Hotze Wijnja, Ph.D . Division of Crop and Pest Services

1. Glyphosate and Triclopyr Herbicides: Regulatory Review of Human Health and Ecological Effects Hotze Wijnja, Ph.D. Division of Crop and Pest Services Massachusetts Department of Agricultural Resources Pesticide-Safety Workshop

2. Outline • Review of Pesticides for Registration • Federal level: EPA Pesticide Program • State Level: • Registration by Pesticide Board Subcommittee • Special Reviews for Rights of Way and Aquatic herbicides • Glyphosate and Triclopyr • Human Health and Ecological Effects • Risk assessment by US Forest Service • Risk assessment for use on Cape Cod

3. Levels of Review for Registration of Pesticides • At the federal level by US EPA • At the state level by Pesticide Board Subcommittee • Special reviews for specific uses: Joint review with MassDEP for herbicide use in • Rights-of-Way • Lakes and Ponds

4. 1. EPA Regulates Pesticides Under Authority From: • Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) • Requires registration of all pesticides by EPA • Federal Food, Drug and Cosmetic Act (FFDCA) • Requires EPA to set pesticide tolerances for all pesticides used in or on food • Food Quality Protection Act (FQPA) • Amended both FIFRA and FFDCA

5. EPA Regulatory Authority for Pesticides • EPA must find that a pesticides poses a "reasonable certainty of no harm" before that pesticide can be registered for use on food/feed. • Analysis of aggregate exposure, cumulative effects, sensitive populations (infants), and endocrine-disrupting effects

6. EPA Registration Program • Evaluation of new and existing pesticides • Registration of products for pest control • Ensure protection of human health and the environment • Registration permits the distribution, sale, and use according to specific use directions and requirements on the product label • A product label is a legal document

7. Evaluation for Registration • Human health risk • Short-term acute effects • Long-term effects such as cancer and reproductive • Aggregate exposure (food, water and residential) • Cumulative risks (includes other pesticides) • Occupational risks • Effects on wildlife, fish and plants • Acute and chronic • Including endangered species

8. Evaluation for Registration • Human Health Risk • Short-term acute effects • Long-term effects such as cancer and reproductive • Aggregate exposure (food, water and residential) • Cumulative risks (includes other pesticides) • Occupational risks • Effects on wildlife, fish and plants • Acute and chronic • Including endangered species

9. EPA Risk Assessment Four-step process assessment: • Step One: Hazard Identification • How toxic is the substance? • Step Two: Dose-Response Assessment • "The dose makes the poison.“ • Step Three: Exposure Assessment • Dietary, residential, recreational, occupational • Step Four: Risk Characterization • RISK = TOXICITY x EXPOSURE

10. Risk Cup Concept Each use of a pesticide contributes a specific amount of exposure (risk) to humans. This is compared to the acceptable amount of risk (risk cup) which can not be exceeded.

11. Risk Management and Regulatory Decisions • Consideration of risk assessment and peer review • Consideration of risk mitigation measures • General Use or Restricted Use • Consideration of existing alternative pesticides • Coordination of risk management with registrants • Label Review and Approval

12. Review of Registered Pesticides • Programs for re-evaluation of registered pesticides • Ensure adherence to the highest standards for protection of human health and the environment • Registration review • Re-evaluation on a regular cycle • Special review • Initiated when unreasonable adverse effects occur

13. 2. Pesticide Regulation at the State Level • MDAR is responsible for regulating the use of pesticides in Massachusetts • Registration of pesticides • Licensing and certification of applicators • Enforcing federal and state laws and regulations • Pesticide Program Objectives • Regulate the use of pesticides • Protect human health and the environment

14. Pesticide Board Subcommittee • Registration of Pesticides in MA • Five members from the Pesticide Board • Director of Food Protection Program, MDPH – Chairperson • Commissioner of MDAR or designee • Commissioner of MDPH or designee • Commissioner of MDCR or designee • Commercial Applicator

15. Subcommittee Registration Classification • Subcommittee determines potential to cause unreasonable adverse effects when used as labeled • Classification of Registration • Not to register • Register – unclassified/ General Use • Register and classify for Restricted Use (e.g. classification as a potential groundwater contaminant) • Register for Special Local Need

16. Registration Classification • Classification as State Restricted Use Pesticide based on: • Potential for groundwater contamination • Subsurface termiticide use • Toxicity concerns • Other Subcommittee concerns For example, toxicity to specific non-targets such as honey bees

17. Groundwater Protection List CCCGA Winter Meeting

18. 3. Special Review for Rights-of-Way and Aquatic Herbicides in MA • Specific Regulations for Rights-of-Way management • Sensitive Area Materials List • Aquatic Herbicides: • Licensed use of approved herbicides (those included in GEIR) • Special review process for herbicides to be approved for rights-of-way and aquatic use

19. Special Review Process • Cooperative review by MDAR and MassDEP • Scientific review of herbicide products includes: • Physical and chemical characteristics • EPA registration standard and status • Primary and secondary data sources • If necessary, additional data will be requested from registrant • Review addresses both active ingredients and “other” or “inert” ingredients

20. Rights-of-Way Management Regulations (333 CMR 11.00) • Provide provisions for sensitive areas within rights-of-way • Sensitive area restrictions include: • Only herbicides listed on the “Sensitive Area Materials List” shall be used • Criteria and procedures for review of herbicides for use within sensitive areas are established in a Cooperative Agreement between MDAR and MassDEP (1987)

21. Sensitive Area Materials List • Herbicides specified to be acceptable for use in sensitive areas • Currently Listed Active Ingredients: • Glyphosate • Metsulfuron-methyl • Sulfometuron-methyl • Fosamine • Imazapyr • Triclopyr

22. Protocol for Active Ingredients • Environmental fate and transport characteristics • Transport • Water solubility • Partitioning characteristics • Vapor pressure (volatility) • Speciation at ambient pH • Persistence • Hydrolysis half-life • Photolysis half-life • Soil half-life

23. Environmental Fate Evaluation • Supported by computer modeling by using EPA-approved models for environmental exposure assessments. • Models generate predicted environmental concentrations in soil and water for situations specified with the input parameters, including • Chemical properties • Application characteristics • Soil and meteorological input

24. Toxicity Criteria • Mammalian toxicity • Acute: LD50 values; Irritant effects • Chronic/ Subchronic • No Observed Adverse Effect Levels (NOAEL) • Lowest Observed Adverse Effect Levels (LOAEL) • Reproductive and developmental toxicity • Carcinogenicity • Mutagenicity

25. Aquatic Life Toxicity Criteria • Acute (fish and invertebrates) • Lethal Concentration (LC50) values • Chronic/Subchronic • No Observed Effect Concentration • Lowest Observed Effect Concentration • Reproductive and developmental toxicity

26. AvianToxicity Criteria • Acute • Lethal Dose (LD50) values • Chronic/Subchronic • No Observed Effect Concentration • Lowest Observed Effect Concentration • Reproductive and developmental toxicity

27. Amphibian Toxicity Criteria • Acute • Lethal Dose (LD50) values • Chronic/Subchronic • No Observed Effect Concentration • Lowest Observed Effect Concentration • Reproductive and developmental toxicity

28. Risk Characterization • Based on comparison of predicted environmental concentrations with: • “No Observed Effect Levels” or “Lowest Observed Effect Levels” • LC50 values • Hazard Index (HI), or • Risk Quotient (RQ) • Comparison of HI or RQ with Levels of Concern established for various classes of organisms

29. Sensitive Area Materials List Examples of Active ingredients and approved products

30. Review Criteria for “Other” Ingredients • Surfactants and detergents are a common component of herbicide formulations • Concerns for potential effects on aquatic organisms • Review protocol similar to active ingredient protocol • Environmental fate and toxicological information will be considered • Supplemental information may be obtained through use predictive tools approved by EPA

31. List of Approved Surfactants Recently completed a risk assessment of commonly used surfactants in herbicide products Resulted in a list of approved surfactants for use in Sensitive Areas of Rights-of-Way New requests for herbicide products containing surfactants that are not listed will have to undergo a review following the same criteria

32. List of Approved Surfactants Polyethoxylated ethylamines (POEA) Alkylphenol ethoxylates (APE) Alcohol ethoxylates (AE) Phosphate ester ethoxylates (PE) Organosilicones (OS) The need for re-evalution will be considered when new data become available

33. Herbicide Reviews for ROW • Fate & transport • Toxicological characterizations – humans, non-target organisms • Use & application characteristics (e.g., Limited and No-Spray Zone; Application Rate and Frequency) • Exposure assessments & risk characterization Active Ingredient & Product Surfactants & other adjuvants Approved Not Approved Apply use restrictions Still unacceptable Acceptable

34. Components of Herbicide Review Process for Sensitive Areas of Rights-of-Way Legislation: 333 CMR 11.00 Rights-of-Way Management Regulations DEQE/DFA Cooperative Agreement Relative to Section 4(1) (E) of 333 CMR 11.00 Rights-of-Way Management Regulations. July 1987 HERBICIDE EVALUATION TECHNICAL UPDATE No. 1 Methods for the Evaluation of Herbicides for Use in Sensitive Areas of Rights-of-Way June 2010 Statement of Policy on Restricting the Use of Surfactants as Part of the Evaluation Process for Herbicides Proposed for Use in Sensitive Areas of Rights-of-Way. March 1989 Surfactant Ecological Risk Assessment (Wijnja, 2010) HERBICIDE EVALUATION TECHNICAL UPDATE No. 2 List of Approved Surfactants for Use in Sensitive Areas of Rights-of-Way – June 2010 Reference: Wijnja, H. 2010. Ecological Risk Assessment of Surfactants Associated with Herbicide Application in Rights-of-Way Areas. Massachusetts Department of Agricultural Resources. Boston, MA February 2011 Ver 2.0

35. Summary of Regulatory Review These levels of review and evaluation for registration and addition to the Sensitive Area Materials List and the rigorous regulatory process for rights-of-way are in place to ensure: Protection from potential impacts on human health and the environment from the selective use of these herbicides Allow the benefits of selective use of herbicides to maintain rights-of-way

36. Glyphosate • First registered by EPA in 1974 • Widely used non-selective herbicides • Mode of Action: Inhibition of plant enzyme Acute Toxicity (mammalian) • Low by oral exposure (LD50 >4320 mg/kg (rat) • Low by dermal exposure (skin, eye) (2 g/kg) • Not a skin sensitizer • Very low by inhalation (4.43 mg/L) • Product formulations may cause irritation due to other ingredients

37. Glyphosate: Chronic Toxicity • Dog study 1(yr): No effects; NOEL > 500 mg/kg/d • Rat (2 yr): decreased body weight, effects on eyes and liver at high doses (NOEL = 362 mg/kg/d • Reproductive and Developmental Effects: • No link to effects in rats except at very high doses • Fetuses gained weight more slowly • Some fetuses had skelatal abnormalities • No reproductive effects by glyphosate, AMPA, POEA

38. Glyphosate: Chronic Effects • Carcinogenicity: • Animal studies have not shown evidence that exposure to glyphosate is linked to cancer • Classified as “Evidence of non-carcinogenicity in humans” • Endocrine Disruption: no evidence of effects • Fate in the Human Body: • Any glyphosate taken in through skin or mouth goes through the body in less than a day

39. Glyphosate: Environmental Fate • In soil: break down by microbes to several smaller compounds, ultimately to CO2, water and salts • Typical field half-life ranges is about 47 d • Binds strongly to soil, immobile in soil • In water: microbial break down • Half-life: few days to 90 days • No significant exposure to air expected (very low volatility)

40. Glyphosate: Ecotoxicity Birds: Practically non-toxic (LD50 >200 mg/kg) Fish: slightly to practically non-toxic (LC50 24-140 mg/L); products: 1.3 – 1000 mg/L Aquatic Invertebrates: Slightly to practically non-toxic (LC50 55-780 mg/L; products: 3-16 mg/L) Amphibians: Moderately to slightly toxic to product formulations (LC50 6.6-18.1 mg/L) Honey bees: practically non-toxic Earthworm: practically non-toxic

41. Triclopyr • First registered by EPA in 1979 • Selective herbicide used to control woody and herbaceous weeds in non-crop areas • Two common forms: • Triethylamine (TEA) • Butoxyethyl ester (BEE) • Mode of Action: Mimics the effects of plant hormones (auxins)

42. Triclopyr • Acute Toxicity (mammalian) • Low by oral exposure (LD50 830-1847 mg/kg (rat)) • Mildly irritating to corrosive to the eyes • Non-irritating to the skin of rabbits; skin sensitizer on guinea pigs • Low toxicity by inhalation • Fate in body: • Low rate of absorption • Rapidly eliminated

43. Triclopyr: Chronic Effects • Rat study (13 weeks); • Effects on kidneys and liver at 20 mg/kg • Dog study: (183- 228 d) • Effects on body weight, food consumption, blood chemistry, liver and kidneys at 20 mg/kg. • No effects at lower at 2.5 and 5.0 mg/kg doses • Fate in body: Elimination with 2 – 3 days

44. Triclopyr: Chronic • Carcinogenicity • No tumors in male rats and mice (2 yr study) • Increase of number of tumors in female rats and mice • Classified as: “Not classifiable as to human carcinogenicity” • Reproductive and Developmental Effects • Rat and rabbit studies show low potential for effects • At high levels, decrease in live fetuses and skelatal effects

45. Triclopyr: Environmental Fate • In soil: breaks down to several smaller compounds, ultimately to CO2, water and salts • Half-life ranges from 1.1 to 90 days • Mobile in soil • In water, breaks down by exposure to sunlight • Half-life is 1-10 days • No significant exposure to air expected (low volatility)

46. Triclopyr: Ecotoxicity • Birds: Practically non-toxic (LD50 >735 mg/kg) • Fish: • TEA: practically non-toxic LC50 >100 mg/L); • BEE: moderately to highly toxic (LC50 0.1 - 10 mg/L ) • Aquatic Invertebrates: • TEA: practically non-toxic (LC50 1496 mg/L) • BEE: moderately toxic (LC50 1.7-12 mg/L) • Honey bees: practically non-toxic

47. USDA Forest Service Risk Assessments Use Pattern • Conifer release, site preparation, noxious weed control, and rights-of-way management Glyphosate • Human Health Assessment: • Low mammalian toxicity, very few specifics can be identified • Developmental effects are most sensitive endpoint • Formulations vary around the world; some studies from South America suggest potential endocrine and genotoxic effects

48. Forest Service Risk Assessment • Risk characterization: Hazard Quotient (HQ) • HQ = Estimated Dose/ Reference Dose • Level of concern HQ > 1 • Workers: minimal concern • General public: only concern for exposure by consuming vegetation shortly after treatment • Ecological • LOC exceeded for Aquatic organisms for product formulations with POEA; • Care should be taken with the use of such formulations near water bodies

49. Forest Service Risk Assessment Triclopyr • Level of Concern exceeded for: • Workers based on worst-case scenarios • General public: only concern for exposure by consuming vegetation shortly after treatment • Ecological: • Level of Concern exceeded for large mammals and birds consuming contaminated vegetation • Sensitive non-target plants can be affected

50. MDAR Herbicide Assessment on Cape Cod Objectives: • Evaluate the fate of herbicides used in utility rights-of-way in common soil on Cape Cod • Evaluate the effects on groundwater and surface water for: • Human health • Ecological (aquatic life) effects