Environmentally induced, occupational diseases with emphasis on chronic kidney disease of

13 Pages·2016·2.53 MB·English

by  Shehani A. Wimalawansa

WimalawansaandWimalawansaAnnalsofOccupational
andEnvironmentalMedicine (2016) 28:33
DOI10.1186/s40557-016-0119-y
REVIEW Open Access
Environmentally induced, occupational
diseases with emphasis on chronic kidney
disease of multifactorial origin affecting
tropical countries
Shehani A. Wimalawansa1 and Sunil J. Wimalawansa2*
Abstract
Background: Environmentally induced, occupational diseases are increasing worldwide, especially inrural
agricultural communities. Poverty-associated malnutrition, environmental hazards and pollution, and lack of access
to clean water, safe sanitation, and modern healthcare facilities are often associated withthese chronic illnesses.
Method: The authors systematicallyreviewed occupational public health issues that have been related to the
environment. General interpretationsof results were included as per theguidelines of the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses. Pertinentpublicationsfrom research databases were reviewed on(A) the
risk–benefits, (B) theprevalence of risk factors for various diseases, (C) the benefits of notignoring the risk factors (i.
e., broader evidence), and (D) therisks,effects, and outcomes ofdifferent typesof interventions. The authors used
chronic kidney disease ofmultifactorial origin (CKDmfo) as anexample to explore the theme. Emphasis was given
to theregions withemerging economies and developing countries located in thevicinity of theequator.
Findings: Geographical, socio-economic and aetiological similarities existfor many chronic non-communicable
diseases thatare affecting tropicalcountries around the equator. The authorsidentified manufacturing,mining, and
agriculture as the biggest polluters ofthe environment. Inaddition, deforestation and associated soilerosion,
overuse of agrochemicals,and irresponsiblefactory discharge (e.g., chemicals and paint, from rubber and textile
factories, etc.), allcontributeto pollution. To decrease the escalating incidences of environmentallyinduced
diseases, governments should work proactively to protect the environment, especially watersheds, and take steps to
minimise harmful occupationalexposures and strictly enforce environmentalregulations.
Conclusion: Creatingpublicawareness ofenvironmental issues and their relationshipto publichealth is essential.
Thisincludes regular monitoring and periodicpublication of thequalityof water, air and soil; preventing
deforestation and man-made soil erosion, increasing forest and ground cover,preventing occupational injuries,
judicious and safe use of agrochemicals, sustainable agriculture and development programs, and implementing
legislation to protect and conservewater heriageand theenvironment. These actions are essential both for a
healthier environment and for the health of thepeople who live inthat environment. Suchmeasureswould also
decrease public health threatsfrom such, including global-warming-related erratic environmental changes and the
occurrence and thespread of non-communicablediseases,such as CKDmfo.
Keywords: Agrochemicals,Agriculture, Agribusiness,Contamination, Human diseases, Kidney disease, Occupational
hazards, Premature death, Prevention,Policies, Pollution, Water
*Correspondence:[email protected]
2CardioMetabolicInstitute,Somerset,NJ,USA
Fulllistofauthorinformationisavailableattheendofthearticle
©2016TheAuthor(s).OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.0
InternationalLicense(http://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinkto
theCreativeCommonslicense,andindicateifchangesweremade.TheCreativeCommonsPublicDomainDedicationwaiver
(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page2of13
Background Water quality fluctuates continuously depending on
Theanthropogenicimpactonfauna, flora[1],andthebio- the season; whether it is the farming season, climate
physical (soil, air, water) environment [2] is well known. In conditions such as drought, rain, floods, as well as agri-
addition, anthropogenic effects on resources, food and en- cultural and mining practices, and from industrial
ergy production have also been studied [3]. It is also well discharges, but can also fluctuates even within a day. Be-
documented that, consumption and even bathing in pol- cause water quality changesoccurrapidlyandcan differs
luted water could leads to many human diseases and pre- markedlyevenwithin alocalarea.Thus,broaderconclu-
mature deaths. To maintain clean water, watersheds and sions cannot be made from sporadic or random testing
water bodies must be protected and properly maintained of water samples from the field; such data are unreliable
[4].Officialswhohaveauthorityovertheenvironmentneed and the conclusions made are usually misleading. There-
to understand the ecosystems and processes operating in fore, one should not make generalized or sweeping con-
and around watersheds and how they are affected by an- clusions about an entire region or the status of a disease
thropogenicactivities. by extrapolating analytical data from few sets of water
Watershedsmustbeprotectedfromhydrological,chem- samples collected at a few times of the day or infre-
ical,andbiologicalpollution,andshouldbeprovidedwith quently overtheyear.
an integrated support system for the maintenance of the
soil–waterenvironmentandtherestorationofaquaticsys- Surfaceandgroundwaterquality
tems [5]. Environmental protection agencies (EPAs) need Similarly, the ground water table fluctuates depending on
to draft and implement laws requiring analyses of ecosys- the climate (markedly vary between rainfall and drought
tem functions, ecological health indicators, future public periods)andsecondarytoover-utilizationofgroundwater
health and environmental risks, and assessments of the viaagro-tubewells.Monsoonrainandintermittentstorms
healthofrivers,lakes,estuaries,coasts,andwetlands[5]. may result in temporary replenishment of the ground
A major worldwide concern is that fresh water and water table and wells but the associated flooding causes
food are being contaminated secondary to expanding contaminationofmostwatersources.
unsustainable development associated anthropogenic ac- Meanwhile, water retention in catchments depends on
tivities, as well as agriculture and agrochemical overuse. the availability of forest and ground cover, soil conditions
Matters are made worse by the human and industrial and erosion, and the rateof rainfall;adverse conditionsof
waste and agricultural runoff, all of which cause pollu- anyofthesecandirectlyaffecttheenvironmentandindir-
tion, while some may cause serious diseases. Water pol- ectly aggravate environmentally-related diseases, such as
lution from microbes causes identifiable diarrheal CKDmfo as well as vector-borne diseases. In addition to
illnesses. Whereas, contaminations due to chemicals and the ongoing climatic changes, modification of any of the
toxinsareinsidiousandmay cause prematuredeaths. above-mentioned resources can adversely affect the water
Plannersandauthoritiesneedtotakeintoaccount,point cycleandthus,thehumanhealth.
(e.g.,factoriesandindustrialsources)[6,7]andnon-point Over the past five decades, short-sighted, over-zealous, -
sourcesofwaterpollution(e.g.,runofffromagrochemicals environmentally detrimental programs have been imple-
and livestock, discharge from municipalities and mining) mented in manydeveloping countriestoachievefor short-
[8–10].WiththeGreenRevolution,non-pointsourcepol- term gain. These have adversely affected water quality,
lutionhasemergedasthemajorconcern. soil, air, fauna and flora, and human and animal health.
Contributing factors include the overuse of both syn-
Watersourcesandquality thetic and organic agrochemicals, deforestation and
Drinking water comes from surface and ground sources, associated soil erosion, diversion of streams and rivers,
including rivers, reservoirs, lakes, streams, springs, and nitrogen and phosphorus-related eutrophication of res-
underground aquifers [4]. When rainwater and surface ervoirs,andtheproliferationoftoxichumanwaste.
watertraveloverthegroundorunderground[11,12],they This review focuses on common sources of water pol-
collect contaminants, including naturally occurring sub- lution and their effects on human health with special
stances, such as salts and minerals, and manmade sub- reference to chronic kidney disease of multifactorial ori-
stances such as agrochemicals, agricultural and factory gin (CKDmfo), also known as chronic kidney disease of
waste,andanimalandhumanwaste[4,13].Consequently, uncertain aetiology/origin (CKDu, CKDuo). Figure 1 il-
all sources of fresh water contains a certain amount of lustrates the common sources and factors that lead to
contaminants. Environmental protection agencies and water pollution.
regulatory standards institutes in each country provide
localqualitystandardsforwaterand,regulatetheamounts Modesofwaterpollution
ofcontaminantsallowableinthewaterprovidedbypublic Reservoirs receive water from rainfall, drainage from
(e.g.,municipalities)andprivatesystems. streams and rivers, and runoff from upland areas and
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page3of13
treatment and discharge of sewage have led to a dra-
matic reduction in the contamination of watersheds and
surrounding ecosystemsfrom thissource [28].
However, the implementation of regulations for agro-
chemicals and animal waste lag behind these efforts in
most agricultural communities, particularly in developing
countries [25, 26, 29]. The participation of all stake-
holders, including the public, private industry, techno-
crats,legislators,governmentagencies,andenvironmental
organizations [30] is essential for protecting and cleaning
up water and environmental contaminations and related
environmentalbio-hazards[25,26,31].
Muddy water is contaminated water; mostly secondary
to deforestation and agriculture-related upland soil ero-
sion. Displaced silt and clay from upland streams in-
crease the sediment load in rivers and downstream
reservoirs. Silting necessitates dredging, which further
contaminate water, thus, negatively affecting fauna and
flora and disrupting their life-cycles, and endangering
the food chain. Such would also hinder transportation,
navigation,andinterfereswith recreationalactivities.
Fig.1Thecommonfactorscontributingtowaterpollution.Also A turbid or excessively muddy waters also harms
shownaretheinteractionsandinterconnectednessofthefactors aquaticorganisms.Inadditiontodecreasingthedissolved
leadingtowaterpollutionandadversehumanhealthandtherole oxygen content and the sunlight reaching on millions of
ofsocioeconomics,behaviour,andoccupationalandenvironmental
living organisms, clay particles injure the gills of fish and
componentsinthegenesisofCKDmfo
adversely affect their spawning and survival. Like-
wise, muddy water also disrupts photosynthetic activities
watersheds. Most rivers originate at higher elevations, andputstheaquaticecologicalbalanceintodisarray.
wherethereismorerainfallandgreaterforestcover.Defor-
estationleadstolessabsorptionofwaterandinturnfiltra- Chronickidneydiseaseofmulti-factorialorigin(CKDmfo)
tion of contaminants. Contaminants from households, Atypical chronic kidney diseases started to appear in the
farms(animalwasteandagrochemicals),andindustriesalso early 1960s in the Balkan regions [32–35] and later ap-
enter streams and reservoirs located hundreds of kilo- peared in several other equatorial countries, including in
metres downstream from the original contamination. In Central America [36–42]. In addition to been a fatal dis-
addition, water from many rivers are diverted to reservoirs ease,CKDmfoisamajorsocio-economicissueandagrow-
foragriculturalpurposesand/orforpowergeneration. ingenvironmentalandoccupationalhealthproblemacross
Water pollutants include household waste, fertilisers, SouthAsia,andMesoamerica.Itisanexampleofanenvir-
pesticides, insecticides, heavy metals from from phos- onmentallyinduced,occupationalexposuredisease.
phate fertiliser, discarded batteries and workshops, and CKDmfo has been increasingly manifesting in equatorial
chemical waste from rubber and apparel production, ve- (tropical) countries during the past four decades. The dis-
hiclerepairshops,andotherindustriesthatusechemicals ease is found primarily in the dry-zonal agricultural soci-
[14–19]. For many substances, permitted upper limits etiesofeconomicallypoorregionsclosertotheequator.
(thresholds) in drinking water have been established [20] Climate change, and consumption of food or water
by the World Health Organization, by EPAs, and internal contaminated with heavy metals, fluoride, and toxins
standards institutes, such as the Standards Institute Sri cause various non-communicable diseases and illnesses
Lanka [21–23]. These organisations have produced safe- leading to protracted suffering and death. In addition to
upperlimits(maximumallowablelimits;MAL)manycom- causing prolonged, extreme droughts and flooding, cli-
ponents, including for heavy metals, fluoride, agrochemi- mate change also causes excessive heat exposure [43],
cals,andtotaldissolvedsubstances[24]. dehydration, heat exhaustion, heat stroke, renal stone
In most countries, the non-point sources of plant nu- formation, and exacerbation of pre-existing chronic dis-
trient pollution through agricultural practices are main ease,includingkidneyfailure (heat-shocknephropathy).
contributors to water pollution and nutrient-related eu- Typically, CKDmfo affects low-income agricultural
trophication [25–27]. Although water contamination workers, predominantly males, aged 30 to 60 years, living
with raw sewage is a serious issue, laws regulating the inlow-lying,flat,tropicaldry-zonalareas.Thediseaseisnot
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page4of13
associated with common causes of chronic kidney failure, Severalrecentstudiesfailedtodetecthigherthanthemax-
suchasdiabetesorhypertension,andismostlyasymptom- imumallowablelimits(MAL)ofanyofthepostulatedcom-
aticuntilkidneyfunctionismoderatelyimpaired[44–47]. ponentsofheavymetals,fluoride,salinity,oragrochemicals
SriLankahasbeenafflictedwithanepidemicofCKDmfo inthesoil,water,orfoodofthisregion.Consequently,none
for more than two decades; the disease has caused the of these items though hypothesized as a single cause, have
deaths of thousands of people, mostly middle-aged, male beenlinkedasthecauseofCKDmfo[54,58–60].Moreover,
farmers [46, 48, 49]. More people have succumbed to none of the compounds measured (except water fluoride
CKDmfo than died during the 2004 tsunami in Sri Lanka contents in certain villages) are higher than those deemed
[50].Althoughasinglecausativefactorhasnotdetermined, safebytheWorldHealth OrganizationandtheU.S.Envir-
data suggest that certain levels of unhealthy exposures to onmentalProtectionAgency[59].
unhealthyenvironment(acontaminatedsoil–watersystem) Nevertheless,theadditiveorsynergisticeffectsofacom-
arelikelycontributingtothisdisease[51]. binationoffactors,includingconsumptionofcontaminated
Sri Lanka reports the highest incidence of CKDmfo in water,evenwiththese componentsatlowerthanthemax-
SouthAsia,witharound180,000peopleaffectedandapproxi- imumallowedexposurelevelswhenassociatedwithclimate
mately 50,000 reported deaths since 1992 [47, 50, 52–54]. change, malnutrition, and/or harmful behaviours could
Effective early diagnosis and preventive, and treatment cause this major epidemic. For example, current data sug-
strategies are still lacking [52, 55]. Likewise, environ- gest that the consumption of water polluted with certain
mentally friendly and maintainable agricultural practices nephrotoxins associated with unsustainable development
and food security are needed, as is the enhancement of practicestogetherwithexposuretotheconsequencesofcli-
rurallivelihoods[4,53]. mate change and possible heat-stress nephropathy and so
Dependingonthestudiesreportedglobally,thecorrela- forth,cancausechronicrenaltubulardamage[43,47].
tions described between environmental pollutants and Victims are primarily from dry zonal regions in the
CKD of unknown aetiology (CKDu; CKDmfo) vary affected, predominantly agricultural countries and mostly
greatly. Reported pollutants in the global arena include consumeshallowwellwaterthatisthoughttobecontam-
arsenic in subterranean water tables in India [42], aristo- inated. However, approximately 15 % of the CKDmfo-
lochic acid in the Balkans and in certain parts in China affected families rely on drinking water from other than
[32, 34, 35], heavy metal exposure in Central America shallow-wells: from deep-tube wells, canals, and reser-
and South America [38, 39, 56], and a combination of voirs. Therefore, it is unwise to assume a single source or
various chemicals in Egypt [41] and in Sri Lanka [52]. In type of water, or a presumed/unknown contamination as
spite of the temporal associations and justifiable specula- thecauseofCKDmfo[46,49,61,62].
tions, the use of agrochemicals has not yet scientifically
proventobelinkedtocausationofCKDu/CKDmfo.
Although contributory, none of the affected countries AgrochemicalsandCKDmfo
to-date has identified agrochemicals as the sole cause of Published data support a plausible, temporal correlation
this deadly disease [52]. Therefore, labelling the disorder between exposureto agrochemicals and increased risk of
with such names as “agricultural nephropathy” or “agro- chronic diseases, such as certain cancers, neurodegener-
chemical nephropathy” is misleading and only further ative disorders, cardiovascular diseases, asthma, mito-
delaystheidentificationofthetrue cause(s). chondrial dysfunction, oxidative stress, birth defects,
Nevertheless,consideringthetemporalassociationofthe endocrine disruptions, and reproductive disorders [63].
“introduction” of agrochemicals in early 1960s', the indis- Therefore, from a risk perspective, minimising pollution
criminate and overuse of agrochemicals, flat terrain, with fromsuchchemicalsshouldbegivenahighpriorityirre-
poor drainage in the affected regions, scarcity of potable spectiveofwhether itislinked toCKDmfoornot.
water,andconsumptionofwaterthatiscontaminatedwith Nevertheless, increased agricultural output essential to
several chemical components, agrochemicals are likely to feed the world’s ever-increasing population, which is
beoneoftheagentscontributingtoCKDmfo[57]. greatlyreliesonagrochemicals,thus,theuseofagrochem-
Although no causality has been established for the icals has become standard practice worldwide. Globally,
CKDmfo in Sri Lanka, it has been established that expos- lessthan8%offoodcultivationsuseorganicmethods.Of
ure to combinations of various nephrotoxins and chemi- this type of cultivation, 80 % is used for animal feeding
calsoveralongperiod,evenatlower exposurelevels(i.e., (pasture)toproduceorganicmeat.
lower than the MAL), can lead to bio-accumulationof SriLankaandinallotherCKDu-affectedcountries(and
harmful agents, which lends further support the idea of regions), these chemicals are extensively used throughout
multifactoriloriginandforacausalrelationship[33]. thecountry,butonlypeoplelivingincertaingeographical
InSriLanka,thediseasefirstappearedintheearly-1990s areas only are experiencingthis disease. This suggests the
and affected mostly the North Central Province(NCP). contributionsofotherfactorsinthegenesisofCKDmfo.
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page5of13
Factors such as climate change, prolonged dry seasons,
behavioural issues,malnutrition,illegallybrewed alcohol,
medication abuse, and microbial-induced toxins all re-
main as possible contributing factors. With reference to
the hill country in Sri Lanka, agrochemicals are used at
ratesseveraltimesgreater(and5to10foldhigheramounts
than recommended by the department ofagriculture) than
intheregionthatismostaffectedwithCKDmfo:theNCP.
Thus, the agrochemical-based hypothesis cannot explain
why only certain geographically demarcated areas are
affected, whereas people in other regions (sometimes
adjoiningvillagesandregions)exposedtothesamenephro-
toxinsarenotaffected.
Other than the nitrates and phosphates found in water,
no meaningful quantities of pesticides (insecticides, weedi-
cides,ornematocides)havebeenreportedinfooditemsby
any analytical study published to date. Similarly, no pesti-
cide residues have been detected in cadaveric tissue sam-
ples. The latter is important with reference to countries
Fig.2Hypotheticalinteractionsandinterrelationshipsofexcessive
thathavebannedcertainpesticidesoveradecadeorso. andirresponsibleuseofagrochemicalsandthedevelopmentof
If trace amounts of such substances are detected in CKDmfo,ahypothesisthathasnotbeenfullytestedorproven
blood, urine, or tissue samples, as some have 'claimed'
(stating, unpublished data), that finding indicates the (a)
illegal importation of banned pesticides into the country perhectarebasis[e.g.,triplesuper-phosphate(TSP),pes-
or (b) imported food has been contaminated with such ticides, glyphosate, etc.], such as those in the Hill Coun-
substances. In addition, no data are available regarding try region, are not affected with CKDmfo. Whereas, the
the hypothetical claim or detection of 'pesticide–metal' prevalence of the disease among adults are over 10 % in
complexesinrenal oranyothertissues. some oftheCKDmfoaffected villagesintheNCP.
If traces of heavy metals or pesticides are detected in
urine or tissue samples, that does not prove the particu- DoagrochemicalsorbadpracticescontributetotheCKDmfo?
lar substance is causally related to the failure of a given Usingthecorrectamountofagrochemicals(whetherin-or-
organ. When an organ such as the brain, liver, or kidney ganic or organic; as recommended by the department of
begins to fail, it loses internal dynamics and the ability agriculture) at the correct time of the farming season,
to control what is retained and excreted. Thus, the find- wouldincreasethe cropoutput,whileminimisingenviron-
ing of comparatively high levels of arsenic in urine or of mental harm [64–66]. On the other hand, the excessive
traces of a heavy metal or pesticide residue in renal tis- use of agrochemicals contributes not only to hyper-
suedoesnot meanthatthese substances are causing dis- eutrophicationofwaterinreservoirsbutalso to contamin-
ease. Instead, it is a consequence of the disease. Figure 2 ationofthesoilandwaterwithheavymetalsandothernat-
illustrates one such, agrochemical-based hypothesis as urallyoccurringchemicalconstituentsinfertiliser[4,66].
the cause ofCKDmfo. In most ofthe affected countries, including Sri Lanka,
many of these problems can be traced back to the elim-
Contaminationofwaterandfoodviaherbicidesand ination or "reduced" communication between village-
pesticides level agricultural officials and farmers that began in the
To increase the output, farm crops such as potatoes and late 1970s [4]; i.e, after the abolition of agricultural ex-
vegetables require regular application of fertilisers (i.e., tensionservicesbythegovernment.Removalofthisim-
organic or agrochemicals) and pesticides. When pesti- portant advisory service to farmers led to several
cides are applied inhigher than therecommendedquan- negativeoutcomes,includingfertiliseroveruse.
tities, insects gradually become resistant to them, so In addition, most farmers in developing countries who
more pesticides are needed to control pests, leading to a use agrochemicals do not use protective gear and thus
cycle ofescalating chemicaluse[51]. frequently are exposed to higher concentrations of toxic
Tea estates apply herbicides such as glyphosate three chemicals and are at a higher occupational risk for ex-
times a year, but none of the plantation workers are af- periencing chemical-induced acute and chronic diseases.
fected with CKDmfo. Similarly, workers who regularly These observations are applicable to almost all farmers in
use the largest quantities of pesticides and fertilisers on SriLankaandotherCKDu-affectedcountries.Nevertheless,
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page6of13
the excessive or careless use of agrochemicals do not ex- to leach out of farmlands, ending up in reservoirs lo-
plainthesporadicgeographicaldistributionofthisdisease. catedhundredsofkilometresaway[68,69].
InCKDmfo-affectedcountries,onaper-hectarebasisof
Theroleofchemicalandorganicfertilisers arableland,fertiliserusagehastripledsincethelate1970s
Since the advent of the Green Revolution, the use of or- [51]. Once the soil has reached its threshold for holding
ganic and natural fertilisers has decreased and the use of fertiliser,thesechemicalsleachintowaterways;themoney
chemical fertilisers has increased. Currently, more than spent on fertilisers is wasted and the chemicals cause
95 % of farmlands worldwide are cultivated using chem- environmentalpollution(Fig.3).Farmersbegantousein-
ical fertilisers. Organic fertilisers include manure, crop creasing amounts of pesticides to overcome pest resist-
residue, tree leaves, animal waste, and compost [21], all ance,and inordertoobtaindesiredhigheryields[66,70].
of which can be locally produced, with much of the nu- The result was not always the intended one; more is not
trientsbeingderived from natural sources. alwaysbettereveninagriculture(Fig.3)[51,66].
However, the amounts of organic fertiliser generated
havenotchangedsignificantly overtime,with theexcep- Environmentalpollutionfromheavymetals
tion ofricestrawandwheat husks,whichhave increased The term heavy metal usually refers to chemical ele-
becauseoftheuseof harvestingmachinesincommercial ments that have a high atomic number and is toxic to
farms that return the straw back to the fields. Neverthe- living beings at low concentrations. Similar to the World
less, the quantities of organic fertiliser needed to provide Health Organisation (WHO) and EPA, the Sri Lanka
the nutrients for growing plants (e.g., kilograms per hec- Standards Institute has also identified heavy metals such
tare) are orders of magnitude higher than the amounts as arsenic, cadmium, lead, mercury, selenium, and hexa-
of chemical fertiliser needed. Thus, such increase from valent chromium, etc., as toxic substances [62, 63] and
the current usage incommercialfarmingisimpractical. havestipulated the MALs of these in drinking water, fer-
Even if the use of organic fertilisers were to be maxi- tiliser, and farm soil [23]. Table 1 lists some of the key
mised, these would be only enough for less than 10 % of heavy metals that are harmful if gets into the body.
farming needs. On the plus side, in industrialised coun- However, these are used commonly in many industries
tries, the use of organic fertilisers, manure, and animal and in households, and take less precautions during
dung has decreased the instance of hyper-eutrophication their use and disposals due to inadequate awareness of
of water bodies [22]; whilst the reverse is true in devel- theirdangers.
oping countries. Mostpeopleinevitablyuseandhandleheavymetalsdur-
With appropriate use, organic fertilisers have no adverse ing day-to-day activities. Most of these materials, instru-
environmental issues [64, 65]. However, since, many types ments,andtechnologiesusingheavymetalsaredesignedto
of organic fertilisers bio-accumulate toxins and heavy improve human lifestyles, add conveniences to peoples’
metals, with time, the excessive use of organic fertilisers lives and increase prosperity. However, the misuse of
couldunintentionallyintroducesignificantamountsofthese heavy metals, especially their improper handling during
toxiccomponentsintofarminglands. production cycles and disposal, can inflict a heavy toll on
Four decades ago, soil in the rice fields in southeast theenvironmentandconsequentlyonpeoples'health[71].
Asian countries, including Sri Lanka, (particularly in the
midcountry, wet zone areas of central province [67], later Environmentalpollutionwithheavymetalsandhuman
colonised as the NCP) were deficient in phosphorus, but diseases
fulloffishandotherlivingbeings.Thelatterisnon-exiting Aroundtheworld,manypeoplehavecontracteddiseases
now.Phosphorusdeficiencywasoneofthereasonsforthe brought about by ingesting heavy metals and inhaling
introduction of Triple Super Phosphate (TSP) in agricul- fumes; the symptoms of such diseases can be subtle [72,
ture,whichledtomarkedincreaseinpaddy-yield. 73]. Consequently, many go undiagnosed, with the true
The availability of cultivation loans, strong extension causesnotlinkedtomorbidityormortality,andthus,the
services, good paddy prices, and most importantly, the number of documented deaths related to heavy metal
large fertiliser subsidies helped not only increasing the poisoninghavebeenunderestimated.TheBlacksmithIn-
paddy output but also eradicating the phosphate defi- stitute, an environmental health group based in New
ciency though the use of TSP and Single Super Phos- York City, in 2011 estimated that the number of people
phate (SSP). with heavy-metal–related diseases in the world is, 7.2
However, during the past three decades, potato and million related to lead; 5.0 million to mercury; and 1.8
vegetable growers in the Hill Country regions have million tochromiumVI[74].
began to add excess phosphate fertiliser to their farm Whilst fertiliser is commonly contaminated with heavy
lands [51]. Thisled to phosphate build-up in soil beyond metals, these are added to pesticides such as insecticides
the critical threshold, and excess phosphate has begun to increase their toxicity. However, some unscrupulous
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page7of13
Fig.3Anexampleofproductivity,showingtheyieldoutputcurveinresponsetotheincreasinguseoffertiliserinrice,potato,andvegetable
cultivations.Cropoutputincreaseswithincreasingamountsofrightfertilisermixture,butatacertainpoint[MC=M×R],itstartstoplateauand
mayevendecline.Thus,moreisnotalwaysbetter(adaptedfromWimalawansaetal.,[51,66])
manufacturers use fertiliser as a mode of disposing che- them in soil. Meanwhile, each compact fluorescent
micals and heavy metals, including cadmium and lamp/light bulb contains approximately 3 mg of mer-
lead [52]. Such contaminants at higher than acceptable cury, while arsenic and cadmium can be found in phos-
limits are not rare in fertiliser consignments shipped phate fertilisers and pesticides [14, 75], all of which are
from some industrialised countries into emerging econ- common modes of contaminating the environment, of
omies anddevelopingcountries,including SriLanka. which the EPA has little or no control. The lack of recyc-
Other products containing heavy metals that are ling and proper disposal systems in emerging economies,
imported to these counties include batteries, vehicles, including Sri Lanka, is likely to cause further escalating
fluorescent bulbs, materials and parts, paints and chemi- majorchronichealthissuesinyearstocome.
cals,medicalequipment,andagrochemicals.Forexample, Largequantitiesofheavymetalsindevelopingcountries
inSriLankawithapopulationof21million,isa substan- areasyetnotrecycled,andendupasdomesticandindus-
tialimporterofheavymetals.Examplesofimportedgoods trialwaste, aportionofwhicheventuallypollutes soil and
containing heavy metals include an estimated, 650,000 watersystems,andeventuallywillgetintothefoodchain.
cars, 22 million mobile phones (each with a battery and Tocounteractthisimpendingdisaster,reliableinventories
spare batteries), and millions of other household batter- must be developed that capture the amount and types of
ies and fluorescence bulbs; most of which are unfortu- heavy metals imported, recycled, reused, and properly
natelynotrecycled. disposed.
Each middle class family purchases 20 to 30 batteries To prevent anthropogenic heavy metals entering the
per year and disposes of them in the garbage or buries ecosystem, an introduction of a culture of safe-recycling
Table1Commonusesandharmfuleffectsofheavymetals[hazardouswaste]onhumanhealth[23,72]
Substance Use Harmfuleffect MALinpotable
watera(mg/L)
Cadmium Batteries,electroplating,TSP,SSP,tobacco,illegallybrewedalcohol Proteinandsugarinurine;renaldamage 0.005
Lead Paint,batteries,alloys,welding,olderwaterpipesandjoints Nervoussystemandbraindamage,lowered 0.05
IQ,liverandkidneydamage
Mercury Thermometers,fluorescentlampsandtubelights,thermostats, Nervoussystemandbraindamage, 0.001
thermometers,medicalequipment,batteries renaldamage
Hexavalent Steelmanufacturing,chromeplating,magnetictapes,dyesand Acarcinogen,kidneydamage,skindiseases 0.05
(VI)chromium paints,tanningofleather,textileindustry,tobaccosmoke
Arsenic Insecticides,nematocides,woodpreservative,alloyswithcopper Cancersinlung,bladder,andskin;keratosis 0.05
andlead(carbatteries),pesticides,volcanicash anddermatitis
aMALmaximumallowablelimit.Source:SriLankaStandardsInstitute[23]
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page8of13
is essential in all developing countries and emerging existing chronic disease. Over the last century, global
economies as soon as possible. This can be based on the mean temperature has risen by approximately one de-
established principles and safe-practices used in eco- gree [80], but has been associated with increased fre-
nomicallyadvancednations. quency of unpredictable weather, melting polar ice-caps,
rising sea levels, severe flooding, heat waves and human
Excessheavymetalsinwaterandsoil ill health [81]. However, a direct connection between
Small quantities of heavy metals, including arsenic, cad- heat stress, local environmental changes secondary to
mium, lead, and chromium, have been detected in soil global warming, potable water shortages, and behav-
samples and a few water samples in regions and coun- ioural and dietary sugar changes with CKDmfo has not
tries that are affected with CKDmfo. However, the soil been studied in-depth orconfirmed [52].
distribution of various heavy metals is not unique to Duetoheavyexertion,lackofshadeduringwork,apro-
CKDmfo-affected regionsincountrieswith ahighpreva- longed work hours during the day with little breaks,
lence of this disease or other common non- strenuous working conditions, and drinking insufficient
communicable chronic disorders [4, 52, 53]. If levels of water during work, outdoor workers are particularly at
thesecontaminantsconsistentlyexceedpermissiblelimits riskforheatstressanddehydration[82–85].Nevertheless,
(e.g., MAL), threatstohuman healtharelikely[75]. the outdoor workers (mostly expatriates) who work long-
Most samples analysed by different research groups hours getting daily exposure to scotching sun in middle-
recentley, in regions with a high prevalence of chronic eastern countries, do not seems to develop CKDu-like
diseases such as CKDmfo, including in Sri Lanka, show syndrome.
levels of heavy metals within the EPA and WHO allow- Experimental studies in mice have demonstrated, re-
able limits [42, 76, 77]. It is unclear how such low levels current daily heat exposure and dehydration causing
can affect humans across a large region like the NCP. chronic renal tubulo-interstitial disease with fibrosis and
However, because some of the chemicals, especially inflammation [86], similar to that observed in CKDmfo
heavy metals, bio-accumulate during the human life- [81]. However, whether this is due to chronic rhabdo-
span, in the long term these can cause chronic ill health. myolysis,elevatedserumuricacidlevels,othermetabolic
Therefore, if left unchecked, the presence of heavy derangements, a combination of these factors, or some-
metals, even though the levels are less than the MAL, thing else, is unknown. Moreover, it is unclear whether
ultimatelymayleadtoseriousillnesses,includingchronic thismodelisapplicabletohumans.
occupationaldiseases[49]. It is plausible that the toxicity of exposure to certain
In addition to the metallic load, the release of ionic nephrotoxins (released to the environment as a conse-
compounds, such as cadmium, manganese, hexavalent quence of having unsustainable development practices)
chromium, lead, and nickel, into the water (and eventu- can be additive in the presence of heat stress and
ally into food) depends on chemical parameters, such as chronic recurrent dehydration. Nevertheless, the rise of
dissolved organic carbon, ionic strength, temperature, global temperature by one degree [81], causing CKDmfo
pH, particle size, the presence of protective agents such seems highly unlikely.
as zinc, selenium and other antioxidants, and the fre- For example, outdoor workers in the Middle-East,
quency and depth of dredging of canals and reservoirs, where theaveragetemperateduringsummerexceeds10°
etc. [77–79]. It is known that the toxic effects of heavy C than in the highest temperate exposure by the agricul-
metals are modified in the presence of other ions. De- tural workers in CKDmfo affected regions, do not seem
crease ofcadmiumtoxicity inthe presenceof zincis one to develop CKDmfo/CKDu-like disease. Moreover, due
such example. to mechanised practices, the intensity of manual labour
With reference to CKDmfo in Sri Lanka, except for associated with rice- as well-as corn- and sugarcane-
fluoride, none of the other components have been de- farming practices are less now, compared to several
tected at levels higher than MAL in water samples [52]. decades ago. For example, in south east Asia, there is a
Considering all data, currently there is no scientific evi- reduction of the number of strenuous working days an-
dence to support the theory that heavy metals in water nually, in paddy fields from an average of 90 to 42 (i.e.,
or food, water ionicity (salinity, phosphate, etc.), nitrate, overa50%reductionof hardlabour).
orhardness ofwatercause CKDmfo[4,53].
GeographicaldistributionofCKDintheworld
Theroleofheat-stressandchronicdehydration Most of the CKDuo-affected countries have hundreds of
In addition to causing prolonged and extreme droughts years of traditional, sustainable agricultural practices. As
and flooding, climate change has led to excessive heat populationsaroundtheworldincreased,toincreaseyields,
exposure, dehydration, heat exhaustion, heat stroke, in- farmers began to abandon traditional cultivating methods
creased renal stone formation, and exacerbation of pre- when synthetic agrochemicals were introduced in the
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page9of13
early1960s[36,87].Thisledtoimprovedfoodsecurityin water, sanitation, education, and modern healthcare
many emerging economies and in developing countries. [46,91].
Whether this Green Revolution has anything to do with Despite claims by certain people, the geographical
theCKDmfo/CKDuisyettobedetermined. distribution of CKDmfo and the hardness of the
Organic farming as shown above, has its own issues. water in all affected countries, including Sri Lanka,
Recent data suggest that the use of organic farming is do not coincide, suggesting that the latter does not
likelytodecreasetheexcessiveuseofphosphatesandni- contribute to the development of chronic kidney fail-
trates which in turn reduces the leaching into the water ure [46]. In fact, some areas in Sri Lanka, such as the
system in comparison with the use of chemical fertilisers Jaffna Peninsula and the Puttalam and Ampara dis-
in agro-fields [88, 89], though not everyone agrees about tricts have two to three times greater water hardness
this[90]. and higher electrical conductivity and salinity in their
Worldwide, there are several commonalities in the drinking water than that in the CKDmfo-affected re-
CKDmfo/CKDuo-affected countries, including a drought- gions; NCP and the Kurunagala and Badulla districts
stricken climate and proximity to the equator (Bangladesh, [52], [48].
Sri Lanka, southern China, India, South America, and cer-
tain eastern European Balkan countries) (Fig. 4). Most of Discussion
the affected nations are tropical and have developing or Because of the unique chemistry of the water molecule,
emerging economies that are predominantly agriculture water is easy to pollute; it has the ability to dissolve al-
based. It is noteworthy that all of these countries receive most any substance [4, 92]. Therefore, some degree of
aidandloansfromtheWorldBank,theInternationalMon- water pollution is inevitable. Nevertheless, proactive en-
etaryFund,andindustrializednations. vironmental and public health interventions are essential
Countries that are receiving such aid packages or to prevent pollution and ill health [93]. Public health in-
loans are expected and have been obligated to follow terventions are usually intended to prevent future catas-
some policies and procedures that may be imperil and trophes [94]. However, certain actions can be taken now,
not appropriate for these countries, citizens, or their which do not depend on decisions on how to safeguard
economy. How these undesirable, imposed practices af- people inthefuture.
fecting the economy (in fact, a poverty-trap) of recipient Multi-country ecological studies have revealed that
countries, healthcare and chronic health conditions have there are key environmental factors that contributes to
not been addressed. All affected communities are rela- chronicillhealthanddiseasesincludingcancer,isadverse
tively less wealthy and have insufficient access to clean environmental issues and pollution, not genetics [95–97]
Fig.4GlobaldistributionofCKDu/CKDmfo.Allaffectedcountriesarelocatedclosetotheequatorandhaveagriculture-basedeconomies.Redcircles
indicatethatthecausesforCKDu/CKDmfoareunknown;yellowcirclesindicatecountriesinwhichsomeofthepotentialcausesareunderstood.Some
commonalities,especiallytheproximitytotheequatorofaffectedcountries,arehighlighted.Themapisfromthepublicdomain,modifiedto
indicatelocations
WimalawansaandWimalawansaAnnalsofOccupationalandEnvironmentalMedicine (2016) 28:33 Page10of13
Therefore, a cleaner environment and healthier lifestyles However,astheCKDmfonameimplies,acombination
(both of which can be proactively improve) need to be of these factors (including unknown nephrotoxins) to-
emphasised.Sucheffortswouldreducetheescalatinginci- gether with harmful behaviour and chronic dehydration
dences of cancer and almost all other non-communicable are likely to cause this disease. Among the recent
diseases, improve the health status and the economy of epidemics, CKDmfo may be one of the first diseases
thenation,andtheburdenonhealthcarebudgets. manifesting due to global warming and unsustainable
Imposing a strict quality control program on locally developmental practices. Regardless of the cause, pre-
produced and imported agrochemicals and regulating vention and continued investigation of the possible
the release of fertilisers to farmers based on soil testing causes of this disease must be continue; these activities
are likely to decrease the agrochemical usage and shouldprovideapathtoeradicationofthe disease.
overuse-associated, environmental pollution. As the dis- Few social support structures exist in the NCP and in
cussion of the proposed causes of CKDmfo has shown, mostvillages in developingcountries. Foundationsshould
the search for agreement on the cause or causes of these beestablishedtoprotectpeoplefromday-to-daylifeissues
diseases is likely to continue for many more years, thus, and unexpected events and to provide access to emer-
focusing on the available resources and evidence for pre- gency care, suchas inthe aftermath of hurricanes, floods,
vention is the best way forward for eradication of com- tsunamis, and so forth. Properly taking care of a those
municable aswell as non-communicable diseases. In this who are affected and taking firm and effective steps to
regards,CKDmfoisnotanexception. prevent the disease are prime responsibilities of health
Tocurtailchronicdiseaseassociatedescalatinghealthcare ministries and departments of health. Having a tested
costs, countries must address the root causes of these ill- emergency preparedness plan that can launch immediate
nesses. Adequate environmental protection and prevention programs of support in the event of emergencies at the
of diseases should be part of that effort. Such preventative community and regional levels is crucial to preventing
approaches lead to reduction in morbidity and mortality deathsandcontainingcommunicablediseases.
and are often more cost-effective than spending taxpayer With reference to the current calamity of CKDmfo, it
moneyonexpandinghospitals,purchasingexpensivemed- is essential to provide clean drinking water and safe
ical equipment, organ transplants, and treating escalating sanitary facilities as a priority for all affected regions and
non-communicablediseases. the entire country. Chronic disease management pro-
With agrochemicals being one of the key sources of grams in the country need to coalesce and synergise to
environmental pollution, agribusinesses have a corporate be cost-effective [98]. Despite the existence of CKDmfo
social responsibility at least to invest in educating for more than two decades, access to safe, clean water
farmersontheproperuseofsuchchemicalsandprovide has been provided to less than 10 % of the needy popu-
subsidised or free protective gear to them [49]. On the lationinthedistrictsaffectedbythisdiseaseinSriLanka
other hand, farmers must be accountable for the proper andotheraffected countries[52].
use of agrochemicals and protecting themselves when Considering that most shallow wells are contaminated
handling these chemicals, and for taking care of the en- (perhaps with unknown nephrotoxins) in CKDmfo-
vironmentandalllivingbeingsaroundthem. affected areas, and streams and reservoirs are increas-
Thus, it is paramount that agriculture-related personals ingly getting polluted, facilities should be developed ur-
areeducatedonvariousmeansofpreventingenvironmen- gently at least on a provincial basis to test for water
talpollution,theprotectionofthemselvesandothers,and qualityandfood contamination.
the reasonable and responsible use and disposal of agro- In the interim, potable water can be successfully and
chemicals and containers. For such a program to be suc- cost-effectively provided through reverse osmosis units,
cessful, approaches should be collaborative, not purely untilcentrallypurified,safe,pipe-bornewatersuppliesare
punitive,andshouldofferincentives. made available in these regions. It is scandalous that in
Available data do not support any of the postulated both rich and poor countries, people in rural villages are
agents, chemicals, heavy metals, fluoride, salinity/ion- not provided with safe running water, while the govern-
icity, or individual agrochemical components, such as ment provides excellent facilities to wealthy and city pop-
phosphate or glyphosate, as causative factors for ulations. Gross inequalities in the supply of drinking
CKDmfo. Whereas, water and food pollution together water, lack of safe sanitation, and correctable healthcare
with prolonged drought associated issues and condi- disparitiesarenotethicallyacceptableinmodernsociety.
tions, and harmful personal behaviour are plausible
causes of this deadly disease. Because of the plausibil- Conclusion [Box offering]
ity of multiple factors playing a role in the genesis of Whatisalreadyknownonthissubject?
this disease, the appropriate terminology is CKDmfo, Environmentalpollutionleadstovarioustypesof humanill
rather than CKDu. health and occupationally acquired diseases. Human ill