Exposure to Agrochemicals and Cardiovascular Disease

12 Pages·2016·0.27 MB·English

International Journal of
Environmental Research
and Public Health
Review
Exposure to Agrochemicals and Cardiovascular
Disease: A Review
MatomeM.Sekhotha*,KotsediD.MonyekiandMaseziE.Sibuyi
DepartmentofPhysiologyandEnvironmentalHealth,SchoolofMolecularScienceandAgriculture,
UniversityofLimpopo(MankwengCampus),PrivatebagX1106,Sovenga0727,SouthAfrica;
[email protected](K.D.M.);[email protected](M.E.S.)
* Correspondence:[email protected];Tel./Fax:[phone]
AcademicEditor:PaulB.Tchounwou
Received:13November2015;Accepted:3February2016;Published:18February2016
Abstract: Introduction: Intheagriculturalworldthereisacontinuouslossoffood,fiberandother
commoditiesduetopests,diseaseandweedsbeforeharvestingtime. Theselosseshadcreatelots
of financial burden to the farm owners that might lead to shutting down of their daily business.
Worldwide,thereisanoverallveryhighlossofagriculturalproductsduetoweedsgrowthalone.
Tocounteractthisproblemmostfarmersresorttotheuseofagrochemicalstoincreasetheirproduction
butcompromisingthehealthoftheirfarmworkers. Thepurposeofthestudywillbetoassessthe
relationshipbetweentheagrochemicalparticlesandcardiovasculardiseasesamongfarmworkers.
Method: Non-systematicreviewwasusedtocollectdata. Thefollowingdatabasewereuse: Medline,
EBSCO,andScienceDirecttosearchfortheexistingjournalarticles. Results: Thisstudyaddressesthe
relationshipbetweenagrochemicalsparticlesandcardiovasculardiseasesinthefarmingindustries
usingliteraturereview. Discussion: Otherresearchershadalreadydoneanextensiveresearchon
the pathway of potential mechanisms linking the ultrafine particulate matter to cardiovascular
diseases. Theoutcomesofthoseinvestigationsweretheclinicalresultsofeventsthatmightleadto
thedevelopmentofmyocardialinfarction,congestiveheartfailure(CHF),stroke,arrhythmiaand
sudden death. Xenobiotic compounds that maybe implicated in the pathophysiology of human
cardiovasculardiseases,willbeexaminedandincludedinthisstudy. Thereiscompellingevidence
suggestingthattoxicfreeradicalsofpesticidesplayanimportantroleinhumanhealth. Conclusion:
Thereisacloserelationshipbetweenagrochemicalsparticleandcardiovasculardiseases.
Keywords: agrochemicals;farmworkers;cardiovascularsystem;bloodcirculatorysystem;ultrafine
particles;particulatematter;nanoparticles
1. Introduction
Intheagriculturalworldthereisacontinuouslossfood,fiberandothercommoditiesduetopests,
diseaseandweedsbeforeharvestingtime. Theselosseshadcreatedlotsoffinancialburdentothe
farmownersthatmightleadshuttingdowntheirdailybusiness. Thelossofagriculturalcommodities
mayreachaproportionof25%inEuropeancountriesduetouncontrollableweedsgrowth. Whereas,
in less developed areas like Asia accounts of half potential products yield loss without the use of
agrochemicals[1]. Thelossofagricultureproductsplayscriticallyimportantrolesintheeconomyof
manydevelopingcountries[2]. Inordertocounteractthislossthefarmerscannotsurvivewithoutthe
useoftheagrichemicalsinincreasingtheirproductionyieldandsecuringjobsformillionsoffarm
workersandproducingfoodfortheworldpopulation.
The ultrafine particulate residue matter generated from the use of agrochemicals may pose
health risks to farmworkers health. The numerous cohort studies have examined the relationship
Int.J.Environ.Res.PublicHealth2016,13,229;doi:10.3390/ijerph13020229 www.mdpi.com/journal/ijerph
Int.J.Environ.Res.PublicHealth2016,13,229 2of12
betweenlong-termexposureofambientfineparticulatematterď2.5µm(PM )andnon-accidental
2.5
andcardiovascularmortality[3]. Cardiovasculardiseasecalledacutemyocardialinfarction(AMI)is
amedicaltermforaneventcommonlyknownasaheartattack. AnAMIoccurswhenbloodstops
flowingproperlytotheheart,andaconsequentinadequateoxygenatedbloodsupplymightaffectthe
heartmuscleandproperfunctioningoftheheart. Thismightbeduetooneofthecoronaryarteries
thatsuppliesoxygenatedbloodtotheheartorfromthebodythatdevelopsablockageduetounstable
build-upofbloodcells,cholesterol,lipidsandparticulatematterinbloodpathway.
Currently,therehavebeenmanyepidemiologicalstudiesillustratingtheassociationbetween
agrochemicalsparticlesandvarioushumanbodysystems. Thesestudiesservetofillthevacancyof
epidemiologicalevidenceinthecomprehensivesummaryofenvironmentaltoxicology. Thepurpose
ofthestudywillbetoassesstherelationshipbetweentheagrochemicalparticlesandcardiovascular
disease among farmworkers. This article will provide a summary of subgroup of the results of
cardiovascular risk from exposure due to agrochemicals among farmworkers. This will include
the epidemiological studies, mechanisms of infiltration of agrochemicals particle in the heart and
oxidativestress.
2. Methodology
2.1. StudyIdentification
This project is based on non-systematic approach method to review the existing literature.
Publications articles that showed cardiovascular diseases due agrochemical exposure were
identified through the following databases: PubMed, Science Direct and EBSCO search engines.
A preliminary total of 150 related published research articles up to 2015 were selected using the
various combination of keywords: “cardiovascular”, “agrochemicals”, “pesticides”, “herbicides”,
“insecticides”,“farmworkers”withnorestrictionsofpublicationtypesanddates. Thereferencelist
ofrelevantpublicationsidentifiedwerecheckedforadditionalstudiesandrecentarticlesinrelevant
journalsusedtocompileanadequateinformationfordiscussion. Thewholesearchwaslimitedto
studiespublishedinEnglishinandpeerreviewedjournalsonly.
2.2. CriteriaofInclusion
Thenon-systematicreviewandidentificationofeligiblestudieswereperformed. Thetitlesand
abstract were screened to determine their relevance to the objective of the study. The full text of
potentiallyrelevantstudieswasthenexaminedandappliedeligibilitycriteriaappliedtothestudy
(Table 1). Articles that were used the farmworkers must be healthy or without any prior medical
conditionsandnon-cigarettesandalcoholdrinkers.
Articles were considered eligible to review if fulfilled the following six inclusion criterion as
shownintheTable1.
Table1.Inclusioncriteriaforresearcharticlestobeusedincompilingthisnonmeta-analysisresearch.
Number Criterion
Itmustbeanoriginalepidemiologicalstudyusingacase-control,crosssectionalprospective
1
studydesignandothertypeofreviews
2 PapershouldbewritteninEnglish
3 Theagrochemicalsshouldbemeasuredinactualbloodsamples
Thereportedmeasurementofassociation,includeoddsratios(OD),andrelativerisk(RR)
4
andconfidenceinterval(CIs)forcardiovascularrisk
Studiesshouldusethebiomarkersofanyagrochemicalscompoundsusedinthe
5
agriculturalindustries
6 Cardiovascular(CDV)wasconfirmedbyself-reportedquestionnairesorhospitaldiagnoses
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3. Results
InstudybyWeichenthaletal.[4]statisticalanalysishazardratios(HR)andtheir96%Confidence
interval(CI)wereestimatedusingCoxproportionalhazardmodel. Threeseparatemodels(minimal,
moderate and fully adjusted) were used to evaluate the relationship between ambient PM
2.5
and non-accidental and cardiovascular mortality. Potential confounding factors included in the
abovementionedmodelswereaddedatdifferentmodels. Simplemodelswereexaminedwithoutany
confoundingfactorsfirst-minimalmodel.Thiswasfollowedbymoderatelymodelsincludingpotential
importantbehavioural/personalfactors,andfinallyadjustedmodelsincludedsocioeconomicand
educationalbackground. SensitivityanalysesresultedinstrongerrelationshipbetweenambientPM
2.5
concentrationandcardiovascularmortalityamongmen. Thereweresignificantpositiveassociation
betweenPM andcardiovascularmortalityinallthreemodelsformenascomparedwithwomen
2.5
(Adjusted model-HR = 1.66; 95% CI: 1.04, 3.36; minimal model-HR = 1.32; 95% CI: 1.00, 1.76 and
moderatelymodel-HR=1.41;95%CI:1.00,2.02)(Table2).
Each agrochemical concentration was log-transformed to improve the level of normality in a
studyconductedinUnitedState. Theadjustedconcentrationwasusedtocalculatetheassociation. For
eachagrochemicalbothlipidstandardizedandwet-weightconcentrationage,sex,race,education,
familyincome,smoking,alcoholuse,diabetes,serumcotinineandBMIwereadjustedaspotential
confounders. Additional,logisticregressionanalyseswereconductedtoestimatetheoddratioofthe
agrochemicalsinperipheralarterialdisease(PAD)againstsubjectswithoutPAD.Subjectswithobesity
addedasconfounderofPADhadsignificantincreasedmeanlipidsstandardizationvalueofp,p’-DDE
(OR=1.47;95%CI:1.08,1.99)(Table2). Mostwet-weightconcentrationofagrochemicalsalsoshowed
significantassociationthatweresimilartothoseofthelipidstandardizedconcentration.
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Table2.Studycharacteristics.
Agrochemical Health
Geographical Sample
Citation StudyDesign Productof Outcome ReportedFindings(OD,RRIMetc.) ConfoundingFactors
Location Size
Exposure Assessment
Model1:(obesity)OR0.304,95%CI:0.246,0.889*
Model2:(currentsmoking)OR1.382,95%CI:0.588,3.249* Hypertension;Obesity
Cardiovascular Model3:(Hypercholesterolemia)OR0.633, cigarettesmoking;
Castanedaetal.[5] Michigan 300 Crosssectional Particulatematter
system 95%CI:0.207,1.939* Type2diabetes;
Model4:(Diabetes)OR2.552,95%CI:0.885,7.359 Hypercholesterolemia
Model5:(Hypertension)OR0.459,95%CI:0.155,1.361*
Palpitations Malaise
Tsimbirietal.[6] Kenya 801 Crosssectional Pesticides chestpainleg pvalue<0.002 Headache
swelling Respiratory
Minimaladjusted:
HR1.08,95%CI:0.75,1.55(All);
HR1.16,95%CI:0.77,1.74(Men);
HR0.84,95%CI:0.39,1.82(Women)
Moderatelyadjusted:
North Cardiovascular HR1.25;95%CI:0.81,1.94(All)
Retrospective Ischemicheart
Weichenthaletal.[4] Carolinea 93,378 cohortstudy PM2.5compounds mostprecise HR1.52;95%CI:0.92,2.51(Men); diseaseCerebrovascular
andIowa exposure HR0.68;85%CI:0.28,1.67(Women)
Fullyadjusted:
HR1.31;95%CI:0.84,2.04(All)
HR1.66;95%CI:1.00,2.78(Men)
HR0.62;95%CI:0.25,1.55(Women)
Lipidstandardized
ObeseOR1.47;95%CI:1.08–1.99
Non-obese0.92;95%CI:0.63,1.34
p,p’DDE
Trans-nonachlo Wet-weight(Withoutlipidadjustment)
Mortalityby
Oxychlordane Obese:1.52,95%CI:1.15,2.03
Minetal.[7] UnitedState 31,126 Retrospective causeofdeath Diabetesmellitus
Diedrin p<0.05 Nonobese:0.92;95%CI:0.64,1.30
SumofffiveOC
Wetweight(WithLipidadjustment)
pesticides
Obese:1.56;95%CI:1.01,2.44
Non-obese:0.85;95%CI:0.54,1.32
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Table2.Cont.
Agrochemical Health
Geographical Sample
Citation StudyDesign Productof Outcome ReportedFindings(OD,RRIMetc.) ConfoundingFactors
Location Size
Exposure Assessment
HR1(0–50days)0.76(51–100days);
95%CI0.76–1.47,
Myocardial
HR1.06p-value0.93(101–250);
Carbamates, infarction
95%CI0.71–1.230.97(>250days);
organochlorides mortality
95%CI0.75–1.260.57Highexposure;
organophosphates FamilyhistoryofMI
95%CI0.57–1.38;HR0.88
pyrethroids Smokingcigarette
NorthCarolina Prospective Herbicides 1(0–50days) Obesity
Millsetal.[8] 54,069
andIowa Study Fumigants Myocardial 1.10(51–100days)95%CI0.83–1.46 Hypertension
Fungicides infarction 1.14(101–250)95%CI0.91–1.43 Diabetes
incidence 1.19(>250days)95%CI0.96–1.4 Alcoholicdrinkers
1.12Highexposure95%CI0.84–1.48
1(0–50days)
Myocardial 1.10(51–100days)95%CI0.83–1.46
infarction 1.14(101–250)95%CI0.91–1.43
incidence 1.19(>250days)95%CI0.96–1.4
1.12Highexposure95%CI0.84–1.48
*p<0.1.
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4. Discussion
4.1. EpidemiologicalStudies
AstudythatwasconductedinNaivashwhichissituated80kmNorthWestoftheKenyanrift
valleyshowedthatmostofthefarmworkercomplainofhealthissuesrelatedtoagrochemical. Most
farms were green house, floriculture and horticulture with an extensive usage of wide variety of
agrochemicalsthroughouttheyeartocontrolthedevelopmentofplantsandweeds[6]. Thelarge
proportions of farmworkers were predominant spraying agrochemicals most of the time. Also,
farmworkersthatperformremovalofweeds,plantingandharvestingreportedthehighestproportion
of symptoms potentially related to pesticide exposure over a period of time. The total number
of 247 (34.5%) farmworkers showed cardiovascular symptoms (palpitation, chest pain and leg
swelling) [6] (Table 2). There was an indication that a higher proportion of flower farm labours
thatcontinuouslyusingtheagrochemicalsexhibitedhighincidentofcardiovasculardiseaseduring
theirlifetime. Thesefindingshadbeenlinkedwithhandlingandusageofagrochemicalovertime.
The following: edema, pallor and tachycardia were some of the common symptoms related to
cardiovasculardiseaseofagrochemicalsexposure. Therewasatotalof26(23malesand3females)
farmworkersresponsibleforsprayingdutiesintheflowersection. Thetotalof13(50.0%)ofthese
farmworkerscomplainofpalpitation,chestpainandlegswelling. Themeancomparisoncomplainant
andnon-complainantsofthesprayuserwassignificantlydifferentwithp-value<0.05[5](Table2).
Theoverexposuretoagrochemicalsandhealthconsequencesneedstobetakenintoconsiderationby
thefarmersandgovernmentsectorstoreducetherateofmortalityduetocardiovasculardiseases.
A study conducted in North Carolina and Iowa reported that the use agrochemicals were
positively associated with either myocardial infarction (MI) mortality or incidence among farm
workers[4](Table2). Farmerswerealsoexposedtoseveraltypesofparticulatesmatter,including
diesel exhaust and high level of dust containing endotoxin and mold. A study in Sweden found
an elevated risk of ischemic heart diseases mortality among those who experienced occupational
exposuretodueagrochemicalexposure[8]. InNorthCarolinaandIowatheoccurrenceofmortality
andincidenceamongfarmworkerswereduetoagrochemicalsastheriskfactorforMIdevelopment.
Theparticipantsofolderage,whiteraceandthosewithfamilyhistoryofMI,cigarettesmokers,
obesity,hypertensionanddiabeteswerealsoassociatedwithanincreasedriskofMI(Table2). Also
alcoholicdrinkersweremorelikelytoexperienceMIifcomparedtonondrinkers[4]. Currently,there
isanextensiveliteraturethatshowedthatconfoundersinTable2mighthavethenegativeimpacts
farmworkers. In all the study the baseline was established that to exclude the farmworkers with
riskfactorsthatmightcausecardiovascularconditions. AnecologicalstudyinMontana,Minnesota
and North and South Dakota found that those living in the countries with wheat production and
exposedtoagrochemicalsweremorelikelytodiefromacutemyocardialinfarctionoveraperiodof
time[9]. ThepathophysiologicalmechanismsofparticulatematterexposureandMIhavebeenwell
characterized.Allonetal.[10]hypothesizedthatthepathophysiologyofparticulatematter(PM)occurs
throughaninflammationleadingtotheincreaseofplasmafibrinogen. Therearelotofunreportedcase
ofdeadorsickfarmworkersduetoagrochemicalexposurewithoutknowingthecauseofthatmight
causedeath.
A study conducted in North Caroline and Iowa reported a total number of 839 non-fatal
myocardialinfarctionamongthe32,024participantsintheincidenceanalysisoveramedian5.0years
follow-upperiod[8]. Fatalandnon-fatalmyocardialinfarctioncaseswerecausedbytheusageof
individualagrochemicalsoveraperiodoftime.Theobjectiveofthatstudywastoassesstheassociation
astowhetheragrochemicalsapplicatorsandotheragriculturalexposurestoberelatedtofataland
non-fatalmyocardialinfarctionamongmaleandfemalepesticideapplicatorsinAgriculturalHealth
Study over a period of time. Of the 49 individual pesticides that qualify for both mortality and
incidenceanalysis,6hadbeensignificantlypositiveassociatedwitheithercardiovascularmortalityor
incidenceoccurrenceofagrochemicalexposure[7].
Int.J.Environ.Res.PublicHealth2016,13,229 7of12
In Table 3, a hazard ratio of more than 1 for one agrochemicals indicate that agrochemicals
applicatorsmorelikelytobeaffectedwithalethaldoseof50(LD ).
50
Table3.Thesummarizedassociationofpesticidesusageandnon-fatalmyocardialinfarctionnon-fatal
incidenceandmortalityamongmaleandfemalepesticidesapplicators,AgriculturalHealthStudy,
1993–2006[7].
Males Women
Pesticides HazardRatio Outcome Agrochemicals OddsRatio Outcome
1.54; 2.1;
Ethylenedibromide Chloropyrifos
95%CI1.05–2.27 95%CI1.2–3.7
1.34; 3.2;
Maneb/mancozeb Mortality Insecticides Coumaphos
95%CI1.49–3.86 95%CI1.5–7.0
2.40; 2.5;
Ziram Carbofuran
95%CI1.49–3.86 95%CI1.3–5.0 Myocardial
1.20; 2.5; infarction
Aldrin Pendimethalin
95%1.01–1.43 95%CI1.2–4.9
1.24; Non-fatal Herbicides 1.8;
Dichlorodiphenyltrichloroethane 95%CI1.04–1.46 myocardial Trifluralin 95%CI1.0–3.1
infarction
2,4,5-trichlorophenoxyacetic 1.21; 2.5;
Fungicide Metalaxyl
acid 95%CI1.03–1.43 95%CI1.1–5.3
Any agrochemical particles with the same active ingredients as mentioned above Table 3
has the chances of falling with the same 95% confidence interval range that might lead to health
complications [11]. The worst agrochemical associated with mortality of male applicators was
Ziramamongagrochemicalssprayapplicatorswhereasdichlorodiphenyltrichloroethaneshowedan
associationwithnon-fatal(withoutdetectableeffectofmortality)myocardialinfarction. Nopesticide
wasassociatedwithbothmortalityandnon-fatalmyocardialinfarction. Table3,illustratethatthe
impact of agrochemical can have on both gender lethal dose will depended on the exposure time.
AstudybySriernstörmetal.[11]hadreportedthathighprevalenceofcardiacconsequencesamong
thefarmworkersthatapplyagrochemicalsovertime. Themostcommonagrochemicalsusedwere
organophosphateandcarbamatesherbicide.
Amongfemaleapplicatorsacutetoxicityofchlorphyrifos,coumaphosandcerbofuranpesticides
varyfromslightlytohighlytoxicthatdependsonexposuretime. Chlorphyrifos, coumaphosand
cerbofuranallinhibitacetylcholinesterasetovaryingdegreewhichisresponsibletomonitortheheart
beat[12].AnecologicalstudyperformedinMontana,MinesotaandNorthandSouthDakotafoundthat
thoselivingincountieswithhighwheatproduction,useasasurrogateforherbicidesexposurewere
morelikelytodiefromacutemyocardialinfarction[9]. Therelationshipbetweenagrochemicaland
healthisofgreatinterestinfieldoftoxicology. Astudyinratssuggestedthatmyocardialirregularities
occur for up to 6 months after an acute high-level of exposure to a cholinesterase inhibitors [13].
Thepeoplewithothercardiovascularconfounderssuchasobesity,hypertensionandstrokewerelikely
toincreasetheexacerbationofhealthcomplicationswhenexposedtoagrochemicalsoveraperiod
of time. The same results were found in South African whereby women were designated for soft
labour[14].
Agrochemicalsultra-fineparticlehavethepotentiallytocausetheperipheralarterydisease(PAD)
alsoknownasperipheralvasculardisease(PVD).ThedevelopmentofPVDisduetothenarrowing
ofthearteriesthatsupplytheheartorbrainbythepresenceofultrafineparticlesorfattyacid[14].
Theendresultsofthisdiseasemayincludevariousformofinfectionortissuedeathorcoronaryartery
disease[15]. Thisblockagemightbeduetoinfiltrationofultrafineparticlethatcaneasilygetstuckin
thepathwaysofbloodflow. Theoutcomeofthisblockagecanbeatherosclerosis[16]. Thediseaseis
associatedwithelevatedcardiovascularmorbidityandmortalityinmostcountries[17,18]. Inaddition
to the conventional risk factors, it had been shown that organochloride (OC) pesticides might be
contributed to the development of PAD. Therefore, the confounders may increase the chances of
cardiovasculardiseasesasstatedinthepreviousparagraph. AlsotherecentstudiesusingtheNational
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HealthandNutritionExaminationsurvey(NHANES)datahadshownapositiveassociationbetween
concentrationofOCpesticidesandself-reportedcardiovasculardiseaseamongfarmworkers[19].
Peripheral artery disease was linked to two body systems namely: integumentary and
cardiovascularsystem. Thismightposeevenabiggerchallengebecauseintensivestudieshadbeen
carryingouttoshowthecloserelationshipbetweenskinandagrochemicals. Whereby,integumentary
system was of the route of absorbing agrochemicals particles. Therefore, individual farmworkers
hadmorethanonerouteofgettingaffectedbytheultrafineparticles. Theendresultswillbeinthe
bloodcirculatorysystemthatmightleadtotheblockageofbloodflowwhichwillultimatelycause
cardiovasculardisease.
PollutantswithaerodynamicdiameterofPM andotherconfounders(hypertension,obesity,
2.5
stress and smoking) had been generally associated with increased risks of myocardial infarction
(MI), stroke, arrhythmia and heart failure exacerbation within hours of exposure in susceptible
individuals [20]. The distribution of airborne ultrafine particulate matter due to agrochemicals
particlesandresidualcompoundshavebeenlinkedwithendothelialdysfunctionandvasoconstriction
that increase blood pressure prothrombotic and coagulant change, systematic inflammatory and
oxidativestressresponse,autonomicimbalanceandarrhythmiaandprogressionofatherosclerosis.
As consequence there was a significant relationship between agrochemicals residue with PM .
2.5
The ultrafine particles have the ability to penetrate and pass all different vessels until reaching
thecardiacsystemtocreatebloodflowblockage. Theblockageofthebloodflowtothetargetsite
of the heart might lead to development of other health conditions that might cause death due to
cardiovasculardisease(Table2).
Therefore,mostaffectedpeoplewillbefarmworkersthatworkdirectlywithagrochemicalsinthe
fieldcloseproximitywiththeground. Whereby,theotherhealtheffectoftheblockagewasunbearable
causedbyparticulatetosusceptibleindividualonthefarm. Thesusceptibleindividualmaytheones
withotherhealthconditionsasshowninTable2. Cardiovasculardetrimentalconsequencesdueto
ultrafine particles (UFPs) exposure had been observed in epidemiological studies (Table 2). Once
agrochemicalsparticlesdepositedintothelungUFsinmightgaintheaccesstothebloodcirculation
bydifferenttransferroutesandmechanisms,resultingindistributionthroughoutthebody,including
thebrain[20]. Theparticulatematter(PM)isauniquelyimportantpublicissueamongstlistofnovel
factorsthatmightcausehealthcomplications. Inparticulate,particulatematter(PM)inhalationisone
oftheestablishedtriggermechanismofcardiovasculareventsthatmightoccurswithinanhourto
daysofexposuredependingonconcentrationlevelofagrochemicalsparticles. Moreover,thepresence
ofagrochemicalsultrafineparticleinthebodysystembeyondservingasimpletriggeredthatelicits
numerous adverse biological responses have the potentially to cause death. This could likely be
explained by translocation of UFPs from the respiratory epithelium migrating towards the blood
circulationsystemandsubsequenttoxicitytowardsvascularendothelium. Thismightalterblood
coagulationmechanism,triggeringautonomicnervoussystemreflexactioneventuallyalternatingof
thecardiacfrequencyandfunctionmechanismofthecardiacmusclemechanismthatmightleadto
cardiovasculardisease. AsurvivalanalysisofinUnitedState(US)Medicaredataforatotalnumber
of19,600survivorsofacuteMIin21citieshadshownthetotalriskofanadversepostMIoutcome
death[20]. ThisnumberwasduetosubsequentMIorfirstadmissionforcongestiveheartfailuredue
toadverseincreaseexposurelevelofagrochemicalswithPM concentrationsoveraperiodoftime.
10
Ingeneral,findingsfrompreviousstudiessupportedacausalrelationshipbetweenchronicPM
2.5
exposure and mortality. These relationships might cause the change in the biological mechanism
including altered autonomic functions, impaired vascular function and increased pulmonary and
systemicinflammation[21].
AstudythatwasdoneinUSshowedtheconversely,positiveassociationbetweenPM particles
2.5
andcardiovascularsystemmortalityinmenoveraperiodoftimeTheagrochemicalswithambient
PM wasassociatedwith26%–28%increasesincardiovascularmortalityinHarvardsixcities[22].
2.5
ThefindingsofpreviousstudyconductedbyWeichenthaletal.[6]; Waggoneretal.[23]suggested
Int.J.Environ.Res.PublicHealth2016,13,229 9of12
thatlong-termexposuretoambientPM concentrationmayhadadversehealtheffectamonghealth
2.5
population. The previous evidence also suggested a strong relationship between ambient PM
2.5
cardiovascularmortalityamongwomenandmenfarmworkers[6,24,25].
4.2. MechanismofInflitrationofParticulateMatterintheHeart
4.2.1. Blood
The pathway of potential mechanisms that is, linking the ultrafine particulate matter and
cardiovasculardiseasewasoutlinedbyFranklingetal.[26]. Theendresultswillbeclinicalevents
that might lead to myocardial infarction, congestive heart failure (CHF), stroke, arrhythmia and
sudden death. The infiltration of particulate matter in the blood circulatory system was through
differentpathwaysi.e.,ingestion,inhalationanddermalcontact[24,27]. Thepresenceofagrochemical
particlesinthebloodcirculatorysystemraisesaconcernforhealthresearchers,scientistsandhealth
professions. Thelastplacesfortheparticulatematterwillbeeitherinthebrain,heart,lungorliver.
Accumulationofparticlesoverperiodoftimemightleadtotheobstructionofbloodflowtosensitive
areas in the human body. This obstruction mechanism of blood flow may lead to serious health
complicationswhichmayultimatelycausedeath. Previousstudiesshowedthatpesticidesexposure
ofteninducesacuteandchronichumandiseases[28]. AstudyconductedinChinashowedthatthe
level of agrochemicals with PM in blood samples was high among farmworkers over time [29].
10
ThesameauthorfoundoutthattherewereextensivelongandshorttermhealtheffectsonChinese
farmer workers exposed to agrochemicals containing PM . The high and medium toxic levels of
10
agrochemicalparticlesweremostharmfultothefarmworkersandtheirfamilymembers. Astudy
byGressetal.[5]alsoprovidedanextensiveanalysisofthecriticalroleinwhichglyphosate-based
herbicidesmarkedlyaffectcardiovascularsysteminmammals.
4.2.2. OxidativeStress
Reactive oxygen species and their highly destructive nature have been known for at least
50years. Thedevastatingpathophysiologyeffectsofoxidativestressduetoagrochemicalsultrafine
particulatematteronvitalbodyorganarestillofgreatinteresttotheresearchers,scientistandhealth
professions[30]. Thexenobioticcompoundshavetheabilitytoproducefreeradicalsthatmightleadto
adversehealtheffectwheninhaledoringestedorincontactwithhumanskin. Thesefreeradicalsfrom
agrochemicalscompoundsmaybeimplicatedinthepathophysiologyofmanyhumandiseases. There
isanevidenceofanimbalancebetweentheproductionoffreeradicalsandtheabilityofthebodyto
counteractordetoxifytheirharmfuleffectthroughneutralizationbyantioxidantthatisanimportant
mechanismofreducingthepossibilityofatherosclerosisdevelopment[30]. Agrochemicalparticles
recognizedasapotentialhazardtothebiologicalsystem. Particulatemattermayleadtothepalpation
and/orblockageheartincreasingthebloodpressurethatmightleadtosuddendeath[5,6]. Someof
agrochemicalsmightbeindirectlyaffectthenormalfunctionsoftheheart.
AstudyconductedinArgentinaobservedthatthepresenceofhighconcentrationlevelsofheavy
metals in the blood sample of farmworkers was due to continuous usage of agrochemicals with
metals as active ingredients [31–33]. This might be due to long exposure to having heavy metals
to control aliens’ plants. Other laboratories had also demonstrated a positive correlation between
plasmaheavymetalsandincreasedcardiovasculardiseaseincidence,suggestingtheelevatedplasma
level of ceruplasmin (CRP) that should be considered as a risk factor for coronary disease [31–35].
The involvement of xenobiotic-induced oxidative stress by PM agrochemicals is well known in
2.5
theetiologyofmanyhumandiseasesbyweakeningthecardiacmusclethatwillaffectthenormal
functioningoftheheartandpotentiallylead[36].
Int.J.Environ.Res.PublicHealth2016,13,229 10of12
5. Conclusions
Thedevelopmentsofagrochemicalcompoundstoxiceffectamongstfarmworkersneedfurther
investigation.Theamountofliteratureavailablethatlinktheparticlematterlessorequalstoparticulate
matter2.5tocardiovascularsystemneedanadequateinvestigation. Asstateintheabovementioned
paragraphs adverse effects of low dose PM from agrochemicals mixtures on the cardiovascular
2.5
systemislargelyunknown. Theagrochemicalswithpotentialtoxicitytohumanhealthwillcontinue
beusedbyfarmworkersaslongasthegeneralpopulationneedtofoodtosurvive. Butthehealth
effectsofagrochemicalshaveaseriouscatastrophicimpactonhumanhealth. Theneedformorefood
placethefarmworkerstoproducesmorefruitsandvegetablebyusingagrochemicaltokeepupwith
thedemandscompromisingtheirhealthstatus. Thedetrimentalconditionsinwhichthefarmworkers
areplacedbythefarmownersarehighlyaffectedbytheunequaleconomicstatusoftheworldand
labourexploitationworldwide. Theunderlyingetiologicalmechanismsofagrochemicalparticulate
matterandcardiovascularsystemneedfurtherinvestigationinrelationtootherconfounders. Itis
clearthatagrochemicalhaveseriouseffectsonhumanhealthespeciallyonthecardiovasculardisease
whichwasthefocusofthisarticle. Also,themechanismsofpreventingusageofagrochemicalsas
wellastheiradsorptionthroughtheskinmaybeanotherfocusofthefutureresearch. Thiswillhelpin
understandingthePADetiologicaldevelopmentinrelationwithcardiovasculardisease.
Thewidevarietyagrochemicalsusedfarmersaswellastheprevalenceofunreportedcasesof
mortalityduetocardiovascularsystemisofseriousconcerntothehealthprofessionwhichmightnotbe
thecaseforagriculturalsectors. Theprevalenceofunreportedcaseofmortalityduetocardiovascular
systemisofseriousconcern. Thenumberoffarmworkersthatuseagrochemicalsthenretiredduetoill
healthnormallydiewithoutknowingthecauseoftheirdeath. Insteadmostcomplainofwidevariety
ofdiseasesandhealthconditionswiththelackofclearevidenceofthecauseoftheirdeath. Thisisa
commoncircumstanceinundevelopedcountriesduetofinancialconstrainsthatwillabletoconduct
forensicpathologicalinvestigationofthedeceased. Thebanningofagrochemicalintheagricultural
sectors will produce devastating economics effects and people will suffer worldwide. Therefore,
differentstakeholdersintheagriculturalandgovernmentsectormustplayasignificantroletocurb
anddecreasetheagrochemical-cardiovascularconditioninordertodecreasemortalitypercentage.
Acknowledgments:Iwillliketothankmywife(NomsaM.Sekhotha)andmytwolovelydaughters(Lesediand
Naledi)fortheirsupport. Also,liketothanktheUniversityofLimpopocommunitiesforprovidingguidance
duringtheprocessofcompilingandpublishingthismanuscript.
Author Contributions: Matome M. Sekhotha—compiling the manuscripts (90%), Kotsedi D Monyeki (2%),
MaseziESibuyi(8%).
ConflictsofInterest:Theauthorsdeclarenoconflictofinterest.
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