© Benaki Phytopathological Institute
Hellenic Plant Protection Journal
8:
33-45, 2015
DOI 10.1515/hppj-2015-0006
Laboratory of Pesticides Toxicology, Department of
Pesticides Control and Phytopharmacy, Benaki Phy-
topathological Institute, 8 St. Delta Str., GR-145 61 Ki-
fissia, Attica, Greece
* Corresponding authors:
icance of NNDs for plant protection; never-
theless they imply their ubiquitous presence
in the environment.
NNDs are systemic insecticides with
chemical structures based on nicotine moi-
ety (Figure 1). Consequently, their mode of
action is similar to that of nicotine. Research
studies have shown that NNDs bind in sev-
eral and sometimes different domains in the
insect nicotinic acetylcholine receptors [for
the description of these receptors see the
chapter by Jones and Sattelle, 2010] that re-
sults in differentiation of their bioactivity
(Matsuda
et al
., 2005; Tomizawa
et al
., 2007a;
Tomizawa
et al.
, 2007b). Briefly, NNDs target
the nicotinic receptors and provoke excita-
tion of the nerve cells, causing trembling
and shaking and eventually paralysis. The
latter can lead to the death of the insects,
depending on dose and exposure duration.
Active substances of NNDs have been al-
leged as one of the factors that lead to the
development of the honeybee colony col-
lapse disorder (CCD) syndrome (Vanengels-
dorp
et al
., 2009). NNDs in particular seem
to interplay in CCD (Lu
et al
., 2014), howev-
er further research is needed to elucidate
CCD causality, since combined stress that
REVIEW ARTICLE
Neonicotinoids and their Metabolites in Human
Biomonitoring: A Review
K.M. Kasiotis* and K. Machera*
Summary
Neonicotinoids (NNDs) constitute a major class of insecticides with a broad and versatile
spectrum of applications in agriculture. Hence, their residues are found in several environmental com-
partments and can be transferred
via
several pathways to numerous organisms. Despite their pro-
found impact on honeybees and wild bees (impairment of memory, impact on immune system), their
presence in humans is far less reported, possibly due to the low to moderate toxicological effects that
they elicit. The aim of the present review is to emphasize on developments in the biomonitoring of
NNDs. It focuses mainly on chromatographic analysis of NNDs and their metabolites in human biologi-
cal fluids, discussing key features, such as sample preparation and analytical method validation. None-
theless, case reports regarding intoxication incidents are presented, highlighting the significance of
such cases especially in the developing world.
Additional Keywords:
LC-MS, urine, Imidacloprid
Introduction
Insecticides are substances of chemi-
cal or biological origin that are used to con-
trol insects. Amongst the plethora of insec-
ticides, neonicotinoids (NNDs) comprise
a significant class of insecticides with nu-
merous applications in agriculture. NNDs
family includes, imidacloprid (IMI), thiame-
thoxam (THIAM), clothianidin (CLOTH), thi-
acloprid (THIAC), acetamiprid (ACET), di-
notefuran (DINOT), nitenpyram (NITEN),
nithiazine (NITH), imidaclothiz (IMCL), flonic-
amid (FLON), the fourth generation member
sulfoxaflor (SULF) and cycloxaprid (CCLX).
Exemplary compound of NNDs is IMI, whose
sales in 2008 were estimated to ca. 5,450
tones in 2010 (Pollack, 2011) and its produc-
tion was estimated at ca. 20,000 tones [see
(Simon-Delso
et al
., 2015) and references
therein]. The above data indicate the signif-
