Conjugates of estrogenic chemicals, endogenous as well
as xenobiotic, are mainly excreted via bile into the intestine.
Therefore, measurement of estrogenic activity in bile
yields useful information about an organism's internal
exposure to (xeno-)estrogens. Although previous studies
in The Netherlands have reported estrogenic activity in male
fish bile, the contribution of natural hormones and
xenobiotic substances to this activity is unknown. To
identify compounds responsible for estrogenic activity in
fish bile, we developed a bioassay-directed fractionation
method for estrogenic chemicals. In this approach, the in
vitro reporter gene assay ER-CALUX (Estrogen Responsive
Chemical Activated Luciferase Gene Expression) was
used to assess estrogenic activity in deconjugated bile
samples and to direct RP-HPLC fractionation and chemical
analysis (by GC−MS) of estrogenic compounds. The
method was applied to bile from male breams (Abramis
brama) collected at three locations in The Netherlands. At
one of these locations, the River Dommel, extremely
high levels of plasma vitellogenin and a high incidence of
intersex gonads in these male breams have previously
been observed, indicating the exposure to estrogens. In
this study, the natural hormones 17β-estradiol, estrone, and
estriol accounted for the majority of estrogenic activity
in male bream bile. At the River Dommel, the synthetic
contraceptive pill component ethynylestradiol was found in
effective concentrations as well. The detected natural
and synthetic hormones may be responsible for the estrogenic
effects observed in wild bream from this location.
Furthermore, a large number of xenobiotic chemicals was
detected at relatively high levels in bile, including triclosan,
chloroxylenol, and clorophene. Although chloroxylenol was
shown for the first time to be weakly estrogenic, these
compounds did not contribute significantly to the estrogenic
activity observed.
An increasing part of drinking water in Europe is prepared from surface water. At the same time, a growing number of emerging contaminants is being discovered in surface water. This review provides an overview of classes of emerging contaminants nowadays detected in the aquatic environment that are of relevance for drinking water production. These comprise e.g. endocrine disrupting compounds, such as hormones and compounds with hormone-like properties, pharmaceuticals, illicit and non-controlled drugs, sweeteners, personal care products, complexing agents, nanoparticles, perfluorinated compounds, flame retardants, pesticides, and fuel additives. The individual compounds are observed in concentrations that are generally considered too low to cause acute effects. Nevertheless, health effects due to long-term exposure to a mixture of low concentrations of all kinds of emerging contaminants cannot be excluded with current knowledge. Moreover, contamination of drinking water with man-made substances is considered unwanted in principle. The precautionary principle is used to motivate that prevention of emission of emerging contaminants into the environment is the preferred approach to safeguard sustainable drinking water production. In the mean time, extensive monitoring of the sources and development and application of advanced treatment techniques are used to prepare safe drinking water.
In vitro bioassays are valuable tools for screening environmental samples for the presence of bioactive (e.g., endocrine-disrupting) compounds. They can be used to direct chemical analysis of active compounds in toxicity identification and evaluation (TIE) approaches. In the present study, five in vitro bioassays were used to profile toxic potencies in sediments, with emphasis on endocrine disruption. Nonpolar total and acid-treated stable extracts of sediments from 15 locations in the Rhine Meuse estuary area in The Netherlands were assessed. Dioxin-like and estrogenic activities (using dioxin-responsive chemical-activated luciferase gene expression [DR-CALUX] and estrogen-responsive chemical-activated luciferase gene expression [ER-CALUX] assays) as well as genotoxicity (UMU test) and nonspecific toxic potency (Vibrio fischeri assay) were observed in sediment extracts. For the first time, to our knowledge, in vitro displacement of thyroid hormone thyroxine (T4) from the thyroid hormone transport protein thransthyretin by sediment extracts was observed, indicating the presence of compounds potentially able to disrupt T4 plasma transport processes. Antiestrogenic activity was also observed in sediment. The present study showed the occurrence of endocrine-disrupting potencies in sediments from the Dutch delta and the suitability of the ER- and DR-CALUX bioassays to direct endocrine-disruption TIE studies.
Effect-directed analysis (EDA) is
a commonly used approach for
effect-based identification of endocrine disruptive chemicals in complex
(environmental) mixtures. However, for routine toxicity assessment
of, for example, water samples, current EDA approaches are considered
time-consuming and laborious. We achieved faster EDA and identification
by downscaling of sensitive cell-based hormone reporter gene assays
and increasing fractionation resolution to allow testing of smaller
fractions with reduced complexity. The high-resolution EDA approach
is demonstrated by analysis of four environmental passive sampler
extracts. Downscaling of the assays to a 384-well format allowed analysis
of 64 fractions in triplicate (or 192 fractions without technical
replicates) without affecting sensitivity compared to the standard
96-well format. Through a parallel exposure method, agonistic and
antagonistic androgen and estrogen receptor activity could be measured
in a single experiment following a single fractionation. From 16 selected
candidate compounds, identified through nontargeted analysis, 13 could
be confirmed chemically and 10 were found to be biologically active,
of which the most potent nonsteroidal estrogens were identified as
oxybenzone and piperine. The increased fractionation resolution and
the higher throughput that downscaling provides allow for future application
in routine high-resolution screening of large numbers of samples in
order to accelerate identification of (emerging) endocrine disruptors.
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