Page 1 o 38
C i ical e iew on he s abili y o illici d ugs in sewe s and
was ewa e samples
Ann-Ka h in McCall a, Richa d Bade b, Julie Kinyua c, Foon Yin Lai d, Phong K. Thai d,e, Ad ian 5
Co aci c, Lube us Bijlsma b, Alexande L.N. an Nuijs c, Ch is oph O a,*
a Eawag, Swiss Fede al Ins i u e o Aqua ic Science and Technology, CH 8600 Dübendo ,
Swi ze land 10
b Resea ch Ins i u e o Pes icides and Wa e , Uni e si y Jaume I, A da. Sos Bayna , E-12071
Cas ellón, Spain
c Toxicological Cen e, Depa men o Pha maceu ical Sciences, Uni e si y o An we p (UA),
Uni e si ei splein 1, 2610 An we p, Belgium
d The Uni e si y o Queensland, The Na ional Resea ch Cen e o En i onmen al Toxicology (En ox), 15
39 Kessels Rd., Coope s Plains, B isbane, QLD 4108, Aus alia
e Queensland Uni e si y o Technology, In e na ional Labo a o y o Ai Quali y & Heal h, 2 Geo ge
S ee , B isbane, QLD 4001, Aus alia
* Co esponding au ho . Tel.: +41 58 765 5041. E-mail add ess: Ch is oph[email p o ec ed] 20
Page 2 o 38
Abs ac
Was ewa e -based epidemiology (WBE) applies ad anced analy ical me hods o quan i y d ug 25
esidues in was ewa e wi h he aim o es ima e illici d ug use a he popula ion le el. T ans o ma ion
p ocesses du ing anspo in sewe s (chemical and biological eac o s) and s o age o was ewa e
samples be o e analysis a e expec ed o change concen a ions o di e en d ugs o a ying deg ees.
Igno ing ans o ma ion o d ugs wi h low o medium s abili y will lead o an unknown deg ee o
sys ema ic unde - o o e es ima ion o d ug use, which should be a oided. This e iew aims o 30
summa ize he cu en knowledge ela ed o he s abili y o commonly in es iga ed d ugs and,
u he mo e, sugges a mo e e ec i e app oach o u u e expe imen s. F om o e 100 WBE s udies,
a ound 50 men ioned he impo ance o s abili y and 24 included es s in was ewa e . Mos ocused on
in-sample s abili y (i.e., sample p epa a ion, p ese a ion and s o age) and some ex apola ed o in-
sewe s abili y (i.e., du ing anspo in eal sewe s). While consis en esul s we e epo ed o a he 35
s able compounds (e.g., MDMA and me hamphe amine), a a ying ange o s abili y unde di e en o
simila condi ions was obse ed o o he compounds (e.g., cocaine, amphe amine and mo phine).
Was ewa e composi ion can a y conside ably o e ime, and di e en condi ions p e ail in di e en
sewe sys ems. In summa y, his indica es ha mo e sys ema ic s udies a e needed o: i) co e he
ange o possible condi ions in sewe s and ii) compa e esul s mo e objec i ely. To acili a e he la e , 40
we p opose a se o pa ame e s ha should be epo ed o in-sewe s abili y expe imen s (labo a o y
and ull-scale). Finally, a bes p ac ice o sample collec ion, p ese a ion, and p epa a ion be o e
analysis is sugges ed in o de o minimize ans o ma ion du ing hese s eps.
Keywo ds: T ans o ma ion, sewage epidemiology, sample p ese a ion, psychoac i e subs ances, 45
biodeg ada ion.
Page 3 o 38
Con en
1 In oduc ion ..................................................................................................................................... 4
1.1 En i onmen al p ocesses in sewe ne wo ks ........................................................................... 6 50
1.2 S abili y o illici d ug bioma ke s du ing was ewa e ea men p ocesses and in he
en i onmen ......................................................................................................................................... 7
2 Summa y o e iewed s udies ......................................................................................................... 8
2.1 Gene al se up ........................................................................................................................... 8
2.2 Cocaine and me aboli es ........................................................................................................ 19 55
2.3 Amphe amine and amphe amine- ype subs ances ................................................................. 20
2.4 Opia es ................................................................................................................................... 21
2.5 Cannabinoids ......................................................................................................................... 23
2.6 O he subs ances .................................................................................................................... 23
3 Discussion ..................................................................................................................................... 24 60
4 Recommenda ions o u u e in-sewe expe imen s ...................................................................... 27
5 Recommenda ions o p ese ing illici d ugs in was ewa e samples .......................................... 30
6 Conclusions ................................................................................................................................... 31
Acknowledgemen s ............................................................................................................................... 32
7 Re e ences ..................................................................................................................................... 33 65
Abb e ia ions
6-MAM 6-monoace yl mo phine
AMP Amphe amine
BE Benzoylecgonine 70 COC Cocaine
COCA Cocae hylene
COD Codeine
EDDP 2-e hylidene-1,5-dime hyl-3,3-diphenylpy olidine
EME Ecgonine me hyl es e 75 KET Ke amine
LSD Lyse gic acid die hylamide
MBDB Me hylbenzodioxolylbu anamine
MDA 3,4-me hylenedioxyamphe amine
MDEA 3,4-me hylenedioxy-N-e hylamphe amine 80 MDMA 3,4-me hylenedioxy-me hamphe amine
METH Me hamphe amine
MOR Mo phine
MTD Me hadone
no -BE No -benzoylecgonine 85 no -COC No -cocaine
SPE Solid-phase ex ac ion
SPM Suspended pa icula e ma e
THC Δ9- e ahyd ocannabinol
THC-COOH 11-no -9-ca boxy-THC 90 THC-OH 11-hyd oxy-THC
TSS To al suspended solids
VSS Vola ile suspended solids
WBE Was ewa e -based epidemiology
95
Page 4 o 38
1 In oduc ion
Was ewa e -based epidemiology (WBE) is a ecen ly in oduced moni o ing ool in d ug
epidemiology. I p o ides objec i e in o ma ion abou he le els and pa e ns o d ug use a he
popula ion le el and as such is complemen a y o exis ing su ey-based me hods. I has also he
po en ial o se e as an ea ly wa ning sys em o he use o new psychoac i e subs ances (NPS, e.g., 100
Kinyua e al., 2015; Reid e al., 2014) and o in es iga e he e ec i eness o in e en ion p og ams
(e.g., Bu ga d e al., 2014; Cas iglioni e al., 2014). The p inciple o WBE is p edica ed by he ac ha
subs ances a e exc e ed as pa en compounds and/o me aboli es - subsequen ly e e ed o as
bioma ke s (o illici d ugs) - a e consump ion and anspo ed h ough he sewe ne wo k o
was ewa e ea men plan s (Figu e 1). 105
Figu e 1. Sys em bounda ies used in was ewa e -based epidemiology.
The concen a ions o bioma ke s in he was ewa e (ci) can be quan i ied wi h ad anced analy ical
ins umen s, such as liquid ch oma og aphy coupled o andem mass spec ome y (LC-MS/MS). 110
Consump ion es ima es a e calcula ed acco ding o Eq. 1:
(1)
Page 5 o 38
whe e Q = was ewa e olume, ci = concen a ion o d ug i, m i = mola mass a io (pa en o
me aboli e), P = popula ion o no maliza ion, ei = d ug-speci ic pha macokine ic exc e ion a e
(a e age o dis ibu ion o u ina y exc e ion, e.g., an Nuijs e al., 2011a; Zucca o e al., 2005) and pi 115
= pu i y o d ug. In 2005, WBE was applied o he i s ime, back-calcula ing he cocaine use o
communi ies in I aly (Zucca o e al., 2005). Since hen, s udies ha e compa ed empo al and spa ial
d ug use ends by consump ion di e ences be ween u al and me opoli an a eas (e.g., I ine e al.,
2011; an Nuijs e al., 2009a; an Nuijs e al., 2011b), among di e en coun ies (e.g., O e al., 2014;
Thomas e al., 2012) and du ing special e en s ( es i als, holidays (e.g., Lai e al., 2013)) o name 120
some o se e al applica ions.
Mos illici d ugs may o may no ha e lici medical pu poses, bu hey a e p oduced, a icked and/o
consumed illegally on a la ge scale (Uni ed Na ions O ice o D ug and C ime, 2014). In his e iew,
we ocus on he mos equen ly used illici d ugs and hei me aboli es: cocaine, amphe amines and
amphe amine- ype subs ances, opia es, cannabinoids and selec ed o he illici subs ances, such as 125
ke amine (KET) and lyse gic acid die hylamide (LSD).
One o he main challenges in WBE is o educe he unce ain y o each a iable in he back-
calcula ion equa ion (Eq. 1). High unce ain y is ela ed o he exc e ion a es based on
pha macokine ic li e a u e (Cas iglioni e al., 2013) and he chemical analysis o he bioma ke s in he
complex was ewa e ma ix. Nume ous e o s ha e ocused on imp o ing he accu acy ( ueness and 130
p ecision) o di e en analy ical me hods, and in e -labo a o y s udies we e conduc ed in o de o
e alua e and ha monize he di e en analy ical p ocedu es being used (Cas iglioni e al., 2013;
Thomas e al., 2012). Unce ain ies associa ed wi h he popula ion es ima es ha e ecen ly been
concep ually educed (Lai e al., 2015; O’B ien e al., 2014), as well as he unce ain y ela ed o
was ewa e sampling (O e al., 2010). Fu he mo e, sample collec ion, s o age and p epa a ion 135
me hods ha e been e alua ed, deducing c i ical, subs ance-speci ic pa ame e s: i) sol en and
empe a u e used du ing he e apo a ion o solid-phase ex ac ion (SPE) ex ac s, and ii) bioma ke
s abili y in he was ewa e ma ix and silanisa ion o glasswa e (Bake and Kasp zyk-Ho de n 2011a).
To u he minimize unce ain y o WBE, a be e unde s anding o in-sewe and in-sample s abili y o
bioma ke s is needed (Fig. 1). 140

Page 6 o 38
Cas iglioni e al. (2013) es ima ed ha he unce ain y ela ed o he s abili y o he bioma ke s du ing
in-sewe anspo is less han 10%. Howe e , hey also concluded ha mo e esea ch is needed. O he
s udies u ge he conside a ion o he s abili y o he illici d ug bioma ke s in he back-calcula ion
me hod ( an Nuijs e al., 2009b; Ös man e al., 2014).
While in-sample s abili y has been s udied o some deg ee o mos o he bioma ke s (e.g., Bake and 145
Kasp zyk-Ho de n, 2011a; Chen e al., 2013; Ös man e al., 2014), hei in-sewe s abili y unde he
in luence o a ying en i onmen al condi ions is no well unde s ood. The sewe is conside ed a
biological and chemical eac o , in luenced by physical p ocesses (H i ed-Jacobsen e al., 2013).
Residence imes o 30min o 12h ( a ely up o 24h) in mos ca chmen s and po en ial en i onmen al
p ocesses acili a e o ma ion o ans o ma ion p oduc s (Heue e al., 2015a). Consequen ly, he 150
omission o bioma ke -speci ic in-sewe ans o ma ion may add an unknown le el o unce ain y.
Ye , only ew s udies ha e in es iga ed in-sewe s abili y o selec ed bioma ke s unde en i onmen al
condi ions (Sen a e al., 2014; Thai e al., 2014; an Nuijs e al., 2012) and accoun ed o s abili y in
he back-calcula ion o d ug use (Bake e al., 2014; Ös man e al., 2014).
In his e iew, we summa ize and c i ically e alua e he a ailable scien i ic li e a u e ocusing on he 155
s abili y o he mos equen ly used illici d ugs du ing i) in-sewe anspo and ii) in-sample s o age.
Using his in o ma ion, mo e insigh is ob ained ega ding he unce ain y o WBE associa ed wi h
s abili y and, addi ionally, sugges ions o bes p ac ices in u u e s abili y s udies a e p o ided.
1.1 En i onmen al p ocesses in sewe ne wo ks
In gene al, wo majo ca ego ies o p ocesses de e mine he o e all a e o illici d ug bioma ke s in 160
he sewe ne wo k. Fi s , mass ans e p ocesses ha lea e he s uc u e o he chemicals unchanged,
e.g., anspo , mixing and ans e among di e en phases and/o compa men s (so p ion,
sedimen a ion, and up ake by o ganisms). The second ca ego y includes p ocesses ha al e he
s uc u e o he compounds, e.g., chemical and/o biological ans o ma ion eac ions (Schwa zenbach
e al., 2003b). Fo he emainde o he manusc ip , he e m ans o ma ion will be used o e e o any 165
o hese h ee p ocesses, al hough physical p ocesses a e a he ans e , no ans o ma ion, p ocesses.
Page 7 o 38
Was ewa e con ains a la ge numbe o soluble, colloidal, and suspended componen s (e.g., nu ien s,
me als, mic opollu an s and pa hogenic and nonpa hogenic mic oo ganisms). I s con en a ies in ime
and space, which a o s o inhibi s speci ic en i onmen al p ocesses. In addi ion, sewe designs and
ope a ion modes in luence he p e ailing condi ions, e.g., oxygen concen a ions ( edox po en ial), pH, 170
empe a u e, low eloci ies and sedimen s (Figu e 2). The domina ing p ocesses ha may in luence
bioma ke concen a ions in he sewe a e mos likely esidence ime, abio ic and bio ic
ans o ma ions (e.g., hyd olysis, deconjuga ion, biodeg ada ion), as well as so p ion o SPM. Fu he ,
he p esence o bio ilms on he sewe walls should be accoun ed o (H i ed-Jacobsen e al., 2013).
175
Figu e 2. C oss-sec ions o g a i y d i en and p essu ized sewe s.
1.2 S abili y o illici d ug bioma ke s du ing was ewa e ea men p ocesses
and in he en i onmen
I is no ewo hy ha compounds may also be ans o med h ough nume ous p ocesses, e.g., 180
chlo ina ion o ozona ion, du ing was ewa e ea men o pho odeg ada ion in he en i onmen .
E ec s o hese p ocesses and esul ing ans o ma ion p oduc s we e beyond he scope o his e iew.
To ully assess hei a e, anspo and oxicological impac on he na u al en i onmen ,
comp ehensi e moni o ing and addi ional in es iga ions a e needed (Bijlsma e al., 2013; Heue e al.,
2015a). Se e al e iews a e a ailable o hese pe inen opics (Bijlsma e al., 2013; Boix e al., 2014; 185
Pos igo e al., 2011a, 2011b; Rodayan e al., 2014; Heue e al., 2015a).
Page 8 o 38
2 Summa y o e iewed s udies
Mo e han 50 WBE s udies men ioned he impo ance o s abili y, om which 24 ac ually in es iga ed
in-sewe o in-sample s abili y o some ex en . O e all, a clea dis inc ion be ween in-sewe and in-
sample s abili y is lacking in he cu en li e a u e. 190
2.1 Gene al se up
In-sewe s abili y expe imen s should accoun o all ele an p ocesses occu ing in sewe
compa men s: i) he bulk liquid (was ewa e wi h suspended pa icula e ma e (SPM)), ii) he bio ilm
g owing on he sewe walls, iii) he sedimen s, and i ) he sewe a mosphe e in g a i y sewe s. Mos
s udies only in es iga ed he s abili y in he bulk liquid. No expe imen s o da e ha e in es iga ed he 195
e ec o sewe sedimen s o he sewe a mosphe e on bioma ke ans o ma ion. Focusing on illici
d ugs, only one pilo -scale sewe eac o s udy included he sewe wall bio ilm (Thai e al., 2014).
Conside ing he physico-chemical p ope ies o mos bioma ke s (Table S1) and hei hyd ophilic
cha ac e , p ecipi a ion and e apo a ion seem negligible (Te nes and Joss, 2006).
In his e iew, we conside all labo a o y s udies using un il e ed was ewa e a a ypical pH a ound 7-200
8, a empe a u es abo e 10°C as in-sewe s udies. None heless, he expe imen al se ups o hese
s udies di e ed in complexi y wi h di e en deg ees o app oxima ion. Se e al esea ch g oups
conduc ed s abili y s udies as pa o a alida ion me hod, and only a ew publica ions showcased an
exclusi e ocus on analy e s abili y in was ewa e . Consequen ly, he main s udy condi ions a e
summa ized in Table 1. Usually, he concen a ion o bioma ke s in spiked, un il e ed was ewa e was 205
moni o ed in glass o plas ic con aine s, in he da k, unde cons an pH and empe a u e, o e pe iods
o 12-72h. Six publica ions conside ed he ac ion o bioma ke ha bound o SPM o sludge (in
was ewa e ea men plan s).
Page 9 o 38
Table 1. O e iew o expe imen al condi ions
Publica ion
in-sewe s abili y s udy
in-sample s abili y s udy
so p ion o SPM s udy
Ma ix
Sc eening
Spiking le els
Sampling in e al
Expe imen al con aine
pH
Tempe a u e
Redox condi ions
Bake and Kasp zyk-
Ho de n, 2011a
x
un il e ed WW
a ge
1 µg/L
0, 12, 24, 72 h
ambe silanized
glass bo les
pH 7.4
19 °C
NA
x
un il e ed and il e ed
WW
1 µg/L
0, 12, 24, 72 h
pH 7.4 and 1.8
2°C and
19°C
xa
il e ed WW ( il e ype
no epo ed)
1 µg/L
0, 2, 4,6 weeks
pH 2
-20°C
Bake and Kasp zyk-
Ho de n, 2011b
x
un il e ed WW
a ge
none
no ele an
ambe silanised
bo les
NA
NA
NA
Bisceglia and Lippa,
2014
x
WW (coa sely il e ed
11µm Wha man Nb1)
a ge
3-600x he
backg ound
concen a ions
> 10 x o e 24 h
1-L glass
E lenmeye lask
pH 7.3
9°C, 23°C,
31°C
NA
Boix e al., 2014
x
WW, su ace wa e
suspec
1000 µg/L
0, 1, 3, 7, 10, 17
days
NA
NA
oom
empe a u e
NA
Bu ga d e al., 2013
x
un il e ed WW
a ge
1 µg/L
8 x o e 72 h
glass con aine
NA
max. 20°C
NA
Cas iglioni e al., 2011a
x
un il e ed WW
a ge
1-5 µg/L
0, 1, 3 days; 3
eeze- haw cycles
glass bo les
NA
4°C, -20°C
eeze-and-
haw
NA
Cas iglioni e al., 2006
x
un il e ed WW
a ge
0.5-5 µg/L
0, 3 days
glass bo les
NA
4°C
NA
Cas iglioni e al., 2015
x
un il e ed WW
a ge
0.1 µg/L
0, 3, 6, 24, 48 h
glass bo les
NA
4°C; oom
empe a u e
NA
x
un il e ed WW
0.1 µg/L
0, 3, 6, 24, 48 h
glass bo les
NA
oom
empe a u e
NA
Page 16 o 38
3,4-me hylene-
dioxy-Ne hyl-
amphe amine
(MDEA)
1
<10% ans o ma ion in un il e ed WW 19°C a pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
6
High: ans o ma ion <10% up o 24 h a 4°C and 20°C; <20%
deg ada ion a -20°C o e 123 d
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2006; Chiaia e al., 2008; González-Ma iño e al.,
2010; Heue e al., 2015b; Ös man e al., 2014
me hylbenzodioxolyl-
bu anamine (MBDB)
1
<20% ans o ma ion in un il e ed WW 19°C a pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
2
High: ans o ma ion <10% up o 24 h a 4°C and 20°C
Bake and Kasp zyk-Ho de n, 2011a; Ös man e al.,
2014
me hylenedioxypy o ale one*
(MDPV)
1
in un il e ed WW no ans o ma ion a 22°C
Ma dal e al. 2014
1
ans o ma ion <10% a e 24 h a 22°C in was ewa e ; in u ine s able o e
14 d a oom empe a u e, 4°C and -20°C
Ma dal e al. 2014
me hylphenida e* ( i alin)
0
NA
NA
1
36% ans o ma ion a 4°C and 88% ans o ma ion a oom empe a u e
o e 24 h in was ewa e ; in milliQ <10% ans o ma ion
Ös man e al., 2014
i alinic acid*
0
NA
NA
1
<10% ans o ma ion a e 72 h in was ewa e a 20°C
Bu ga d e al., 2013
mephed one*
0
NA
NA
1
in was ewa e <10% ans o ma ion du ing 24 h a oom empe a u e and a
4 °C
Ös man e al., 2014
Opia es
he oin
1
in un il e ed WW >90% ans o ma ion a 19°C and pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
3
Low: ans o med 66% a e 12 h a 2°C and 79% a 19°C; 50%
deg ada ion a -20°C o e 7 d and >90% o e 123 d
Bake and Kasp zyk-Ho de n, 2011a; González-
Ma iño e al., 2010; Heue e al., 2015b
6-mono-ace yl-
mo phine* (6-
MAM)
3
Low: 88% ans o ma ion o e 12 h @ 20°C in g a i y sewe labo a o y
eac o --> ca. 100% ans o ma ion expec ed o e 24 h. In aising main
sewe 87% ans o ma ion occu ed o e 12 h.
Bake and Kasp zyk-Ho de n, 2011a; Sen a e al.,
2014; Thai e al., 2014
5
Low: deg aded quickly in WW (6% ans o ma ion a 20°C o e 12 h); bu
ela i ely s able in milliQ; High: <20% deg ada ion a -20°C o e 3, 7, 17,
27 d
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2006; Heue e al., 2015b; Ös man e al., 2014;
Sen a e al., 2014
me hadone* (MTD)
3
Va iable: in un il e ed WW <10% loss a 19/20°C and pH 7.4; +10% a
20°C in un il e ed WW pH 7.5; may be p one o so p ion
Bake and Kasp zyk-Ho de n, 2011a; Sen a e al.,
2014; an Nuijs e al., 2012
8
Va iable: <20% di e ence a oom empe a u e and 4°C; may be p one o
so p ion; >40% deg ada ion a -20°C o e 123 d
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2006; Rosa Boleda e al., 2011; Chiaia e al., 2008;
González-Ma iño e al., 2010; Heue e al., 2015b;
Ös man e al., 2014; Sen a e al., 2014
2-e hylidene-1,5-
dime hyl-3,3-
1
in un il e ed WW ca.20% loss a 19°C and pH 7.4; may be p one o
so p ion
Bake and Kasp zyk-Ho de n, 2011a

Page 17 o 38
diphenyl-
py olidine*
(EDDP)
5
Va iable: less han 15% di e ence a e 24 h; may be p one o so p ion; ca.
40% deg ada ion a -20°C o e 3, 7 and 123 d
Bake and Kasp zyk-Ho de n, 2011a; Rosa Boleda e
al., 2011; Cas iglioni e al., 2006; Heue e al., 2015b;
Ös man e al., 2014
mo phine* (MOR)
2
Va iable: in un il e ed WW up o 50% loss (19°C, pH 7.4); up o 20%
inc ease (20°C, pH 7.5) ( ans o ma ion p oduc o o he subs ances)
Bake and Kasp zyk-Ho de n, 2011a; Sen a e al.,
2014
5
Va iable: di icul o judge because o he gene a ion o mo phine om
o he d ugs; gene ally ela i high s abli y a 4°C in un il e ed WW o e 24
h; <20% deg ada ion a -20°C o e 3, 7, 17, 27 d
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2006; Heue e al., 2015b; Ös man e al., 2014;
Sen a e al., 2014
mo phine-3β-D-
glucu onide
1
comple e ans o ma ion in un il e ed WW pH 7.5 20°C
Sen a e al., 2014
2
Low: a pH 7.5 o e 24 h a 20°C >80% ans o ma ion in WW; 96%
ans o ma ion in WW a 4°C o e 3 d; high: in WW a pH 2 o e 78 h a
20°C
Cas iglioni e al., 2006; Sen a e al., 2014
oxycodone*
1
<10% ans o ma ion in un il e ed WW a 19°C and pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
4
High: s able (<20% ans o ma ion) a 19°C and pH 7.4; <10% deg ada ion
a -20°C o e 3, 7, 17, 27, 123 d
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2006; Heue e al., 2015b; Ös man e al., 2014
en anyl*
1
<20% ans o ma ion in un il e ed WW a 19°C and pH 7.4; may be p one
o so p ion
Bake and Kasp zyk-Ho de n, 2011a
3
Va iable/medium: <10% deg ada ion in il e ed WW a oom empe a u e;
<20% loss in un il e ed WW 19°C and pH 7.4 bu 62% loss a e 72h unde
same condi ions; may be p one o so p ion high: in milliQ
Bake and Kasp zyk-Ho de n, 2011a; Rosa Boleda e
al., 2011; Ös man e al., 2014
bup eno phine*
1
<10% ans o ma ion in un il e ed WW a 19°C and pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
1
Va iable: ca.30% o ma ion in il e ed WW a oom empe a u e; <10%
deg ada ion in un il e ed WW a 4°C and 19°C and pH 7.4; high: in milliQ
<10% ans o ma ion
Bake and Kasp zyk-Ho de n, 2011a; Ös man e al.,
2014
codeine* (COD)
1
High: <20% ans o ma ion/ o med in un il e ed WW a 19°C and pH 7.4
Bake and Kasp zyk-Ho de n, 2011a
4
Va iable: High: In il e ed/un il e ed WW <20% ans o ma ion o e 24 h
a 4°C, 19°C and oom empe a u e; may be o med om o he subs ances;
<10% deg ada ion a -20°C o e 3, 7, 17, 27, 123 d; Low: 80% ans o med
in dilu ed ac i a ed sludge pH 7
Bake and Kasp zyk-Ho de n, 2011a; Heue e al.,
2015b; Ös man e al., 2014; Wick e al., 2011
Cannabinoids
e ahyd o-cannabinol (THC)
1
<20% ans o ma ion in un il e ed WW pH 7.5 20°C; may be los due o
so p ion
Sen a e al., 2014
1
NA - almos no THC is exc e ed in human u ine (Ka ch and Jenkins, 2006;
Pos igo e al., 2011; Lai e al., 2011); in spiked un il e ed WW s o ed a -
20°C 50% deg ada ion o e 7 days and >90% a e 123 d
Heue e al., 2015b
THC-COOH*
1
<20% ans o ma ion in un il e ed WW pH 7.5 20°C; may be los due o
so p ion
Sen a e al., 2014
Page 18 o 38
4
Va iable: may be los due o so p ion; High in WW a 4°C and 20°C o e
72 h; high on SPE ca idges o e h ee weeks a -20°C; high a -20°C o e
3, 7, 17, 27, 123 d; Low a pH 2 o e 24 h
Boix e al., 2014; Cas iglioni e al., 2006; González-
Ma iño e al., 2010; Heue e al., 2015b; Sen a e al.,
2014
THC-OH
1
<20% ans o ma ion in un il e ed WW pH 7.5 20°C
Sen a e al., 2014
1
<20% ans o ma ion a pH 7.4, pH 2, 10°C and 20°C in un il e ed WW
Sen a e al., 2014
O he subs ances
ke amine* (KET)
2
High: <10% ans o ma ion in un il e ed WW pH 7.5, 20°C
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2015
3
High: a 4°C and oom empe a u e a WW pH and acidi ied o pH 4 and in
milliQ wa e a 4°C and oom empe a u e
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2015; Ös man e al., 2014
no ke amine
(no KET)
2
High: <10% ans o ma ion in un il e ed WW pH 7.5, 20°C
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2015
3
High: a 4°C and oom empe a u e a WW pH and acidi ied o pH 4 and in
milliQ wa e a 4°C and oom empe a u e
Bake and Kasp zyk-Ho de n, 2011a; Cas iglioni e
al., 2015; Ös man e al., 2014
lyse gic acid die hylamide*
(LSD)
1
<10% ans o ma ion in un il e ed WW pH 7.5, 20°C
Bake and Kasp zyk-Ho de n, 2011a
4
High: in WW pH and acidi ied o pH 2 a oom empe a u e and a 4°C;
Medium: in WW a oom empe a u e up o 24% ans o ma ion; in milliQ
wa e a 4°C and oom empe a u e (40% ans o ma ion); o e 3, 7, 17, 27,
123 d a -20°C >20 and <50% deg ada ion
Bake and Kasp zyk-Ho de n, 2011a; Chiaia e al.,
2008; Heue e al., 2015b; Ös man e al., 2014
2-oxo-3-hyd oxy-
LSD
1
<20% ans o ma ion in un il e ed WW pH 7.5, 20°C
Bake and Kasp zyk-Ho de n, 2011a
3
High: a WW pH and acidi ied o pH 2 a oom empe a u e and a 4°C; in
milliQ wa e a 4°C and oom empe a u e
Bake and Kasp zyk-Ho de n, 2011a; Chiaia e al.,
2008; Ös man e al., 2014
Page 19 o 38
2.2 Cocaine and me aboli es
In-sample s abili y o cocaine (COC) and i s me aboli es has been widely s udied o e a ange o 220
di e en condi ions. These s udies ocused mos ly on in-sample s abili y o COC and i s main
me aboli e, benzoylecgonine (BE), which is used o back-calcula ion. S abili y o COC was gene ally
low unde all es ed condi ions (Table 2). Hyd olysis o COC seems pH-dependen (Wa ne and
No man, 2000), and acidi ica ion o he sample can p ese e COC concen a ions a low and high
empe a u es o e a leas h ee days (Table 2). T ans o ma ion o COC can also be p e en ed using 225
p ese a i es (e.g., sodium me abisul i e (Na2S2O5), sodium azide (NaN3)), and COC concen a ion
changes seemed negligible a e ex ac ion on o SPE ca idges (HLB) (Chen e al., 2013; González-
Ma iño e al., 2010).
The was ewa e ma ix seems o ha e an in luence on he ex en o ans o ma ion (Cas iglioni e al.,
2006, 2011a; Gheo ghe e al., 2008). COC concen a ions emained sligh ly highe o e h ee days in 230
un il e ed samples compa ed o il e ed was ewa e (20°C, pH 7) (Chen e al., 2013). A -20°C and pH
7, COC concen a ions in un il e ed was ewa e only sligh ly dec eased o e h ee weeks (Chiaia e al.,
2008), and ano he s udy epo ed ha COC can be s able o e 24h in Milli-Q wa e a 4°C and 25°C
(Ös man e al., 2014). Fu he mo e, i is impo an o no e ha so p ion o SPM o COC and i s
me aboli es seems o be negligible (Bake and Kasp zyk-Ho de n, 2011b), bu COC concen a ions in 235
was ewa e samples dec eased du ing eeze-and- haw cycles (Cas iglioni e al., 2011).
In-sewe s abili y o COC was ela i ely low o e 12h a pH 7.1-7.5 and 20°C in a s udy conside ing
ae obic and anae obic sewe bio ilms, in which ans o ma ion o COC appea ed o be s onge unde
ae obic condi ions, compa ed o anae obic in-sewe condi ions (Thai e al., 2014).
Unlike COC, i s main me aboli e BE showed high in-sample s abili y unde a ious condi ions (Table 240
2). In-sewe s abili y o BE wi h ae obic and anae obic bio ilms has been shown o be high a 20°C
o e 12h (Thai e al., 2014), whe eas one s udy e ealed a dec ease o BE unde ae obic and anae obic
condi ions wi h ac i a ed sludge biomass a 21°C o e 24h (Plósz e al., 2013). In o ma ion on o he
COC me aboli es is lis ed in Table 2.
Page 20 o 38
2.3 Amphe amine and amphe amine- ype subs ances 245
This g oup encompasses compounds wi h chemical s uc u es simila o ha o amphe amine (AMP).
I includes me hamphe amine (METH), 3,4-me hylenedioxyme hamphe amine (MDMA) and i s
me aboli e 3,4-me hylenedioxyamphe amine (MDA), 3,4-me hylenedioxy-N-e hylamphe amine
(MDEA), me hylbenzodioxolylbu anamine (MBDB), as well as, he no el syn he ic ca hinones,
ca hinones HCl, me hylenedioxypy o ale one (MDPV), mephed one, me hylphenida e ( i alin) and i s 250
me aboli e, i alinic acid.
In-sample s abili y o AMP in un il e ed was ewa e has been consis en ly shown o be high a pH 7 a
4°C and 20°C o 24h in mos s udies (Table 2). Howe e , Bake e al. 2011a epo ed an inc ease
(26%) o AMP concen a ions a 2°C and pH 7 and a 73% inc ease in AMP a oom empe a u e o e
24h. AMP is also a me aboli e o METH, and he pha maceu icals, selegiline and dex oamphe amine 255
(K aeme and Mau e , 2002; Heue e al., 2015a). Howe e , in-sample s abili y o METH is high in
un il e ed was ewa e a pH 7 a 4°C and oom empe a u e (Table 2) and subs an ial in-sewe
ans o ma ion o METH o AMP is hus unlikely. AMP and METH we e epo ed as highly s able
unde all es ed condi ions, pa icula ly a e addi ion o NaN3 o he samples o e h ee weeks, ins an
eezing (-20°C) o e 123 days, and a e acidi ica ion o e h ee weeks (Table 2). 260
MDMA, MDA and MDEA showed high in-sample s abili y in un il e ed was ewa e a pH 7 and a
4°C and 20°C o 24h (Table 2). In addi ion, hey we e s able a e ins an eezing (-20°C) and
acidi ica ion o 24h up o h ee weeks. One s udy in es iga ing he s abili y o MBDB in un il e ed
was ewa e a 2°C and a 20°C, bo h a pH 7, epo ed a medium s abili y wi h lowe concen a ion
a e 12-24h (Bake and Kasp zyk-Ho de n, 2011a). 265
The ans o ma ion o MDPV and 12 me aboli es – h ee o hem p e iously epo ed as human
me aboli es – was in es iga ed in was ewa e a 22°C, and no signi ican dec ease o MDPV (high in-
sewe and in-sample s abili y) was obse ed in a 10-day expe imen (Ma dal and Meye , 2014).
Fu he expe imen s demons a ed he glucu onidase ac i i y in was ewa e , since he signal o ou
glucu onide phase II me aboli es dec eased by mo e han 99% a e one day (Ma dal and Meye , 270
2014).
Page 21 o 38
One s udy in un il e ed was ewa e ound ha in-sample s abili y o mephed one is high a 4°C and
oom empe a u e o e 24h (Ös man e al., 2014). Simila ly, mephed one was s able in u ine a 4°C,
oom empe a u e and -20°C o e a leas 2 days (Johnson and Bo ch-Jones, 2013). Me hylphenida e’s
in-sample s abili y in was ewa e anged om medium (a e 24h a 4°C) o low (a oom empe a u e, 275
Bu ga d e al., 2013; Ös man e al., 2014). In Milli-Q wa e , me hylphenida e was s able o 24h bo h
a 4°C and a oom empe a u e (Ös man e al., 2014). Ri alinic acid had a high in-sample s abili y in
was ewa e o 72h a 20°C (Bu ga d e al., 2013).
Few s udies ha e in es iga ed he in luence o sewe bio ilm o SPM on s abili y. The in-sewe
s abili y s udy conduc ed by Thai e al. (2014) ound a non-signi ican inc ease o METH (<5% a e 280
12h) in he p esence o ae obic bio ilm. Subedi e al. (2014) showed no so p ion o METH, MDMA
and MDEA and a medium loss (30 – 40%) due o so p ion o SPM o MDA and AMP. In con as ,
Bake e al. (2011b) ound <10% o AMP so bed o SPM (Bake and Kasp zyk-Ho de n, 2011b).
In gene al, he in-sample s abili y o AMP, METH, MDMA, MDA and MDEA in un il e ed and
il e ed was ewa e samples a di e en empe a u es ha e yielded simila esul s, demons a ing ha 285
hese compounds had a high s abili y wi h he excep ion o AMP, o which a highe change in
concen a ion was epo ed in some expe imen s (>20%) (Bake and Kasp zyk-Ho de n, 2011a;
Ös man e al., 2014) (Table 2).
2.4 Opia es
He oin use had been es ima ed by measu ing i s me aboli e 6-monoace yl mo phine (6-MAM), 290
howe e , 6-MAM i sel has low in-sample s abili y and can ans o m quickly o mo phine (MOR) in
he was ewa e ma ix. A was ewa e sample can lose up o 42% 6-MAM a e 24h a 19°C (Bake and
Kasp zyk-Ho de n, 2011a). Simila ly, in-sewe s abili y is low, since up o 90% o 6-MAM was los a
20°C a e 12h in he s udy wi h sewe bio ilms, pe o med by Thai e al. (2014). A eliable unbiased
bioma ke o he oin has no ye been ound. 295
Al hough he s abili y o mo phine (MOR) is high in was ewa e samples, he es ima ion o use o
he oin om MOR concen a ions is di icul , because i is used i sel as a pha maceu ical and is a
me aboli e o o he opia es (e.g., e hyl mo phine, 6-MAM, codeine (COD)). The associa ed

Page 22 o 38
glucu onides o MOR, mo phine-3β-D-glucu onide and mo phine-6β-D-glucu onide, can be measu ed
in was ewa e , bu hey ha e a low s abili y and quickly deconjuga e o MOR (Table 2). 300
Mos o a COD dose is exc e ed wi h u ine, ei he as unchanged COD o as a conjuga e. COD is
highly s able in was ewa e samples (Table 2), and i s consump ion can, he e o e, be es ima ed by
measu ing he load o COD in was ewa e . Jelic e al. (2015) also epo ed high in-sewe s abili y.
Howe e , COD exhibi ed low s abili y in ba ch expe imen s wi h dilu ed ac i a ed sludge om
was ewa e ea men plan s (Wick e al., 2011). 305
Mos was ewa e s udies o da e measu ed bo h me hadone (MTD) and i s main me aboli e EDDP, bu
he consump ion o MTD was only es ima ed using he pa en compound. Bo h MTD and EDDP seem
o be s able in was ewa e bo h unde in-sample s o age condi ions (a 4°C, Ös man e al., 2014) and
simula ed in-sewe condi ions (a 19°C and pH 7, an Nuijs e al., 2012). Howe e , a po ion o MTD
and EDDP can adso b o SPM in was ewa e . Bake and Kasp zyk-Ho de n (2011a) obse ed a 310
signi ican educ ion o spiked MTD (23%) and EDDP (72%) in un il e ed was ewa e a e 72h a
19°C, mos likely due o so p ion p ocesses. O e all, he s abili y o MTD and EDDP is a iable
depending on he condi ions and SPM/bio ilm con en .
Bup eno phine has a a iable s abili y in was ewa e samples (Table 2). I is a ela i ely hyd ophobic
compound and elimina ed p ima ily ia eces as ee d ug wi h low concen a ions occu ing in u ine. 315
Oxycodone and en anyl a e he apeu ic opia es ha ecei e inc easing a en ion as d ugs o abuse. To
da e, all was ewa e s udies used he pa en compounds as bioma ke s, al hough each d ug has speci ic
me aboli es (e.g., no oxycodone and no en anyl, Basel , 2008). Ös man e al. (2014) ound bo h
compounds s able unde s o age condi ion, bu Bake and Kasp zyk-Ho de n (2011) obse ed
signi ican deg ada ion o en anyl in un il e ed was ewa e (62%) a e 72h a 19°C and pH 7.4. This 320
again may be a ibu ed o adso p ion o SPM, since only 6% o en anyl was los du ing he same
pe iod in il e ed was ewa e . Based on he e iewed s udies, en anyl had a medium in-sample
s abili y, whe eas oxycodone was highly s able.
Page 23 o 38
2.5 Cannabinoids
Cannabis’s p ima y ac i e compound is Δ9- e ahyd ocannabinol (THC), which a e consump ion is 325
me abolized o mo e han 20 me aboli es, he wo main ones being 11-no -9-ca boxy-THC (THC-
COOH) and 11-hyd oxy-THC (THC-OH) (Ka ch and Jenkins, 2006). These me aboli es a e exc e ed
as glucu onide conjuga es, howe e in was ewa e , hey a e hyd olyzed/deconjuga ed o he pa en
me aboli e (Cas iglioni e al., 2008). Fo his eason, THC-COOH is no mally used o es ima e
cannabis consump ion in WBE s udies (Cas iglioni e al., 2011b; Lai e al., 2011). Howe e , he e a e 330
analy ical di icul ies especially associa ed wi h he sample ea men and de ec ion o THC-COOH
due o i s highe lipophilici y compa ed o o he illici d ugs (Vazquez-Roig e al., 2013). This
some imes may hampe he inclusion o THC-COOH in analy ical me hods o ou ine mul i-class
de e mina ion o illici d ugs.
In-sample s abili y es s wi h aw was ewa e (pH 7-8) showed high s abili y o e 72h wi h minimal 335
impac o empe a u e (Table 2). Howe e , a e longe s o age imes a 4°C, deg ada ion became
mo e signi ican a e se en days (González-Ma iño e al., 2010). F ozen samples we e s able up o 4
mon hs (Heue e al., 2015b). Acidi ica ion o samples o pH 2 (wi h H3PO4) inc eased he
ans o ma ion o THC-COOH and THC-OH in was ewa e (Khan and Nicell, 2012; Sen a e al.,
2014). A pH 2, THC-COOH was ound o ha e enhanced adso p ion (loss o 54%), compa ed o only 340
10% loss a unadjus ed pH 7.4 (Sen a e al., 2013). This was also ound in a simila s udy whe e only
1.3% o THC-COOH was expec ed o ha e adso bed o SPM a en i onmen al pH condi ions (pH ≈
7.5) (Khan and Nicell, 2012).
2.6 O he subs ances
The s abili y o lyse gic acid die hylamide (LSD) in was ewa e a pH 7.4 and acidi ied o pH 2 a 345
oom empe a u e and a 4°C a e 24h was high (Table 2). The me aboli e 2-oxo-3-hyd oxy-LSD also
exhibi s high s abili y and only sligh ly dec eased (10-20%) in was ewa e pH 7.4 a oom empe a u e
a e 24h, while acidi ica ion and/o lowe ing he empe a u e p e en ed his (Bake and Kasp zyk-
Ho de n, 2011a; Chiaia e al., 2008).
Page 24 o 38
The in-sample s abili y o ke amine (KET) and i s me aboli e no KET was s udied o di e en 350
condi ions: empe a u e (4°C, oom empe a u e), pH (2, 7.4), and ime (12-72h) (Table 2). Bo h KET
and no KET had a high s abili y in all analyzed condi ions.
3 Discussion
The e iewed s udies clea ly show ha concen a ions o se e al subs ances dec eased in un il e ed
was ewa e unde di e en condi ions. In o de o explain disc epancies o a gi en bioma ke among 355
di e en s udies wi h a iable was ewa e ma ices, he e ec s o chemical, biological and physical
p ocesses need o be conside ed.
Biological and chemical ans o ma ion p ocesses
In he absence o app op ia e abio ic con ols, i is di icul o di e en ia e be ween chemical and
biological ans o ma ions. Se e al o he in es iga ed bioma ke s, e.g., COC and 6-MAM, ha e 360
chemical s uc u es (es e s) ha a e p one o abio ic o bio ic hyd olysis in was ewa e . Abio ic con ol
expe imen s we e only ca ied ou in h ee s udies (Wick e al., 2011; Ma dal and Meye , 2014; Sen a
e al., 2014).
O he impo an , chemically o biologically media ed, p ocesses a e conjuga ion and deconjuga ion.
THC, mo phine and MDPV a e exc e ed in conjuga ed o m (e.g., as glucu onides and sul a es) and 365
end o deconjuga e du ing in-sewe anspo (Boleda e al., 2007; D’Ascenzo e al., 2003; E genidou,
2015, Ma dal and Meye , 2014).
S udies o biological ans o ma ion (bio ans o ma ion) mechanisms ela ed o bioma ke s in sewe s
a e sca ce (Ma dal and Meye , 2014). Bio ans o ma ion can occu unde ae obic and anae obic
condi ions, whe eby illici d ugs demons a e a ini y o bac e ial enzymes and se e as co-me abolic 370
(non-g ow h) subs a es (Sieg is and Joss, 2012). In mos o he e iewed s abili y s udies, he edox
condi ions (ae obic/anae obic) we e no measu ed o moni o ed, e en hough he edox po en ial
in luences bac e ial ac i i y, and bio ans o ma ion is highe unde ae obic han anae obic condi ions
(Thai e al., 2014). The ex en o bio ans o ma ion, he e o e, depends on he ype and amoun o
ac i e biomass in he sewe , which may a y among di e en ne wo ks (Ro h and Lemme , 1994). 375
Page 25 o 38
I is s ill no well unde s ood which species o bac e ia a e esponsible o biological ans o ma ion o
o ganic mic opollu an s in was ewa e ea men p ocesses (Sieg is and Joss, 2012). Fu he , he
mic obial communi y in was ewa e ea men plan s de ia es om sewe communi ies (H i ed-
Jacobsen e al., 2013). The condi ions in he ac i a ed sludge p ocess in was ewa e ea men a e
selec ed o a o g ow h o speci ic mic oo ganisms, such as ni i ying and phospho ous-accumula ing 380
bac e ia (Henze e al., 2002). Unde he condi ions p e ailing in sewe s, as -g owing he e o ophic
bac e ia ou compe e he slowe g owing o ganisms, such as ni i ying bac e ia (H i ed-Jacobsen e
al., 2013). The e o e, he use o ac i a ed sludge o mimic in-sewe ans o ma ion may no be
ep esen a i e o he ac i e mic obial communi y in sewe s. Only one s udy ha in es iga ed he
s abili y o illici d ug bioma ke s included sewe wall bio ilm (Thai e al., 2014), and he esul s 385
implied ha bio ilm is an impo an pa ame e ha needs o be aken in o accoun .
Ano he ac o ha may explain some o he a iabili y in s abili y is he in luence o o he o ganic
and ino ganic cons i uen s o SPM, such as eces and oile pape (na u al polyme s, cellulose). These
ac o s ha e no ye been in es iga ed o hei po en ial e ec on ans o ma ions.
Two o he key en i onmen al a iables in luencing chemical and biological eac ions a e empe a u e 390
and pH. Mos s udies epo ed o in es iga ed he e ec o hese a iables on he s abili y. Was ewa e
empe a u es in sewe s can a y om 10°C in win e up o 30°C in summe (Tchobanoglous and
Bu on, 1991). The e iewed ans o ma ion s udies we e conduc ed a cons an empe a u e, ei he a
low empe a u e (2-10°C) o a oom empe a u e (19-23°C). Resul s show a empe a u e dependence
o he ans o ma ion a es o COC, 6-MAM and mo phine-3β-D-glucu onide (Sen a e al., 2014). 395
Simila ly, (chemical and biological) hyd olysis a es o COC in was ewa e we e highe a 31°C
compa ed o 23°C and 9°C. The ans o ma ion a e coe icien s we e la ge han hose epo ed in
deionized wa e a simila pH and empe a u es, con i ming ha biologically media ed hyd olysis can
play an impo an ole in was ewa e (Bisceglia, 2007; Bisceglia and Lippa, 2014).
The e iewed s udies ypically s a e one pH alue, omi ing whe he pH was eco ded a he beginning 400
o end o he expe imen o equen ly moni o ed. A ecen s udy ound ha bio ans o ma ion is pH-
dependen , whe e he neu al ac ion o ionizable subs ances (e.g., amines) induced a highe mic obial
up ake (Gulde e al., 2014). Du ing he anspo o illici d ug bioma ke s in sewe s o o e he cou se
Page 32 o 38
Mo e esea ch is needed o he d ugs wi h a iable beha io o ew pe o med s udies, such as THC-
COOH, en anyl, mephed one and ca hinones.
 The ew s udies o-da e show ha in-sewe ans o ma ion is compound-speci ic, in luenced by
he p e ailing en i onmen al condi ions in sewe s ( empe a u e, sewe ype). The e is a lack o 565
s udies sys ema ically in es iga ing he in luence o he di e en en i onmen al condi ions (pH,
suspended pa icula e ma e , bio ilm) on he ans o ma ion o illici d ugs.
 In o de o compa e di e en s udies and en i onmen al condi ions, a ep oducible expe imen al
app oach wi h quali y con ols o in-sewe ans o ma ion s udies is needed. The e o e, his
e iew ecommends a bes -p ac ice app oach o u u e in-sewe s abili y s udies. 570
 Fu he , we summa ize he bes s a egies o assu e good in-sample s abili y o illici d ugs in he
ield o was ewa e -based epidemiology. In mul i-compound s udies, mos illici d ugs had a high
s abili y a neu al pH and -20°C o a leas h ee weeks. Al e na i ely, acidi ica ion o he
sample p ese ed mos d ugs, excep o THC and me aboli es.
Acknowledgemen s 575
Financial suppo by he Eu opean Union’s Se en h F amewo k P og am o esea ch, echnological
de elopmen and demons a ion SEWPROF (p ojec no. 317205) is g a e ully acknowledged. Phong
Thai is pa ly suppo ed by a UQ Pos doc o al Resea ch Fellowship and a QUT VC Resea ch
Fellowship. Alexande an Nuijs acknowledges a pos -doc o al ellowship om Flande s Funds o
Scien i ic Resea ch (FWO). Lube us Bijlsma acknowledges he inancial suppo om Gene ali a 580
Valenciana (G oup o Excellence P ome eo 2009/054, P ome eo II 2014/023; Collabo a i e
Resea ch on En i onmen and Food Sa e y ISIC/2012/016). Special hanks o Julianne
McCall o p oo eading he manusc ip .

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