Slides for a lecture given at the University of Vienna postgraduate course on Toxicology/Science of Chemical Safety (Universitätslehrgang Toxikologie/Chemical Safety für Postgraduierte). See... http://www.meduniwien.ac.at/krebsforschung/research/research-units/chemical-safety-and-cancer-prevention/en/
Exposure assessment for occupational epidemiology part 2Retired
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.
Exposure assessment for occupational epidemiology part 2Retired
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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All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Keynote presentation on Current and Future Trends in Exposure Science Retired
Slides from my keynote at the ISES workshop in Bilthoven. I discuss the role of exposure science in improving population health, in the past and in the future. I cover lead poisoning and air pollution and show that we have solved these problems. The future will present new and different problems. We need to use the exposome paradigm to guide future research.
Exposure assessment for occupational epidemiology part 1Retired
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.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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There are a number of conditions that present acutely, predominantly with pain and/or swelling
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The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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6. Interception sampling… ‘ Generic’ protocols that prescribe sizes, numbers, location and method of attachment of patches are given by WHO, US-EPA, OECD Possible to use whole suit, gloves, hood, socks… “ actual” and “potential” exposure
13. Dermal exposure to metals… Source: http://www.herag.net / Hughson GW, Cherrie JW. (2005) Comparison of measured dermal dust exposures with predicted exposures given by the EASE expert system. Annals of Occupational Hygiene;49(2):111–123. CaCO 3 Zn Pb Sb Ni
14. Schneider et al conceptual model Schneider et al. (1999) Conceptual model for assessment of dermal exposure. Occup Environ Med vol. 56 (11) pp. 765-73. Surface contamination layer Air compartment Clothing outer layer Skin contamination layer Source Clothing inner layer
30. Inhalation and dermal exposure Authors Substance Workplace Corr Comment Fent et al (2008) HDI Spray painters 0.79 Log transformed data Day et al (2007) Beryllium Cu-Be alloy plant 0.63 McClean et al (2004) PAH Asphalt workers 0.59 Based on pyrene analysis Hughson et al (2010) Nickel Various Ni production 0.48 Log-transformed hand data Sobus et al (2009) PAH Asphalt workers 0.32 Not statistically significant Cocker et al (2009) MbOCA Polyurethane elastomers None Aprea et al (2009) Imidacloprid Greenhouse None
31. Spraying paint… For spraying of low-volatility agents there seems to be a fairly strong association between inhalation and dermal exposure Photo from Dhmiter Bello
32. Correlation between measures… Fent K, Jayaraj K, ball LM, Nylander-French L. (2008) Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers. J. Environ. Monit.;10(4):500-507.
33. Contribution of skin to total exposure… Authors Substance Workplace % skin Comment Borak et al (2002) PAH Creosote impregnation >90% Aprea et al (2009) Imidacloprid Greenhouse work >78% Est. absorbed dose Sheenan et al (2008) Benzene Cleaning ≈ 50% Low levels Bader et al (2008) NMP Simulation 47% Vapour uptake at rest Chen et al (2008) PAH Metal machining 37% Lindsay et al (2006) Toluene Coating work <9% Kim et al (2007) Jet fuel Fuel cell maintenance 4% PBTK model Chao et al (2006) Jet fuel Fuel cell maintenance 3% Xing et al (2011) PCB Recycling 0% Diet main source Vermeulen (2006) Benzene Shoe manufacture 0%
34.
35.
36.
37. Protection factor paradign Simulated data Cherrie JW, Semple S, Brouwer D. (2004) Gloves and dermal exposure to chemicals: Proposals for evaluating workplace effectiveness. Annals of Occupational Hygiene;48(7):607–615.
Thank you and my thanks to the organisers for inviting me to give this Keynote address. It is always an interesting and informative exercise to try to review work in a specific area and try to draw out some lessons, and I hope that you will find this talk a helpful beginning to our discussions about exposure measurement.
Dermal exposure measurement is a broad field and I have had to limit the scope somewhat. I have chosen to look only at occupational studies, although I suspect that much of what I have to say will also be relevant to environmental exposure, and I have mostly kept to the last ten years. The brief version of the talk is that we have made progress but that it is slow and if we are to really improve things we are going to have to work differently in the future.
Over the last 40 years interest in dermal exposure has grown enormously or at least as measured by the number of published scientific papers with the term in the title or abstract. Interest in dermal exposure measurement has also grown since with a significant number of papers being published since the start of the 1990s. However, interest in measurement has not grown as fast as other aspects of occupational dermal exposure and we are still a very small scientific field publishing 20 – 30 papers per annum.
The methods that we have available have been around for a long time and they are all very practical pragmatic techniques. We can either reply on interception, removal or in-situ assessments (Questionnaires, which one might reasonably include here are going to be dealt with by Dr Bello in the next talk). Not all techniques are applicable in all situations. Clearly relying on washing or wiping for materials that are either rapidly transferred into the body or are lost to the environment would not be sensible. A lot of work has been done on sampling recovery, the distribution of exposure across the body, the appropriateness of sampling only part of the skin. For wiping and washing there are also issues about the number and timing of samples collected.
Need to assess the sampling efficiency, the recovery efficiency, stability, maximum sampling capacity,
Important developments in the last ten years are the “Standards” describing the measurement methods and strategies, the latest of these being finally agreed just last month. Fortunately these documents summarise the key knowledge. relating to these methods. They also attempt to standardise the terminology used by researchers and others.
Over the last ten years there has been increasing interest in dermal exposure to metals, mainly from the perspective of risk assessment. These data show the exposure loading on the hands and forearms, which tend to be the most highly exposed, for 19 different scenarios for four metals and CaCo3. The data span almost four orders of magnitude with substances where there is greater use of engineering control measures. We have looked at estimates of the maximum likely loading from immersing your hand in powder and concluded that it is around 10 mg/cm2, i.e. at the top of this scale.
The Schneider et al conceptual model, which was developed as part of a European capacity building initiative, was intended as a way of understanding what was going on in relation to exposure processes and it can be used as a tool to guide the development of research questions. It comprises a series of compartments that are linked and may exchange contaminant (this is a simplified schematic of the published model). Importantly we underline that it is not the mass on the skin contamination layer that determines uptake but rather the concentration of the substance.
In fact we measure the Dermal exposure mass, or the dermal exposure mass loading, or … However, we don’t measure the concentration. Often we don’t even report the concentration in the source.
We developed a prototype sampler to measure Something more biologically relevant, particularly for volatile agents although the concept is applicable to all substances of interest. It’s based on a diffusion membrane and an adsorbent material. The IOM sampler worked well but suffered because the permeability of the available membranes was higher than the skin and so it was necessary to adjust the results for uptake of vapour. The device needs further development. NIOSH have independently developed a POD for PAH sampling for asphalt workers, although the details are not yet published.
Another attempt to measure exposure in a biologically relevant manner is the wet-work sampler that we developed. This is based around measuring the difference in temperature from two thermocouples – one located on the skin and the second about a millimeter above the skin. By counting the spikes in the measurement and the duration the reading is above the baseline we can assess both duration of wetness and number of wet events. Some further measurements using this device will be reported in the next session at this conference.
Dermal exposure not routinely undertaken to control risk. The main focus is research, for example to: Understanding exposure routes (for health impact assessments) Assessing the effectiveness of protective clothing Epidemiological studies Increasingly in Europe industry is undertaking work to develop datasets for use in regulatory approval Under the REACH Regulations In other regulatory systems
Vermeulen and colleagues carried out a study in the rubber industry to investigate the importance of different pathways in relation to the Schneider et al model. They measured air concentration, dermal exposure loading. They showed that; Hand (wrist) contamination was on average highest Strong correlation between hand (wrist) and whole body contamination
In addition they looked at the correlation between the measured values in different compartments by the stage of the production process. They found that this differed by process stage. For example, in curing there was a moderate correlation between near-field air concentration and the load in the skin contamination layer but no association between surface levels and the load in the SCL. However, in pre-treatment the reverse was the case, with moderate correlation between surface load and SCL load, but no association between air concentrations and the load in the SCL.
A more systematic look at the published literature identified 271 papers that were potentially relevant, and screening these got it down to 21 for review.
In fact there were only seven that had data on the correlation between inhalation and dermal exposure measures. These danged from 0.79 in spray painters to no correlation for greenhouse workers. Not surprising but we need to better understand these associations so that we can decide when we might expect to find some benefits in reduced dermal exposure from intervening to reduce inhalation exposure.
The paper by Fent shows a strong correlation between the inhalation exposure (concentration x duration spent painting) and dermal dermal loading. This is probably because the spraying process is the main source of contamination in the workplace.
There were 10 paper that provided some information about the relative contribution from dermal exposure to overall exposure. Sometimes based on an analysis of biological monitoring information in relation to air and dermal exposure data, sometimes on estimates of intake using models. One paper used a PBTK model to relate the various measures and estimate the contributions form different pathways. Interestingly these show that for many of the more volatile agents the proportion from dermal exposure was relatively small.
The paper from Borak et al shows data from 34 workers involved in impregnating timber with creosote. In this case they estimated that more than 90% of the uptake was from skin contact.
The data from Kim and colleagues and a second paper by Chao et al show that the majority of naphthalene uptake was by inhalation. Kim used a PBPK model to link the various measurements made.
There are very few research studies that have looked at the effectiveness of PPE – just 13 since 2000 on glove of clothing protectiveness.