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BIO4101 – Pesticides and the environment
Pesticide Toxicity
BIO4101 – Pesticides and the environment
Measures of Toxicity
● Any chemical is toxic in the right dose – e.g. common table salt can kill a human – Therefore, almost all pesticides are toxic
● Toxicity: inherent capacity of a substance to produce injury or death of an organism
BIO4101 – Pesticides and the environment
Dihydrogen monoxide
● Death from inhalation ● Tissue damage from prolonged exposure ● Major component of acid rain ● Gas can cause severe burns ● Found in carcinogenic biopsies ● Associated with school-yard violence ● www.dhmo.org
BIO4101 – Pesticides and the environment
Measures of Toxicity
● Acute toxicity: toxicity due to short term exposure (24-96hr)
● Subchronic toxicity: toxicity due to a short term exposure (3-6 months)
● Chronic toxicity: Toxicity due to long term exposure (years, lifespan, generations)
BIO4101 – Pesticides and the environment
Laboratory toxicological studies Development of
regulatory options
Evaluation of public health, environmental, economic,
social, and political consequences of regulatory options
Extrapolation methods
Exposure characterization
ANALYSIS Effect
charactertization Epidemiology and population-level
studies
Measurements of exposure and
dose
Problem Formulation and Hazard Identification
Risk Characterization
DATA GATHERING RISK ASSESSMENT RISK MANAGEMENT
Identification of mitigation options
Research needs identified
Regulatory decision
Risk communication
Regulatory Process (PMRA)
BIO4101 – Pesticides and the environment
EXPOSURE TOXICITY TOXICITY
PROBABILITY
RISK
Assessment of hazard based on a
ratio of single deterministic exposure and toxicity values
Ranking of concerns in the
absence of specific exposure
information
Assessment of risk based on likelihood of exposure and/or
toxicity
TOXICITY EXPOSURE
Process of Risk Assessment
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BIO4101 – Pesticides and the environment
Health Risk Assessment (humans) ● Toxicity ratings based on
data from experimental animals – No data from humans except
accidental ● Usually expressed as LD50
(sometimes LC50) – Lethal dose (concentration) to
50% of experimental population
– Expressed as mg/kg (or ppm)
BIO4101 – Pesticides and the environment
Example: LD50 = 10 ● 10mg of pesticide applied to animals
weighing 1kg, it would kill 50% of experimental population
BIO4101 – Pesticides and the environment
Concentration Response of Fish to DDT
C
Concentration
LC50
99.9 99 90 70
100
30 10
1 0.1
Perc
ent m
orta
lity
BIO4101 – Pesticides and the environment
Same LD50 but Different Slopes Pe
rcen
t mor
talit
y B A
LC50 LC99
99.9 99
90 70
30 10
1 0.1
50
100
BIO4101 – Pesticides and the environment
Substances Considered Highly Toxic ● Oral Toxicity:
– Produces death in ≥50% of animal population upon administering 50mg orally per kg of body weight in a single dose
● Toxicity on Inhalation: – Produces death in ≥50% of animal population at dose
of 200ppm or less (continuous inhalation for 1hr or less)
● Toxicity by Skin Absorption: – Produces death in ≥50% of animal population (rabbits
only) at a dose of 200mg/kg (continuous contact for 24hrs or less)
BIO4101 – Pesticides and the environment
Hazard Ratings
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BIO4101 – Pesticides and the environment
Other Tests for Health Risk Assessment
● Mutagenesis tests ● Sub-chronic oral toxicity
– Objective: to find the No Observed Effect Level ● Multi-generation reproduction studies ● Teratology (foetal development) ● Chronic oral toxicity (over lifetime)
BIO4101 – Pesticides and the environment
Acute Oral Lethal Dose Toxin Type Amount for 70kg person Botulinus toxin Microbial 0.000000014 g Parathion Insecticide 0.14 g Nicotine Insecticide 3.7 g DDT Insecticide 8.1 g Caffeine Food 13.4 g Codeine Pharmaceutical 42 g 2,4-D Herbicide 42 g Malathion Insecticide 54 g Aspirin Pharmaceutical 95 g Atrazine Herbicide 126 g Salt Food 300 g Glyphosate Herbicide 350 g Sugar Food 3000 g
Table 49
BIO4101 – Pesticides and the environment
Guidelines ● Connotation of “highly toxic” does not
mean it is not used ● Therefore guidelines are provided (EPA,
PMRA) – Application procedure – Dosage – Ventilation – Exposure…
BIO4101 – Pesticides and the environment
Misuse of Pesticides
BIO4101 – Pesticides and the environment
PHI
MRL
0 2 4 6 8 10 12 Days after application
0.1
1.0
10
Con
cent
ratio
n of
the
pest
icid
e in
the
crop
(mg/
kg)
Residue Limits and Pre-Harvest Interval
Fig. 191
BIO4101 – Pesticides and the environment
PHI Variations in Dissipation Rates Food Pesticide Pest PHI (days) Celery Carbaryl Leafhopper 3 Corn Carbaryl Corn Borer 1 Lettuce Dimethoate Aphid 7 Pepper Dimethoate Aphid 30 Apple Captan Apple scab 7 Cherry Captan Brown rot 2
● Properties of pesticides and environmental conditions – Hydrolysis, photodecomposition, vaporisation
● Metabolism on surface and inside plant – Enzymes & micro-organisms
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BIO4101 – Pesticides and the environment
100
0 Dose
LOAEL NOAEL
Best-fitting dose- response model
Lower confidence interval on line
% o
f ani
mal
s re
spon
ding
No Observed Adverse Effect Level
BIO4101 – Pesticides and the environment
Acceptable Daily Intake
ADI (mg/kg) human = NOAEL (animal)
Safety factor (100)
From To Uncertainty Factor Average Sensitive human >10 Animal Human >10 Database inadequacies >10
US EPA guidelines
BIO4101 – Pesticides and the environment
Maximum Permissible Levels
MPL (mg/kg) food = ADI x 60kg
Food factor
Food Food Factor (kg/day) Vegetable/Fruit 0.4 Milk & products 0.5 Corn & products 0.2 Meat & products 0.2
For average North American
BIO4101 – Pesticides and the environment
For example: Endosulfan insecticide
MPL (mg/kg) fruit/veg = 0.0075 x 60kg
0.4 = 1.12 mg/kg
● This number is THE LAW ● It is inspected in the field by PMRA and elsewhere in
delivery chain, customs by CFIA ● Enforceable for all products produced and sold in the
country (even imports) ● Detected levels usually far below MPLs ● Detection tools by GC/MS sophisticated to ppm/ppb
BIO4101 – Pesticides and the environment
Transport and Fate in the Environment
Short distance Long distance Degradation
Photodegradation
Erosion
Biological degradation
Crop removal
Long distance transport of dust and vapor
Volatilization
DESORBED
Erosion
Runoff
Biological degradation Leaching
ADSORBED
SOIL Water table
Photolysis Transport of
residue in fish
Transport
Uptake Chemical
degradation
Uptake
Adsorption and exudation
Sedimentation
WATER Resuspension
Volatilization
Adsorption- desorption
Transport of residues in birds
Precipitation of rain and dust
AIR Precipitation of
rain and dust Dust storm
Spray drift
Fig. 158
BIO4101 – Pesticides and the environment
Bioaccum/magnification Potential ● 1) Amount available to organism from
environment – Persistence, transportability, dosage
● 2) Rate of intake by organism – Concentration in environment, quantity
organism consumes over time ● 3) Rate of elimination by organism
– Metabolism, rate at which metabolites produced, lipophilicity
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BIO4101 – Pesticides and the environment
Metabolic Degradation
Chemical bound as a terminal residues in
proteins, cellulose or lignin (only in plants)
Conjugated chemical
Detoxified chemical
(less toxic)
Chemical Phase-1 metabolism
Phase-2 metabolism
Phase-3 metabolism
Excretion
Excretion
Excretion
Fig. 130
BIO4101 – Pesticides and the environment
Enzymatic Detoxification
Binds to enzyme at the site of action and causes toxic effect
PESTICIDE
Enzyme for phase-1 metabolism
Enters organism
PHASE-1 Enzyme PHASE-2
OH
COOH
NH 2
HS
O-sugar
N-sugar
S-amino acid
COO-amino acid Fig. 131
BIO4101 – Pesticides and the environment
Effects of Lipophilicity
Water solubility
High Kd
Low Kd
Ads
orpt
ion
Fig. 160
Water solubility in µg/L (log scale)
Bio
mag
nific
atio
n in
fis
h (lo
g sc
ale)
Fig. 168
BIO4101 – Pesticides and the environment
Pesticide Breakdown ● Persistence = ability to resist breakdown ● Environmental degradation of pesticides
occurs principally via: – 1) microorganisms – 2) photochemical breakdown
BIO4101 – Pesticides and the environment
Microbial Degradation ● Diversity of microbial species in soil
allows for a wide variety of organic molecules to be catabolized
● Particularly bacteria and fungi ● Dependent on temperature, moisture, pH,
aeration, solubility of chemical
BIO4101 – Pesticides and the environment
Effects of pH on Adsorption in Soil
pH 3.5 6 9
Kd
Fore
st
Agr
icul
tura
l
Fig. 161
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BIO4101 – Pesticides and the environment
Microbial Degradation: metabolites
● Slight modifications in chemical structure can change persistence dramatically – e.g. 2,4-D and 2,4,5-T differ only by
chlorinated side group – 2,4-D is readily broken down but 2,4,5-T is
highly persistent
BIO4101 – Pesticides and the environment
Toxic Metabolites ● Intermediate or end-point metabolites
may be more toxic than originals ● The photochemical breakdown of
chlorinated compounds may lead to the production of dioxins – Polychlorinated dibenzodioxins (PCDD) – Lipophilic mutagens and carcinogenic
BIO4101 – Pesticides and the environment
2,4,5-T and 2,4-D with their Dioxins
C l C l
C l C l
O N a C l
C l C l
O C l
C l C l
C H 2 C O H O
O N a C l
C l C l +
O O
C l C l
C l C l
O C l C l C l
C l
C l C H 2 C O H O
N a O H Benzene 2,4,5-T
2,3,7,8,-TCDD Chlorinated Furan
Heat
C l 2 O H O H
C l
C l
O C l
C l
C H 2 C O H O
O H C l
C l
C l
O O
C l C l
O C l O
C l
C l C l
C l C H 2 C O H O
N a O H Phenol 2,4-D
2,8-dichlorodioxin
Heat
C l 2
N a O H Heat N a O H
1,3,6,8-TCDD
Fig. 173 Fig. 174
BIO4101 – Pesticides and the environment
Photochemical Degradation ● There exist sufficient energy in ultraviolet
component of sunlight (290-450 nm) to cause a number of chemical reactions: – Oxidation, reduction, isomerization,
elimination etc…
BIO4101 – Pesticides and the environment
Questions?