The Carcinogenicity of Metals: Human risk through occupational and environmental exposure

448 Pages·2013·7.838 MB·English

by  Alan B. G. Lansdown

The Carcinogenicity of Metals
Human Risk through Occupational and Environmental Exposure
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Issues in Toxicology
Series Editors:
Professor Diana Anderson, University of Bradford, UK
1 Dr Michael D Waters, Integrated Laboratory Systems, Inc, N Carolina, USA
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7- Dr Timothy C Marrs, Edentox Associates, Kent, UK
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9 Titles in the Series:
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1 1: Hair in Toxicology: An Important Bio-Monitor
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9 2: Male-mediated Developmental Toxicity
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03 3:CytochromeP450:RoleintheMetabolismandToxicityofDrugsandother
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0. Xenobiotics
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oi: 4: Bile Acids: Toxicology and Bioactivity
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c. 6: Silver in Healthcare
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p:// 9:BiomarkersandHumanBiomonitoring,Volume1:OngoingProgramsand
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3 10:BiomarkersandHumanBiomonitoring,Volume2:SelectedBiomarkersof
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2 Current Interest
ber 11: Hormone-Disruptive Chemical Contaminants in Food
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Oct 12: Mammalian Toxicology of Insecticides
. n 31 13:TheCellularResponsetotheGenotoxicInsult:TheQuestionofThreshold
o for Genotoxic Carcinogens
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he 14:ToxicologicalEffectsofVeterinaryMedicinalProductsinHumans:Volume1
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Disorders and their Origins in Environmental Exposures
17: Chemical Toxicity Prediction: Category Formation and Read-Across
18: The Carcinogenicity of Metals: Human Risk through Occupational and
Environmental Exposure
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The Carcinogenicity of Metals
Human Risk through Occupational and
Environmental Exposure
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18 Alan B. G. Lansdown
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9 Imperial College London, UK
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n IssuesinToxicologyNo.18
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er ISSN:1757-7179
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Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposesorfor
privatestudy,criticismorreview,aspermittedundertheCopyright,DesignsandPatents
Act1988andtheCopyrightandRelatedRightsRegulations2003,thispublicationmaynot
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reproductionoutsidethetermsstatedhereshouldbesenttoTheRoyalSocietyof
Chemistryattheaddressprintedonthispage.
TheRSCisnotresponsibleforindividualopinionsexpressedinthiswork.
PublishedbyTheRoyalSocietyofChemistry,
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CambridgeCB40WF,UK
RegisteredCharityNumber207890
Forfurtherinformationseeourwebsiteatwww.rsc.org
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97 I should like to dedicate this publication to my grandchildren, Emma, Rosie,
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3 Molly, Caroline and Christopher. Whatever aspirations they may develop
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s.rs This volume is also dedicated to my wife, Veronica, who has given me loving
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htt Iacknowledgewithsinceregratitudethefruitfulconversationsandconstructive
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7- Foreword
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10. The ancient Egyptians had knowledge of the dangers of antimony, copper,
doi: crudearsenicandlead,and,inanumberofculturesinthelastthreemillennia,
g | minerals have been used as poisons. A more clearly defined role for the wide-
or
c. spreadeffectsoftheseelementsonhumanhealthandindiseasestateshasbeen
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bs.r identifiedandcharacterisedduringthelasttwocenturies.Initially,theneedfor
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n comparative epidemiology developed, conditions induced by large local ex-
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13 cessesofparticularmineralswerealsoidentifiedandcouldbeattributedtothe
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er 2 effects of this excess (arsenic in drinking water in central Europe, say). Ob-
ob servations relating to the effects of therapeutic interventions had also shown
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O thatmercuryanditssalts,goldandsilver,allusedinmannerthatwashopedto
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d o Thatwe needmany minerals invaryingamountsisclear forreasons set out
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h inearlychaptersofthisbook.Aswithvitamins,itisalsoclearthatanexcessive
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ubli intake can be harmful – and that acute and chronic toxicity may result from
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exposure to excessive intake. These exposures may occur for a number of
reasons and from varied sources, many of which have been recognised in
comparatively recent times.
Occupational disease (wrist drop in painters) was recognised as a marker of
toxicexposureandhelpedtodefinethecauseofthetoxiceffectsseen.Inaclear
historical example, mining of uranium-bearing ore in Schneeberg (Germany)
and Jachimov (Czechoslovakia) both for metals and the manufacture of ur-
aniumdyeshadbeencarriedoutforcenturiesandwasknowntobeassociated
with lung disease – both pulmonary fibrosis and carcinoma of the lung, al-
though this distinction was not evident to contemporary observers when the
link was published in 1879. The development of industry and of industrial
processestogetherwiththegradualdevelopmentofhealthcarerelatingtothose
IssuesinToxicologyNo.18
TheCarcinogenicityofMetals:HumanRiskthroughOccupationalandEnvironmentalExposure
ByAlanB.G.Lansdown
rAlanLansdown2014
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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viii Foreword
workinginindustryandbetterrecordkeepingrelatingtoworkersandthelocal
environment (an often undervalued element in identifying causality in disease
processes) made clear that industrial development has produced well-defined
problems such as the presence of organic mercury compounds in effluvia
7 (Minamata Bay).
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7- posures to levels of toxin that did not produce acute illness or evident direct
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71 toxicity, were harder to identify. Although potentially carcinogenic actions of
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97 minerals were often investigated after singular associations between occu-
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18 pations and uncommon tumours had been identified, modern methods of
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97 diagnosis and record keeping were needed to provide the means to question
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3 potential causality between exposures and common tumours. These associ-
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or causative factors in disease. Although causes may be defined in a number of
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s.rs ways, in pragmatic terms it is clear that if the elimination of a causal factor
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htt posure to minerals examined in this book. But the epidemiological approach
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1 of action that is clearly defined for it to be capable of translation between
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ed This book is a comprehensive survey of a major health concern (carcino-
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bli genesis) relating to the use of minerals. It considers all those elements about
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of carcinogenicity that is internationally adopted in regulatory circles and
which is clearly set out in initial chapters.
Sir Colin Berry
Emeritus Professor of Pathology,
Queen Mary’s College, London, UK
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10. Metals have played a decisive role in the development of human civilisations
doi: fromearliesttimes.Theyhaveshapeddevelopmentsinengineering,scienceand
g | medicine and in the past century many Nobel Laureates were founded on re-
or
c. search using metals. Marie Curie focussed her early research on the magnetic
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bs.r properties of steel but was later to perform fundamental research into the
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n arsenic-related therapy Salvarsan as one of the first effective cures for syphilis
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13 and other infections prevalent at the time. Countless other memorable con-
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er 2 tributions could be included, but whilst we accept the value of metals and
ob metalloidelementsinindustryandmedicine,sincethe1950satleast,clinicians,
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. n 3 daily use or to which humans are exposed in daily life or in occupational en-
d o vironmentsandinmedicineareentirelysafe,andthatamodicumofriskarises
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h through excessive exposure, abuse or accident.
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studies,experimentalstudiesinanimalsandinvitroexperimentsrelatingtothe
toxicity of metal and metalloid elements for which evidence of carcinogenicity
has been presented. Human carcinogenic risk is substantiated in relation to
arsenic, beryllium, thorium, chromium, radioactive elements, probably lead,
andsomenickelandcobaltcompounds,andrespirablesilica particles,butthe
carcinogenicity of iron, aluminium, titanium, tungsten, antimony, bismuth,
mercury,cis-platin,preciousmetals,andcertainrelatedcompoundsinhumans
is unresolved. The toxicity and carcinogenicity of each element is specific but
correlatespoorlywithitspositioninthePeriodicTable.Carcinogenicitydiffers
accordingtothevalencyoftheionanditsabilitytointeractwithandpenetrate
membranes in target cells and to bind, denature or induce mutations by
genotoxic or epigenetic mechanisms. The influence of lifestyle, environmental
IssuesinToxicologyNo.18
TheCarcinogenicityofMetals:HumanRiskthroughOccupationalandEnvironmentalExposure
ByAlanB.G.Lansdown
rAlanLansdown2014
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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x Preface
contaminants and human factors in the interpretation of epidemiological
studies isdiscussed.Furtherstudiesareindicatedtoinvestigatetheinteraction
between xenobiotic elements and genotype as an explanation for regional
variations in population response. The relevance of experimental studies in
9 isolation in predicting human risk through metal exposures is questioned.
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71 mutagenic and clastogenic changes, but they provide limited information on
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97 target organ susceptibility, inherent protective mechanisms within the intact
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18 body or immunomodulation.
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