Toxicology Flashcards
Science of the action of medicines, their nature, preparation, administration
and effects
Pharmacology
One of the oldest branch of pharmacology;
Traditionally, thought of as the science of poisons affecting human lives;
The study of harmful action of chemical on biological tissues
Toxicology
Toxicology involves understanding of
Chemical reactions and interaction of biological mechanisms
Toxicology includes studies on the
metabolism and excretion of poisons;
action of poisons;
treatment of poisoning;
systematic chemical and physical analyses and diagnosis
biocidal agricultural chemical are collectively known as;
the largest group of poisonous substances used today;
intended to prevent, destroy, repel, or mitigate ant pests
Pesticides
kinds of pesticides
Insecticides;
miticides or acaricides;
nematicides;
fungicides;
bactericides;
rodenticides;
molluscicides
forced entomologist to study the properties of insecticides
the necessity to use insecticides properly
the most numerous and valuable pesticides
insecticides
a subdiscipline of medical technology;
determine tolerance levels of pesticides in man;
specifically concerned with the selective toxicity of chemical to insects without affecting mammals
insecticides toxicology
interested in the elucidation of the mechanism of action of toxicants
insecticide toxicologist
a discipline based on the study of a particular group of toxic chemical rather than on their effects in a particular group of animals
insecticide toxicology
process by which a chemical crosses the various membrane barriers of a living organism
absorption
refers to the ability of a poison to produce adverse effects;
capacity of a substance to produce injury
toxicity
poisons work by altering normal body functions
type of toxicity;
based on the number of exposures and the time of symptoms to develop
Acute toxicity;
Chronic toxicity
short term exposure and adverse effects occurs within a relatively short period of time
acute toxicity
high acute toxicity may be deadly even if a very small amount is absorbed
acute toxicity is determined by applying different concentration of a pesticide to lab animals and mortalities are taken at predetermined levels
dose of concentration resulting to 50% mortality of the test population
LD50 or LC 50
the smaller the value of ld 50 the more toxic is the compound
3 routes of application on where acute toxicity values are generally determined
Acute oral;
Acute dermal;
Acute inhalation
a requirement for a new compound introduced into commerce;
important in poisons which could be swallowed;
oral toxicity
Very important if it is possible that skin contact can result from the normal use or handling of the compound;
Assessed thru exposure of skin of experimental animals to the pesticide material and then observing resultant mortalities expressed as LD50
Dermal toxicity
Very important because of occupational exposures by virtually all handlers of pesticides;
Determined by vaporizing the pesticide in an enclosed chamber;
Result is expressed as LC50 or the concentration in ambient air that causes 50% mortality
Inhalation toxicicty
The single dose of a toxic substance administered by any route, other than by inhalation, that causes the death of 50% of an animal population
LD50 (Lethal Dose 50)
The lowest dose of a substance reported to have caused death in humans or animals
LD Lo (Lethal Dose low)
The concentration of a material in the air that kills 50% of a group of test animals when administered as a single exposure in a specific time period (usually 1 hr)
LC50 (Lethal Concentration 50)
This is due to a repeated or long-term exposure and happens over a longer period of time;
refers to harmful effects produced by long-term exposure to pesticides;
Symptoms are exhibited only after prolonged exposure which may take years;
No way to determine which one elicited the effect if a person had been exposed to several pesticides
chronic toxicity
Main organs that are evaluated in the determination of chronic toxicity
liver and kidney
what does chronic toxicity affect
reproduction;
weight;
behavior;
formation of tumors;
teratogenic effect;
delayed neurotoxicity
the amount available for interaction with metabolic
processes or biologically significant receptors after crossing the relevant;
Total amount of a substance administered
does
proportion of a population that demmonstrated a defined effect in a given time or dose
response
time taken for the reactant concentration to fall one-half its initial value
half life
ability of an organism to show less response;
refers to the acquired resistance
tolerance
pesticides = ____ % in total agrochemical inputs
18.2
insecticides = ____ % of the total pesticides trade in the country
56
crop that gets the largest gross of insecticide application
rice
most commonly used insecticides
organophosphate, carbamates, pyrethroids
term for mixed pesticides
cocktail
most used chemical among the organophosphates
endosulfan
was misused as a molluscicide for golden snail control when organotin compounds became scarce due to regulation
endosulfan
year on when the endosulfan was severely restricted
1993
first recorded use of insecticides
2500 BC by sumerians
earliest insecticides
inorganic sulfur (1000 BC);
Arsenic (900 AD);
lead arsenate, calcium arsenate, sodium arsenate, sodium fluoride, cryolite, and boric acid;
nicotinoids (17-18);
natural pyrethroids (18-19);
rotenoids (19);
pyrethrum and derris (1750 - 1880 europe;
a source of rotenone
derris (controls leaf eating caterpillars)
pyrethrum is from
chrysantheum flowers
Nicotine
firs used:
isolated by:
synthesized by:
1763
posselt and reimmann (1828)
pictet and rotschy (1904)
Effective against aphids and other soft-bodied insects;
high concentration from leaves of Nicotiana tabacum and N. rustica.
nicotine
the first rotenoid to be used;
from plant species in the family leguminosae
rotenone
he isolated rotenone and named it NICOULENE
geoffroy (1892)
named rotenone and isolated it from derris (Derris elliptica, D. malaccensis, D. philippinensis, Lonchocarpus utilis, L. uruca and Tephrosia vogelli)
nagai rotenone (1902)
derived from flowering plants Chrysanthemum, family Asteraceae
natural pyrethroids
contain the highest concentration of the insecticidal metabolite pyrethrin
C. cinerariaefolium and C. coccineum
based from pyrethrum compounds consisting of 6 esters
synthetic pyrethroids
discovered ddt
paul muller (1939(
controlled louse vectors and mosquito vector of malaria
ddt
was the most widely used pesticide in the world until 1960s
ddt
discovered ddt to be hazardous
rachel carson (silent spring0
number of countries where ddt is banned
86
Discovery of organophosphorous compounds designed as nerve gases chemical warfare led to the development of the organophosphorous insecticides (Ops
Continuous efforts to find more selective insecticides with lower mammalian toxicity than the Ops led to the production of
carbamates
newer groups of insecticides with improved efficacy and novel mode of action and broader selectivity
PYRETHROIDS AND NEONICOTINOIDS
are synthesized to produce the new generation insecticides such as Bt, pyrethroids , spinosads and pheromone
BIO- RATIONAL PESTICIDES
year of first commercial planting of gmo corn
1996
contain the highest concentration of pyrethrin;
where natural pyrethroids are derived from
Asteraceae: Chrysanthemum cinerariafolium and C. coccineum
EPA (US)
Environmental Protection Agency
FPA (PH)
Fetilizer and Pesticide Authority
3 separate activities in insecticide production
synthesis;
formulationl;
dilution
Formulation of product in liquid or solid in the same place or sent to a formulator
Formulating the pesticides
FORMULATING THE PESTICIDE
a.i. mixed with carrier suited to the type of formulation
Liquid pesticide: 200-liter drums for large scale, 120liter jugs for small-scale, smaller-amber colored or polyethylene plastic bottles of 125 ml – 1 L for much smaller scale; dry formulations: 250 g sachets to 10 kg
Dilution
the final product consists of 0.5 to 1 percent of the original a.i
Why regulate pesticides?
To provide man and the environment with
maximum possible protection from potential adverse effects
Why regulate pesticides?
To provide man and the environment with
maximum possible protection from potential adverse effects
Duties of chemical company
Identify uses of pesticide;
Test its effectiveness of it in different environmental conditions;
Provide data on: chemical structure, production, formulation, fate persistence, environmental impact;
Submit registration data package
registration data package includes
- Studies on acute, chronic, reproductive and developmental toxicity to mammals, birds and fish
- Pesticide’s environmental fate, degradation and translocation to other sites
- Ecological studies on its harmful effects to, an on nontarget plants and animals
continued use of a pesticide is supervised by the
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) (1997)
European Food Safety Authority (Europe)
Regulates all registration matters and for the Prior Informed consent (PIC) procedures
FPA
international information exchange sponsored by the UN to assist countries throughout the world in decisions on whether to allow import of chemicals of concern including pesticides
Prior Informed Consent (PIC)
A form with data regarding the properties of a particular substance, providing relevant health and safety information on hazardous chemicals
Material SAfety Data Sheet (MSDS)
MSDS includes
Physical data, toxicity health effects, first aid, reactivity, storage, disposal, protective equipment for handling and specific country and supplier
Benefits of insecticide use
- Higher yield, lower losses, higher quality products, more uniform products and higher profit for the producers
- Higher quality with less wastage, lower cost, uniform product for ease of handling for the processors
- Lower risk of bio-contamination for the caterer
- More uniform products with fewer blemishes and increased sales for the retailer
- Higher quality products, possibly lower costs for the consumer
- Eradication of vectors by those concerned in public health
- Best treatment for structural pests
Consequences of insecticide use
- Inappropriate use caused problems of toxicity to nontarget organism
- Residue on crops or environmental contamination
- Development of resistance
- Need for frequent subsequent application
- As persistent organic pollutant
- Pesticide misuse causes health impacts in farming communities
list of pesticide health impacts in farming communities
-increased mortality
-dermal contamination
-depression in cholinesterase level
- fetal abnormalities
-spontaneous abortion among pregnant women
-allergic reaction
FPA enacted policies in banning use of hazardous pesticides as early as in the
1980s
pesticides that cannot be brought into the PH
Banned pesticides
Pesticides that can only be used only under specified conditions
Restricted
used as an alternative to organotin
GAS
process of determining the biological activity of a substance and comparing its effect with those standard preparations on a test organism
Bioassay
test within an organism
In vivo
test outside the body
In vitro
Types of bioassay
Injection method;
Topical method;
Immersion method;
residual contact toxicity test;
leaf dip method;
antifeedant test;
diet incorporation test;
in plant assay test;
high throughput screening;
basic screening technique where a test fluid is injected into the blood stream of a common large insect using a tuberculin syringe and a calibrated micrometer head;
eliminates the differences in surface activity, penetrability and other properties of the body wall, digestive tract or the respiratory system of different insects
Injection method
Insecticide is applied topically to the outer surface of the insect using a micropipettor or a special syringe;
used to measure the relative toxicity of test compounds, particularly contact poisons.
Topical methods
also known as“larval dip” method;
another form of topical application using diluted solution of formulated insecticide ;
suited for small bodies insects
immersion method
involves coating a thin film of diluted solutions of formulated insecticide onto a leaf, filter paper, glass or plastic surfaces and insects are released unto the treated surface and thus exposed to the insecticide.
residual contact toxicity test
closely simulates field exposure condition;
Insects are released on the treated leaf surface and allowed to feed.
leaf dip method
developed by Schwinger and Kraus in 1983 which involves painting half the nether surface of a leaf with methanol – dissolved compounds and the other half with methanol only and insects are introduced to the treated leaf and allowed to feed
antifeedant test
incorporates the toxicant in the artificial diet;
used to assess effects of insect growth regulators (IGRs)
diet incorporation test
use to assess the effects of systemic insecticides on sucking insects;
can be used to assess crystal Bt tocxins on larvae with slight modifications
in plant assay
designed to screen efficiently hundreds or thousands of chemicals in a short period of time with limited manpower;
ideal for aquatic pests
high throughput screening
did the idea of probit analysis
Chester ittner bliss (1934)
Wrote thr probe analysis
David Finney (1952)
Could be plot against the logarithm of the dose to obtain a more or less straight line
Probit or Probability unit
the preferred statistical method in biological analysis;
transforms the sigmoid dose-response to a straight line
Probit analysis
Compounds designed primarily to kill insects;
derived from Latin suffix -cida = “killer”
insecticides
a situation in which a population, after having been suppressed rebounds to numbers higher than before suppression occurred;
consequence of insecticide resistance and destruction of natural enemies
Pest resurgence
insects previously considered not pests being released control and become major pest
secondary pest outbreak
how do insecticides enter the insects body
oral route;
dermal route
Exert toxic action only after being introduced into the alimentary canal
stomach insecticides
Cause toxicity when insects come in contact with them AND TRANSPORTED to site of action via the circulatory system
contact insecticides
contact insecticides penetrates the insect’s exoskeleton through
respiratory system;
exoskeleton;
soft membrane;
other pathway system
TRANSLOCATED TO THE UNTREATED PARTS IN CONCENTRATIONS THAT MAKE TRANSLOCATION SITES TOXIC
systemic insecticides
formal process by which insecticides are named
insecticides nomeclature
3 designated names of insecticides
approved common name;
trade name, brade name;
chemical name
is the US common name for insecticides are officially selected by the __________ and approved by the _____________
Entomological Society of America;
American National Standards Institute and the International Organization for Standardization
Name given by the manufacturer or formulator
Trade name
Provides a description of the insecticides structure
chemical name
chemical name is formed by following the _______ developed by the __________
“Definitive Rules for the Nomenclature of Organic Chemistry”;
International Union of Pure and Applied Chemistry
The quality of being toxic or poisonous;
Degree or intensity of virulence of a poison;
refers to a substances inherent poisonous potency
Toxicity
TO understand toxicity and how to use insecticides efficiently and safely, we must first understand their
Mode of action
involves all the ANATOMICAL, PHYSICAL AND BIOCHEMICAL RESPONSES to a chemical, as well as its FATE in the organism
Insecticides mode of action
ALL INSECTICIDES BLOCK METABOLIC PROCESSES IN INSECTS, BUT DIFFERENT COMPOUNDS DO THIS IN DIFFERENT WAYS.
major insecticide groups based on mode of action
nerve poison;
muscle poison;
Physical toxicants
affect the insect’s nervous system mostly as narcotics, axonic poisons and synaptic poisons
nerve poisons
nerve poison that has a mostly physical mode of action;
Fat-soluble, lodge in fatty tissues including nerve sheaths and lipoproteins of the brain
narcotics
nerve poison that has a mostly physical mode of action;
Fat-soluble, lodge in fatty tissues including nerve sheaths and lipoproteins of the brain
narcotics
act primarily by interrupting /disrupting normal axonic transmission of the nervous system;
induce changes in axonic membrane permeability,
causing repetitive discharges resulting to: Convulsions Paralysis Death
Axonic poisons
type of nerve trans. conveying an impulse from an arrival point along the axon to another neuron, muscle, or gland, or from a receptor cell
Axonic transmission
an elongated extension of the cell body that transmits nerve impulses to other cells
Axon
arise from the flow of positive sodium and potassium ions thru the cell membrane, CAUSING DEPOLARIZATION.
nerve impulses
creates a wave of action potential (the impulse) that passes quickly down the axon.
Depolarization
work by keeping the sodium gates OPEN
Pyrethroid and DDT insecticides
act by interrupting synaptic transmission
Synaptic poisons
type of impulse trans. which is mainly chemical
Synaptic transmission
junction or gap between neurons and other cells
synapse
COMPLETED REACTION
from a sensory neuron thru an interneuron and directly to a motor neuron
REFLEX REACTION
forms and transmits an impulse across the synapse (gap) to the next cell
acetylcholine
returns the synapse to the resting state;
breaks down the acetylcholine
acetylcholinesterase
Inhibition causes BUILD-UP OF acetylcholine and a MALFUNCTION of the transmitting system, which leads to symptoms of:
restlessness;
hyperexcitability;
tremors and convulsions;
paralysis;
death
Inhibition of acetylcholinesterase by carbamates is reversible but not so with organophosphates.
other synaptic poisons
nicotine;
nicotine sulfate;
neonicotinoids;
spinosyns;
Formamidines
Poison by mimicking acetylcholine at the synapse
neonicotinoids
causes death by affecting the enzymes involved with other chemical transmitters
Formamidines
Poison that have direct influence on muscle tissue
Muscle poisons
disrupts the excitable membrane of muscle resulting to increase in 02 consumption followed by flaccid paralysis and death
ryanodine
Block metabolic process by physical rather than chemical means;
refined oil applied to surface of water;
dormant oil applied to trees;
abrasive dust
Physical toxicants
a stomach poison and an abrasive dust
boric acid
this material is relatively pure form of the insecticidal compound that comprises the active ingredient
technical grade material
mixed with TGM to make the insecticide convenient to handle and easy to apply
auxiliaries
Toxic compound responsible for the insecticidal activity
active ingredient
why are insecticides formulated in many forms
For storability ;
ease of application;
safety to the applicator and environment;
improved biological afficacy
factors to consider in choosing the right formulation
content of active ingredient;
ease in handling and mixing;
safety of the applicator;
nature of pest to be controlled;
efficacy against pests;
habitat of pests;
type of application equipment available;
risk of drift and runoff;
possible crop injury;
cost
components of insecticide formulations
active ingredient;
inert materials;
synergists
Most important component in a formulation;
Substance that prevents, repels or kills the pest
Ai
Other materials added to the formulation that helps in the application of the a.i.
Inert materials
types of inert materials
solvent;
carriers or diluents;
adjuvant;
preservatives;
perfume;
coloring materials
A liquid that dissolves the a. i.. It distributes the solute evenly throughout the solution
Solvent
liquids or solids added to a formulation to aid in the delivery of a.i.
carriers or diluents
chemical that improves toxicity and effectiveness.
Adjuvant
Types of adjuvant
Surfactants;
Stickers;
Extenders;
Plant penetrants;
Drift control adhesivesl
Defoaming agents;
Thickeners;
physically alter the surface tension of a spray droplet;
enlarge the area of pesticide coverage
Surfactants
Surfactant that carry a negative charge
Anionic surfactant
Surfactant that carry a positive charge
Cationic surfactant
Surfactant that have no charge
Non-ionic surfactant
examples of anionic surfactants
sodium n-dodecylbenzene sulfonate, decenyl succinate
Examples of cationic surfactants
Dodecyltrimethylammonium bromide, alkylbenzene quaternary ammonium halide
Examples of non-ionic surfactants
Tween 20, Sterox SK
materials that increase the adhesion of solid particles to target surfaces.
Sitckers
function like stickers by retaining pesticides longer on the target area, slow down evaporation and inhibit degradation by sunlight
Extenders
enhances penetration of some pesticides into plants.
Plants penetrants
improve on target placement of the pesticide spray by increasing droplet size
Drift control adhesives
is a function of a droplet size
dirft
tend to drift away from target site
Fine drops (100 microns or less)
can reduce or eliminate the foam or frothy “head” in sprayer tanks produced by the formulation
Defoaming agents
increase the viscosity ( thickness) of spray mixtures
thickeners
slowing this down is very important in systemic pesticides
evaporation
Antioxidants to slow down decomposition of a.i
Preservatives
Gives a pleasant odor to the pesticide
Perfume
Added to differentiate them from non-toxic ones
Coloring materials
chemicals that do not possess insecticidal property but enhance the efficacy of the a.i
Synergists
Examples of synergists
piperonyl butoxide (PBO)
piperonyl butoxide (PBO) increases the effectivity of
pyrethrin
List of conventional insecticide formulations
Wettable powder (WP) Dustable powder (DP) Granules (GR) Solution concentrate (SL) Emulsifiable concentrate (ES) Suspension concentrates Seed treatments Fumigants Baits
list of new generation insecticides formulations
Oil-in-emulsion (EW)
Suspoemulsion (SE)
Controlled-release formulation
Water-dispersable granules (WG)
Gelatinized fluids
Ultra-low-volume (ULV) liquids
Microencapsulated product (ME)
Water-soluble packets (WSP)
Attractants
rate of penetration of any material thru the insect cuticle is dependent on the
Nature of the cuticle as a membrane;
nature of the material
SINGLE LAYER OF CELLS CALLED EPIDERMIS BOUNDED ON THE INSIDE BY A BASEMENT MEMBRANE AND ON THE OUTSIDE BY THE CUTICLE
insect integument
layers of cuticle
epicuticle;
exocuticle;
endocuticle
Outer surface impregnated by lipids or wax and maybe overlaid by grease or heavy layer of wax, or a thick layer of cement;
Epicuticle
oppose the entry of insecticides to a certain extent
cement and wax layers
hard, dry and rigid and as such is insoluble with water
exocuticle
contains chitin which is embedded in a matrix of arthropodin (water soluble protein)
endocuticle
secretes wax
dermal glands
the cuticle is perforated by
pores
the cuticle is a two-phase system: OUTER PHASE (EPICUTICLE) = HYDROPHOBIC INNER PHASE(EXO- & ENDOCUTICLE)=HYDROPHILIC
traverses the two phases of the cuticle;
extends form the hypodermis to the epicuticle
lilophylic elements
very important in the penetration of the insecticide to the insect’s body
texture of the epicuticle
greatly affects the rate of penetration
polarity of the insecticides
the epicuticle is _____ in nature
apolar
3 major factors affecting the amount of insecticide penetrating the insect body
- Lipid solubility or polarity of the insecticide
- Affinity of the compound for the cuticular components other than lipids ( protein, chitin)
- Solubility of the compound to the hemolymph
can enhance insecticide penetration
use of solvent
main channels of diffusion of the insecticides in the
presence of a solvent are thru the
hydrophilic elements
antity of the original active ingredient or its biologically -active transformation product which remains in or on a substrate after weathering factors have taken effect.
residues
more toxic metabolites
heptachlor epoxide from heptachlor; photodeildrin from deildrin; paraoxon from parathion; sulfoxide/sulfone from aldicarb
from heptachlor
heptachlor epoxide
from deildrin
photodeildrin
parathion
paraoxon
from aldicarb
sufoxide/sulfone
Factors affecting the rate of insecticides bbreakdown
chemistry of the insecticide2;
chemical and physical properties of spray additives;
chemistry of spray water;
environmental factors;
plant factors;
the largest environmental reservoir of insecticides
SOIL
Factors affecting fate of insecticdes in the soil
Soil type;
Moisture;
Temperature;
Cover crops;
Mode of cultivation;
Application and formulation
Residue characteristics of insectices in soils
Organocholorides;
Organophosphates;
Carbamates;
Botanicals
highly persistent in the soil
Organochlorines
breakdown in the soil is slow;
increased persistency in acidic soils
organophosphates
have soil half life of 7-28 days
carbamates
short persistence on soil
Botanicals
Process by which biological organisms increase their pesticide content in relation to their position in the food chain
Biological magnification or biological concentration
If a pesticide reaches bodies of water, e.g. lakes, it would tend to concentrate on the aquatic plants by
Simple differential affinity
EFFECTS OF ACCUMULATION OF PESTICIDES IN THE BODY OF BIOLOGICAL ORGANISMS
Death;
egg shell thinning;
degenerative liver lesions;
abnormal reproduction;
hypersensitivity
any substance or mixture of substances in food for humans and animals resulting from the use of a pesticide
pesticides residues
the maximum concentration for a pesticide residue resulting from the use of a pesticide according to GOOD AGRICULTURAL PRACTICE (GAP)
Maximum residue limit
GAP is recommended by
Codex Alimentarius Commission
he officially recommended or authorized usage of pesticides under practical conditions at any stage of products’ storage, transport, distribution, and processing of food, agricultural commodities and animal feed
Good agricultural practice
to less toxic forms or in some instances more toxic products
Degradation
into some ecosystems
TRANSFER/TRANSLOCATION OR BIOCONCENTRATIO
ENVIRONMENTAL ALTERATION OF INSECTICIDAL RESIDUES
Degradation;
Transfer/translocation or bioconcentration;
immobilization
Type of degradation
Microbial degradation;
sunlight degradation
microbes that degrades insecticides
Saccharomyces cerevisiae, Pseudomonas phaseolicola, P. cepaphia, Lactobacillus bulgaris, Trichoderma harzianum Aspergillus niger, Fusarium solani, Rhizoctonia solani
Compounds that facilitates transfer of light energy into receptor chemical
photosensitizers
Residue levels in man are affected by
race;
age;
food habits;
life style;
common health hazards form pesticide exposure
eye and skin irriitaiton;
asthma;
kidney and neurological disorders
severe cases of exposure may lead to
paralysis;
blindness;
death
undesirable effects of pesticides
Development of resistance;
destruction of non-target organisms;
pests resurgence;
secondary pests outbreak;
adverse environmental effects;
Dangers to human health
selection for insects that are genetically resistant to the chemicals
Development of resistance
situation in which a population after having been suppressed, rebound to numbers higher than before suppression occurred.
pest resurgence
resistance is a selection process
Monophagous pests develop resistance faster than polyphagous ones
Use of non-persistent pesticides leads to slower resistance
Pests with short life cycle develop resistance faster =
ways to avoid resistance
reduce pesticide application;
Spot application;
use NP pesticides;
encourage natural enemies;
Use of negatively correlated insecticides