silent epidemic nriagu

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Environmental Pollution 50 (1988) 139-161

A Silent Epidemic of Environmental Metal Poisoning?

Jerome O. Nriagu

National Water Research Institute, Box 5050, Burlington,Ontario L7R 4A6, Canada

A B S T R A C T

The main objective of this paper is to prov oke and stimulate debate on thehealth effects of long-term, low-level exposure of human populations to toxicmetals. Over one bil l ion (]09) human guinea p igs are now being exposed toelevated levels of toxic metals and metal lo ids in the environment. The numberof persons suffering fr om subclinical me tal poisonin g is believed to be several

mill ion. A large portion of the cases are in developed countries but the urbanareas of developing countries have become 'hot-spots ' of met al pollution, andthe populatio ns o f such countries are particularly susceptible to environ-men tal toxins . As a g lobal problem, the potent ia l heal th effects of metal l ichazards s hould be a ma tter of public health concern, especially i f the emissionsof toxic metals into the environment continue at the current rate.

INTRODUCTION

Metals and their compoun ds are indispensable to the safety and econom y ofmost nations and have been key factors in the liberation of moderncivilization from hunger, disease and discomfort. Few, if any, of the metalsknown to mankind have not found some application in industry, and thenumber of commercial uses continues to grow with the development ofmodern science and technology. Inevitably, each industrial processgenerates wastes which must be discharged into the environment, along withthe ever growing list of new metallic compounds . It has been estimated thatthe toxicity of all the metals being released annually, into the environment,

139Environ. Pollut. 0269-7491/88/$03-50 Elsevier Applied Science Publishers Ltd, England,1988. Printed in Great Britain


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140 Jerome O. Nriagu

far exceeds the combined total toxici ty of a l l the radioact ive and organicwastes , as measu red by the q uan t i ty of water neede d to di lute such wastes tothe dr ink ing water s tand ard (Nr iagu an d Pacyna , in press) . Po l lu tan t meta ls

a re non-degrad able and the con t inu ing bui ld-up of such toxins in mankin d ' sl i fe-support systems has to be of some heal th concern.This repo rt ad vances the pro vocat iv e view that the curren t levels of toxic

meta l s in some envi ronmenta l compar tments may be h igh enough tocons t i tu te a th rea t to hu m an hea l th . Some may a rgue tha t such a propos i t ioncanno t be subs t an t i a t ed by h a r d scientific data. Nevertheless, i t isincontes t ib le tha t each envi ron men ta l comp ar tm ent has a l imi ted car ry ingcapaci ty for metal pol lut ion, and, with enough t ime, the current ra tes ofmetal inpu ts wil l beco me stressful to m any ecosystems. My p rim ary aim is toprovo ke an d s t imula te fur ther d i scuss ions on the presen t and fu ture hea l thimpl ica tions of long- te rm exposure o f man kind to e levated envi ronmen ta llevels of metals. This very pr ofo un d experiment , in which o ne bi l l ion(109 )human guinea pigs are being exposed to undue insul ts of toxic metals , hasyet to receive the scientific attention that i t clearly deserves.

S O U R C E S O F T R A C E M E TA L S IN T H E E N V I R O N M E N T

Trace metals are re leased into the enviro nm ent f rom a wide spectrum of natu-ra l and an thropogenic sources (Nr iagu , 1978; Moore and Ramamoor thy,1984; Adria no, 1986). The pr incipal anth rop og enic sources of t race metals inthe a tmosphere , however, a re smel t ing of meta l l i c o res , indus t r ia lfabr ica t ion and commerc ia l appl ica t ions of meta l s , as wel l as burn ing offossil fuels (Table 1). Le ad a nd arsenic are nota ble exceptions, the princ ipalsources of these e lements being the use of leaded gasol ine and the spraying ofarsenic pest ic ides . Metal pol lut ion in soi ls is der ived most ly f romatmospheric fa l lout , coal f ly ash and bot tom ash, urban refuse, animalwastes , and agricul tural a nd food w astes (Table 1). On the other hand, theprincipal sources of pol lutant metals in natural waters are the discharge ofdomest ic and industr ia l ( including mine and smelter) waste-waters and thedumping of sewage s ludge (Table 1) . For most metals , the order ofmagnitudes of input is soi l > water > air. Al though considerable a t tent ionhas been paid to the a tmospheric cycle of the t race e lements (see, forexample, Nr iagu and Davidson , 1986) , mu ch less has been do ne toun ders tand the fa te and effects of metal pol lut ion in soi ls and natu ral w aters .

S ince the tu rn of th i s cen tury, the ever-expanding technologica ldeve lopment has resu l ted in the consumpt ion of huge quant i t i es o f t race

meta ls (Table 2). Betw een 1930 an d 1985, the m ine pro du cti on of A1, Cr, Cu,Ni an d Z n in crease d by 114-, 18-, 5-, 35- an d 4 -fold, respectively. Th e p oin t


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A silent epidemic o f environmental me tal poisoning? 141

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TA B L E 2

Global Emissions of Trace Metals into the Atmosphere, Waterand Soi l (in 1 000 metric tonnesyr-~)a

Element Air Water Soil

Arsenic 18.8 41 82Cadm ium 7.6 9.4 22Chrom ium 30 142 896Copper 35 112 954Mercury 3.6 4.6 8'3Indium 0.02 - -Manganese 38 262 1 670Molybdenum 3.3 11 88Nickel 56 113 325Lead 332 138 796Antimony 3"5 18 26Selenium 3'8 41 41Tin 6.4 - -Thallium 5.1 - - - -Vanadium 86 12 132Zinc 132 226 1 372

a From Nriagu and Pacyna (in press).

t h a t n e e d s t o b e e m p h a s i s e d is t h a t t h e m i n e - p r o d u c e d m e t a l s w i ll u lt i m a t e l ybe was ted in the b iosphe re ; on a cum ula t iv e bas i s , the quan t i ty o f tox icmeta l s d i sper sed in th i s way i s cons ide rab le .

Tr a c e m e t a l s a r e o m n i p r e s e n t i n t h e e n v i r o n m e n t , o c c u r r i n g i n v a r y i n gcon cen t ra t io ns in a ir, bed r ock , so i l, wa te r and a ll b io log ica l ma t te r (Bowen ,1979) . In p re tech no log ic a l t imes , the cyc ling o f each t r ace m eta l w as bas ica l lya t a s t ead y s ta te and a t igh t con t ro l w as main ta ined on i ts d i s t r ibu t io n in anyg iven ecosys tem. Ca lc u la t io ns us ing the da t a in Tab le 1 s t rong ly sugges t tha tt h e a n t h r o p o g e n i c i n p u t s h a v e n o w o v e r w h e l m e d t h e n a t u r a l b i o g e o c h e m i -ca l cyc les o f t r ace meta l s in man y ecosy s tem s ( see a l so, An drea eet a l . , 1984).The impl ica t ion i s c lear : the g rea t ly inc reased c i r cu la t ion o f tox ic meta l s inso il s, a ir and wa te r, r e su l t s in the inev i tab le bu i ld - up o f such tox ins in theh u m a n f o o d c h a in . T h e i n c r e a se d e n v i r o n m e n t a l e x p o s u r e i s i m p l i c a t e d int h e w e l l - d o c u m e n t e d e l e v a t i o n s in t h e c o n c e n t r a t i o n s o f se v e ra l t ra c ee l e m e nt s i n b o d y f l ui ds a n d o rg a n s y st e m s o f c o n t e m p o r a r y p o p u l a t i o n s(Pat terson , 1980; Dra sch , 1983) . So m e of the toxic meta ls ( specifica l ly Pb, Cd,Hg , T1 and Ag) have no benef ic ia l e ff ec ts in hum ans and the re i s no k no wnh o m e o s t a s i s m e c h a n i s m f o r t h em . A n y l o n g - t e r m e x p o s u r e m a y t h e re f o re b e

e x p e c t e d t o p r o g r e s s i v e l y c a u s e m o r e s e v er e d i s r u p t i o n s i n th e n o r m a lf u n c t i o n i n g o f t h e o rg a n s y s t e m s w h e r e t h e m e t a l s a r e a c c u m u l a t i n g .


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A silent epidemic of environmental me tal poisoning? 143

S I G N S O F E N V I R O N M E N TA L M E TA L P O I S O N I N G

Curre n t envi ronm enta l l eve ls o f tox ic meta l s ra re ly produce m orbid i ty or

death in the general population. The first step in this discussion, therefore,mus t address the basic def init ion of an adverse heal th effect. M an y years ago,the Worl d H eal th Organ izat ion def ined heal th as 'a s ta te of comp letephysical , mental , and social wel l-being, and not merely the absence o f diseaseor infirm ity' (Callahan, 1977). M ore recently, Sherwin (1983) defined heal thas ' the homeostasis of the cel lular ecology, and a s ta te where there has n otbeen an inordinate loss, reversible or irreversible, of the structural and/orfunctional reserves of the body'. He defined an adverse health effect as ' thecausat ion, promotion, faci l i ta t ion, and/or exacerbat ion of a s t ructuraland/or func t iona l abnormal i ty, wi th the impl ica t ion tha t the abnormal i typro duc ed has the potent ia l of lowering the qual i ty of li fe , contr ib ut ing to adisabl ing il lness , or leading to a pr em ature death ' . I have ado pted Sherwin 'sdef ini t ion, which, by analogy with the impacts of contaminants onecosystem heal th , implies that a large segment of the 'wel l popu lat ion ' can besuffering from metal poisoning with out even real is ing it.

I t has been kno w n since ancient t imes that the sym ptoms of metal toxici tyare usual ly nonspecif ic and retrospect ive, ra ther than ear ly-warning orprospective. Alterat ions in the vi ta l s igns become m anifested only af ter theintoxicat ion process has advanced to the s tage where the homeostat icmechanisms can longer main ta in the body func t ions wi th in the acceptednormal range. Within the spectrum of possible adverse heal th effects ,envi ronm ental metal p oisoning is most l ikely to be (a) subclinical , rangingfrom ear ly lesions to n ascent c l inical diseases in which the pat ient e i ther doesnot show an y sy mpto ms or fa ils to recognise them, and (b) hypeinopenia , orin a s ta te of heal th where there has been an inordinate deplet ion of thefunctional integrity of the cell , t issue or organ.

The ear ly biological indicators of the metal interact ions w ith subcel lularbiochemical systems are usual ly e i ther metabol i tes of the system affected(porphyrinurias , for example) or represent some specif ic funct ion of thecellular system being impaired (e.g. , proteinurias). With the possibleexcep tion of lead, the curre nt level of sensit ivity of clinical tests is inade qua tefor the diag nosis o f such a subtle bi ochem ical or so-called 'no-effect' distresssyndrome.

Figure 1 i l lustra tes the con t inu um in the effects of lead poisoning, f romthose that are dis t inct ly adverse to those tha t only reduce the abi l i ty of thebod y to cope w ith other forms of toxic st ress . The far rangin g impact of Pbon haeme biosynthesis includes reduct ions in such funct ions as cel lular

energet ics , oxygen t ransport , neurotransmit ter funct ions, suppression ofhepat ic detoxif icat ion of cer ta in drugs and xenobiot ics , and impaired


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A silent epidemic of environmental m etal poisoning? 145

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b iosyn thes i s o f such imp or t an t compo unds a s 1 , 2 , 5 -d ihyd roxyv i t amin D(EPA, 1986). Manife s ta t ions o f reduc t ion in the rese rve capac i ty o f someorgan sy s tems have n o kn ow n th re sho ld and have been obse rved a t b lood P b

(PbB) conc en t ra t io ns as low as 60 #g l i t r e -1 (EPA, 1986). In sp i te o f recen tev idence to the con t ra ry, many hea l th o ff ic ia l s s t i l l app ly the ' th resho ldhea l th e ffec t ' concep t in eva lua t ing the hea l th s ign i f icance o f par t icu la rtoxici ty effects and their c l in ical management .

I t goes wi th out say ing tha t ou r u nde rs tan d in g of the hea l th effects o f long-te rm expos ure to low doses o f meta ls s ti ll has a lo t o f loose ends . Th e ac tua lfo rm of the do se- re spo nse curve w hich preva il s a t the low levels o fenv i ronmen ta l exp osu re i s ba s i ca l ly u nknow n fo r mos t me ta l s . T he re i ssome ev idence to sugges t tha t po l lu tan t meta ls have synerg is t ic tox ic i ty(Fern, 1971; Wong e t a l . , 1982) so that the r isks in the low-dose, low-rateexposu re r eg io n may be con s ide rab ly enhanced (Z e i see t a l . , 1987). Thein te rac t ive tox ic ity o f meta ls and organ ic con ta mi nan ts has ye t to beexplored in the hu m an pop ula t ion . As po ten t ia l cofac tors in o ther d iseases ,t race metals can e l ic i t their toxici ty in a disguised manner.

The impac ts o f indus t r ia l ac tiv it ies on meta l levels in the env i ron m ent hasa l ready been no ted . Th e e leva ted base line exposure to meta ls can (a) lead togross un der-e s t ima t ion of the ac tua l e ffects o f low doses ; (b ) nega te the u sua lmed ica l a s sum p t ion tha t t h e cu r r en t ' no rm a l ' exp osu re is syn on y mo us w iththe so-cal led 'no-effect ' expo sure; an d (c) great ly redu ce any m arg in o f safetytha t mig h t have ex is ted in te rms of par t icu la r meta l in tox ica t ion .

P R E VA L E N C E O F S U B C L I N I C A L E F F E C T S O F M E TA LP O I S O N IN G IN T H E G E N E R A L P O P U L AT I O N

This sect ion deals with the avai lable evidence on the ear l ies t adverse heal theffects which can entai l ser ious a l tera t ions in cel lular ecology but may notcome to c l in ica l a t ten t ion un t i l the s t ruc tura l o r func t iona l damage hasreach ed an end-stage. I t is based on the defini t ion of an adve rse heal th effectas p rev ious ly def ined . In th is connec t ion , i t shou ld be re -emphas ised tha tme dical d iagno sis is st il l bedevil led by confl ic t ing c la ims o n the s ignif icancetha t shou ld be a t tach ed to so me o f the ea r ly b io log ica l s igns o f subcl in ica lpo ison ing by meta ls . Ac tua l exper imenta l ver i f ica t ion of the long- te rmhea lth effects of low-level exp osu re to toxic metals re ma ins diff icul t (h um ansubjec ts a re ra re ly cand ida tes fo r s tudy) and expens ive . Ep idemio log ica ls tud ies usua l ly es t imate the p robab i l i ty o f hea l th e ffec ts based on thein te rp re ta t io n of exper ime nta l and s ta ti s tica l da ta . Th e researcher 's

p reconcep t ions and pred ispos i t ions , as wel l as d i ffe rences in the exper i -men ta l p ro toco ls , al l com e in to p lay in the in te rpre ta t ion of the da ta . A lso ,


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A silent epidemic of environmental metal poisoning? 147

the debate becomes no m ore rati onal wh en the key issue is econom ic benefitsversus risks of exposure to env iro nmen tal levels of trace metals. It sh ould beobvious that the following assessment of the worldwide risks of metal

poisoning is far from being universally accepted.

Lead poisoning

Environmental exposure to low levels of lead has been associated with awide range of metabolic disorders and neuropsychological deficits (NAS,1980; EPA, 1986). The well-known toxic (metabolic and cellular) effects oflead in asymp to mat ic children include (i) impa irme nts in haeme, vitamin Dand red blood cell nucleotide metabolism, (ii) perturbations of calcium

homeostasis in the hepatocytes, bone cells and brain cells, and (iii)neurologi cal damag e (Rosen, 1985; L ans do wn and Yule, 1986). Alt hou ghmany of the biochemical and neurological changes associated with leadtoxicity have been observed at PbB c oncen trat ions as low as 60 #g litre-1(Table 3), the threshold for possible medical intervention has been set at250 -30 0~g l itr e- 1 (CDC, 1985).

TABLE 3Lowest Observed Blood Lead Concentrations Associated with Lead-Induced Metabolic

Changes (Health Effects?) n Children a

Effect Blood lead concentrationwhen firs t observed

(Itg lit re- 1)

Inhibition of erythrocyte ALA-D hInhibition of vitamin D metabolic processesIQ deficitsHearing lossPerinatal changes in haeme metabolismInhibition of Py-5-N c and ALA-D activityImpairment of post-natal growth and development

(mental and physical)Elevated levels of zinc protoporphyrin in red

blood cellsIncreased levels of ALA in blood and soft tissuesChanges in electrophysiological functioning of

the nervous systemsReduction in nerve conduction velocityInhibition of globin synthesis

< 40-6040-60~60

6080-100< 100


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result in PbB concen trati ons of 200#g lit re-1 or more, is well over onebillion. Fo r example, Levin (1987) has estimat ed the number of people in theUSA exposed to drin king water with a Pb co ncent ratio n above 20 ~g litre - 1

is abo ut 42 million; it is believed tha t exposure to 20 gg lit re- 1 Pb in drinkin gwater can result in PbB concen trati ons above 150#glitre -1. Levin's

TA B L E 5

Summary of Es t imated Annual Non-Monet i sed Benef i t s of ReducingExp osu re to Le ad from 50 ~tg li tr e-1 to 20 pg litre 1 for Sam ple Yea r 1988"

Reduction in numbers(4/'people at rigk

Es t imated popula t ion exposed todr inking water exceeding proposed MCL

Children's heal th benefi tsChi ldren requi r ing medica l t rea tmentLoss of 1-2 IQ points

4 IQ points5 IQ points

Chi ldren requi r ing compensa tory educa t ionChildren at r isk of s tature decrementFoetuses at r iskIncreased r isk of haematological effects

Adult heal th benefi tsCases of hyper tens ion

(males, aged 40-59)Hear t a t t acks

(white males, aged 40 59)St rokes

(white males, aged 40-59)Deaths

(white males, aged 40-59)Reduced r i sk to pregnant women

(women, aged 15~,4 (same as foetuses))

42 millio n b

29 000230000

11 000100

2900082000

68000082400

130000

240

80

240

680000

" Table from Levin (1987).b Tota l po pul at io n served by comm unity water systems: 219 mil l ion.

estimates of the number of children, nubile women and adult males atincreased risk o f experiencing various adverse health effects due to the leadin their drinking water (Table 5) should be disconcerting to some publichealth officials. In addi tion, drink ing wate r represents only a mino r rout e o f

Pb exposure for the human po pulat ion in the United States (Mahaffey et al. ,1982).


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Mercury poisoning

There a re cur ren t ly no kn ow n b iochemica l ind ica tors o f ce l lu la r d is tress

a s soc ia t ed w i th m ercu ry po i so n ing . S c reen ing fo r ch ron ic H g po i son ing i sno t a lways feas ib le and the c l in ica l symptoms of acu te po ison ing in thegenera l popula t ion a re equ ivoca l (C la rkson , 1984) .

I t has been es t imated tha t the num be r o f person s in Japan cert if ied o rsuspec ted of hav ing Hg po ison ing is abou t 8000 (Asami , 1984). On awor ld wide scale, the nu m be r a ff licted wi th H g in to x ica t ion may be assum edto be 5 -10 t imes the nu m be r o f cases in Japan , o r app rox im ate ly 40 000 to80 000 ind iv idua ls . S ince the co ns um pt ion off i sh an d seafoods is the p r im aryexposure rou te fo r Hg (spec i f ica l ly methy lmercury) , mos t o f the s t r ickenpeople a re l ike ly to be fou nd in smal l f ish ing v i llages a rou nd the wor ld .

Arsenic poisoning

T h e m o s t i m p o r t a n t e n v i r o n m e n t a l r o u t e o f A s e x p o su r e is c o n t a m i n a t e ddr ink ing wate r, e spec ia l ly g roundwater. In genera l , As i s der ived f romnatura l sources bu t in some cases min ing ac t iv i ties have been impl ica ted( B u a t - M e n a r d et al., 1987).

There a re few, i f any, ea r ly b ioc hemica l wa rn ing s igns o f chron ic A spo i son ing an d c lini ca l symp to m s have to be u sed to m easu re the acu te hea l theffec ts . Ep idem io log ica l inves t iga t ions in man y p ar t s o f Europe , N or th andS ou th A m er ica , and A s ia h ave dem ons t r a t ed a c lo se a s soc ia t io n be tw een A sexpo sure and var ious sk in d isorders , inc lud ing sk in cancer (WH O, 1981;Pershagen, 1983).

In the mo s t de t a i l ed o f the ep idemio log ica l s tud ie s don e in Ta iw an , Tseng(1977) found a very s t rong pos i t ive cor re la t ion be tween As in take f romdr ink ing con tam ina ted w a te r, and bo th sk in cance r an d the pe r iphe ra lvascu la r d isorde r kn ow n as ' b lackfoo t ' d isease . The p reva lence ra tes fo r sk incancer, hy per p ig me nta t ion and kera tos is were ab ou t 11, 184 and 71 per 1000in the survey of 40 000 people , ou t o f the to ta l expo sed po pu la t io n o f 100 000pe r sons. W hen a d ose - r e sp on se mo de l w as app l i ed to the Ta iw an da ta andthe curve ex t rap o la ted to en v i ro nm enta l leve ls , i t was p red ic ted tha t the li fe -t ime r isk o f sk in cancer f rom dr ink ing w ate r wi th o n ly 2 pg l it re - 1 As w ouldbe 1 per 1000 (Calabrese , 1983). I f th is pre dic t ion were to ap pr ox im atereal ity, the nu m be r o f perso ns in end emic a reas a t r i sk o f con tac t in g a rsen ic -induced sk in cance r s w ou ld c l ear ly run in to h u nd re ds o f t h ousan ds . A s amat te r o f fac t , we l l over 250000 people in Chi le were exposed fo r severa ldecades to A s con cen t r a t ions in d r ink ing w a te r w h ich w e re co ns ide rab ly

h igher than the leve l known to cause sk in d isorders (WHO, 1981) . In


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A silent epidemic o f environmental meta l poisoning? 153

addi t ion, no one can say with cer ta inty that a s i tuat ion l ike that does notexist in some p ar ts of develop ing countr ies , for example, in C hina (see Buat-M e n a r d et aL, 1987). In an a rea wi th contam ina ted groun dwater, the ad ded

exposure to As f rom envi ron menta l sources wi ll fu r ther e rode the marg in ofsafety for the unaffected segment of the populat ion.

Poisoning by o ther metals

The preceding discussions have dwelt on the 'b ig four ' toxic metals ofenvi ronmenta l concern . Table 1 , however, shows tha t many o ther tox icmetals an d metal loids are a lso re leased in large quant i t ies into the differentenvi ron menta l com par tments . S ince these meta l s accumula te in mam mal iant issues , even at low exposure doses , they must represent an environmentalheal th hazard. Aluminium, for example, has been implicated as a con-foun ding factor in the aet iology of Alzheimer 's disease (Perl , 1985) . Initself , AI is not a typical 'environmental ' poison, but i ts chemistry andtoxicity are strongly influenced by the acidity of rainfall (Driscoll , 1985).Another example worth mentioning is thal l ium, which is re leased in largequant i t ies f rom cement plants , with up to 2% T1 observed in f lue dusts(Kjel ls t rom et al,, 1984) . One suspects that a s ignif icant nu mb er of personsl iving within the 'hot spots ' around cement factor ies could be adverselyaffected by this highly toxic e lement . The ear ly warnin g s igns ofT1 poison ingin the general populat ion have yet to be ascer ta ined.

I t would be a fa ta l mis take to presume tha t envi ronmenta l meta lpo isoning i s on ly a problem in deve loped countr ies . Some of the deve lopingcount r ies have become major producers of non- fe r rous meta l s , and manyindustr ies in these countr ies tend to be dir t ier and employ less s t r ingentenvi ron menta l co nt ro l measures . In fac t, the h ighest concent ra t ions of Pb inthe a tmosphere a re now be ing repor ted in the urban a reas of the deve lopingcoun tr ies (Lansd ow n an d Yule, 1986), and there is every indicat ion th at theenv iron me ntal levels of man y toxic metals will r ise s teadily in such par ts ofthe wor ld . On soc io logica l g rounds a lone , popula t ions in deve lopingcountr ies are l ikely to be more suscept ible to environmental metals as aresul t of (i) the high po pu lat io n d ensi ty and poo r hy gienic cond i t ions in thecrow ded ci ties ; (ii) the prep ond eran ce o f the grou ps co nsidered to be most a tr isk , no tab ly ch i ldren and pregna nt wom en; (iii) poo r nu t r i t iona l and hea l ths tatus; and (iv ) cons um pt ion of a h igh pro por t io n of foods grown local ly inmeta l contamina ted a reas . Other endemic hea l th problems can a l soinf luence the course and severi ty of metal toxici ty in the developing

countr ies .


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T R A C E M E TA L S AS C O N F O U N D I N G FA C TO R S I N O T H E RD I S E A S E S

In the i r work and p lay, hum an be ings a re exposed to com plex mix tures oftoxic substances a t re la tively low doses . These conta mi nan ts are n ow b eingincreas ing ly impl ica ted in the ae t io logy of a l a rge numb er o f our co mm ondiseases and ai lments. In terms of the quan t i t ies being emit ted, toxic metalsmust be cons idered as an imp or tan t cofac tor o r co nfou nder in some ofthese diseases.

Cardiovascular diseases

I t has been kno wn for a long t ime tha t a num ber of trace metal s, no tab ly Pband Cd, possess card io toxic proper t ies and can cont r ibu te to card iomy-opathy. T hese metals affect the cardiov ascular m etabol ism by act ing on theren in-angio ten s in , k i l l ik re in-k in in , adrenerg ic , and pros tag landin systems(Carmignan i et al. , 1983) . Interference in calcium-act iva ted processes ,smooth-musc le tone , essen t ia l meta l metabol i sm and damage to card iactissues can also increase the blo od pressure (EP A, 1986). Th e possible role ofmetals in cholesterol accumulat ion is unclear.

Schroeder (1965) was the first to draw attention to the possible l inkbe tween human hype r t ens ion and the concen t r a t i on o f Cd in d r ink ingwater. Since then, a number of s tudies have found s t rong correla t ionsbe tween hyper tens ion and Cd concent ra t ions in b lood and p lasma, ur ine ,kidn ey cortex an d othe r t issues (see NA S, 1979, for a go od review). Hig herincidence of cardiovascular diseases , including hypertension, has beenrepor ted in popula t ions l iv ing in a reas po l lu ted wi th C d (Hickeyet al. , 1967;No gaw a, 1981). The concen t ra t ion o f a i rborne Cd was found to be s t ronglycorrela ted with hypertensive and atherosclerot ic hear t disease in 26 largecities in the U SA (Carroll , 1966). M or e recently, Borellaet a l . (1987) foun d asignif icant posi t ive correla t ion between both systol ic and diastol ic bloodpressure levels and low envi ron men ta l exposure doses of cadmium .

The role of Pb in hum an hyp ertensio n is less equivocal , most ly due to twolarge-scale epidemiological s tudies: (a) the Bri t ish Regional Heart Studyinvolving 7735 middle-aged (4049 years old) men and (b) the SecondNa t iona l H ea l th Asses smen t and Nu t r i t i ona l Eva lua t ion Su rvey (NHA NE SII) of 10 000 representat ives of the non -inst i tut ional ised pop ulat io n of theUn ited States . These s tudies provid e highly convincing evidence for robu stand s ta t is t ical ly s ignif icant associat ion between PbB levels and increasedblood pressure in adul t m en (Pococket al. , 1984; Pirkl e et al. , 1985; Schwartz,

1986; Schwartz et al. , 1984) . The N H A N ES I I st udy found tha t t here l a t i onsh ip r ema ins s ign i f i can t a t PbB concen t r a t i ons a s l ow a s


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A silent epidemic o f environmental me tal poisoning? 15 5

60 pg l i t re - 1,imply ing tha t the re is no th res ho ld fo r the e ffec t o f Pb o n b loo dpressure . The ' no th resh o ld e ffect ' is supp or te d by s tud ies on an imals w hichcons is ten t ly f ind a s t rong pos i t ive cor re la t ion be tween hyper tens ion and

exposure to low Pb doses over re la t ively long periods (see EPA, 1986).O f the mi l l ions o f hype r t ens iv e sub jec t s w or ldw ide , how ma ny have b eenaffec ted by long- te rm expos ure to t race m eta ls in the i r env i ron me nt? Lev in(1987) es t imated tha t the redu c t ion o f Pb in d r ink ing wate r in the US A c ouldreduce the n um be r o f cases o f hyper te ns ion by 130 000 (Table 5). As sum ingtha t the wor ldw ide case load i s on ly 3 -5 t imes tha t o f the U ni ted S tates, thenu m be r o f persons th a t m ay be a ffl ic ted is es t imated to be 40000 0 to650000 . I t shou ld a lso be o f concern tha t the re may be synerg ism in thecard io tox ic i t ies o f no t on ly the t race meta ls themse lves , bu t be tween the

t r ace me ta l s and o rgan ic co n taminan t s (Mur thyet aL,

1975; Lewiset al.,

1976; Der et al . , 1976). Even if the curr ent e nv iro nm en tal levels are be low thepres sor d ose ( i.e. no t causin g a r ise in ar ter ia l pressure) , no one is sure w hatmar g in o f sa fe ty st ill ex is ts fo r the la rge n um be r o f suscep tib le ind iv idua lsbe ing sub jec ted to undue t race meta l insu l t s .

Reproductive impairments

D emograp h ic ev idence s t ron g ly sugges t s t ha t r ep rodu c t ive impa i rmen t stha t resu l t in the inab i l i ty to conce ive , spontaneous abor t ion , p rematureb i r th , low b i r th weigh t , morpholog ica l and func t iona l b i r th defec ts , andpe r ina ta l m or t a l i t y a re beco ming more f r equen t and w idesp read (N isbet an dK arch , 1983) . A b ou t 1 5% o r mo re o f N o r th A m er ican coup le s nowexperien ce som e diff iculty in conceivin g (Th om as, 1986), and in the U nitedSta tes a lone about 7 mi l l ion couples have been es t imated to be in fe r t i le(Mosher, 1980) . Es t imates (made in the USA and o ther count r ies ) o frepro duc t ive a t tem pts tha t fa il o r a re impai red , range f rom 30% to 80%, thela rge u ncer ta in ty be ing d ue to the d i ff icu lty in es tab l i sh ing the f requency ofconcep t ion f a i lu re s and ve ry ea r ly spo n taneous abo r t ions (N i sbe t andKar ch, 1983; Jack son , 1985). Th e decl ining fecu ndity has becom e a matt er ofsom e concern , espec ia l ly in deve loped count r ies .

In a r e cen t comp rehens ive r ev iew o f chemica l haza rd s to h u m anrep roduc t ion , N i sbe t and K a rch (19 83 ) conc lu ded tha t ' T he f r equen cy o fsome types o f r ep rodu c t iv e impa i rm en t ha s ch anged in time, at a r a t e m uchmo re rap id to be exp la ined by gene t ic chang es o r changes in o ther in t r ins icfac tors . .. . In som e cases , the f requency of var ious k inds o f repro duc t iveimpai rment can be assoc ia ted s ta t i s t ica l ly wi th var ious env i ronmenta lfactors ' . The y also no ted tha t in terms of dose an d effects , a c loseconco rdan ce ex is ts be tw een h u ma ns and some o f the m os t s ens it ive an ima ls .

S om e t r ace me ta l s a re n o to r ious foe to tox in s and mu s t be cons ide red a s


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one of the key 'en viro nm enta l factors' th at affect different s tages in male andfemale reprodu ct ion. Lead, for example, is associated with a wide range ofnega t ive pregnancy outcomes , inc lud ing ear ly mem bran e rup ture , low b i r th

weight , spontaneo us abor t ion , compl ica t ions dur ing p regnancy, increasedper ina ta l mor ta l ity, inh ib i ted po s tna ta l g row th and deve lopment , etc. (EPA,1986). The effects on the male reprod uct ive system include erect i ledysfunc t ion , as thenospermia , hypospermia , t e ra tospermia and changes insemen cytology (pr incipal ly sperm count , morphology and moti l i ty) (Bel land Thom as , 1980). The nu mb er of p regn ant w om en (and foetuses) in theUn ited States , es t imated to b e a t r isk of heal th effects f rom Pb in dr inkingwater a lone is c lose to 700 000 (Table 5). On the oth er h and, the nu m ber ofconcept ions by women wi th PbB above 200#gl i t re -1 i s es t imated to be

abou t 430 000 assuming tha t nub i le wom en (1 54 0 years o ld) compr ise 24%of the US A p opu la t ion and tha t 6 -7% of them are pregnant a t any g iven t ime(Levin, 1987). Co ncep t ions by w om en with PbB over 300/~g l i t re-1 nu mb erwell o ver 50 000.

Other meta ls tha t can adverse ly affect hum an reprodu c t ion inc lude As,Sb, Be, Cd, Hg, C r, Co, N i an d A1. Thes e elem ents are also released in largequant i ti es in to the envi ron men t and m ay be cont r ibu t ing to the reproduc t ivefa ilu res be ing exper ienced by con temp orary popula t ions .

Gene mu ta t ions and ch romosome abe r r a t i ons i n human popu la t i onshave also been l inked to environmental factors . The frequency of differenttypes of genet ic d i sorder ( inc lud ing congeni ta l anomal ies and chro mo som aldefects) have been estimated to be about 105 cases per 1000 livebirths(Leona rd et al . , 1983). Trace metals sh ould be considered as one of thefactors for such defects; the genotoxic effects of heavy metals actuallyinc lude gene muta t ions , chromosomal aber ra t ions , l es ions in DNA,increases in the f requency of s is ter-chromatid exchanges, impairment ofspindle form ation , e tc. (Babichet al . , 1985). Fu rthe rm ore , heavy metals cana l te r the cons t i tu t ion , func t ion and f ide l i ty of DNA synthes i s andrep l ica t ion ; can inh ib i t DN A and RN A biosynthes i s; and can in ter fere wi thD N A repair, and w ith R N A crossl inkage and pair ings, e tc . (Jennet te , 1981).Metals a lso play pivotal roles in membrane t ransport processes , redoxfunct ions, hydroly t ic processes and in the act ivat ion o f the macrom olecule s(Martel l , 1981) . Exp osure to e levated levels of t race m etals in theenvironment , c lear ly represents a genet ic hazard to human beings but themagni tude of th i s p roblem remains to be de te rmined .

Immune suppression and allergies

The effects of metals on these diseases has received li t t le scientific study.Nevertheless , several s tudies have demonstrated that exposure to a number


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A silent epidemic o f environmental metal poisoning? 157

of heavy m eta ls can rende r tes t an imals h igh ly s .uscep tible to en doto x ins an dinfec t ious agen ts (EPA, 1986). Meta l - ind uced im mu no -su pp ress ion of tenoccurs a t low doses w hich e lici t no ev iden t tox ic ity in the o rgan ism. In the

absence o f hard sc ien ti fic da ta , one can on ly specu la te on the poss ib le ro le o ft r ace me ta l s in the inc rea sing n um b er o f peop le w ho a re r epo r t ed ly comingdown wi th a l le rg ies , co lds and o ther v i ra l in fec t ions . Immuno-suppress iveme ta l s c an a lso enha nce the ac tiv ity o f o the r env i ron men ta l c a rc inog ens o rtheir metabolic der ivat ives .

Cancer

A t l ea st 18 me ta l s and me ta l lo id s and /o r t he ir com po un ds have been show nto be in i t ia to rs o r p ro mo ters o f ca rc inogenic act iv ity in an imals : the meta ls

are A1, Sb, As, Bi, Be, Mn, Ti, Cd, Cr, V, Co, Cu, Fe, Pb, Ni, Se, La and Zn(Jennette, 1981; Babich et al . , 1985). In general , the assessment ofcarc inogenic i ty to a su spec ted meta l o r i ts com po un ds has been l imi ted toh igh leve ls o f expo sure in the workp lace env i ron m ent o r as a resu l t o facc iden ta l sp i l l s o r food con tamina t ion (Nordberg and Andersen , 1981) .Curren t ev idence tha t meta l po l lu t ion induces cancer in the genera lpo pula t ion , is scan ty and inconc lus ive (No rdb erg a nd And ersen , 1981).However, the deba te has no t p roper ly addressed two key i ssues (a ) thepossible effects of widespread low level exposures to a m i x t u r e o f

carc inogen ic co n ta mi nan ts (Fern , 1971; B lum er and Reich , 1980; Nisbe t andKarch , 1983), and (b) im mu no -su pp ress ion caused by tox ic meta ls and i tsro le in cancer ind uc t io n and metas tas i s . The geno tox ic i ty o f heavy meta lshas a l ready b een no ted . I t wou ld app ear tha t exp osure to e leva ted levels o fca rc inogen ic me ta ls i n th e env i ro nm en t c an ind uce cance r in a sma l l num berof the mo s t suscep t ib le ind iv idua ls . The exac t num be r o f cases remain sinde te rm ina te on the bas is o f cu r ren t ly ava i lab le scien ti fic ev idence.

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