Pesticides

Mechanism of action of glyphosate

Blocks amino acid pathways /Protein synthesis e.g tryptophan

Shikimic acid pathway

EPSPS enzyme inhibitor

LD50

Lethal dose 50%. Dose that kills 50% of test population.

Measures Acute toxicity only

WHO LD 50 classification for pesticides acute toxicity

WHO LD 50 classification for pesticides acute toxicity

1a = extremely hazardous, < 5mg/kg

1b = highly hazardous, 5-50mg/kg

2 - moderate 50-2000mg/kg

3- slightly hazardous 2000-5000

U - unlikely - more than 5000

WHO classification does not take chronic low dose into account.

True

Classification system of pesticides

Type e.g. insecticide, herbicide

Toxicity - LD 50

Chemical composition e.g. organophosphate, carbamate, pyrethroid

Inert and active ingredients must be reviewed

True

Chronic health effects of pesticides

Neuro - parkinson's

Pysch- ADHD, anxiety

Resp - Asthma

Malignancy - leukemia

Pesticides are Neurotoxic, carcinogenic, mutagenic, teratogenic, respiratory and endocrine disruptors

True

A highly toxic pesticide with low exposure may pose less risk than a low-toxicity pesticide with chronic exposure.

True

Low toxicity glycophoshate chronic exposure is possibly higher risk than acute exposure to parathion

True

Who are the vulnerable groups

Pregnant

Breastfeeding

Children

Organophosphates have minimal bioaccumulation and environmental persistence

True

Paraquat

Oxidative Stress/ROS/Redox cycling

Ground water contamination

Bio-accumulation

Paraquat lung fibrosis,hepatotoxic, renal toxic

No antidote

Organophosphates: mechanism of human toxicity

Inhibits acetylcholinesterase enzyme at synapes

Phosphorylation of serine hydroxyl groups of the enzyme forming and OP-ACHe complex. Loss of an alkyl group(ageing) with time leads to irreversibility against oxime reactivation

Accumulation of acetylcholinesterase in the autonomic nervous system and central nervous system synapses

Overstimulation of acetylcholine receptors.

Exhaustion at synapses

Paralysis

Key elements of pesticide risk assement

Type of pesticides including it's chemical composition and active and inert ingredients

Concentration, frequency, duration of exposure

Individual susceptibility such as age, genetics

Symptoms of chronic OP exposure

Anorexia, malaise,weight loss

Neurobehavioral

Dermatitis

Cancer

Glyphosate health effects

Low acute toxicity

Chronic toxicity is a concern - IARC 2A - probably carcinogenic in humans , sufficient evidence in animals

**GENOTOXIN/DIRECT DNA DAMAGE

**ENDOCRINE DISRUPTOR

associated with increased risk.

Hepatic, renal, endocrine disruptor, non Hodgkin's lymphoma and breast ca

Muscurinic effects

Salivation

Lacrimation

Urination

Defecation

Gastrointestinal distress Emesis

Miosis

** Parasympathetic effects

Nicotinic effects

Cardiac Para and sympathetic effects - tachycardia, high BP

NMJ:

Skeletal somatic motor effects - fasciculations, tremors, muscle weakness paralysis

CNS ACH receptor effects

Confusion, headaches, seziures, coma and respiratory depression.

Respiratory muscurinic effects

Bronchospasm, wheeze,secretions

10 GHS TOXICITY HEALTH HAZARD

1. ACUTE TOXICITY

2. SKIN CORROSION/IRRITATION

3. EYE IRRITATION/INJURY

4. RESPIRATORY AND SKIN SENSITISATION

5. GERM CELL MUTAGENICITY

6. CARCINOGENICTY

7. REPRODUCTIVE TOXICITY

8. STOT - SINGLE

9. STOT- REPEATED

10. ASPIRATION

ENVIRONMENTAL PATHWAYS

SOIL, WATER, AIR POLLUTION

BIOACCUMULATION

GROUND WATER CONTAMINATION

IMPACT ON BEES, NON TARGET ORGAN SPECIES

BIOLOGICAL EXPOSURE MONITORING

MONITORING THE INTACT CHEMICAL OR METABOLITE IN BODY TISSUE OR FLUIDS

BIOLOGICAL EFFECT MONITORING

MONITORING THE BIOCHEMICAL OR PHYSIOLGICAL(intensity)EFFECT WITHIN THE HUMAN BODY

(EARLY REVERSIBLE ADVERSE EFFECTS)

EXPOSURE MONITORING STEPS

AMBIENT/AIR MONITORING

BIOLOGICAL EXPOSURE MONITORING

BIOLOGICAL EFFECT MONITORING

DIAGNOSIS OF OCCUPATIONAL DISEASE AND SCREENING

Cholinesterase monitoring conditions

Plasma vs Whole blood vs Red Cell

Valid Baseline

• 2-3 months no exposure

• 2 tests, three days to 2 weeks apart

• Agree within 15-20%

Cholinesterase interpretation (Biological effect monitoring)

HCS regulations > 30% drop from baseline significant exposure

Cholinesterase decline: Actions to take

if > 20% drop from baseline for plasma or rbc — reassess work activities

if > 30% drop from baseline for red cell — remove from exposure, > 40% drop in plasma —remove from work

**REMOVAL INCLUDES NO EXPOSURE TO CATEGORY 1 AND 2 PESTCIDES!!

AND RETURN ONLY IF AT 80% OF BASELINE

BIOLOGICAL SAMPLE FOR PARAQUAT

URINE

Cholinesterase interpretation

Valid individual baseline

Red Cell - Chronic exposure, red cells, nerve endings/ nervous system effects, interindividual variability, genetics, anemia

plasma(pseudo/butyryl) - recent or acute exposure, liver synthesis, liver disease, alcohol, pregnancy, genetics

Whole is the composite of both

Carbamates

reversible inhibition of acetylcholinesterase.

Can be assessed with both rbc and plasma cholinesterase. Note the quick recovery of bche even during transport of sample

Don't use pralidoxime

Copper containing Pestcides

Molluscs, fungi, algae, bacteria

Boats, sewers

Human teratogen

Dermal effects(WEAK SENSITISER)

Pyrethoids

Common houselhold

Unknown effects - ? neurodevelop, reproductive and cardiovascular disease, parkinsons

Mechanism of Actions

Glycophosphate - protein/amino acids, shimikate pathway

Dicamba(auxin) - growth hormones

Atrazine - Photosynthesis, endocrine disruptors

Paraquat- ROS, mitochondria

Organophosphates chronic

Weight loss, anorexia, vision, neurobehavioral

Other subacute: neuropathy, intermediate syndrome

WHO LD 50 CLASSIFICATION ALIGNS WITH GHS ACUTE TOXICITY, BUT NOT CHRONIC HEALTH EFFECTS OF LOW DOSE EXPOSURE

TRUE

PESTICIDE CLASSIFICATION

• TYPE OF PEST E.G. INSECT, RODENT, HERB/WEED

• TOXICITY - LD 50 CLASSES (EXTREME- SLIGHYLY HAZARDOUS)

1A,B - EXTREME, HIGH <5, 5-50

2- MODERATE - 50- 2000

3- SLIGHT >2000

• CHEMICAL HERBICIDES - ORGANOPHOSPHOROUS VS TRIAZINE VS QUAT VS AROMATIC E.G. PARAQUAT, DICAMBA

Organophosphate poisoning

Cholinergic syndrome

Plasma cholinesterase in Emergency department

Decontamination, abc, atropine and pralidoxime

Ageing

Time dependent irreversibility of the organophosphate acetylcholinesterase complex