Exposure Assessment: a conceptual introduction

Prologue

Rick woke up drenched in sweat in the middle of a nightmare. The temperature outside the room was freezing; inside in closed doors, the room was warm; outside was cold, the the air was thick and heavy. Embers of the fireplace glowed faintly in the lobby and cast an eery shadow; the door of the fireplace was slightly open; Rick left them that way last night to light up the wood and eventually forgot to shut them.

An oppressive thickness hung in the air in the lobby, making hard to breathe. His eyes burnt; Rick let out a raucous cough. Suddenly the morning alarm on his phone went off. It was five in the morning. He walked across the lobby to his daughter’s room. Teresa, his daughter, was asleep in her room next to the fireplace.

Rick checked into Teresa’s room. Teresa lay on the bed. Her limp lifeless arm dangled from her bed and Rick could see the sihouette of her body in the darkness. No heave. He flipped the light switch; a soft glow of the led lamp filled the room; Rick squinted. Teresa’s cheeks were unusally cherry red, a streak of dark dry crimson blood flowed down her nostrils, and her long hair reached into the night. She was not going to wake up. Ever. Everything suddenly went dark for Rick; the ground beneath shook, and he dropped into floor unconscious.

Inspector Meg was perplexed. What was going on in this house? Two deaths? What was the clue?

What is exposure?

Exposure refers to the contact of an agent with the human body. Our skin can come in contact with air, water, chemicals. While exposure is our contact with the environment, the amount that enters is referred to as dose. Here we shall review exposure, and how can we measure exposure of different agents in the environment.

In exposure assessment, we identify how much of these agents are prsent in the physical environment, and we talk in terms of how much of these can gain an entry into our system. Mere presence of an agent in the environment may not cause harm, as long as they do not find a way to enter the human body; even after entry to the body, if the body is can metabolise and neutralise or expel from the body und unchanged, the toxin cannot do harm. In any case, in exposure assessment, the extent to which the toxin or the micro-organism is present in the physical environment and the amount that enters the body need to be quantified. Exposure assessment has a critical input into health risk assessment.

But that process itself is complex. the At the least,

1. We must identify the process that generates the agent of interest
2. How the agent is transported
3. What are the pathways of entry of the agent in the body (inhalation (breathing), ingestion (eating/drinking), contact (skin)
4. Fate of the agent and its mechanism of action. Quite often, the exact amount of the exposure cannot be estimated by measuring the agent in the environment, it is contextual to measure the offending agent or the corresponding metabolite in the tissues.

Consider an air pollutant, carbon monoxide. Carbon monoxide (CO)is produced by combustion of fossil fuels (wood, coal, or oil). Imagine a fireplace in a house where wood is incompletely burnt and produces carbon monoxide, which disperses out of the fireplace in the air, and concentrates in the room where people are sleeping; depending on the breathing rates of the people asleep, the gas will enter the lungs in high or low dose, then diffuse out of the lung and enter the blood stream. In the blood stream, CO binds to haemoglobin, the oxygen carrying molecule in red blood cells converting them to carboxyhaemoglobin and in the process severely reduces oxygen carrying capacity of the blood and this leads to death (almost similar to choking by depriving of oxygen). If the room is well ventilated and there is a draught of air that allows easy exchange of air between outside nd inside of the house, the harm from CO inhalation will be minimised (see the NOAA website for more information). Else, people run a risk of death in a poorly ventilated house. Therefore, in the esitmation of CO as an exposure, it is important not only to measure total concentration of CO in the air, but also the ventilation rate of both humans and the household or the context where this occurs. This draws attention to an important principle of exposure assessment: assess the entire process.

As this example suggests, exposure assessment is not simple. If the skin, nostrils, mouth, the linings in the alimentary canal and the respiratory passages in the body are conceptualised as gateways, then depending on the control of flow of the agent, the amounts of the exposure will vary between outsides and inside of the body. How much of a toxic agent will finally enter the body is dependent on:

1. Breathing rate. — for air borne particulate matter. Therefore in an exercising or hard working person, who has higher brething rate, for the same concentration of particulate in air, higher exposure wil result
2. Exchange between outside and inside of the body. —The pollutant or contaminant (“agent”) can also be measured in vivo, that is, how much of the agent is available at the body tissue as a function of being exposed. This measurement is further complicated by human genetic propensity to metabolise, remain unaffected and excrete. Often, the metabolc process itself is the problem; in the sense that during metabolism, some compounds change into others that are more harmful.

Consider inorganic arsenic as a toxin. Inorganic arsenic is present in soil, and in the groundwater, and carried by water from the Springs in parts of the world. Arsenic is also produced during copper smelting and then it is air borne and is inhaled (for more information on arsenic exposure from the World Health Organisation, read this). We can therefore be exposed to inorganic arsenic through inhalation and through drinking and eating of food.

After inorganic arsenic enters human body, it is carried by blood stream to liver and there, inorganic arsenic undergoes sequentiual processes of reduction and methylation (addition of methyl group) and this leads to excretion of arsenic through kidney; but this reduction and methylation itself are harmful to human body and is believed to result in steps that lead to formation of pigment disorders and cancer (Yu 2000 article, see).

While assessment of inorganic arsenic in drinking water is very important for exposure assessment, it is also important to assess inorganic arsenic in urine (where it is excreted) and methylated fractions of arsenic (which indicates the body’s capacity to excrete or metabolise and therefore possible risk of disease from arsenic and exposure to arsenic). As this varies between children (less affected) and adults (more affected), in the exposure assessment and subsequent health risk assessment, consideration of age becomes an important issue. Read this article to learn more about arsenic

1. Production. — This can be human activity or industirial activity or entertainmnt activity, commercial activity, political activity, economic activity, industrial, commercial, others include (shipbreaking, deforestation, electricity generation, mining, setting up industries, industrial pollution, making and playing music, software writing and hardware development, dumping of stuff in landfill, almost any human activity that we can think of). Besides natural phenomena can also be responsible: ozone depletion, seasonal change, earthquake, tsunami, sea level rise, biodiversity loss, the list can be virtually endless. Whatever be that may be, something or some process produces a toxin or gives rise to a biological agent that gets out of the Pandora’s box
2. Dispersion. — In dispersion the toxic agent is carried away from its source elsewhere. This can be through any fluid (air or water, and indeed other relatively static media such as soil where the toxin can leach through the pores). Other examples might be carriage. If it is put on a truck then the truck movement disperses it; if it is train or ship then these are the movers, or other organisms or humans who carry them carry the microgoorganism a ship or vessel, or if we can carry certain type of algal bloom while tramping and carry them to hour our homes.
3. Contact. — The agent then coes comes in contact with human body. How? It can come in contact with the skin, bt but if the skin is intact then it does not have mch mjch much of a chanc chance to get deeper; it can hae have an efe effect or impact on the skin itself thought though as in burn or discoloration; it can enter the body through food but the gut is still in theory “outside of the body” in the sense that it is oep open at both ends; it can get absorbed into th the inside of the body from the epide epid epithelial tissues that line the gut and thus gain an entry into the disdigestive system. From th digestive system the toxin can get carried to liver and exert i their actions on the metabi metabolic pocesss of the body; if from the lungs, they can get as far as he alveoli and then either get rejected or get absorbed; this is the inhalation route; so, ingestion, ihalation, and dermal contact; if these are sound waves, then thy they can coe come in contact with the tympanic membrane and can impact the functions of the nerve and impac da impact damage.
4. Internalisation. — The exposure is then internalised and then we measure te the impat impat impact it has on the insides of the body. The biological measuremnts. For example, we measure inorganic arsenic in the waterou outside but the true measure of the health impact of arsenic is not given by the inorganic arsenic outside but hte methylated i arsenic inside. Similarly the true impact of the problem caused by exposure to mercury is not just ow much mercury is present in teh environment, but also the methylated mercury inside the body.

Classification, measurement, modelling

Three concepts are discussed in exposure assessment — humans can be classified on the basis of their levels of exposure, the exposure itself can be measured in the environment and what need to be considered for the measurment of the exposure, and for those exposures that cannot be accurately measured in the environment, they can be modelled on the basis of what is known or how models of their production and dispersion can be built and how they reach individuals.

Measurement of contaminants in the air

Classification. — At the level of areas, households, and individuals, exosure to air pollutants can be classified as exposed to high contamination or not. Air pollution can be measured on the basis of ambient air quality (outdoor air) or indoor air quality. The relationship between outdoor air quality and indoor air quality is complex and depends on the rates of exchange of air between the inside and outside of the house. So, in theory, one can have good quality of air indoors but poor quality of air outside, and this often complicates the results of studies on air quality and health. The contaminants in the air can be myria a myriad and there are several strategies to measure their exposure levees. The air pollution can be outdoors or. Confined outdoors (ambient air qualiry); they can also be indoor air and these are different from outdoor air quality. While there may be some correlation between indoor and outdoor air quality the extent to which humans are exposed depend on the airflow, amount of activities such as heavy work or rest and the temperature of the breathed air. There can also be different sources of air pollution and likewise, different strategies to measure air quality. Sometimes, air quality or air pollutants cannot be directly measured; in these cases, proxy measures or indirect surrogate measures are used to estimate the extent of pollutants in the air.

Measurement Strategies. — Air quality can be measured by any of the following ways:

Air quality data readings are taken for ozone, nitrogen dioxide, sulphur dioxide (all in parts per million), particulate matter (PM) in micrograms per litre, and visibility data.

1. Direct active measurement of ambient air by passing a specific volume of air through a pump and collection of the air particles on a filter and the filter is then weighed

2. Passive measrement. — Air pollutants and the extent to which we are exposed can also be measured passively by a static samunf process where an active pump is not involved

3. Satellite or suggo surrogate data. — Ambient air quality can also be measured by analyses of satellite data or from visibility statistics from the local airport visibility data. These are then validated by correlating these measurements with the directly collected data

Measurement of Air Pollution from Satellites (MAPS) - understanding the chemistry of the atmosphere

4. Aggregate versus personal level measurements. — However, these measurements are only suitable for measuring air quality in aggregate levels and thus, any analyses where these are used are also measured using health effects whose data are collected at aggregate levels.

5. Indoor air data quality measurement. — Indoor air quality canbe additionally collected using samplers that are worn on the body or instLjed on the wall or asks where. Elsewhere. The idea is to add up different levels of exposure by first identifying or calculating the amount of pollutants or agents in the environment and the amount of volume and the amount of time spent in that context.

6. In other contexts, the proportion of time one spends in specific concentrations are tallied and these are added up. This addition is referred to as time weighted averaged exposure. Thus total concentration of contaminant in the air (ug/l) * volume breathed * % of time spent in the context. These are then summed up to reflect total amount of contaminants that each individual is exposed to.

For example, let’s say in a house there are three rooms. In each room Mr X spends different amounts of time and the air quality of the three roooms are different (one room is closer to the fireplace where the suspendend particularte matter concentration is high and therefore the q air quality is low and PM10 concentration is high ; in the other room, which is very well ventialated and closer to the garden, and is open most of the day is the air quality is veyr hihgh and has very low concentraiton of PM10; and the thir d room is in between. Say Mr X lives 50% of the time in room 2, 20% of the time in romm room 1 and 30% of the time in room 3. The PM10 to which Mr X is exposed will be calculate calculated for each dday something like:

PM10 in room 1 * 0.20 + PM10 n room 2 * 0.50 + PM10 in room 3 * 0.30

This above method of calculation of exopsure to a particular agent or toxin or contaminant
7. Air quality in indoor and outdoor (ambient) can be quite different based on the level of exchange of air between the inside of the house and the outside world (Read this comprehensive review by Myers and Maynard (2005)). The contaminants depend on the level of ventilation and the type of fuels burnt and the activities conducted at the household levels. The difference in the air quality between the inside and outside of the house therefore will be different if the windows are closed and house remains unventilated most of the time, or if fossil fuels are burnt in the household, etc.

Modelling of Air Quality. — A range of models are used for mathematically modelling quality of ambient air. Read here for a brief review

Measurement of Contaminants in water, soil, and radiation

Pathways and classification. — Water borne contaminants enter the body through different routes. For example, water can both be consumed as a drink or splashed on the body and people use water for bathing when mists of water enter the body through the inhalation. All these factors need to be taken into account when expsosure o to a contaminant in water must be considered. For example, in the estmation of exposure to arsenic in drinking water, the concentration of arsenic in drinking water is estimated for all possible sources of arsenic in drinking water — water that is dirctly consumed and water that is present in other forms (for example in soup or porridge). The different sources are measured and added up. Different sources need to be taken into account:

1. Piped water supply. — the contaminants can come from the pipes themselves; the pipes can burst in extreme temperature (cold temperature)
2. Ground water supply. — Chemicals in the soil can leak and leach into the groundwater and then these can be pumped up and when this water is made available for drinking
3. Surface water supply. — Surface water can be contaminanted in a number of ways by chemical pollution, or growth of biological materials.

Exposure assessment in Food. — Food is frequently a source of toxin or contaminants, and therefore needs to be assessed. Read here for instance about acrylamide concentration in potato chips and other food items in New Zealand and how this was investigated. This is usually done in a number of diferent ways:

1. Dupliate food package consumed and then using this to identify the different types of food consumed per household or for each member of the household.
2. Measuring the portion size with cups and spoons and measuring the amount of toxin that can be present in the specified quantitiy of food consumed.
3. Market basket approach by identifying the differnet quantities and variety of the food consumed for an entire popultion and then for the specific sample within the popultion, the aount of toxin that can present in the specific food items are spearately identified and calculated.
4. Using Food Frequncy Questionnaire. — A food frequency questionnaire is a questionnaire used in cross sectional surveys to identify the pattern and amount of specific items of food consumed. While these are great ways to identify the pattern and amount of food consumed, being cross sectional surveys of questionnaires, there are problems associated with them like in any cross sectional surveys (validity of the questionnaire, the face, content and construct validity and recall bias).

Exposure to radiation. — Radiation can be (1) ionising radiation where particulate matter collide with tissues can cause harm, and (2) non-ionising radiation such as electromagnetic radiation (microwaves) that impact tissues in different ways. Either can be source of significant changes such as cancers and these need to be carefully assessed. Direct exposure can be assessed both at source but also at the levels of the body tissues.

Exposure modelling

Exposure modelling refers to the mathematical modelling of exposure patterns. This is particularly useful for those those exposure for which accurate first hand measurement is impossible. Also, where measurement of surrogate indicators are unavailable, or unreliable, exposure modelling can provide very vital information. Computational models based on known parameters are used to derive exposure modelling. These mathematical models simulate human exposure and human health effects for their measurements.

Questionnaire based exposure assessment

In epidemiological studies, assessment of exposure are often based on developing questionnaires and surveying participants on their level of exposure to the factor of interest. For example, in a study on the exposure to Asbestos dump site and presence of respiratory problems, the participants were asked on the frequency of their visits to the Asbestos dump site and on the basis of this reported frequency of visits, they were categorised in terms of their exposure to the asbestos. In another studies, food frquency questionnaires can be used to assess the exposure of individuals to specific items of interest. For example, in a study on exposure to arsenic dissolved in cooked rice, food frequency questionnaires were used to assess food based exposure to arsenic in drinking water in addition to direct measurement of arsenic and micronutrients.

The following issues should be considered for questionnaires:

1. Questionnaires need to be validated using face, content and consruct validity to so that the questionnaires can measure exactl what they are meant to measure
2. Questionnaire based measuresment are open to reporting bias. The participant can misreport the extent to which the participant is exposed to the onject of interest.

Epilogue

This was a brief introduction to the topic of exposur exposure assessment for environmental epidemiology. Exposure is the refers to the fact that an agent or a toxin or an environmental entity is comes in contact with the human i tissues but til the human tissues internalise the external agent, this cannot do any harm. The amount of the agent that passes from the external environment to the internal tissue is referred to as h the dose of the agent. The body prsents several different barriers to the offending or external agent: the skin, the gatronintestingal tract, the ciliary movements in the lung, or associated passages, the metabolic and immunological processes. Exposure can be assessed using direct measurement in the environment, or by using surrogate markers that are present in the human tissues (for example exhaled carbon monoxide for and using carboxyhaemoglobin concentration or by measuring the cholinesterase activity for exposure to pesticides, or methylaed arsenicals in arsenicals for exposure to inorganic arsenic in drinking waer).

Coming back to where we began, Rick and Teresa died reportedly due to their exposure to carbon monioxide emitted from the fireplace as teh fireplace was kept burining with wood throughout the night and the door of the fireplace was kept sllighglty slightly open and it let the carbon monoxide escape. The chimney of the ire fireplace also was not sowrking and wa had not been cleaned for ages. Tis led to acu accumulation of carbon monx monoxide in the house and h led to the deth of the two members of the household.