Predicting effects on fish from mixtures of endocrine disrupting chemicals at the catchment scale

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Predicting effects on fish from mixtures of
endocrine disrupting chemicals at the catchment
scale
Richard Williams

• Andrew Johnson Centre for Ecology and Hydrology
• Martin Scholze
• Andreas Kortenkamp School of Pharmacy,
  University of London
• John Sumpter Brunel University

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Overview

• Background to Steroid Oestrogens and how they
  reach rivers
• Estimating inputs to rivers and therefore
  exposure concentrations through catchments
• Converting this to possible effects
• Single chemicals and mixtures
• Concluding remarks and what we are doing now

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(b) the intersex condition
Effects observed in Freshwater Fish
(a) Vitellogenin Induction
Eggs within the testis here!
The worst effects were observed downstream of
sewage works
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Chemicals

• Endocrine disruptors
• Estradiol (E2)
• Estrone (E1)
• Ethinylestradiol (EE2)
• Nonylphenol (NP)

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How a steroid oestrogen gets into a river, the
conceptual picture!
Some may be excreted but rendered Inactive as
sulphate conjugates
Sewage Works
Potential in-sewer transformations
Further removal in sewage treatment
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Risk
Effect Concentrations
Exposure Predictions

Risk Maps Individual Chemicals Mixtures
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As the primary source of steroid oestrogens is
ourselves, we should be able to predict sewage
influent and ultimately effluent concentrations

• Define our human population
• Work out what each member excretes

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Defining our human population with regard to
steroid oestrogens
1 in 57 females pregnant (0.9 total population)
Males 50 total population (but not all
excreting)
Menopausal on HRT 2.5 total population
Menstrual females 30 total population
Menopausal not on HRT 11 total population
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Example Generating a per head normalised
excretion value for E2
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Predicting how much EE2 will arrive at an STW
Taken by around 17 of all females
26 ug/d EE2 ingested
43 metabolised within the body
2-hydroxy-17a-ethinylestradiol
30 in faeces but 77 of this as free EE2 6 ug/d
Following deconjugation gives 10.5 ug/d combined
free EE2 in raw sewage influent (40 of
that ingested).
2-methoxy-17a-ethinylestradiol
27 or 7.1 ug/d dose in urine
63 of that in urine present as free or
glucuronide conjugates ie 4.5 ug/d in urine
11 as conjugated metabolites or as EE2 sulphate
conjugates
2-methoxy-17a ethinylestradiol
17a-ethinylestradiol3-sulphate
17a-ethinylestradiol3-glucuronide
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Predicting Exposure
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Aire/Calder
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Exposure Prediction
E1 E2 EE2
E1 E2 EE2 NP
STW
Some measured data
Steroid Removal
From population served
U/S INPUTS
RIVER
River flow characteristics Half lives for
chemicals
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E1 Concentration (pg/L)
D
i
s
c
h
a
r
g
e

s
i
t
e
s

R
i
v
e
r

n
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i
m

9
0


p
g
/
L

0

-

1
5
1
1
5
1

-

2
0
1
8
2
0
1
8

-

4
1
0
5
4
1
0
5

-

7
2
8
3
7
2
8
3

-

2
3
8
9
6
2
3
8
9
6

-

6
1
8
7
0
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Effects Concentrations and Risk Individual EDCs

• End Point Vittellogenin production in male Fat
  Head Minnows

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Effects Concentrations and Risk Mixtures of EDCs

• Assumed additivity based on similar action of the
  mixture components
• Need to account for the fact that the chemicals
  have different potency
• EC50 for Estradiol 0.025 ug/L
• EC50 for Estrone 0.058 ug/L

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Effects Concentrations and Risk Mixtures of EDCs

• Assumed additivity based on similar action of the
  mixture components
• with zi being the concentrations of the
  individual substances present in a mixture
• ECxi are those concentrations that alone would
  cause the same quantitative effect x as for the
  given fixed mixture effect level x

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Effects Concentrations and Risk Mixtures of EDCs

• We just want to classify in effect categories
• So we still only need to know the EC10, EC50 and
  EC95 values for the constituents of the mixture
• Thus the Medium effect class is given by

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Effects Concentrations and Risk Mixtures of EDCs

• So for each reach concentration we evaluate sums
  like
• E1/EC10E1 E2/EC10E2 EE2/EC10EE2 NP/EC10NP
  gt0.1?
• E1/EC10E1 E2/EC10E2 EE2/EC10EE2 NP/EC10NP
  gt1.0 ?
• E1/EC50E1 E2/EC50E2 EE2/EC50EE2 NP/EC50NP
  gt1.0 ?
• E1/EC95E1 E2/EC95E2 EE2/EC95EE2 NP/EC95NP
  gt1.0 ?

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Estradiol
99 No/Low Effect
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Estrone
96 No/Low Effect
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Ethinylestradiol
51 No/Low Effect 45 Medium Effect
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Nonylphenol
Nonylphenol
88 No/Low Effect 3 Severe Effect
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All Endocrines
25 No/Low Effect 62 Medium Effect 3 Severe
Effect
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But is the risk of an effect static?

• No!
• Changing population patterns
• Development of new contraceptive pharmaceuticals
• Changing patterns of discharges from industry
• Different river flow regimes under climate change

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All Endocrines
25 No/Low Effect 62 Medium Effect 3 Severe
Effect
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All Endocrines 2080 Flows
3 No/Low Effect 50 Medium Effect 43 High
Effect
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All Endocrines low NP 2080 Flows
3 No/Low Effect 63 Medium Effect 34 High
Effect
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Conclusions

• In river stretches where none of the chemicals
  individually was estimated to induce effects, the
  impact of the mixture was predicted to be
  profound.
• Significant underestimations of the impact of
  estrogenic chemicals will occur if mixture
  effects are not taken into account.
• Demonstrated a practical way of combining PECs
  with effect levels to give RISK MAPS - Approach
  could be a useful management tool
• Environ. Sci. Technol.2006 ASAP Article  DOI
  10.1021/es052554d

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Scale

• This is a catchment risk assessment
• But.
• Steroid inputs derived from literature on human
  endocrine system
• Lumped in-stream degradation rates microbial
  action
• Concentration addition and Risk is based on
  endpoints determined at the microscopic scale

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Taking this work forward

• Environment Agency Risk Assessment Project
• Objective
• To undertake a national catchment-based risk
  assessment of steroid discharges from STWs to the
  aquatic environment using the LF2000 WQX model

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How the project outputs will be Used by the Agency

• To prioritise river reaches that are at risk from
  STWs that may require improvement in future water
  industry investment rounds (2009 and beyond).
• To extend the risk assessments of steroid
  discharges to cover all relevant European sites
  to inform the reviews of consents that need to be
  undertaken under the Habitats Regulations.