Toxicology-Principles of Industrial Chemistry 1 Chemical- Any substance that participates in a chemical reaction or occurs as a result of that reaction. Element-An element is a substance that cannot be broken down into simpler substances. Each element has a set of properties that distinguish it from other elements. Elements can be composed of single atoms or two or more atoms of the same type. Atom-Uniquely defined by its atomic number (Z) (number of protons). Neutral atom: number of protons = number of electrons. Atomic ion: number of protons ≠ number of electrons. Molecule-A molecule is formed when two or more atoms join together chemically (bonds). Examples: Molecular hydrogen (H2) Molecular oxygen (O2) Molecular nitrogen (N2) Electrically charged (+/-) molecules are called ions. Chemical Reactions-Chemical reaction is a rearrangement of atoms such that “what you end up with” (products) differs from “what you started with” (reactants). Factors that affect the rate of a chemical reaction are: Concentration of the reactants; Temperature of the reactants; Particle size of the reactants; Pressure; Presence of catalysts. Periodic Table Arrangement of elements according to increasing atomic number. Horizontal rows are called periods. Vertical columns indicate groups or families. Regularly repeating nature of elemental properties is seen: Elements in the same group have the same number of electrons in their outermost shells. Chemical Bonds-Ionic Bonds: Metal + Non-metal Transfer of electrons Example: NaCl Covalent Bonds: Non-metal + Non-metal Sharing of electrons Example: H2O, Cl2, O2, CO2 Metallic Bonds: Metal + Metal Sharing of free electrons. Oxidation Reactions A reaction where electrons are lost. The agent that accepts the electrons is called an oxidizing agent. Reduction Reactions A reaction where electrons are gained. The agent that donates the electrons is called a reducing agent. Redox Reactions A reaction where both oxidation and reduction occur. Compound Compounds are formed when atoms of different elements combine with each other. Chemical reactions are required for compound formation. A chemical formula shows the kinds and proportions of atoms in a compound. Ex: NaCl stands for sodium chloride (salt) from sodium (Na) and chlorine (Cl). Mixtures Combination of two or more substances without any chemical reaction. The substances are not chemically bonded together. Example: Sugar + Water Sugar Solution. Separation of Mixtures Filtration Centrifugation Sublimation Crystallization Simple distillation Fractional distillation Decantation Chromatography . Filtration An insoluble solid from a liquid /Centrifugation Solid held in suspension from a liquid/Sublimation Two or more solids, one of which sublimes/Crystallization Pure solids from the impurities suspended in the solution (separated in the form of crystals)/ Simple Distillation Pure liquid (solvent) from a solution of a solute Fractional Distillation Miscible liquids with different boiling points Fractional Distillation Miscible liquids with different boiling points/Decantation Immiscible liquids/Chromatography Substances with different solubility in the same solvent . Chromatography-Physical method of separation that distributes the components to separate between two phases. Mobile phase: mixture dissolved in a fluid. The mobile phase carries the mixture through the stationary phase (a structure holding another material). Constituents of the mixture travel at different speeds and thus get separated. Some important terms Chromatograph Equipment that enables the separation. Chromatogram Visual output of the chromatograph. Analyte Substance to be separated from the mixture. Eluent Solvent that carries the analyte. Eluate Mobile phase leaving the chromatograph. Applications of chromatography Quality Control in Food Industry: To separate and analyze additives, vitamins, amino acids, preservatives. In diagnostics: To test for alcohol in blood; To test for drugs in urine samples. Pharmaceuticals: To separate chiral compounds (two isomers identical in every way except the alignment of molecules): Example: Thalidomide Environmental Testing Laboratories: Identify presence of trace quantities of PCBs in waste oil; DDT in ground water. Monitor air quality. Toxicology-Principles of Industrial Chemistry 2 Functional Groups Specific groups of atoms or bonds within molecules that are responsible for the characteristic chemical reactions of those molecules. Enzymes Globular proteins that catalyse chemical reactions in living organisms Properties Specific/ Increase rate of the reaction /Unchanged at the end of the reaction – reusable Need them Reactions too slow to maintain life / Can’t increase temperatures/pressure in cells (fatal) Mechanism of action The substance an enzyme acts on is a substrate. The enzyme binds to the substrates by its active site to form the Enzyme-substrate complex. A restricted region on an enzyme molecule which binds to the substrate is the active site. It is basically a pocket formed by the folding of the protein. The active site involves a small number of key residues that actually bind the substrates. The rest of the protein structure is needed to maintain these residues in position. Principles of Toxicology Factors responsible for toxicity - Length of exposure/ Amount /Tolerance/ Density/ Size/ Shape /Solubility in body fluids/ Frequency of exposure/ Interactions with other substances/ Site and route of exposure. Measures of Effect Gross effects to organs or tissues may be detected as symptoms or signs. Signs are measurable indicators of disease such as raised body temperature. (Quantitative) Symptoms are physical complaints such as feeling feverish. (Qualitative) Effects may be local or systemic. Effects may be acute or chronic. Measures of Dose Dose measurements should relate to the chemical concentration in the target organ. Critical organ concentration represents the dose at which adverse effects are observed. In practice dose is measured indirectly as exposure. Experimental Exposure, Occupational Exposure, General Environmental Exposure, Measurement in Body Compartments (Biological Monitoring). Dose - effect and dose - response relations: Assumptions 1. There is a causal relationship between the toxic agent and the measured response. 2. The response is related to the size of the dose. Leads to further assumptions that: There are biological sites of action, The response is related to target organ concentration, The target organ concentration is related to administered dose. Dose-effect Relations effect Relations The relationship between dose and the magnitude of a specific effect in a specified proportion of the population. Dose-effect relationships of a chemical: related effects Where the under-lying biochemical mechanism is common, various dose-effect relations may be sequential eg. Lead . Dose-effect relationships of a chemical effect relationships of a chemical - Independent effects in different organs Toxic materials may have different effects in different critical organs that are not sequential eg. Cadmium Dose-response relations response relations The response is defined as that proportion of the population showing an effect of a defined magnitude: The dose-response relation is the correlation of dose and response eg. for lethality . LD50 is the dosage (mg/kg body weight) causing death in 50% of exposed animals . PRINCIPLES OF TOXICOLOGY - OF TOXICOLOGY – II Toxic responses Toxico-kinetics Describes the passage of the chemical through the body. Absorption- Biotransformation- elimination Toxico-dynamics Describes the consequent cellular and functional changes . Determining thresholds for harm There are different approaches to determining the threshold of harm, used for a range of purposes: 1. The largest constant concentration that can be tolerated for 24 hrs/day, for a lifetime with no adverse effects. 2. The largest constant concentration that can be tolerated for 8 hrs/day, 5 days/week, for a working lifetime with no adverse effects. From: Roach, S. Health Risks from Hazardous Substances at Work, Pergamon Press, 1992 For chemicals with short BHTs the threshold of harm will be similar using either of the above definitions. However, chemicals with long BHTs will tend to accumulate, so the threshold of harm will be less when defined as in 1., because it does not allow for any exposure-free time. 3. The largest average concentration that can be tolerated for 8 hrs/day, 5 days/week, for a working lifetime with no adverse effects. From: Roach, S. Health Risks from Hazardous Substances at Work, Pergamon Press, 1992 For chemicals with short BHTs the peak concentration rather then the average will determine the threshold for harm, so the above definition may give a different and lower value for threshold of harm when compared to definition 2. (Some high peak values can occur, even when the average is within acceptable limits.) For chemicals with long BHTs it is the total load of chemical in the day that is important in determining the threshold of harm and the values will be similar whether defined as in 2. or 3. Toxico-dynamics There are a number of general mechanisms of toxicity. They are not mutually exclusive but provide a useful way to group toxic substances. 1. Interference with communication systems 2. Binding to important structural or functional bio-molecules 3. Disturbance of calcium homeostasis 4. Targeted toxicity 5. Carcinogenesis Interference with Communication Systems Binding to receptors for transmitters or hormones - disturbs normal function directly or indirectly through blocking access to endogenous substances. Eg morphine; d tubocurarine Inhibit enzyme breakdown of transmitter. Eg organophosphate insecticides Interfere with ionic current across nerve membrane and generation of nerve impulse. Eg DDT interferes with closing sodium gates Non-specific depression of nervous system activity related to lipid solubility. Eg many organic solvents . Carcinogenesis If DNA adducts are not repaired they may go on to produce mutation through cell division. Mutation can underpin cancer. Some carcinogens are genotoxic because they stimulate proto-oncogenes that regulate growth. Some carcinogens are promoters rather than initiators. Eg. They may impair DNA repair or immune surveillance, or may indirectly affect uptake or elimination of a mutagen. Disturbance of calcium homeostasis Tissue injury is often associated with calcium accumulation – from enhanced influx into the cell, impaired removal from the cell or release from intracellular stores. Calcium plays a role in many cellular activities (nerve signalling, muscle contraction etc) so disturbances can affect a wide range of functions. Eg. Lots of industrial chemicals, such as aldehydes, alkanes, alkenes, nitrophenols are thought to disturb calcium homeostasis. Targeted toxicity Some chemicals target specific cells. • Eg. Manganese targets cells in basal ganglia in the brain, disturbing motor function. • Eg. Thalidomide (drug originally used to treat morning sickness) targets developing limb bud cells – leads to poorly developed limbs. Principles of Toxicology - III Toxicodynamic interactions Two toxic substances in combination can have effects on the body which are either: • Additive • Synergistic • Potentiation • Antagonistic • Indifferent . Additive Effects • The chemicals act on the same target organ and their effects add together. (Usually substances with similar effects.) Eg. Many solvents, such as toluene and methyl ethyl ketone, act on the same target organ and cause narcosis Synergistic Effects • The effect of the combination is greater than the sum of the individual effects. Eg. Asbestos dust and cigarette smoke together result in a greatly increased incidence of lung cancer. The effect is multiplicative Potentiation Effects • Potentiation occurs when one substance does not have a toxic effect on a certain organ or system but when added to another chemical makes that chemical much more toxic. Eg. Isopropanol is not hepatotoxic, but when administered with carbon tetrachloride, the hepatotoxicity of carbon tetrachloride is much greater than that when it is given alone. Antagonisitc Effects • The effect of the combination is less than the individual effects. This is the basis of many drug antidotes. Eg. Selenium reduces the toxicity of mercury – forms a complex with protein. Eg. Zinc reduces testicular damage from cadmium exposure . Types of Antagonism • There are 4 major types: • Functional Antagonism: • Occurs when two chemicals counterbalance each other by producing opposite effects on the same physiologic function. • Chemical Antagonism: (Inactivation) • Chemical reaction between two compounds that produces a less toxic product. • Dispositional Antagonism: • Occurs when the absorption, biotransformation, distribution or excretion of a chemical is altered so that the concentration and / or duration of the chemical at the target organ is diminished. • Receptor Antagonism: (Blockers) • Occurs when two chemicals that bind to the same receptor produce less of an effect when given together than the addition of their separate effects or when one chemical antagonizes the effect of the second chemical. TOXICITY TESTING METHODS Assessing Toxicity To ascertain the toxicity of a substance we can use: Literature searching Analogy Acute toxicity tests (exposure for 24hrs, 1 month, 3 months) Mutagenicity tests Carcinogenicity tests Reproductive/developmental toxicity tests Behavioural toxicity tests Daily examination includes: Signs of intoxication Lethargy Behavioral modifications Food consumption Acute Toxicity Tests Eyes Eye irritation Usually use rabbits. (why?) A drop of of material is instilled in each eye and one eye washed thoroughly after 1 minute. Chronic Toxicity Testing Dosing is typically conducted from 90 days 2 years and is generally through feeding and/or inhalation. Chronic testing regimes allow the investigation of the effects of life time exposure, therefore the highest experimental dose used should not cause premature death. Chronic Testing Criteria of Response 1. Pathology in organs or tissues 2. Growth rate changes 3. Organ weight (oedema, hypertrophy) 4. Physiological function tests 5. Biochemical studies 6. Behavioural studies 7. Reproductive effects 8. Teratogenic effects 9. Carcinogenicity Criteria of Response Short-Term Tests for Mutagenicity and Carcinogenicity Ames Test Uses mutant strain of bacterium (Salmonella typhimurium). Engineered strain cannot make its own histidine (an amino acid). Presence of mutagen enhances ‘back mutation’ to wild type, which can make its own histidine from other amino acids. If the substance is a mutagen the colonies can grow on the histidine deficient medium. Colonies are counted. If mutagenesis does not occur the bacterial test culture cannot reproduce, as there is insufficient histidine. No colonies are produced. May add liver extract to provide mammalian enzyme systems for metabolic activation. Limitations of Ames Test Will not detect carcinogens with mode of action not attributable to direct DNA damage. Will not detect chromosome deletions. Highly toxic compounds may poison system, masking carcinogenic effects. Some non-carcinogens may be bacterial mutagens. OCCUPATIONAL HYGIENE Hazard Actual / potential sources of harm to health, safety or wellbeing of exposed individuals. Risk Likelihood / probability that harm will occur as a result of exposure. Types of Hazards • Environmental health hazards • Physical (noise, heat, light, radiation) • Chemical (gases, vapors, mists, dusts, fumes) • Biological (micro-organisms) • Electrical safety hazards • Defective wiring • Structural safety hazards • Moving machinery • Ergonomic hazards • Workplace design, man-machine interaction • Psycho-social hazards • Shift work, bullying. Routes of entry Respiratory System Orally Skin Placenta . Main route of entry: • Respiratory system: • Aerosols (airborne particulates) • Dusts • Mists • Fumes • Smoke • Gases & Vapors • Gas • Vapor . Pillars of occupational hygiene Anticipation • Vital skill – requires experience • Advice through SDSs, literature, peers • Recognition • Knowing the hazards and processes which may affect health • Evaluation • Measuring exposures • Comparison against standards • Evaluation of risk • Control • Providing hazard control . Limitations of hygiene standard • Not fine lines between healthy and unhealthy work environments • Should not be used as a scale of relative toxicity • Should not be used for nonoccupational exposures • Should not be used for extended and uninterrupted exposures TLV-TWA Threshold Limit Value – Time Weighted Average TWA concentration for a typical 8- hour workday, 5 days a week (40hr work week) to which nearly all workers may be repeatedly exposed, day after day, for a working lifetime without adverse effect . TLV-STEL Threshold Limit Value – Short Term Exposure Limit A STEL is defined as a 15 minute time-weighted average which should not be exceeded at any time during the work day, even if the 8-hour TWA is within the TLV-TWA Exposures above the TLV-TWA up to the STEL should not be longer than 15 minutes and should not occur more than 4 times a day There should be at least 60 minutes between successive exposures in this range. An averaging period other than 15 minutes may be recommended when this is warranted by observed biological effects . TLV-C Threshold Limit Value – Ceiling Value The concentration which should not be exceeded during any part of the working exposure . Sampling Strategies Factors Influencing Sampling Strategy Purpose of Measurement (aims and objectives of monitoring) Health risk assessment Compliance with OELs Evaluation of controls Compliance with legislation Data for epidemiological studies Validation/comparison of methods Factors Influencing Strategy Design for Air Monitoring . Sources of Variability in Air Concentration Variability in workplace, work activities, timing of processes, external factors such as draughts, wind direction, etc. Worker exposure is from 2 sources: General background Specific to tasks performed Concentrations of pollutants subject to temporal (over time) and spatial variation - likely to be in a constant state of flux e.g. Change in process, sources, ventilation, climate, even seasonal changes. 3. Variables in getting measurements representative of exposure Location of sampler Personal sampling To truly represent breathing zone and personal exposure Static sampling used: To check performance of controls As a surrogate of personal exposure In identifying and measuring sources of contaminants and defining areas of unacceptable contamination In assessing trends in baseline concentration Where continuous monitoring is required . 4. Selection of Monitoring Equipment Consider technical aspects: Specificity (for that particular chemical) Sensitivity (smallest change detectable) Accuracy (how closely measures true value) Precision (reproducibility) Recovery efficiency Transport loss/sample stability Environmental Monitoring of Air Contaminants Involves taking a sample of environmental air over a known duration and then analysing the sample for chemical composition and concentration of contaminants. Environmental monitoring uses - Personal sampling – in breathing zone Static sampling - of ambient air in vicinity of work Snap or grab sampling – provides a snapshot in time Continuous monitoring – shows peaks and troughs in concentration throughout shift. Continuous integrated sampling – provides a value for average exposure during shift. Types of Sampling Grab Short term Long term Continuous Bulk Sampling Taken and analysed for identification purposes. Not possible to relate the results to the airborne concentrations. Can be use to show spread of contamination. Particle size Total inhalable dust is the fraction of airborne material which enters the nose and mouth during breathing and is therefore liable to deposition anywhere in the respiratory tract. The particle sizes of total inhalable dust are up to 100 microns. Respirable dust is that fraction that penetrates to the deep lung where gas exchange takes place. The particle sizes of respirable dust are up to 10 microns. Elements of a Sampling System Sampling train Pump Filter Sampling Head / Size Separator. Useful Features of Pumps Automatic flow control Pulsation dampening Capacity to operate at a reasonable backpressure Reasonable flow range Good battery capacity Intrinsically safety Key Issues Maintenance Must be performed regularly and recorded for each pump Check automatic flow compensation and internal inline filters Battery charge Nickel-Cadmium batteries prone to “memory effect”. Cycling of pumps can overcome effect in most cases Use of appropriate chargers Internal flowmeters Not accurate due to design flaw (one end must be open to atmosphere) Direct Reading Instruments Many different instruments Many different operating principles including: Electrochemical Photoionization Flame ionization Chem-iluminescence Colorimetric Heat of combustion Gas chromatography Many different gases & vapour From relatively simple to complex Uses of Direct Reading Instruments • Where immediate data is needed • Personal exposure monitoring • Help develop comprehensive evaluation programs • Evaluate effectiveness of controls • Emergency response • Confined spaces For difficult to sample chemicals • Multi sensors • Multi alarms • Stationary installations • Fit testing of respirators • Video monitoring Advantages Direct reading Continuous operation Multi alarms Multi sensors TWA, STEL & Peaks Data logging Limitations Often costly to purchase Need for frequent and regular calibration Lack of specificity Effect of interferences Cross sensitivity Need for intrinsically safe instruments in many places Battery life Sensors Finite life, poisoning, lack of range A Strategy for Monitoring Which hazardous agents are believed to be present in the work environment, including byproducts? What is the nature of the work process and how is the hazardous agent used or generated and dispersed through the workplace atmosphere? What variations are there in individual work practices? Which routes of entry into the body are likely to be involved? Where should samples be taken from? When should samples be collected and over what time period? How many samples should be collected? What sampling and analytical methods are appropriate? What factors need to be considered when interpreting the sampling results? How do we measure hazards and assess risks to health in the workplace? Quantify hazards using: Dose Measurement - Environmental Monitoring (Hygiene) - Biological Monitoring (Hygiene & Occupational Health) Effect Measurement - Health Monitoring (Occupational Health) Compare to “standards” to assess risk. Interpret in terms of task and duration of exposure. Requires knowledge of the work process, substances in use, limitations of sampling and analytical equipment and safety culture. Monitoring Vapors and Gases Types of Sampling strategies Personal sampling Device work by worker to measure individual exposure In breathing zone (300mm radius from nose / ears) Static sampling Ambient air in vicinity of work Fixed location (area sampling) Continuous integrated sampling Provides a value for average exposure concentration during the shift – cumulative result Not adequate for monitoring chemicals with peak / STEL standards – only records average concentration over time of sample Good method for sampling chemicals that has chronic health effects and TWA exposure standards . Snap / Grab sampling Provides a snapshot in time, usually about 5 min Useful in making initial assessment of the workplace Continuous grab sampling techniques most appropriate for monitoring chemicals that have acute effects / Peak values / STEL values Continuous monitoring Shows peaks / troughs in concentration throughout shift . Active & Passive Sampling There are two types of sampling: Active: air is drawn through the collection medium by means of a rechargeable battery operated pump Passive: relies on the passive diffusion of the contaminant into the collection medium . Occupational Hygiene vs Environmental studies Similarities Measurement of the same substances / chemicals Use of similar equipment Key difference: GOAL / INTENT Environmental Monitoring (Occupational Hygiene): Goal is to determine the potential health effects from exposure on workers Environmental Monitoring: Goal is to determine the impact on the environment and general population . Definitions – Gas & Vapours Gas- substance which is “air like’ but neither a solid or liquid at room temperature Vapour-the gaseous form of a substance which is a solid or liquid at room temperature Typical air contaminants For our purposes: Gases & Vapors - Vapor Mists Fume/ Dusts - Dust Aerosol Fibre Aerosols Includes: Dust Fume Mist Smog Smoke Nano particles Aerosol – refers to a group of liquid / solid particles suspended in a gaseous medium, 0.001 – 100μm in size Methods of analysis Organic Vapours Gas chromatography (GC) complete with a flame ionisation detection (FID) Inorganic Gases GC/thermal conductivity methods Photometric and micro-colometry Chemiluminescence Organic Particulate Matter High pressure liquid chromatography (HPLC) Infra-red (IR) or ultraviolet (UV) spectrometry Metals and their Compounds ICP (Inductively coupled plasma) Atomic Absorption (AA) Mineral Dusts Microscopy, Gravimetric analysis X-ray diffraction (XRD) Health Hazards: Gases Simple asphyxiants Chemical asphyxiants Irritants Others Metals in the workplace Specific Fume Hazards Zinc Metal fume fever Vanadium (filler wires) Highly irritant to eyes throat, and RT Cadmium (Cadmium plate and silver solder) Highly irritant to lung Possibility of chronic Effects on liver and kidney Lead (e.g. lead-base painted steel) Possible effects on blood, gut and nervous system Manganese (Manganese / Steel alloys) Possibility of acute pneumonitis and chronic effects on N.S. Usually levels are too low for such toxic effects WELDING FUME Mixtures of airborne gases and fine particles The degree of risk will depend on: the composition of the fume, the quantity of fume in the air which is breathed, the duration of exposure Metal toxicity 80 / 105 elements in the periodic table are metals Less than 30 have been shown toxic to humans Also need to consider metalloids: Arsenic Selenium Some metals are essential trace elements: Iron (constituent of haemoglobin) Cobalts (in vitamin B12) Manganese (enzyme co-factor) Chromium (insulin co-factor) Toxico-kinetics Differences in metal structure influences: Routes of Entry Distribution Accumulation Metabolism Excretion Toxico-dynamics In general toxicity results from binding to functionally important molecules e.g.: Enzymes Cell Membrane Components Can result in damage to a wide range of organs & tissues Monitoring Particulates Deposition in the respiratory tract Sedimentation Principally small particles 0.1 – 2µm diameter Interception Irregular shaped particles Impaction Very important for large particles > 10µm diameter Diffusion Only very small particulates < 0.5µm diameter Biological Monitoring What is Biological Monitoring? Biological monitoring is the measurement of a substance or its metabolite in biological material in order to provide a quantitative estimate of its uptake into the body by all routes of exposures. It is used to assess exposure by employing methods to determine the dose of a chemical agent (or metabolite) that has been absorbed into the body through the various routes of entry. Objectives of Biological Monitoring Biological monitoring attempts to measure the internal dose of a worker’s exposure to a substance Result is referenced against recognized Biological Limit Values for assessment of risk. (e.g.., Biological Exposure indices (BEIs) developed by ACGIH – see later) Main goal is to ensure current or past exposure of the worker is not a health risk Types of Biological Monitoring Biological Monitoring of Exposure Biological Monitoring of Effective Dose Biological Effects Monitoring Biological Monitoring of Susceptibility When to Collect Biological Sample? Prior to work shift During work shift End of work shift Beginning of workweek End of workweek What Has To Be Considered? Extent & rate absorption Properties of chemical Solubility in lipids & water Route of exposure Once absorbed Where distributed to Susceptibility of tissues – pH, permeability Water soluble - may be in total body water Non polar - may be in the body fat Elimination depends on: Metabolism oxidation, reduction, hydrolysis or combinations Excretion routes faecal, urinary, exhalation, perspiration & lactation May be excreted without metabolism CHOICE OF INDICATOR & TIMING IS CRITICAL Biological Half-Life Is the time required for half of a substance to be removed from the body by either a physical or chemical process Half lives vary significantly for different substances and hence the importance of sample collection times Lead in bones T1/2 = 20 years Lead in blood T1/2 = 35 - 40 days Arsenic in urine T1/2 = 1 - 2 days Mercury in urine T1/2 = 40 days Mercury in brain several years Advantages & Disadvantages Internal measure of exposure and estimates the amount of a chemical that has been absorbed into the body Includes all routes of absorption – skin, gastrointestinal tract, lungs Takes account of exposure from nonoccupational sources Takes account of individual differences in metabolism and work rates (amount of physical energy expended) Advantage: All routes of exposure assessed and provides a more accurate assessment of health risk than atmospheric monitoring Compared with environmental monitoring, a biological parameter of exposure is more directly related to adverse health effect Can: Assist with assessment of body burden Reconstruct past exposure in absence of other exposure measurements Test efficacy of PPE and engineering controls Monitor work practices Disadvantage Collection of samples may be uncomfortable, invasive and inconvenient Venepuncture (blood samples) / Urine collection Logistical considerations are required when organizing biological monitoring for an entire industry’s workforce Workforce consent needs to be obtained prior to sample collection Ethical approval required from certain institutions Provisions required for storage, transport and analysis of samples Adequate toxicological data must exist for that particular chemical in order to make sense of the result Limitations Only possible when sufficient toxicological information has been gathered on mechanism of action and/or metabolism Only of practical value when relationships between external exposure, internal dose and adverse effects are known Not useful for locally acting irritant or sensitizer exposure assessment Invasive technique such as blood collection often required Sample collection timing may be inconvenient Care must be taken to avoid contamination of specimen Does not take into account individual susceptibility as does biologicaleffect monitoring Specimen may require refrigeration or a preservative - or may deteriorate on storage Interactions may occur with medications and alcohol Individual differences in metabolism occur Baseline values may be required for optimal interpretation of results Specific techniques are limited in number . Noise assessment & control Physical Characteristics of Noise Sound Propagation • Sound is a fluctuation in pressure above and below the ambient pressure of a medium that has elasticity and viscosity. • The medium may be a solid, liquid, or gas. • Sound is also defined as the auditory sensation evoked by these oscillations in pressure For workplace noise, air is the medium. The word “noise” is often used to describe unwanted sound, but it is also often used interchangeably with sound as in “sound source” or “noise source”. Properties of Sound • Amplitude • Period • Frequency • Speed • Wavelength Period (T) is the time it takes to complete one full cycle Frequency (f) is the number of times per second a complete wave passes a point. The number of cycles per second is termed Hertz (Hz). The period and the frequency are simply related by the following equation T = 1/f (seconds) Speed (c) of sound in air is governed by density and air pressure which in turn relates to temperature and elevation above sea level. The speed of sound in air is approximately 343 m/s. Sound travels about 1 kilometre in 3 seconds. Wavelength (λ) is the length of one complete cycle, and is measured in metres (m). It is related to the frequency (f) and speed of sound (c) by: Wavelength (λ) = c/f metres Sound and noise Originates when a vibrating source causes variations in atmospheric pressure, detected by the ear & interpreted by the brain Noise is defined as unwanted / unintelligible sound Effects of Noise Exposure Hearing Loss = most important Presbycusis – hearing loss with age Types of hearing loss TTS – Temporary threshold shift PTS – Permanent threshold shift Tinnitus Acoustic trauma Acoustic shock Identifying Noise Problems Observation (listening, looking) Note sources of noise in environment Check for health effects Hearing loss – ask about TTS after finishing work Tinnitus Annoyance and stress Acoustic shock Telephone call center workers – screeching fax Measuring noise Equipment Sound level meter (SLM) Type meter (Type 1 or Type 2) Frequency ranges Area / Static noise monitoring Dosimeter Personal monitoring Factors to consider Equipment ranges Frequency weightings (A or C) Fast / Slow responses Measuring RMS / spot SPL Continuous / Impulse sound Frequency selection Octave band analysis Measuring ‘average’ sound level Equivalent continuous sound level Leq,8 hr . Noise Mapping A noise map is a reasonably accurate drawing showing the relative positions of all relative equipment in a workplace One of the first steps in a hearing conservation program Accurate measurements of noise levels obtained – the more measurements, the more accurate the noise map Connecting lines drawn between equal sound levels produce a topography . Hierarchy of Control Examples Elimination No noise in workplace Substitution Replace noisy equipment with quieter ones Engineering Controls Reduce / Eliminate noise at the source Administration Buy quiet policies Job rotation Personal Protective Equipment Appropriate hearing protection devices