A case of thallium intoxication by walking in a field Forensic Science International: Reports

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Forensic toxicology

A case of thallium intoxication by walking in a field

Domenico Di Candia, Lucie Biehler-Gomez, Gaia Giordano, Cristina Cattaneo *

SezioneDiMedicinaLegale,DipartimentoDiScienzeBiomedicheperLaSalute,UniversitàDegliStudiDiMilano,Milan,Italy

ABSTRACT

Thalliumintoxicationsarearareoccurrenceinforensicsciences.Thispaperreportsacaseofchronicthallium poisoninginacouplehospitalizedinMilan,Italy,inwhichtoxicologicalanalyseswereperformedbytheInstituteof LegalMedicineofMilanontherequestoftheJudicialAuthority.Preliminaryanalysesconfirmedthepresenceof thalliuminthebloodandurinesamplesofthecouple.Afterpositiveresultswereobtainedfromthebiological samples,theJudicialAuthoritylearnedthatthesonofthecoupleusedthalliumpowderillegallyinhisfieldandthat thefatherhelpedhissoninthatfieldalmosteveryday.Therefore,theJudicialAuthoritysuspectedthatthemanhad accidentallycontaminatedthehouseenvironment,thusintoxicatinghiswife.Consequently,theyrequestedthe seizingofmultipleitemsfromtheirresidencytoverifythishypothesis.Eachobjectwassampledinternally(content orinternalsurface)andexternally(surfaceofthecontainer)andtheconcentrationsofthalliumwereevaluatedusing ICP-MSanalyses.Positiveresultsofitemsindicateathalliumcontaminationcausedbyanexternalvector.Indeed, theysuggestthatnoneoftheelementsanalyzedwasthecontaminantresponsiblefortheintoxicationbutthe examinationofthesolesoftheman’sshoesarguedinfavorofanexternalcontamination(theson’sfield),suggesting thathewastheaccidentalmeanoftransportationoftheheavymetalintothehouse.Thispaperpresentsararecaseof chronicthalliumintoxicationinadomesticsettingwherecontaminationoccurredfromanillegalusageofthallium inafield.

ARTICLE INFO

Keywords:

Thalliumpoisoning Toxicologicalanalysis

Inductivelycoupledplasmamassspectrometry analysis

ICP-MSanalysis Chronicintoxication Accidentalcontamination

1. Introduction

Heavymetalsarecompoundsthatarenormallypresentinnature[1].

Their toxicitycan give rise toimportantmorbidity andmortality in humans both in cases of acute and chronic exposures. The clinical diagnosis of heavy metalpoisoning can be delayed due tothewide spectrumof symptomsandthedifficultidentificationof some heavy metalsbecauseoftheircolorless,odorlessandtastelessfeatures[2–7].

Examplesofheavymetalsthatsatisfythecharacteristicsdescribedabove includeantimony,arsenic,chromium,lead,mercuryandthallium.

Thallium salts (mainly sulfates) arestill used as insecticidesand rodenticides,althoughitisbannedintheUnitedStatesofAmerica,Italy andothercountries[5,8,9].Theseproductshavebeenresponsiblefor intentional poisoning eventsas well asaccidental contaminations of agricultural food products, mainly grain and rice [10]. Thallium poisoning can be accidental, criminal, suicidal, occupational or therapeutic[8,11–14].

Inthepresentpaper,theauthorsreportacaseofchronicthallium poisoningofacouple,broughttotheInstituteofLegalMedicineofMilan andinvestigatedbytheJudicialAuthority.Theaimofthetoxicological analysesperformedwastoverifythehypothesisoftheJudicialAuthority, namely,thatthemanhadbeenaccidentallyintoxicatedintheson’sfield

(wherepowderofthalliumwasusedasinsecticideandrodenticide)and thenaccidentallycontaminatedthehouseenvironmentandhiswife.

2. Materialandmethods 2.1. Circumstantialdata

Thispaperreportsthecaseofamarriedcouple,whowerebroughtto theEmergencyRoomofahospitalinMilan,followingtheonsetofvarious symptomsincludingnausea,abdominalpainandalopecia.Infact,the couplewenttothehospitalthreetimesinthecourseofasinglemonth;the lasttime,thedoctorsdecidedtohospitalizethemsuspectingapoisoning, given the aggravation of their symptoms. To verify the diagnosis, biologicalsamplesof thecouple(specifically,blood andurine) were analyzed.

2.2. Material

Biologicalsamples(bloodandurineofthecouple)wereanalyzedto verifythehypothesis(basedonthesymptoms)ofthalliumintoxication.

Urinesampleswerecreatininecorrected,becausecreatinineisanindexof renalfunctionandheavymetalscausekidneymalfunction.Giventhe

* Correspondingauthorat:SezionediMedicinaLegale,DipartimentodiScienzeBiomedicheperlaSalute,UniversitàdegliStudidiMilano,ViaLuigiMangiagalli37, 20133Milan,Italy.

E-mailaddress:cristina.cattaneo@unimi.it(C.Cattaneo).

http://doi.org/10.1016/j.fsir.2020.100102

Received16March2020;Receivedinrevisedform4May2020;Accepted4May2020 Availableonline14May2020

ForensicScienceInternational:Reports2(2020)100102

ContentslistsavailableatScienceDirect

Forensic Science International: Reports

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positiveresultsobtainedfrombiologicalsamples,theJudicialAuthority wasalertedbythehospitaltoinvestigatethemeanofcontaminationof thecouple.Forthisreason,objectsandfoodwereseizedfromthehouseof thecouple(listedinTable1).

Theexternalwashingofitems(i.e.whenthesurfaceofanitemcannot be sampled, toxicological analyses are performed after the external washingoftheitems),externalandinternalsurfacesandthecontentsof differentitemsofthehousewereinvestigated,aslistedinTable1.

2.3. Methods

Toxicologicalanalyseswereperformedonbiologicalsamplesandon differentitemsofthehouse(i.e.externalwashing,externalandinternal surfaces,contents),aslistedinTable1.

Thesamplesweremineralized inmicrowavewith6mLofHNO3 Ultrapurand2mLofH2O2UltrarexII[15].Thepreliminaryanalyses wereperformedinsemiquantitativemodeusingtheAgilentICP MS 7500 series instrumentation and automatic sampler at Asx-510 Autosampler.

2.4. Validationdata

Adosageoftheconcentrationsofthallium wasperformedonall elementswhichtestedpositive.Forthispurpose,acalibrationlinewas preparedusingastandardsolution(BackerInstra)ataconcentrationof 10ppm.Appropriatedilutions of thissolutionwere carriedoutand differentsampleswerepreparedinordertosetup6calibrationpoints ofa concentration of0.1–0.2–0.5–1–2–4ppb.A solution of yttrium (BackerInstra)ataconcentrationof10ppbwasused asaninternal standard.

MethodDetectionLimit(MDL)wascalculatedfromthreetimesthe standarddeviationof10externalmeasurementsofunspikedsamples.The endogenous content in the unspiked samples was subtracted before determiningaccuracyandprecision.Foraccuracy,therecoveryofsix preparationsspikedatdifferentconcentrations(0.1–0.2–0.5–1–2–4ppb) was maintained in a range between 90%–110%, thus meeting the acceptancecriteriaforaccuracy(Table2).Thesamerequirementswere metincalculatingprecision(repeatability)forsixpreparationsspikedat different concentrations meeting the % Relative Standard Deviation (RSD)criteriawithavalue20%(Table3).

LimitofDetection(LOD)forthalliumwascalculatedandevaluatedto be less than 25ppb. In order to evaluate the ruggedness, a second operator,onadifferentday,preparedandanalyzedsixsamplesspikedat differentconcentrationswithfreshlymadesolutions.Ruggednesswas calculatedasoperator/daytooperator/dayprecisionchangeinthemean.

Fortheelementintopic,thesecondanalyst/daymeanforallsixsamples waswithin16%ofthemeanresultofthepreviousdayandfirstanalyst.

The%RSDforall12preparationswas20%.

Stabilitywascalculatedbyrunningthesixspikedsolutionsmadeby the second analyst after storing them at room temperature for approximately 48h. Concentrations were calculated, and the mean valueswerecomparedtothesamplespreviouslyanalyzedinorderto establishsolutionstabilityofthespikedsamples.Themeanchangewas maintained within 20% from initial results and the solutions was thereforeconsideredasstable.

Specificitywasassessedbyquantifyingthespikedsamplesagainstthe calibrationstandardsolutionandmeetingtheaccuracyrequirements.

Table1

ItemstestedforpresenceofThallium–includeamountsdetected.

Sample Positivity Thallium

concentration

Man’sblood Thallium 56.5ng/mL

Woman’sblood Thallium 16.2ng/mL

Man’surine Thallium 329.7ng/gof

creatinine

Woman’surine Thallium 168.0ng/gof

creatinine Externalwashingofsugarcontainer Thallium 3.7ng/mL Externalwashingofbicarbonatecontainer Thallium 15.4ng/mL Externalwashingofbiscuitbox Thallium 6.2ng/mL Filterofthevacuumcleaner Thallium 232.1ng/g Externalwashingofornament1 Thallium 34.7ng/mL Externalwashingofornament2 Thallium 21.2ng/mL Externalwashingofornament3 Thallium 7.4ng/mL Externalwashingmeasuringcup3 Thallium 12.6ng/mL Externalwashingofthecoffeebox Thallium 1.2ng/mL

Surfaceofthesoap Thallium 18.7ng/g

Externalwashingofthetoothpastetube Thallium 8.8ng/mL Externalwashingofthesolesoftheman’s

shoes

Thallium 1440ng/mL

Negative results: sugar; bicarbonate; wine vinegar; liquid coffee; crackers;

biscuits;wine;packagingofthedishwashingdetergent;dishwashingdetergent;

externalwashingofwinebottle;externalwashingofhypodermicsyringe1and2;

measuringcup1and2;finesalt;bigsalt;pepper;insecticide;potatopeel;insideof potato;rice;pasta;coffeepowder;surfaceofbread;insideofbread;chocolates;

candies;candypaper;insideofthesoap;insideofthetoothpaste;bathfoam;

washingofthecontainerofthebathfoam;Washingofthesolesofthewoman’s shoes.

Table2

Theacceptancecriteriaforaccuracy.

Certifiedvalue(ppb) Measure1 Recovery% Measure2 Recovery% Measure3 Recovery%

0.1 0.103 103 0.098 98 0.101 101

0.2 0.201 101 0.198 99 0.203 101.5

0.5 0.497 99.4 0.507 101 0.501 100

1 1.04 104 1.01 101 0.98 98

2 1.987 99.3 2.01 100 2.04 102

4 4.03 100.7 4.07 101.8 3.97 9.3

Table3

Sixcalibrationspointsspikedatdifferentconcentrations.

Replicates(ppb) 1 2 3 4 5 6 SD %RSD

0.1 0.0056 0.0055 0.0058 0.0055 0.0061 0.0053 0.00028 4.97

0.2 0.0074 0.0079 0.0078 0.007 0.0073 0.0075 0.000331 4.43

0.5 0.0081 0.0078 0.0084 0.008 0.0076 0.0078 0.000281 3.53

1 0.0098 0.0101 0.0099 0.01 0.0102 0.0101 0.000147 1.47

2 0.016 0.0158 0.0162 0.0161 0.0159 0.0157 0.000187 1.17

4 0.0271 0.027 0.0268 0.0269 0.0271 0.0272 0.00792 0.54

D.DiCandiaetal. FSIR2(2020)100102

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Quality control (QC), expressed as trueness, was performed by analyzingthecertifiedreferencemulti-elementsyntheticurineSERO- NORM TRACE ELEMENTS URINE L-1 (rif.210605 lotto 1011644) digestedwiththesameprotocolofthesamples.VariabilityoftheQC wasnevergreaterthan6%.

3. Results

Thetoxicologicalanalysesreportedpositiveresultsforthebiological samplesofthecoupleandfortheexternalsurfaceofdifferentitems,as detailed inTable1.Inparticular,theman’sbloodandurinesamples reported 56.5ng/mL and 329.7ng/g of thallium and creatinine, respectively. The woman’s biological samples noted 16.2ng/mL of thalliuminbloodsamplesand168.0ng/gofcreatinineinurinesamples.

Thecontentsandtheinternalandexternalsurfaceoftheitemsseized fromthehouseofthecouplewereanalyzedtoevaluatethepresenceof thalliuminthehouseenvironment.Theexternalwashingandexternal surface of the majority of the items (including the sugar container, bicarbonatecontainer,biscuitbox,vacuumcleaner,ornaments1,2and3, measuringcup3,coffeebox,surfaceofthesoap,toothpastetubeandsoles oftheman’sshoes)gavepositiveresults.Allinternalsurfacesandcontents ofitemsgavenegativeresults,whereasonlysomeexternalwashingsor surfaces werenegative(such aspackagingof dishwashingdetergent, hypodermicsyringes1and2,candywrappers,winebottle,potatopeels, surfaceofbread,containerofthebathfoam,solesofthewoman’sshoes).

Thehighestconcentrationofthallium(1440ng/mL)wasdetectedonthe solesoftheman’sshoes.

4. Discussion

After the onset of the same symptoms (including nausea, abdominal pain and alopecia) in a married couple, the doctors suspectedanintoxication.ThecouplewenttotheEmergencyRoom threetimesinamonthandtheywerehospitalizedthelasttime,after theaggravationoftheirsymptoms.Therefore,analysesonbloodand urinesampleswereperformedtodeterminewhichsubstancecaused thesymptoms.

As the results of the biological samples revealed a positivityto thallium, the JudicialAuthority suspected thatthe couple hadbeen chronicallyintoxicatedbythemetal.Asaresultofourinvestigations, chronicintoxicationwasconfirmed.Indeed,normallevelsofthalliumin bloodsamplesremainbelow8ng/mL[16],whereasafteralethaldose, levelsarereportedat1000 8000ng/mL[17].Therefore,thethallium levelsofthecouple(56.5ng/mLinbloodsamplesofthemanand16.2ng/

mLinthewoman’ssample)arehigherthanthenormallevelsofthallium andbelowthelethaldoseinserum.Urineisthemostcommonlyused sampleforthedetectionofchronicthalliumexposure[18].Thelevelsof thalliuminurineincasesofnon-exposedindividualsarebelow1.1mcg/g of creatinine (creatinine corrected) [18–21] or below 1 mcg/L (uncorrected) [21,22], while the concentration of thallium after an acute intoxication are reported at 1800–2000mcg/L [17]. Urinary thallium levels in cases of prolonged exposure to thallium due to environmentalcontamination[22,23],poisoningofapopulationthat livednearacementplant[24]orworkerspopulationexposedtothallium [19,25] report concentrations of the metal included in the ranges betweennon-exposedindividualsandacutepoisoningindividualswhich correspondstothevaluesofthecoupleunderinvestigation:3.29mcg/gof creatinineintheman’surinesampleand1.68mcg/gofcreatinineinthe woman’s urinary sample. Furthermore, the couple arrived at the EmergencyRoomwithseveresymptoms,includingnausea,abdominal pain and alopecia. These symptoms are consistent with early and intermediatestagesofthalliumpoisoning,suggestinganexposureofupto two weeks[26–32]. Therefore,given thecharacteristic symptoms of thallium poisoning presented bythe couple and thepositive results obtainedfromtheirbiologicalsamples,theJudicialAuthorityconfirmed

the chronic thallium intoxication of the couple. However, further investigationswererequestedtounderstandhowthecouplehadbeen exposedtothallium.

TheJudicialAuthoritylearnedthatthesonofthecoupleillegallyused thalliumpowderinhisfield,asrodenticideandinsecticide,andthatthe father would go to work in that field almost every day. Thus, the hypothesiswasthatthemanhadbeenintoxicatedinthefieldandthen accidentallycontaminatedthehouse,inadvertentlypoisoninghiswife.

To verify this hypothesis, toxicological analyses were requested on variousitemsofthehouseofthecoupleaswellasonthesolesoftheman’s andwoman’sshoes.

Asaresult,notallitemsresultedpositivetothallium.Infact,the internalsurfaceandthecontentsofallitemsgavenegativeresults.From theresultsobtained,itcanbeinferredthatnoneoftheitemsanalyzedwas directlyresponsibleforthepoisoning.Indeed,thepresenceofthemetal wasonlydetectedontheoutersurfaceoftheitemsoronthecontainersof thespecimenstested,suggestingthattheitemscameintocontactwith thallium solely through their external manipulation. It is therefore arguable that none of the elements inside the house acted as a contaminant,butthattheywereallcontaminatedbyanexternalsource.

Furthermore, these positive results were obtained on materials of everydayuse,suchasthesurfaceof thesoap,biscuitbox,toothpaste container(amongothers),indicatingachronicexposuretothemetal insteadofanoccasionalcontamination.

Higher levelsof thallium weredetectedin the plasma andurine samples of the man (56.5ng/mL and 329.7ng/g of thallium and creatinine,respectively)withrespecttothebiologicalanalysesofhis wife (16.2ng/mL of thallium in blood samples and 168.0ng/g of creatinineinurinesamples)suggestingthatthemanwasmoreexposedto themetalsource.Moreover,thehighestconcentrationofthalliumon itemswasdetectedunderthesolesoftheman’sshoes(1400ng/mL), whereasthesolesofwoman’sshoesgavenegativeresults.Thesolesofthe woman’s shoes were analyzed to exclude that the intoxication was deliveredfromasourcedifferentfromtheson’sfield.Indeed,giventhat thewomandidnotworkinthatfield,ifsomespecificpersonalobjectsof thewoman (such astheshoes, thatare directlyin contactwith the environment)werecontaminated,thesourceofcontaminationwouldbe differentfromtheson’sfield.Thelowerlevelsofthalliuminthebiological samplesofthewomanandthenegativeresultsobtainedonthesolesofthe woman’s shoessuggest that thesource of contamination was not a commonenvironmentofthecouple.

Consequently,thehighestconcentrationofthalliumobtainedfrom thesolesoftheman’sshoes,whichheusedtoworkinhisson’sfieldevery day,areconsistentwithasourceofcontaminationintheson’sfieldwhere thalliumpowderwasusedasinsecticideandrodenticide.Therefore,the positiveresultsobtainedsolelyontheexternalwashingorsurfaceofitems andonthesolesoftheman’sshoescorroboratethesuspicionsofthe JudicialAuthority:theman,contaminatedworkingintheson’sfield,was themeanoftransportationofthemetaltotheresidence,whichresultedin theaccidentalintoxicationofhiswife.

5. Conclusion

Thehightoxicityof thalliumisoftenassociatedwithanacuteor chronicintoxicationwithafataloutcome.Inthispaper,wereportacase of chronic intoxication of a couple, caused by environmental and accidentalintoxications,inwhichbiologicalsampleswereanalyzedwith ICP-MS analyses. The complexity and specificity of the analytical techniquessuitablefortheidentificationofthemetalrenderedthese poisonings difficult to diagnose; indeed, in the present case, the hypothesisofintoxicationwasconsideredonlyaftertheaggravationof thesymptoms.However,afterthepositivityobtainedfromthebiological samplesofthecouple,thehypothesisof intoxicationbyametalwas confirmed,allowingthedoctorstotreatthecoupleforchronicthallium intoxicationandsavethem.

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Ethicalapproval

Thisarticledoesnotcontainanystudieswithanimalsperformedby anyoftheauthors.Allproceduresperformedinstudiesinvolvinghuman participants were in accordance with the ethical standards of the institutional and/or national research committee andwith the1964 Helsinki declaration andits lateramendments orcomparableethical standards.

Informedconsent

Informed consent was obtained from all individual participants includedinthestudy.

DeclarationofCompetingInterest

Theauthorsdeclarethattheyhavenoconflictofinterest.

References

[1]D.Ibrahim,B.Froberg,A.Wolf,D.E.Rusyniak,Heavymetalpoisoning:clinical presentationsandpathophysiology,Clin.Lab.Med.26(2006)67–97,doi:http://dx.

doi.org/10.1016/j.cll.2006.02.003.

[2]R.D.Ash,M.He,Detailsofathalliumpoisoningcaserevealedbysinglehairanalysis usinglaserablationinductivelycoupledplasmamassspectrometry,ForensicSci,Int.

292(2018)224–231,doi:http://dx.doi.org/10.1016/j.forsciint.2018.10.002.

[3]D.E.Rusyniak,A.Arroyo,J.Acciani,B.Froberg,L.Kao,B.Furbee,Heavymetal poisoning:managementofintoxicationandantidotes,EXS.100(2010)365–396,doi:

http://dx.doi.org/10.1007/978-3-7643-8338-1_11.

[4]L.E.Davis,J.C.Standefer,P.M.Kornfeld,D.M.Abercrombiej,C.Butler,Acutethallium poisoning:toxicologicalandmorphologicalstudiesofthenervoussystem,Ann.

Neurol.10(1981)38–44,doi:http://dx.doi.org/10.1002/ana.410100108.

[5]R.Riyaz,S.L.Pandalai,M.Schwartz,Z.N.Kazzi,Afatalcaseofthalliumtoxicity:

challengesinmanagement,J.Med.Toxicol.9(2012)75–78,doi:http://dx.doi.org/

10.1007/s13181-012-0251-1.

[6]H.A.Chandler,G.P.R.Archbold,J.M.Gibson,P.O’Callaghan,J.N.Marks,R.J.

Pethybridge,Excretionofatoxicdoseofthallium,Clin.Chem.36(1990)1506–1509.

[7]F.Ratti,A.Facchini,E.Beck,S.Cazzaniga,S.Francesconi,C.Tedesco,A.Terrani,G.

Ciceri,R.Colombo,M.Saini,V.M.Petrolini,G.Citerio,“Familialvenoms”:athallium intoxicationcluster,IntensiveCareMed.44(2018)2298–2299,doi:http://dx.doi.

org/10.1007/s00134-018-5403-6.

[8]S.Galvàn-Arzate,A.Santamarìa,Thalliumtoxicity,Toxicol.Lett.99(1998)1–13.

[9]W.J.Meggs,R.S.Hoffman,R.D.Shih,R.S.Weisman,L.R.Goldfrank,Thallium poisoningfrommaliciouslycontaminatedfood,Clin.Toxicol.32(1994)723–730,doi:

http://dx.doi.org/10.4213/dm1210.

[10]M.Mercurio-Zappala,R.S.Hoffman,Thallium,in:R.S.Hoffman,M.A.Howland,N.A.

Lewin,L.S.Nelson,L.R.Goldfrank,N.E.Flomenbaum(Eds.),Goldfrank’SToxicol.

Emergencies,10thed.,McGrawHillEducation,NewYork,2011,pp.1364–1372.

[11]T.Xiao,F.Yang,S.Li,B.Zheng,Z.Ning,ThalliumpollutioninChina:ageo- environmentalperspective,Sci.TotalEnviron.421–422(2012)51–58,doi:http://dx.

doi.org/10.1016/j.scitotenv.2011.04.008.

[12]S.Galván-Arzate,A.Martínez,E.Medina,A.Santamaría,C.Ríos,Subchronic administrationofsublethaldosesofthalliumtorats:effectsondistributionandlipid peroxidationinbrainregions,Toxicol.Lett.116(2000)37–43,doi:http://dx.doi.org/

10.1016/S0378-4274(00)00200-9.

[13]J.L.Allsop,Thalliumpoisoning,Intern.Med.J.2(1953)144–160.

[14]D.F.Thompson,Managementofthalliumpoisoning,Clin.Toxicol.18(1981)979–

990,doi:http://dx.doi.org/10.3109/15563658108990328.

[15]N.W.Wakid,N.K.Cortas,Chemicalandatomicabsorptionmethodsforthalliumin urinecompared,Clin.Chem.30(1984)587–588.

[16]G.Zhao,M.Ding,B.Zhang,W.Lv,H.Yin,L.Zhang,Z.Ying,Q.Zhang,Clinical manifestationsandmanagementofacutethalliumpoisoning,Eur.Neurol.60(2008) 292–297,doi:http://dx.doi.org/10.1159/000157883.

[17]R.C.Baselt,Dispositionoftoxicdrugsandchemicalsinman,seventh,biochemical publications,FosterCity,California(1978).

[18]Healtheffects,in:L.S.Inc(Ed.),Toxicol.ProfileThallium,U.S.Depar,ATSDR’S ToxicologicalProfiles,1992,pp.27,doi:http://dx.doi.org/10.1201/

9781420061888_ch149.

[19]K.H.Schaller,G.Manke,H.J.Raithel,G.Bühlmeyer,M.Schmidt,H.Valentin, Investigationsofthallium-exposedworkersincementfactories,Int.Arch.Occup.

Environ.Health47(1980)223–231,doi:http://dx.doi.org/10.1007/BF00381680.

[20]U.Emers,Environmentalexposuretothallium,Sci.TotalEnviron.71(1988)285–292, doi:http://dx.doi.org/10.1016/0048-9697(88)90199-4.

[21]J.F.Staff,R.J.Cotton,N.D.Warren,J.Morton,Comparisonofurinarythalliumlevels innon-occupationallyexposedpeopleandworkers,Int.Arch.Occup.Environ.Health 87(2014)275–284,doi:http://dx.doi.org/10.1007/s00420-013-0859-8.

[22]T.Xiao,J.Guha,C.Q.Liu,B.Zheng,G.Wilson,Z.Ning,L.He,Potentialhealthriskin areasofhighnaturalconcentrationsofthalliumandimportanceofurinescreening, Appl.Geochem.22(2007)919–929,doi:http://dx.doi.org/10.1016/j.

apgeochem.2007.02.008.

[23]B.Campanella,M.Onor,A.D’Ulivo,R.Giannecchini,M.D’Orazio,R.Petrini,E.

Bramanti,Humanexposuretothalliumthroughtapwater:astudyfromValdicastello CarducciandPietrasanta(northernTuscany,Italy),Sci.TotalEnviron.548–549 (2016)33–42,doi:http://dx.doi.org/10.1016/j.scitotenv.2016.01.010.

[24]R.Dolgner,A.Brockhaus,U.Ewers,H.Wiegand,F.Majewski,H.Soddemann, Repeatedsurveillanceofexposuretothalliuminapopulationlivinginthevincinityof acementplantemittingdustcontainingthallium,Int.Arch.Occup.Environ.Health52 (1983)79–94,doi:http://dx.doi.org/10.1007/BF00380610.

[25]R.L.Marcus,Investigationofaworkingpopulationexposedtothallium,J.Soc.Occup.

Med.35(1985)4–9.

[26]A.Saha,H.G.Sadhu,A.B.Karnik,T.S.Patel,S.N.Sinha,H.N.Saiyed,Erosionofnails followingthalliumpoisoning:acasereport,Occup.Environ.Med.61(2004)640–642, doi:http://dx.doi.org/10.1136/oem.2003.009464.

[27]D.Moore,I.House,A.Dixon,G.Williams,G.Volans,J.Henry,R.A.C.Hughes,G.M.

Cochrance,P.L.Atkinsons,H.Milburn,GrandRoundsGuy’shospital-thallium poisoning,Br.Med.J.306(1993)1527–1529.

[28]J.O.Aasly,T.Norway,Thalliumintoxicationwithmetallicskindiscoloration, Neurology.68(2007)1869,doi:http://dx.doi.org/10.1212/01.

wnl.0000266596.53985.8e.

[29]I.Tromme,D.VanNeste,F.Dobbelaere,E.Al,Skinsignsinthediagnosisofthallium poisoning,Br.J.Dermatol.138(1998)321.

[30]F.AlHammouri,G.Darwazeh,A.Said,R.A.Ghosh,Acutethalliumpoisoning:seriesof tencases,J.Med.Toxicol.7(2011)306–311,doi:http://dx.doi.org/10.1007/s13181- 011-0165-3.

[31]G.DeGroot,A.N.P.VanHeijst,Toxicokineticaspectsofthalliumpoisoning.Methods oftreatmentbytoxinelimination,Sci.TotalEnviron.Sci.Publ.B.V.71(1988)411–

418,doi:http://dx.doi.org/10.1016/0048-9697(88)90213-6.

[32]O.Grunfeld,G.Hinostroza,Thalliumpoisoning,Arch.Intern.Med.114(1964)132–

138,doi:http://dx.doi.org/10.1001/archinte.1964.03860070178025.

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