Comparative Biochemistry and Physiology Part A 120 (1998) 43 – 49

Review
The fate of organic xenobiotics in aquatic ecosystems: quantitative and
qualitative differences in biotransformation by invertebrates and fish

D.R. Livingstone *
NERC Plymouth Marine Laboratory, Citadel Hill, Plymouth, De6on PL1 2PB, UK

Received 24 March 1997; received in revised form 5 August 1997; accepted 22 August 1997

Abstract

Biotransformation of natural and man-made foreign compounds (xenobiotics) proceeds via introduction of a functional group
(phase I metabolism) and subsequent attachment of a polar moiety to the group (phase II metabolism). The biotransformation
fate of xenobiotics depends on the activities, complement and inducibility of the biotransformation enzymes. Previous analysis of
the dependence of in vivo rates of biotransformation on tissue parent compound concentration for marine invertebrates revealed
that hydrocarbons are metabolised more slowly than xenobiotics already containing functional groups, and crustaceans metabolise
both types of xenobiotics faster than molluscs (Livingstone D.R., Persistent pollutants in marine ecosystems, pp. 3 – 34, Pergamon,
Oxford). Use of the same approach showed that fish metabolise pentachlorophenol (PCP) and benzo[a]pyrene (BaP) faster than
certain aquatic invertebrates, viz. rates of biotransformation to total metabolites (pmol min − 1 g − 1 wet wt.) at a tissue parent
compound concentration of 10 nmol g − 1 were, respectively, 19.2 9 3.7 (Carassius auratus) and 4.8 9 6.6 (molluscan species)
(PCP), and 19.1 96.3 (fish species) and 2.190.2 (crustacean species) (BaP). The higher rate of biotransformation of BaP in fish
is consistent with higher levels of total cytochrome P450 and inducible cytochrome P4501A (CYP1A) activity. The similar rate of
metabolism of a hydrocarbon (BaP) (requires initial metabolism by cytochrome P450) and a functional group compound (PCP)
by fish may also be due to the high levels of cytochrome P450, compared with the situation in invertebrates where rate-limiting
cytochrome P450 may be responsible for the lower rates of hydrocarbon compared with functional group compound metabolism.
© 1998 Elsevier Science Inc. All rights reserved.

Keywords: Benzo[a]pyrene; Biotransformation; Fish; Aquatic invertebrates; Organic pollutants; Organic xenobiotics; Pen-
tachlorophenol

1. Introduction chain transfer [17]. Natural xenobiotics comprise a wide

Natural and man-made organic foreign compounds
(xenobiotics) enter and are dispersed in aquatic ecosys-
tems by various routes, including direct discharge, di-
rect use, land run-off, atmospheric deposition, in situ
production, abiotic and biotic movement, and food-
Abbre6iations: BaP, benzo[a]pyrene; CYP1A, cytochrome P4501A;
GST, glutathione S-transferase; MFO, mixed-function oxygenase;
PAH, polynuclear aromatic hydrocarbon; PCP, pentachlorophenol.
* Tel.: + 44 1752 633100; fax: + 44 1752 633102; e-mail:
D.Livingstone@pml.ac.uk
range of chemicals including plant products, animal
toxins and natural hydrocarbons, whereas the produc-
tion of man-made xenobiotics (contaminants) increases
daily in variety and quantity. Knowledge of the fate
and effects of natural xenobiotics on biota is important
in relation to evolutionary and ecological processes,
whereas the same for contaminants is critical for pollu-
tion monitoring, impact assessment and environmental
management [15].
All animals possess a suite of biotransformation en-
zymes, usually present in highest levels in the liver

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PII S1095-6433(98)10008-9
44 D.R. Li6ingstone / Comparati6e Biochemistry and Physiology, Part A 120 (1998) 43–49
Table 1
Specific activities of some phase I and II biotransformation enzymes in the major tissues of xenobiotic metabolism in fish, echinoderms,
crustaceans and molluscs
Enzyme amount or activity (mg−1 protein) Fish
Total cytochrome P450 content (pmol mg−1) 3229 35 (38)
BPH activitya (pmol min−1 mg−1) 3079208 (9)
FMO activityb (nmol min−1 mg−1) 0.3590.21 (3)
UDPGT activityc (pmol min−1 mg−1) 3949105 (10)
GST activityd (nmol min−1 mg−1) 7769 139 (12)
Activities g−1 wet wt. are mainly for liver (fish), pyloric caeca (echinoderm), hepatopancreas (crustacean) and digestive gland (mollusc), and
measured in cytosolic (GST) or microsomal fractions. Values are mean 9S.E.M. or range (n = number of species).
ND, no data.
a
B[a]P hydroxylase.
b
Flavoprotein monooxygenase (substrate: N,N-dimethylaniline, methimazole, others).
c
UDP-glucuronyl transferase (substrate: p-nitrophenol).
d
GST (substrate: 1-chloro-2,4-dinitrobenzene).
Data from [13,14,18,4,21].
(vertebrates) or tissues associated with the processing of
food (invertebrates). The major function of these en-
zymes is to convert hydrophobic lipid-soluble organic
xenobiotics to water-soluble excretable metabolites. The
enzymes of phase I metabolism (oxidation, reduction,
hydration, hydrolysis) introduce (or modify) a func-
tional group (−OH, −COOH, − NO2, etc.) into the
xenobiotic, to which conjugase and other enzymes of
phase II metabolism attach a large polar moiety (glu-
tathione, sulphate, glucuronide, amino acid, etc.). Bio-
transformation affects the disposition, residence time,
and toxicity (detoxication or activation) of a xenobiotic
in an organism. Knowledge of the major quantitative
and qualitative similarities and differences in biotrans-
formation pathways between different animal groups is
necessary for the (a) design of toxicity tests, (b) devel-
opment of biomarkers, (c) modelling of chemical fate in
ecosystems, and (d) understanding of the selective role
of biotransformation in animal ecology and evolution
[13,16]. Previous studies [13,14,16] used a quantitative
approach to identify differences in rates of biotransfor-
mation between different marine invertebrate groups
and for different groups of compounds. The present
paper extends aspects of this approach to compare
biotransformation and bioaccumulation in marine in-
vertebrates and fish.
2. Quantitative differences: enzyme activities and in
vivo rates of biotransformation
Most types of enzymes responsible for biotransfor-
mation in mammals have also been found or indicated
in fish and marine invertebrates, including phase I
cytochrome P450 monooxygenase or mixed-function
oxygenase (MFO) system, flavoprotein monooxygenase
system (FMO; EC 1.14.13.8), epoxide hydratase (EC
4.2.1.64) and flavoprotein reductases; and phase II glu-
Echinoderm Crustacean Mollusc
63 912 (2) 328970 (14) 73 9 10 (9)
8.495.5 (2) 40 931 (10) 21.29 3.4 (5)
ND ND 0.63 9 0.13 (2)
ND 10 (1) 3800 (1)
11 – 52 (5) 12029 842 (6) 4230 9 2184 (4)
tathione S-transferase (GST), UDP-glucuronyl trans-
ferase (EC 2.4.1.17), UDP-glucosyltransferase,
sulphotransferase, and amino acid conjugases
[13,20,24,6]. Isoenzymes of cytochrome P450 are of
central importance in the metabolism of many xenobi-
otics and endogenous compounds, and levels of total
cytochrome P450 are usually an order of magnitude
higher in fish than aquatic invertebrates (Table 1),
paralleling their generally higher levels of metabolic
activity as reflected in the activities of key regulatory
enzymes of intermediary metabolism such as phospho-
fructokinase (EC 2.7.1.11) [14]. Levels of the monooxy-
genase activity benzo[a]pyrene (BaP) hydroxylase
(mainly catalysed by cytochrome P4501A (CYP1A) in
vertebrates) are similarly higher in fish than aquatic
invertebrates, although wide variability is seen in differ-
ent feral fish species due to the inducible nature of
CYP1A by xenobiotics (Table 1). High levels of total
cytochrome P450 (comparable with those in fish) are
also found in some crustacean species, such as the spiny
lobster, Panulirus argus [13], but these are not paral-
leled by proportionally higher levels of BaP hydroxy-
lase activity (Table 1). Less is known of the specific
activities of other phase I and phase II biotransforma-
tion enzymes in aquatic invertebrates, but at least some,
such as those of GST and FMO, are indicated to be
more similar in fish and some invertebrate groups than
is seen for the MFO system (Table 1).
The potential for biotransformation of many organic
xenobiotics, such as polynuclear aromatic hydrocar-
bons (PAHs), can be greatly increased in fish and other
vertebrates by 10–100-fold induction of CYP1A activ-
ity [24], compared with only several-fold or less eleva-
tion of BaP hydroxylase activity in aquatic
invertebrates or levels of a CYP1A-immunopositive
protein in molluscs [13,16]. Phase II enzymes, such as
GST, are also inducible by exposure to organic xenobi-
otics, but the responses are generally much less marked
 D.R. Li6ingstone / Comparati6e Biochemistry and Physiology, Part A 120 (1998) 43–49
than for CYP1A [13,6]. Relatively few direct studies
have been carried out on the quantitative consequences
of induced enzyme activities on in vivo biotransforma-
tion, but increased first-pass metabolism of BaP was
demonstrated in intestines of toadfish (Opsanus tau)
following 10-fold pre-induction of putative CYP1A-ac-
tivity [35]. Indirect evidence indicates that in vivo bio-
transformation may also be increased in marine
invertebrates as a result of enzyme induction, viz. in-
creased metabolism of 2,5,2%,5%-tetrachlorobiphenyl was
seen in contaminated compared with clean field popula-
tions of the nereid polychaete Nereis di6ersicolor [7],
and increased resistance to pentachlorophenol (PCP)
correlated with increased sulphotransferase activity in
the clam Tapes philippinarum [11].
Using the pooled data of a large number of published
studies on the in vivo biotransformation of a wide
range of xenobiotics (PAHs, organochlorines, nitroaro-
matics, phenols, organophosphates, phthalates, etc.) by
some 30 aquatic invertebrate species, whole body in
vivo rates of biotransformation to total metabolites
were shown to be linearly dependent on tissue parent
compound concentration over up to six orders of mag-
nitude of the two parameters [13,14,16]. The regression
equations for the relationships revealed differences in
metabolism between different groups of xenobiotics,
viz. aliphatic and aromatic hydrocarbons were
metabolised more slowly than xenobiotics already con-
taining functional groups; and between different inver-
tebrate groups, e.g. crustaceans metabolised both
hydrocarbons and ‘functional group compounds’ faster
than molluscs. Thus, for a tissue parent compound
concentration of 10 nmol g − 1 wet wt., the calculated
mean rates of biotransformation were (in pmol min − 1
g − 1; all rates in the text are given in wet weight):
crustacean, 3.6 (functional group compound) and 1.1
(hydrocarbon); mollusc, 2.7 (functional group com-
pound) and 0.4 (hydrocarbon) [14]. Although correla-
tion coefficients for the regression equations (which also
included equations for polychaetes and echinoderms)
were high (mostly \0.96), exceptions were also seen for
individual cases which fell well outside these generalised
relationships, viz. lobster Homarus americanus
metabolised BaP 100 times slower than both P. argus
and the predicted relationship for crustaceans.
The same approach can be used to compare rates of
biotransformation with total metabolites between inver-
tebrate groups and fish. Thus, calculating tissue parent
compound concentrations and rates of biotransforma-
tion from literature data, a linear dependence of the
latter on the former is seen for the general biocide PCP
for molluscan species and goldfish (Carassius auratus)
(respectively, Fig. 1A and B), and for the ubiquitous
PAH contaminant BaP for crustacean and fish species
(respectively, Fig. 2A and B). Although comparison of
these regressions should be viewed with some caution
45
because parent compound concentrations are over dif-
ferent ranges (compare x-axes of Figs. A and B) and
both whole animal and liver/hepatopancreas data are
used for BaP (Fig. 2), some useful comparative obser-
vations can be made. The different xenobiotic concen-
tration ranges would seem not to be too great a
consideration given that the published data for mol-
luscs and crustaceans showed the biotransformation
rate to be linearly dependent on parent compound
concentration over a range of 0.01–1000 nmol g − 1 [14]
compared with the 0.02–120 nmol g − 1 used in Figs. 1
and 2. However, the limitations of the data are appar-
ent from the high standard errors of some of the rates
of biotransformation calculated from the regression
equations of Figs. 1 and 2 (Table 2).
Considering PCP, the calculated biotransformation
rate from the regression equation of Fig. 1B for a tissue
parent compound concentration of 1 nmol g − 1 is 1.34
pmol min − 1 g − 1 for C. auratus compared with an
observed rate for rainbow trout (Oncorhynchus mykiss)
at approximately the same tissue concentration of PCP
of 1.5 pmol min − 1 g − 1 (Table 2), indicating that the
rate of biotransformation of this compound is similar
for two fish species at least. In contrast, using the
regression equations of Fig. 1 and a tissue PCP concen-
tration of 10 nmol g − 1 wet wt., the calculated biotrans-
formation rate for C. auratus was about 5-fold greater
than for the molluscan species (Table 2). Similarly,
higher rates of biotransformation for fish compared
with marine invertebrates are also apparent for BaP.
Thus, using the regression equations of Fig. 2 and a
tissue parent compound concentration of 10 nmol g − 1,
the rate of biotransformation was about 10-fold higher
in the fish than the crustacean species (Table 2). The
same result is obtained if individual comparisons of
same ‘tissue-types’ are made. Thus, the observed whole
body rate of metabolism of BaP at a tissue parent
compound concentration of 0.6–0.7 nmol g − 1 was 0.06
pmol min − 1 g − 1 in the shrimp Pandalus platyceros [13]
compared with 0.49 pmol min − 1 g − 1 in bluegill sunfish
(Lepomis macrochirus) calculated from ref. [9]. Simi-
larly, the rate of biotransformation of BaP in hepato-
pancreas of P. argus was similar to that in liver of carp
(Cyprinus carpio) but at about a 8-fold lower BaP tissue
concentration in the latter, viz. 5.3 pmol min − 1 g − 1 at
24.2 nmol g − 1 for P. argus [13] compared with 6.2
pmol min − 1 g − 1 at 3.1 nmol g − 1 for C. carpio (calcu-
lated from [27].
Overall, the higher rates of in vivo biotransformation
of PCP and BaP by fish compared with marine inverte-
brates (Table 2) are consistent with their higher levels
of biotransformation enzyme activities, at least as far as
the MFO system is concerned (Table 1). Interestingly,
the similar rates of metabolism by fish indicated for
both the hydrocarbon BaP (requires obligatory phase I
metabolism by cytochrome P450 before phase II
46 D.R. Li6ingstone / Comparati6e Biochemistry and Physiology, Part A 120 (1998) 43–49

Fig. 1. Dependence of whole animal in vivo rates of biotransformation to polar products on tissue parent compound concentration for the
metabolism of PCP by several gastropod (Physa sp., Haliotis fulgens, H. rufescens) and bivalve (Crassostrea gigas) molluscan species (A) or
goldfish (C. auratus) (B). Data for A taken from [13,16]. Data for B calculated from [26]. The regression equations (S.E. of intercept and slope
in parenthesis) and correlation coefficients (in square parenthesis) are A, y =0.23(0.07)x+2.55(5.88), [0.91]; B, y = 1.98(0.32)x− 0.64(0.5), [0.96].

metabolism can take) and the functional group com-
pound PCP (can undergo direct phase II metabolism
via conjugation to its hydroxyl group) is presumably
due to their proportionally higher levels of total cy-
tochrome P450. The lower rates of biotransformation
of hydrocarbons compared to functional group com-
pounds observed for crustaceans and molluscs (see
before) was interpreted as being due to either the MFO
system being rate-limiting, or that several enzymes
could act on the functional group substrates simulta-
neously [13,14]. Comparison of phase II enzyme data
between fish and aquatic invertebrates is difficult be-
cause of the limited enzyme database (Table 1) and the
indication of significant qualitative differences in bio-
transformation pathways (see below).
3. Qualitative differences: enzyme activities and in vivo
biotransformation
The database to identify qualitative differences in
biotransformation pathways in different animal groups
 D.R. Li6ingstone / Comparati6e Biochemistry and Physiology, Part A 120 (1998) 43–49 47

Fig. 2. Dependence of in vivo rates of biotransformation to polar products on tissue parent compound concentration for the metabolism of BaP
by several crustacean (Callinectes sapidus, Eohaustorius washingtonianus, P. platyceros, P. argus, Rhepoxynius abronius) species (A) or fish
(Cyprinus carpio, Lepomis macrochirus, Opsanus beta, Parophrys 6etulus) species (B). Data for A taken from [13] for either whole animal or
hepatopancreas [13]. Data for B calculated from [36,9,10,27] for whole animal or liver and liver-derived metabolism (bile) for an exposure
temperature range of 18–23°C. The regression equations (S.E. of intercept and slope in parenthesis) and correlation coefficients (in square
parenthesis) are A, y = 0.22(0.01)x− 0.19(0.12), [0.99]; B, y =2.05(0.54)x−1.32(0.88), [0.89].

is limited. Although the metabolism of xenobiotics
generally differs for any two species, phylogenetic
trends in the distribution of biotransformation enzymes
and pathways, likely related also to such selective pres-
sures as lifestyle, habitat and diet, are indicated to exist
[17,16]. The multiple forms of cytochrome P450, partic-
ularly members of the CYP1A, CYP2 and CYP3A
subfamilies, are of central importance in the biotrans-
formation of many xenobiotics [12]. Identical or related
members of such isoforms have been found or indicated
in fish [24,19] and invertebrates such as molluscs
[16,37,38]. Unique forms also exist in aquatic inverte-
brates, viz. CYP10 in the snail Lymnaea stagnalis [32],
and CYP2L in P. argus [2]. Both the number of CYP
forms and their inducibility by exposure to xenobiotics
is indicated or seen to be different for different animal
groups. Although both tend to increase up the phyloge-
netic tree (i.e. are greater for vertebrates than inverte-
48 D.R. Li6ingstone / Comparati6e Biochemistry and Physiology, Part A 120 (1998) 43–49
Table 2
Comparative rates of biotransformation of PCP and BaP by fish and marine invertebrates
Species or animal group Compound Data source
Goldfish (C. auratus) PCP Regression equationa
Rainbow trout (O. PCP Observedb
mykiss)
Goldfish (C. auratus) PCP Regression equationa
Molluscs PCP Regression equationc
Fish BaP Regression equationd
Crustaceans BaP Regression equatione
Rates are g−1 wet wt.
Calculated from a Fig. 1B; b
[25]; c Fig. 1A; d
Fig. 2B; and e Fig. 2A.
brates), other factors, particularly diet (i.e. input of
natural xenobiotics), are also indicated to be important
as selective pressures as, for example, large numbers of
constitutive and inducible CYP genes are now being
identified in insects [22,3]. Differences are also evident
in the catalytic properties of enzymes, with the major
primary metabolites of BaP being quinones in bivalve
molluscs and diols and phenols in higher invertebrates
(crustaceans and echinoderms) and vertebrates [16].
In the case of phase II metabolism, glucosidation is
indicated to predominate over glucuronidation in
aquatic invertebrates compared with fish and other
vertebrates [13,16]. This is particularly evident for the
biotransformation of PCP, for which sulphate conjuga-
tion occurred in all the following species, but glucosida-
tion was seen in red abalone (Haliotis rufescens) [33],
abalone (Haliotis fulgens) [23] and sea urchin (Strongy-
locentrotus purpuratus) [34], whereas gluronidation oc-
curred in killifish (Oryzias latipes) [28], striped bass
(Morone saxatilis) [5], topsmelt (Atherinops affinis) [1]
and other fish species [25]. The same situation of glu-
curonide versus glucoside formation is observed for the
metabolism of the organophosphorous insecticide feni-
trothion by mullet (Mugil cephalus) and O. latipes [29]
compared with the snail Physa acuta [30] and shrimp
Palaemon paucidens [31]. However, in contrast, no glu-
coside and only sulphate conjugation of fenitrothion
was detected in the snail Cipangopaludina japonica [30]
and waterflea (Daphnia pulex) [31].
4. Bioaccumulation of organic xenobiotics: rates of
uptake compared with rates of biotransformation
Uptake of organic xenobiotics from the water-
column is largely passive in all organisms, and therefore
the rates of uptake are generally similar in both inverte-
brates and fish, with bioconcentration in exposure stud-
ies being predictable from log octanol/water partition
coefficients [39,8]. In contrast, rates of biotransforma-
Tissue parent compound Rate of metabolism (pmol min−1
concentration (nmol g−1) g−1) (mean9 S.E.)
1.0 1.34 9 0.82
1.0 – 1.5 1.5
10.0 19.2 9 3.7
10.0 4.82 9 6.61
10.0 19.1 96.3
10.0 2.05 90.19
tion are intrinsic to the animal and dependent of the
particular complement, activities and regulation (in-
ducibility) of enzymes, which are generally higher in
fish than aquatic invertebrates. In the case of hydrocar-
bons in molluscs, it has been shown that rates of
bioconcentration (which is an underestimate of uptake
as it includes simultaneous depuration) are an order of
magnitude higher than rates of biotransformation, so
accounting for the marked bioaccumulation of these
compounds observed in these organisms [14]. The dif-
ferences in rates of biotransformation between aquatic
invertebrates and vertebrates clearly accounts for the
bioaccumulation of readily metabolisable xenobiotics,
such as PAHs, to highest levels at the bottom of food
chains in marine invertebrates, whereas recalcitrant
xenobiotics, such as particular PCB congeners, bioaccu-
mulate along food chains reaching highest levels in top
predators, such as vertebrates [17]. A similar scenario of
greater bioaccumulation of parent compound in inver-
tebrates than fish can be illustrated for PCP, with
different rates of biotransformation (Table 2) being
contrasted with similar indicated rates of uptake, viz. at
a water-column exposure concentration of 50–60 ppb,
rates of ‘uptake’ (in pmol min − 1 g − 1) were 18 for O.
latipes [28] and 30 for M. saxatilis [5], compared with
32 for S. purpuratus [34]. Other factors also will affect
persistence of a xenobiotic in organisms, including ex-
cretory mechanisms for removing metabolites which are
indicated of limited efficiency in invertebrates [13,14].
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