Exposure assessment for occupational epidemiology part 1
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The aim of this lecture is to provide an introduction to occupational exposures and the strategies used in epidemiological studies to assess exposure of subjects.
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Exposure assessment for occupational epidemiology part 1
- 1. INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org Exposure assessment 1 John Cherrie
- 2. Learning objectives… The aim of these sessions is to provide an introduction to occupational exposures and the strategies used in epidemiological studies to assess exposure of subjects At the end of the sessions you will: • understand how measurable exposures are defined • know about the types of exposures that occur in industry and what they depend upon • know about the strategies that have been used in epidemiological studies to estimate exposures and their strengths and weaknesses
- 3. Summary… • Asbestos and other mineral fibres • Exposure – definitions • Agents, circumstances and exposure routes • Measurement of exposure • Variability in exposure • Modelling exposure • The exposome
- 4. Definition of exposure… “In epidemiology exposure denotes any of a subject’s attributes or any agent with which he or she may come into contact that may be relevant to his or her health.” Armstrong, White and Saracci (1990)
- 5. From source to dose…
- 6. Routes of exposure... • Inhalation • exposure level in air inhaled, duration of exposure • Dermal • concentration on skin, area of skin exposed, duration of exposure • Ingestion • mass of chemical being swallowed, duration of exposure
- 7. Asbestos… • Doll (1955) lung cancer • Wagner et al (1960) mesothelioma • 1964 New York conference • Stanton and Wrench(1972) and Pott and Friedrichs (1972) in vivo induction of mesothelioma • Mid-1970s glass and rockwool industries commission studies
- 8. A serious public health risk...
- 9. Risk of lung cancer… 𝑅𝑅 = 𝛼(1 + 𝐾𝐿 .CE) where 𝛼 is the intercept representing the background rate of lung cancer KL is the lung cancer “potency factor”, and CE is cumulative exposure
- 10. Lenters et al review… Lenters et al. (2011). A meta-analysis of asbestos and lung cancer: Is better quality exposure assessment associated with steeper slopes of the exposure-response relationships? Environmental Health Perspectives, 119(11), 1547–1555. KL Chrysotile
- 11. Biological relevance… • The chosen exposure metric should be biologically relevant • what substance / agent? • what averaging time? • what sub-fraction of an aerosol? Cherrie and Aitken. Measurement of human exposure to biologically relevant fractions of inhaled aerosols. Occup Environ Med (1999) vol. 56 (11) pp. 747-52
- 12. Consider the disease process… Proportional Discrete Reversible Airway inflammation, mechanical injury to musculoskeletal system Asthma attack, dermatitis Irreversible Asbestosis Lung cancer, mesothelioma, immune sensitisation After Smith and Kriebel
- 14. Fibre definition… • Fibres are harmful because… – they are thin (d < 3mm) – they are long (l > 5mm) and – because of their shape (l/d > 3) • also because they are persistent in the lung
- 15. Modern measurement… • Personal sampling is straightforward • More relevant to personal exposure • Are more biologically relevant • Can provide information on temporal variation • Biomonitoring increasingly undertaken
- 16. Historic measurement… • Often made using different instrumentation • May be analysed differently from modern methods • Quality assurance may have been limited • May not relate to personal exposure • May just be for short periods within the day Cherrie. (2003) The beginning of the science underpinning occupational hygiene. The Annals of Occupational Hygiene. 47 (3): 179-85
- 17. Near-field Far-field Cherrie, J. (1999). The effect of room size and general ventilation on the relationship between near and far-field concentrations. Applied Occupational and Environmental Hygiene, 14(8), 539–546.
- 18. Cherrie, J. (1999). The effect of room size and general ventilation on the relationship between near and far-field concentrations. Applied Occupational and Environmental Hygiene, 14(8), 539–546.
- 19. Coke works...
- 22. Between and within worker variation… Symanski, E., Maberti, S., & Chan, W. (2006). A meta-analytic approach for characterizing the within-worker and between-worker sources of variation in occupational exposure. The Annals of Occupational Hygiene, 50(4), 343–357. http://doi.org/10.1093/annhyg/mel006 Ratios of the 97.5th and 2.5th percentiles of the log-normally distributed exposures of each group of workers Between Within
- 23. Within and between worker variation Symanski, E., Maberti, S., & Chan, W. (2006). A meta-analytic approach for characterizing the within-worker and between-worker sources of variation in occupational exposure. The Annals of Occupational Hygiene, 50(4), 343–357. http://doi.org/10.1093/annhyg/mel006
- 24. Within and between worker variation Symanski, E., Maberti, S., & Chan, W. (2006). A meta-analytic approach for characterizing the within-worker and between-worker sources of variation in occupational exposure. The Annals of Occupational Hygiene, 50(4), 343–357. http://doi.org/10.1093/annhyg/mel006
- 25. Things change over time…
- 26. Temporal changes in exposure levels… Creely KS et al. (2007) Trends in inhalation exposure--a review of the data in the published scientific literature. Ann Occup Hyg.; 51(8): 665-678. Aerosols
- 27. Temporal changes in exposure levels… Creely KS et al. (2007) Trends in inhalation exposure--a review of the data in the published scientific literature. Ann Occup Hyg.; 51(8): 665-678. Gases and vapours
- 28. Modelling exposure and dose… Source-receptor model Dose model
- 32. Modelling internal exposure… Alveolar air Lung blood Slowly perfused tissue Richly perfused tissue Liver Fat Inhaled air Exhaled air Metabolism
- 33. Two-thirds of the deaths in the world are caused by noncommunicable diseases, especially cancer and cardiovascular disease Only about 10% of this mortality attributed to genetic variation
- 34. The exposome is composed of every exposure to which an individual is subjected from conception to death. Chris Wild
- 35. The exposome… The exposome is composed of every exposure to which an individual is subjected from conception to death • It comprises: • processes internal to the body such as metabolism, gut microflora, inflammation… • external exposures including infectious agents, chemical contaminants, diet… • social, economic and psychological influences.
- 36. Agnostic investigations… • Steve Rapport recommends searching for potential causes without any prior hypothesis • Approach lends itself to “omics” technologies • Although other approaches can also adopt this approach • Follow-up with more focused epidemiological and mechanistic studies
- 37. Summary… • Exposure assessment is key to designing an informative occupational epidemiological study • Exposure can be conceptualised in different ways • Intensity and duration • Exposure metrics should be biologically relevant • Exposure is subject to considerable random variation and changes over time • Models can be informative • The exposome is coming…
Editor's Notes
- Thanks. I’m an exposure scientist working at the IOM and Heriot Watt University in Edinburgh UK. I started out working on a large epidemiological study investigating cancer risks in workers making synthetic mineral fibres – long enough in the past that they were called man-made mineral fibres. I’ve been involved in various studies – mostly cancer studies – mostly focussed on the exposure assessment. I also work on air pollution problems and occupational exposure assessments for regulation.
- I hope that at the end of these sessions you’ll…
- In this first lecture we focus mostly on exposure – what it is and how we can assess it. And we’ll finish up with something about the exposome.
- This is a rather old and all encompassing definition of exposure, but it clearly recognises the breadth of what we mean by “exposure”, which really encompasses everything related to a subject except their genome. For external agents it is the “contact with” that determines exposure.
- It’s helpful to think about the chain that links the source of the agent, lets say this is asbestos fibres in a roof product, and the ultimate diagnosis of disease in an individual. As we disturb the asbestos-containing material …
- For hazardous substances like asbestos… Inhalation exposure level often expressed as mass per unit volume of air (e.g. mg/m3) Cumulative exposure is often used as a summary measure…
- 8
- Meta KL = 0.13 For chrysotile 0.04 Amphiboles 0.33 Mixed fibre types are intermediate
- Think about the disease process and how the exposure is relevant to this – the timing of the exposure related to the onset of disease or symptoms.
- Chrysotile and amphibole bio-persistence Refer back to Lenters
- Measurement data is attractive for modern occupational epidemiology Mention biomonitoring
- Exposure varies throughout the workplace
- Measurements made in a number of jobs over seven years. Note the log scale. 0.1 to >100 micro-g/m3
- Muck of the variation is explained by area of work and the tasks carried out – pitch, ovens etc…
- Symanski and others… Around 60 studies over 10 years