Thursday, April 30, 2015

More on Gypsy Moth Spraying: Bioaerosols and Medical Symptomatology

I had really hoped that after my first and then second posts on gypsy moth spraying that I could get off the topic and move on to more interesting discussions, but the topic is like the bad guy in a horror movie: you think you have dealt it a death blow only to have it re-emerge for another fight. Like my last post, this one is going to be a bit shambolic as I will attempt to cover several topics that have been raised since the last blog posting. 

On being a paid “shill”
As my regular readers know, I have previously discussed the “shill gambit” in my post “On “Bullies”, “shills” and using labels to shut down legitimate debate”. In that post I was talking about other scientists being called shills, but I wasn’t fooling myself. I knew full well that as I continued to blog about evidence-based decision making, it was only time before I was labelled a “shill”. Now admittedly, I have been called it a couple times on the topic of pipelines, but if pipelines get people excited then spraying for gypsy moths turns it up to an eleven. In the last week I have been called any number of names from “shill” to “unethical” with a few people pointing out that my work as a government scientist, and the owner of a money-making blog, puts me in position of a conflict of interest. I’m afraid to say that both my employer and my wife would be a bit surprised by that line of reasoning. My employer because they didn’t realize that I had left my job to go work for the government and my wife because she knows nothing about the slew of slush money apparently coming my way from unknown “corporate interests”. To put this all to rest, let’s start with the obvious. I do not work for the government. I work in the private sector. I do not get paid to blog, and since my blog site has no ads I derive no income from my blog. I blog on my own time, and never on the company dime, as I enjoy my real job far too much to put myself in any conflict of interest on that front. It goes without saying that since I blog on my own time, the opinions expressed here are entirely my own. For those of you wondering, some friends at work read my blog but my wife does not.

On Bioaerosols and Inhalation Risk
A number of people have directed me to a Facebook page: StopGypsyMothSpraying. At the site is a prominent link to an undated New Zealand TV article on Btk spraying (ref) which I believe refers to spraying conducted in New Zealand in May 1999. The story features a very likable epidemiologist Dr Simon Hales from the University of Otago in Wellington, New Zealand. Dr. Hales brings up some very important points about spraying programmes. Specifically he points out that at the time of the spraying, in May 1999, very little was known about the science of bioaerosol dispersion of this particular compound. For those of you not familiar with the term a bioaerosol is simply a suspension of airborne particles that contain living organisms. The Foray 48B spray is a bioaerosol made up of Btk (a biological organism) in a liquid suspension. Most of the “inert” compounds discussed in my previous posts relate to the liquid suspension. To explain, you can’t simply spray raw bacteria into the air. The sprayed material consists of an active agent (the Btk) in a liquid. If designed correctly, the suspension will not clump and when sprayed correctly will produce uniform droplet sizes which will disperse in a manner that effectively covers the area being sprayed. The chemistry of these suspensions is very tricky and most of the suspensions are the result of years of study (and are thus patented and not shared with competitors). As I discuss in my previous post, the components are known to regulators but are not shared openly to protect all the work invested in producing the recipes. You need the right particle size to get effective coverage and to ensure that the compound hits and stays on the target. For the keeners out there I include a reference that details particle sizes and how they relate to the effectiveness of sprays (ref). 

In the clip from the television programme, Dr. Hales points out that not a lot was known about this topic at the time. That being said, a lot of research has been carried out and many of Dr. Hales’ concerns have been addressed. An example of this is a report titled: “Bioaerosol Health Effects and Exposure Assessment: Progress and Prospects” (2003). It indicated that in some cases, under the wrong wind/humidity conditions, droplet sizes can vary from designated parameters and respirable particles can result in both allergic and non-allergic responses in sensitive populations. The Annals of Occupational Hygiene did a major issue on the topic in 2014. I have attached a copy of the feature editorial which discusses the state of the art in the field (Advancing the Science of Bioaerosols’ Exposure Assessment 2014 ref). The literature indicates that for endpoints like cancer there exists no identified mechanism to elicit the response and thus the likelihood of cancer as a result of the spraying is extremely low (below the de minimis risk level). Moreover, the research indicates, when sprayed under the correct environmental conditions, only a very, very small percentage of the spray actually reaches respirable size. Specifically, Foray 48B spray droplet size is calibrated for ~120 μm. This is far larger than the maximum respirable size of <10μm. In the testing, approximately 0.17% of the volume of spray was determined to be <14 μm in size in bench tests (ref). So while it is clear that the possibility exists that respirable particles will be produced by the spraying, the recent literature dismisses the likelihood that it serves as a significant health risk for the typical community. The language used was pretty certain:
  • Some people may experience minor eye, nose, throat and respiratory irritation. The HRAs [health risk assessments] raised the possibility of asthma aggravation of asthma [sic], which was considered biologically plausible, although epidemiological research and surveillance from the WSTM [white spotted tussock moth] operation did not support this.
  •  Some people would find the odour of F48B unpleasant. Some people may experience nausea, headache or other symptoms if exposed to unpleasant smells.
  • Available evidence does not support any effects during pregnancy on either mother or fetus, or effects on prematurity, miscarriage rates, birth weights, congenital abnormalities.
On Hospitalization and Asthmatics:
In keeping with the sensationalization of the topic, nothing beats the headline from The Province Newspaper on Tuesday: “Two hospitalized as spraying continues in Surrey and Delta against the gypsy moths”. Reading that headline, I thought it might be time to set up the barricades to protect us from the hoards of people rushing to escape Cloverdale for the kinder, gentler world of Langley. Upon reading the article I discovered that The Province was being a bit liberal with the use of the term “hospitalized”. The story describes two individuals who went to the Surrey Memorial Hospital Emergency Room after encountering the spray. Based on my reading of the story, neither “patient” was admitted but rather as a representative of the Health Service noted: “they were fine and they were released”. Now my understanding is that the definition of “hospitalize” includes the requirement for “treatment”. The simple act of walking into an ER and asking to see a doctor really doesn’t count as being “hospitalized” in my books...unless you are trying to drive readers to your online article....

Regarding asthmatics, here we have a group that clearly represents an “at-risk” population that was specifically described the earlier risk assessments. That being said this population has not been ignored in the research and the risk to them has been studied. Specifically, during the 1999 spraying in Victoria, a matched-pair cohort study was carried out to establish the risk to this population (The effects of aerial spraying with Bacillus thuringiensis Kurstaki on children with asthma). The result was reassuring. There were no differences in asthma symptom scores between subjects exposed to the spray and control subjects located outside of the spray zone.  Moreover a larger study conducted at the same time (Human Health Surveillance during the aerial spraying for control of North American Gypsy Moth on Vancouver Island, British Columbia) had a similar conclusion: 

Results to date show no apparent relationship between aggravation of asthma in children and aerial spraying of Foray 48B. As well, no short-term health effects were detected in the general adult population nor in hospital emergency room visits.

So when people claim that no studies have been done on this topic, the correct response is “balderdash”. Surrey and Delta are not the first places this spray has been used. It has been in use for almost two decades in a large number of jurisdictions and each and every one did a risk assessment prior to the spraying and all have found the spray to be safe. Of note, I keep reading a comment that Foray 48B was “banned in New Zealand” but I have yet to find any support for this statement and attribute it to an unsubstantiated urban myth.

The Big Conspiracy
The strangest set of comments have dealt with some unspecified conspiracy between government agencies around the world to ignore the few enlightened individuals on this topic. As I mentioned previously, I have been informed that I am either a witting member of the conspiracy or simply an unwitting dupe. I’m not sure which version I prefer, but do not believe either case. As I mentioned in an earlier post: “Public Sector Compensation - You Get What You Pay for” most of the civil servants in the technical end are underpaid with respect to their private sector peers and many work in the public sector out of a sense of public duty. I cannot believe that every one of these people has been bought out by the dark forces. I think it more likely that if such a conspiracy existed we’d have read about it on WikiLeaks or through some other journalistic enterprise. As for the peer-reviewed literature, it is categorical in that researchers have been unable to demonstrate links to any effects beyond minor discomfort associated with ingesting the spray. The particles, when applied according to specifications, are not respirable and thus would not cause effects in non-sensitized populations. Given the number of exposures necessary to sensitize the population, only the most highly susceptible would appear to even have a chance of having issues. For the vast majority of the population symptoms are limited to minor headaches, a minor odor and a bad taste in the mouth. It is possible that the suspension solution may have food additives that may result in minor reactions but given the minute quantities ingested these symptoms would be expected to disappear shortly after exposure ceased. That being said all studies repeat the same warning: most negative reactions in affected communities will be linked to adverse effects promoted by expectation, otherwise known as “the nocebo effect”.

Monday, April 27, 2015

More on Gypsy Moth spraying: Toxicity redux

Much as I expected, my post on "the nocebo effect" and spraying for gypsy moths” drew a whirlwind of criticism on Twitter and in my email inbox. The major concern had to do with the fact that in my post I dealt with Btk in general and did not concentrate on the specific formulation used for spraying in Surrey and Delta: Foray 48B. Now Foray 48B is a proprietary formulation of Btk produced by Valent BioSciences and is sold in Canada by Valent’s Canadian Agent: Valent Canada Inc.  Valent’s Canadian page for Foray 48B is here while a more detailed set of documents is available at Valent’s US website. The intent of this post is to address my previous deficiency and in doing so build on my previous series of posts on risk assessment and toxicology since, as many of you know, the intent of this blog is to enhance evidence-driven decision-making in British Columbia and understanding the science is the best way to do that. 

Now as I noted above, I did a series of posts explaining the basics of risk assessment and toxicology in February. Unfortunately, due to the nature of my blogging platform (read free and simple since I am a chemist and not a web designer) it is not terribly easy to figure out what I have written in the past so I will summarize here. The intent of that series of posts was to help me out in situations like this. You see talking about Foray 48B would be very hard if my audience didn’t understand the language of the field. The posts started with “How Big and Small Numbers Influence Science Communication Part 2: Understanding de minimis risk” which explained how the science of risk assessment establishes whether a compound is “toxic” and explained the importance of understanding dose/response relationships. It explained the concept of a de minimis risk. That is a risk that is negligible and too small to be of societal concern (ref). The series continued with “How Big and Small Numbers Influence Science Communication Part 3: Understanding "Acceptable" Risk” which, as the title suggests, explained how to determine whether a risk is “acceptable”. I don’t have the space to recap that post here so feel free to read that post then come back...I will wait here for you...okay I see you are back so let’s continue. I then went on to explain how a risk assessment is actually carried out in “Big and Small Numbers in Science Communication Part 4: the Risk Assessment Process. I finished off the series by pointing out the danger of relying on anecdotes in a post titled: Risk Assessment Epilogue: Have a bad case of Anecdotes? Better call an Epidemiologist.  Now anyone who has read all those previous posts can probably figured out what I am going to write next but that would be less fun for me so I will continue here.

The most common comment was by far the easiest to answer: I was informed “that the compound had an MSDS then it must, by definition, be dangerous”. This is simply incorrect. A Material Safety Data Sheet (MSDS) is a basic requirement of the Workplace Hazardous Materials Information System (WHMIS). Now I agree that WHMIS does indeed have the word “hazardous” right in its title but that doesn’t mean that it only regulates “hazardous” materials. Rather the system provides a consistent method to supply employers and workers with information about chemicals and compounds used in their workplace. WHMIS was developed to provide a uniform system to communicate the risks associated with “controlled products”. So there you have another set of scare quotes. You see the unspoken secret about WHMIS is that it covers pretty much every compound that is used in an industrial setting. The reason for this is that due to the nature of industrial processes almost any chemical can have dangerous properties. MSDSs are available for some of the most terrifying compounds out there from distilled water, to Coca-Cola, to table salt? So you are probably wondering: how can distilled water be considered a hazard? Well let’s look at the MSDS. Distilled water is incompatible with: “Strong reducing agents, acid chlorides, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride”. Moreover, as any first year chemist who loves seeing cool reactions will tell you, when you mix distilled water with sodium metal the reaction can be very entertaining. So to ensure the safety of employees, MSDSs exist for virtually every compound used in an industrial/commercial setting.

The next common comment was: look at the MSDS and all those restrictions on its use. Now while there are standards for use in preparing an MSDS, we live in a litigious society and some companies can be extremely cautious when they write an MSDS. Consider this MSDS for distilled water: it includes a pretty detailed description of the necessary skin protection when encountering distilled water. It is so entertaining I will present it unedited: 

Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm

Now that is some scary stuff! Think about it for a moment, they are warning you not to touch distilled water unless you are wearing gloves. Forget those hospital-issued latex gloves, they aren’t enough to protect you from this dangerous substance, you need to use nitrile gloves. Remember not just any nitrile gloves are enough either, the only safe gloves need a minimum thickness of 0.11 mm. The part I find hardest to figure out is what substance you are expected to use to “wash hands” after exposure to that nasty distilled water! Now not only is that water dangerous to touch, it also has a reported LD50 under the toxicological Information. Specifically rats die when administered an oral dose of >90 ml/Kg. Even more frightening is the fact that distilled water has been “investigated as a mutagen”. According to the Sigma-Aldrich MSDS for distilled water: “To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated” According to the David Gray & Co MSDS: distilled water can be a “very slight eye irritant” and “excessive inhalation may cause drowning”. Based on these MSDSs I would be considered derelict as a father if I put my beautiful daughter in the tub for fear of the potential mutagenic exposure. Can’t let her outside while it is raining as water is an inhalation risk and I will also have to weigh her regularly to ensure I don’t administer too heavy a dose of water through that sippy cup!

Another common complaint was that the compound may not be appropriate for use because according to “A Health Professional Gives Facts about Foray 48B” posted at the No spray zone web site, the material is not even organic. Well while the “certified organic” label is reserved for foodstuffs and is certified by the various appropriate governmental bodies, the Organic Materials Review Institute (OMRI ™) certifies the raw materials and chemicals used in the production of “certified organic” foodstuffs. Unlike normal users of products, the OMRI™ gets to look at the actual chemical composition of a product being considered for certification. As indicated at their Website: Foray 48B has received  certification as for use in certified organic food production. So when “A Health Professional Gives Facts about Foray 48B” the first thing you may want to check is the background information. First and foremost what kind of health professional are you talking about (a toxicologist maybe?). In this case the “Health Professional” is actually an undefined “Mental Health Professional”. So what that means is that the person is apparently not trained in toxicology, epidemiology or other applicable field. Moreover, when this “mental health professional” informs you that “Foray 48B is not "certified organic" you may want to check with the OMRI™ anyways, because well, because. Given an unnamed “mental health professional” on one hand, and the body authorized to certify chemicals as organic by the United Sates Department of Agriculture on the other, you may want to trust the body authorized to certify compounds and formulations as organic.

The final point was that a large percentage of the Foray 48B is made up of mysterious “inert” ingredients. Well as noted OMRI™ got to look under the hood at that list and they still decided to certify the compound as organic.  As for better toxicological data, I have linked to a New Zealand assessment of Foray 48B that includes details of testing up to an including the feeding of Foray 48B to people. Yes they had test subjects take capsules of the stuff daily for five days, they were that confident that it would cause no harm. As described in the document on the use of Foray 48B: 

“Foray’s inert ingredients, which include various carriers, suspension agents, and stabilizers are classified by the Environmental Protection Agency (EPA) as inert ingredients of minimal toxicological concern to non-target organisms and the environment (EPA’s List 4B and 3)”

“All inert ingredients in Foray formulations are included in 40 CFR 180.1001. This list has been designed by the EPA as ‘exempt from the requirements of a residue tolerance on raw agricultural commodities” VBC verifies that none of its Btk formulations contain toxic inert ingredients, such as benzene, xylene, or formaldehyde”

So yes Foray 48B has proprietary compounds that are not on the MSDS, but that compound list is considered to pose an acceptable risk by the EPA , is certified as organic and appropriate for use on organic foodstuffs and is certified to be used up to and on the day of harvest. Yes read that again, you can apply the stuff to plants on harvest day and send them to your local organic market and they will still be considered both safe to eat and organic. 

Honestly at this point I am just banging a drum here folks. The data is pretty overwhelming. The compound has been certified as safe in Canada, the US, New Zealand and every other place where it has been sprayed. It is a certified organic mixture that provides a safe and effective method of controlling a financially devastating pest with a risk that is below the de minimis level. For those people out there complaining about symptoms like sore throat, and difficulty breathing I would direct you to the pollen outlook for the Vancouver because my family has been suffering from the same symptoms described in all the news stories and we are well outside the spray area. We are, however, sitting in the middle of the pollen season and the days suitable for spraying (dry days immediately after a rainfall) are exactly the same days that are most suited for spore dispersal by trees, flowers, grasses, molds and mushrooms. As someone who tracks pollen levels for my work, I can tell you that the best way to avoid waking up with a headache and dry throat is to take a Claritin before you go to bed and if that doesn’t work then sleep with your bedroom windows closed until the end of the pollen season because based on the toxicology that is the most likely culprit for your symptoms.

Sunday, April 26, 2015

On "the nocebo effect" and spraying for gypsy moths

This week my inbox has been flooded by emails about the decision by our Ministry of the Environment to spray for gypsy moths in parts of Surrey and Delta. For those of you outside the British Columbia lower mainland you might not know about gypsy moths. As a province dependent on the export of both agricultural and forest products British Columbia is particularly sensitive to the presence of European and Asian gypsy moths. Both are invasive species that can devastate deciduous trees (read destroy fruit trees) and the presence of gypsy moths can result in our wood products being banned for export. Based on these concerns our government has an integrated program including ministries ranging from the Ministry of Agriculture, to the Ministries of Forests and Environment. This program includes trapping moths, identification of outbreaks and, if necessary, spraying. While the gypsy moth can cause devastation to our economy, it is possible to control it using a safe and effective, non-toxic, aerial spray called Btk. The best thing about Btk is it is the essence of a directed, organic response to infestations. You see Btk is not a chemical pesticide but rather is a formulation of naturally occurring bacteria mixed in a non-toxic solution appropriate for aerial dispersal. As anyone familiar with our environment knows bacteria exist throughout our environment. Each and every one of us carry three to four pounds of bacteria in and on our bodies. Without our natural gut bacteria we would be unable to digest certain foods and people who lose these bacteria either need a transplant or they become extremely ill and in rare cases can die. Due to our interactions with bacteria, our bodies are well suited to their presence and bacteria are similarly adapted. While some bacteria can make you sick, other bacteria (like Btk) cannot. There are literally thousands of studies demonstrating that Btk is harmless to people and pets. More details here. Ironically Btk can’t even hurt adult gypsy moths, their eggs or their pupae. It only works when ingested during the caterpillar stage of their life cycle at which point it gets into their guts, infects them and kills them. I simply lack the space to write about how safe this spraying is which brings us to the topic of this post: The nocebo effect.

So what is the “nocebo effect”? Well let’s start with something everyone knows: the “placebo effect”. The placebo effect is a long understood effect where, in the absence of an active ingredient, a “placebo” (often a sugar pill) has the same effect as if an actual pharmaceutical had been used. The placebo effect has been long understood, heck I first saw it discussed in a MASH episode back in the late 1970’s. Research on the placebo effect is both thorough and extensive. In a review article from 2012 over 2200 studies were identified (ref) demonstrating or discussing trials demonstrating the existence of the effect. The scientific basis of the placebo effect is also well-understood. Human perceptions are driven by our neurochemistry and human neurochemical responses are understood to vary with mood and perceptions. Interestingly enough even the simple act of smiling can cause a biochemical response improving one’s mood (ref). Convince a person with a minor illness that the sugar pill you are giving them will make them feel better and often that is all it takes. As everyone knows, the placebo effect does not work on everyone, nor does it work every time. All that is certain is that on a small percentage of people, in a small number of circumstances, it can have a real effect.

Let’s get back to the “nocebo effect”, it is essentially the placebo effect’s less attractive younger sibling. You could say it is Stephen Baldwin to the placebo effect’s Alec Baldwin. In keeping with the Baldwin theme, while Alec Baldwin is well known for being a liberal-Democrat Stephen is known as an ardent Republican. So while the placebo effect has the ability to help you feel better in the absence of any active ingredients, the nocebo effect has the ability to make a person feel poorly in the absence of any active stimuli. As described in this review paper the nocebo effect is not as well studied as the placebo effect but it has been demonstrated to be real. It is important to recognize a couple things about the nocebo effect. First and foremost, people who “feel bad” or claim to be “sick” via the nocebo effect are neither lying nor are they fakers, rather they are doing one of two things. They are either associating actual symptoms from other causes to the “nocebo” or they are having phantom symptoms based on their minds playing tricks on them. Think about this in your daily lives. Every parent of young children dreads the arrival of the “pink sheet” from your elementary school. For those of you without young children, the “pink sheet” is the warning announcement the schools send home to tell families that one of the children in their child’s class has been diagnosed with lice. The sheet asks parents to check their kids for lice. Try watching a group of parents when their kids hand them the “pink sheet” and watch as virtually every parent in the group starts itching their heads. You would think someone had spread a dose of itching powder into the group. This is the nocebo effect in action. An itchy head is no longer just something you get from life; it is now all about lice. Until you have had a chance to check your kids and yourselves every itch is a sign that you are one of the unlucky ones. There are any number of celebrated cases where people have be shown that their “illnesses” were all in their minds but by far the most entertaining one is described in this article from Daily Tech. In that case a community complained about health issues associated with radio towers even though the radio towers had been turned off during the time the community members claimed they were being made ill by the towers. I have neither the time, nor the space to talk about fears of WiFi in this article, but I think we can all agree that any case where a transmission tower is turned off and people still complain it is making them sick is an example of the nocebo effect.

So let’s go back to the gypsy moth spraying. When a mother on television claims that following the spraying for gypsy moths she felt a sore throat, it could be that she didn’t look at the pollen count for the morning and woke up with a sore throat from exposure to high levels of pollen or it could be that she simply had a dry throat that on any other day would be solved with a glass of water. In either case once the “sore” throat is associated with the Btk spraying in a person’s mind, it will be that factor that makes it the cause of the “illness” thereafter. Regardless of the amount of research that shows otherwise, every time a community is told that there is going to be aerial spraying you will get a dozen or so people who claim to have symptoms of various indistinct illnesses all of them “caused” by the spraying. Ironically, the illnesses are indeed associated with the spraying but not in the way you would expect. It is not the spray itself but rather by the simple fact that spraying is occurring that caused people to display their symptoms.

This brings us back to a topic of a previous post “On Science Communication and the Difficulty Relaying Scientific Information to the Public” which introduced the concept of “dread risk”. As I describe in my previous post: dread is a term used by Dr. Paul Slovic in his seminal article on risk communication called "Perceptions of Risk". For those of you without access to journal articles Dr. Roger Pielke discusses the topic in a blog posting. I have previously suggested that any reader who wants a non-technical but compelling read on the subject of Risk should get the book by Dan Gardner of the same name. For those of you not interested in too long a read, dread risks are risks associated with factors that cannot be seen or felt using our normal senses and can have serious or life-threatening consequences, often a long time after the initial exposure. In this the aerial spraying for Btk has features associated with dread risk. The spray, once released, is invisible to the touch, cannot be smelled [author's correction: the Foray 48B formulation has a very minor odour associated with one of the ingredients used to hold the Btk in suspension] but can sometimes leave a minor residue on surfaces. This makes it an ideal source of dread risk. The problem is that based on all the existing science Btk does not cause any short-term, medium term or long-term risk to humans, animals or anything that is not a caterpillar. Unfortunately, as is the case in many other endeavours, a solid basis in science is never enough to calm all the fears in a population that is mostly science-blind. All our regulators can do is to continue spraying, all the time trying to educate the population about the fact that the spraying does not represent a real risk to human health.