Endocrine disrupting chemicals in aquatic ecosystems: Impacts on new policies and guidelines, and economic benefits for the UK.
Submitting InstitutionUniversity of Exeter
Unit of AssessmentEarth Systems and Environmental Sciences
Summary Impact TypeEnvironmental
Research Subject Area(s)
Environmental Sciences: Environmental Science and Management
Biological Sciences: Ecology
Agricultural and Veterinary Sciences: Fisheries Sciences
Summary of the impact
Research led by Professor Charles Tyler at the University of Exeter has
provided critical data on the widespread adverse oestrogenic effects of
endocrine disrupting chemicals in wild fish populations in the UK. This
has triggered the UK government to take action through investment in
research and development of policies and guidelines. The research has led
to world-wide recognition that endocrine disrupting chemicals are an
emerging policy issue, a £40 million demonstration project with the UK
government and water industry, and multi-million pound benefits to the UK
in terms of improved water quality and safeguarding freshwater wildlife.
Charles Tyler's research team at the University of Exeter has carried-out
internationally-recognised research on the effects on fish of exposure to
effluents from wastewater treatment works (WwTW). They have identified the
Endocrine Disrupting Chemicals (EDCs) that produce feminising responses
and thereby undermine fish reproduction, and the sustainability of wild
The team has proven that WwTW effluents feminise male fish (e.g., )
and the causative chemicals inducing these feminised responses include
steroid, natural, and synthetic oestrogens discharged in waste waters
(e.g., ). The team also established the widespread prevalence of a new
group of EDCs that act as anti-androgens and have feminising effects in
fish, and they played a significant role in helping to understand the
effects of mixtures of EDCs on fish reproduction and health (e.g. ).
Tyler's applied research in this area has developed methods that have
been adopted for international test guidelines for testing EDCs in fish. A
major research activity is the development and application of molecular
approaches to unravel the mechanisms of endocrine disruption . Applying
these molecular approaches the team has recently shown feminised male fish
in wild populations in UK rivers have a reduced reproductive capability
with potential impacts for the sustainability of wild fisheries .
Further recently funded (NERC) work is now applying genome wide sequencing
methods to understand the mechanisms of adaptation to EDCs in wild fish
Working with Kudoh in Biosciences at Exeter, Tyler's team recently
developed a transgenic fish that is highly sensitive to environmental
oestrogens and provides an unrivalled whole systems model of informing on
the potential health impacts of exposure to environmental oestrogens .
The model developed is now being trialled for chemical and drug screening
through a BBSRC funded Flexible Interchange Partnership with AstraZeneca.
Further (NERC) funded work by Tyler (with Kudoh) is developing transgenic
fish models for EDCs with other modes of action (e.g., anti-androgens).
Tyler's work has further developed models for assessing effects of EDCs
on behaviour to show lower threshold of effect compared with tissue
disruptions, illustrating much wider ramifications of exposure to EDCs on
population dynamics. This work is reported in leading environmental
journals and government publications and is highly cited.
In recognition of this research work on EDCs, in 2012 Charles Tyler was
awarded The Fisheries Society of the British Isles Beverton Medal for
ground breaking research in fish biology.
References to the research
Key references to research that underpins the impact described in this
1. Rodgers-Gray TP, Jobling S, Kelly C, Morris S, Brighty G, Waldock MJ,
Sumpter JP, Tyler CR (2001). Exposure of juvenile roach (Rutilus
rutilus) to treated sewage effluent induces dose-dependent and
persistent disruption in gonadal duct development. Environmental
Science & Technology 35, 462-470. #
2. Nash JP, Kime DE, Van der Ven LTM, Wester PW, Brion F, Maack G,
Stahlschmidt-Allner P, Tyler CR (2004). Long-term exposure to
environmental concentrations of the pharmaceutical ethynylestradiol causes
reproductive failure in fish. Environmental Health Perspectives
112, 1725-1733. #
3. Thorpe KL, Cummings RI, Hutchinson TH, Scholze M, Brighty G, Sumpter
JP, Tyler CR (2003). Relative potencies and combination effects of
steroidal estrogens in fish. Environmental Science & Technology
4. Filby AL, Thorpe KL, Maack G, Tyler CR (2007). Gene expression
profiles revealing the mechanisms of anti-androgen-and estrogen-induced
feminization in fish. Aquatic Toxicology 81, 219-231.
5. Harris CA, Hamilton PB, Runnalls TJ, Vinciotti V, Henshaw A, Hodgson
D, Coe TS, Jobling S, Tyler CR, Sumpter JP (2011). The
Consequences of Feminization in Breeding Groups of Wild Fish. Environmental
Health Perspectives 119(3), 306-311. #
6. Lee O, Takesono A, Tada M, Tyler CR, Kudoh T (2012). Biosensor
zebrafish provide new insights into potential health effects of
environmental estrogens. Environmental Health Perspectives 120(7),
# References that best indicate the quality of the underpinning research.
Grant support related to this research:
Tyler was PI (or co PI; NERC, Env Agency, DEFRA, EU, BBSRC, Wellcome
Trust, approx £3M over reporting period) for the funding for all of this
work and since 2000 he has received 19 CASE awards with industry partners
and 7 CASE awards with government and regulatory authorities. Examples of
these grants as PI are:
• NERC: Population-level Consequences of Exposure of Fish to Oestrogenic
Wastewater Treatment Works Effluents (2009-2011, £560 000 with £340 000 to
• NERC: Knowledge transfer — Impacts of inbreeding on the responses to
pharmaceuticals and fitness consequences in fish — a molecular approach
(2008-2009, £82 224).
• Severn Trent Water: Impacts of EDCs in WwTW effluents (2008-2009, £71
• The Environment Agency: Impacts of EDCs in the River Itchen
(2008-2009, £31 500).
• DEFRA: Application of Reporter Gene Assay for Screening Endocrine
Disrupting for OECD test guidelines (2009-2010, £20 300).
• AstraZeneca — DTI KTP: Implementation of Molecular Tools into chemical
testing (2009-2010, £60 000).
Details of the impact
The research outlined in Section 2 has influenced strategic policy
decisions by UK government agencies, the EU, and organisations globally.
Examples of this include: the £40M UK National Endocrine Disruption
Programme [a]; the development of OECD Test Guidelines for the
detection of endocrine disrupters; and within REACH (Registration,
Evaluation, Authorization, and restriction of Chemicals) where
internationally the registration of new chemicals will now need to provide
evidence for a lack of endocrine disrupting activity [b-d].
Additional examples of the international influence of the work include the
development of chemical test guidelines by the US EPA [e] and the
significant investments (tens of £M) in programmes of research into
endocrine disruption in Japan.
The research influenced the development of guidelines for the testing of
chemicals by the Organization for Economic Cooperation and Development
(OECD). Research on fathead minnow has informed the development of several
tests adopted by the OECD. A short-term screening test for estrogenic and
androgenic activity, and aromatase inhibition in fish was adopted in
September 2009 [b], an assay to assess early-life stage effects of
EDCs on fish sexual development was adopted in July 2011 [c], and
an in vivo reproductive screening assay, the Fish Short Term
Reproduction Assay, was adopted in October 2012 [d]. The US
Environmental Protection Agency's Endocrine Disruptor Screening Program
has based its general validation principles on the harmonized
scientifically peer-reviewed principles by the OECD [e]. The
Norwegian company Biosense commercialised the vitellogenin assay developed
by Tyler and his colleagues, developing them in accordance with the
recommendations from the OECD.
Gina Solomon, Senior Scientist for the Natural Resources Defence Council
referenced Tyler's research as part of her witness testimony before the US
Congress Committee on Energy and Commerce, Subcommittee on Energy and
Environment in February 2010, in the session addressing the risks of EDCs
in drinking water [f].
The research is listed as supporting evidence in the listing of the
chemical 4-(1,1,3,3-tetramethylbutyl)phenol, 4-tert-octylphenol as a
substance of very high concern. The European Chemicals Agency adopted this
listing on 9 December 2011, stating that the conclusion was based on
"strong evidence from high quality studies of adverse effects in two fish
species, which are oestrogen mediated" [g].
In September 2012, The International Conference on Chemicals Management
(ICCM) adopted a resolution to include EDCs as an emerging issue under the
Strategic Approach to International Chemicals Management (SAICM). Tyler's
work was presented by Professor Susan Jobling from Brunel University, as
part of the technical briefing on EDCs [h]. His work is further
explicitly mentioned in the United Nations Environment Programme and the
World Health Organization. Report (2012) on the State of the science
of endocrine disrupting chemicals [i].
The Department of Environment, Fisheries and Rural Affairs (Defra) has
supported Tyler's research as it has direct relevance to policy needs. A
spokesperson for the Chemicals & Emerging Technologies Division at
Defra said the research "...informed our approach to implementing the
Water Framework Directive as it set the evidence baseline against which we
could objectively assess Commission proposals."
The research helped provide sufficient data to "act as a policy trigger
for taking action" (area manager at the Environment Agency). The National
Endocrine Disruption Demonstration Programme was funded by the Environment
Agency and the water industry and was managed by UK Water Industry
Research (UKWIR); all ten water and sewerage companies in England and
Wales participated in the programme, which produced extensive data
regarding the occurrence, treatment and release of various EDCs from
conventional wastewater treatment works. The collaborative programme was
considered to yield "valuable efficiencies" by "avoiding the need to fund
separate work programmes" [j].
The impact of the research has largely been facilitated by Charles
Tyler's active participation in expert panels, authorship of government
reports and as an advisor to government. Tyler was the UK Coordinator for
the UK-Japan Joint Research on Endocrine Disruptors between 2005 and 2010
and is currently its Chief Science Advisor (2010-2015). Tyler has been an
expert witness to the European Commission and has advised the US EPA, EA
Significant economic benefits have been realised in the UK as a result of
the work of Tyler's team at Exeter. An independent evaluation of these
benefits, using HM Treasury "Green Book" methods, attributed the following
economic impact to the research produced at the University of Exeter: Long
term collaborative links between the Tyler lab and industry partners, such
as AstraZeneca, Syngenta and UK water companies, has resulted in an
estimated total of £4.9M efficiency savings each year.
Sources to corroborate the impact
[a] UK Water Industry Research (2013) Completion of the monitoring
programme at WwTW [website] <http://www.ukwir.org/site/web/news/endocrine-disrupting-compounds-edcs?xpm64409=65123>
[b] OECD (2009) OECD Guideline for the Testing of Chemicals: 21-day
Fish Assay: A Short-Term Screening for Oestrogenic and Androgenic
Activity, and Aromatase Inhibition. Adopted 7 September 2009. Test
No. 230 < http://www.oecd-ilibrary.org/docserver/download/9723001e.pdf?expires=1367588135&id=id&accname=guest&checksum=0A29327F8994CDDCA12BF8624B3128DB>
[c] OECD (2011) OECD Guideline for the Testing of Chemicals: Fish
Sexual Development Test. Adopted 28 July 2011. Test No. 234 <http://www.oecd-ilibrary.org/docserver/download/9723401e.pdf?expires=1367587536&id=id&accname=guest&checksum=E7304C4B026C4C406060AE3E364FC5FB>
[d] OECD (2012) OECD Guideline for the Testing of Chemicals: Fish
Short Term Reproduction Assay. Adopted 2 October 2012. Test No. 229
[e] US Environmental Protection Agency Endocrine Disruptor Screening
Program (2012) Universe of Chemicals and General Validation
Principles. Jointly developed by the Office of Chemical Safety &
Pollution Prevention, the Office of Water and the Office of Research and
[f] Solomon GM (2010) Testimony of Gina M. Solomon at hearing entitled: Endocrine
disrupting chemicals in drinking water: risks to human health and the
environment. US House of Representatives, Committee on Energy and
Commerce, Subcommittee on Energy and Environment. One Hundred Eleventh
Congress, Second Session. February 25, 2010.
[g] European Chemicals Agency (2011) Member State Committee Support
Document for Identification of 4-(1,1,3,3-tetramethylbutyl)phenol,
4-tert-octylphenol as a Substance of Very High Concern.
[h] Jobling, S. (2012) Endocrine Disruption in Wildlife Populations.
PowerPoint presentation given at the Third Session of the ICCM. 17-21
September 2012, Nairobi, Kenya.
[i] Bergman Å, Heindel JJ, Jobling S, Kidd KA, Zoeller RT (eds.) (2012) State
of the science of endocrine disrupting chemicals. United Nations
Environment Programme and the World Health Organization. ISBN:
[j] Burke, M. (2004) U.K. to tackle endocrine disrupters in wastewater. Environmental
Science and Technology, 38 (9):362A-363A. DOI: 10.1021/es040631j