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[(th)20.7(at)-210.8(sp)21(ec)18.5(i)20.9(ca)12.8(ll)20.6(y)-214.2(u)0(s)15.3(e)0(s)-204.8(r)0(e)19.7(s)0(p)15.3(i)0(r)20.7(a)0(t)19.5(o)0(r)20.9(y)-220(tr)20.7(ac)18.5(t)-220.1(c)0(e)18.5(l)0(l)20.6(s)-219.8(cu)19.7(lt)20.6(ur)20.9(ed)-210.7(un)20.8(de)19.7(r)-219.9(A)0(L)18.8(I)]TJ
0 -1.1116 TD
[(co)19.7(nd)20.8(it)14.8(io)20.7(ns)-197.8(an)13.9(d)-208.4(e)0(x)19.7(p)0(o)20.8(s)0(e)14.1(d)-208.4(vi)20.7(a)-215.4(a)0(i)19.5(r)-208.4(is)-203.7(va)19.7(li)20.6(da)19.7(te)19.6(d)-214.2(b)0(y)-198(E)0(U)18.8(R)0(L)-206(E)0(C)18.6(V)0(A)19.1(M)]TJ
T*
[(an)19.7(d)-335.2(t)0(h)15(e)0(r)19.7(e)-336.3(is)-324.7(a)-336.3(c)0(l)19.5(e)0(a)18.5(r)-335.1(la)13.8(ck)-325.9(of)-324.7(ha)19.7(rm)19.6(on)20.8(iz)19.6(at)13.8(io)20.7(n/)20.7(st)20.9(an)19.7(da)13.9(rd)20.9(iz)19.5(at)19.6(io)20.7(n)-335.2(i)0(n)]TJ
0 -1.1174 TD
[(th)20.7(e)-203.8(w)0(a)18.8(y)-202.7(su)21(ch)-193.4(me)18.4(th)20.7(od)20.8(s)-202.5(a)0(r)19.7(e)-203.8(cu)19.7(rr)20.9(en)19.7(tl)14.8(y)-196.9(u)0(s)21(e)0(d)13.9(.)-199.3(Th)19.6(is)-192.2(is)-192.2(a)-198.1(m)0(a)18.4(j)0(o)15(r)-196.9(pr)15.1(ob)20.8(-)]TJ
0 -1.1116 TD
[(le)19.5(m)-209.7(f)0(o)20.9(r)-214.2(ha)19.7(za)18.5(rd)-198(an)19.7(d)-214.2(r)0(i)20.7(s)0(k)-197.8(a)0(s)19.9(s)0(e)14.1(s)0(s)21.2(m)0(e)18.4(n)0(t)-198.2(a)0(s)-204.8(t)0(h)20.7(e)-209.6(re)19.7(li)20.6(ab)19.7(il)14.8(it)20.6(y)-208.4(a)0(n)19.7(d)-208.4(re)19.7(pr)15.1(o-)]TJ
T*
[(du)20.8(ci)19.5(bi)14.9(li)20.6(ty)-411.3(of)-411.1(re)19.7(su)21(lt)20.6(s)-421.4(a)0(n)19.7(d)-421.6(he)19.7(nc)19.7(e)-422.7(t)0(h)20.7(e)-422.7(co)19.7(nc)19.7(lu)20.7(si)15.1(on)20.8(s)-421.4(t)0(h)20.7(a)0(t)-412.4(c)0(a)18.5(n)-421.6(be)]TJ
T*
[(dr)20.9(aw)18.8(n)-294.8(f)0(r)20.9(o)0(m)-279.9(s)0(u)21(c)0(h)-285.6(e)0(x)19.7(p)0(e)19.7(r)0(i)20.7(m)0(e)18.4(n)0(t)20.7(s)-288.9(ar)14(e)-290.2(a)0(t)-280(p)0(r)20.9(e)0(s)19.9(e)0(n)13.9(t)-289.2(ra)19.7(th)20.7(er)-279.8(li)14.8(mi)19.5(te)19.6(d.)]TJ
1.0137 -1.1174 TD
[(Against)-211.4(this)-211.8(background,)-212.6(a)-209.6(workshop)-216.8(on)-209.5(ALI)]TJ
/F5 1 Tf
18.0682 0 TD
[(in)-209.7(vitro)]TJ
/F6 1 Tf
3.093 0 TD
(mod-)Tj
-22.1749 -1.1116 TD
[(els)-217.5(for)-222.1(respiratory)-221.8(toxicology)-214.2(research)-226.3(was)-218.3(organized)-220.8(in)-215.4(Paris)]TJ
T*
[(on)-393.9(March)-400.4(21,)-397.3(2016,)-393.7(to)-394(bring)-397.3(together)-403(the)-396.3(major)-393.9(parties)-401.7(in)]TJ
0 -1.1174 TD
[(Europe)-250.8(with)-247.4(a)-249.9(stake)-255.4(in)-244.2(the)-252.3(use)-246.2(of)-249.8(ALI)]TJ
/F5 1 Tf
15.269 0 TD
[(in)-244.2(vitro)]TJ
/F6 1 Tf
3.1736 0 TD
[(lung)-246.4(cell)-248.9(mod-)]TJ
-18.4426 -1.1116 TD
[(els.)-526.2(The)-524(workshop)-522.1(was)-523.5(organized)-526.1(under)-525(the)-523(auspices)-524.7(of)]TJ
T*
[(NanoReg2,)-212.3(a)-209.6(European)-208.1(Union)-213.9(\(EU\)-funded)-211.1(Horizon)-211.4(2020)-206(re-)]TJ
0 -1.1174 TD
[(search)-263.3(and)-263.7(innovation)-260.2(program)-263.5(in)-261.5(conjunction)-262.5(with)-259(INERIS,)]TJ
0 -1.1116 TD
[(France,)-301.3(and)-304(TNO,)-303.4(The)-299.4(Netherlands.)]TJ
1.0137 -1.1116 TD
[(In)-244.1(total,)-246.6(around)-249.6(60)-244.1(scientists)-249.4(from)-247.5(academia,)-249.8(industry,)-248.4(and)]TJ
-1.0137 -1.1174 TD
[(regulatory)-416.7(bodies)-410.9(attended)-415.7(the)-407.8(1-day)-415.6(workshop.)-410.3(The)-408.8(main)]TJ
0 -1.1116 TD
[(aims)-208.3(were)-214.9(to)-203.9(discuss)-215.8(the)-206.2(current)-211.7(state-of-the-art)-218.3(exchange)-209.3(ex-)]TJ
T*
[(perience)-313.1(in)-301.8(terms)-313.1(of)-301.7(practical)-314.4(aspects)-310.4(and)-304(to)-307.6(discuss)-307.9(how)-309.4(to)]TJ
T*
[(move)-450.3(forward)-447.4(with)-449(the)-442.3(airliquid)-450.4(approaches)-453.2(with)-443.3(regard)]TJ
0 -1.1174 TD
[(to)-284.6(future)-290.1(implementation)-292.7(in)-284.6(a)-290.2(regulatory)-290(context.)-284.4(The)-287.9(work-)]TJ
0 -1.1116 TD
.0116 Tc
[(sh)4.7(op)-219.9(con)4.7(s)-.8(i)4.6(s)-.8(ted)-219.9(o)4.7(f)-219.8(a)-221(s)4.9(e)-2.2(ri)4.6(es)-213.9(of)-219.9(p)4.7(l)-1.1(enary)-219.9(l)4.6(ectur)4.8(e)-2.2(s)4.9(,)-222.2(s)4.9(h)-1(o)4.7(r)-1(t)-220(o)4.7(ral)-220(p)-1(r)4.8(e)-2.2(-)]TJ
T*
0 Tc
[(s)-12.4(e)-8(n)-12.6(t)-7(a)-13.8(t)-7(i)-12.7(o)-12.6(n)-6.9(s)-12.4(,)-245.3(p)-12.6(o)-6.9(s)-12.4(t)-7(e)-13.8(r)-248.7(p)-6.9(r)-12.6(e)-8(s)-12.4(e)-8(n)-12.6(t)-12.7(a)-8(t)-12.7(i)-7(o)-12.6(n)-6.9(s)-12.4(,)-245.3(a)-13.8(n)-6.9(d)-248.8()-6.7(n)-12.6(a)-8(l)-12.7(l)-12.7(y)-6.9(,)-245.3(a)-226.9(di)15(sc)19.9(us)21(si)20.9(on)-221.1(le)19.6(d)]TJ
25.504 67.8551 TD
[(by)-244.1(a)-255.7(p)0(a)19.7(n)0(e)19.7(l)-254.7(of)-244.1(ex)19.7(pe)19.7(rt)15(s.)-240.5(Th)19.6(is)-244(ar)19.7(ti)14.8(cl)19.5(e)-249.9(d)0(o)15.1(c)0(u)19.7(m)0(e)18.4(n)0(t)20.7(s)-254.3(th)20.7(e)-255.7(o)0(u)20.8(t)0(c)19.5(o)0(m)19.6(e)0(s)-245.1(o)0(f)]TJ
0 -1.1174 TD
[(th)15(e)-342.1(w)0(o)14.2(r)0(k)20.9(s)0(h)21(o)0(p)-336.3(a)0(n)19.7(d)-346.7(pr)20.9(ov)20.8(id)20.7(es)-337.2(a)-347.8(s)0(e)19.9(r)0(i)20.7(e)0(s)-337.2(o)0(f)-336.2(r)0(e)19.7(c)0(o)19.7(m)0(m)18.4(e)0(n)19.7(d)0(a)13.9(t)0(i)20.6(o)0(n)20.8(s)-346.5(fo)20.9(r)]TJ
0 -1.1116 TD
[(th)15(e)-451.5(f)0(u)20.9(t)0(u)20.7(r)0(e)-446.8(d)0(e)19.7(v)0(e)19.7(l)0(o)20.7(p)0(m)19.6(e)0(n)13.9(t)-450.5(of)-445.7(th)20.7(e)-451.5(m)0(e)18.4(t)0(h)20.7(o)0(d)20.8(s)-455.9(ei)19.5(th)20.7(er)-446.8(in)-440.1(th)14.9(e)-451.5(m)0(a)18.4(i)0(n)]TJ
T*
[(te)13.8(xt)-342.2(or)-342(in)-347.9(th)20.7(e)-353.6(S)0(u)15.2(p)0(p)20.8(l)0(e)19.6(m)0(e)18.4(n)0(t)20.7(a)0(r)19.7(y)-358.2(Da)18.8(ta)-343.3(\(S)21(up)15.1(pl)20.7(em)18.4(en)19.7(ta)19.6(ry)-342(Da)13(ta)-343.3(ar)19.7(e)]TJ
T*
[(av)13.9(ai)19.5(la)19.6(bl)20.7(e)-290.2(o)0(n)20.8(l)0(i)14.8(n)0(e)-279.8(a)0(t)-280(w)0(w)19.1(w)0(.)17.6(l)0(i)20.6(e)0(b)19.7(e)0(r)14(t)0(p)20.7(u)0(b)20.8(.)0(c)17.3(o)0(m)19.6(/)0(a)19.5(i)0(v)20.7(t)0(\))20.7(.)]TJ
1.0137 -1.1174 TD
[(After)-243.8(presenting)-249.5(background)-243.7(information,)-248.7(the)-240.7(article)-247.7(deals)]TJ
-1.0137 -1.1116 TD
[(with)-224.4(the)-217.7(current)-223.2(knowledge)-226.4(and)-217.6(practices)-227.7(of)-221(ALI)-218.4(approaches,)]TJ
T*
[(in)-296.1(terms)-295.8(of)-295.9(atmosphere)-297.9(generation,)-300.4(exposure)-298.9(principles,)-299.2(and)]TJ
0 -1.1174 TD
[(cell)-220.1(models)-210.5(available.)-220(Then,)-211.8(the)-217.7(outcomes)-213.9(of)-215.3(the)-211.9(expert)-216.4(panel)]TJ
0 -1.1116 TD
[(discuss)-8.4(ion)-274.1(are)-270.5(presen)-8.7(ted,)-273(highlighting)-273.1(the)-275.3(validation)-278.8(process)]TJ
T*
[(and)-321.2(the)-321.4(challenges)-326.8(to)-319.1(overcome)-318.8(the)-321.4(validation)-324.9(of)-319(ALI)-322.1(tech-)]TJ
0 -1.1174 TD
[(niques)-7.7(.)-412.4(Finally,)-421.5(several)-420(recommendations)-421.1(are)-414.5(presented)-422.2(to)]TJ
0 -1.1116 TD
[(implement)-308.8(the)-298.3(validation)-301.8(process.)]TJ
/F1 1 Tf
8.9663 0 0 8.9663 313.0582 566.6455 Tm
(Background)Tj
/F6 1 Tf
9.843 0 0 9.843 323.0361 550.2046 Tm
[(Respiratory)-303.5(health)-297.2(and)-292.4(disease)-298.9(related)-299.4(to)-296.1(ambient)-299.5(air)-298.3(pol-)]TJ
-1.0137 -1.1116 TD
[(lution)-243.1(are)-241.7(a)-238.4(major)-244.1(concern)-241.6(worldwide.)]TJ
7.3823 0 0 6.5614 463.4077 543.6282 Tm
(4)Tj
9.843 0 0 9.843 469.4739 539.2628 Tm
[(Apart)-238(from)-241.7(air)-240.7(pollu-)]TJ
-15.891 -1.1174 TD
[(tion,)-209.7(numerous)-212.6(chemicals)-211.7(and)-206.1(particles)-209.4(need)-214.1(to)-203.9(be)-210.7(assessed)-207.4(in)]TJ
0 -1.1116 TD
[(the)-534.5(context)-534.4(of)-537.8(the)-528.7(EU)-534.2(REACH)-540.4(\(registration,)-532.9(evaluation,)]TJ
T*
[(authorisatio)-10.1(n,)-471.1(and)-476.8(restriction)-481.2(of)-474.5(chemicals\))-483.5(regulation)-474.5(for)]TJ
0 -1.1174 TD
[(pu)15.1(lm)13.7(on)15.1(ar)14(y)-352.4(t)0(o)20.7(x)0(i)14.9(c)0(i)13.8(t)0(y)15(.)-349(He)13(al)13.8(th)-342.1(ef)14(fe)14(ct)13.8(s)-352.2(d)0(u)15.1(e)-347.8(to)-347.9(in)20.7(ha)13.9(la)13.8(ti)14.8(on)-342(of)-342(su)15.3(b-)]TJ
0 -1.1116 TD
[(st)15.1(an)13.9(ce)12.8(s)-444.4(a)0(r)14(e)-440(th)15(er)14(ef)14(or)15.1(e)-445.8(o)0(f)-434.1(c)0(o)13.9(n)0(s)15.3(i)0(d)20.7(e)0(r)14(a)0(b)13.9(l)0(e)-435.5(i)0(n)15(t)0(e)13.8(r)0(e)14(s)0(t)-434.1(t)0(o)-434.3(m)0(a)12.7(n)0(y)-434.2(a)0(n)13.9(d)]TJ
T*
[(fo)15.1(rm)-233.8(th)15(e)-244.2(b)0(a)13.9(s)0(i)15.1(s)-237.1(fo)15.1(r)-243(t)0(h)15(e)-238.4(us)15.3(e)-244.2(a)0(n)19.7(d)-243(de)13.9(ve)13.9(lo)15(pm)19.6(en)13.9(t)-243.1(o)0(f)]TJ
/F5 1 Tf
18.3216 0 TD
[(in)-232.7(vi)13.8(tr)15.1(o)]TJ
/F6 1 Tf
3.116 0 TD
[(mo)13.8(de)13.9(ls)]TJ
-21.4376 -1.1174 TD
[(of)-192.2(th)15(e)-192.3(r)0(e)14(s)0(p)15.3(i)0(r)15(a)0(t)13.8(o)0(r)15.1(y)-196.9(tr)20.7(ac)12.8(t.)-189(As)-187.2(we)13.1(ll)-186.8(as)-187.5(st)15.1(ud)15.1(yi)14.9(ng)-186.5(th)15(e)-198.1(e)0(f)14()0(c)14.1(a)0(c)18.5(y)-196.9(of)-186.5(ne)13.9(w)]TJ
0 -1.1116 TD
[(ph)15.1(ar)14(ma)12.7(ce)12.8(ut)14.9(ic)19.5(al)13.8(ly)-215.4(ac)18.5(ti)14.8(ve)-210.7(co)13.9(mp)13.9(ou)15.1(nd)15.1(s,)]TJ
7.3823 0 0 6.5614 454.7904 455.9243 Tm
(5)Tj
9.843 0 0 9.843 460.6298 451.5589 Tm
[(a)-221.1(m)0(a)12.7(j)0(o)15(r)-214.2(us)15.3(e)-221.1(o)0(f)-209.5(t)0(h)15(e)-221.1(mo)13.8(d-)]TJ
-14.9925 -1.1116 TD
[(el)13.8(s)-208.2(i)0(s)-198(t)0(o)-198.2(e)0(x)13.9(a)0(m)18.5(i)0(n)15(e)-209.6(th)14.9(e)-203.8(p)0(o)15.1(t)0(e)13.8(n)0(t)14.9(i)0(a)19.6(l)0(l)14.8(y)-208.4(to)15(xi)14.9(c)-203.8(e)0(f)14(f)0(e)14(c)0(t)13.8(s)-202.5(of)-198(di)14.9(ff)15.1(er)13.9(en)13.9(t)-202.8(t)0(y)14.9(p)0(e)13.9(s)]TJ
T*
[(of)-457.2(compo)-7.9(unds)-453.5(rangin)-7.9(g)-456.1(from)-454.8(chem)-8(icals)-457.1(to)-451.6(\()-6.8(nano\)p)-7.7(articl)-9.3(es,)]TJ
0 -1.1174 TD
[(s)-6.7(uch)-511.3(as)-510(Ag,)]TJ
7.3823 0 0 6.5614 363.9117 423.0424 Tm
(6)Tj
9.843 0 0 9.843 372.6424 418.6771 Tm
(SiO)Tj
7.3823 0 0 6.5614 387.9495 417.033 Tm
(2)Tj
9.843 0 0 9.843 391.6345 418.6771 Tm
(,)Tj
7.3823 0 0 6.5614 394.129 423.0424 Tm
(7)Tj
9.843 0 0 9.843 402.8597 418.6771 Tm
(CeO)Tj
7.3823 0 0 6.5614 420.8881 417.033 Tm
(2)Tj
9.843 0 0 9.843 424.6298 418.6771 Tm
[(,)-510.3(and)-511.3(TiO)]TJ
7.3823 0 0 6.5614 467.3196 417.033 Tm
(2)Tj
9.843 0 0 9.843 471.0613 418.6771 Tm
(,)Tj
7.3823 0 0 6.5614 473.4991 423.0424 Tm
(8)Tj
9.843 0 0 9.843 482.2298 418.6771 Tm
[(multi)-7.1(wall)-513.6(carbon)]TJ
-17.187 -1.1116 TD
[(nanotu)-7.9(bes,)]TJ
7.3823 0 0 6.5614 355.6345 412.1007 Tm
(9)Tj
9.843 0 0 9.843 362.3243 407.7353 Tm
[(or)-301.7(complex)-305.1(combu)-7.9(stion-d)-7.7(erived)-308.5(aeroso)-8.7(ls)-7.9(.)]TJ
7.3823 0 0 6.5614 527.4707 412.1007 Tm
[(101)-12(2)]TJ
9.843 0 0 9.843 323.0361 396.7936 Tm
[(Many)-565.2(different)-571.1(models)-567.6(have)-565.4(been)-565.4(used)-569.8(ranging)-567.7(from)]TJ
/F5 1 Tf
-1.0137 -1.1174 TD
[(in)-434.3(vivo)]TJ
/F6 1 Tf
3.3234 0 TD
[(animal)-436.6(experiments)-437.3(to)]TJ
/F5 1 Tf
9.7224 0 TD
[(in)-434.3(vitro)]TJ
/F6 1 Tf
3.5422 0 TD
[(models)-429.4(using)-437.4(lung)]TJ
-16.588 -1.1116 TD
(cells.)Tj
7.3823 0 0 6.5614 333.6944 379.2188 Tm
(13)Tj
9.843 0 0 9.843 344.466 374.8535 Tm
[(In)-342(the)-344.4(latter)-343.3(case,)-345.2(many)-346.6(different)-346.5(types)-340.7(of)-342(exposure)]TJ
-3.1909 -1.1116 TD
[(scenarios)-364.5(have)-358.1(been)-358.1(used)-356.7(and)-355.8(indeed)-360.4(the)-355.9(cells)-359.2(used)-356.7(can)-357(be)]TJ
0 -1.1174 TD
[(animal)-379(or)-376.5(human)-382.3(derived.)-376.4(Despite)-379.6(differences)-379.5(between)-380.8(the)]TJ
0 -1.1116 TD
[(various)-388.9(models,)-386.8(the)-390.5(core)-386.8(ambition)-386(is)-388(to)-382.5(model)-388.2(what)-386.7(likely)]TJ
T*
[(ha)13.9(pp)20.8(en)19.7(s)]TJ
/F5 1 Tf
3.4443 0 TD
[(in)-209.7(vi)19.5(vo)]TJ
/F6 1 Tf
2.8568 0 TD
[(as)-210.5(cl)19.6(os)21(el)19.5(y)-220(a)0(s)-210.5(p)0(o)20.8(s)0(s)21.2(i)0(b)15(l)0(e)-210.8(w)0(i)19.8(t)0(h)]TJ
/F5 1 Tf
10.4884 0 TD
[(in)-203.9(vi)13.8(tr)20.9(o)]TJ
/F6 1 Tf
3.0642 0 TD
[(te)19.6(ch)19.7(ni)20.7(qu)20.8(es)14.1(.)]TJ
-18.84 -1.1174 TD
(ALI)Tj
/F5 1 Tf
1.8949 0 TD
[(in)-227(vitro)]TJ
/F6 1 Tf
3.1333 0 TD
[(inhalation)-232.7(models)-227.8(are)-230.2(increasingly)-230(being)-231.4(used)]TJ
-6.0419 -1.1116 TD
[(in)-336.4(research)-335.8(and)-327(this)-332.8(comes)-331.4(with)-333.8(some)-334.9(advantages,)-335.8(not)-331.7(least)]TJ
T*
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T*
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[(sibility)-337.6(to)-342.1(further)-337.2(reduce)-344.1(the)-338.7(aerosol)-344(size)-340.7(by)-342(evaporation)-338.4(of)]TJ
T*
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[(aerosol)-286.4(state)-284.4(is)-290.1(reached)-283(where)-290.9(it)-284.7(is)-284.4(composed)-288.6(of)-284.4(the)-281.1(nonvol-)]TJ
0 -1.1116 TD
[(atile)-278.9(compound)-281.9(only.)-278.7(This)-282(method)-279.8(is)-284.4(particularly)-282.1(interesting)]TJ
T*
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0 -1.1174 TD
[(to)-376.7(be)-377.7(produced,)-383.2(which)-382.1(can)-380(be)-377.7(achieved)-382.2(by)-382.3(electrospraying)]TJ
0 -1.1116 TD
[(dispersions)-623.5(of)-624.2(low)-620.6(concentrations)-630.8(of)-618.5(solid)-621.9(material)-630.2(\(as)]TJ
T*
[(shown)-363.3(by)-365.1(Fu)-364.9(et)-366.4(al.)]TJ
7.3823 0 0 6.5614 387.8361 554.5699 Tm
(23)Tj
9.843 0 0 9.843 395.2062 550.2046 Tm
[(\).)-367.4(Here)-364.7(the)-367.5(initial)-366.6(droplets)-367.1(are)-362.7(already)]TJ
-8.5704 -1.1116 TD
[(in)-468.9(the)-471.1(100)-164.6(nm)-470(range.)-472(After)-474.1(evaporation)-476.6(of)-468.7(the)-471.1(water,)-473(the)]TJ
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[(dry)-297(aerosol)-303.7(particles)-307.3(can)-299.4(be)-302.9(as)-302.7(small)-301.7(as)-302.7(several)-304.8(nanometers.)]TJ
/F5 1 Tf
1.0137 -2.2232 TD
[(Powders)-229.6(and)-233.7(bulk)-230.3(material.)]TJ
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12.0666 0 TD
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[(dry)-216.4(powders)-222.6(is)-215.2(somewhat)-220.5(similar)-223.4(to)-215.4(nebulization)-224.6(of)-215.3(liquids)-221(in)]TJ
0 -1.1116 TD
[(that)-282.3(it)-284.7(requires)-287.5(a)-284.5(feeding)-286.6(technology)-284.3(to)-284.5(establish)-288.7(the)-281.1(powder)]TJ
T*
[(mass)-403.8(ow)-401.4(and)-407.6(the)-402(supply)-404(of)-405.3(external)-404.2(energy)-406.3(for)-406.4(its)-400.8(deag-)]TJ
0 -1.1174 TD
[(glomeration.)-514.8(Powder)-515.3(feeding)-517(can)-512.5(be)-516(metered)-519.4(by)-509.1(various)]TJ
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[(mechanisms)-379.6(that)-380.2(include)-378.9(spiral)-382.2(screws,)-381.4(groves,)-379.6(or)-376.6(holes)-381(in)]TJ
T*
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[(facilitated)-483.9(by)-480.3(statio)-8(nary)-477.8(or)-486(transient)-484.7(high)-476.8(air)-488.4(speeds,)]TJ
7.3823 0 0 6.5614 531.4392 434.0408 Tm
(2629)Tj
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[(scraping)-316.3(mechanisms,)-313.9(or)-313.2(mutual)-314.5(collisions)-317.6(between)-311.7(powder)]TJ
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(30,31)Tj
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(externally)Tj
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(32)Tj
9.843 0 0 9.843 465.5054 396.7936 Tm
[(\),)-298.2(or)-301.7(collisions)-306.1(of)-301.7(ag-)]TJ
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[(glomerates)-609(with)-604.5(surfaces)-610.9(\(uidized)-611.3(bed)-603.5(with)-610.3(dispersion)]TJ
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T*
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[(brous)-299(materials)-308.5(such)-299.1(as)-302.7(carbon)-302.6(nanotubes.)]TJ
7.3823 0 0 6.5614 479.3384 357.3354 Tm
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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[(IN)-305.8(VITRO)]TJ
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[(INHALATION)-301(WORKSHOP)-302.6(2016)]TJ
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(37)Tj
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[(A)-289.9(method)-291.4(to)-290.3(generate)-295.8(zinc)-294.8(oxide)-289(particles)]TJ
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T*
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T*
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(38)Tj
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[(A)-347.5(method)-354.7(has)-349.8(also)-351.1(been)-346.6(developed)]TJ
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(39)Tj
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[(This)-270.5(approach)-277.2(effec-)]TJ
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T*
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3.0584 0 TD
(and)Tj
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1.751 0 TD
[(in)-296.1(vitro)]TJ
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3.2773 0 TD
(experiments.)Tj
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[(ALI)-224.2(exposure)-224(units)-224.4(have)-219.8(to)-221.2(be)-228(properly)-223.2(interfaced)-223.2(with)-224.4(the)]TJ
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[(generation)-360.3(method.)-352.4(This)-356.9(can)-357(be)-354.7(done)-351.2(by)-353.5(placing)-361.6(a)-353.6(mixing/)]TJ
T*
[(equilibration)-322.5(volume)-314.4(between)-317.5(generation)-320(and)-321.2(exposure)-316.2(sys-)]TJ
0 -1.1174 TD
[(tem.)-481.6(The)-478(volume)-481.4(ows)-477.2(of)-474.5(the)-482.6(aerosol)-482.2(generation)-481.3(system)]TJ
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T*
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T*
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8.9663 0 0 8.9663 62.022 517.8329 Tm
[(Exposure)-263.3(of)-260.9(cell-based)]TJ
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10.3569 0 TD
[(in)-260.6(vitro)]TJ
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3.1741 0 TD
[(systems)-260.5(to)-260.9(study)-264.3(biological)]TJ
-13.531 -1.2266 TD
[(effects)-303(of)-298.8(airborne)-301.5(compounds)]TJ
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1.1128 -1.8336 TD
[(General)-405.5(principles/background)-412.1(on)]TJ
/F3 1 Tf
15.5417 0 TD
[(in)-406.1(vitro)]TJ
/F2 1 Tf
3.4713 0 TD
[(airborne)-409(expo-)]TJ
-20.1258 -1.2203 TD
(sure.)Tj
/F6 1 Tf
9.843 0 0 9.843 90.8787 479.4518 Tm
[(The)-385.8(exposure)-391.1(itself)-382.3(has)-390.2(in)-382.5(principle)-387(one)-384.6(simple)-389.2(but)]TJ
-2.9317 -1.1116 TD
[(major)-301.7(task:)-300.5(to)-301.8(establish)-300.2(an)-302.9(effective)-302.7(contact)-305.2(between)-305.9(the)-298.3(bi-)]TJ
T*
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7.3823 0 0 6.5614 222.1228 461.9337 Tm
(40)Tj
9.843 0 0 9.843 232.781 457.5684 Tm
[(tissue,)-339.4(or)]TJ
/F5 1 Tf
4.0376 0 TD
[(ex)-332.8(vivo)]TJ
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-21.3858 -1.1174 TD
[(material)-301.9(\(e.g.,)-297(precision-cut)-305.9(lung)-298.3(slices)]TJ
7.3823 0 0 6.5614 217.3039 450.9353 Tm
(41)Tj
9.843 0 0 9.843 224.674 446.57 Tm
[(\),)-298.2(and)-298.2(the)-298.3(exposure)]TJ
-16.5246 -1.1116 TD
[(atmosphere.)-347.4(This)-351.1(includes)-345.3(an)-348.9(intensive)-346.5(and)-344.3(dened)-348.6(contact)]TJ
T*
[(with)-310.8(the)-315.6(gas)-309.5(phase)-312.9(as)-314.2(well)-312(as)-308.4(with)-316.6(the)-309.9(particle)-312.2(phase)-312.9(of)-313.2(air-)]TJ
0 -1.1174 TD
[(borne)-208.2(material)-215.5(and)-206.1(to)-209.7(establish)-213.8(dose)-207(metrics)-212.9(as)-210.5(a)-209.6(fundamental)]TJ
0 -1.1116 TD
[(requirement)-305(of)-301.7(any)-298.2(successful)]TJ
/F5 1 Tf
12.4525 0 TD
[(in)-301.8(vitro)]TJ
/F6 1 Tf
3.2773 0 TD
(testing.)Tj
-14.716 -1.1116 TD
[(Moreover,)-355.2(any)-355.8(articial)-359.3(exposure)-356.5(effects)-356.6(on)-353.5(the)-355.9(exposed)]TJ
-1.0137 -1.1174 TD
[(biological)-232.7(material)-232.8(have)-225.6(to)-232.7(be)-228(avoided.)-226.7(Since)-232.4(the)-229.2(original)-229.2(en-)]TJ
0 -1.1116 TD
[(vironment)-352.4(of)-353.5(any)-355.8(biological)-353.7(test)-351.2(system)-354.3(is)-353.5(the)-350.2(liquid)-352.6(phase)]TJ
T*
[(whereas)-512.9(the)-511.4(original)-511.4(environment)-511.2(of)-509(the)-511.4(exposure)-512(atmo-)]TJ
0 -1.1174 TD
[(sphere)-308.2(is)-301.6(by)-301.7(denition)-305.1(the)-304.1(gas)-303.8(phase,)-304.8(there)-307.4(are)-305.1(mainly)-303(three)]TJ
0 -1.1116 TD
[(possible)-303.6(ways)-300(to)-301.8(go)-301.7(for)-302.7(a)-296(combination:)]TJ
1.0022 -1.7222 TD
[(\(1\))-498.6(by)-272.9(transferring)-274.7(the)-275.3(test)-270.6(material)-278.8(from)-270.5(the)-275.3(gas)-275(phase)-272.6(to)]TJ
1.6646 -1.1116 TD
[(the)-304.1(liquid)-300.7(phase,)]TJ
-1.6646 -1.1116 TD
[(\(2\))-498.6(by)-399.6(transferring)-401.4(the)-396.3(biological)-399.8(test)-397.3(system)-400.4(to)-399.7(the)-396.3(gas)]TJ
1.6646 -1.1116 TD
[(phase)-301.4(for)-302.7(a)-301.8(time)-300.8(intermittently)-307.8(to)-296.1(\(1\),)-300.4(above)-7.8(,)-297.2(or,)]TJ
-1.6646 -1.1174 TD
[(\(3\))-498.6(by)-399.6(transferring)-401.4(the)-396.3(biological)-399.8(test)-397.3(system)-400.4(to)-399.7(the)-396.3(gas)]TJ
1.6646 -1.1116 TD
[(phase)-301.4(continuously.)]TJ
-1.653 -2.229 TD
[(In)-134.6(re)25.5(al)19.5(it)26.3(y,)-137(th)26.5(es)19.9(e)-146.2(t)0(h)20.7(r)16.2(ee)-137(st)20.9(ra)25.5(te)19.6(gi)26.5(es)-135.6(ha)19.7(ve)-135.8(b)16.2(e)0(e)18.5(n)-145.1(ap)25.4(pl)20.7(ie)25.3(d)-150.8(d)16.2(ur)20.9(in)26.5(g)-150.8(p)16.2(re)19.7(-)]TJ
-1.0137 -1.1116 TD
[(vi)20.7(o)16.2(u)0(s)-209.4(d)0(e)19.7(c)0(a)24.3(d)0(e)19.7(s)-219.8(to)-209.7(es)19.9(t)16.1(a)0(b)19.7(l)16.1(is)20.9(h)-220(c)0(e)18.5(l)16.1(l-)20.7(ba)25.4(se)19.9(d)]TJ
/F5 1 Tf
14.4799 0 TD
[(in)-250(vi)19.5(t)16.1(r)0(o)]TJ
/F6 1 Tf
3.139 0 TD
-.0182 Tc
[(m)-18.2(e).2(th)-18.2(od)-18.2(s)-267.9(f)-18.2(o)8.4(r)-284.2(te)-18.2(st)-18.2(-)]TJ
-17.6189 -1.1116 TD
0 Tc
[(in)20.7(g)-364(a)0(i)25.3(r)0(b)20.9(o)0(r)20.9(n)16.2(e)-370.9(m)15(at)19.5(e)15(r)0(i)20.7(a)0(l)25.3(.)-366.3(Al)19.8(re)25.5(ad)19.7(y)-364(m)0(o)19.6(r)16.2(e)-370.9(t)0(h)26.5(a)0(n)-354.7(4)0(0)-359.3(y)16.2(ea)18.5(rs)-353.3(ag)19.7(o)16.2(,)-366.3(ce)18.5(l)16.1(l)]TJ
0 -1.1174 TD
[(su)21(sp)26.8(en)19.7(si)26.7(on)20.8(s)-398.3(f)0(r)20.9(o)0(m)-389.3(a)15(lv)20.7(eo)25.4(la)19.6(r)-398.5(m)0(a)24.2(c)0(r)19.7(o)0(p)26.6(h)0(a)19.7(g)0(e)25.4(s)-404.1(w)15.3(e)0(r)19.7(e)-399.7(us)21(e)15(d)-404.3(t)16.1(o)-404.3(st)26.7(ud)20.8(y)]TJ
0 -1.1116 TD
[(th)20.7(e)-278.7(b)16.2(io)20.7(lo)26.5(gi)20.7(ca)24.3(l)-277.7(e)0(f)19.7(f)0(e)25.5(c)0(t)-268.4(o)0(f)-267.1(c)0(h)25.4(e)0(m)18.5(i)0(c)25.3(a)0(l)-268.4(g)0(a)25.4(s)0(e)19.9(s)-277.4(su)21(c)15(h)-283.3(a)15(s)-277.4(ni)20.7(tr)26.5(og)20.8(en)-268.3(d)16.2(i)0(o)20.7(x)0(-)]TJ
T*
[(id)20.7(e)-284.5(b)0(y)-278.7(b)0(u)26.6(b)0(b)20.8(l)0(i)26.3(n)0(g)-278.7(t)0(h)20.7(e)-284.5(ga)19.7(s)-288.9(t)16.1(hr)20.9(ou)26.6(gh)-278.7(th)20.7(e)-284.5(c)0(u)19.7(l)0(t)26.3(u)0(r)20.9(e)-290.2(m)15(e)0(d)19.7(i)16.1(um)19.6(.)]TJ
7.3823 0 0 6.5614 267.9306 192.9259 Tm
-.0162 Tc
(42)Tj
9.843 0 0 9.843 72 177.5621 Tm
0 Tc
[(This)-259(strategy)-258.8(is)-255.6(still)-259.3(used)-258.8(for)-256.7(setting)-262.5(up)-255.6(new)-258.8(methods)-257.7(such)]TJ
-1.0137 -1.1116 TD
[(as)-463.9(the)-465.4(hanging-drop)-469.5(exposure)-465.9(model.)]TJ
7.3823 0 0 6.5614 216.4535 170.9858 Tm
(43)Tj
9.843 0 0 9.843 228.4157 166.6204 Tm
[(Here)-468.3(human)-462.9(lung)]TJ
-16.9047 -1.1116 TD
[(cells)-307.4(\(A549)-311.6(cell)-306.5(line\))-306.4(are)-310.9(used)-304.9(in)-307.6(suspension)-311.2(culture)-309.8(to)-301.8(then)]TJ
T*
[(be)-331.7(exposed)-326.6(to)-330.6(gaseous)-332.2(chemicals)-332.6(inside)-330.4(a)-330.6(small)-330.5(drop)-326.9(under)]TJ
0 -1.1174 TD
[(static)-291.4(exposure)-293.1(conditions)-288.8(in)-290.3(a)-290.2(closed)-291.1(vessel.)-294.3(Strategies)-291(cor-)]TJ
0 -1.1116 TD
[(responding)-254(to)-250(\(2\))-250.9(\(above\))-251.9(are)-253.3(represented)-252.8(by)-249.9(intermittent)-253.7(ex-)]TJ
T*
[(posures)-308(of)-307.4(cells)-307.4(or)]TJ
/F5 1 Tf
7.7814 0 TD
[(ex)-309.8(vivo)]TJ
/F6 1 Tf
3.1851 0 TD
[(material)-307.6(to)-307.6(the)-304.1(atmosphere)-309.4(using)]TJ
-10.9665 -1.1174 TD
-.0217 Tc
[(ha)-6.7(lf)-5.5(-l)-5.6(l).1(ed)-224.4(ro)-5.5(ll)-5.6(er)-224.4(bot)-5.6(tle)-6.7(s)]TJ
7.3823 0 0 6.5614 148.5921 105.2787 Tm
-.0246 Tc
(44,45)Tj
9.843 0 0 9.843 166.4503 100.8567 Tm
-.0214 Tc
[(or)-224.1(til)-5.3(ted)-5.2(,)-220.7(ro)-5.2(tat)-5.3(i).4(n)-5.2(g)-218.3(mu)-5.2(lti)-5.3(wel)-5.3(l)-218.5(p)-5.2(l).4(a)-6.4(t).4(es)-5(.)]TJ
7.3823 0 0 6.5614 293.9527 105.2787 Tm
-.0315 Tc
(46)Tj
9.843 0 0 9.843 72 89.9149 Tm
0 Tc
[(With)-294.9(respect)-299.1(to)-296.1(the)-292.6(key)-298.2(feature)-299.2(of)-295.9(biological)-296.1(relevance,)-301.5(it)]TJ
-1.0137 -1.1116 TD
[(is)-226.8(possible)-223(that)-230.5(the)-223.5(cellular)-231.5(organization)-224.4(of)-226.8(the)-223.5(biological)-227(cell)]TJ
0 -1.1174 TD
[(or)-272.9(tissue)-272.6(material)-273.1(used)-276.1(in)-267.3(such)-270.3(approaches)-280.4(may)-270.6(be)-268.3(relatively)]TJ
0 -1.1116 TD
[(far)-303.9(away)-301.3(from)-299.3(the)]TJ
/F5 1 Tf
7.6086 0 TD
[(in)-301.8(vivo)]TJ
/F6 1 Tf
3.0584 0 TD
[(situation)-305.1(in)-296.1(the)-304.1(human)-301.6(lung.)]TJ
15.8507 67.9184 TD
[(Also,)-221.8(with)-224.4(respect)-224.2(to)-227(exposure)-224(relevance,)-226.6(it)-221.3(has)-223.1(to)-221.2(be)-222.2(taken)]TJ
-1.0137 -1.1174 TD
[(into)-235.1(account)-236(that)-230.5(the)-235(presence)-232.1(of)-232.6(culture)-234.9(medium)-235(as)-227.8(the)-235(com-)]TJ
0 -1.1116 TD
[(pound)-264.7(of)-255.6(primary)-263.6(contact)-264.9(with)-259(the)-258(test)-264.8(material)-261.6(will)-259.1(result)-261.2(in)]TJ
T*
[(a)-284.5(relatively)-285.7(low)-280.8(efciency)-285.2(of)-284.4(contact)-282.2(between)-288.7(the)-281.1(test)-282.1(atmo-)]TJ
T*
[(sphere)-440.7(and)-436.4(the)-436.6(cells.)]TJ
7.3823 0 0 6.5614 398.6645 686.0974 Tm
(47)Tj
9.843 0 0 9.843 410.3432 681.7321 Tm
[(Moreover,)-441.6(it)-434.4(will)-437.6(lead)-438.8(to)-434.3(physico-)]TJ
-9.8837 -1.1174 TD
[(chem)-8(ical)-346.8(modications)-350.9(of)-347.7(the)-350.2(airborne)-351(test)-345.5(material.)-357.1(In)-342(the)]TJ
0 -1.1116 TD
[(simplest)-448.9(case)-451.2(this)-448(will)-443.4(lead)-450.4(to)-445.8(a)-445.8(change)-447.8(in)-445.8(particle)-450.4(sizes.)]TJ
T*
[(Howev)-8.4(er,)-381.1(depending)-381(on)-382.3(the)-384.7(test)-385.8(material,)-385.9(it)-382.6(may)-380.1(also)-385.6(lead)]TJ
0 -1.1174 TD
[(to)-278.8(chemical)-279.9(changes)-281.7(in)-273(the)-281.1(test)-276.3(atmosphere)-280.6(in)-273(case)-284.2(of)-272.9(chem-)]TJ
0 -1.1116 TD
[(ically)-303.1(reactive)-307.4(components)-302.5(in)-301.8(a)-301.8(complex)-299.4(mixture.)]TJ
7.3823 0 0 6.5614 511.3133 631.2754 Tm
(48)Tj
9.843 0 0 9.843 323.0361 615.9683 Tm
[(Also,)-262.1(exact)-256.8(dose)-258.8(can)-259.1(be)-256.8(hard)-259(to)-255.8(accurately)-264.7(measure)-259.9(due)-257.9(to)]TJ
-1.0137 -1.1174 TD
[(unknown)-256.3(physicochemical)-265.7(properties)-255.3(and)-257.9(kinetics)-253.2(of)-255.6(the)-258(test)]TJ
0 -1.1116 TD
[(material)-342.2(in)-342.1(specic)-339.3(culture)-338.6(media.)-340.9(As)-342.7(a)-336.3(result,)-339.5(these)-341.8(strate-)]TJ
T*
[(gies)-379.9(do)-370.8(not)-377.8(represent)-376.1(the)-373.2(primary)-378.8(route)-375.4(of)-370.8(exposure)-379.5(of)-370.8(the)]TJ
0 -1.1174 TD
[(inner)-433(biological)-434.3(surfaces)-432.3(of)-434.1(the)-430.8(human)-428.4(respiratory)-434.9(system)]TJ
0 -1.1116 TD
[(to)-301.8(inhaled)-304(atmospheres.)]TJ
/F2 1 Tf
8.9663 0 0 8.9663 323.0361 539.2628 Tm
[(ALI)-378.9(exposure.)]TJ
/F6 1 Tf
9.843 0 0 9.843 388.0062 539.2628 Tm
[(Contrasting)-371.6(to)-370.9(this,)-370.8(cultures)-368.3(lifted)-371(to)-365.2(the)]TJ
-7.6143 -1.1174 TD
(ALI)Tj
7.3823 0 0 6.5614 329.4991 532.6298 Tm
(42)Tj
9.843 0 0 9.843 341.1779 528.2644 Tm
[(seem)-439.7(to)-440.1(offer)-438.5(the)-436.6(basis)-438.4(for)-441(a)-434.2(perfect)-443.2(translation)-441(of)]TJ
-2.8568 -1.1116 TD
[(the)-298.3(biological)]TJ
/F5 1 Tf
5.8461 0 TD
[(in)-296.1(vivo)]TJ
/F6 1 Tf
3.0526 0 TD
[(organization)-299.3(of)-295.9(the)-298.3(respiratory)-302.4(system)]TJ
-8.8987 -1.1116 TD
(to)Tj
/F5 1 Tf
1.1001 0 TD
[(in)-313.3(vitro)]TJ
/F6 1 Tf
2.9893 0 TD
[(.)-314.4(B)0(y)-314.3(culturing)-316.7(tissue,)-316.3(cells,)-316.6(or)]TJ
/F5 1 Tf
12.3834 0 TD
[(ex)-315.6(vivo)]TJ
/F6 1 Tf
3.2024 0 TD
[(material)-319.2(on)]TJ
-19.6752 -1.1174 TD
[(microporous)-596.1(membranes)-597.4(while)-595.3(feeding)-591.9(and)-591.9(humidifying)]TJ
0 -1.1116 TD
[(them)-312.2(only)-304(from)-310.8(the)-309.9(basal)-307.3(side,)-308.4(a)-307.5(biological)-313.4(barrier)-309.6(model)-307.5(is)]TJ
T*
[(set)-321.2(up)-319(separating)-319.8(the)-315.6(inhaled)-321.3(air/exposure)-322(atmosphere)-320.9(com-)]TJ
0 -1.1174 TD
[(partment)-358.2(from)-345.4(a)-353.6(blood/liquid/culture)-353.7(medium)-350.2(compartment)]TJ
0 -1.1116 TD
[(in)-250(a)-249.9(construction)-251.9(that)-247.7(is)-249.8(highly)-248.8(relevant)-254.4(to)-244.2(the)]TJ
/F5 1 Tf
18.4138 0 TD
[(in)-244.2(vivo)]TJ
/F6 1 Tf
2.9547 0 TD
(setting.)Tj
-20.3548 -1.1116 TD
[(With)-490.7(respect)-489.2(to)-491.9(exposure)-489(relevance,)-491.6(ALI)-489.2(models)-492.8(offer)]TJ
-1.0137 -1.1174 TD
[(unique)-301.6(proper)-7.7(ties.)]TJ
1.0137 -1.1116 TD
[(Due)-206.9(to)-203.9(the)-206.2(exposure)-212.5(situation)-207.2(of)-203.8(the)-206.2(models)-204.8(that)-207.4(expose)-210.3(the)]TJ
-1.0137 -1.1116 TD
[(biological)-278.8(system)-279.4(continuously)-273.8(to)-273(the)-275.3(atmosphere,)-278.3(the)-275.3(expo-)]TJ
T*
[(sure)-230(agent)-232.6(does)-224.2(not)-228.1(interact)-231.5(with)-230.2(cell)-225.9(culture)-229.1(medium,)-232.7(which,)]TJ
0 -1.1174 TD
[(especially)-321.1(for)-308.5(particles,)-316.5(can)-310.9(result)-318.8(in)-307.6(changes)-316.3(of)-313.2(the)-309.9(proper-)]TJ
0 -1.1116 TD
[(ties)-305.1(\(dissolution,)-304.7(agglomeration\).)]TJ
1.0137 -1.1116 TD
[(As)-296.6(a)-296(result,)-299.2(it)-290.4(is)-295.9(possible)-297.8(to)-296.1(conduct)-298.2(exposure)-298.9(approaches)]TJ
-1.0137 -1.1174 TD
[(from)-293.6(real-life)-290.2(atmosphere)-9.9(s)-288.9(b)0(y)-284.4(taking)-290.3(the)-292.6(exposure)-293.1(setup,)-286.5(in-)]TJ
0 -1.1116 TD
[(cluding)-291.4(the)-292.6(biological)-290.3(test)-287.9(system)-291(to)-290.3(the)-292.6(source)-290.9(of)-284.4(the)-292.6(expo-)]TJ
T*
[(sure)-466.1(atmosphere.)]TJ
7.3823 0 0 6.5614 381.9967 335.3952 Tm
(49)Tj
9.843 0 0 9.843 393.9023 331.0298 Tm
[(This)-460.6(is)-462.9(also)-460.5(the)-459.6(experimental)-463(basis)-461.4(to)]TJ
-8.2133 -1.1174 TD
[(consid)-7.7(er)-245.2(relevant)-254.4(factors)-257.6(such)-247.3(as)-250.8(physicochemical)-259.9(properties)]TJ
0 -1.1116 TD
[(of)-388.1(the)-384.7(test)-385.8(atmosphere,)-387.7(different)-386.8(experimental)-388.1(methods)-384.4(for)]TJ
T*
[(generation)-262.4(and)-257.9(characterization)-262.4(of)-255.6(test)-253.3(aerosols)-258.5(and)-257.9(to)-255.8(estab-)]TJ
T*
[(lish)-505.6(an)-504.5(unhindered,)-512.2(dened)-504.1(contact)-506.8(between)-507.5(the)-505.7(biologi-)]TJ
0 -1.1174 TD
[(cal)-414.7(test)-414.6(system)-411.9(and)-413.4(the)-413.5(test)-414.6(material)-417.1(in)-411.3(the)-407.8(airborne)-414.4(state.)]TJ
0 -1.1116 TD
[(Hence,)-261(also)-258.9(from)-253.2(the)-258(point)-253.4(of)-255.6(exposure)-252.8(relevance,)-261.2(ALI)-258.8(mod-)]TJ
T*
[(els)-303.9(exhibit)-303(a)-301.8(large)-301.7(range)-301.5(of)-301.7(possibilities.)]TJ
1.0137 -1.1174 TD
[(The)-224.5(ALI)-224.2(exposure)-224(situation)-224.5(described)-226.4(above)-226.7(could)-225.7(be)-222.2(seen)]TJ
-1.0137 -1.1116 TD
[(as)-268.1(an)-268.3()50.8(ALI)-271.4(microclimate)47.2()-266(condition.)-274.1(Two)-264.6(main)-266.1(mass)-271.4(trans-)]TJ
T*
[(ports)-247.3(control)-245.3(this)-246.4(state:)-251(the)-246.5(mass)-242.6(ow)-245.9(of)-244.1(liquid)-248.9(culture)-246.4(media)]TJ
0 -1.1174 TD
[(throug)-6.7(h)-392.7(the)-396.3(membrane)-400.6(toward)-400.4(the)-402(cells)-399.6(and)-396.1(the)-396.3(uid)-396(ow)]TJ
0 -1.1116 TD
[(necessary)-215.7(to)-209.7(transport)-212.7(the)-206.2(airborne)-212.8(test)-207.2(material)-215.5(to)-209.7(the)-206.2(surface)]TJ
T*
[(of)-301.7(the)-304.1(biological)-301.9(test)-305.1(system.)]TJ
1.0137 -1.1174 TD
[(A)-249.6(range)-249.7(of)-244.1(setup)-248.5(specic)-252.9(factors)-251.8(can)-247.5(then)-247.6(have)-248.6(a)-249.9(large)-249.8(im-)]TJ
-1.0137 -1.1116 TD
[(pact)-358.2(on)-359.3(this)-355.8(scenario.)-355.5(Cell-specic)-364.5(characteristics)-363.4(\(e.g.,)-354.5(the)]TJ
T*
[(forma)-7.8(tion)-286.9(of)-284.4(cell/cell)-291.7(contacts)-294.6(that)-288.1(provide)-285.4(epithelial)-291.6(barrier)]TJ
T*
[(activity\),)-235(pore)-235.9(sizes,)-235.6(and)-229.1(pore)-235.9(densities)-231.1(of)-232.6(the)-235(membrane,)-237(hy-)]TJ
0 -1.1174 TD
[(drophobicit)-7.9(y)-335.2(o)0(f)-336.2(the)-338.7(membrane)-343(surface,)-342.7(ow)-338.1(rate)-340.9(of)-336.2(the)-338.7(gas)]TJ
0 -1.1116 TD
[(ux,)-277.3(humidication)-277.4(of)-272.9(the)-275.3(test)-276.3(atmosphere,)-272.5(pressures)-282.3(of)-272.9(cul-)]TJ
T*
[(ture)-247.6(media)-245.3(and)-246.4(test)-241.8(atmosphere,)-249.5(characteristics)-254(of)-244.1(the)-240.7(culture)]TJ
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