Aquatic Toxicology 49 (249) 289 – 304
In vivo and in vitro metabolism and organ distribution of
nonylphenol in Atlantic salmon (Salmo salar )
Augustine Arukwe
a,b,
*, Re ´mi Thibaut
c
, Kristian Ingebrigtsen
d
, Trine Celius
e
,
Anders Goksøyr
a
, Jean-Pierre Cravedi
c
a
Department of Molecular Biology, Uniersity of Bergen, HIB, P.O. Box 7800, N-5020, Bergen, Norway
b
School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, Uniersity of California, Dais, Dais,
CA 95616, USA
c
Laboratoire des Xe ´nobiotiques, INRA, BP3, 31391, Toulouse Cedex 9, France
d
Department of Pharmacology, Microbiology and Food Hygiene, Norwegian College of Veterinary Medicine,
P.O. Box 8146 Dep., 0033, Oslo, Norway
e
Department of Biochemistry, Biochemistry Building, Wilson, Rd., Michigan State Uniersity, East Lansing,
MI 48824 -1319, USA
Received 20 May 1999; received in revised form 16 July 1999; accepted 15 September 1999
Abstract
In the environment, nonylphenol (NP) occurs predominantly as a degradation product of nonylphenol ethoxylate
(NPE). They can be found in many types of products including detergents, plastics, emulsifiers, pesticides, and
industrial and consumer cleaning products. As a consequence of their use in a variety of products, they are quite
common in rivers and other aquatic environments that receive sewage discharges. Because of its enhanced resistance
towards biodegradation, toxicity, estrogenic effects, and ability to bioaccumulate in aquatic organisms NP has been
regarded as the most critical metabolite of APEs. We have studied the in vivo and in vitro metabolism and organ
distribution of NP in juvenile salmon. Fish were exposed in vivo to waterborne [
3
H]-4-n-NP for a period up to 72 h
or were administered a single oral dose of [
3
H]-4-n-NP. In vitro biotransformation of NP was studied by exposure of
cultured salmon hepatocytes to [
3
H]-4-n-NP in the presence or absence of a CYP1A-inducer, -naphthoflavone
(NF). Our results show that 4-n-NP was mainly metabolized in vivo, to its corresponding glucuronide conjugates
and hydroxylates. The major route of excretion was the bile. The half-life of residues in carcass and muscle was
between 24 and 48 h in both waterborne and dietary exposure. In whole body autoradiography, intragastric
administered [
3
H]-4-n-NP was mainly present in the gastrointestinal tract and bile. NP-derived radioactivity in fish
exposed via water was more evenly distributed in the organs compared to intragastric exposure and were observed in
the intestinal contents, liver, kidney, gills, skin, abdominal fat and brain. In vitro pretreatment of hepatocytes with
NF had no effect on rates or patterns of NP biotransformation. The in vitro metabolic rate of NP were 118 pmol
NP metabolized/h/0.5 ×10
6
cells without NF, and 98 pmol NP metabolized/h/0.5 ×10
6
cells when NF was added
to the culture medium. © 2000 Elsevier Science B.V. All rights reserved.
www.elsevier.com/locate/aquatox
* Corresponding author. Tel.: +47-55-584527; fax: +47-55-584373.
E-mail address: augustine.arukwe@mbi.uib.no (A. Arukwe)
0166-445X/00/$ - see front matter © 2304 Elsevier Science B.V. All rights reserved.
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