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[(dev)12.8(ice)11.5(s,)-298.1(typ)13.8(ica)11.5(lly)-291.5(usi)14(ng)-301.7(car)11.7(to)15(miz)11.5(ers)13(,)-302.9(hav)12.8(e)-307.5(dem)17.4(ons)14.2(tra)12.7(ted)-298.3(tha)18.4(t)]TJ
0 -1.1174 TD
[(the)-482.6(lim)18.3(ite)12.6(d)-490.7(num)18.5(ber)-482.5(of)-486(co)13.9(nst)14(itu)13.7(ent)12.7(s)-490.5(i)0(n)-480.4(e-c)11.7(iga)12.7(ret)12.7(te)-487.3(ae)12.8(ros)14.2(ols)]TJ
0 -1.1116 TD
[(are)-472.1(ten)12.7(s)-484.7(t)0(o)-474.6(tho)13.8(usa)13(nds)-475.4(of)-474.5(tim)12.5(es)-475.5(low)13(er)-475.6(on)-480.3(a)-480.3(per)12.8(-pu)14(ff)-480.2(ba)13.9(sis)]TJ
T*
[(tha)12.7(n)-312.1(i)0(n)-307.6(c)0(o)13.9(nve)12.8(nti)13.7(ona)12.8(l)-312.2(cig)12.7(are)11.7(tt)14.8(e)-313.3(smo)12.9(ke.)]TJ
7.3823 0 0 6.5614 210.9543 444.9825 Tm
[(12,1)22.1(3)]TJ
9.843 0 0 9.843 230.5133 440.6172 Tm
[(Ma)13(ny)-307.5(of)-307.4(the)-304.1(tox)13.8(i-)]TJ
-17.1178 -1.1174 TD
[(can)11.7(ts)-301.6(in)-296.1(tob)13.9(acc)10.5(o)-306.4(smo)12.9(ke)-297.1(are)-299.3(sim)12.8(ply)-291.4(not)-297.2(pre)12.8(sen)13(t)-300.7(i)0(n)-301.8(e-c)11.7(iga)12.7(ret)12.7(te)]TJ
0 -1.1116 TD
[(aer)11.7(oso)14.2(ls)-365(at)-372.1(det)12.7(ec)12.8(tab)12.7(le)-372.1(lev)12.7(el)13.8(s)-375.3(whe)11.9(n)-369.7(ass)13.2(ess)13.2(ed)-372(usi)14(ng)-365.1(mac)10.4(hin)13.8(e-)]TJ
T*
[(bas)13(ed)-233.7(aer)11.7(oso)14.2(l)-231.6(gen)12.8(era)11.7(tio)13.7(n)-237.2(o)0(r)-226.8(are)-230.2(at)-233.9(lev)18.4(els)-229(equ)12.8(iva)12.7(len)12.7(t)-237.4(t)0(o)-226.9(the)-229.2(tol)13.7(-)]TJ
T*
[(era)11.7(nce)11.7(s)-294.6(all)12.6(owe)11.9(d)-294.8(i)0(n)-290.3(m)0(e)12.7(dic)12.7(ina)12.7(l)-295(pro)14(duc)12.8(ts.)]TJ
7.3823 0 0 6.5614 216.2267 401.159 Tm
[(111)18.7(9)]TJ
9.843 0 0 9.843 72 385.7952 Tm
-.0215 Tc
[(A)-230.8(r).5(ec)-6.5(ent)-230.1(r).5(e)-6.5(v).4(iew)-230.8(o).4(f)-235.7(c)-.7(hemic)-6.5(a)-.7(l,)-232.3(toxi)-5.4(cologi)-5.4(cal,)-232.3(a)-.7(nd)-229.9(c)-6.5(linic)-6.5(al)-230.1(stu)-5.3(d).4(-)]TJ
-1.0137 -1.1116 TD
[(ies)-310.5(f).4(or)-304.9(bo)-5.4(th)-304.9(e-ci)-5.5(garett)-5.5(e)-306.1(liqui)-5.5(ds)]TJ
11.9802 0 TD
-.0207 Tc
[(and)-309.8(aerosols)-303.8(i)1.1(ndicated)-309.8(that)-304.2(they)]TJ
-11.9802 -1.1116 TD
0 Tc
[(c)20.8(o)21.9(n)16.2(t)21.8(a)20.8(i)21.8(n)-231.5(r)22(e)20.8(d)21.9(u)21.9(c)15(e)20.8(d)-225.7(l)21.8(e)15(v)21.9(e)20.8(l)21.8(s)-231.3(o)21.9(f)-225.7(h)16.2(a)20.8(r)22(m)20.7(f)22(u)21.9(l)-231.6(c)20.8(h)21.9(e)20.8(m)20.7(i)16.1(c)20.8(a)20.8(l)21.8(s)-231.3(a)20.8(n)21.9(d)-231.5(em)18.5(is)20.9(si)20.9(on)20.8(s,)-234.7(in)20.7(-)]TJ
0 -1.1174 TD
-.0202 Tc
[(d)-20.2(u).6(c)-20.2(e)-1.7(d)-222.9(s)-20.2(ig)-20.2(ni)-20.2()-5.1(c)-20.2(an)-20.2(tl)-20.2(y)-212.6(l)-20.2(es)-20.2(s)-212.1(c)-20.2(yt)-20.2(ot)-20.2(ox)-20.2(ic)-20.2(i)-6.4(t)-20.2(y,)-219.5(a)-20.2(n)-.5(d)-222.9(r)-20.2(es)-20.2(ul)-20.2(te)-20.2(d)-213.6(i)-20.2(n)-212.6(f)-20.2(ew)-20.2(er)-222.9(c)-20.2(a)-1.7(r)-20.2(-)]TJ
0 -1.1116 TD
0 Tc
[(di)20.7(ov)20.8(as)14.1(cu)19.7(la)19.6(r)-243(a)0(n)19.7(d)-248.8(re)19.7(sp)21(ir)20.7(at)13.8(or)20.9(y)-243(f)0(u)20.9(n)0(c)19.7(t)0(i)14.8(o)0(n)20.8(a)0(l)-233.9(e)0(f)19.7(f)0(e)19.7(c)0(t)13.8(s)-242.8(wh)20(en)-233.7(co)13.9(m)15(p)0(a)13.9(r)0(e)19.7(d)]TJ
T*
[(wi)19.8(th)-457.3(re)19.7(po)20.8(rt)15(ed)-452.6(da)13.9(ta)-452.7(on)-457.2(to)20.7(ba)13.9(cc)18.5(o)-461.9(c)0(i)13.8(g)0(a)19.7(r)0(e)19.7(t)0(t)20.6(e)0(s)19.9(.)]TJ
7.3823 0 0 6.5614 229.8897 335.3952 Tm
(1)Tj
9.843 0 0 9.843 238.1669 331.0298 Tm
[(Ro)19.8(ma)18.4(gn)20.8(a)-468.8(e)0(t)-458.5(a)0(l)19.6(.)]TJ
-17.8954 -1.1174 TD
[(re)19.7(po)20.8(rt)15(ed)-325.9(e-)19.7(ci)19.5(ga)19.7(re)19.7(tt)14.8(e)-330.6(a)0(e)18.5(r)0(o)15.1(s)0(o)21(l)-335.3(to)-324.9(be)-325.9(si)20.9(gn)20.8(i)20.9(ca)12.8(nt)20.7(ly)-324.9(le)19.6(ss)-324.4(cy)19.7(to)20.7(to)15(xi)20.7(c)]TJ
0 -1.1116 TD
[(th)20.7(an)-245.3(to)20.7(ba)19.7(cc)18.5(o)-248.8(s)0(m)19.8(o)0(k)20.8(e)-255.7(in)-238.5(b)21(ro)20.9(bl)20.7(as)14.1(ts)20.9(,)]TJ
7.3823 0 0 6.5614 194.1165 313.455 Tm
-.0162 Tc
(20)Tj
9.843 0 0 9.843 203.8676 309.0897 Tm
0 Tc
[(an)19.7(d)-248.8(F)0(a)19.8(r)0(s)15.3(a)0(l)19.5(i)0(n)20.7(o)0(s)-238.2(e)0(t)-245.4(a)0(l)19.6(.)-251.1(co)19.7(n-)]TJ
-14.4108 -1.1116 TD
[(cl)19.5(ud)20.8(ed)-222.2(th)20.7(e)-232.6(s)0(a)19.9(m)0(e)-217.7()0(n)15.2(d)0(i)20.7(n)0(g)20.8(s)-231.3(in)-215.4(my)19.6(oc)13.9(ar)19.7(di)20.7(al)-222.4(ce)18.5(ll)20.6(s.)]TJ
7.3823 0 0 6.5614 235.6724 302.5133 Tm
-.0162 Tc
(21)Tj
9.843 0 0 9.843 245.1968 298.1479 Tm
0 Tc
[(Sc)19.8(he)13.9(f)21(er)-216.4(et)-222.4(al)19.6(.)]TJ
-18.6096 -1.1116 TD
.0119 Tc
[(fo)5(un)5(d)-294.5(c)3.9(ell)-288.8(v)-.7(i)4.9(a)-1.9(b)5(ili)4.9(ty)-288.7(was)-294.3(l)4.9(ower)-294.4(i)4.9(n)-294.5(p)5(r)-.7(imary)-294.5(h)5(uman)-288.7(br)5.1(onchi)4.9(al)]TJ
0 -1.1174 TD
[(cell)4.8(s)-421.1(e)3.8(xp)4.9(osed)-415.5(to)-415.5(to)4.9(bacco)-415.5(s)-.6(mo)4.9(ke)-416.7(t)4.8(h)-.8(an)-415.5(i)4.8(n)-415.5(e-cig)4.9(a)-2(rett)4.8(e)-416.7(a)-2(ero-)]TJ
0 -1.1116 TD
.0126 Tc
[(so)5.7(l.)]TJ
7.3823 0 0 6.5614 76.3653 269.6314 Tm
.0145 Tc
(22)Tj
9.843 0 0 9.843 86.57 265.2661 Tm
.0119 Tc
[(Husari)-260(et)-260(al.)-262.2(f)-.7(o)5(u)-.7(n)5(d)-265.7(e-cig)5(a)-1.9(rett)4.9(e)-266.8(a)3.9(er)5.1(os)5.2(ols)-259.7(e)-1.9(x)5(h)-.7(i)4.9(b)-.7(i)4.9(t)-.8(ed)-259.9(si)4.9(g-)]TJ
-2.494 -1.1116 TD
-.0215 Tc
[(n)-34.1(i)-28.5()-34(c)-29.5(a)-35.3(n)-34.1(t)-28.5(l)-34.2(y)-414.3(l).3(ess)-344.9(t).3(oxic)-340.5(e)-.7(ffects)-344.9(o).4(n)-345.1(l).3(ungs)-344.9(of)-339.3(experimental)-345.3(animals)]TJ
0 -1.1174 TD
[(and)-247.3(o).3(n)-253.1(A)-.5(549)-247.3(cell)-247.5(c)-.8(ultures)-247.1(t).2(han)-253.1(s).5(moke)-248.5(from)-248.5(t).2(obacco)-247.3(products.)]TJ
7.3823 0 0 6.5614 293.9527 247.6913 Tm
-.0315 Tc
(23)Tj
9.843 0 0 9.843 62.022 232.3842 Tm
-.0212 Tc
[(Wieczorek)-356.4(e)-.4(t)-362.2(a)-.4(l.)-358.7(\(in)-356.4(p).7(ress\))-356.3(c)-.4(ompared)-362.1(t).6(wo)-356.4(e-cigarette)-363.3(a)5.3(e)-.4(rosols)]TJ
0 -1.1116 TD
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[(from)-530.9(b).2(lu)-529.6(GO)]TJ
/F11 1 Tf
5.5293 0 TD
0 Tc
()Tj
/F6 1 Tf
1.3938 0 TD
-.0216 Tc
[(disposable)-530.7(and)-529.5(b).3(l)-5.5(u)-529.5(PLUS)]TJ
/F11 1 Tf
10.5518 0 TD
-.0221 Tc
(+)Tj
/F6 1 Tf
1.9237 0 TD
-.0214 Tc
(rechargeable)Tj
-19.3987 -1.1174 TD
[(cartridge-based)-310.6(devices)-304.6(with)-310.6(the)-306(s).6(moke)-306(from)-311.8(a)-306(reference)-306(c)-.7(iga-)]TJ
0 -1.1116 TD
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[(rette)-306.1(\(3R4F\))-310.6(in)-304.9(an)]TJ
/F7 1 Tf
7.3033 0 TD
[(in)-310.8(vitro)]TJ
/F6 1 Tf
3.139 0 TD
[(battery)-304.9(of)-310.6(established)-304.9(a)-.8(ssay:)-310.8(neutral)]TJ
-10.4423 -1.1116 TD
[(red)-615.9(uptake)-617.1(\().4(NRU\))-615.9(for)-615.9(c)-.8(ytotoxicity,)]TJ
/F7 1 Tf
15.3727 0 TD
[(in)-616(vitro)]TJ
/F6 1 Tf
3.7553 0 TD
-.0224 Tc
[(micr)-6.2(onucleus)]TJ
-19.128 -1.1174 TD
-.0216 Tc
[(\(IVM\))-535.3(for)-529.5(g).3(enotoxicity,)-537.6(a)-.8(nd)-529.5(the)-536.5(b).3(acterial)-529.7(r).4(everse)-536.5(mutation)]TJ
0 -1.1116 TD
[(\(Ames\))-253(assay)-258.8(f).4(or)-253.1(mutagenicity.)-255.4(R)5.1(es)-5.2(ults)-252.9(from)-254.3(t).2(his)-252.9(s).5(t)-5.5(udy)-253.1(showed)]TJ
T*
[(that)-287.7(the)-288.7(e)-.7(-cigarette)-282.9(fresh)-281.8(w)-.4(hole)-288.7(aerosol)-287.7(resulted)-287.5(i).3(n)-287.5(a)-288.7(signicant)]TJ
T*
-.0218 Tc
[(2501000-fold)-374.2(reduction)-374.2(i)0(n)]TJ
/F7 1 Tf
11.1162 0 TD
-.0216 Tc
[(in)-368.3(vitr)-5.2(o)]TJ
/F6 1 Tf
3.2658 0 TD
-.0218 Tc
[(cytotoxic)-375.4(r).2(esponse)-375.4(i)0(n)-374.2(t)0(he)]TJ
-14.382 -1.1174 TD
[(BEAS-2B)-444.3(cell)-437.6(line)-444.4(c)-.9(ompar)-5.5(e)-.9(d)-437.5(w)-.6(ith)-443.3(cigarette)-438.7(smoke)-444.4(and)-437.5(d).2(is-)]TJ
0 -1.1116 TD
-.0216 Tc
[(played)-230(no)-235.8(mutagenetic)-231.2(response)-237(i).2(n)-230(T)-.8(A100)-230(or)-235.8(TA98)-230(or)-235.8(genotox-)]TJ
T*
[(icity)-506.5(in)-500.7(V79)-506.5(cells.)-503.1(I).4(n)-500.7(a)-.8(ddition,)-503.1(Wieczorek)-506.5(e)-.8(t)-500.9(a)-.8(l.)-508.8(\(in)-500.7(p).3(ress\))]TJ
0 -1.1174 TD
[(showed)-207.1(device)-208.3(type)-208.3(could)-207.1(i).1(mpact)-207.2(t).1(he)-208.3(cytotoxicity)-207.1(of)-207.1(the)-208.3(aerosol.)]TJ
0 -1.1116 TD
-.0214 Tc
[(Aerosol)-333.7(g).5(enerated)-327.8(from)-329(b).5(lu)-333.5(GO)-328.6(was)-333.3(s).7(ignicantly)-327.8(more)-334.7(ac)5.1(tive)]TJ
T*
[(than)-322(blu)-322(P).7(LUS)]TJ
/F11 1 Tf
5.8519 0 TD
0 Tc
(+)Tj
/F6 1 Tf
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-.0222 Tc
[(aerosol)-322.9(in)-328.6(the)-324(N)-1.1(RU)-323.7(as)-5.8(say,)-319.4(although)-322.8(these)-324(r)-6(e-)]TJ
-6.7043 -1.1174 TD
-.0216 Tc
[(sponses)-327.8(were)-329.1(subs)-5.2(tantially)-328(less)-327.8(cytotoxic)-329.1(t).2(han)-328(c)-.8(igarette)-329.1(smoke)]TJ
0 -1.1116 TD
(exposure.)Tj
7.3823 0 0 6.5614 98.1354 61.3984 Tm
-.0315 Tc
(24)Tj
9.843 0 0 9.843 109.9275 57.0331 Tm
-.0214 Tc
[(The)-496(b).5(lu)-494.8(GO)-489.9(device)-496(operates)-494.6(a)-.6(t)-489.2(a)-496(much)-494.8(higher)]TJ
20.637 67.9184 TD
-.0209 Tc
[(pow)5.9(e)-.1(r)-252.3(l).9(evel)-246.8(than)-246.6(blu)-246.6(P)1.2(LUS)]TJ
/F11 1 Tf
10.4423 0 TD
0 Tc
(+)Tj
/F6 1 Tf
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-.0215 Tc
[(;)-247.4(a)-.7(lthough)-247.2(this)-247(may)-247.2(g).4(enerate)-248.4(l).3(arger)]TJ
-10.9722 -1.1174 TD
-.0217 Tc
[(pu)-5.5(ff)-270.4(volumes)-270.3(and)-270.5(d).2(eliver)-270.4(higher)-270.4(doses)-270.3(per)-270.4(puff)-270.4(t).1(o)-270.5(t).1(he)-271.6(user)-270.4(than)]TJ
0 -1.1116 TD
-.0186 Tc
[(th)3.3(e)-303.1(b)3.3(l)3.2(u)-307.7(P)3.5(L)2.2(US)]TJ
/F11 1 Tf
5.3508 0 TD
0 Tc
(+)Tj
/F6 1 Tf
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-.0215 Tc
[(product,)-307.2(the)-311.7(d).4(ifferences)-310.4(seen)-310.6(is)-310.4(this)-304.6(s)-5.1(t).3(udy)-304.8(may)]TJ
-6.1917 -1.1116 TD
-.0217 Tc
[(be)-340.7(due)-335(t)-5.6(o)-333.8(changes)-339.4(i).1(n)-333.8(t).1(he)-340.7(chemical)-339.7(nature)-340.7(of)-333.8(the)-340.7(aerosol.)-336.1(P).4(ub-)]TJ
T*
[(l)-5.5(i).2(shed)-512.3(clinical)-518.2(research)-512.3(has)-517.8(s).5(hown)-512.3(t).2(hat)-518.2(a)-.8(dult)-518.2(s).5(moker)-5.4(s)-512.1(who)]TJ
0 -1.1174 TD
[(s)-5.2(w)-.5(itch)-541.1(t).2(o)-546.8(e)-.8(-cigarettes)-546.6(h).3(ave)-548(s).5(ignicantly)-546.8(lower)-546.8(e)-.8(xposure)-548(t).2(o)]TJ
0 -1.1116 TD
[(carcinogens)-230(and)-224.4(t)-5.6(oxicant)-5.6(s)-224.2(f).3(ound)-230.1(in)-224.4(cigarette)-231.3(smoke,)-226.7(w)-.6(ith)-224.4(reduc-)]TJ
T*
[(t)-5.7(i)0(ons)-385.6(largely)-385.8(i)0(ndis)-5.4(tinguishable)-386.9(from)-387(c)-1(omplete)-392.7(s).3(moki)-5.7(ng)-385.8(cessa-)]TJ
0 -1.1174 TD
-.0214 Tc
[(t)-5.3(i).4(on)-299(or)-298.9(use)-300.1(o).5(f)-298.9(licensed)-299(n).5(icotine)-300.1(r).6(eplacement)-299.1(p).5(roducts.)]TJ
7.3823 0 0 6.5614 517.6062 642.2172 Tm
-.0315 Tc
[(2)-7.6(52)-7.6(7)]TJ
9.843 0 0 9.843 323.0361 626.91 Tm
0 Tc
[(In)-226.8(su)21(mm)18.4(ar)19.7(y,)-223.4(it)-221.3(ha)19.7(s)-237.1(b)0(e)19.7(e)0(n)-222.2(d)0(e)19.7(m)0(o)19.6(n)0(s)15.3(t)0(r)20.7(a)0(t)19.5(e)0(d)-222.2(t)0(h)20.7(a)0(t)-228.1(o)0(l)20.7(d)0(e)19.7(r)-231.4(ge)13.9(ne)19.7(ra)19.7(ti)20.6(on)]TJ
-1.0137 -1.1116 TD
[(e-)14(ci)19.5(ga)19.7(re)19.7(tt)20.6(e)-457.3(a)0(e)18.5(r)0(o)15.1(s)0(o)21(l)0(s)-445.6(a)0(r)19.7(e)-457.3(ch)13.9(em)18.4(ic)19.6(al)19.5(ly)-445.8(si)20.9(mp)19.6(le)-447(wh)14.2(en)-446.8(co)19.7(mp)19.6(ar)19.7(ed)]TJ
0 -1.1174 TD
[(wi)14.1(th)-388.2(ci)19.5(ga)13.9(re)19.7(tt)20.6(e)-399.7(s)0(m)14(o)0(k)20.8(e)0(.)-391.6(T)0(h)19.6(e)-399.7(in)15(ha)19.7(la)19.5(ti)20.6(on)-393.9(of)-388.1(e-)14(ci)19.5(ga)19.7(re)19.7(tt)20.6(e)-405.4(a)0(e)18.5(r)0(o)20.9(s)0(o)21(l)0(,)]TJ
0 -1.1116 TD
[(co)13.9(mp)19.6(ar)19.7(ed)-377.7(wi)19.8(th)-376.7(ci)19.5(ga)19.7(re)19.7(tt)20.6(e)-388.2(s)0(m)19.8(o)0(k)20.8(e)0(,)-380.1(h)0(a)19.7(s)-381(th)15(e)-382.4(p)0(o)15.1(t)0(e)19.6(n)0(t)20.7(i)0(a)19.6(l)-387.1(to)-376.7(in)20.7(du)20.8(ce)]TJ
T*
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0 -1.1174 TD
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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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T*
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T*
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