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Rachel Carson and the pesticide debate: DDT as a paradigm
Andy Smith
MRC Toxicology UnitUniversity of Leicester
Agenda
• A little background on Rachel Carson and Silent Spring
• A short history of DDT use and human hazard
• Some general comments 50 years on
Background to Rachel Carson1907‐1964
• Rachel Carson seems to have been torn between writing, and later at college, natural history especially marine biology
• After periods at a PA college and Johns Hopkins she worked forUS Bureau of Fisheries writing for radio and magazines
• Eventually she was appointed as one of the first female aquatic biologistsanalysing field data and writing reports for the public
• Later became editor of publications for the US Fish and Wildlife Service
• Under the Sea‐Wind (1941) and then The Sea Around Us (1951) wonmany prizes and allowed her to work independently as a scientific writer
• The Edge of the Sea was published in 1955
Rachel Carson and Pesticides
• From 1957 Carson seems to have followed the increasing widespread use of pesticides in the US with concern
• Her writings and comments aggregated reports elsewhere of the effects of pesticides
• Culminated in the publication of Silent Spring (1962)
• She was attacked by chemical industry and by USDA but backed by Kennedy’s Sience Advisory Committee
• DDT was especially a lead chemical for criticism in the book. The greatest worry for humans was cancer
• Rachel was given many awards before and after death
DDT: past and present
Many issues to be learned from DDT story about known toxicity to animals compared with perceived toxicity to people
Environmental considerations
Still pertinent questions to be debated and clarified
SMITH, A.G. (2000) How toxic is DDT? Lancet356, 267‐268
• Insecticides prior to DDT, organophosphates and pyrethrins were not particularly effective
• Could also be very toxic such as arsenic compounds
SyntheticsNatural products
Cl2
PCBsInsecticidesDDTLindane AldrinDieldrinToxapheneKepone
PentachlorophenolHexachlorobenzene
2,4‐D2,4,5‐T ‘Dioxins’
1940‐1950s many materials were chlorinated
Most now banned but can be considerable residues around
Fungicides/herbicides
Discovery of DDT as insecticide• 1874 DDT first prepared by Zeidler
• 1939 Paul Müller (Geigy): DDT kills insects
• 1940‐41 Checks plague of Colorado beetles on Swiss potato crop
Seemed to be no acute hazards to man
• 1942‐43 DDT harnessed to War machine in UK and US
• 1943‐44 DDT attributed with major contribution to stopping typhus
in Naples
An epidemic had never been stopped in mid winter before
A few months earlier in Sicily the 7th and 8th armies suffered
` more casualties from malaria than from battle
• The discovery of DDT indubitably heralds a new era in man’s ceaseless fight for mastery against disease Sir Ian Heilbron
• The excellent DDT powder which has been fully experimented with and found to yield astonishing results will henceforth be used on a great scale by the British ...and by the American and Australianforces in the Pacific and India... Sir Winston Churchill
• 1948 Paul Muller received Nobel prize in Physiology and Medicine
• In many ways a similar story to penicillin (initial high enthusiasm followed by overuse)
‘We were told that every service man had to have a shirt impregnated with DDT before D Day’
‘I took some home and made a weak acetone solutionand sprayed it on the kitchen window and then polished it off.
I carefully observed the clinical progress of house flies that momentarily settled on the surface. Within 20 minutes they exhibited the characteristic extension and twitching of the back legs and rolled over to kip on their backs and become ex‐flies.
I still can’t conceive how so few molecules could have been absorbed to cause death’.
1990
Prof Pat Lawther’s DDT exploits in 1943
During and after World War II the use of DDT etc contained diseases like typhus and malaria‐ seen as wonder chemical Effect of DDT on malaria and estimated economic loss in India
From Hayes 1982
God bless General Peron DDT and organisation defeat malaria in Argentina
Problems came from too much enthusiasm without backup research of the long term
consequences
CCl3
ClCl
CCl3
ClCl
CHCl2
Cl
O H
Cl
CCl3
CHCl2
CH2CH3
Cl
Cl CCl3
O
O
Cl
Cl
CCl3
Cl
O H
Cl
OCH3CH3O
CH3
COOCH2CH3
CH2CH3
Other analogues
p,p‐DDT
o,p‐DDTp,p‐DDD
Ethylan
Methoxychlor Dicofol Acetofenate
Chlorobenzilate
Dichlorodiphenyltrichoroethane or 2,2,2‐trichloroethane‐1,1diyl)bis(4‐chlorobenzene)
p,p'-DDA
*
*
p,p'-DDD
p,p'-DDMU
p,p'-DDOH
p,p'-DDT
p,p'-DDNU
p,p'-DDE
ClCl
ClCl
OH
Cl Cl
OH Cl
Cl
Cl Cl
OH Cl
Cl
C H2
Cl
ClCl
ClCl
ClCl
ClCl
ClCl
ClCl
ClCl
CCl3
CCl2
CCl2
CCl2
CCl2
CCl2
CH2Cl
CHCl
COCl
CH2OH
CHO
CHCl2
COOH
HO
p,p'-DDA
*
*
p,p'-DDD
p,p'-DDMU
p,p'-DDOH
p,p'-DDT
p,p'-DDNU
p,p'-DDE
ClCl
ClCl
OH
Cl Cl
OH Cl
Cl
Cl Cl
OH Cl
Cl
C H2
Cl
ClCl
ClCl
ClCl
ClCl
ClCl
ClCl
ClCl
CCl3
CCl2
CCl2
CCl2
CCl2
CCl2
CH2Cl
CHCl
COCl
CH2OH
CHO
CHCl2
COOH
HO
Slow metabolism‐species dependent rates and routes
Toxicity of chlorinated insecticides to animals
• DDT and chlordecone cause severe tremours
• Lindane and dieldrin cause convulsions
• Most induce hepatic drug metabolism enzymes
• Complete metabolism is usually poor
• Most cause liver enlargement and are nongenotoxic carcinogens‐relevance to humans? Poor mutagens
• Some, such as o,p‐DDT and chlordecone, have reproductive effects apparently as oestrogens
• Effects on fertility etc now of most interest
Potential sites of action of chlorinated insecticides on nerves
GABA‐gated Cl channelGABAA receptor blockade
Modulation of voltage‐gated sodium channels
DDTType 1 Pyrethroids
Lindane Dieldrin etc
Toxicity to humans at high dosesInsecticide Effect
DDT, methoxychlor,chlorobenzilate, dicofol
Parathesia, dizziness, anorexia, nausea, lethargy, tremours
Lindane (BHC) Parathesia, nausea, headaches, convulsions
Aldrin, telodrin, isodrin, aldrin,dieldrin, endosulfan, heptaclor, chlordane, toxaphene
Dizziness, ataxia,hyperexcitibility, malaise, seizures, myoclonic jerking, loss of consciousness, convulsions
Chlordecone, mirex Loss of memory, fatigue,tremours, loss of sperm
Low exposures (1950s to 90s)have few reported effects
1962‐ First major publicity that widespread indiscriminate use of pesticides could have profound effects on wildlife and perhaps humans1972 banned in US and subsequently in other countries
Plankton
Sediment
Chlorochemicalsfrom air, waste, sewerage and rivers
Bioaccumulation in sea, lakes and land
Possible egg shell thinning in birdsLoss of some raptors
USA production of DDT and BHC(106 pounds)
020406080
100120140160180
1945 1950 1955 1960 1965 1970
DDTBHC
Any production now in India and possibly China
• Problem was use of DDT in general pest spraying, for non health targets and on commercial crops especially in the US
• Amounts per/acre were much greater than used for mosquitos
• Effects assumed to be due to DDT were other insecticides like dieldrin
• Lovelock’s invention of electron capture GC (at MRC) allowed detection of minute levels Detection equals proven cause or association?
• Other insecticides eg malathion and pyrethroids replaced DDT especially where resistance occurring‐ unfortunately more expensive but good for business!
• Consigned to dustbin of failed chemicals detrimental to human health!!!
• Continues to be used in some areas of the world to the present day
Gradual banning of DDT across many parts of the worldConsumption of organochlorines (μg/day) by Arctic indigenous women (20‐40 years old) Kuhnlein et al 1995
Baffin Island
DDT 24.2
Chlorobenzenes 7.3
HCH 6.6
Chlordane 22.7
Dieldrin 4.9
Toxaphene 48.5
PCBs 44.6Sea mammals eaten (n=131)
Sahtu‐Dene/Metis
0.51
0.48
0.55
0.66
0.11
1.18
2.96Fish, duck, caribou (n= 92)
• ‘Dosage alone determines poisoning’ but in what?
• The use of all pesticides is a balance between desired effects in targets (pests) and inadvertent effects on wildlife or people
• Insecticides usually have very low toxicity to humans (compared with pests) and this, and restricted exposure, protects people against untoward effects
• In contrast, drugs are given at relatively high doses and it is genetic variation in response and ‘other factors’ that determine adverse effects in patients
• Can never guarantee absolutely no risk
• Where is the balance?PARACELSUS
(Philip Threophrastus Bombast von Hohenheim)1493‐1541
Carcinogenicty was one of the original main concerns highlighted by Rachel Carson
Poor evidence for mutagenicity
Liver tumours in mice at high exposures
Promotion of DEN etc tumours
Classicnongenotoxiccarcinogen?
Poor evidence for association with breast cancer
Poor evidence for association with liver cancer in
people
Threshold probably above exposure
levels
(1995)
• DDE , like vinclozolin and flutamide, modulates the expression of androgen receptor regulated genes in castrated male rats‐
• Exposure in utero can show changes in ano‐genital distances of rats
• Prostate development modulated by in utero or lactational exposure to DDE
• This added to concern about DDT
15 years ago the DDT story seemed to be dead
2001 Stockholm Convention on Persistent Organic Pollutants
DDT was to be included in list of chemicals to be bannedIntense lobbying by all sides but prevented inclusion
Data on regions where DDT had not been used for malarial in some countries suggested increase in deaths e.g Sri Lanka, Mozambique, Madagascar
2006 Agreed by WHO and USAID that could be used for malaria in restricted operations such as Indoor residual spraying
Effects which have been proposed as linked to endocrine disruptors in the environment including DDT
Males
Reductions in sperm counts and quality
Cryptorchidism and hypospadias
Testicular and prostate cancer
Females
Breast cancer
Polycystic ovaries
Children
Altered physical and mental development
Human health consequences of DDT use(Pine River Statement, Environmental Health Perspectives 2009)
• Little evidence for liver cancer risk but possibility of pancreatic cancer associated with diabetes link
• Little evidence of breast cancer link in many studies but perhaps if exposed prepuberty (Cohn 2007)
• Evidence for child growth rate and maternal DDT exposure is weak
• Weak evidence for association with urogenital birth defects e.g cryptorchidism/hypospadia
• Neurodevelopment impairment?
• Immune system impairment?
Data on human male effects ‐controversy
Prenatal DDT exposure and testicular cancer(Cohn 2005)
Limpopo area in SA. Little effect of DDT on semen, fertility and hormonal levels of vector control workers(Dalvie 2004)
Increased urogenital effects associated with mothers’DDT levels (Bornman 2009)
Sperm chromatin integrity affect by DDT (de Jager 2009)
No association of prenatal DDE with growth in boys In Mexico (Cupul‐Uicab 2010)
Considerable media reporting
Many acrimonious disagreements and accusations
Perception not facts• In toxicology this can be a big problem
• For instance, continual controversy about DDTuse in, say Zambia and Zulu Natal.
• View may change depending on your priorities and country eg Natal (SA) v USA or even between individuals.
• Accusations of sort of colonial chemophobia by US, Sweden and others
• In many ways it encapsulates our dichotomousviews of chemicals:
Don’t need nasty pesticidesv
We will starve and die of diseases without them
Opposing views
At the moment ‘unbiased’ opinion is that there is noconvincing evidence for detrimental effects on
humans of indoor residual spraying for DDT
The most recent WHO evaluation, DDT in indoor residual spraying: Human Health Aspects,
was conducted by an Expert Consultation and published in March 2011.
It concluded that in general, levels of DDT exposure reported in studies were below levels of concern for health. In order to ensure that all exposures are below levels of concern, best application measures must be strictly followed to protect both residents and workers.
WHO is working with countries and partners to strengthen capacities to plan, implement and evaluate integrated vector management, to develop, test and introduce chemical and non‐chemical alternatives to DDT, and to improve the use and management of insecticides for vector control.
WHO is working with the Secretariat of the Stockholm Convention to support Member States in complying with the obligations of the Convention, including reporting on the use of DDT for vector control.
Question. Would it have been better never to have introduced DDT?
Question. Should DDT be kept in the arsenal in the light of climate changes, evolving of insects etc, or just absolutely banned worldwide?
Risk‐benefit calculations very difficult to make
Arguments will undoubtedly continue whatever the evidence
Sometimes views of some scientific studies are perception not evidence
50 years on from Silent Spring
September 2012
Sunday Times
Guardian
Obviously, this needs checking out.
Is this an example of how millions of £/$ are spent downstream of a perceived problem?
Parkinsonism
If not careful the concept of chemical‐induced benefits is at risk
Can we afford that?
Economic benefitsDirect contribution of the downstream chemistry-using industries to UK GDP, 2007
0
20
40
60
80 AerospaceAutomotiveqConstructionElectronicsEnergyExtractionFarmingFood & drinkForestry & paperHealthHome & personal carePackagingPrintingTextilesWater
£billion
Source: Oxford Economics, EPSRC, RSC
Nature Sept 2012
• Post 1945 over use and poor regulation had profound effects on the distribution of chemicals in the environment and biosphere
• Silent Spring brought public and political attention to this and set in motion controlling and health regulations still with us today
• However, with increasing scientific data risks have been more carefully assessed and concepts of toxicity have changed
• All assessments must be based on the best scientific informationavailable and not on perceptions or dubious evidence
• Sometimes there is a view that all chemicals are toxic even atincredibly low levels and that we do not need them
• We do, probably more than many people accept
LegacyThanks
Chris Curtis(MRC LSHTM)
SMITH, A.G. (2012) DDT and other chlorinated insecticides, in Mammalian Toxicology of Insecticides (Ed. T. Marrs) Royal Society of Chemistry..
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