Endocrine active compounds in the environment and impact on human health

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Endocrine active compounds in the
environment and impact on human health
Prof. Dr. Elke Dopp
University of Duisburg-Essen, Center of Water and Enivronmental Research,
Germany and IWW Water Center, Mülheim a.d. Ruhr, Germany
International Conference on „Women and Global Health“, Amity University Lucknow, India, Febr. 27th–March 1st 2017

Introduction
The United Nations outlined the 2030 Agenda for Sustainable Development
in 2015. It included 17 comprehensive Sustainable Development Goals
which are all interlinked.
Although access to water, sanitation and hygiene is a human right,
billions of people in developing countries are still faced with daily challenges
accessing even the most basic of services, specifically the poor and
vulnerable in communities.
Hygiene is an important aspect for women and girls to access the economic,
educational, and social opportunities they deserve. Proper hygiene removes
disease as a barrier for equality, economic growth, and more. The role of
hygiene in water and sanitation must be addressed
from scientific and social perspectives.

„Water is Life, but Water Quality is Health“
Joan Rose
European Water Framework Directive (WFD) requires a
“good” chemical and biological status for all water
bodies until 2027
Increasing concentrations of micropollutants (e.g.
pharmaceuticals, personal care products) in effluents
of waste water treatment plants, in surface water
bodies and finally in drinking water
Effects on the ecosystem (toxic, carcinogenic or
endocrine) and human population

Micropollutants with endocrine activity….
Definition: Endocrine disruptors are chemicals that may interfere with
the endocrine system of organisms and induce adverse developmental,
reproductive, neurological, and immune effects in both humans and
wildlife. (-can cause diseases)
Possible effects: Alteration of hormonal functions
Normal function Altered function Blocked function
….can disturb the endocrine system of an organism

Result of altered hormonal function
Receptors can be blocked by substances (e.g. chemicals, pharmaceuticles)...
Mayer and Arteaga, Clinical Cancer Research, 2010
… can alter cellular function, result in changed gene expression / transcription
/ translation and can finally lead to tumor development

Global cancer statistics
-hormon-dependent cancer
types are most relevant
-Breast cancer is the most
common cancer in women
worldwide, with nearly 1.7
million new cases each year

Ways of contamination
Surface water
Drinking water

Substances found in the water cycle
•Pharmaceuticals
–Beta blocker
–Radio-opaque
substances
–Hormones e.g.
contraceptives
–Chemotherapeutic
agents
–Analgetics
–etc.
•Personal care products
–Musk fragrances
–etc.
•Biocides
–Herbicides
–Fungicides
–Insecticides
–etc.
Concentrations: up to several μg/L environmentally active doses

Detection and effects of micropollutants
9
Toxicologically harmless Possible risk
Influence of ecosystem?
Influence of human health?
Chemical analyses
Biological effects

Early detection of biological effects

Chemical
molecular,
cellular
Organ Individual



Population
Exposure
Hazard Toxicological
Risk

Cellular test systems for detection of
toxicity
/Calux

Salient aspects about endocrine active
substances
•Low-Dose Effects
•Act at extremely low serum concentration, typically in the picomolar to nanomolar
range
•Usually at doses lower than those used in the standard testing paradigm of the US
EPA for evaluating reproductive and developmental toxicity
•Non-monotonic Dose Responses
•Importance of mixtures
•In nature contaminations occur in mixtures
•Combination of many EDCs at low doses produce
significant effects even though each chemical is present at low doses individually
•Age at exposure
•Very prone during development
•Delayed functions
•Exposure to EASs at early development when cells are differentiating and tissues are
developing, can result in harmful health effects during puberty and adulthood
•Transgenerational, Epigenetic Effects
•Diethylstilbestrol (DES) causing rare vaginal tumor in granddaughters of patients

In vitro Bioassay: CALUX
•CALUX: Chemically activated luciferase gene
expression
•Genetically modified organisms (luciferase
gene): U2-OS cells and breast cancer cells
•Measured effects:
estrogen, androgen, activation, inhibition
Luminescence
Inhibition

Detection of EAS in water samples

Removal of substances by wastewater treatment
EAS-Mixture
Reduction of micropollutants by oxidative treatment
Mechanical treatment Biological treatment Post treatment
Ozonation
conventional
Transformation
products

Removal efficiency
Elimination of micropollutans in WWTP
Duisburg after ozonation
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Injektor Diffusor Injektor Diffusor Injektor Diffusor Injektor Diffusor Injektor Diffusor
Carbamazepin Diclofenac Sulfamethoxazol Metoprolol 1-H Benzotriazol
3 mgO3/l 4 mgO3/l 5 mgO3/l 6 mgO3/l 7 mgO3/l 10 mgO3/l

Removal strategy in Europe

Proactive approach on improved regulation

Current Regulations/Guidelines
European Union
European Water Framework Directive
REACH (Registration, Evaluation, Authorisation and Restriction of
Chemicals)
Thresholds for single substances in the environment, in water, food etc.
Germany (Federal Environment Agency)
GOW (Thresholds for compounds without known effects)
0.1 μg/L proven not to be genotoxic; no other data available
0.01 μg/L to ≤ 0.1 μg/L highly to weak genotoxic
0.3 μg/L proven not to be geno-, neuro- or immunotoxic
1 μg/L proven not to be geno- or neurotoxic as well as no effect on
reproduction
USA (EPA and FDA)
Whole effluent toxicity (WET) tests for the use in Clean Water Act (CWA)
Threshold of toxicological concern (TTC)
< 1.5 μg/day Compounds with structural alerts for carcinogenicity
> 1.5 μg/day Compounds without structural alerts for carcinogenicity

Conclusions

IWW Rheinisch-Westfälisches Institut für
Wasserforschung gemeinnützige GmbH
IWW Rheinisch-Westfälisches Institut für Wasser
Beratungs- und Entwicklungsgesellschaft mbH
Moritzstraße 26
45476 Mülheim an der Ruhr
Telefon: +49 (0) 208 4 03 03-0
Fax: +49 (0) 208 4 03 03-80
Prof. Dr. Elke Dopp
e.dopp@iww-online.de
Phone: +49 (0) 208 4 03 03-362
IWW Rheinish-Westphalian Institute
for Water Research
Consulting and Development Services
Moritzstrasse 26
45476 Muelheim an der Ruhr
Germany
Phone: +49(0)0208-40303-0
Fax: +49(0)208-40303-80