Environmental Engineering Reference
In-Depth Information
barrier.retards.or.prohibits.the.movement.of.the.material,.regardless.of.the.concen-
tration.gradient..Therefore,.a.nanoparticulate.form.of.a.material.may.have.no.effect,.
whereas.a.molecular.form.may.invoke.toxicity.simply.because.the.larger.nanopar-
ticulate.form.cannot.reach.the.site.of.action..Conversely,.steric.inhibition.to.trans-
port.may.cause.a.nanomaterial. to.accumulate.in.a.particular.physiological.region,.
resulting.in.a.unique.toxicological.response..For.example,.a.molecular.toxicant.that.
causes.systemic.toxicity.may,.when.in.nanoparticulate.form,.cause.only.toxicity.at.
the.point.of.environmental.contact.because.of.steric.inhibition.to.absorption.of.the.
nanoparticle..However,.risk.assessment.must.consider.variations.in.response..Many.
of.the.physiological.barriers.to.particulate.exposure,.absorption,.and.even.response,.
tend.to.vary.greatly.within.the.general.population..This.may.result.from.physiologi-
cal.conditions.(age,.disease.state,.etc.),.co-exposure.to.other.environmental.factors,.
and/or.genetic.predispositions..As.a.result,.it.will.be.important.to.quantitatively.con-
sider.this.variability.when.selecting.toxic.endpoints.and.predicting.the.proportional.
response.of.the.exposed.population.in.any.risk.assessment.
9.1.2 i
nFlammatOry
and
i
mmune
-b
ased
m
eChanisms
The.general.understanding.of.the.toxicity.of.nanomaterials.is.still.evolving.with,.in.
some.cases,.surprising.results..Initial.research.shows.that.inlammatory.and.immune-
based.mechanisms.of.toxicity.may.be.particularly.important.for.nanomaterials..For.
example,.the.most.signiicant.toxicity.currently.attributable.to.a.nanomaterial.results.
from. exposure. to. single-walled. carbon. nanotubes.. Such. exposure. can. cause. pul-
monary. inlammation. manifesting. in. granuloma. and. ibrosis.. The. relative. impor-
tance.of.inlammatory.and.immunogenic.responses.can.signiicantly.complicate.risk.
assessment. because. such. responses,. as. an. adverse. effect,. vary. widely. within. the.
general.population..The.same.toxicant.exposure.could.elicit.responses.in.different.
people.ranging.from.no.effect.to.life.threatening.
Intrapopulation. variability. confounds. attempts. to. quantify. the. probability. and.
magnitude.of.immunogenic.or.inlammatory.response..Sensitivity.may.not.only.vary.
with.genotype,.but.also.with.factors.such.as.age.and.exposure.history..Thus.it.is.very.
dificult.to.predict..The.
a priori
.identiication.of.sensitive.sub-populations.will.be.
challenging. and. may. require. the. development. of. screening. methods. not. currently.
employed.in.environmental.risk.assessment..The.signiicance.of.this.variability.will.
depend.on.the.relative.prevalence.of.a.predisposition.to.response.within.the.general.
population..Current.advances.in.toxicogenomics.will.provide.the.basis.for.character-
izing.sub-population.sensitivities.and.is.likely.to.become.a.signiicant.consideration.
in.the.risk.assessment.of.nanomaterial.exposure.
9.1.3 C
ritiCal
v
ariables
The.toxicity.of.a.nanomaterial,.as.with.any.agent,.depends.on.the.chemical.proper-
ties.that.determine.its.potential.interactions.with.various.cellular.targets.in.an.organ-
ism.. Deining. exposure. as. the. presentation. of. the. potential. toxicant. to. the. target.
organism.at.the.environmental. boundary.(
ex integument
),.the.toxicity.then.can.be.
considered.as.the.intersecting.functions.of.absorption,.distribution,.response.(which.
is.the.combination.of.damage.and.repair.relative.to.homeostasis),.metabolism,.and.
