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Occupational lung disorders due to metals
Prof Tony CantrellNational Institute for Occupational Health &University of the WitwatersrandJohannesburgSouth Africa
I hope that this talk will steer us away from the rigid way of thinking about toxic metals to new approaches for old
problems.
Dealing with some aspects from existing wisdom and also looking at what the future may come up with.
This presentation is not meant to form a mini reference file on the subject of metals and lung disease, but should
rather help us develop an approach to understanding what happens when we insult our lungs with metals at work and
in the environment.
Non-specific metal toxicityNon-specific metal toxicity
Metals are generally toxic in the human body, even if some are essential to our wellbeing in trace amounts
As soluble divalent cations, or in other chemical forms, they interact with susceptible sites on enzymes, proteins, active receptors, DNA, membranes etc
Who are exposed? workers – children – hobbyists – the general population
Gradually the environmental background of non-degradable toxins is building up as industrial volumes accelerate
Some specific disease entities involving the lungs include:
Irritation of the lungs, asthma, chronic bronchitis, COPD, cancers
Metal Fume Fever – cutting, smelting, galvanizing
Cadmium fume causes pneumonitis distinct from Metal Fume Fever Acute chemical pneumonitis - gold amalgum retorters inhale mercury
vapour – The ACGIH BEI for elemental mercury in urine is 35 microg Hg/litre.
– The patient was measured as excreting 11 000 microg Hg/litre. – Acute chemical pneumonitis, but died of kidney failure
Hard Metal Disease
Beryllium Disease
Uranium induced malignancies - Slimes dams and old milled dust in air Concern was old cyanide!
Lifetime [50 year] cumulative whole body dose of 1 sievert.
An additional statistical risk of developing lung cancer = 5%
Chromiun, Nickel, Vanadium
Well known to cause variety of occupational asthma and lung cancers, and other occupational diseases
Chromium: lung not the only target site septal defects, rodent ulcers, carcinoma of the tongue etc. Mechanism assumed to be via chronic irritant action [hexavalent ion]
Nickel: Respiratory sensitizer, probable lung carcinogen
Vanadium: Respiratory irritant in association with SOx and ammonia
Metal Fume FeverMetal Fume Fever
Caused by the inhalation of finely divided fume [<1 micron] Caused by the inhalation of finely divided fume [<1 micron] of some non-ferrous metalsof some non-ferrous metals
Frequently encounteredFrequently encountered
Self limiting without interventionSelf limiting without intervention
SymptomsSymptoms– Flu-like illness of short duration, metallic taste in mouth, throat Flu-like illness of short duration, metallic taste in mouth, throat
irritation and dry cough , tight chest, cold shiversirritation and dry cough , tight chest, cold shivers– Onset: 3-10 hours post exposure, resolving on its own within Onset: 3-10 hours post exposure, resolving on its own within
48 hours48 hours
Follwing an attack, a temporary period of tolerance for 1 or Follwing an attack, a temporary period of tolerance for 1 or 2 days2 days
Metal Fume FeverMetal Fume Fever
Caused by heavy exposure to finely divided ZnO dust and Caused by heavy exposure to finely divided ZnO dust and fume during dip galvanizing of hot corrugated iron sheets, fume during dip galvanizing of hot corrugated iron sheets, casting molten metal, flame cutting and weldingcasting molten metal, flame cutting and welding
Copper and magnesium fume have similar effects. Brass Copper and magnesium fume have similar effects. Brass ‘Foundrymans Ague’‘Foundrymans Ague’
Cadmium pneumonitisCadmium pneumonitis
Acute exposure at low concentrations > symptoms = MFF. Acute exposure at low concentrations > symptoms = MFF. Occupational history is critical for the differential DxOccupational history is critical for the differential Dx
Irritation of the URT with cough, irritation of the throat, Irritation of the URT with cough, irritation of the throat, metallic taste, dyspnea, chest painmetallic taste, dyspnea, chest pain
Onset may be delayed for 4-8 hoursOnset may be delayed for 4-8 hours
At higher exposure: pulmonary oedema, chemical At higher exposure: pulmonary oedema, chemical pneumonitis, GIT and fluid balance problemspneumonitis, GIT and fluid balance problems
Exposure for as little as a shift can lead to wheezing, chest Exposure for as little as a shift can lead to wheezing, chest pain, persistent cough and respiratory failure 3-7 days laterpain, persistent cough and respiratory failure 3-7 days later
Higher exposures may lead to progressive pulmonary Higher exposures may lead to progressive pulmonary fibrosis and impaired lung function. At this stage multiple fibrosis and impaired lung function. At this stage multiple organ systems will also be affectedorgan systems will also be affected
Hard Metal DiseaseHard Metal Disease
This is a chronic interstitial lung disease caused by cobalt This is a chronic interstitial lung disease caused by cobalt fume and dustfume and dust
aka - Giant cell interstitial pneumonitisaka - Giant cell interstitial pneumonitis
Affects workers exposed to cobalt fume/dust while making or Affects workers exposed to cobalt fume/dust while making or using tungsten/carbide hardened toolsusing tungsten/carbide hardened tools
Latency of 6-48 monthsLatency of 6-48 months
Present with dyspnea on exertion, cough , fatiguePresent with dyspnea on exertion, cough , fatigue
Show lung infiltrates and possibly restrictve lung function Show lung infiltrates and possibly restrictve lung function defectdefect
Hard Metal DiseaseHard Metal Disease Symptoms & FindingsSymptoms & Findings
– Chest tightness, coughChest tightness, cough– ClubbingClubbing– Diffuse, interstitial infiltratesDiffuse, interstitial infiltrates– Exertional dyspneaExertional dyspnea– Inspiratory ralesInspiratory rales– Restrictive defectRestrictive defect– Sputum productionSputum production– Weight lossWeight loss
If cobalt exposure continues, progressive fibrosis with respiratory If cobalt exposure continues, progressive fibrosis with respiratory failure may developfailure may develop
Cobalt may also > occupational asthma, bronchitis, bronchiolitis Cobalt may also > occupational asthma, bronchitis, bronchiolitis obliterans, and acute chemical pneumonitis at high cobalt obliterans, and acute chemical pneumonitis at high cobalt exposureexposure
Welding exposes the worker to metal fumes of variable Welding exposes the worker to metal fumes of variable compositioncomposition
Millions worldwide use the processMillions worldwide use the process
High temperatures up to 4000 High temperatures up to 4000 ooC produce hazardous fumes and gasesC produce hazardous fumes and gases
An Antonini An Antonini et al et al revue examined the effect of welding fume on respiratory revue examined the effect of welding fume on respiratory health [Am J Resp Hlth 2003 43:350]health [Am J Resp Hlth 2003 43:350]
Full-time welders exhibitFull-time welders exhibit– Metal fume feverMetal fume fever– Airway irritationAirway irritation– Lung function changesLung function changes– Susceptibility to lung infectionSusceptibility to lung infection– Possible increase in incidence of lung cancerPossible increase in incidence of lung cancer
But mechanisms are not clear, and further work is neededBut mechanisms are not clear, and further work is needed
Exposures associated with welding
What causes Welders’ Lung?
Iron siderosis, deposits in the lung
Manganese respiratory irritant, neurotoxic
Cr & Ni lung cancers,, septal defects, skin ulcers
Cu & Zn metal fume fever
Cd brown CdO fume, lung irritation, kidney, Ca prostate?
Lead divalent ion [Pb2+] effects, lung cancers?
Fluoride URT irritation, chronic bone disease, fluorosis
Ozone irritant, lung fibrosis
NOx acute & chronic effects on lungs
+ the effects of PPE, radiation, very hot air and high work rate
Mixed exposure at its worst!
Does lead cause lung disease?Does lead cause lung disease?
Not the usual target organ [marrow, kidneys, CNS, sperm]Not the usual target organ [marrow, kidneys, CNS, sperm]
Not a classical carcinogenNot a classical carcinogen
Yet the lung are the main portal of entry to the body. Non-Yet the lung are the main portal of entry to the body. Non-specific divalent toxicity must have some negative effects!specific divalent toxicity must have some negative effects!
The IARC have classified Pb and its compounds as The IARC have classified Pb and its compounds as probableprobable human carcinogens based on increased prevalence of lung, human carcinogens based on increased prevalence of lung, kidney and bladder tumors in workers occupationally kidney and bladder tumors in workers occupationally exposed to lead. exposed to lead. – 1 of 6 cohort studies on smelter workers showed a significant 1 of 6 cohort studies on smelter workers showed a significant
2-fold increase in lung cancer. 2-fold increase in lung cancer. – Is this playing with numbers?Is this playing with numbers?
Confounders to consider include conditions in the industry, Confounders to consider include conditions in the industry, trace contaminants [alloys, recycling] and other factorstrace contaminants [alloys, recycling] and other factors
The role of nanoparticles in the lungsThe role of nanoparticles in the lungs
EngineeredEngineered nanoparticle technology is developing fast, with the nanoparticle technology is developing fast, with the attendant production and analytical skillsattendant production and analytical skills
This has generated new interest in ultrafine particles created in This has generated new interest in ultrafine particles created in industrial processes and which can be inhaledindustrial processes and which can be inhaled
Their small size will affect retention, dwell time and fate in the Their small size will affect retention, dwell time and fate in the lungslungs
May not necessarily damage the lung itself, but small size allows them to penetrate what is normally a defensive barrier. Affects toxicity, alters possible target organs. Affects a spectrum of exposure diseases.
Nanoparticles IINanoparticles II
Some Swedish workers postulate that very small Mn particles may track up nerve fibres into the brain. But this is only one form of exposure. Normal miners also develop Mn toxicity from exposure to much larger particles.
Metallic nanoparticles in the workplace are generated at very high temperature, such as encountered in welding. This could include second stage fume formation from larger dust particles.
Exposure to this type of vapour has been shown to result in
increased heart rate, increased autonomic control in workers.
American and Swedish laboratories are working on characterizing high temperature process aerosols for distribution in the URT.
Need for new measurement methods for conceptual understanding of NP technology and its attendant hazards
Need for different methods of hygiene, control and PPE
NIOH nickel case study: not known as IDLH till now
Into the future with berylliumInto the future with beryllium
Beryllium is the second lightest metal which makes excellent Beryllium is the second lightest metal which makes excellent alloys for components in a variety of aerospace, defense and other alloys for components in a variety of aerospace, defense and other applications [Be/Cu]applications [Be/Cu]
But inhalation of beryllium dust or fumes causes But inhalation of beryllium dust or fumes causes chronic chronic beryllium disease [CBD]beryllium disease [CBD] andand lung cancerlung cancer
CBD is a rare disease characterized by diffuse interstitial CBD is a rare disease characterized by diffuse interstitial pulmonary granulomatosis. Presents with dyspnea and dry coughpulmonary granulomatosis. Presents with dyspnea and dry cough
CXR show fine granular shadows throughout the lungsCXR show fine granular shadows throughout the lungs
Compromised lung function and blood gasesCompromised lung function and blood gases
Accumulation of CD4(+) T cellsAccumulation of CD4(+) T cells
Mimics sarcoidosis and must be considered in the differential DxMimics sarcoidosis and must be considered in the differential Dx
Recent work in the Netherlands and in the USA has shown that only 5-15 % of exposed workers get interstitial disease!
The use of genomic analysis may explain why genetic and/or susceptibility variation may predispose certain individuals to CBeDisease
Silver & Sharp [Occup Env Med (2006) 48:4, 434-43] have reported that the predictive value of the HLA-DPB1-Glu69 marker for susceptibility to beryllium disease is 12%.
Not yet at the stage of clinical application, such techniques are assisting occupational medicine to enter the 21st Century in style.
The challenge to us is to keep abreast with modern technology!
A genomic micro-array showing up and down regulated genes from a typical analysis
