Glen Sampson

The Public DebateThe public perceives “pesticides” as a unique

class of chemicals more “dangerous” than chemicals in prescription

and over-the-counter medications more “toxic” than chemicals that occur naturally in

food and the environment.Pesticides are intentionally designed to be toxic

to plant, animal, or microbial pests just as antibiotic drugs are intentionally designed to be toxic to specific disease bacteria.

Many natural chemicals in our food supply can also be toxic to living organisms.

Conclusions drawn by the scientific communities represent their best professional judgment based on many years of education, research, and experience.

It is impossible to test or prove safety under every imaginable scenario.

However, the overall testing program is comprehensive;it examines the responses to pesticide levels much

higher than humans or animals would normally encounter.

The public is expected to place confidence in scientific and regulatory professionals

As a society we are ill-informed on the mandatory, comprehensive evaluation process that precedes the registration of every pesticide product.

a common misperception is that pesticides can be classified as “safe” or “not safe.”

No chemical either natural (produced by plants or other organisms) or synthetic (produced by man), can be determined completely safe.

The effort to develop conclusive evidence of safety is ongoing, but absolute safety can never be guaranteed.

ToxicologyToxicology is the scientific study of the

harmful effects of chemicals on living organisms: humans, animals, and plants.

Toxicological testing evaluates:whether short-term exposure to a pesticide will

produce acute effects (e.g., eye and skin irritation, death)

whether long-term, continual exposure will cause chronic effects (e.g., impaired liver function, reproductive abnormalities, cancer).

Understanding the biological mechanisms that underlie effects observed in animals allows toxicologists and risk assessors to predict the chances of harm to human populations exposed to the pesticide.

Consideration of exposure levels and effects produced at specific doses is essential in determining toxicity.

Pesticide ToxicologyFactors that influence the effects:

Toxicity of the chemicalDoseLength of exposureRoute of entry

Pesticide RiskToxicity

Ability of a chemical to cause injuryDepends on:

Dose Exposure

Risk – HazardProbability that harm will result from given use of a

chemicalDepends on:

Toxicity Exposure

Low Exposure - Low toxicity Low risk Low Exposure - High Toxicity Moderate risk High Exposure - Low toxicity Moderate risk High exposure - High toxicity High Risk

ExposureThe duration and magnitude of exposure

determine the severity of the poisoning. In other words, the increment of time during which exposure to the dose occurs (duration), plus the size and number of doses (magnitude) combine to determine the severity of the poisoning.

A pesticide will trigger an adverse response when a person is exposed long enough to a dose large enough to cause harm.

Toxicology ConcernsThe degree of hazard which the compound

(its metabolites) present to the spray operator, to consumers and to animals (domestic and others)Operator

Acute toxicitySkin and mucous membrane irritationSensitivity to repeated exposure

ConsumerShort term and long term studiesTeratogenicity, mutagenicity,

neurotoxicity, carcinogenicity, reproduction, immunosuppression, endocrine disruption

Effect of the Chemical on the AnimalSpecies-SpecificIndividual-Specific

Toxic effects can vary with the size, sex, age, and general health of the test animals.

Routes of ExposureThe site of exposure to the pesticide impacts

the rate of absorption into the bloodstream, as well as its distribution pattern.Ingestion or oral exposureInhalation or respiratory exposureDermal (through the skin ) or Ocular (through

the eyes)

Movement Within the Bloodstreamtransport of a pesticide within the body depends on

whether the pesticide is absorbed through the skin, lungs, or GI tract.

Uptake by Organs, Tissues, and CellsMetabolism Within Cells

Pesticides are subjected to chemical alterations by enzymes in the body. Metabolism takes place primarily in the liver.

Pesticide Storage Sites Within the BodyPesticides may accumulate in body tissues, proteins,

fat, and bone.Excretion and Elimination From the Body

Absorption

• Through skin, eyes, ear canals

• Most vulnerable areas

• eye

• groin area

• absorbs 10x faster than forearm

• 95% absorb through skin

Body Part Amount Absorbed

Eye 100%

Groin area 100%

Ear canal 47%

Scalp 32%

Abdomen 19%

Foot 14%

Palm of hand 12%

Forearm 9%

Inhalation

• Breathing in dusts, mists, fumes

Ingestion

• Through the mouth

• smoking, eating, licking lips, blowing out nozzles

Injection

• By veterinary needles, staples, nails,

• High pressure fluids forced under the skin

Dose-Response

The Swiss physician Paracelsus (1493-1541), the father of toxicology, believed the relationship between dose and response to be inseparable.

Paracelsus asked,“What is it that is not poison? All things are poison

and nothing is without poison. The right dose differentiates a poison and a remedy.”

The specific point on the dose-response curve where the more susceptible animals are first affected by a pesticide dose is termed the threshold level:

LOEL – the lowest dose that produces a measurable response in the most sensitive animals.

NOEL - “no observed effect level”

Toxicology Studiesall pesticide active ingredients and product

formulation containing the active ingredient undergo this testing.

Acute toxicity - how poisonous after single dose, short term exposureOral LD50Dermal LD50Inhalation LD50Eye irritationDermal IrritationSkin sensitization (allergy)Antidote

Toxicology StudiesChronic Toxicity -adverse effects of repeated

exposure over a long time.Short term

90 day oral 90 day dermal 90 day inhalation 1 year feeding

Long term 2 year chronic feeding Lifetime oncogenicity (tumors - benign or malignant)

Toxicological Studies

Toxicology StudiesReproductionTeratogenicity (birth defects)Mutagenicity (altering genes)CarcinogenicNeurotoxicityImmunosuppresionEndocrine disruptionExposure studies

Reproduction studiesThe effects of the pesticide on male and

female reproductive processes, from egg and sperm production and mating through pregnancy, birth, nursing, growth and development, and maturation.

The studies are conducted through two generations of offspring—that is, three generations including the parents.

Measuring ToxicityAcute

LD50 (mg/kg body weight)LC50PPM (1ppm=1mg/L)

ChronicNo uniform measure for mostCholinesterase levels

Organophosphates - irreversible (antidote - atropine) Carbamates - reversible (antidote - atropine)

Classification of PesticidesLD50

50 or less Very ToxicBetween 50 and 500 ToxicBetween 500 and 5000 Moderately

toxic > 5000 Low

Toxicity

Examples of Acute oral LD50Nicotine 53DDT 87Paraquat 120Caffeine 192Fenitrothion 2502,4-D 600Table salt 4000Glyphosate 4320Chlorothalonil 8000Bt 20,000

Reversible vs. IrreversibleReversible

if its effects subside or disappear when exposure ends.

Irreversibleadverse pesticidal effects persist even when

exposure is eliminated

Other Effects of ToxicityLocal vs. Systemic

Immediate vs. Delayed

Additive vs. Antagonistic vs. Synergistic

Toxicity Characterized by EffectDeath is the ultimate toxic effect, occurring when critical

bodily functions are altered or inhibited. Irritation is observed when a pesticide affects cells of the

skin or eye; Skin sensitization is an allergic reaction following

multiple exposures over a period of time. The initial exposure “sensitizes” the person, and subsequent exposures cause the individual to react to the chemical by developing a “rash.”

Mutagenicity (also called genotoxicity) results from a change in the genetic material of a cell. a gene mutation that changes the DNA genetic code; and a structural mutation that causes structural chromosome

damage. Disruptions in genes or chromosomes can lead to diseases (including cancer) and birth defects. A mutagen is of concern when it damages egg or sperm cells, enabling the defect to be passed on to successive generations.

Toxicity Characterized by EffectTumours (also called neoplasms) are abnormal

growths of tissue; benign or malignant

4 types of malignant tumours Leukemias are cancers of red blood cells, certain

white blood cells, and the tissues that produce these cells.

Lymphomas are cancers that affect organs of the lymphatic system, such as lymph nodes.

Sarcomas are cancers of connective tissues such as bone, muscle, and cartilage.

Carcinomas are cancers of the internal or external epithelial tissues.

Pharmacokinetics: Absorption,Distribution, Excretion, and MetabolismDetermine how a pesticide moves into, gets distributed

within, and finally leaves the body. The studies are designed to address several major areas

of interest:The quantity of pesticide absorbed;The distribution of the pesticide in tissues, organs, blood,

and urine;The identity, quantity, and location of the major metabolites;The ability of the pesticide to be stored in tissues and

organs;The routes of excretion; The differences in the absorption, metabolism, excretion,

and distribution of a pesticide when animals are administered single doses versus repeated doses, or small doses versus large doses.

Hazard AssessmentNo observable effect level - NOEL

The highest dose that will cause no effect

Acceptable Daily Intake - ADI1/100 of the NOEL

Maximum Residue Limit – MRLMaximum allowable residue in food or drinking waterTakes into account the toxicological acceptability of

residue arising from practical use

Hazard assessment of 2,4-DAt high doses - 40-150 mg/kg body weight per

dayPeripheral nerve damage, birth defects, fetal

toxicityNOEL

20 mg/kg body weight/dayADI

1/100 (0.01) NOEL - 0.2 mg/kg body wt/day Not an environmental mutagen Not found to be carcinogenic in lab studies

Mandatory Incident ReportingRequired by Pest Control Products Act.Any adverse incident must be reported,

investigated and results published in the public registry

http://www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/index-eng.php#rd-dh

Incident Report 2011-2572An incident report was submitted to the PMRA by

Syngenta Crop Protection Canada on June 24, 2011 an unknown product containing the active ingredient

paraquat. Involved the death of an adult male who had

accidentally ingested some herbicide containing 37% paraquat.

The individual was landscaping at his home and mistook a container of the product for a water bottle.

He was hospitalized for five days and treated for renal failure and pulmonary fibrosis. On the fifth day he was removed from life support and passed away.

Incident Report 2011-2572The effects reported are highly consistent with

paraquat poisoning. Based on the estimated volume ingested, the individual likely received a lethal dose of paraquat.

The specific product implicated in this incident is not known. There are no products currently registered in Canada containing 37% paraquat, and products containing paraquat are not permitted to be sold to the general public.

This incident resulted from the accidental ingestion of a pesticide. The individual affected should not have had access to the pesticide involved and it is not known how the product was obtained in this case.