職業(yè)環(huán)境與健康2全英班8年制

1、職業(yè)環(huán)境與健康Occupational Environment and Health (part 2)Prof. Wen ChenSchool of Public HealthSun Yat-sen UniversityEmail: Oct 11, 20172Lecture outline Heavy metals Lead（鉛）Mercury（汞）Organic solventsBenzene（苯）Trichloroethylene (TCE, 三氯乙烯）n-Hexane（正己烷）3 Standard atomic 207.2 Soft and malleable, with a good

2、ductility Low melting point: 327.5oC 400500 oC，Pb smoke (Pb2O) Density, absorption of radiation, sound and vibration Chemical properties (e.g. combines with nitrogen) Resists acid and corrosionProperties:Lead (Pb) poisoning4Annual production5 Lead mining Lead smelting and recycling Storage battery m

3、anufacture Transportation and communication Exterior paints Electronic manufactureOccupational exposure6 Kohl and certain herbal remedies Ingestion of food or water contaminated with lead Seawater products can contain lead if affected by nearby industrial waters The use of lead for water pipes is pr

4、oblematic in areas with soft or acidic water Dissolvedcarbon dioxide in water leads to formation of soluble lead bicarbonate Oxygenated water may similarly dissolve lead as lead(II) hydroxideEnvironmental exposure7The source of children exposure Ingestion of applied lead-based paint such as chewing

5、on old painted window sillsThe applied dry paint deteriorates, it peels, is pulverized into dust and then enters the body through hand-to-mouth contact or contaminated food and water In China, the application of yellow lead powder in heat rash treatment lotion8Distribution 90-95% long bones (largest

6、 pool, half-life of 20 years) Skin and muscles (intermediate pool) Released during osteolysis 4% brain,liver, kidneys 10% blood (90% bound to red cells Crosses placenta, fetal BBB is open9Release of lead during osteolysisPregnancy increases mobilization of lead from maternal skeleton Mobilization of

7、 lead from the skeleton during the post-natal period is larger than during pregnancyLead is released in menopausal bone lossLead levels have second peak in middle age- more in men than womenLead follows calcium into and out of bone.10Cardinal symptoms of lead intoxicationAcuteGI effectscolic, severe

8、 painsevere constipationAcute encephalopathyAcute nephropathyChildrenGrowth retardationBehavioralSymptoms Chronic toxicity CNS neurobehavioral abnormalities PNS motor neruopathy, wrist and foot dropHematologic anemia, basophilic stipplingAbdominal colic, constipation, livid faceRenal tubular damage

9、can result in chronic nephritis, gout, hypertensionReproductive toxicity high-level exposure has been shown to reduce fertility in male12Wrist dropbasophilic stipplingLead colicA form of pain that starts and stops abruptly. It occurs due to muscular contractions of a hollow tube (intestinal tract) i

10、n an attempt to relieve an obstruction by forcing content out. It may be panied by vomiting and sweating.1314Inhibition in heme synthesis pathway (early and important alterations)鉛中毒病人出現(xiàn)的異常血紅素前體化驗(yàn)所見ALA(氨基酮戊酸)升高（血、尿）卟膽原升高（尿）尿卟啉升高（尿）糞卟啉升高（尿、 血）FEP升高、ZPP升高(紅細(xì)胞)FEP-游離原卟啉游離原卟啉+Zn2+結(jié)合ZPP鋅原卟啉 琥珀酰輔酶A+甘氨酸 AL

11、A卟膽原尿卟膽原糞卟啉原Pb糞卟啉原氧化酶原卟啉亞鐵絡(luò)合酶Fe2+血紅素 珠蛋白血紅蛋白PbPb線粒體ALASALAD尿卟啉原合成酶原卟啉原脫羧酶胞質(zhì)內(nèi)co-proporphyrinogen decarboxylaseFerrochelataseProtoporphyrine IXCo-proporphyrinogen-氨基乙酰丙酸脫水酶mitochondrion urine urine or blood15Other mechanisms Binding to the sulfhydryl groups found on many enzymes Mimicking and displaci

12、ng other metals which act as cofactors in many enzymatic reaction, among the essential metals that lead interacts with are calcium, iron, and zinc.16Heme synthesis and lead toxicityPb inhibits -aminolevulinic acid dehydratase -ALA in urinePb inhibits co-proporphyrinogen decarboxylase Co-proporphyrin

13、ogen in urinePb inhibits ferrochelatase Protoporphyrine IX accumulates in RBCsFEP, ZPP tests are based on this metabolism pathway GradeCriteria(GBZ37-2002) Treatment Lead absorption Exposure history; No poisoning symptoms Examination: urine lead 0.39 mol/L Measure urine and or 0.48mol/24h; or blood

14、lead 2.41mol/L; blood lead every or diagnostic lead remove test: urine lead 1.45mol/L 3-6 month Mild Neuro-symptoms panying with digestive fort; and reach one of the following limit: After treated with a. Urine ALA 30.5mol/L or 45.8mol/L/24h; chelating agents, b. Urine Co-proporphyrinogen (+); may r

15、eturn to work. c. FEP 2.31mol/L, or ZPP2.08mol/L diagnostic lead remove test: urine lead 3.86mol/L or 4.82mol/24h With one of the following symptoms: After treated with Moderate Abdominal colic; Anemia; PNS neuropathy chelating agents, may return to work Severe With one of the following symptoms: Mu

16、st be off the Lead paralysis ; CNS neuropathy lead-exposure work Supportive therapy Diagnosis and treatment 18Treatment (chelation) CaNa2-EDTA （依地酸二鈉鈣） Succimer or DMSA （二巰基丁二酸鈉）Requires close monitoringInefficient process, typically reducing body burden only 1 - 2 %Chelating agents may not signific

17、antly reduce tissue levels, esp. in CNS19 mended lead level 0.48mol/l (10 g/dl)= elevated.0.72mol/l (15 g/dl)=substantially elevated. Notifiable level.1.20mol/l (25 g/dl)= dangerously elevated.2.20mol/l (45 g/dl) = Symptomatic.20Mercury poisoning (Hg)水銀 Three forms of mercury elemental Hg0(metallic

18、Hg) property: liquid and volatile at room temperature, aliphatic, deposit on floorinorganic (mercurous Hg1+ or mercuric Hg2+) -more toxic organic mercury -generally most toxic21 Sources of exposure Mining and smelt Amalgams: silver/gold extraction Manufacturing of thermometers and electrical switche

19、s Electrode, photograph, pharmacy Dental offices: amalgam based dental fillings Food chain - seafood Other contaminated Chinese medicine, cosmeticsAmbient WaterSedimentsEdible FishInorganic MercuryMethyl-MercuryMethyl-MercuryIn HumansBiomethylationBioaccumulationExposureDischargeBiotransformation of

20、 Mercury70%-90% of Hg is methylated23 AbsorptionElemental Inhalation of vapor 80% absorptionSkin absorption possible, GI - poorInorganic GI absorption 10% (many salts are corrosive)Organic GI absorption 90% DistributionKidney, liver, heart, CNSBinding to metallothionein (MT)Excretion: kidneyHalf lif

21、e: 60 days24 Hg0 is oxidized to Hg2+ and binds to sulfhydryl (-SH) groups of enzymes, result in inhibition of enzyme activity. Irreversibly inhibits selenium-dependent enzymes and may also inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-O-methyl transfer

22、ase.Mechanism of toxicity25Critical organ for toxicity is the brainReadily crosses the blood brain barrier and the placentaAccumulates in the brain, slowly converted to Hg2+ Although the toxicity is mediated through binding to sulfhydryl groups in critical enzymes, it is unclear if toxicity is from

23、MeHg or Hg2+Toxicity of methylmercury MeHg26 Acute toxicity mon except vapor from elemental Hg Can produce interstitial pneumonia CNS impairment: acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. Oral symptoms DermatitisHealth e

24、ffects27 Chronic toxicity more common CNS: Erethism irritability, memory loss, anxiety, psychosis, sweat, tremor, spasticity, hallucination, dementia Kidney: albuminuria, red cells in urine Stomatitis brown band in oral cavity from Hg deposition Reproductive system organic Hg Minamata diseaseHealth

25、effects (cont)28Methylmercury poisoning in Minamata bay, Japan Epidemic in the 1950s in Japan More than 100 deaths Striking incidence of congenital anomalies of exposed women Blindness (tunnel vision) Spasticity DementiaFetal Minamata syndromeGradeCriteria(GBZ37-2002) Treatment Exposure history and

26、with three of the following clinical observations: After treated withMild neurasthenis syndrome; stomatitis and gingivitis; chelators, may return tremor; urine Hg2+ to work With two of the following clinical observations: Should leave the Moderate abnormal disposition; heavy tremor; toxic agents-exp

27、osed kidney impairment work With the following symptoms: Must leave the Severe cerebellum dysiaxia; mental disorder toxic agents-exposed work Diagnosis and treatment (Chronic)30 Chelation for elemental and inorganicBAL (Sodium dimercaptosulphonate （二巰基丙磺酸鈉） for severe inorganic poisonings Use for el

28、emental is disputed DMSA (Sodium dimercaptosuccinate) more effective and less toxic Organic none appreciably remove Hg from CNS Treatment31Benzene poisoningProperties Colorless liquid Sweet odor Highly flammable Volatile Readily dissolves in organic solvents, slightly soluble in waterC6H632Extensive

29、ly used in industry because it is an excellent solvent Used in plastics, resins, nylon, and synthetic fibers, some rubbers, lubricants, dyes, detergents, drugs, pesticides Used as solvents in printing ink Starting material for synthesizing other compounds (paints, adhesives and plastics)Exposure33 B

30、enzene manufacture General environmental problems due to improper disposal, leakage from dumpsitesthis results in contaminated drinking water Exposure (cont)34Distribution Very aliphatic -readily cross to blood stream Bone marrow disposition CNSMajor route of exposure via respiratory system 35 High

31、exposure levels can cause death by CNS depression or cardiac arrhythmias Benzene concentrations of about 20,000 ppm are fatal to humans within 5 to 10 minutes Skin exposure causes dermatitis Inhalation of high concentrations may result in bronchial irritation or pulmonary edema.Others: eye redness,

32、sores, irritationHealth effects: acute toxicity36 Chronic toxicity: Hematopoietic toxicity Blood disorders of aplastic anemia (hemorrhage, purpura) and myelogenous leukemia CNS toxicity Dizziness, headache, nausea, weakness, drowsiness Others: infertility, liver and kidney injuries37Diagnosis Criter

33、ia: GBZ68-2008 History of exposure Inspection and determination of concentration at work place Clinical manifestation: symptoms, signs, laboratory examination: hemogram Grading: mostly depend on the severity of blood alterations38Treatment Acute Immediate removal of the patient from exposure, admini

34、stration of oxygen, and monitoring and treatment of cardiopulmonary status are the first considerations. There is no antidote for benzene poisoning Treatment for benzene toxicity is supportive and symptomatic39 In treating persons chronically exposed to benzene, the most important actions are to rem

35、ove the patient from the source of benzene exposure and to prevent further exposure. Improve hematopoiesis: vitamins, glucocorticoid, testosterone, Chinese medicine Treatment of aplastic anemia and leukemia According to the remedy applied by internal medicine Treatment of chronic poisoning 40A 50-ye

36、ar-old diesel mechanic has recurring nosebleeds, fatigue, and weight lossCase studyA head, ear, nose, and throat exam shows a hyperemic inflamed pharynx, bleeding gums, and pale conjunctive.The extremity exam finds numerous ecchymoses （瘀斑）and petechiae （瘀點(diǎn)）in variable stages of healing on the upper

37、and lower extremities.Hb 10.2 (14.0-18.0); hematocrit (Hct) 32.6% (44.8-52.0); red blood cells 3.32 (mm3) (4.3-6.0); white blood cells 1,500/mm3(5,000-10,000); platelets 50,000/mm3(150,000-400,000). 41Pretest What is the problem list for this patient? What is the differential diagnosis? What additio

38、nal testing would you mend? What measures would you take to manage the case and treat this patient?42Trichloroethylene (TCE) poisoningColorless solvent, volatile, non-flammableSweet odorHalf life in air = 7 days.Used as a degreaser for metal parts, as a refrigerant, used in cleaners (extract oils, f

39、ats, and greases).Highly mobile in soil, will attach to particulates and seep into groundwater.43 Route of exposure Inhalation Oral Dermal Major environmental releases Air emissions from industrial degreasers Industrial waste water44Health effectsAcute exposure CNS effects - Dizziness, headache, lig

40、ht headedness Eye, nose, and throat irritation Nausea and vomiting Exposure to large amounts may cause heart problems such as cardiac arrhythmias45 Nerve, kidney, and liver damage Animals increased liver, lung, and kidney tumors Humans probable carcinogenHealth effects (cont)Chronic exposure: 46TCE poisoning & allergic reactionsevere erythema exfoliative dermatitis 47 The dermal effects are usually the consequence of direct skin contact with concentrated solutions, but occupational exposure also involves vapor contact. Severe erythema