ecological health risk of joint effect of biological and chemical environmental factors

7/27/2019 Ecological Health Risk of Joint Effect of Biological and Chemical Environmental Factors

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InternationalJournalofEnvironmentandResource(IJER)Volume2Issue2,May2013 www.ijer.org

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EcologicalHealthRiskofJointEffectofBiologicalandChemicalEnvironmentalFactorsViktor.S.Rukavishnikov,Larisa.M.Sosedova

FederalStateBudgetaryInstitutionEastSiberianScientificCenterofHumanEcology,SiberianBranchofthe

RussianAcademyofMedicalSciences,Angarsk,Russia

[email protected]

AbstractTheobjectiveofthispaperistostudycommonmechanisms

andpatternsofjointeffectofbiologicalandchemicalfactors

on thehumanbody starting from experiments on animals.

The subchronic experimental studywas performed on 700

guinea pigs (inhalation with sulphur dioxide and AD).

Aspects of risk evaluation isolated andjointwith chemical

factor biotechnological products presented as

microorganismsproducers of feed additives and a final

albuminiferousproductareconsidered in this study. Itwas

showedthatapplicationofADandsulfurdioxidedevelopsa

response in the form of sensitization, allergopathy and

toxicoallergopathy characteristics and patterns of pigs

organism response to exposure of products of

biotechnologicalsynthesishavebeendetermined.

KeywordsJointEffect;ChemicalandBiologicalFctors;SulphurDioxide;AD;SDT;HDTIntroduction

The development of the biotechnological industry

yieldsopportunities tosolve theproblemsofmaterial

and food resources, environmental pollution, energy

supply,andpublichealthcare,aswellas tomeet thedemands of humanity, in addition, it also opens

possibilities toproducenew kinds of goods.Modern

production technologies include biotechnological

methods used in manufacture of feed additives,

hydrolytic yeast, interferon, enzymes, antibiotics,

aminoacids,plantprotectionproducts,farmingmulti

enzyme systems, insulin, and other bioactive

substances. Manufacture of these products involves

similar hygienic parameters determined by the

biologicalnature ofmaterialsused in theproduction

process and of the final products. Biotechnologicaladvances canbe limitedbypossibilityof abiological

environmental pollution resulted from the way that

these new products are obtained. Some studies have

addressed strategies to solve the toxichygienic andecologicalproblems causedbybiologicalpollutionas

opposedtowellstudiedchemicalpollution.Moreover,

the isolated exposure effects of the introduction of a

biological factor are considered by many to be an

uncommonevent(N.I.Sheina,2011).

There are no approved criteria used to evaluate the

jointeffectsofbiologicalandchemicalfactors.Thedata

presented herein is derived from longterm studies

performedat theEasternSiberianScientificCenterof

HumanEcologyof theSiberianBranchof theRussianAcademyofMedicalSciences (ESSHESBRAMS) that

concern theoreticalandpracticalaspectsof ecological

riskevaluationofthejointeffectsofabiologicalagent,

the dust of an albuminiferous productmanufactured

using amicrobiological synthesis of yeastlike fungi

Candida,andachemicalsulfurdioxide.

TheinitialstudywastriggeredbyaneventinAngarsk

city in October 1988for patient complaints on

bronchospasm whichdrew the attentionofAngarsk

cityemergencymedicaldepartments(L.M.Sosedova,2003). The Angarskiy biotechnological plant having

operatedfor10yearsreleasedanalbuminiferousdust

(AD),abyproductofthemicrobialsynthesis,intothe

air of the surrounding residential area.Quantities of

AD released into the air were higher than the

maximumpermissibleamounts.InOctober1988,there

wasnowindduringa7dayperiodand,consequently,

therewasnodispersionofpollutantsaccumulating in

theair.Differentcommissionsinvestigatingthesource

of the patients illnesses failed to reach a conclusion.

They reported that either AD or a chemical factor(sulfur dioxide)was themain cause of the patients


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illnesses. Sulfur compounds such as sulfur dioxide

were the most common air pollutants which was

known that during that period the concentration of

sulfurdioxideintheairhaddramaticallyincreased.(2

4mg/m3)(L.M.Sosedova,2003).

Materials and Methods

Anexperimental studywasperformedon700guinea

pigs provided by General Scientific Center VB

Vector (Novosibirsk, Russia) inwhich each group

included 812 mature laboratory animals. The

experimentsonanimalswereperformedaccording to

the European Convention for the Protection of

VertebrateAnimalsUsed for Experimental and other

Scientific Purposes (ETS 123) Strasbourg, 1986. The

studies were carried out in accordance with the

approved protocol by the Bioethical Committee of

ESSHE SB RAMS, standard study operational

procedures, and sanitary guidelines for settings,

equipment, and maintenance of experimental

biologicalclinics(vivaria).Sterilesawdustwasusedas

bedding for allanimals. Standard combinedgranular

complete diet feeding (extruded) for laboratory

animals was used for small laboratory animals.

Unlimitedtreatedtapwaterwasprovidedinstandard

drinkers for all animals. The animals were kept incontrolled environmental conditions with air

temperatureof1822 andarelativehumidityof60

70%. Setting lighting was naturalartificial. Newly

arrivedanimalswereplacedincagesinquarantinefor

7days.

Microbiologicalproductsofbiotechnologicalsynthesis

areknown tobealbuminiferous allergens,which can

causenotonlyhypersensitivity(sensitization)butalso

smalldose (SDT) or highdose (HDT) tolerance.

Therefore, threebaselinemodelsunderAD exposurewere examined: sensitization, SDT and HDT.

Sensitizationofguineapigswasachievedby injection

of 500 g AD mixed with incomplete Freunds

adjuvantunder thehind limbaponeurosis.To induce

tolerance, a150 g (SDT)ora 5000 g (HDT)water

soluble AD polysaccharide antigen was injected

intracardially into experimental animals under light

ether anesthesia for 14 days before sensitization.

Inhalationprimingwithsulfurdioxidewasperformed

byplacingguineapigsinprimechambersfor4hoursperday foreach in theperiodof10days.Thesulfur

dioxide concentration (24mg/m3), temperature, and

humidityweremaintained at the same level. Sulfur

dioxide inhalationwasperformedon threeoccasions:

14 daysbeforeAD injection, simultaneousness with

ADinjection,and14daysafterADinjection.

The animals were tested for hypersensitivity 2128

days post priming termination. Instant and delayed

type hypersensitivity were determined by mast cell

destruction (E.F.Chernushenko, 1978).Thepresence

of skinsensitizing antibodies was detected using

Ovaryspassivecutaneousanaphylaxistest (Z.Ovary,

1952).Othertestsincludedthepositiveintracutaneous

allergytest,reproductionofanaphylacticshockevent,

antigenspecific rosetting and antigenspecific

leukocytefixation(S.M.Pogorelskaya,1986),moreover,

passiveallergytransmissionwasassessedbymeansof

leukocyte mass (C. Prausnitz, 1962) and blood

histaminecount (G.V.Selyuzhitsky,1983).Neutrophil

functions were analyzed by phagocyte number,

phagocyte index, blood phagocytic activity, and

metabolic activitywithmelamineformaldehyde latex

ina spontaneousand latexstimulatedHCTtest (R.V.

Petrov,1989).Lymphokineproductionwasmonitored

by leukocyte fixation triggeredbymitogens such as

concanavalin and phytohemagglutinin (S.M.

Pogorelskaya,1986).AntigensproducedintheRussian

MycologicalCenter (St.Petersburg)wereused in the

reactionstodeterminespecific immuneresponses.An

integrated approachwas applied to the experimental

studies,which allowed analysis homeostasis changes

using the principle doseorganism status and

determining a common parameter for each animal

group(V.V.Sadovskiy,1996).Statisticaldataanalysis

was performed using Statistica 6.0 software for

Windows(licenseAXXR004E642326FA).Differences

amongstudyandcontrolgroupswereanalyzedusingStudents test. If comparison samples were not

normally distributed (according to the Kolmogorov

Smirnovcriterion),thenonparametricMannWhitney

Utestwasused.

Result and Discussion

The experimental model allowed evaluation of the

guineapigsresponse tocombinedexposure tosulfur

dioxideandAD[L.M.Sosedova,2003;L.M.Sosedova,

2010]. This exposure can induce responses that varywith the sequence of administration or intensity of


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exposure(Figure1).

FIG.1TYPESOFORGANISMRESPONSEOFGUINEAPIGSTO

JOINTEFFECTOFALBUMINIFEROUSDUSTANDCHEMICAL

FACTOR

Theexperimentalfindingsshowedsensitizationinhalf

oftheanimalsexposedtobothADandsulfurdioxide.

Moreover, the intensity of the sensitizationwas 50%

higherinsomeanimalscomparedwiththosethatwere

only exposed to AD. Allergopathy and toxico

allergopathywasfound in25%oftheanimals ineach

group. It was possible that the final response

depended on the phenotype of the

immunoallergologicreactiontoallergens.Considering

primary sensitization, SDT and HDT, the following

effectsonhealthweredetermined:

Sulfurdioxideinhalationledtodevelopmentofallergopathy in animals sensitized to AD.

Inhalation simultaneously with or prior to

sensitization toADhad insignificant effect on

theintensityoftheresponse.

Sulfurdioxideinhalationmadetheanimalslosetheir smalldose immunological tolerance,

whichcausedthemtobecomesensitizedtoAD.

Sulfur dioxide inhalation with or post HDTresultedinatoxicallergopathiceffect.

Thus,priorinhalationofsulfurdioxidedidnotleadto

HDT but caused apparent allergopathy in

experimental animals. The results of experimental

modeling of the combined effects of albuminiferous

dust (a byproduct of biotechnology) and sulfur

dioxide(achemical)madethefollowingconclusions:

A response to the combined effects ofbiological and chemical factorsdeterminedby

itsbaseline prenosological conditionsmaybe

diverse: The sequence of exposure tobiological and

chemical factors was important in

understanding an animals quantitative and

qualitativeresponsetoexposure;

Itwasimportanttoconsiderbothspecificandnonspecific characteristics of a physiological

systemfunctioningtakingintoaccountthekeyroleofimmunestatuschanges[L.M.Sosedova,

2003;L.M.Sosedova,2010]

Hygienicmodelingalloweddevelopmentofamethod

to study the combined effects of biological and

chemical factors (L.M. Sosedova, 2010) and yielded

severalsignificantprinciples.

The threebaselinemodels (sensitization, SDT,and HDT) should be created for an

experimental study of biological factor

exposureofanynature.

Chemical exposure should occur in thefollowing sequence: prior to, simultaneously

with, and postAD injection to determine the

mostdetrimentalsequenceofadministration.

Tounderstand the featureof theresponseandevaluation of an animals condition, and

analyzehomeostasischanges, itwas important

toemploytheprincipledoseorganismstatus

toevaluatealleffectsasawhole.

Increases residential were modern productiontechnologiesused in theplants located inornear the

residential area and the methodological principles

outlinedheremaybecome thebasis forbiomodeling

to study the combined effects of differentbiological

andchemicalfactors.

Theseexperimentalstudiesmayallowidentificationof

the cause of the increase in patient complaints of

bronchospasmodic syndrome at emergency

departments inOctober 1988 inAngarsk citv [L.M.

Sosedova,2003;L.M.Sosedova,2010].Theoperationofthebiotechnological plant released large amounts of

AD into the air of the residential area.AD exposure

over several years might cause a prenosological

responsedifferentdependingonimmunoallergological

phenotype and the quantity of absorbed allergen in

sensitive populations. Some people developed latent

sensitization to AD;while others developed SDT or

HDT; i.e. the organism as a system adaptedwith a

high degree of selfregulation using additional

resources reformed to thenew levelof compensatory

adaptation [L.M. Sosedova, 2003;G.M. Bodienkova,1996].

Albuminiferous

dust

Noeffect Sensitization Smalldose

toleranceHighdose

tolerance

+Chemicalfactor

Sensitization Toxico

allergopathyAllergopathyCrosssectional

sensitization


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A prenosological response to AD, and subsequent

exposure to a chemical factor led tovarious types of

bronchospasms with allergic or toxic components.

Various types of responsesmightbe responsible for

different conditions in people, thus physicians

registered bronchospasms of both an allergic and atoxicnature.

Thus, the causal or primary factor that prepared an

animal to develop bronchospasm was AD, a by

product of a microbial synthesis, and the modified

triggerorrisk factorwasachemical.Epidemiological,

hygienic, and allergological studies suggested

sulfurous anhydride which might have been the

chemical pollutantwhich could causebronchospasm

by itself due to its irritating [C. A. Frenga, 1999; F.

Riedel,1988].Chemicalfactorexposuretoabodywith

modifiedspecificreactivity toADcancauserecurrent

bronchospasmodic allergic or toxicallergic reactions

evenwhenADwasabsentintheair.InFebruary1995,

asimilareventoccurred inAngarskcity,althoughthe

biotechnologicalplantwasnotinoperationatthattime.

The larger the population that develops sensitization

orHDT to ADwas, the greater the possibility of a

widespread event was. Clinical pathologies can be

influenced by contact of an organism with other

albuminiferous allergens and the increasing kinds of

pollutants in both industrial and agricultural areas

(pollen, hair, down, medicine, food, etc.) may have

antigenic determinants in common with proteins of

biotechnologicalsynthesis.

Extrapolationoftheresultsofexperimentalstudieson

humans allowed us to suggest about the nature and

causesof the formationof thepopulationofAngarsk

bronchospasm. Analysis of experiments on animals

showedthedevelopmentofseveralformsofresponse

whenexposedtoADandsulfurdioxide:sensitization,

allergopathy and toxicoallergopathy. Similar

symptoms of bronchospasm detected and affectedpatients.

Thelackofmonitoringoftotalbiologicalairpollution

includingtheareaswithbiotechnologicalplantsdidnt

allow prediction or evaluation of unfavorable events

associated with mass cases of acute toxicallergic

disorders. It should be considered unreasonable to

place biotechnological plants in industrial cities or

downwindofchemicalplants,sinceitwasriskytothe

population of the combined effects ofbiological and

chemical factors.Moreover, ultraviolet and radiation

exposuremaycausecreationofnewcompoundswith

unexpectedqualities.

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ecological health risk of joint effect of biological and chemical environmental factors

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