from silent spring to silent night - environmental science · 2016-08-08 · from silent spring to...

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Produced by and for Hot Science - Cool Talks by the Environmental Science Institute. We request that the use of these materials include an acknowledgement of the presenter and Hot Science - Cool Talks by the Environmental Science Institute at UT Austin. We hope you find these materials educational and enjoyable. Dr. Tyrone Hayes January 30, 2009 From Silent Spring to Silent Night # 58

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Page 1: From Silent Spring to Silent Night - Environmental Science · 2016-08-08 · From Silent Spring to Silent Night # 58. From Silent Spring Placeholder slide to Silent Night Dr. Tyrone

Produced by and for Hot Science - Cool Talks by the Environmental Science Institute. We request that

the use of these materials include an acknowledgement of the presenter and Hot Science - Cool Talks

by the Environmental Science Institute at UT Austin. We hope you find these materials educational

and enjoyable.

Dr. Tyrone Hayes

January 30, 2009

From Silent Spring to

Silent Night

# 58

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Placeholder slideFrom Silent Spring

to Silent Night

Dr. Tyrone Hayes

University of California at Berkeley

January 30th, 2009

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N N

N

Cl

N

H

N

H

ATRAZINE

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ATRAZINE

IS AN HERBICIDE

USED WITH

MONOCOT CROPS

(CORN, SORGHUM)

AND STONE FRUITS

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ATRAZINE

HAS BEEN USED

FOR 48 YEARS

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ATRAZINE

80 MILLION POUNDS

USED ANNUALLY

IN THE U.S.

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ATRAZINE

IS USED IN

MORE THAN

80 COUNTRIES

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ATRAZINE

BUT NOW OUTLAWED

IN ALL OF EUROPE

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1

Laboratory

Model

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Testes

Ovaries

Testis

Ovaries

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O

OH

Testosterone

T

Page 13: From Silent Spring to Silent Night - Environmental Science · 2016-08-08 · From Silent Spring to Silent Night # 58. From Silent Spring Placeholder slide to Silent Night Dr. Tyrone

O

OH

TestosteroneHO

OH

Estrogen

Aromatase

EATRAZINE

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Atrazine-

Treated

Males

Control

Females

6

0

1

2

3

4

5

Blo

od

te

sto

ste

ron

e (

ng

/mL

)

Control

Males

Hayes et al. 2002

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A

AA

B

B

A,B

B

B

Control

Males

Females

Malformed

0.1 1.0ATRAZINE (ppb)

7

6

5

4

3

2

1

0Aro

mata

se (

CY

P19)/

EF

-1-a

E-0

4

Hayes, unpubl. data

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0

2

4

6

8

10

12

Su

ccessfu

l P

air

ing

s

Control Atrazine

Hayes, unpubl. data

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Control

Males

Atrazine-

Treated

Males

0

33

66

100

Pe

rcen

t F

ert

ile

Hayes, unpubl. data

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1

Laboratory

Model

2Comparative

Studies

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Leopard

Frog

Testeseggs

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3

Field

Studies

1

Laboratory

Model

2Comparative

Studies

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ARE THE EFFECTIVE DOSES (> 0.1 PPB)

ECOLOGICALLY RELEVANT?

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Runoff Temporary

Pools

PrecipitationPermanent

Water

0.001

0.01

10,000

1,000

100

10

1

0.1

Atr

azin

e (

pp

b)

Intersexes (Hermaphrodites)

DRINKING WATER

2.9 – 29 million

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Atrazine use (kg/km2)

Zero or data missing

Less than 0.4

2.5 to 9.29.3 to 28.7More than 28.7

0.4 to 2.4

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Atrazine No Atrazine

92% Hermaphrodites 0% Hermaphrodites

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1

Laboratory

Model

3

Field

Studies

2Comparative

Studies4Field

Simulations

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Atrazine

Metolachlor

Alachlor

Nicosulfuron

Methoxyacetyl

PropiconazoleTebupirimphos

Cyfluthrin

Cyhalothrin

SPRING

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Nu

mb

er

at

Meta

mo

rph

osis

X Data

40 50 60 70 80 90

Y D

ata

0

2

4

6

8

10

12

tank001

tank002

tank003

X Data

40 50 60 70 80 90

Y D

ata

0

2

4

6

8

10

Plot 1

tank016

tank017

tank018

X Data

40 50 60 70 80 90

Y D

ata

0

2

4

6

8

10

Plot 1

tank032

tank033

tank033

40 60 80

Control

Atrazine and

S-metolachlor

Mixture of

9 compounds

0

3

6

9

12

0

4

6

8

10

2

0

4

6

8

10

2

Time (days)

Hayes et al., 2006

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0.6 ppb Atrazine 15.3 ppb Atrazine

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Time to complete tail reabsorption (days)

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80Bo

dy W

eig

ht

(mg

)

Control Atrazine + S-met Mix4000

3000

2000

1000

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40 50 60 70 80 90

TR

1000

2000

3000

4000B

W

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000B

W

40 50 60 70 80 90 100

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

40 50 60 70 80 90 100 110

TR

1000

2000

3000

4000

BW

Time to complete tail reabsorption (days)

Bo

dy w

eig

ht

(mg

)

Control Cyfluthrin Nicosulfuron Tebupiromphos

S-metolachlor Metylaxyl Propiconazole -chyalothrin Atrazine

Atr + S-met

(0.1 ppb)

Atraz + S-met

(10 ppb)Bicep II

(0.1 ppb)

Bicep II

(10 ppb)

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

40 50 60 70 80

TR

1000

2000

3000

4000

BW

Alachlor

MIX

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CONTROL MIX

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Stress hormone

(Corticoids)

Immunosuppression,

Decreased growth,

Retarded development,

Inhibited metamorphosis

pesticides

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Pesticide-treated

Males

Control

Males

0

1

2

3

4

Blo

od

Co

rtis

on

e (n

g/m

L)

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Stress hormone

(Corticoids)

density

desiccation

temperature

pesticides

pesticides

Stress hormone

(Corticoids)

PESTICIDES

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Kesieker,

2002

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-- Forson and Storfer, 2006

Atrazine increases rana virus susceptibility

in the tiger salamander, Ambystoma Tigrinum

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1

Laboratory

Model

3

Field

Studies

2Comparative

Studies4Field

Simulations

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2001 2003

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1

Laboratory

Model

3

Field

Studies

2Comparative

Studies4Field

Simulations

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1

Laboratory

Model

3

Field

Studies

2Comparative

Studies4Field

Simulations

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Santa Margarita Atascadera Salinas

29

31

33

35

37

Sta

ge

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Santa Margarita Atascadera Salinas

Len

gth

(m

m)120

60

0

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Margarita Atascadera Salinas

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Yeast injection (g/ml)

Perc

en

t to

tal

0

20

40

60

80

100

0 0.0125 0.05 0.125 0.2 0.125 0.20 0.0125 0.05 0 0.0125 0.05 0.125 0.2

Santa Margarita Atascadera Salinas

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FROM

TO

Page 69: From Silent Spring to Silent Night - Environmental Science · 2016-08-08 · From Silent Spring to Silent Night # 58. From Silent Spring Placeholder slide to Silent Night Dr. Tyrone

SILENT

NIGHT

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“In ecoepidemiology,

the occurrence of an

association in more

than one species and

species population is

very strong evidence

for causation.” (Fox,

ref. 10, page 368). AMPHIBIANS

FISH

REPTILES

BIRDS

MAMMALS

AMPHIBIANS

FISH

REPTILES

BIRDS

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Pipidae

Hylidae

Bufonidae

Ranidae

AMPHIBIANS

FISH

REPTILES

BIRDS

MAMMALS

AMPHIBIANS

FISH

REPTILES

BIRDS

MAMMALS

“There is no direct scientific

information to assess this

hypothesis.”

from EPA, Statement of Anne Lindsay, page 10

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Sperm productionSperm production

TestosteroneTestosterone

Atrazine

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In rats

(Kniewald et al. 2000)

0

3

6

9

12

18S

perm

nu

mb

er

( x

10

8)

15P < 0.001

60 120

Atrazine (mg/kg)

Control

Males

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In humans

Swan et al. 2003

Control

Males

Sub-fertile

Males

0

.03

.06

.09

.12

.18A

tra

zin

e le

ve

l (p

pb

) .15 P < 0.009

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Control

Males

Sub-fertile

Males

Field

Workers

(Average)

0

40

80

120

160

240 A

tra

zin

e le

ve

l (p

pb

) 200

Lucas et al. 1993

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Atr

azin

e le

ve

l (p

pb

)

Control

Males

Sub-fertile

Males

Field

Workers

(Average)

0

400

800

1200

1600

2400

2000

Applicators

(Maximum)

Lucas et al. 1993

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“Atrazine has been a

vital tool for US farmers

for nearly 50 years.”

--Tim Pastoor, Letter to the editor

Terra Haute Tribune Star

Jan 3, 2008

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TestosteroneTestosterone

Sperm production

Laryngeal growth

Sperm production

Atrazine

Estrogenaromatase

Vitellogenesis

OogenesisMammary tumors

Prostate cancer

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Atrazine (mg/kg)

0 50 100 150 200 250

Se

rum

estr

og

en

(p

g/m

l)

0

20

40

60

80

100

120

140E2+E1

Seru

m T

esto

ste

ron

e (

pg

/ml)

0

5

10

15

20

*

Stoker 2000

P < 0.05Rodents

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Control

Females

0

15

30

45

60

75

Ma

mm

ary

tu

mo

r in

cid

en

ce

(%

)

Rodents

10 70 500 1000

Atrazine (ppm)

P < 0.01

Stevens et al. 1994

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Sanderson et al. 2001

Control Atrazine

treated

Rela

tiv

e C

YP

19

ex

pre

ssio

n

Or

aro

mata

se

ac

tiv

ity

0

1

2

3

4

6

5

P < 0.05

Human Cells

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P < 0.0001In humans

Kettles et al. 1997

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“The increase in all cancers combined seen in the overall study group

was concentrated in the company employee group.” (page 1052)

“The increase in prostate cancer in male subjects was concentrated in

company employees.” (page 1052).

“The prostate cancer increase was further concentrated in actively

working company employees.” (page 1053)

“all but one of the cases occurred in men with 10 or more years since

hire”. (page 1052)

“Analyses restricted to company employees also found that the

prostate cancer increase was limited to men under 60 years of age.”

(page 1053).

MacLennan et al. 2002

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MacLennan et al. 2002

Control

Males

Exposed

Males

Pro

sta

te c

an

cer

Incid

en

ce

(Ob

serv

ed

/Exp

ecte

d)

0

4

8

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“Atrazine has been used safely

for more than 47 years.”

-- Tim Pastoor

Syngenta Crop Protection

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Pipidae

Hylidae

Bufonidae

Ranidae

AMPHIBIANS

FISH

REPTILES

BIRDS

MAMMALS

AMPHIBIANS

FISH

REPTILES

BIRDS

MAMMALS

“There is no direct scientific

information to assess this

hypothesis.”

(EPA, page 10)

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?

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ERER

O

OH

TestosteroneHO

OH

Estrogen

Aromatase

ER

Letrozole

Aromatase

HO

OH

Estrogen

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HO

OH

Estradiol

Aromatase

ATRAZINE

ER

Letrozole

Aromatase

O

OH

TestosteroneHO

OH

EstrogenHO

OH

Estrogen

Aromatase

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“Novartis Oncology offers treatments

for cancers that range from breast

cancer to leukemia to bone cancer to

carcinoid tumors.” – novartis.com

Clinical Trials of drugs in development…

Image source: FDA and USA.gov

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HO

OH

Estradiol

Aromatase

ATRAZINE

ER

Letrozole

Aromatase

O

OH

TestosteroneHO

OH

EstrogenHO

OH

Estrogen

Aromatase

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HO

OH

Estradiol

Aromatase

ATRAZINE

ER

Letrozole

Aromatase

O

OH

TestosteroneHO

OH

EstrogenHO

OH

Estrogen

Aromatase

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“…use of atrazine according to

the label instructions will not

likely result in harm to human

health or the environment.”

-- Office of Pesticide Programs

US EPA, 2008

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Working

Hypothesis

Apical Effects1

Ecological

RelevanceYES

STOPNO

Sex Steroid

Measurements2

Aromatase

Activity ?3

Aromatase

Inhibitor

Study

4

YES

YES

NO Test for

Alternative Effects

NO Test for

Alternative Effects

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Working

Hypothesis

Apical Effects1

Sex Steroid

Measurements2

Aromatase

Activity ?3

Aromatase

Inhibitor

Study

4

Ecological

RelevanceYES

YES

YES

STOPNO

NO Test for

Alternative Effects

NO Test for

Alternative Effects

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Neural

Damage

Immune

Failure

Prostate

And

Mammary

Cancer

Abortion

Prostate

Disease

Impaired

Mammary

Development

Control Atrazine

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Impaired

Growth and Development

Neural

Damage

Immune

Failure

Abortion

Prostate

Disease

Prostate

And

Mammary

Cancer

Impaired

Mammary

Development

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Impaired

Growth and Development

Abortion

Prostate

Disease

Impaired

Mammary

Development

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“The ultimate decision

is much bigger than science…

…it weighs in public opinion.”

-- Stephen Bradbury

US EPA, Dec 3, 2006

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Thank you

Dr. Tyrone Hayes

University of California – Berkeley

[email protected]

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Dr. Tyrone B. Hayes

Dr. Tyrone B. Hayes's work is transforming biology one battle

at a time. From a very early age, he knew that hews

interested in biology, amphibians in particular. Always

fascinated by frogs and toads, this fascination turned into

reality and a career. Dr. Hayes's work paves the way for an

integrative approach to understanding how an organism

reacts to changes in its environment.

Recently his work has gained international recognition for

demonstrating how atrazine, a widely used pesticide which is

now found in many water sources, has been shown to alter

reproductive development (act as an endocrine disruptor) in

frogs even at extremely low levels. Beyond his integrative

work in conservation, he has won numerous teaching

awards, conservation awards, and recognition as a leader in

the scientific community.

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