Occupational exposure to chemicals. Toxic and genotoxic effects

Occupationalexposure tochemicals.Toxic and genotoxic effectsLead and mercury case studyJ. Volf2012

Prologue• Every year, 168,000 EU citizens diefrom work-related accidents ordiseases and 7 million are injured inaccidents, notes the resolution, whichwas drafted by Karima Delli (Greens/EFA,FR) and adopted with 371 votes in favour,47 against and 15 abstentions.(EUDecember 2011)Source:http://www.europarl.europa.eu/news/cs/pressroom/content/20111215IPR34231/html/Reinforcing-EU-legislation-on-health-and-safety-at-workJ. Volf 3

Contents• Occupational chemical hazardidentification/assessment– Elementary basis of the toxicology (repetition)• Exposure assessment in occupational/industrialtoxicology• Occupational Healht Risk assessment• Prevention on occupational poisoning• Ethical aspects of the occupational risk analysis• Exercise – solvents, Case study II, Lead• Case study III MercuryJ. Volf 4

This Lesson Outcomes• Knowledge/information– Toxicology repetition– About occupational safetyprogram UN– The basicsoccupational/industrialtoxicology– About occupationalexposure standards andmeasurements– About representativechemical substances• Skills– Recognize thecharacteristic smell ofsome industrial solvents– Use several informationsources of MAC• Attitudes– Ethical aspectsoccupational exposure tochemicals as a part ofoccupational medicine.– Ethical aspects ofepidemiological study inoccupational medicineJ. Volf 5

Why we are talking about occupationalexposure to chemicals?• MD‘s role for patients/clients– Have to be able recognize the etiology ofdiseases – occupational risk– Participated on prevention• The MD‘s role in consultation for employ,employer, trade unions– Use nature authority for health benefits,wellbeingJ. Volf 6

MD and occupational exposure tochemicals• GP – symptoms, syndromes of suspectpoisoning /intoxications– Rare but exists– Occupational anamnesis– Preventive examination of employ• Specialist– Communication with all field of medicine– Special diagnosis and treatment ofprofessional poisoningJ. Volf 7

The repetition of toxicologyJ. Volf 8

History• Phillip von Hohenheim (1493–1541) was analchemist, physician, astrologer etc.• ‗father of toxicology‘. Of course,most of usknowhim as ―Paracelsus‖,• A title that he took late in his life that means, ―equal to or greaterthan Celsus‖, who was a Roman from the first century known for histract on medicine• “All things are poison and nothing iswithout poison, only the dose permitssomething not to be poisonous.”J. Volf 9

What is a toxin?τοξικόν toxikonThis term refers to toxic substances that areproduced naturally (nature origin)J. Volf 10

What is a toxicants?This term refers to toxic substances thatare produced by or are a by-product ofhuman made activitiesJ. Volf 12

What is toxicology?1stThe study of the nature, effects, anddetection of poisons and the treatment ofpoisoning.J. Volf 13

What is toxicology?2ndToxicology is a branch of medicine, biology,chemistry and some others (e.g.pharmacology, genetic, law) concerned withthe study of the adverse effects of chemicalson living organisms. It is the study ofsymptoms, mechanisms, treatments anddetection of poisoning, especially thepoisoning of people.See more: http://en.wikipedia.org/wiki/ToxicologyJ. Volf 14

Toxico kinetics(pharmacokinetics)– what the body does with the substance (absorption,distribution, biotransformation, excretion)Clearance – measure of the body´s ability to eliminate asubstanceBioavailability – the rate and extent to which asubstance becomes available to target placeAge- or gender- related dependency of kineticsJ. Volf15

Toxicodynamics(pharmacodynamics)-what the substance does to the body(effects and mechanisms of actions):Stochastic or non-stochastic effect(threshold)Organ-specific toxic effectAcute – sub-chronic – chronic effectDelayed effect: mutagenic, carcinogenic,teratogenic, allergenicJ. Volf16

The toxicological paradigmJ. Volf17

Xenobiotic metabolism•Phase I: oxidation, reduction,hydrolysis•Phase II: conjugation•Biotransformation via intestinalmicro-flora: reduction, deconjugationJ. Volf18

Factors influencing xenobiotic metabolismSusceptibility factorsInduction of expression of the enzyme protein(upregulation)Repression of the expression of the enzymeprotein (downregulation)Direct activation of the enzymatic functionDirect inhibition of the enzymatic functionJ. Volf19

Free radicals•Chemical entities with one or more unpairedelectrons.•Biological effects:•Reaction with virtually all molecules in living cells•Cytotoxic and genotoxic effects•Damage of cellular membranes,•Interaction with proteins,•Interaction with lipids (lipid per oxidation)•The degree of damage will depend on the balancebetween radical formation and radical inactivationJ. Volf20

Genomics• Gene sequencing, which applies various biochemical• and bioinformatics tools to study the DNA of organisms.• Genotype analysis that looks at genetic variation betweenindividuals and in populations.• Epigenetics that studies reversible changes in gene functionthat can be passed from parent to child.• Transcriptomics (or gene expression profiling) is the studyof mRNA—the intermediary step between genes and proteinsthat indicates genes that are active (as opposed to dormant orsilent).• Proteomics is the study of proteomes, which are collectionsof proteins. Proteins carry out the functions encoded bygenes.• Metabolomics is the study of the products of biologicalprocesses. Such products change in response to such thingsas nutrition, stress, and disease states.J. Volf21

Processes in the toxicologycancerogenic substancesJ. Volf 22

Chemical carcinogensTypeGenotoxic: DirectIndirectInorganic carcinogensExampleAlkylating agentsPAHs, Aromatic amines,nitroarenes, mycotoxinsNi, Cr, Cd, AsEpigenetic (nongenotoxic):CytotoxicSolid bodies, fibresTumor promotorsHormonesImmunosuppressantMitogens, proliferating agensAsbestosTCDD, DDTEstradiol, DESAzathioprine, cyclosporin APeroxisome proliferators J. Volf Phthalates, clofibrate 23

The control questions I?• What is a difference between toxic andtoxicant?• What is a toxicodynamic?• What is a toxicokinetic?• What is initiating faze in cancerdevelopment?

Occupational/industrialtoxicology/hygieneJ. Volf 25

What is occupationaltoxicology?• Occupational /industrial toxicologyincludes the effects ofindustrial/occupational toxicants onhealth of employ.• Theory:„Exposure healthy employee toknown concentration of the knownsubstances„• The field combines both regulation,research, and risk assessment.J. Volf 26

The algorithm of an industrialhygiene• Health hazard recognition.• Health hazard evaluation.• Health hazard control.• Employee education and training.• Audit of the program‘s effectiveness andupdate of the program for continuousimprovement.Source and more:http://www.aist.org/safetyfirst/Safety_Mar09.pdfJ. Volf 27

Risk Assessmentin occupational medicine• Standard and transparent process haw tomove from data to information• Legal duty for employer• A tool of the occupational diseases, andpoisons preventionJ. Volf 28

The risk-based industrialhygiene assessment• Type of hazard (chemical, physical, andbiological)• Toxicity• Quantity in use• Duration of use• Past monitoring data• Established occupational exposure models• Source and more: http://wwwgroup.slac.stanford.edu/esh/eshmanual/references/IHGuideSurvey.pdfJ. Volf 29

How to assess the risks in yourworkplace?1 Identify the hazards2 Decide who might be harmed and how3 Evaluate the risks and decide onprecautions4 Record your findings and implement them5 Review your assessment and update ifnecessaryJ. Volf 30

Occupational exposureJ. Volf 31

Occupational exposure• The exposure to potentially harmfulchemical, physical, or biological agents thatoccurs as a result of one's occupation.– Medical aspects– Legal aspectsSource: http://www.reference.md/files/D016/mD016273.htmlJ. Volf 32

Occupational exposure• Not only doses makes difference between„toxicologies―.(mg.m -3 vs µg. m -3 )• Differences exist in exposure scenario(8hours vs.24 hours, only in the adulthood)• Exposure assessment (limits TLVs,OEL,MAC) Can be individualygague.Personal protecting equipment.• Optionality ? (USA principles?)J. Volf 33

Occupational exposure routes• Inhalation– Dust (partly p.o. exposure)• Particles• Fibres– Aerosols (mist, fog)– Vapours– Gaseous• Cutaneos /skin absorptionJ. Volf 34

The particles fractions as defined inEN481 (1993)• inhalable fraction (the mass fraction of particles which canbe inhaled by nose or mouth); since there are no experimental dataon inhalable fraction of particles with an aerodynamic diameter of >100 μm, particles > 100 μm are not included in the inhalableconvention,• thoracic fraction (the mass fraction of particles that passesthe larynx); the median value of the particle size is 11.64 μm with ageometric standard deviation (GSD) of 1.5 μm. It has been shownthat 50 % of the particles in air with an aerodynamic diameter of 10μm belong to the thoracic fraction,• respirable fraction (the mass fraction of particles thatreaches the alveoli); the median value is 4.25 μm with a GSD of 1.5μm. It has been shown that 50 % of the particles with anaerodynamic diameter of 4 μm belong to the respirable fraction.J. Volf 35

Exposure charactersJ. Volf 36Source:Thomas Kensler, PhD , Bloomberg School of Public Health

Maximum AllowableConcentration (MAC)• The maximum exposure to a biologicallyactive physical or chemical agent that isallowed during an 8-hour period (aworkday) in a population of workers, orduring a 24-hour period in the generalpopulation, which does not appear tocause appreciable harm, whetherimmediate or delayed for any period, in thetarget population. (From Lewis Dictionaryof Toxicology, 1st ed) J. Volf 37

The threshold limit value(TLV)• is a level to which it is believed a worker can be exposedday after day for a working lifetime without adversehealth effects. Strictly speaking, TLV is a reserved termof the American Conference of GovernmentalIndustrial Hygienists (ACGIH).• TLVs, along with biological exposure indices (BEIs), arepublished annually by the ACGIH.• See http://www.acgih.org/home.htmJ. Volf 38

TLV („gold― standard)• Time weighted average (TLV-TWA): averageexposure on the basis of a 8h/day, 40h/weekwork schedule• Short-term exposure limit (TLV-STEL): spotexposure for a duration of 15 minutes, thatcannot be repeated more than 4 times per day• Ceiling limit (TLV-C): absolute exposure limitthat should not be exceeded at any timeJ. Volf 39

Guidance for Interpreting theCarcinogenicity Notation (US)Carcinogenicity• Goal to synthesize information to be useful topracticing industrial hygienist• 5 category system that evolves to reflectadvances in science• Exposures to carcinogens should be kept to aminimum – For A1 agents with a TLV ® and forA2 and A3 agents exposure by all routes shouldbe controlled• For agents with no designation – no human oranimal data available to assign

The example of regulation• DIRECTIVE 2008/112/EC OF THE EUROPEANPARLIAMENT AND OF THE COUNCIL of 16December 2008 amending Council Directives76/768/EEC, 88/378/EEC, 1999/13/EC and Directives2000/53/EC, 2002/96/EC and 2004/42/EC of theEuropean Parliament and of the Council in order toadapt them to Regulation (EC) No 1272/2008 onclassification, labelling and packaging of substancesand mixturesJ. Volf 41

Occupational exposureassessmentJ. Volf 42

The exposure measurementstrategy I• Qualitative (What)– technology assessment and– literature review– Qualitative analysis of occupationalenvironment• Quantitative (How much, many)– Assessment of the potential employeeexposures– Observance of OEL, MACs, TLVs, PELJ. Volf 43

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J. Volf 47NIOSH http://www.cdc.gov/niosh/docs/77-173/pdfs/77-173.pdf

The exposure tactics• Air concentration– Personal air sampling• Active• Passive– Area air sampling (active, passive)– Wipe sampling– Biological exposure test (urine, blood, alveolar air• Direct• IndirectJ. Volf 48

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Personal samplingJ. Volf 50http://www.foi.se/upload/projects/EIHH/presentations/hakan-wingfors.pdf

Working area/stationarymeasurements• Results can be used for exposure limitscomparison only with time activitiespatterns record (TLW, PEL) usually 8 hourshifts• Simple• Cheaper• Les representative for individual exposure• Norm regulate the statistics or resultsJ. Volf 51

Biological monitoring/analyses• Biological exposure indices (BEI)• Biological exposure tests CZE (BET)• Cytogenetic analysis:– Biomarker of exposure to gene-toxiccarcinogens– Biomarker of early adverse effect (reversible)J. Volf 52

The BEI ® – Definition• Biological monitoring … entailsmeasurement of the concentration of achemical determinant in the biologicalmedia of the exposed and is an indicatorof the uptake of the substance.• The BEI ® determinant can be thechemical itself; one or more metabolites;or a characteristic reversible biochemicalchange induced by the chemical.http://www.google.cz/url?sa=t&rct=j&q=biomeonitoring%20tlv&source=web&cd=1&ved=0CCQQFjAA&url=http%3A%2F%2Fwww.acgih.org%2Ftlv%2FTLV03Pres_BEI.ppt&ei=OM5DT-P_POih4gTnqsW1CA&usg=AFQjCNFlLn5Ocz1mGDZDC188B4XF80Lwxw

Guidance for Interpretingthe BEI ® Notation• Refers to existence of a Biological ExposureIndex (BEI ® ) for the agent• Biomonitoring serves as a complement toexposure assessment by air sampling• Most BEIs ® based on direct correlation to TLV ®(conc. of determinant at TLV ® exposure)• BEIs ® used as guidelines in evaluation ofpotential hazards

BET IJ. Volf 55

BET IIJ. Volf 56

Chromosomal aberrations and cancer riskThree epidemiologic studies:Nordic countries – Italy – Czech Republicfound a significant association between the numberof chromosomal aberrations in population and therisk of cancerElimination or reduction of occupational exposure istherefore very important to preventoccupationally-related neoplasmsSource: Prof. Černá presentation 2012

Control questions II?1. What inform MD result from biologicalexposure indicators/tests?2. What are differences between work areaand personal sampling?3. Why and when we use cytogeneticanalyses?4. Do you know any tests used ingonotoxicology?

Ethical aspects in theoccupational/industrial toxicologyJ. Volf 68

Specific occupational medicine„schism― to serve• Employer– Be protected againsthealth problems• occupational diseasesoccurrence– Give information• about technology• hazard substance,• concentrations in theoccupationalenvironment• etc• Employee– Is a client (or patient)– Has a right beprotected– Has a right to know– Has a right to work– Has a duty to giveinformation, samplesparticipate preventiveand periodical medicalexaminationJ. Volf 69

Occupational medical doctor• Have to protect candidates or workersagain discrimination, social and health risk• Prevent the poisoning, occupationaldisease• Have to be „fair― to employer• In any case protect medical secret –health status and susceptibility of worker• Decide …..APTUS(A)J. Volf 70

Ars medici/evidence basedmedicinehttp://www.rozmanitosti.eu/zboziJ. Volf 71

Preventive measurments inindustrial/occupationaltoxicologyJ. Volf 72

Preventive measurements• Legal tools (convention, acts, agreements)– Some hazards substances are prohibit– Some work (job) are prohibit for women• Technology– Without hazard substances– Sealing (close technology)– Ventilation• Organisation– Brakes– PPE• PromotionJ. Volf 73

World• UN• ILO International LaborOrganization/Office (1919/1946)http://www.ilo.org/global/lang--en/index.htm#a3• WHOJ. Volf 74

Introduce• International Programme on ChemicalSafety• IPCS WHOJ. Volf 75Source:WHO Geneva

USA• American Conference of GovernomentalIndustrial Hygienists (1938 /1946)• http://www.acgih.org/home.htm• Thershold Limit Values (1941)• OSHAJ. Volf 76

EU Occupational health agencyOSHA EUhttp://osha.europa.eu/enJ. Volf 77

REACHREACH is the European CommunityRegulation on chemicals and their safeuse (EC 1907/2006). It deals with theRegistration, Evaluation, Authorisation andRestriction of Chemical substances. Thelaw entered into force on 1 June 2007.More: http://ec.europa.eu/environment/chemicals/reach/reach_intro.htmJ. Volf 78

Carcinogens and Mutagens at workEU• DIRECTIVE 2004/37/EC OF THE EUROPEANPARLIAMENT AND OF THE COUNCILof 29April 2004 on the protection of workers fromthe risks related to exposure to carcinogensor mutagens at work (Sixth individualDirective within the meaning of Article 16(1)of Council Directive 89/391/EEC) (codifiedversion)• http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:229:0023:0034:EN:PDFJ. Volf 79

EU statistics• COMMISSION REGULATION (EU) No349/2011 of 11 April 2011 implementingRegulation (EC) No 1338/2008 of theEuropean Parliament and of theCouncil on Community statistics onpublic health and health and safety atwork, as regards statistics on accidentsat workJ. Volf 80

EU Directives OSH• Exposure to chemical agents and chemical safety - OSH directives• Directive 2009/161/EU - indicative occupational exposure limit values– of 17 December 2009 establishing a third list of indicative occupational exposure limit values inimplementation of Council Directive 98/24/EC and amending Commission Directive 2000/39/EC (Text withEEA relevance)• Directive 2009/148/EC - exposure to asbestos at work– of 30 November 2009 on the protection of workers from the risks related to exposure to asbestos at work(Text with EEA relevance)• Directive 2006/15/EC - indicative occupational exposure limit values– of 7 February 2006 establishing a second list of indicative occupational exposure limit values inimplementation of Council Directive 98/24/EC and amending Directives 91/322/EEC and 2000/39/EC• Directive 2004/37/EC - carcinogens or mutagens at work– of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagensat work (Sixth individual Directive within the meaning of Article 16(1) Directive 89/391/EEC)• Directive 2000/39/EC - indicative occupational exposure limit values– of 8 June 2000 establishing a first list of indicative occupational exposure limit values in implementation ofCouncil Directive 98/24/EC on the protection of the health and safety of workers from the risks related tochemical agents at work.• Directive 98/24/EC - risks related to chemical agents at work– of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agentsat work (fourteenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EEC)• Directive 91/322/EEC - indicative limit values– of 29 May 1991 on establishing indicative limit values by implementing Council Directive 80/1107/EEC onthe protection of workers from the risks related to exposure to chemical, physical and biological agents atwork.J. Volf 81

Information sources• Books• Journals• D bases• Poison (Toxicological)Control Centres• Toxicological information centres andPhone lines (call centres)J. Volf 82

Information data sources• http://epp.eurostat.ec.europa.eu/portal/page/portal/health/health_safety_workJ. Volf 83

Toxicological Databases (free)II• http://ull.chemistry.uakron.edu/erd/index.html• http://www.atsdr.cdc.gov/toxpro2.html• http://potency.berkeley.edu/cpdb.html• http://www.epa.gov/ecotox• http://ace.ace.orst.edu/info/extoxnet• http://www.epa.gov/gap-db/gapdb.htm• http://toxnet.nlm.nih.gov/• http://www.state.nj.us/health/eoh/rtkweb/rtkhsfs.htm• http://193.51.164.11/cgi/ihound/chem/ih_chem_frames.html• http://www.cdc.gov/niosh/ipcs/icstart.htmlJ. Volf 84

Toxicological Databases (free)II• http://www.inchem.org• http://www.epa.gov/iris/index.html• http://www.cdc.gov/niosh/idlh/idlh-1.html• http://www.cdc.gov/niosh/npg/pgdstart.html• http://www.osha-slc.gov/sltc/healthguidelines/index.html• http://ntp.niehs.nih.gov/• http://www.cdc.gov/niosh/pel88/npelname.html• http://solvdb.ncms.org/index.html• http://www.uvp5.univ-paris5.fr/teletox/• http://www.egora.fr/html/rechercher_htm/toxin_gp.htmJ. Volf 85

Poison centres• Czech poison centre Phone: 224 91 92 93http://www.tis-cz.cz/http://www.who.int/gho/phe/chemical_safety/phe_poison_centres_20110701.xlsJ. Volf 86

http://www.aapcc.org/dnn/default.aspxJ. Volf 87

Source of an additional information• http://www.ilocis.org/en/default.html• http://www.hse.gov.uk/risk/fivesteps.htm• http://www.atsdr.cdc.gov/training/toxmanual/pdf/module-1.pdfJ. Volf 88

International Labor Organization (ILO)Chemical Control• Occupational exposure to chemicals toxic andgenotoxic Toolkit see:http://www.ilo.org/legacy/english/protection/safework/ctrl_banding/toolkit/icct/index.htmJ. Volf 89

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Control questions III?1. Do you know effective preventivemeasure on occupational toxicology?2. Do you know the name of internationaland important national agencies foroccupational medicine/industrial hygieneor occupational health and safety?3. What do you know about poisonscentre?

ExercisesJ. Volf 92

Olfactory sens• Is very important tool in any medicine• It is more important in industrial toxicology• Olfactometrie is common use methodologyTask use the nose for recognise thecemical substance – solvent– CAVE! Protect your olfacory sens with „goodsmell practice―

The solution?Will be given after the exerciseJ. Volf 94

Exercise• There is a set of samples– A– B– C– D– EJ. Volf 95

Case studiesJ. Volf 96

Important occupational hazardouschemical substances– Lead– Mercury– Cadmium– Industrial solventsJ. Volf 97

Lead• http://www.ila-lead.org/leadinformation/lead-the-facts• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874356/pdf/bcp0053-0451.pdfJ. Volf 98

LeadOccupational exposure: battery manufacturing, lead smeltersAcute toxicity of inorganic lead:Intestinal colics, nausea, constipation, diarrhea, abdominal pain, capillaryspasm, irritation, encephalopathy, ataxiaChronic toxicity of inorganic lead:Affect hematopoetic system (micro-or normocyte anemia based on theinteraction with hemoglobin synthesis in bone marrow). GIT (abdominalpain, constipation, diarrhea),Organic lead: Central and peripheral nervous system (loss ofconcentration, impaired memory, in children negative impact onintelligence)Source: Prof. Černá presentation 2012

Lead (cont.)Kidney (nephropathy)Cardiovascular effect (?)Reproduction, carcinogenicityThe big age dependent toxic effects!!!!CAVE! Small children. (parents clothes)Plumbemia BLL 10 μg/dLTherapy: BAL, EDTAMore: http://www.websters-dictionary-online.com

Source: Prof. Černá presentation 2012Correlation between blood lead leveland effectsB-Pb mg/lEffect>150 Inhibition of -aminolevulinic aciddehydratase100-200 Impaired intellectual and cognitivedevelopment of children200-600 Increased erythrocyte protoporphyrin conc.>400 Increased urinary coproporphyrin and -ALAconcentration500-600 Chronic encephalopathy in children>800 Chronic encephalopathy in adults600-800 Peripheral neuropathy700-1000 Impaired renal function800-3000 Acute lead encephalopathy

Mercury• http://www.biomedcentral.com/content/pdf/1471-227X-10-7.pdfJ. Volf 102

Elemental mercury vapour.MercuryAcute toxicity: inhalation - rare, pneumonia, emphysema,orally – GIT problemsChronic: akrodynia, nephrotic syndrome, gingivitis, tremormercurialise, erethism, polyneuropathyMercury salts:Acute: Orally erosive effect, hemorrhagic vomiting, renaldamageChronic (see vapour)Methyl mercury:Acute: CNS effect; paresthesia, ataxia, loss of sensation,difficulties with speaking and hearing.Chronic: similar to acuteTeratogenic, mutagenic, carcinogenic effects

Cadmium•Very long biological half-life (10 – 30 y)•Occupational exposure to Cd dust or aerosols•Inhalation exposure – 40 to 50 % of inhaled Cd isabsorbed•Absorption from GIT is about 2 – 8 % (higher resorption inwomen)•Albumin-bound Cd – liver - metalothionein•Cd does not cross substantially the placenta barrier•Renal cortex is the target organSource: Prof. Černá presentation 2012

Cadmium – adverse health effectsCarcinogen for human (Class 1 according to IARC)Kidney dysfunction (proteinuria, increased excretion ofalbumins, globulins, 2 -microglobulinsOsteoporosis, interference with calcium metabolismItai-Itai disease (osteomalacia)Hypertension??Source: Prof. Černá presentation 2012

Aromatic hydrocarbonsBenzene, toluene, xyleneBenzene:According to ILO convention in 1972, the use of benzeneis prohibited if suitable substitute products are availableInhalation is dominant route of human exposureOccupational exposure: petrochemical industry, petrolstationEnvironmental exposure: ambient air, indoor air, smokingSource: Prof. Černá presentation 2012

Benzene – kinetics and health effects• Inhalation and dermal absorption,• Because of lipophilic character the highest level isin organs with the high lipid amount• Acute toxicity:•Mild form - dizziness, excitation, euphoria,headache, nausea, vomiting•Severe form – visual disturbance, shallowand rapid pulse, breathlessness, profoundCNS depression, loss of consciousness,collapseSource: Prof. Černá presentation 2012

Benzene – chronic and delayed effects•Hematopoetic disorders:•Erythropoetic system: aplastic anemia, erythroblastic myelosis, acuteerythremia•Leukopoetic system: leukopenia, leukemia, lymphocytosis•Thrombopoetic system: thrombocytopenia•Carcinogenicity (leukemia)•ImmunotoxicitySource: Prof. Černá presentation 2012

TolueneEmissions of motor vehicles, mineral- oil industry,industrial use as solvent etc.Inhalation, dermal absorptionAcute and chronic toxicity:Euphoria, irritation, narcotic effectPseudoneurasthenic syndrome (mental lability, sleepdisturbance, chronic fatiguePsychoorganic syndrome (changes in mental performance, lossof personality)Reproductive toxicitySource: Prof. Černá presentation 2012

Halogenated hydrocarbonsUse:Lipophilic compounds, mostly used as solvents:dichloromethane, trichloroethylene, trichloroethane(chloroform), tetrachloroethylene (perchlorethylene).Vinyl chloride = monomeric constituent for PVCKinetics: inhalation absorption, extensivebiotransformationSource: Prof. Černá presentation 2012

Halogenated hydrocarbonsAdverse health effects:Irritation, anesthetic effect, depressive effects on CNSDamage to parenchymal organs (liver, kidney)Mutagenicity, potential carcinogenicityReproductive and developmental toxicitySource: Prof. Černá presentation 2012

Organophosphate insecticidesLarge and well-defined class of pesticidesThe toxicity is the result of excessive stimulationof cholinergic nerves based on the ability to inhibitacetylcholinesterase.Rapid hydrolysation of acetylcholin at thepostganglionic membrane of the synapse.Organophosphates bind more tightly to theenzymes active site that does acetylcholine.Accumulation of acetylcholine at the receptorSource: Prof. Černá presentation 2012

Organophosphate insecticidesSymptoms of toxicity result from cholinesterase inhibition:Headache, giddiness, nervousness, blurred vision,weakness, nausea, cramps, diarrhea.Sweating, miosis, vomiting, cyanosis, convulsions, coma,cardiac arrhythmia, respiratory failure.Delayed neuropathyTherapy: atropineSource: Prof. Černá presentation 2012

The endJ. Volf 114