Environmental Engineering Reference
In-Depth Information
inlammation,.DNA.damage,.and.apoptosis.(cell.death).[49].
The.mechanism.for.this.
oxidative.stress.response.is.neither.always.clear.nor.consistent..In.some.systems,.the.
oxidative. stress. appears. to. be. due. to. direct. production. of. reactive. oxygen. species.
(ROS).by.the.nanoparticles.[39,.55]..In.others,.it.appears.the.damage.may.be.medi-
ated.through.a.direct.inlammation.response.to.the.nanoparticles..The.studies.to.date.
also.suggest.that.toxicity.increases.directly.with.the.surface.area.per.unit.mass.of.the.
nanomaterial.[23,.26,.34,.38,.45,.57-59].
While.the.lung.is.the.primary.target.of.nanomaterials.[31,.54,.57],.studies.show.
that.the. nanoparticles.can. enter. circulation. and. migrate.to. various. organs. and. tis-
sues,. where. they. can. accumulate. and. damage. organ. systems. that. are. sensitive. to.
oxidative.stress.[40,.44,.57]..Structural.impacts.such.as.vascular.thrombosis,.acceler-
ated.development.of.atherosclerosis,.other.adverse.cardiovascular.effects,.and.neuro-
degeneration.are.common.toxic.responses.to.oxidative.toxicants..Because.the.study.
of.nanotoxicity.is.in.its.infancy,.many.of.the.studies.to.date.are.
in vitro
.studies.and.
therefore.do.not.consider.pharmacokinetic.factors..Much.more.study.is.required.in.
evaluating.the.toxicity.of.nanomaterials,.particularly.
in vivo
.systems,.before.the.true.
toxicological.nature.of.these.materials.can.be.discerned..[24,.25,.39,.50].
. ConClusions
The.health.risk.assessment.of.nanomaterials.requires.certain.considerations.not.com-
mon. with. typical. toxicants.. First,. the. characterization. of. nanomaterials. will. vary.
signiicantly.based.on.whether.the.material.is.quantiied.on.a.mass.or.molar.basis.
because.of.the.potential.for.high.variability.for.the.same.chemical.based.on.the.size.
distribution.of.the.particle.considered..If.a.nanomaterial.will.be.assessed.based.on.its.
activity.as.a.nanoparticle,.then.an.approach.similar.to.that.used.for.the.assessment.of.
exposure.to.ibers.should.be.used,.rather.than.the.typical.approach.that.characterizes.
risk.on.a.per-mass.basis..Second,.nanomaterials'.physical.size.introduces.novel.fac-
tors.related.to.exposure.and.absorption.based.on.steric.factors.that.affect.both.dosing.
rates.and.
in vivo
kinetics..Consequently,.variations.in.the.sensitivity.of.the.popula-
tion.become.of.paramount.importance.to.predicting.adverse.response..The.third,.and.
likely.the.most.troublesome,.consideration.is.that.the.types.of.toxicological.response.
will. likely. vary. between. molecular. and. nano-sized. forms.. Nanomaterials. are. less.
likely. to. induce. systemic. effects. and. more. likely. to. act. as. contact. toxicants.. Fur-
thermore,.the. size. of. the. material's.particles.makes. it. likely. that.the. physiological.
responses.will.be.of.an.immune.or.inlammatory.nature..These.adverse.effects.based.
on.defensive.mechanisms.typically.do.not.follow.dose-response.but.rather.threshold.
kinetics,.and.also.demonstrate.high.variability.within.the.population,.depending.on.
individual.sensitivities.
.
list oF sYMbols
A
Surface.area
A
Y
Surface.area.at.
Ydt
.
A
GI
Cellular.surface.presented.to.the.gastrointestinal.(GI).tract
A
CC
Cellular.surface.presented.to.the.central.compartment
