Dr. Willie McKinney presents on the the importance of a toxicological risk assessment on your products before releasing them for public consumption at the Cannabis Science Conference in Providence, RI

” Proper Risk Assessments of Cannabis Products”

Good morning everyone I am grateful to have the opportunity to speak to you about the topic that I am very passionate about so I’m going to talk to you about risk assessment and toxicological evaluation programs but before I do that I have some disclosures as mentioned we’re consulting firm and we provide scientific and regulatory advice and support to abstract take about four to his abstract and all the studies were sponsored by abstracts that are going to talk about and a AVD advance failure devices these factors provided well they participated in conversations about the study design and they provided product samples and we tested the products in independent laboratories you have been you have received the disclosure so when you have a company there are several questions that you have to consider how much are we going to spend on marketing why don’t we have a different revenue but I think one of the most important questions you should consider but sometimes I find this the last queson that at least small companies consider is do you have confidence that the ingredients used in your cannabis products will not cause harm to your consumer now why is this an important question seems obvious but I’m going to talk about it anyway most of you are wearing August 2019 there were several reports of lung injury to the CDC and the CDC classified those long injuries as evolving which is E vapor and vapor associated on injury well there were several cases and the cases peaked in 2019 and ultimately unfortunately 2800 people experience long injury and unfortunately 68 people died this lung injury was linked to ingredients used in illicit products listed THC products to be to be clear and with further study the ingredients were vitamin acetate and some other ingredients now some of you may say well those were enlisted products illegal and came over how does that impact because I’m doing things the right way well let me tell you how something like this happens there’s not one company that gets the blame it’s the entire industry and this could create a moral panic and weight regulators up and wake up the lawyers as well all right so that’s one thing you have to think about the other thing is this is a great example of innovation on wild these people were extremely innovative and thought they were delivering a product that the consumer wanted and they did not do any testing they added these ingredients and they put these products on the market now and these products cost hard and when there’s harm in the population I mentioned glorious let’s talk about that for a moment I’ve done a little bit of litigation support and I can tell you in a situation like this you will be asked does your product contain vitamin E acetate and most of you know what you’re adding to your products and you would say no then the plaintiff’s attorney would show some analytical they assured that your product does contain vitamin associated and you would be looking like wow well that’s because the product that they pulled was a year old and there’s chemistry going on and the chemists will challenge me on this but somehow vitamin D is in there or from family from manufacturing so the point I’m making is it’s important to do testing there’s another reason here’s an if you don’t test your product other people will here’s the study that suggests that vaping CBD causes more lung injury and inflammation than failure nicotine fake products and the authors go on to say that and interpretations and flavors exacerbated the response and they conclude that there is simply a lack of robots that have evidence about cannabis safety when delivered from vaping products and so the question I have for you is are they talking about your product how do you distinguish whether or not your product is causing this problem if you don’t have the data then ultimately they may be talking about your product one company decided to do things differently and that company is abstract so abstract is a company that extracts turkeys from various sources that

they put these turkeys together in a land where they sell isolates for their clients to use in cannabis products and they approached us we couldn’t regulatory science advisors and asked us to help develop a regulatory science framework to support the use of their turning gland formulation in cannabis inhalation products and we decided yes we will help you and one of the first things we did was we need to define the product what actually is the product now for abstracts the product is liquids right now if the consumer were either pushing the limits on their skin or adjusting the liquids we would have simply looked at the ingredients done italics assessment or risk assessment and we would have been done and that is not the case here these liquids are then put into a device one must look at the device independently as well because the devices have electronics and that’s most of you know devices can cause acute harm if you’re like me, and you shouldn’t do this if I need to charge something I go find my bucket of charges and I pull one out and if it fits I charge well you could ultimately flow the battery that way so I wouldn’t advise that you do that but also the materials used in the device made leach metals into the liquids so you need to understand and evaluate the material but ultimately the product is these two things together and the consumer is exposed to the aerosol so we really want to understand the risk to the consumer when they inhale this parasol so before I’m going to go into a little bit of detail but the first question I have or I’m going to try to address is what makes a risk what is risk well a risk is hazard plus exposure and hazard is simply something that has the ability to cause injury and in this case the shark represents a hazard and can cause injury This salty because of the tears of misunderstood sharks that still doesn’t mean I’m going to swim with one so let us assume that this is Steven Spielberg shark this is Jones and it is dangerous it is a potential hazard and now there’s a diver in the water the shark doesn’t seem concerned so the hazard the likelihood of harm is done but the next photo shows you that the two have come the human and the shark have come in contact and the shark is hardly so there’s a higher high probability of harm therefore the risk there are four steps to a risk assessment hazard identification dose response assessment exposure assessment and risk characterization I don’t want to take break down and go into detail into one of these steps for you and what we did they created a pilot blend with abstracts ultimately to evaluate those steps and develop the program for them and the first phase is screening and so you want to perform a literature search and determine whether the term pain is associated with one of the priority health such as does it cause cancer does it lead to neurotoxicity just the chemical or turf pain cause reproductive or developmental toxicity effects now if you look and you don’t see any data that does not mean that everything is OK all right and typically if you don’t see data there’s a couple of things that you can do you can generate the data or you can look at the structure of the Turkey and if it’s similar to the structure of another molecule that has experimental data you can leverage that experimental data and make some decisions there overtimes I’ll just say if a formulation contains an ingredient that is a potential carcinogen sometimes there’s a business decision made that we really need to leave this ingredient in the formulation I would strongly advise that you reformulate but some people don’t want to do that in that case a lot of studies that you need to do to defend the use of that that formulation for example if you’re adding a carcinogen how would recommend you do it to your car system which is quite expensive and very well and that’s on the market by the way it’s easier to reformulate folks the next thing we do is we look at whether or not the turfing is genotoxic in other words doesn’t directly damage DNA and does it cost long a respiratory irritation or sensitization and we do this

using a predictive modeling and looking at databases and things like that again if you choose to add one of these ingredients to your formulation you need to do testing significant testing on your formulation to basically say that it’s ok the next step in a risk assessment is a dose response assessment now a dose response is simply the relationship between the dose of exposure and the effect of interest and the main thing you have to think about with the dose response is extrapolation toxicologists basically expose animals or cells to that high doses they try to distract them to low doses then we also extract right from the animal studies to humans and we had uncertainty factors and things like that however the process of extrapolation is different with the chemical and alchemical is classified either as a carcinogen or non- carcinogens are cancer causing agents it’s believed that there is no threshold there is no level below which there is no harm so what you do is you do a probability assessment or you mathematical equations and you determine the probability of that end up with a risk of 100 million I I’m not the person that says this acceptable typically authoritative body systems that as an acceptable level for non-cancer causing agents there is a threshold there’s a level below which if you are exposed for a lifetime it is unlikely that you will that these chemicals will cause harm to the population and so that’s the level that we try to find and identify for our client and the terpenes that they have and we used the pilot plan to do that so let’s just talk about one Turkey here so this is neutral which is interpreting that has a rose spell about and our clients like to use this so we evaluated it and what we found is that it doesn’t damage the DNA it’s not carcinogenic it’s not a neurotoxin and there were no alerts in terms of it causing respiratory so that’s the time looks like it’s a liOle answer but we also found that there’s a level below which if you’re exposed to this to you wrong there’s a low probability or low likelihood of harm and that is 1.09 milligrams per cubic meter well how does that relate to what my client is adding and are they below that level well we did some conversions and we came up with 21,800 micrograms per day is the level below which your consumers should be below now so that is a maximum use level but to determine whether or not the ingredient used in the formulation is acceptable we needed to do an exposure assessment how much product are people using how much aerosol are they emailing what is the consumer exposed to so we leveraged sales and survey data to estimate the daily consumption and we made some assumptions which is worst case we assumed 100% transfer rate from E liquid to vapor zone 100% absorption meaning everything you inhale stays in but we know people exhale so it’s a very conservative assumption and in general we found that our estimates were consistent with some general publications so we felt good about our exposure estimates and you can see the column in terms of milligrams per kilogram per day for exposure so now we know the maximum use level we have an idea of what summers are that they are exposing themselves to free each ingredient in this pilot formulation now we have to put the two together when you do that what you’re looking for is a margin of exposure and that’s the ratio between the exposure dose over the acceptable daily intake so a margin of exposure less than one OK you’re adding the reading at a level below the likelihood that it will cause harm if consumers when you factor in exposure you’re still OK if the humidity is greater than one you need to generate more data or reformulate always through our reformulate and so when we look at our pilot formulation there were two ingredients that had a margin of exposure rather than one mercing and beta caryophyllene so we needed to do some more work what do we do we did studies we did liOle Felicity studies and acute emulation study well that’s we did finish that we’re doing analytical chemistry analysis and biological activity

analysis so that I will talk about two of these little Felicity. What is that? Well, that’s the ability of a chemical or a compound to dissolve in fats, oils, or lipids, and what we recognize is that when I talk to you about evolving, vitamin E acetate is highly lipophilic and quickly went into sales and causing damage, and so there’s a scale and what we did we looked at all the ingredients, and we put well beta-caryophyllene in America, and we tested them, and as you can see they fall within the green area I include diacetyl here because it causes lung injury and that’s just to say that this assay alone can you cannot say that ingredient does not you need to understand the mechanism as well so Turkey would win when you look at beta carried off with the look of italicize value of

7.3 is getting close to 7.5 in an area where I get a little bit uncomfortable however, when you look at the blend, which contains beta curiosity, it has a value of 5.7, that’s why it’s essential as well to look at the formulation as well as the individual ingredients so they were OK we conducted an acute inhalation toxicology study for our inhalation study, and ultimately I’m just telling the outcome of that no results everything is clean so here we put the turkeys at a maximum constant inhalation concentration as possible exposing that, and everything is good so with that we are confident that the ingredients used in the pilot turbine plan are appropriate for their intended use we still have some additional studies to do, but I would recommend that each of you consider if you sell products that you consider developing A regulatory science program to understand the ingredients added to your products with that I’ll take a few questions thank you for your time