Environmental Engineering Reference
In-Depth Information
elimination.. The. manifestation. of. a. toxic. response. often. varies. with. the. route. of.
exposure,.depending.more.on.the.amount,.barriers.to.absorbance,.and.transport.of.
the. toxicant. than. on. the. actual. activity. of. the. toxicant. itself.. Examining. toxicity.
based.on.routes.of.exposure.isolates.the.differential.responses.and.segregates.sub-
populations.with.respect.to.activities.incurring.exposure.and.in.terms.of.an.easily.
measurable. dose. factor.. The. principal. routes. of. exposure. considered. here. are. oral.
ingestion,.dermal.absorption,.and.inhalation.
.
exPosuRe and eFFeCts thRough ingestion
Ingestion.and.inhalation,.rather.than.absorption.through.the.skin,.are.the.most.likely.
method.of.direct.exposure.to.nanoparticles..(See.Section.9.4.on.inhalation.exposure.).
There.are.two.important.considerations.in.assessing.the.risk.related.to.the.ingestion.
of.nanomaterials..The.irst.is.the.potential.direct.toxicity.resulting.from.contact.with.
the. digestive.epithelium..The.second. is.the. potential.for.the. nanomaterial.to.enter.
the. blood. circulation. (central. compartment). via. the. digestive. tract. and. thereby. be.
systemically.distributed.
Increasing. the. size. of. a. compound. or. particle. decreases. its. ability. to. cross. a.
cellular. barrier.. This. can. result. from. steric. hindrance. (the. particle. is. too. large. to.
physically.it.through.a.pore.or.space).or.thermodynamics.(the.rate.of.movement.is.
too.slow.to.be.of.consequence).
The.epithelium.of.the.digestive.tract.contains.tight.junctions.that.limit.the.size.
of.materials.that.can.pass.between.cells.to.enter.the.central.compartment..Particles.
with.an.effective.diameter.greater.than.4.nm.cannot.pass.between.the.cells.[2].and.
therefore.must.undergo.cellular.transport,.either.passively.or.actively..Active.trans-
port,.via.channel.transport.or.endocytosis,.is.subject.to.the.limited.capacity.of.the.
cell.to.transport.material..Passive.transport.is.driven.by.the.diffusion.gradient.and.is.
subject.to.the.permeability.of.intervening.membranes..Passive.cellular.transport.can.
be.considered.a.two-step.chemical.reaction..First,.a.particle.dissolved.in.digestive.
luids.partitions.and.dissolves.in.the.cell's.lipid.bilayer.membrane..Second,.the.par-
ticle.partitions.and.dissolves.in.the.cytosolic.medium..This.process.also.is.subject.to.
thermodynamic.limitations..To.predict.the.rate.of.absorption.for.a.nanomaterial.with.
a.variable.size.and.surface.behavior.requires.that.this.two-step.reaction.be.broken.
into.its.components.
9.2.1 d
iFFusiOn
The.introduction.of.a.molecule.into.the.lipid.bilayer.is.an.endothermic.process..The.
energy.necessary.to.initiate.the.process.is.provided.by.the.combined.partition.gradi-
ent.(i.e.,.differential.afinity.of.a.solute.for.an.aqueous.vs..non-aqueous.medium).and.
concentration. gradient,. and. is. released. once. the. compound. leaves. the. membrane..
The.larger.the.compound,.the.more.energy.is.necessary.for.it.to.transfer.from.the.
aqueous.phase.into.the.lipid.phase.of.the.bilayer..This.may.be.considered.in.terms.
of.the.probability.of.a.hole.forming.in.the.bilayer.large.enough.to.accommodate.the.
compound:.the.larger.the.compounds,.the.lower.the.probability.an.appropriate.sized.
