Toxicity Categories of Herbicides

Fred Fishel UF/IFAS Agronomy Dept. &

Director UF/IFAS Pesticide Information Office

Outline

• History – Early chemical weed control in the U.S.

• EPA requirements for toxicity testing

• Acute toxicity

Paracelsus (1493 – 1541) Swiss physician, botanist, astrologer, alchemist, etc.. "All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.“ Or, more commonly "The dose makes the poison."

Myth or Reality?

• Herbicides have been seen as toxins that poison plants and are equally harmful to the applicator.

Poison Ivy Control

• “Iron or copper sulfate used at a rate of ½ to ¾ pound to 1 quart of water, and arsenate of soda used at the rate of 1 ounce to 6 quarts of water”

• “For applications to be made on the soil for the purpose of destroying root parts, common salt may be used – 8 ounces/ft2” – 10.9 tons per acre

New Jersey Agricultural Experiment Station Circular 206 (1927)

Poison Ivy Control

• “Arsenate of soda is a dangerous poison…”

• “Under no circumstances should he (applicator) permit any of the material to get into his mouth or nose. This danger can be overcome by wearing a small wet sponge or fine piece of cloth over the nose while working the sprayer.”

New Jersey Agricultural Experiment Station Circular 206 (1927)

Poison Ivy Control

• “Oils of various kinds are also excellent weed exterminators. Kerosene or waste oil from garages…”

• “… oils of this kind should not be used around buildings.”

New Jersey Agricultural Experiment Station Circular 206 (1927)

Poison Ivy Control

• “Sulfuric, hydrochloric and nitric acids are positively destructive to the plant.”

• “…care must be exercised in their use, for they will burn clothing and flesh instantly. They will also result in blindness if spattered into the eyes.”

New Jersey Agricultural Experiment Station Circular 206 (1927)

Poison Ivy Control

• “Sodium arsenite, an effective chemical for poison ivy destruction, is not ordinarily purchased in ready-made form.”

• “A chemical formula which has proven valuable is 4 ounces of caustic soda and 8 ounces of white arsenic dissolved in 1 pint of water.”…”The water should be added slowly to the mixture and stirred constantly because of the heat developed.”…”About 1 pint to 10 ft2 would seem a fair estimate.” – 544.5 gallons/acre

New Jersey Agricultural Experiment Station Circular 206 (1927)

Sulfuric Acid Spray: A practical means for the control of weeds

• Used in Italy, France, Spain, Scandinavian countries for a number of years

• 2 to 15% solution of sulfuric acid used, depending on species and size, which costs between $0.60 and $4.50 per acre at 200 gallons solution per acre

• 200 gallons solution per acre will control most weeds

University of Arizona Experiment Station (1928)

Killing field bindweed with sodium chlorate

• Salt – 20 tons per acre

• K.M.G. weed killer (sodium chlorate plus calcium chlorate) – 100 pounds in 100 gallons water per acre

Kansas State Agricultural College Circular 136 (1928)

The Control of Weeds

• According to San Joaquin County Agricultural Commissioner data, 2 men with power sprayer cover 10 acres in 8 hours with 3,000 gallons oil. – Costs: oil at 3.75 cents per gallon

– Labor: $10 per day

– Total cost per acre including depreciation: $12.25

California Agricultural Extension Service Circular 54 (1931)

The Control of Weeds

• Chlorates are fire hazard (oxidizer) – “Clothing, chaff, straw, sacks, wood, etc., covered with

chlorate will readily ignite when dry.”

– “Ashes from smoking tobacco, a match thoughtlessly lighted, or a spark from an exhaust pipe of spray equipment may set a fire.”

– Men should not work alone when using chlorates.

California Agricultural Extension Service Circular 54 (1931)

The Control of Weeds

• Chlorate is particularly combustible with sulfur

• Accidents more likely after spraying and clothes dry – “This danger can be eliminated by having two pairs of

overalls.”

– “Operators of chlorate sprays sometimes wear rubber boots.”

California Agricultural Extension Service Circular 54 (1931)

The Control of Weeds

• Carbon disulfide – Highly explosive, volatile

– Soil injections only

– Cost: $260 to $400 per acre

• Arsenicals – “ALL DEADLY POISON TO LIVESTOCK AND HUMAN

BEINGS.”

California Agricultural Extension Service Circular 54 (1931)

• 2,4-D

• 2,4,5-T + 2,4-D = Agent Orange

The Control of Weeds

Toxicity • The ability of a poison to produce adverse effects

– Range from slight symptoms such as headaches to severe symptoms like coma, convulsions, or death

– Most toxic effects are naturally reversible and do not cause permanent damage if prompt medical treatment is sought

– Some cause irreversible (permanent) damage

Type Number of Exposures Time for symptoms to develop

Acute usually 1 immediate (minutes to hours)

Chronic more than a few one week to years

Toxicity Testing

• All new pesticides are tested to establish the type of toxicity and the dose necessary to produce a measurable toxic reaction

• Testing is done with animals and plants • Generally in mice, rats, rabbits, and dogs • Results are used to predict the safety to humans

Toxicity Testing

• Toxicity tests are based on two premises 1. Information about toxicity in animals can be used to

predict toxicity in human 2. Exposing animals to large doses of a chemical for

short periods of time can predict human toxicity from exposure to small doses for long periods of time

• Both premises have been questioned

Toxicity Testing

Purdue Pesticide Programs

Toxicity Testing (Dose Response)

NOEL = no observed effect level

LOEL = lowest observed effect level

Plateau = level where there’s no increase in response

Purdue Pesticide Programs

Toxicity Testing (Dose Response)

• No single dose-response curve can describe the entire range of toxicological responses exhibited by an experimental animal

• End points may be indirect indicators of toxicity such as observations in behavior or food consumption patterns

• The dose required to produce a given effect (end point) may vary, depending on the pesticide

Toxicity Testing (Dose Response)

• Data used to develop dose-response curves are unique to the test animal

• Dose-response curves may differ depending on the route of exposure: oral, dermal, or inhalation

Testing Requirements for Registration

Efficacy: • High degree of biological

efficacy • Broad spectrum of efficacy • Good plant compatibility • Low risk for resistance

development

User friendly: • Low acute and chronic toxicity • Good formulation qualities • Easy to handle • Low application rate • Good storage stability

Environmental profile: • Low toxicity to non-target

organisms • Sufficient degradation in soil • Low leaching • No significant residues in food

and animal feed

Economy: • Favorable cost/benefit ratio • Competitiveness • Broad spectrum of uses • Patentability

The Innovative

Product

The registration cost is $152 - $256 million per product – 1 in 139,000 make it

EPA Data Requirements

• Product chemistry – Physical and chemical characteristics (pH, stability,

flammability)

• General toxicology

• Wildlife and aquatic toxicity – Avian (aquatic and terrestrial species)

– Aquatic species (freshwater and estuarine invertebrates, fish, and mollusks)

EPA Data Requirements

• Nontarget insect toxicity (honey bees)

• Environmental fate (hydrolysis, metabolism, photolysis, leaching, field/aquatic dissipation)

• Residue chemistry – Metabolism in plants and animals

– Magnitude of residues in crops, processed foods, meat/milk/eggs

EPA Data Requirements

• Spray drift

• Worker exposure and re-entry – Foliar and soil dissipation

– Dermal and inhalation exposure

– Mixer/loader and applicator

– Re-entry personnel

Acute Toxicity Results Dictate Label Language

• Signal words

• Precautionary statements

• First aid statements

• Personal protective equipment

• Application methods

• Re-entry intervals

Acute Toxicity

• Acute toxicity: ability to do systemic damage as a result of a one-time exposure to relatively large amounts of the chemical

• Signal words on the label are based on acute toxicity of the pesticide

• Acute toxicity may be measured as: – Acute oral (through the mouth)

– Acute dermal (through the skin)

– Acute inhalation (through the lungs or respiratory system)

Acute Toxicity

The signal word is generally assigned based on the pesticide's inhalation, oral or dermal toxicity, whichever is the most toxic.

Acute Toxicity

The commonly used term to describe acute toxicity is LD50

• Acute toxicity tests measure mortality following a single exposure

• LD50: dose that’s acutely lethal to 50% of the test population of animals

Toxicity

• LD50 is commonly expressed as mg of toxin per kg of test animal body weight (mg/kg)

• LD50 of 500 mg/kg is less toxic than LD50 of 5 mg/kg

• 1 kg = 1,000 g = 2.2 lb

• 1 mg = 0.001 kg = 0.0022 lb

• Mg/kg = ppm

• 1 ppm = 1 inch in 16 miles or 1 minute in 2 years

High Toxicity = Low LD50

Toxicity

• LD50 values for a single chemical can vary by: – Test species

– Route of exposure Dichlorvos LD50

Oral LD50 (rat) 75 mg/kg

Dermal LD50 (rat) 15 mg/kg

Inhalation LC50 (rat) 1.7 ppm

Oral LD50 (rabbit) 10 mg/kg

Oral LD50 (pigeon) 23.7 mg/kg

Oral LD50 (dog) 100 mg/kg

Oral LD50 (pig) 157 mg/kg

Dichlorvos is an insecticide commonly used in household pesticide strips

Categories of Acute Toxicity

LD50 LD50 LC50

Categories Signal Word Oral mg/kg Dermal mg/kg Inhale mg/l Oral Lethal Dose1

I Highly toxic DANGER, POISON

0 to 50 0 to 200 0 to 0.2 A few drops to a teaspoon

II Moderately toxic

WARNING 50 to 500 200 to 2,000 0.2 to 2.0 Over a teaspoon to one ounce

III Slightly toxic

CAUTION 500 to 5,000 2,000 to 20,000

2.0 to 20 Over one ounce to one pint

IV Relatively non-toxic

CAUTION (or no signal word)

5,000+ 20,000+ 20+ Over one pint to one pound

1Probable for a 150 pound person.

Acute Toxicity

Acute Toxicity

Substance Acute oral LD50 (rat)

Nicotine 9

Caffeine 192

Bleach 192

Aspirin 200

Tylenol 338

Codeine 427

Table salt 3,000

Product (active ingredient)

Acute oral LD50 (rat)/signal word

Aquathol K (endothall potassium salt)

182/DANGER*

Reward (diquat) 886/CAUTION

Weedar (2,4-D) >1,000/DANGER*

Captain (copper carbonate)

>1,000/CAUTION

Renovate (triclopyr) 2,574/DANGER*

Tradewind (bispyribac-sodium)

4,111 (males)/CAUTION

Habitat (imazapyr) >5,000/CAUTION

Galleon (penoxsulam) >5,000/CAUTION

Clearcast (imazamox) >5,000/CAUTION

Clipper (flumioxazin) >5,000/CAUTION

Rodeo (glyphosate) 5,600/CAUTION

Sonar AS (fluridone) >10,000/CAUTION *Corrosive

Acute Toxicity Determines PPE Toxicity Category by Route of Exposure of End Use Product

Route of Exposure

I Danger II Warning III Caution IV Caution

Dermal Toxicity or Skin Irritation Potential

Coveralls worn over long sleeved shirt and long pants Socks Chemical- resistant footwear Gloves

Coveralls worn over long sleeved shirt and long pants Socks Chemical- resistant footwear Gloves

Long sleeved shirt and long pants Socks Shoes Gloves

Long sleeved shirt and long pants Socks Shoes No minimum

Inhalation Toxicity

Respiratory protection device

Respiratory protection device

No minimum No minimum

Eye Irritation Potential

Protective eyewear

Protective eyewear

No minimum No minimum

• The LD50 determines: Signal word Precautionary statements First aid statements

Routes of Exposure • Oral

– Dietary – Drinking water – Hand to mouth

• Dermal – Occupational – Residential – Recreational

• Inhalation • Eyes

Parathion Absorption Through Skin Body region Percent relative absorption

Forearm 8.6

Palm of hands 11.8

Ball of foot 13.5

Abdomen 18.4

Scalp 32.1

Forehead 36.3

Ear canal 46.5

Genitalia 100

Pesticides Most Often Implicated With Illnesses

Rank Pesticide or pesticide class

Child <6 years Adults and those

6 – 19 years Total*

1 Organophosphates 700 3,274 4,002

2 Pyrethrins and pyrethroids

1,100 2,850 3,950

3 Pine oil disinfectants 1,336 903 2,246

4 Hypochlorite disinfectants 808 1,291 2,109

5 Insect repellents 1,081 997 2,086

6 Phenol disinfectants 630 405 1,040

7 Carbamate insecticides 202 817 1,030

8 Organochlorine insecticides

229 454 685

9 Phenoxy herbicides 63 387 453

10 Anticoagulant rodenticides

176 33 209

Source: American Association of Poison Control Centers (1996)

Toxicity

• Chronic toxicity: harmful effects produced by long-term exposure to pesticides – Carcinogenesis

– Teratogenesis

– Mutagenesis

– Blood disorders (hemotoxic effects)

– Endocrine disruption

– Reproductive toxicity

Mitigation Strategies: Aquatic Herbicides

• Examples: – Do not swim/drink from treated water for 5 days

– Do not eat fish from treated water for 10 days

– Do not use water for irrigation of food crops

Summary

• Risk = ƒ(Toxicity x Exposure)

• Follow the label – PPE requirements (lower exposure = lower risk)

• Don’t get complacent

Fred Fishel UF/IFAS (352) 392-4721 weeddr@ufl.edu

Thanks for your attention!