apply herbicide to the field and this kills all the greenery around the wheat or barley or whatever. It allows the harvested wheat about week to 10 days, so it’s a significant flexibility. What this means, Glyphosate once it gets in the plants doesn't go away. It's not metabolized by the plant, it’s not excreted by the plant, there's no microbes inside the plant, so, it doesn't go away. It's probably their in all of our food. USDA doesn't analyze for Glyphosate and AMPA in its Pesticide Data Program.

Male voice: Are you talking about treating the grains here or …?

Dr. Susan: They spray the field. They basically want to kill the wheat so that they can harvest the grain sooner.

Male voices: It also causes the grain to ripen more quickly, and the other thing is it’s cheaper to get rid of all the greenery.

Dr. Susan: Yes, it’s definitely cheaper to harvest it and get rid of all the greenery.

Female voice: All wheat?

Dr. Susan: Most wheat. I don’t know how widespread this is, but it’s starting to be. Then the question is as well, jeez, is it getting into us? A 2013 study from Friends of the Earth in Europe, where they actually grow genetically modified crops extensively and they don’t sell them so much in the grocery stores. They have to label them, they have a label along there. They looked at Glyphosate residues in the urine of 182 participants and they found Glyphosate residues in 44% of them, 18 different European countries. If you think about the U.S., we're probably eating it every day with bread, and so we’d be really interested to do this experiment in the U.S. I know that there’s a group doing that. Anyway, we are exposed through our food to Glyphosate, so the question of some herbicide use.

Next slide. This is kind of my thought right now. The data that we have indicate that the risk will be highest for those that are most exposed, people who are using this occupationally and using it a lot. Applicators, of course, are the group of highest concern. For the general public, exposures from food might be higher if you eat unconventional food, not organic. Your exposures from food might be higher than anything you might get from the occasional brushing up against a plant that might be treated with Glyphosate.

Female voice: What if you had pets or children and if you spray lawns?

Dr. Susan: You wouldn't spray a whole lawn with Glyphosate, it would kill it.

Female: It isn’t the fact if you would or wouldn’t but it’s children. I’m talking about the exposure of pets and children.

Dr. Susan: There may be some exposure scenarios that are hot but the food thing is really bothersome to me because you don't know it's there, and you are a kind of assuming it’s not.

Male voice: We have the precautionary principle here in the city. Personally, for me, that's a classic example, asking the question, is it necessary, is it really necessary to have that extra week at the risk of a lot of unknowns for people who are eating wheat?

Female voice: Does it break down in soil?

Dr. Susan: It breaks down. Half-life is 30 to 60 days in anaerobic soils where it's really cold. That could be a year or half a year, but it does break down.

Male voice: Most crops have a mandate period before harvest that you cannot spray insecticide. Is that not the case with Glyphosate because I assume that nobody does it?

Dr. Susan: EPA assumes it's not carcinogenic, and they assume that a reference dose for Glyphosate is actually quite high. It is 2 mg per kilogram per day.

Male voice: That means it's very low acute toxicity.

Dr. Susan: Low acute toxicity. EPA probably evaluated that risk and said we’re below in your level of concern.

Next slide. What do we do instead? We have a whole shelf full of alternate herbicides. This is an evaluation of herbicides that are used in wheat management. Let’s take a minute to think about what each one means. We've got different herbicides on the vertical axes: Aminopyralid, Clopyralid, Chlorsulfuron, Glyphosate, Triclopyr TEA, 2, 4 – D Acid, Imazapyr, Triclopyr BEE. And the bar is a risk range and it is actual risk. It’s a Hazard Quotient. How much above or below the reference goes? This is for applicators that may wear herbicide-contaminated gloves for 1 hour. This is a calculation so you can actually estimate what these numbers are.

Female voice: And what your basic calculations are?

Dr. Susan: These are the four service spreadsheets. It assumes certain amount of absorption to skin over some period of time. The ones that are in red, you are above the reference dose. Ones in yellow are kind of close to it but not quite in it. The ones in the green are far below the highest dose.

Male voice: Susan, can we just say, the top line is Milestone. Aminopyralid is first one on top. That’s Milestone. Clopyralid is Lontrel or Transline. I don’t know what’s Chlorsulfuron. We don’t use that. Glyphosate is Roundup, Imazapyr is Habitat. Triclopyr is Garlon Turflon. Actually, there’s two Triclopyrs.

Female voice: What’s the difference between these two Triclopyrs?

Dr. Susan: Triclopyr Amine Sulfate doesn’t go through your skin as rapidly. It is less toxic to applicators but if it gets into your eyes, it causes irreversible eye damage.

Female voice: That is Garlon 3A?

Dr. Susan: Garlon 3A is the Triclopyr TEA and Garlon 4 is Triclopyr BEE.

The course is to put these things together basically. Some of these are based on older studies, but they're assuming protective unit that is required.

Male voice: Susan, can I add that the exposures they used on this, for me, the calculations for what we use on our lands are a way, way higher than what we typically use for the Triclopyr. You should keep that in mind.

Dr. Susan: They are just making assumptions based on surface area, exposure, which goes deeper in skin. These are just assumptions, but they are pretty good and they match with experimental data. The model’s been validated pretty well.

Male voice: Susan, I didn’t hear your answer to the big question about what type of glove? The assumption is that it is going through the gloves into your skin.

Dr. Susan: Rubber gloves. It’s like you get some on your hands and you just stick your hands in the gloves. Aminopyralid looks lower, Clopyralid, Chlorsulfuron, Glyphosate looks pretty low based on before these particular assessments were taken into account. There are issues though. If you are looking for a different herbicide, Aminopyralid, Clopyralid and Imazapyr are good broadly but not so good for grass and things like that. Glyphosate had the advantage that it’s broad spectrum. It works on the grasses, and it kills everything essentially. Some of these other ones are selective. None of these are carcinogenic.

Next slide. This is for general exposure. This is based on studies done of applicators working in the field where they do biomonitoring of Glyphosate presence in their urine after working with the herbicide for a day or five days, and they can find out that just working with the herbicide, you're going to be exposed to some extent. There's variability in which applicator gets the most exposure, some people may not wear gloves, other people are very, very careful. There’s variability, but you will have some exposure if you use it.

Next slide. General public. Okay, so you are walking through a recently sprayed area, and maybe you're a woman wearing shorts and a t-shirt. With that much skin exposed, the assumption is that you have got certain amount of surface area that touches the vegetation as you go through. Some of it is absorbed into the body, and you can calculate what the exposure would be. Again, these same ones come to the top, Aminopyralid, Chlorsulfuron, Imazapyr, Glyphosate, etc.

However, a lot of these lower toxicity chemicals are very persistent, very persistent. In fact, Clopyralid and Aminopyralid are ones that last in compost so long that if you mow your grass and put the clippings in the compost pile and then use the compost to fertilize your garden mixture, you'll kill your garden. So, some of these have issues.

Female voice: What about aerobic environments?

Dr. Susan: The question was about anaerobic environment. The soil itself is actually a little bit more anaerobic than that. The anaerobic environment that I was telling you about before was in like a swampy area, where it's muck and deeply anaerobic. If you've got air pockets in your soil, it’s going to degrade, the microbes will chew it up.

Next slide. Let's think about something else to do. I heard some really interesting stuff on the Marin County folks. Chris and Al, they have a really nice presentation showing what can be done with just re-thinking how are you going to design your landscapes. It’s more xeriscaping and hardscaping, where you can use flaming without catching a whole place on fire. Use of landscape cloth and mulch in areas that you want to keep free. And this is from my own garden. I don’t have problems with the weed in that area because my plants just shade everything out. There are a lot of things that you can plant, both from seed or from planting plants.

Female voice: What about healthy soil biology?

Dr. Susan: Healthy soil biology will help you with soil tests like nematodes and fungi and things like that, but it doesn't help with weeds.

Female voice: I want to bring something about hardscaping. I’ve just found out recently that the big box stores that sell blocks, gravel stones, stones, rocks are regularly cooling them in herbicides and pesticides. So, you are doing that in an environment, you put it into water or something that’s cool and it’s so toxic. Big box stores, chip products, if it says weed resistant, they don’t say it’s coded, they say resistant or something like that. It’s cheap.

Dr. Susan: I’m going to stop here. I think that you people in the audience have a lot of experience. I love when you talk about what you are doing because it makes inroads into landscaping, and it doesn’t require so much herbicide.