Environmental Chemistry

Chapter 7:Pesticides

Copyright © 2007 by DBS

Contents

• Organochlorine Insecticides• Toxic Effects – Dose-response relationship• The Distribution of Environmental Pollutants• Organophosphate and Carbamate Insecticides• Herbicide, triazines, 2,4-D, Agent Orange

Background

• Birth defects due to exposure to synthetic chemicals

• Toxicity to mammals and birds• Carcinogenic effects• Xenoestrogenic effects

Gt. Lakes cormorant with crossed bill

Pesticides- Insecticides- Herbicides- Fungicides

Major use is agriculture

80-90% of US households have at least one synthetic pesticide

Insecticides – growing cotton

Herbicides – growing corn and soybeans

Pesticide regulation to date has not paid enough attention to the protection of health

ES&T Article

Organochlorine Insecticides

• Stable:

Against degradation (inert to both hydrolysis and oxidation)

• Hydrophobic:

Very low solubility in water, non-polar

• Lipophillic:

High solubility in hydrocarbon-like environments (fatty materials, organic matter)

• Toxicity:Relatively high to insects but low to humans

1 of the ‘dirty dozen’ listed by UNEP as POP’s…

• Known carcinogen• HCB used as a fungicide for cereal crops,

now being phased out• 99% of Americans have detectable levels

of HCB

POP’s

Phase out of POP’s by the 2004 Stockholm Convention

Organochlorine InsecticidesOrganochlorines In the Environment

• Over 217,000 contaminated sites have been identified by EPA. - An estimated 500,000 tons of dioxin contaminated soil alone is in need of treatment.

• Chlorinated phenols and organochlorines enter the environment as emissions from manufacture, incineration, use as a wood and leather preservative (Creosote) and biocide. - find their way into soil, sludges and sediments)

• The scale and complexity of remediation sites pose problems in applying common treatment processes such as bioremediation

• Incineration is effective, but can produce harmful chemicals during incomplete combustion. Projected cost is also high ($1200/ton).

Concentration Units

• ppm, ppb, etc. (assumes ρ = 1.00 g mL-1)

1 mg L-1 = 1 ppm

1 μg L-1 = 1 ppb

1 ng L-1 = ppt

ppm 1000 10 / 10 x g/g 0.001 = OH g 10

pollutant g 1000 =

OH g 1000

OH L 1.00

mg 1000

pollutant g 1.00 OH of /Lpollutant mg 1000 66

26

2

22

Question

Convert 0.04 μg L-1 to ppm and ppb

0.04 μg L-1 = 0.04 ppb

0.04 ppb x 1 ppm = 4.0 x 10-5 ppm 1000 ppb

Organochlorine InsecticidesDDT

• Prepared by Zeidler in 1874, insecticidal activity discovered by Müller in 1939

• Hailed as miraculous during its use in WWII• Found to be effective against malaria (carried

by mosquitoes) and typhus (carried by lice)• Saved lives of millions of people• Its effectiveness led to overuse in agriculture

– resistance• Now banned in most countries for agricultural

use

DDT

2 planar rings

2 tetrahedral carbons

Para (1,4)

Ortho (1,3)

Meta (1,1)

para-dichlorodiphenyltrichloroethane

p, p’-isomer

Organochlorine InsecticidesAdvantages of DDT

Advantages:• Stability• Persistence of insecticidal action - Low vapor pressure and low solubility in

water gave protection for weeks to months• Cheap to manufacture

• Moderate mammalian toxicity (Rat LD50 100 mg kg-1)

• Broad spectrum of activity

His

tory

of D

DT

‘elixir of death’

Organochlorine InsecticidesMode of Action of DDT

• Pesticides block vital metabolic processes

Other compounds with similar shape may be activeSimilar compounds with different shape are less likely to be active

‘Molecular wedges’ - DDT works by virtue of its shape - wedges into the insect nerve channel

Organochlorine InsecticidesMode of Action of DDT

• The size of the apex (-CCl3 group) corresponds to the size of a hydrated sodium atom

• Affects nervous system• DDT dissolves in lipid membrane of nerve cells• Interferes with normal AXONAL CONDUCTION – apex opens ion channel• Prolonged influx of sodium ions causes the nerves to fire repeatedly and this

causes death of the insect

Dichlorodiphenyldichloroethene, DDE

• DDE is a metabolite of DDT. Also produced slowly during the degradation in the environment

• Greatly affected bird population

• DDE interferes with the enzyme that regulates the distribution of calcium….leads to thin eggshells

DDT

- HCl

Endocrine disrupter (‘gender bender’ agent)

DDT dehydrochlorinase

DDE in Body Fat

Solubility in fat and animal tissue has caused accumulation of DDT and DDE in birds, fish and humans

DDT is now banned in most industrialized countries (circa 1970)

BUT 106 tonnes dispersed world-wide

Lake Ontario Salmon

Tissue levels in N. American wildlife began to decline 10 yrs after ban

Species at risk have recovered

DDE in Body Fat

DDT and DDE in breast milk

Which is more persistent: DDT or DDE?

Estimate the half lives of each

Concentrations have also declined in humans…

Noren and Meironyte, 2000

Question

The fat content of breast milk is ~ 4.2 g / 100mL

Calculate the mass of DDE ingested by a typical breast fed infant in 1972 upon consuming 250 mL.

From Fig. 7-2 concentration of DDE in breast milk was 2500 ng g-1 fat

Mass DDE in 250 mL milk = 250 mL x 4.2 g fat / 100 mL x 2500 ng DDE / g fat

Mass DDE in 250 mL milk = 26250 ng = 26 g

Accumulation of Organochlorines in Biological Systems

Measure of lipophilicity:

Partition Coefficient = concentration o solute in octanol

concentration of solute in water

Kow = [S]octanol/[S]water

e.g. KOW > 106

Strong tendency to partition into lipids

Accumulation of Organochlorines in Biological Systems

Bioconcentration factor, BCF

BCF = concentration of solute in organism

concentration of solute in water

Taking octanol as model for fat:

BCF KOW x % by weight of fat

(assumes fatty tissues have reached equilibrium)

For DDT

log KOW = 6 orKw= 1000000

BCF for DDT lies20000 - 400000

Hence KOw can be used to predict BCF

Higher the KOw morelikely chemical is boundto organic matter in soiland fatty materials

Biomagnification

A chemical whose concentration increases along a food chain is said to be biomagnified

DDT concentration in Lake Ontario Trout

Biomagnification results from asequence of bioaccumulation steps

Biomagnification

25 ppm of fat in the fatof the Cormorants

2 ppm of DDT inNeedlefish

0.5 ppm of DDT in thefat of minnows

0.04 ppm of DDT inPlankton

0.003 ppb of DDT inLong Island seawater

Question

Fish (5.0 % body fat) taken from a particular lake were tested and found to contain 200 ppm DDT in their tissues.

Determine the concentration of DDT in this lake.

From Table 7-2 Log KOW = 6.2, KOW = 106.2

BCF = KOW x (% body fat/100)

BCF = 1.6 x 106 x (5/100) = 7.9 x 104

BCF = concentration in fish / concentration in lake

Concentration in lake = 200 / 7.9 x 104 = 2.5 x 10-3 ppm = 2.5 ppb

DDT Analog(molecular shape)

1. Non-persistent 2. Doesn’t accumulate3. Forms water soluble compounds4. Toxic to insects, non-toxic to mammals – birds + mammals have

enzymatic detoxification pathway

LD50 = 6000 mg kg-1

Other Organochlorine Insecticides

• Toxaphene:

Mixture of hundreds of similar substances (produced from chlorinated camphene- pine tree product) was widely used after DDT ban in 70s

• Toxaphene is extremely toxic to fish• Restrictions were placed in 1982

and a total ban in 1990

Spread of Toxaphene in N. America from SE cotton states

Chlorinated Cyclohexane

(Lindane - 1 of 8 isomers are active)

Agricultural and health care uses (c.f. warfarin)

Used to treat scabies and head lice

Cyclodienes (Banned)

Series of fully chlorinated cyclic hydrocarbons containing a chlorinated endomethylene bridge

Chlordaneb. 1988

Heptachlorb. 1988

Aldrinb. 1974 Dieldrin

b. 1974

Endrin(isomer)b. 1974

[O]

Mirexb. 1978

Extremely effective against fire ant

Other cyclodienes

Endosulfan

Banned in EU, regulated in US

(Not on UN list due to reactivity)

LD50 <100 mg kg-1

One of the more toxic pesticides in use

Confirmed xenoestrogen

Doses as low as 35 mg kg-1 have been documented to cause death in humans

Under consideration for ban

Principles of Toxicology

• Toxicology – study of the harmful effects of chemicals on living organisms

– Animal studies

– Epidemiology – health history of selected groups

• Toxicology studies the relationship between dose and effect, almost all substances can be toxic under the right conditions

‘The dose makes the poison’

Principles of Toxicology

• Acute toxicity:

– Sudden and severe exposure

– Rapid onset of symptoms

• Chronic toxicity:

– Continuous, long-term exposure

– Relatively low dose

– Cancer, birth defects, neurological damage

Same chemical may show both effects

e.g. skin irritation vs. cancer

Toxic EffectsDose-Response Relationships

• Animal tests are acute exposures at high doses due to time constraints

• Results are extrapolated down to environmental levels

Typical dose-response curve

Response is usually death

Toxic EffectsDose-Response Relationships

• Effects at the low end cannot be seen clearly on a linear scale

Typical logarithmic dose-response curve

NOEL – no observable effects level

Toxic EffectsDose-Response

Relationships

The dose of the substanceadministered in toxicity testsis usually expressed as themass of the chemical usuallyin milligrams per unit of testanimal’s body weight(usually kg)

LD50 – does that is lethal to 50 % of the population

The smaller the LD50 value,the more potent the chemical

Question

If a dose of 0.1 μg is sufficient to kill a mouse, what mass would be fatal to you?

What average level of substance would have to be present in drinking water for you to receive a fatal dose in one week?

Ratio mass human : mouse = 200 : 1Mass that would kill you = 200 x 0.1 μg = 20 μg

2 L water d-1 x 7 d w-1 = 14LFor fatal dose 20 μg / 14 L = 1 μg L-1 = 1 ppb

The Dirty DozenOCP US

pesticide use ban

Approx. LD50 rat oral

(mg kg-1)

IARC (W.H.O.)Category

Aldrin 1974 50 3

Dieldrin 1974 100 3

DDT 1970 100 2B

Endrin 1974 3 3

Chlordane 1988 100 2B

Heptachlor 1988 100 2B

HCB 1966 10,000 2B

Mirex 1978 1000 2B

Toxaphene 1990 50 2B

International Agency for Research on Cancer - 1: carcinogenic, 2A: Probably, 2B: possibly, 3: insufficient data

Environmental testing

• Experiments with test animals are used to determine how carcinogenic a compound is, take many years

• The simple Ames test can be used fairly rapidly to distinguish compounds likely to be human carcinogens

Environmental testing

• Development of new pesticides:

– Low Acute toxicity towards non-target species

– Metabolism studies to establish breakdown pathways

– Physiochemical testing to determine distribution in environment

– Residue studies to determine levels in treated crops

– Ecological testing to determine impact on non-target species

Risk AssessmentTo perform risk assessment it is important to know:

Hazard evaluation information (acute, cancer ???)Quantitative dose-response informationAn estimate of the potential human exposure to the chemical

The highest dose at which no observable effects level is called NOEL(expressed in terms of mg kg-1 body weight day-1)

To determine the threshold level for the most sensitive members of the human population, EPA uses Toxicity reference dose or RfD.(RfD is also referred as Acceptable Daily Intake or ADI)

RfD (or ADI) = NOEL/100 (divide by safety factor of 100)

If NOEL for a chemical is 0.01 mg/kg/day, the ADI or RfD for a 80 kg manwould be (0.01 mg/kg/day /100) x 80 kg = 0.008 mg

Environmental Fate

Over 95 % of sprayed pesticides reach a destination other than target species

Decreases biodiversity of the soil

Environmental Fate

Fate in soil is determined by:

1. Adsorption - Binding by soil is critical

2. Leaching

3. Volatilization

4. Uptake

5. Run off

6. Degradation

Environmental Fate

ADSORBED

DISSOLVED

MO DECOMPOSITION

LEACHING

CHEMICAL DECOMPOSITION

VOLATILIZATIONWORMS ETC.

PLA

NT

S

WATER TABLE

PHOTO DECOMP.

UPTAKE

RUN OFF

-

Environmental FateAdsorption

P

P

P

P

P

P

P -

1. Adsorption: To clay or organic matter:

Pesticide is bound to or adsorbed onto surface of clay, can be released as free or solvated pesticide

Equilibrium is influenced by:1) Nature of pesticide2) Water content3) Soil pH and temperature

--

--

- P

P

P

P

P

P

P

Environmental Fate

2. Leaching:

Lower solubility = slower leaching = greater persistence

3. Volatilization:

Influenced by chemical structure (V.P.) and atmospheric conditions

4. Uptake:

By plants etc.

Warm, moist conditions, acidic soil, high solubility = greater uptake

5. Run off / soil erosion:

Effect is greater with least adsorption, erosion caries particle away

6. Degradation:

Microbial, chemical and light induced

Distribution of Environmental Pollutants

• Chemicals distribute according to their physiochemical properties• ‘Fugacity’ = escaping tendency of a substance from a phase, it is

proportional to concentration in a given phase:

f = C Z

(Where f = fugacity, C = concentration, Z = fugacity capacity)

• To calculate fugacity, Z must be known (derived from physiochemical Properties)

• At equilibrium the fugacities of all phases are equal:

fair = fwater = fsediments = fbiota = fsoil …

(no net diffusion between phases)

Distribution of Environmental Pollutants

IMPORTANT!

Fugacities are equal, concentrations are not!!!

Distribution of Environmental Pollutants

Z is a fugacity capacity constant for the substance and the phase. Generally higher the Z value, the greater the tendency to accumulate in that phase…..analogous to equilibrium constant

For a given phase (x) fx = Cx/Zx Or Cx= fx .Zx

If total number of moles preset is is ntotal, and in phase x is nx

Cx = nx/Vx or nx =Cx.Vx ∴ nx= f.Zx.Vx

ntotal = f ΣZxVx

Or f = ntotal

ΣZxVx

Dimensions for a new world

Area 1 km x 1 kmAtmosphere: 6 km highWater column: 80 m deepBiota = 1 ppm by volume (density = 1000 kg m-3)Suspended sediment = 5 ppm by volumeBottom Sediment: 3 cm deep (active layer)

Z(Atmos) = ZA = 4.04 x 10-4 mol m-3 Pa-1

Z(Water) = ZW = 1.3 x 10-2 mol m-3 Pa-1

Z(Biota) = ZB = 374 mol m-3 Pa-1

Z(Sus. Solids) = ZSS = 1856 mol m-3 Pa-1

Z(Bot. Seds) = ZBS = 186 mol m-3 Pa-1

Question

Consider the distribution of 1 mole of trichlorobiphenyl in the six compartment world mentioned above,

Calculate:

(a) volume of each compartment

(b the fugacity (Pa) at equilibrium

(c) the concentration of tri CBP in each compartment

(d) the concentration of tri CBP in biota (mg/kg) (M = 257 g mol-1)

(e) the total amount (moles) of tri CBP in each compartment

(f) the distribution (%) among the compartments

(a) Volume

V(Atmosphere) = 6 x 103 x 1 x 103 x 1 x 103 = 6 x 109 m3

V(Water column) = 80 x 1000 x 1000 = 8 x 107 m3

V(Sus. Solids) = 5/106 x 8 x 107 m3 = 4 x 102 m3

V(Biota) = 1/106 x 8 x 107 m3 = 80 m3

V(Bottom Sediments) = 0.03 x 1000 x 1000 = 3 x 104 m3

(b) feq

Fugacity = n / ΣZxVx = 1 / ΣZxVx

ΣZxVx = ZAVA + ZWVW + ZSVS + ZBVB + ZBSVBS

= 2424000 + 1040000 + 742400 + 29920 + 5580000

= 9816320

f = 1 / 9816320 = 1.02 x 10-7 Pa

(c) C in each compartment

CA = f ZA = 1.02 x 10-7 x 4.04 x 10-4 = 4.12 x 10-11 mol m-3

CW = f ZW = 1.02 x 10-7 x 1.3 x 10-2 = 1.33 x 10-9 mol m-3

CSS = f ZSS = 1.02 x 10-7 x 1856 = 1.89 x 10-4 mol m-3

CB = f ZB = 1.02 x 10-7 x 374 = 3.81 x 10-5 mol m-3

CBS = f ZBS = 1.02 x 10-7 x 186 = 1.90 x 10-5 mol m-3

(d) Concentration (mg kg-1)

C(Biota) = 3.81 x 10-5 mol m-3

= 3.81 x 10-5 mol m-3 x 257 g mol-1

= 0.0098 g m-3 x 1 m3 /1000 kg (density biota)

= 9.8 x 10-6 g kg-1

= 9.8 x 10-3 mg kg-1

(e) Moles tri CBP

Atmosphere, nA = CAVA = 4.12 x 10-11 x 6 x 109 = 0.247 moles

Water, nW = CWVW = 1.33 x 10-9 x 8 x 107 = 0.106 moles

Sus. Solids, nSS = CSSVSS = 1.89 x 10-4 x 4 x 102 = 0.076 moles

Biota, nB = CBVB = 3.81 x 10-5 x 8 x 101 = 0.003 moles

Bottom Seds, nBS = CBSVBS = 1.90 x 10-5 x 3 x 104 = 0.570 moles

1.000 mols

(f) Distribution (%)

Atmosphere, 24.7

Water, 10.6

Sus. Solids, 7.6

Biota, 0.3

Bottom Seds, 57.0

100 %

Organophosphates and Carbamates

Organophosphate and carbamate insecticides are commonly used for small animals as flea and tick powders, sprays, foggers, shampoos, dips, and flea collars

They are also frequently used as household, garden, and farminsecticides.

Chlorpyrifos, parathion, diazinon, famphur, phorate, terbufos, and malathion are examples of organophosphates while carbofuran, aldicarb, and carbaryl, are carbamates. They are all marketed under a wide variety of trade names.

All OP/Carbamate insecticides are fat soluble and therefore are easily absorbed through the skin and then transported throughout the body. These chemicals kill insects and cause poisoning in animals by inhibiting the enzyme, acetylcholinesterase (AChE) which normally functions to degrade acetylcholine in nerve synapses. Inhibition of AChE in the nerves results in a buildup of acetylcholine (ACh) and overstimulation of ACh receptors.http://www.addl.purdue.edu/newsletters/1998/summer/organos.html

Organophosphate Insecticides

Consumption of organophosphatepesticides by various crops in the US

Non persistant:Decompose (hydrolyse) within days-weeks after the accumulation

Unlike organochlorins, organophosphates do not bioaccumulate

Not carcinogenic or teratogenic BUT have higher acute toxicity than organochlorine pesticides

Structurally all organophosphatepesticides contain a central pentavalent P atom, methoxy/ethoxy groups and R- group connected through oxygen or sulfur atom

Organophosphate Insecticides

• The organophosphates, e.g., parathion, are related to the nerve gases developed during World War II (sarin, VX etc.)

• They react irreversibly with the enzyme acetylcholinesterase, which is responsible for inactivating the neurotransmitter acetylcholine

• Some other examples:malathiondiazinonphosmet (Imidan®)chlorpyrifos (Lorsban®)

• Some of the organophosphates are very acutely toxic. Parathion, for example, is 30 times more toxic than DDT

• Each year organophosphates poison thousands of humans throughout the world, causing hundreds of deaths.

Carbamate Insecticides

Carbamate insecticides are inhibitors of acetylcholinesterase, but their action is reversible

Some examples:

carbaryl (Sevin®)aldicarb (Temik®)methomyl (Lannate®)

Features:These compounds are rapidly detoxified and excreted so their risk to warmblooded animals is less than the other agents we have looked at.They are degraded rapidly in the environment so persistence is not a problem. They are, however, a danger to many useful insects, especially honeybees.

Pesticides from Natural Sources

- Obtained from flowers, chrysanthemum- Paralyze insects but not strong enough to kill them- Synthetic pyretrins are called pyrethroids- Common ingredients in domestic insecticides

Mechanism of Action

Oganochlorines & Pyrethroids - Enzymes, axonal membranes (Na+, K+, Ca++, Cl-)

Organophosphates & Carbamates - excess acetylcholine

Herbicides

• Selective herbicide, effective in killing many broadleaf plants

• Replaces weeding

• Most widely used pesticide in USA

• Marketed under many different names: Weed-Bgon (Chevron), Fernoxone (ICI), and Weedone (Union Carbide), to name a few

• Over 30,000 tons of 2,4-D are utilized in the US each year

• Natural degradation in water is slow (6-170 days)

Pesticides in the Hydrologic System

Pesticide movement in the hydrologic cycle

About 1 billion pounds of pesticides areused each year in the United States tocontrol weeds, insects, and otherorganisms. About 80 percent of thisquantity is used in agriculture. Although theuse of pesticides has resulted in increasedcrop production and other benefits, it hasraised concerns about potential adverseeffects on the environment and humanhealth.

In many respects, the greatest potential forunintended adverse effects of pesticides isthrough contamination of the hydrologicsystem, which supports aquatic life andrelated food chains and is used forrecreation, drinking water, irrigation, andmany other purposes. Water is one of theprimary pathways by which pesticides aretransported from their application areas toother parts of the environment

HerbicidesTriazines

Atrazine is a selective triazine herbicide used to control broadleaf and grassy weeds in corn, sorghum, sugarcane, pineapple, christmas trees, and other crops, and in conifer reforestation plantings.

Most heavily used herbicide in US

Toxicity: Atrazine is slightly to moderately toxic tohumans and other animals. It can be absorbed orally,dermally, and by inhalation

Symptoms of poisoning: abdominal pain, diarrhea and vomiting, eye irritation, irritation of mucous membranes, and skin reactions

HerbicidesTriazines

• Mode of action– Blocks photosynthesis

• Side effects– Loss of sensitive plants– Suspected xenoestrogen (feminizes male frogs – EPA says insufficient data)– Suspected teratogen

• Underwent 10 year EPA review and concluded safe for use, currently banned in EU• Degradation

– Dechlorinated and detoxified by MO’s– Half-life is extended once it enters waterways

• Risk Assessment– BCF < 10– Low toxicity– Possible carcinogen

Pesticide Combinations Imperil Frogs2006

http://www.berkeley.edu/news/media/releases/2006/02/02_pesticides.shtml

UC BERKELEY – The pesticide brew in many ponds bordering Midwestern cornfields is not only affecting the sexual development of frogs, but is making them more prone to deadly bacterial meningitis, according to a new study by University of California, Berkeley, scientists.

These physiological effects combine with environmental disruptions to make the life of a frog seem like something out of a horror movie and are likely among the factors causing a decline in amphibian populations worldwide, the researchers said.

Herbicides

EPA Won't Restrict Toxic Herbicide Atrazine, 2004The EPA has decided not to limit one of the nation's most widely used weed killers, a chemical that, according to several recent studies, threatens human health and the environment. The October 2003 decision - which the EPA was required to make under a court-approved consent decree reached with NRDC in 2001 - will allow Syngenta, the main manufacturer of atrazine, and other companies to continue to sell the chemical in the United States with no significant restrictions.

Get to know the views of both sideshttp://www.nrdc.org/health/pesticides/natrazine.asp

http://www.epa.gov/oppsrrd1/reregistration/atrazine/

WASHINGTON, DC, February 21, 2005 (ENS) - The U.S. EnvironmentalProtection Agency (EPA) is illegally negotiating and brokering regulatoryagreements with pesticide manufacturers that are friendly to the industry,according to a lawsuit filed by the Natural Resources Defense Council (NRDC).

Herbicides Chloracetamides

Herbicides Chloracetamides

http://www.monsanto.com/monsanto/layout/products/

Monsanto remains the primary globalproducer of glyphosate, the activeingredient in Roundup® agriculturalherbicides.

Monsanto's herbicide productsinclude more than 90 glyphosatebasedherbicides globally, includingRoundup agricultural herbicides andRoundup branded turf and ornamentalproducts.

These products can be used to controlweeds on the farm, the golf courseand in home gardens, createsustainable agricultural systems thatpreserve top soil, help retain soilmoisture, and provide a valuable toolfor integrated pest managementprograms.

Herbicides Phenoxy Herbicides

Phenoxide ion is reactive towards R-Cl

C6H5O−Na+ + Cl-R → C6H5-O-R + NaCl

By employing R-Cl as Cl-CH2-COOH we can obtain phenoxy acetic acid

Commercial route to large scale production of herbicide 2,4,5-T

Acid-base reaction produces phenoxide ion

Herbicides Phenoxy Herbicides

Summary

The Precautionary Principle

Introduction of new chemicals should follow the precautionary principle

‘When an activity raises threats to the environment or human health, precautionary measures should be taken, even if some cause-effect relationships are not fully established scientifically’

How much contamination can be avoided?What are the alternatives?

How safe is safe?What level of risk is acceptable?