EPA Environmental Science Series: The vulnerability of children to environmental exposures
Seminar 7th June 2018 transcript

This is our second this year. I’m Andrea Hinwood, I’m the Chief Environmental Scientist of EPA Victoria and it's my pleasure to introduce the topic of vulnerability of children to environmental exposures. This is going to be a little bit of a double act. I’m going to do a little bit on setting the scene on environmental exposures in Melbourne and we're very fortunate to have Professor Peter Sly, who I’ll talk about in a minute who's going to talk about the vulnerability of children and some of the information we have about environmental exposures and particularly impacts on our most vulnerable. Our children.

Our event today is being held on the traditional lands of the Wurundjeri people of the Kulin nation and I’d like to acknowledge them as the traditional owners of this land I’d also like to pay my respects to the elders, past and present and the elders of other communities who may be here today.

I’d very much like to welcome our guest speaker Professor Peter Sly, Director of the Children's Health and Environment Program, W.H.O Collaborating Centre for Children's Health and Environment. I’d also like to acknowledge Ms Debra Russell who's on EPA's governing board. For those who don't know, EPA has a new board commencing on the 1st of July and so thanks Deb for coming along. I’d also like to welcome everyone who's live streaming this event in Victoria. We're finding that these events, we're getting many more people live streaming in rather than turning up. I have to confess this is quite hard for a speaker because it's very hard to give a talk to an empty audience knowing that everyone's somewhere else. It somehow constrains you, so it's quite nice to have people in the audience to actually talk to and to get a sense of whether they think what you're saying is okay or not. 

So just a few housekeeping notes prior to starting please switch your phones onto silent for the duration of the event. In the case of an emergency the tones will go off and follow the instructions of on-site staff.

So, what we're here to talk about today are environmental or chemical exposures in particular. I’m not going to talk a lot about microbiological exposures and human exposure and importantly children's exposure. What I want to talk about is why is EPA Victoria interested in this space. We're a regulator of pollution and waste. Our job is actually to protect the environment and humans from the harmful effects of pollution and waste and we do this by a number of means. We regulate industries, we work with particular sectors to reduce chemicals in the environment. We also try to provide information so that people understand about environmental exposures, where people can be exposed and importantly measures they can take, but also EPA can take, to reduce any potential impacts. One of the bits you may not have caught up with is EPA Victoria now has responsibility for environmental health. What that means is in the context of pollution and waste EPA Victoria is providing the human health advice about impacts of, in this case chemicals, but across the board. That's actually a shift, we're actually the only state in Australia that has that responsibility and I think it's going to take us a while to get in that space. So, part of today is to talk about this interface between the environment, what we do in the environment and then what that means in terms of exposure and health outcomes, and you'll probably hear me say a couple of times that if you're not exposed to something you can't have a health effect. So, we always talk about how we can actually reduce those exposures both personally and from a government's point of view how we actually manage sectors to achieve that. So, from EPA's point of view our vision is a healthy environment that supports a liveable and prosperous Victoria now and always. 

There's lots of information about impacts of environmental exposures and I hope what I’m going to talk about in this brief bit now is also how much we don't know and to some extent we have to use means to use surrogates of exposure or ways of assessing exposure which don't necessarily directly mean we measure concentrations in individuals or health outcomes. I just thought it's worth saying that of probably all of our environmental exposures we know most about air and we know internationally that four million people die prematurely each year from emissions in household air pollution i.e. most typically associated with burning coal in the indoor setting. So, seven million people died as a result of air pollution exposure again many of those deaths are attributable to developing countries not countries like Australia nevertheless it is demonstrating there is an effect associated with exposure to air pollutants. Poor water quality accounts for 3.6 percent of the global total disability adjusted life years, so poor water quality is an issue that does affect us and I’ll show some slides on that, we probably don't have the same sorts of diseases associated with it, but we do know that exposure to poor water quality impacts health. In Australia there are estimates that air pollution accounts for 3 000 premature deaths that means air pollution's shortening someone's life and annually this costs us a lot I think we all know what the health sector takes up in terms of our funds generally and any measures we can take to actually reduce that burden on the health system I think would be welcome and would improve quality of life. So, when I talk about environmental exposures I’m talking about a very wide range, we've got a wide range of pollutants in water air soil, but also in common domestic products. I thought this was an interesting graph here which shows the certificates and permits for new chemicals, you can actually find this information on the NICNAS website. So, we are certainly increasing the amount of chemicals we're bringing into the country. They're going to be of a very broad nature, many of them will probably be very helpful and have low toxicity and not be an issue, but then we've actually experienced that in the past where if we think back and we talk about ozone depletion, we introduced chlorofluorocarbons, wonder chemicals at the time, but they depleted the ozone layer and resulted in increased UVB. So we now know that we need to understand a lot more about these chemicals how they behave in the environment and importantly how humans get exposed to them.

When we talk about pollutants generally we talk about those that are produced in high quantities and amounts, like our air pollutants or our criteria air pollutants, so most of us know about particulates or ozone nitrogen dioxide etc because they're emitted from numerous sources and they're present in the environment in relatively high concentrations. There are a whole lot of other chemicals that are produced via a range of different sources which we call our trace chemicals, our air toxics, but also some of our persistent organic pollutants and other pollutants which are produced in trace quantities and are found in low concentrations in the environment, but nevertheless we might have a concern about in terms of their potential health impact. It's worth just talking about exposure generally. What do we mean by exposure? This is about how in terms of human exposure, how do we get exposed to a chemical? So, we can go outside and we've got traffic out there, we walk out the front door we're exposed to some air pollution straight away but we also might consume some fish that have some elevated metals levels in them or in the case of organic pesticides they may have some pesticides in them as well and other products that we consume in the home environment. We know that our brominated flame retardants our PBDEs have been found associated with electronics products etc, they're semi-volatile and they end up in the dust in the home environment. Where do we get exposed? We get exposed from the dust in our home. Now again we're talking about very small amounts and I don't want everyone to be really concerned as, oh my goodness I can't live normally, you can live normally. What I’m trying to talk about here is that there are lots of different sources and we need to pay attention to what we're exposed to and how we reduce exposure. So, indoor exposures, contaminated soil, contaminated water, and air are all sources of potential exposure that may generate some health outcome if the chemicals are in quantities that are high enough and this concept of exposure is really important because we talk about exposure scenarios. So, a really interesting example, and I won't talk about the chemical and I won't talk about the region, was that I was asked to go out and investigate potential contaminated soil and it's actually something that you can see it's visible and the concern is that if it's visible this particular contaminant can become airborne, and I said yes but who's accessing this where's the access where is the human exposure pathway?  Well maybe it could be present in dust and maybe it could travel long distances but because of the nature of the material it's highly unlikely for that to happen however, it might actually be moving into a local waterway. Is that waterway accessed by individuals who might fish? Because there is a direct exposure pathway if that chemical has got into fish in that waterway that people may be recreationally using. So, your expose your pathway and who you are and where you are and what you do is really important. So, when we talk about this area we talk about prenatal exposure and Peter's going to talk a lot about that in terms of developing systems. We talk about postnatal exposure and the activities of children. We talk about what children do in their day-to-day lives in in you know playing outside hand-to-mouth activity etc or putting things in their mouths that maybe they shouldn't but also adults occupational exposure their hobbies. We know that if you're into burning incense maybe you might want to reduce your burning of incense, you do produce pollutants associated with that activity, not something I do and clearly if you're a smoker direct exposure pathway not great. Lifestyle differences some hobbies, if you're actually maintaining your motorbike in your living room there are probably some chemicals that you're using in that environment in a contained space that might create some exposure. So, adults and of course the elderly who spend sometimes more time indoors sometimes they might spend more time outdoors which introduce different exposures depending on what they are doing and how they are doing it. I’m not going to go through this other than to say we often talk about risk. It's about the risk of whether you're exposed and the point of this slide is to say that you need an exposure you need a dose you need an individual risk and if you are more susceptible for some reason your risk will be higher and then you've got a population risk. If you're not exposed in the first instance then your risk is going to be nothing. Risk in my book can never be zero we live in a world with lots of different things and we need to understand this a bit more. So, environmental exposures what do we actually know about them and I’m going to talk about three main ones. Air pollution, water quality and I’ll talk about some of our persistent chemicals that we've started to focus some attention on. So, we know with air pollution we've got wood heaters prescribed burns and wildfires, we've got small to medium enterprises that emit a range of air pollutants, land development, agriculture etc. We've also got the new emerging issues of what I call vehicle wear and tear. So, some of the modelling that we've done shows that we traditionally have had exhaust emissions such as PM2.5 which is an impact on health but actually it's changing to see much more PM10 with interesting chemicals associated with it from the use of our roads much bigger increases in people using vehicles and of course the wear and tear aspect and of course movement stirs out the dust so again you walk out the front of the building we're in and you look at the trams going down the street, just have a look at the material coming up, and some of that will have some interesting composition. So, emissions vary based on the type of activity, where it is, and of course regulatory intervention. Air quality in Victoria is actually pretty good and for the most part we can actually claim to say air quality is good however we haven't really seen appreciable reductions in say particulate matter and importantly particulate matter is an ongoing concern for us and it's largely to do with planned burns wood heaters and our ongoing vehicle fleet etc. At EPA we feel we've probably done a pretty good job at regulating industry for most pollutants however it's some of the diffuse sources that are now creating issues and I just wanted to show you this this is actually exceedances of our national environment protection measure for PM2.5 and really this is mostly PM2.5 comes from combustion sources typically wood heaters planned burns vehicle emissions any combustion type activity. So, if you are into burning your leaves or your rubbish in your backyard incinerator please don't, you produce PM2.5 of an interesting composition but as you can see in 2017 we had a big increase in the exceedances of our national standard which is designed to protect the health of the community at large and most of these have been attributed to bushfires but we also have this urban component and this urban component is comprised of wood heaters some impact from planned burns clearly we always have a vehicle signature in there as well and it's a little bit of concern and it's probably likely to do with an increase in population increase in activities and our population as you all know is rapidly expanding so we have some challenges ahead of us. I also wanted to show you recreational water quality we don't talk about recreational water quality a lot i.e. people's access with water that might be associated with contaminants in general water quality data in terms of chemicals in say Port Phillip Bay or other waterways is actually pretty good but microbial water quality varies quite a bit and again we are seeing some trends that are decreasing the quality of water across our waterways that we monitor and it's something we need to pay attention to because recreational use of water is also increasing and therefore you have direct contact of people swimming in water and exposure perhaps to pollutants that might be of concern. 

We've got old and new chemicals, so in Western Australia we undertook a study of persistent organic pollutants but we also included what we call the old chemicals the metals. We know a lot about metals exposure we know about lots of the sources etc and what was really interesting was that we had 173 pregnant women from Western Australia and we tested blood, urine drinking water, household dust etc and we analysed for a variety of pollutants but we also analysed for some of the metals. We came back with some really odd results and one of them was cadmium and we thought hang on why were we getting these elevated concentrations of metals in our population? We have no known environmental exposures there's no environmental information in Perth that tend to suggest that you've got increased problems so we thought we'd better have a look at food. So, the most depressing thing for me was of course chocolate so I thought cadmium dark chocolate higher concentrations I wasn't fussed about the seaweed the oyster you know concentrations because I don't eat those but I did worry about the chocolate and look at the green tea for manganese and in fact the green tea doesn't come up for cadmium but we also found cadmium and green tea too. So, it just gives you a sense and the reason I put this slide up is to show that there are old chemicals that are common in the food chain. Metals are persistent as are organic pollutants and we need to make sure that we don't lose our eye on these types of chemicals because they still exist they are still being found in the environment there are particular sources that might generate them i.e. your particulate matter that might be associated with wear and tear of vehicles. So, we need to be mindful of our exposure sources. Then I just wanted to briefly mention the emerging contaminants EPA is trying to get a handle on what is our understanding and knowledge about emerging contaminants in the environment. So, we've actually undertaken a couple of studies, we're doing an ambient emerging contaminants assessment which is targeting all of these chemicals on this list a mix of industrial chemicals, pesticides and bromide flame retardants, and that's so we get an idea of what we actually have in the environment in water, soil, sediment, inland waters. We've started to do some preliminary testing for the per and polyfluoroalkylated substances which are the common chemicals associated with firefighting but they were also used in a whole range of other activities and are present in indoor sources as well, and this is just showing some of our fresh water concentrations where the samples were taken. The concentrations in fresh water are pretty good and we've got no major problem there. We also have tested some biota in Port Phillip Bay event very, very small sample and that is now being supplemented and we'll have additional information at the end of next year and you can see some areas where we do have some elevated concentrations but still below our trigger concentrations in terms of consumption and hence human exposure to these chemicals. 

Last year EPA advised against the consumption of biota from the Heart Morass Wetland this was as a result of high concentrations of these firefighting chemicals that had been used in the East Sale defence site. We identified these high concentrations and the issue was a human exposure one that there were recreational fissures and duck hunters who actually access that wetland. So, if you've got a contaminated environment chances are your boat biota might be contaminated which means you've got a source of exposure for people who may be consuming that produce. So, we have done some preliminary work we've tested some waterfowl from three locations in Victoria to better understand the extent and distribution of pfas contamination and we have an interagency working group and we're currently undertaking comprehensive sampling across the State both of fish and waterfowl to get an idea of one what is the spatial distribution of these chemicals what is the likely contact with them via these recreational pursuits and our aim is to provide information but also to inform us as to whether we should be giving the public guidelines on what they should or should not be consuming. 

So, we've got lots of challenges. As I said before we've got a wide variety of chemicals we necessarily have to prioritize our activities and you saw on the slide preceding this one that we are targeting a broad range and that's going to help us target what particular pollutants we should consider from a human exposure standpoint. We also have this issue with Melbourne’s population for those of us that live here we know what's happening out there in terms of infrastructure and traffic and all the rest of it and we're expected to increase to 5.6 million and clearly that will increase urbanisation, it will increase pressure on transport systems, it will increase the potential for runoff going into waterways in terms of pollutants. Storm water runoff is a significant source of pollution for waterways. If we increase all the hard surfaces, we're going to increase that potential so we really have some challenges. We have increasing waste. We've got increasing chemicals and as I say the infrastructure routes traffic and shipping are all associated with a developing city in my view these are also opportunities because we have new technology and new ways of measuring these pollutants and importantly where people are able to understand where the exposure sources are and what measures they can take to prevent exposures and I think it's a partnership between the community, industries, businesses and governments to actually work together to reduce exposures where we are able to but also for people to take the opportunities. So, for me as an asthmatic maybe I don't want to go for that very brisk walk on a cold morning where I know that the predicted air pollution is going to be bad and I take responsibility for my own health. We have a responsibility to target particular sources as well but I think we also need to inform ourselves so that we can reduce these exposures where they matter. 

So, I’m going to finish there and it is my great pleasure now to welcome professor Sly and he's going to talk about the impact of environmental exposures in early life. He's the Director of the Children's Health and Environment Program of the World Health Organisation Collaborating Centre for Children's Health and Environment and he's an NH&MRC Senior Principal Research Fellow and a paediatric respiratory physician. He's got extensive research experience in respiratory physiology, development immunology and children's environmental health. His research aims to understand the mechanisms underlying chronic childhood lung diseases to improve clinical management and to delay or prevent their onset with consequent reductions in adult lung diseases. He's also Chair of the Board of the Directors for the Pacific Basin Consortium for Environmental Health, and he currently serves on international advisory boards and committees including the World Health Organisation Public Health and Environment, the Network for Collaborating Centre in children's Environmental Health, the Canadian Healthy Infant Longitudinal Development Child Study in Canada, and the Infant Lung Health Study in South Africa. I think you'll all agree with me we're in very good hands for this presentation thank you very much.

Thanks Andrea. I also have a day job. 

It's a pleasure to be here. I've known Andrea for quite a long time. I’m originally from Melbourne but I spent 20 years in Perth and interacted with Andrea when she was in Western Australia and we've undertaken a number of research projects together and some of the papers are still coming out. There's one on my desk that I've promised to get back to you, so yes I’m going to talk about vulnerability of children to environmental exposures and if there's one take-home message actually there's two take home messages from this talk. One is that in whatever environment there is children get a higher dose of whatever contaminants or toxicants are there than adults do and I'll go through some of the reasons why that is the case. And secondly exposures in early life make a major difference and increase the lifelong risk of disease. To some extent my generation represents the pinnacle of human evolution. I've changed it, sometimes I say I do but it's my generation and this is because we basically were gestated and grew up before the chemical era before the explosion of the chemicals that Andrea has shown you about. Yes, our environment had some issues as well but and they're different so they're the two take home messages. Children get a higher dose and early life exposure increases the risk lifelong risk for chronic disease.

I don't have any conflicts, so I’m going to talk a little bit about multi-generational and transgenerational exposures, so in utero and beyond before, concept of windows of susceptibility while it's certainly true from a toxological point of view that the dose of the toxic makes the poison it's even more critical when that exposure occurs and I'll show you what I mean by that. I'll go through a little bit about why children are more vulnerable to environmental exposures. I’m going to say a little bit about exposure assessment in children, I’m not an expert in that area, but there are some things that that need to be taken into consideration, and finally talk a little bit about some of the adverse health outcomes from early life exposures.

So, this schematic or this graph, this picture rather, shows a great grandmother down to her great-granddaughter. Exposures that she has during her life have direct effects on her early life, direct effects on her daughter and on her granddaughter but indirect effects on her great-granddaughter. There are epidemiological studies that talk about transgenerational and multi-generational exposures. The way this works is when this woman is pregnant her foetus is being exposed to whatever she's been exposed to. We used to have the concept that the placenta protected the baby from all sorts of things. We now know that is false and almost all toxicants that the mother is exposed to go through the placenta and the baby's exposed to almost all. When this lady was a developing foetus her oocytes are developed in utero, so they are exposed to the toxicants that the great-grandmother is exposed to and so there's direct line of exposure through to her granddaughter. This comes down the maternal line.

So, for people who do mouse experiments and breed things they have these generations called f0 which is the original f1 which is the first generation, f2 and f3, but we don't really talk about that in human terms, but so the direct effects of the developing foetus can be toxic chemicals or genetic through the chemical effects or epigenetics which is where the function of the gene but not the structure of the gene is altered through an environmental exposure. It's a normal part of development and in fact epigenetics is one of the reasons how we develop. Genes are switched on and off at different times to create the beings that we are. So, I mentioned the direct effect on foetal oocytes but down to the fourth generation this can only happen through these epigenetic changes and some of these epigenetic changes, so change in the way the genes are expressed or function, but not the actual structure, can be transmitted from one cell to another during cell division from one generation to another. It doesn't happen in the male line because the sperm are primarily formed around adolescence and so it's exposures around adolescence that will affect the sperm not exposures in-utero so this is a maternal phenomenon.

Now the concept of windows of susceptibility is demonstrated on this graph and what this is supposed to show is at different stages during gestation, so the early embryonic period and then the foetal period and up to full term, development of the central nervous system an exposure that occurs in this period where is red may have major structural effects, whereas exposure occurring in this period where it's green or yellow doesn't have the same effect, and so this can be quite the timing can be quite exquisite. So, something that's occurring during the fifth week or exposure that occurs during the fifth week of pregnancy before the women even know they're pregnant may have a major effect on developing congenital abnormalities in the brain whereas that same exposure in week 7 or 8 may have a completely different or no effect. So, this is the concept of the timing of the exposure and makes it much more complicated of course to study these sorts of things, and that's true for all of the different organ systems that we develop and it's an important concept when you're thinking about how environmental exposures may actually alter disease risk.

Many, but not all, of our organ systems are mature at birth, and on this this shot, this slide shows you know the heart has completely formed its function, it's fully functioning, whereas things like the liver the structure is complete but the function is not full, in that a lot of the detoxification enzyme systems that occur in the liver are not mature at birth. But, things like the brain, the lungs, and the immune system are very immature at birth and there's a lot of postnatal development of the brain, the lungs, and the immune system which means that these three organ systems in particular are vulnerable to both prenatal and postnatal environmental exposures from a structural point of view. Everything is vulnerable from a functional point of view but these three organ systems can have structural abnormalities from environmental exposures after birth.

This is a schematic representation of how the lungs develop in weeks of gestation, the different periods that are talked about, but the development is shown at the bottom. So, airway branching pattern, the tree of the lung, is complete by about 16 weeks gestation. So, environmental exposures that occur before that may alter the structure of the airways. Environmental exposures that occur after that are not likely to fundamentally alter the structure of the airways, and postnatal exposures are not going to fundamentally alter the structure of the airways or the pattern, whereas the alveoli which are the little air cells in the lung, they're the ones that are responsible for gas exchange, so taking oxygen out of the air and getting carbon dioxide out of the body, don't start developing until about 30 second week of gestation, and at birth there are about one-third of the total complex of or total number of alveoli are there. So, two-thirds of them develop after birth and are very vulnerable to environmental exposures.

If you talk about this in other ways, you can say that the major structure for the airways is early, the structure for the alveoli is late. After birth there's rapid growth of alveoli, we don't exactly know when they stop growing but the most rapid period of development is the first 18 to 24 months of life, and along with those airway, those alveoli, the microvasculature in the lung develops at the same time and they're vulnerable to postnatal exposures as well.

This is important because the lung function throughout life is dependent to a large extent, the lung function you're born with, so things that affect lung function in early life, and I'll show you this in a sec, have a major impact on long-term lung function and respiratory health. 

So, there are lots of lots of ways you can end up with low lung function at birth, and this is a schematic I put together, to me there are two main or the three main ways that you can end up with low lung function at birth. You can have exposures that decrease airway growth. You can have exposures that decrease somatic growth, small babies have small lungs, or if you're born prematurely, before the lung development has been completed or it has advanced, then you'll have low lung function at birth. There are direct data in humans on all of these exposures decreasing lung function at birth, ambient air pollution, household chemicals, those things we like to spray inside our house, there's genetics of course, maternal smoking, maternal alcohol consumption, poor maternal nutrition, and as I said premature birth. And the reason, okay this slide's coming later. I'll talk about the long-term risks later.

So, Andrea talked about exposure pathways. In early life there are exposure pathways which are unique. Obviously a trans placental exposure pathway only occurs before birth, but exposures through breast milk, through the skin, inhalation, what we call non-nutritive ingestion and that's basically putting things in your mouth or eating the dust in the house, and ingestion, these are either unique with the double arrows, double signs, or more common and a larger dose in children for the others, than occur in adults.

This occurs because children are actively growing their systems, are supercharged to get the most out of what they eat and what they breathe, and so relative to their body size they breathe more air, they eat more food, and they drink more water per unit body weight than an adult does. They're also actively absorbing, their gastrointestinal system switched on to absorb the maximum nutrients out of the food, but this also means that they absorb more of contaminants, so if they happen to eat lead which is in dust or in paint, they will absorb much more of it. It's estimated that a toddler would absorb somewhere between 40 to 70 percent of ingested lead whereas a non-pregnant adult would absorb a much lower fraction. I’m not really going to talk about it but some of the detoxification enzyme systems are immature in early life, and the blood-brain barrier which is supposed to protect the brain from what's toxicants in the blood, as it does a pretty good job in later life, is immature in infants, and so stuff can affect the brain more easily.

So, the next few graphs I’m going to show you the next few slides I’m going to show you some graphs of the order of magnitude of the increased exposure of infants and young children. So, in this graph this is air minute ventilation litres per kilogram of body weight per day. In the first year of life a baby breathes three times as much air as an adult does, relative to their size.

The same is true for caloric requirements and water requirements to maintain health.

The same is true of the body surface area, and the reason that body surface area is important is because kids often spend time on the floor. They generally in many environments wear fewer clothes than adults do, well most adults, and if they're rolling around in the floor with their skin exposed there's a lot of chemicals that can be absorbed through the skin, and so they have a higher dermal exposure. Now this slide, this is a photograph of one of my granddaughters who was preparing for her second birthday party.

She's got a hand in her mouth, just before I took the photo that foot was in her mouth, there's an apple with a bite out of it, there's various soft toys that are in the mouth, and she's down on the floor, and I didn't pose this, she was just doing it and that's where all the toxicants are. When we think about airborne pollutants or toxicants inside our house, they're not in the air, they are initially but they settle. If you measure the concentrations, if you spray something, if you measure the concentration in the room, concentration gets higher as it gets down to the ground. Where I’m standing my breathing zone is about a meter and a half off the floor. Where you're sitting your breathing zone currently is a meter off the floor, so you're exposed to more than I am right now, and the kids are down on the floor, about 20 centimetres off where the concentrations are higher. 38.43

Also, anything you put in the air, it settles on surfaces, settles on the floor as dust, kids pick it up not necessarily deliberately, but on their toys, on the surfaces and it goes in the mouth. Andrea mentioned exposure to flame retardance in dust, that's how kids get exposed they eat the dust that's on the floor with the flame retardants in it.

Now, I’ll say a little bit about exposure assessment in early life, and the reason I bring this up, even though it's not my area of expertise, is it's difficult and in in essence it's not done.

Toxicologists differ but don't necessarily always agree with me on this point but it's not really done. The internal dose that a child has is related as much to their physiology as it is to what you measure in the environment.

Extrapolations from adults are not valid. Normal risk assessment or exposure assessments add a kidney fudge factor by increasing the dose by a factor of 10 or 100 depending on what they're doing - she doesn't like what I’m saying.

But that's pure guesswork and it's not absolutely, it's not actually based on reality. Where you do make measurements invasive sampling is more difficult, getting blood samples from children, many parents don't like that. Somebody did suggest that you could get blood samples from the pets, particularly cats, because they have similar behaviours to children, but people who have cats are less likely to let you take blood from the cat than they are from their kids.

When you do get samples there's small volume and small volume creates difficulties with the measurement in the labs. The labs are often not optimized for very small volumes, it is getting better, and the biomarkers are not well established in children. You cannot assume that the biomarker that you measure in an adult is relevant to a child, because of the different metabolism and different ways that they handle things. So, classic toxicology, in my view, calculation of the lowest observable effect level. Andrea made me spell out all the abbreviations, or no observable effect levels from short-term studies don't really apply to what we're talking about. Exposures in early life which are often ubiquitous, low level, and you can't do the classic epidemiological studies where you've got to expose an unexposed group. There's also difficulties with non-monotonic dose response curves, and what I mean by that is this. So, you may have, or most assessments assume, are linear or a non-linear, but at least an increasing dose response curve. Where you get dose response curves like this with an inverted u or a u shape extrapolating from one dose to another is impossible if you don't know where you are in the curve, and here are two examples from cell culture systems where prolactin secretion from these cell cultures is measured against the concentrations of bisphenol a, with the u-shaped dose response curve or with DDDE, with our inverted u, so that if you don't know where you are on that range you cannot extrapolate to other doses. So, these are difficulties that occur in early life. Also the kids physiology comes into play, and here with some data from one of our phd students in Brisbane, where she measured bisphenol a in urine, on pulled urine samples from kids at different ages. On the right hand side here is normal urine flow plotted as a function of age and after about three or four years of age the urine flow per day in mls per kilogram per day is relatively constant, but in the younger kids it's much higher. So, if you're measuring a concentration of BPA and urine then extrapolating from what the body burden is, if you don't take into account the age and the physiology of the child, you can get a very wrong result. You can see here her data with the concentrations in nanogram per ml but when it's corrected for urine flow it gives you a very different picture of the body burden or potential body burden related to against age.

Alright. Turning to some of the health effects. As I mentioned, early life exposures are important. We've seen a pattern, a change in the global pattern of disease over the last 30, 40 years.

The World Health Organisation and United Nations set out Millennium Development Goals to improve health in low-income, middle-income countries, to up to the year 2000, and in many ways they’ve been very, very successful. We now see far few children dying from communicable diseases in early life, but we now see more adults living with the burden of chronic disease. There's been a major shift in that global burden of disease. Many of the chronic diseases have well recognized environmental components, so in the respiratory system, asthma, chronic obstructive pulmonary disease, have major environmental components from a neurodevelopmental point of view, IQ, attention deficit hyperactivity disorder, behavioural disturbances, autism spectrum disease, but even sort of violent crime and dementia have recognizable environmental contributions. Overweight and obesity isn't all because we sit on our backsides and eat too much food, there are environmental contributions to type 2 diabetes, metabolic syndrome, and obstructive sleep apnea, which belongs with those metabolic groups. Cardiovascular disease, coronary artery disease, and stroke have major environmental contributions and cancer. Now I’m not going to go through all of these, you'll be pleased to know, but there are documented human study data in all of these areas on environmental contributions to the causation of these diseases.

It's complex. Why don't we know all this stuff? We don't know all this stuff for a number of reasons. One is the complexity and here is just one example, one exposure, and this one, I made this slide for a different talk about plasticizers, so bisphenols and phthalates. This is talking about prenatal exposure, there are evidence of multiple different pathways, epigenetics, changing the way a gene is expressed and functions, endocrine disruption, where it modifies aspects of the endocrine system, interferes with cell development and particular adipocyte precursors, so increasing the risk of obesity or harming growth, babies being, smaller babies being born to mothers who have higher exposures of these plasticizers through mechanisms that we don't understand. But then each of these pathways, the blue arrows show where there are direct data, the dashed red arrows here between epigenetics and asthma/allergies and the adipocyte precursors and asthma/allergies whether a presumed data or animal data to support. But, so, each of these pathways can have an effect on neurocognitive dysfunction, obesity and type 2 diabetes, asthma/allergies and genito urinary and reproductive abnormalities, from the one exposure, which is ubiquitous.

So, turning to some of the disease is more specifically, the major risk factors for respiratory disease, tobacco smoking, personal or environmental tobacco smoke, maternal smoking during pregnancy, fortunately in Australia we're doing pretty well with this. Our rates are down to about 15 percent. The area where we have the biggest problem is probably still teenage girls, and that's really important because the effects on the teenage girls, and their future developing foetuses don't go away just because they stop smoking before they get pregnant.

Indoor air pollution.

Something like three billion people in the world rely on burning biomass for heating and cooking, and what really shocked me, I was in India relatively recently, and I found that, you know India has more billionaires than any other country, but if but if you look at their -  and more poor people too -  but if you look at their population separated into quartiles by socioeconomic status, 25 percent of the top level rely on biomass burning for heating and cooking, which is staggering. Now we don't do that to that extent here, but Andrea's mentioned all those wood heaters, and I used to cycle to work in Perth and on those cold crisp mornings you get out and you'd almost choke from the smell of the green wood that was being burnt in the wood heaters, and they leak, so people inside the houses are being exposed people outside the houses are being exposed. But also air toxic bioair assaults, outdoor air pollution Andrea has mentioned, allergens and occupational agents. When we talk about environmental contributions to disease, you cannot separate that out from individual susceptibility which is related to our genetics, but also other factors, and in many parts of the world it's poverty and it's the rate of early childhood lower respiratory illnesses which magnify all of this, so it's complex.

Now it does matter.

If you look at longitudinal studies in asthma, every study that's ever been done, and the first time they measure lung function asthmatics have lower lung function than the controls. These data are from a famous study from Melbourne which was originally known as the Williams McNichol study and now has got a different name. I've forgotten what it is. Michael?

[Inaudible. Michael answering but not on mic]

There you go, okay, so basically this study was set up in Melbourne in the 50s and 60s. Howard Williams who ran the respiratory department at the Children's Hospital where I did my training, not in those years, set up this study and they surveyed every seven-year-old school child in Melbourne, and they did it because there were debates about which areas of Melbourne had greater rates of asthma than others. They may or may not have answered that question but they did set to put up this longitudinal study. The yellow here are the controls at the top kids who didn't have asthma. They then recruited kids into this longitudinal study, the definite asthmatics of this blue one here, these other two were wheezy syndromes that went by different names in those days, but you can see lung function in the asthmatics is lower. Now, normal is down here. They're well within the normal range but they are lower than the controls. This line here was they put some more severe asthmatics in the study at the age of 10 because they didn't have enough from their community surveys. So, these data together with every other study that's been done looking at asthmatics suggests that low lung function is a primary risk factor for asthma from all of those environmental reasons that I told you, and it matters because of this graph. The way lung function, the way your lungs grow, your lung size doubles from birth to about five years of age. It doubles again, actually doubles to 18 months and doubles to five and then doubles again to adult life, but once you've hit your mid-20s to your early 30s you're on the downslope, your lung function starts to decline. Mine's probably way down here somewhere. 

If you don't reach what your lung function should be, your rate of decline will bring you into the area where you will get sick when you shouldn't. Now, if you do silly things like smoke, then you can accelerate the rate of decline, but it's this lung growth in childhood that determines a lot of the disease risk. It's been estimated from European and American studies that half of the people who get chronic obstructive pulmonary disease do so because they didn't reach their peak lung function, whether they smoked or not, so it's as big a risk as heavy smoking for COPD, not growing your lungs properly, so that's why that's for the respiratory system. That's why it matters. 

Now, I mentioned there are environmental contributions to low IQ, and cognitive and behavioural problems, but also aggressive behaviour and violent crime. I don't have the slide here today but there was actually a lawyer who did this quite nice study in the US, and what they did was they looked at the decline in population blood lead levels, through their biomonitoring program, after they took that out of their gasoline, and took the murder rate and moved the blood levels 20 years on, and there was a quite good correlation between decreases in blood lead and decreases in murder and violent crime, that is biologically plausible because of the behavioural effects of lead.

These exposures, lead, polychlorinated biphenyls, which we never use, we never manufactured in this country, but we used as some coolant fluids in engines and things. We did a survey in Perth and teenagers about 10 years ago, everyone had measurable levels, everyone in this room will have a measurable level of these polychlorinated biphenyls. Maternal smoking, methylmercury from contaminated fish or from other sources, alcohol, maternal infections, and maternal malnutrition decrease IQ. Now, most of these exposures have been shown to cause around about a five to ten point decline in IQ on a population basis. We don't know whether that's the amount you can lose easily, and if you have multiple exposures you lose more or you don't. Those studies really haven't been done properly, but it makes a difference. In this graph here, this is a population of the size of the US some years ago, about 200 million people. A shift, so this is normal IQ curve, bell-shaped curve the average of 100, that gives you 6 million gifted people with an IQ over 130 and 6 million mentally retarded with an IQ under 7, normal population distribution. If you shift the IQ curve five points to the left, you drop your gifted population from six million to two point four, but you increase your mentally retarded population below 70 from six to nine point four million, and these are from these sorts of environmental exposures that have been shown to have, on population basis, five to seven decrements in IQ point decrement.56.03

What about other things? There was a rather nasty, you can't really call it an experiment, but an event when the twin towers in the US were in New York City were knocked down. But, some good researchers used that as an opportunity and measured lots of things afterwards. 
Babies who were being gestated at that time in uterus, in utero, whose mothers had higher levels of the polybrominated diethyl ether flame retardants, and they had increased cord blood levels of these chemicals, had an increased risk of ADHD, and abnormal behaviour the age of two, pesticides DDT metabolite, and organochlorine pesticide, mothers living near contaminated harbors with detectable levels in the cord blood of their babies, they also had abnormal behaviour, phthalates which are plasticizers, they're the ones in linings of cans, they're in the soft plastics, that little rubber duckies that kids like to chew and things like that, lead and pesticides, showing delayed cognitive development in associations with Parkinson's Disease. 

Air pollution also has this effect, very nice study from the Spanish group in Barcelona where they've used functional MRIs of the brain of children during development at school, showing that kids who go to school where the school is located near a busy highway, their brain development is lower, whereas kids who have green space around their school, and the pollution levels are lower, their brain development is more rapid. Not the structure, but the functional development of the of the brain, from air pollution.

Last little bit. I’m going to talk about environmental obesogens and why it isn't just what you eat. Well, it is, but not necessarily the calories.

So, what's an obesogen? Is a chemical or xenobiotic that disrupts normal development and the balance of lipid metabolism, and it can do this in a number of different ways. It can do it by increasing the number of fat cells. It can do it by increasing the way fat cells metabolize fat, so that they can the same number of cells but they store and metabolize fat more differently. They can metabolize the fat to make it more inflammatory. Obesity is an inflammatory disease as much as anything else, and they can do it by say changing the way energy is used within the body. All of these chemicals from animal studies or from human studies have been shown to have this effect on increasing obesity. Now, it seems like it might be a bit of a cop out, it's an excuse, it's not my fault, I don't eat too much it's what my mum was exposed to when she was pregnant with me, and this concept isn't universally accepted. 

One of the reasons is that all of these chemicals are lipophilic. So, if you have more fat and you've been exposed to these chemicals, you're going to have more of it in your fat for that reason alone. So, whether it's cause or effect has always been debated, but what convinced me that there's likely to be some truth in this argument, are these data. Now these come from the [Inaudible] US Biomonitoring Program that they have, and what's shown in this graph, this on the y-axis is the prevalence of diabetes, and here is body mass index. Now, obesity is a disease where your body mass index is over 30. And so here, these people 25 to 29 is normal weight, these are all women under 25, is supposed to be underweight, and over 30 is overweight or obese. But they measured persistent organic pollutants in the blood of these women, and when they stratified these data by the quintiles of the chemicals, these women here with the lowest chemical levels, didn't matter what their body mass index was, they didn't develop diabetes. These women who are underweight, the more chemical they had in the blood, the higher the risk of developing type 2 diabetes, which is associated with being overweight. And if you had both, a greater than 50 risk of having type 2 diabetes. So, these data suggest to me there is definitely something in this. Exactly where the truth lies is challenging.

So, in conclusion.

My message is the impact of environmental exposures is influenced by when they occur. This is the concept of the windows of susceptibility. Children receive a higher dose in any given environment than an adult does. Exposures in early life increase lifelong risk for chronic disease, and most of these exposures we're talking about are avoidable, and what stops people avoiding them is lack of public knowledge about the exposures, about exposure sources, and about why they should care about some of these exposures. And on that I’m going to finish and take any questions you may have. 1.02.06

[Applause]

Thanks, Peter. That's terrific. So, are there any questions we have some coming from our live streaming audience and we have some microphones so if you'd like to put up your hand we'll get a microphone to you so you can ask a question.

I've got a question that was submitted before this presentation to either Andrea or Peter. It's from David. So, do you think the practice of risk assessment commonly used in contaminated site investigations to reduce the cost of compliance, exposes children to high levels of risk when they seek out their playtime adventures, compared to removing or undertaking in-situ chemical or bio-augmented remediation, particularly when the current land use is ongoing or has the potential for off-site migration.

This sounds like a regulatory question to me. 

[Laughter] 

Don't you love that? Blame it on the regulator.

Risk assessment is a tool to aid decision making, it is not the complete answer, it actually helps us determine and assess the risks in a systematic way when we don't have perfect information. So what that means is we don't have a lot of information about some contaminants in soil and about how people get exposed to them, so then this question says we'll just clean it up and remove it, but when you've got a contaminated environment to what concentration do you clean it up to, how do you make that determination, and it's very easy to say background, but what is background now in an urban environment? So, I agree with the person, I will always agree that clean up and remediation of contaminated sites is the priority, and it's something that we absolutely move towards before we do risk assessment, as long as we have an understanding of how much is too much. Risk assessment in my view is a tool that we can help, that helps us in our decision making process. David, I hope that answers your question. If it doesn't, flick me an email and I'll try and clarify it, thank you.

But Andrea, wouldn't it be nice? 

He's going to argue with me!

I’m not going to argue with you. Wouldn't it be nice if you knew the toxicity of what you were being asked to clean up? And the reason we often don't know the toxicity is because all those chemicals Andrea showed coming into the country, maybe a handful actually have toxicity testing done, as far as the exposures I’m talking about, prenatal in utero, early life exposures. There's no requirement for the chemicals to be shown to be safe for humans before they're introduced into our environment.

I’m going to argue with him. There's lots of toxicological testing. I think the issue is when we've got the case of say our per and polyfluoroalkylated substances, they are lovely chemicals because they're great fire retardants etc. The issue is we've now subsequently discovered they're persistent, mobile, and they accumulate, a perfect storm when you're talking about human exposure.

Probably just a very quick question. You were describing how exposures to small children occur because they're generally rolling around on the floor, but I’m slightly conflicted because I believe that the current thinking is that you will develop your immune system by, you know, rolling around on the floor and being exposed to microbials.

Don't be conflicted. Dirt is really good for kids, but it'd be nice if the dirt wasn't contaminated. 

[Laughter}

So, I mentioned the immune system is immature at birth. We have to learn, our immune system learns what to respond to and what not to respond to by exposures. And, one of the problems that we have in generations younger than mine are that a lot of the exposures that I used to be allowed to have, kids don't have any more, and this is the exposures to the environment, to bugs, to dirt. Chemicals is a different matter. Yes, kids should play outside kids, should roll around on the floor, but please don't spray the floor with pesticides before the kids roll around on it.

Thanks, that was really interesting. My name is Fiona I work at Melbourne Uni. I was just curious to know if there is a link to environmental exposures and the prevalence of food intolerances and allergies that seem to be just growing. As my kids get older every year, there's more in their class. 

There's a lot of active research on the causes of food allergies and yes environmental exposures are a major factor, both in a positive and negative way. We're starting to understand. Anne Louise was here. I’m not sure she's still here. There's study going on down in Geelong at the moment, the Barwon infant study, and they have very good data that of how the bugs that are in the maternal bowel during pregnancy influence the risks of allergy afterwards, and certain bugs decrease the risk of food allergy in particular, and the reason the mums have these bugs in their bowel is because of the environment they're exposed to, positive things like dogs, like farm environment, like a more complex microbiological environment, educate the maternal bowel that educates the infant immune system and decreases the risk of allergies. Chemicals have the opposite effect. They take out these so-called good bugs in the bowel of both of the mother and the infant and increase the risk of food allergies. Avoiding allergens in early life increases the risk of food allergy as well. We used to think that you shouldn't have anything, any foods other than breast milk, before 12 months or six or 12 months of age because of the risk of allergies. We now know that's exactly the wrong advice and that's because of the way the immune system learns. The immune system is immature at birth. It has to be exposed to things early on to know what not to react to. There's this phenomenon called immunological tolerance which only occurs to things you've actually been exposed to and foods are in this as well. So, yes, very important for food allergy.

I was very interested in your views on obesogens for obvious reasons. I’m always looking for an excuse for obesity.

[Laughter]

Now, I noticed you didn't have organochlorines up there because they're obviously banned, but I, when I grew up in a developing country they were not banned, where I was and I played with DDT. Now I always joke around that if I go on a diet all my DDT will be released from my body fat into my bloodstream. As a medical professional how will that affect me and how has that affected my kids, who I gave lots of breast milk to.

[Laughter]


Oooooh, yeah right okay. 

[Laughter]


I’m actually giving a talk over the weekend on environmental obesogens at a different venue, and I do have organic chlorines in there. But, you're right. I mean, there's many layers in your question. Obviously in your case it was related to the chemical exposure.

[Laughter]

You are right, if we were to take samples of your fat particularly inside your abdomen, and measure levels of DD… wouldn't be DDT, it'd be the metabolites that that would be there, they would be higher without a doubt. There's also no doubt that if you go on a crash diet, some of those would be released and so crash dieting is not a good not a good idea. There's also unfortunately no doubt that you did pass some of these in your breast milk to your children because they are lipophilic, and they do go in breast milk, however the other benefits your children got from the breast milk will certainly were very important to their development, and I would never suggest that women not breastfeed related to chemical contamination, although there are some circumstances where that has been advised. 

[inaudible]

You don't have to feel guilty, you did a whole lot of good with the breast milk as well as a little bit of bad.

[Laughter]

I also thought it's worth making a point, just because you have an elevated pollutant concentration in your body does not mean you will get that health effect either, so you know, it's risk of an outcome. Many of the studies will show that some of the people that have some of the highest pollutant concentrations that are measured don't have the health outcome of interest. So, we also need to balance the language that we use, that's why we talk about risk, but the other comment, that's why we talk about risk reduction. What we're really talking about here is risk reduction so that we can reduce the potential for health effects in those that may be susceptible for it. 

I mean, I didn't talk about it at all because it's a whole long and complex talk, but genetic susceptibility is a major factor in determining who gets disease when they're exposed. Andrea is exactly right. It's not just the level of the of the chemical that causes the risk. The chemical increases the risk, but it's how your body handles it, how your genetics makeup handles it that determines whether you get the outcome or not.

Time for a quick question, okay last one, thank you.

Thank you, in view of the possible exposure to multiple toxins and pollutants, how do you, do you have any special way in which you relate to the community as to how you avoid hyperneurosis in parents and potential neurosis.

It is a good question. It's a good question, it's a good question. If you look at most of the research that's been done in this area, most of the research focuses on individual chemicals or groups of chemicals, and the reason they do that is because that's the easy thing to do. Studying mixtures is really tough because you don't necessarily know the interaction between different chemicals, but we can say with absolute certainty, apart from some occupational settings, people are almost never exposed to a single chemical, and so what we talk about is a simplistic view in a way, but we also, but what you do to avoid hyperneurosis in the community is, they don't believe us anyway, secondly that you try to talk to them about avoidable exposures, things that they can do or not do that changes their risk. Like, you must not heat food in a plastic container and a microwave, it increases the chemical leeching, the bisphenols and the phthalates into the food. Absolutely known, you mustn't heat baby formula in the bottle in a microwave. If this stuff leeches into the milk, babies don't need their formula heated anyway, but you don't do it in a microwave. So, you talk about avoidable exposures rather than things people don't need to worry about. The reason we even talk about these things, apart from the fact that they matter, is that a lot of people don't understand what they're doing in their homes that increases their risk of disease. So, rather than hyperneurosis, we'll talk about controllable behaviours, and you can't modify your behaviour if you don't understand the risks associated with it.

I think that's a great place to stop this seminar. I think you'll agree that it's been very informative. I've certainly, I think it's great now that I can also explain my weight via significant exposures for some period of time. But thank you very much for attending. I think we've all learnt a lot. I think we've got a lot more to learn and I think we certainly are doing a lot of work to try and establish our understanding of our environment and also the different contributors to human exposure. I think we've got great people researching this area and looking into how we protect the most vulnerable in our society, and who are most precious because they become the adults who are going to look after us in older age, but clearly, no that's a joke, clearly we need to take all the measures that we can. Thank you very much for your attendance. Please keep yourselves informed and we have another seminar series coming up in August and probably again in November. Travel safely and thanks again, thanks to Peter.

[Applause]