Pesticide Toxicity Testing. Fred Fishel Professor, UF/IFAS Agronomy

Transcription

1 Pesticide Toxicity Testing Fred Fishel Professor, UF/IFAS Agronomy

2 Regulation Pre-1970 By U.S. Department of Agriculture and Food and Drug Administration Legal to use any registered pesticide for any pest even if site and pest were not on the label Fisheries, Wildlife, Parks, Forestry, public health and other affected persons not represented (Environmentalists)

3 Poison Ivy Control New Jersey Agricultural Experiment Station Circular 206 (1927) 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.

4 The Control of Weeds California Agricultural Extension Service Circular 54 (1931) 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.

5 Advancing Technology Paul Müller: DDT (1939)

6 Environmental Awareness Era Publication of Silent Spring, by Rachel Carson in 1962, created an awareness of pesticide misuse

7 Environmental Awareness Era Silent Spring Never advocated a complete ban of all pesticides Encouraged responsible and carefully managed use with an awareness of the chemicals impact on the entire ecosystem Advised for spraying as little as possible to limit the development of resistance

8 Environmental Awareness Era Silent Spring U.S. Secretary of Agric. Ezra Taft Benson in a letter to President Dwight D. Eisenhower: concluded that because Carson was unmarried despite being physically attractive, she was probably a Communist.

9 Environmental Awareness Era Rachel Carson: Silent Spring (1962) William Ruckelshaus: 1 st EPA Administrator Dec., 1970

10 Environmental Awareness Era FIFRA amended (1972) Essentially rewritten Mandates that EPA regulate the use and sale of pesticides Strengthen the registration process by shifting the burden of proof to the chemical manufacturer ( tests required to pass registration) Enforce compliance against banned and unregistered products Established an applicator education/licensing program Each state given authority to enforce

11 Food Quality Protection Act of 1996 Significantly amended FIFRA and FFDCA Emphasized safety for infants and children EPA adds 10x safety factor to tolerance settings for protection of infants and children

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

13 The Development of Sonar : Discovery : Environmental fate studies : C 14 nature in plants : Acute toxicology : Subchronic toxicology : Efficacy and use patterns for aquatics : C 14 soil metabolism studies : Chronic toxicity/oncogenicity studies : Residue studies in plants and irrigated crops : C 14 animal metabolism studies : Residue studies in fish, livestock, poultry, milk, and eggs : Avian, aquatic, and nontarget organism toxicity : Reproduction/teratology studies : Residue in potable water and mutagenicity studies EUP granted in 1980 and fully registered in 1985!

14 Toxicity The ability of a substance to produce adverse effects Range from slight symptoms such as headaches to severe symptoms like coma, convulsions, or death Type Number of Exposures Time for symptoms to develop Acute usually 1 immediate (minutes to hours) Most toxic effects are naturally reversible and do not cause permanent damage if prompt medical treatment is sought Chronic more than a few one week to years Some cause irreversible (permanent) damage

15 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

16 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

17 Toxicity Testing Purdue Pesticide Programs

18 Toxicity Testing Purdue Pesticide Programs NOEL = no observed effect level LOEL = lowest observed effect level Plateau = level where there s no increase in response

19 Toxicity Testing 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

20 Toxicity Testing 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

21 Acute Toxicity LC 50 : common term to describe lethal concentration Used with aquatic herbicides since fish and aquatic organisms are in direct contact with water Test organisms are exposed for 96 hours Commonly conducted with bluegill LC 50 = lethal concentration of herbicide to 50% of the test population Measured in mg/l (ppm) High Toxicity = Low LC 50

22 Acute Toxicity LD 50 : common term to describe acute oral toxicity Acute toxicity tests measure mortality following a single exposure LD 50 : dose that s acutely lethal to 50% of the test population of animals

23 Acute Toxicity LD 50 is commonly expressed as mg of toxin per kg of test High animal Toxicity body weight = (mg/kg) Low LD 50 LD 50 of 500 mg/kg is less toxic than LD 50 of 5 mg/kg 1 kg = 1,000 g = 2.2 lb 1 mg = kg = lb mg/kg = ppm 1 ppm = 1 inch in 16 miles or 1 minute in 2 years

24 Acute Toxicity LD 50 values for a single chemical can vary by: Test species Route of exposure Dichlorvos LD 50 Oral LD 50 (rat) 75 mg/kg Dermal LD 50 (rat) Inhalation LC 50 (rat) Oral LD 50 (rabbit) Oral LD 50 (pigeon) Oral LD 50 (dog) Oral LD 50 (pig) 15 mg/kg 1.7 ppm 10 mg/kg 23.7 mg/kg 100 mg/kg 157 mg/kg Dichlorvos is an insecticide commonly used in household pesticide strips

25 Acute Toxicity Categories of Acute Toxicity LD 50 LD 50 LC 50 Categories Signal Word Oral mg/kg Dermal mg/kg Inhale mg/l Oral Lethal Dose 1 I Highly toxic II Moderately toxic III Slightly toxic IV Relatively non-toxic DANGER, POISON 0 to 50 0 to to 0.2 A few drops to a teaspoon WARNING 50 to to 2, to 2.0 Over a teaspoon to one ounce CAUTION 500 to 5,000 2,000 to 20,000 CAUTION (or no signal word) 1 Probable for a 150 pound person. 2.0 to 20 Over one ounce to one pint 5, , Over one pint to one pound

26 Substance Acute oral LD 50 (rat) Nicotine 9 Caffeine 192 Bleach 192 Aspirin 200 Tylenol 338 Codeine 427 Table salt 3,000 Product (active ingredient) Aquathol K (endothall potassium salt) Reward (diquat) Acute oral LD 50 (rat)/signal word 182/DANGER * 886/CAUTION Weedar (2,4-D) >1,000/DANGER * Captain (copper carbonate) Oasis (topramezone) >1,000/CAUTION >2,000/CAUTION Renovate (triclopyr) 2,574/DANGER * Tradewind (bispyribacsodium) Habitat (imazapyr) Galleon (penoxsulam) Clearcast (imazamox) Clipper (flumioxazin) Rodeo (glyphosate) Sonar AS (fluridone) * Corrosive 4,111 (males)/caution >5,000/CAUTION >5,000/CAUTION >5,000/CAUTION >5,000/CAUTION 5,600/CAUTION >10,000/CAUTION

27 Acute Toxicity Determines PPE Route of Exposure Dermal Toxicity or Skin Irritation Potential Toxicity Category by Route of Exposure of End Use Product I Danger II Warning III Caution IV Caution Coveralls worn over long sleeved shirt and long pants Socks Chemical- resistant footwear Gloves Long sleeved shirt and long pants Socks Long sleeved shirt and long pants Socks Shoes Shoes Inhalation Toxicity Eye Irritation Potential Respiratory protection device Protective eyewear Gloves No minimum No minimum No minimum

28 The LD 50 Determines PPE Signal Word Precautionary Statements First Aid

29 Most Acute Reported Pesticide Illnesses to Single + Multiple Exposures ( ) Rank Pesticide category Number % 1 Pyrethroids 2, Chlorinated compounds 1, Organophosphates 1, Pyrethrins Glyphosate Ammonium/ammonia Carbamates DEET Sulfur compounds Triazines Total 9,906

30 Rat Oral LD 50 Values of Most Commonly- Applied Pesticides in Florida Insecticide active ingredient (LD 50 ) Herbicide active ingredient (LD 50 ) 1. Petroleum oils (>5,000) 1. Glyphosate isopropylamine salt (5,600) 2. Aldicarb (0.9) 2. Diuron (>5,000) 3. Carbaryl (500) 3. Simazine (>5,000) 4. Endosulfan (18) 4. Sulfosate (750) 5. Sulfur (>2,200) 5. Bromacil (5,200) 6. Methomyl (30) 6. Triclopyr (713) 7. Chlorpyrifos (96) 7. Pendimethalin (1,050) 8. Dimethoate (250) 8. Atrazine (1,869) 9. Fenpropathrin (70.6) 9. Paraquat (150) 10. Imidacloprid (424) 10. 2,4-D (375) Average LD 50 : 859 Average LD 50 : 2,571

31 I spray herbicides every day. What is my exposure if I do everything correctly? Smith, J.D. and H. Pullum Air Monitoring of 2,4-D and Diquat Used in Aquatic Plant Control Programs. Aquatics 16(1):14-16

32 Air Monitoring of 2,4-D and Diquat Used in Aquatic Plant Control Programs Methods.. 5 independent tests (2,4-D and diquat) Conducted: Okeechobee, Clewiston, and Kissimmee Glass fiber filter on Tyvek lapels of both airboat driver and applicator Suction pump air flow rate of 1 to 3 L/min (NIOSH 2,4- D test protocol standard) OSHA test protocol used for diquat Tested for 2 to 7 hours Smith, J.D. and H. Pullum Aquatics 16(1):14-16

33 2,4-D Results Date Person Hours Exposed Conc. (Mg/Cu.M) 8/22/88 Sprayer 6.5 <0.04 (40 ppt) Driver 4.9 <0.05 Driver 4.4 <0.07 8/23/88 Driver 6.5 <0.04 Sprayer 6.8 <0.04 8/29/90 Sprayer 4.5 BDL Driver 4.6 BDL Sprayer 2.4 <0.10 9/23/93 Sprayer 2.0 <0.12 Driver 2.2 <0.12 Smith, J.D. and H. Pullum Aquatics 16(1):14-16

34 Diquat Results Date Person Hours Exposed Conc. (Mg/Cu.M) 8/22/88 Driver 6.4 <0.01 Sprayer 1.0 <0.08 Sprayer 7.0 <0.01 8/23/88 Sprayer 6.6 <0.01 Driver 2.6 <0.03 2/6/89 Driver 6.4 <0.014 Sprayer 4.2 < /29/90 Sprayer 4.6 BDL Driver 4.6 BDL Sprayer 2.3 < /23/93 Sprayer 2.1 <0.025 Driver 2.3 <0.023 Driver 2.0 <0.026 Smith, J.D. and H. Pullum Aquatics 16(1):14-16

35 Average 2,4-D and Diquat Concentrations 2,4-D Person Avg. Conc. (mg/m 3 ) Driver <0.07 Sprayer <0.07 OSHA Permissible Exposure Limit = 10 (mg/m 3 ) (SF = 143X) Diquat Person Avg. Conc. (mg/m 3 ) Driver <0.02 Sprayer <0.03 OSHA Permissible Exposure Limit = 0.5 (mg/m 3 ) (SF = 17-25X) Smith, J.D. and H. Pullum Aquatics 16(1):14-16

36 Air Monitoring of 2,4-D and Diquat Used in Aquatic Plant Control Programs Why such low exposure? Spray concentration <1% (<1gallon/100gallons) Spray directed from side of boat at idle speed Prevailing wind and idle speed combined to create a dilution/ventilation system to pull mist away from the breathing zone Smith, J.D. and H. Pullum Aquatics 16(1):14-16

37 Thanks for your attention!