PSEP :: Issues :: Outline for Chronic Health Effects of Pesticides

Outline for Chronic Health Effects of Pesticides

GENERAL CONCEPTS - This section should comprise simply and cogently stated definitions and key concepts at a general level using as many familiar terms as possible.
1. What is a Pesticide Formulation? Provide a description of active ingredients, "inerts", contaminants and describe metabolites. Define "inerts" as utilized by EPA in registering pesticides. Identify the EPA categories of "inerts". Labels do not adequately address chronic health effects. Evidence of harmful effects is based upon active ingredients.
2. Human Health Hazards Explain the general types of hazards to humans observed with pesticides, including cancer, genotoxicity, immunotoxicity, reproductive toxicity, neurotoxicity, specific organ system toxicity. Introduce key definitions and concepts, including acute, immediate, reversible, systemic, local, and with greater emphasis on subchronic, chronic, delayed, and irreversible.
3. Dose-Response Relationships Include general theory. Emphasize the over-reliance upon acute toxicology. Give an example which illustrates the importance of the slope of the dose-response curve, LD50 and ED50, MTD, NOAEL, and NOEL with examples as to how this varies with individual chemicals. Stress the importance of different end-points, such as lethality, peripheral neuropathy, and headaches; Describe the inappropriateness of acute toxicity tests (LD50) as predictors for chronic effects.
4. Interactions Discuss exposure to single chemicals vs exposure to several chemicals. Define the following interactions: additive, synergistic, antagonistic, cumulative, potentiation. Identify the factors common to susceptible subgroups which alter the response to a pesticide (e.g., age, sex, reproductive status, genetic background, nutritional status, etc.)
5. Exposure Explain routes of exposure, concentration, duration of exposure, and frequency of exposure. Include explanation of the nature of formulations and methods of application with an emphasis on the ability to control risks.
SPECIFIC CHRONIC HUMAN HEALTH HAZARDS - Focus only on long-term effects on humans with somewhat more detailed explanation than used in section I; While stressing specific chronic health effects, avoid detailed, chemical specific information.
1. Cancer. Include a definition of cancer, types of tumor, and rate of tumor formation. Discuss human cancer epidemiology the way we examine human populations and how we observe cancer. Using materials developed by the American Cancer Society, discuss role of host and environmental factors in carcinogenicity.
2. Reproductive Disorders. Describe sterility, infertility, birth defects, miscarriages, spontaneous abortions, developmental delays, etc.
3. Neurological Diseases. Identify neurotoxic effects, including specific reference to the CNS, neurobehavioral/neuropsychological impacts, delayed neurotoxicity, and the peripheral nervous system.
4. Immunological Problems. Describe the way the body fights infections, and conducts surveillance to fight cancer. Describe allergic reactions, such as anaphylaxis and contact dermatitis.
5. Specific Problems with other organ systems. After briefly reviewing the structure, function and physiology of the major organ systems of contact (#l eye, #2 skin, and #3 lung) and organs of process (#4 blood and lymph system, #5 liver and biliary tract, #6 kidney and bladder), identify the toxic effects on each system. Distinguish between organs of contact and target organs. For example, include optic neuropathy, cataracts, allergic sensitizations, changes in lung function, effects on blood cell production, toxic hepatitis, decreased kidney function, etc.
TOXICOLOGICAL EVIDENCE FOR CHRONIC HEALTH EFFECTS - Include an introductory statement on the scientific underpinnings of toxicology.
1. Types of Evidence
  1. Human Evidence Describe clinical observations and epidemiology, including descriptive and analytical epidemiology, the importance of prospective and retrospective studies, case-comparison and cohort studies, correlations, sample size and the likelihood of observing statistically significant effects. Identify the strengths and weaknesses of epidemiological surveys.
  2. Animal Testing Briefly describe the laboratory testing for the following end-points (including EPA requirements), identifying the strengths and weaknesses of these tests:
    1. Carcinogenesis. Describe EPA's categories of carcinogens. Include list of carcinogens and evidence for a.i. and "inerts"
    2. Teratogenesis - structural deformity. Describe embryogenesis and the impact of pesticides in altering the structural aspects of development. Identify list of teratogenic pesticide a.i. and "inerts".
    3. Reproductive and developmental (non-structural). Describe the female and male reproductive systems, and embryogenesis. Define fetotoxicity, adverse effects on the male reproductive system, adverse effects on the female reproductive system. List pesticide a.i. and "inerts" which adversely affect reproductive and developmental systems.
    4. Genetic toxicity. Describe the nature and role of DNA and RNA, genes, chromosomes, genetic diseases, defining experimental mutagenesis. List genotoxic pesticide a.i. and "inerts".
    5. Neurotoxicity. Describe the central and peripheral nervous systems and the synapse, include details of neurophysiology and biochemistry. Identify neurotoxic effects of pesticides, including specific reference to the CNS, neurobehavioral/neuropsychological impacts, delayed neurotoxicity, and the peripheral nervous system. Describe the classes of pesticides for neurotoxicity potential (i.e., organophosphates, carbamates). List pesticides a.i. and "inerts" characterized as neurotoxic.
    6. Immunotoxicity. Provide a synopsis of the immune system, including cell-mediated immune functions (T-cells and macrophages) and moral immunity (antibodies), and sites of immunologic activity throughout the body. Describe the way the body fights infections, and fights cancer. Describe allergic reactions. List immunotoxic pesticide a.i. and "inerts".
    7. Chronic toxicity involving other organ systems. Review the structure, function and physiology of the major organ systems (#l eye, #2 skin, #3 lung and respiratory system, #4 blood and circulatory system, including reference aplastic anemia, #5 liver and biliary tract, #6 kidney and bladder, using chlordimeform). Identify the effects on each system ascribed to pesticide exposures. List pesticide a.i. and "inerts" which can damage each organ system.
    8. Metabolic Factors. Introduce key definitions and concepts, including absorption rates and routes for skin, lung and gastrointestinal tracts, distribution rates and routes, excretion rates and routes, storage organs, bioaccumulation, enzymes, metabolism to a more toxic form, metabolism to a less toxic form, pharmacokinetics. Provide a specific pesticide example for each, perhaps in a table form.
  3. Ecological Identify evidence derived from observations of pesticide impacts on domestic animals, livestock, wildlife and ecosystems. Describe the nature and extent of aquatic and terrestrial toxicology testing, including laboratory and field testing.
2. Data Gaps As a general introduction, describe the parallel growth of toxicological evidence with the growth of knowledge in human physiology, biochemistry and analytical pathology. Discuss the importance of addressing data gaps. Identify the data gaps in assessing important, but recently recognized hazards (e.g., immunotoxicity, neurotoxicity). Distinguish between regulatory data requirements and the larger domain of scientific evidence.
3. Interpretation of Toxicological Evidence Describe the reasons for and methods of extrapolation. Describe the assumptions inherent in extrapolations from animal studies to human impacts based on animal testing evidence of carcinogenicity and non- threshold effects, including margins of safety, uncertainty factors, No Observed Effects Levels, Low Observed Effect Levels.
EXPOSURE ASSESSMENT - For each section include an introductory statement which focuses on how to measure exposure
1. Routes of Exposure Describe inhalation, dermal absorption and ingestion as routes of exposure. Identify environmental and subject related factors that influence the extent and rate of absorption.
2. Specific Places Where People are Exposed
  1. Occupational Environments
    1. Concentrated Exposure Environments. Describe the potential exposures for factory workers, field spotters and mixer/loaders. Describe control technology and practices which reduce exposures in these situations.
    2. Field Worker Environments. Discuss pesticide residues. Describe the potential exposures for field workers, and the appropriate control technologies and practices which reduce exposures in these situations. Emphasize the role of drift.
    3. By-stander Environments. Describe the potential exposures for by-standers, and the appropriate control technologies and practices which reduce exposures in these situations. Emphasize the role of drift.
  2. Community Environments
    1. By-stander Environments. Describe the potential exposures for by-standers, and the appropriate control technologies and practices which reduce exposures in these situations. Emphasize the role of drift.
    2. Municipal/eradication Environments. Describe the potential exposures for by-standers and other susceptible subgroups, and the appropriate control technologies and practices which reduce exposures in these situations. Emphasize the role of drift and persistent contamination.
  3. Home and Garden Environments (Commercial/Self Application). Describe the potential exposures for by-standers and spread of pesticide-contaminated materials, and the appropriate control technologies and practices which reduce exposures in these situations. Emphasize the role of drift and persistent contamination.
3. Sources of Pesticide Exposure
  1. Food Explain the route of accumulation of pesticide residues on and in food. Describe pesticide tolerance setting, preharvest intervals, and the regulations of pesticides in food, including a description of the nature and extent of food testing by FDA, EPA and state agencies. Define "organic", and the regulation of such foods by the state and federal governments. Include a discussion of bioaccumulation of pesticides in fish, waterfowl and other resources.
  2. Environmental Media
    1. Water. Describe the nature and extent of pesticide contamination of surface waters, groundwater and drinking water supplies (particularly field worker water sources). Identify the monitoring programs for detecting pesticides in water.
    2. Air. Describe the contamination of air by pesticides, including a description of aerial spraying programs, drift and long range transport. Identify the monitoring programs for detecting pesticides in air.
    3. Soil. Describe the contamination of soil by pesticides, including a description of soil fumigation practices. Identify the monitoring programs for detecting pesticides in soil.
4. Environmental Fate of Pesticides Describe the EPA procedures for determining the environmental fate of pesticides. Include descriptions of transformation and transportation processes.
  1. Physical Transport
    1. Drift. Describe optimum droplet size and the influence of temperature, humidity, wind speed and direction, volatility and equipment in altering droplet size and movement.
    2. Rainfall and Fog
    3. Long-range Transport
  2. Chemical Transformation
    1. Hydrolysis
    2. Oxidation/Reduction
    3. Photochemical Reactions
  3. Biological Transformation
    1. Microbial
    2. Bioaccumulation
5. Frequency of Exposure Describe the crop specific practices for pesticide use, including descriptions of frequency of application of a single pesticide product, and seasonal applications of other pesticides.
6. Quantitative/Qualitative Assessment [Awaiting Marion Moses Contribution] Describe the analytical methods for identifying and quantifying pesticide exposures, including biological monitoring. Describe the availability of this technology, and the frequency with which it is employed in monitoring pesticide levels in various environmental media.
7. Control of Exposure Describe use and technology to reduce exposure and risks, e.g., quarantines and reentry times, application equipment, clothing, gloves, "lifestyles", etc. Provide a rank order of control measures to reduce exposures effectively.
RISK ASSESSMENT Describe the assumptions utilized in calculating a population risk estimate. Emphasize how risk changes with target populations, i.e., adult male vs fetus. Emphasize how population risk differs from individual risk. Identify the strengths and weaknesses of each portion of the risk assessment.
CHEMICAL-SPECIFIC INFORMATION These data sheets could be prepared as accessory fact sheets for individual chemicals and/or formulations, and will serve as illustrative examples of information discussed in earlier sections. Lists of chemicals classified by chronic health effects should be included here.
1. Types (e.g., insecticides)
2. Class (e.g., organophosphates)
3. Compound X (specific chemical name)
4. Synonyms
5. Physical and Chemical Properties
6. Inerts, contaminants
7. Formulation (e.g., granules)
8. Application Technique
9. Safety Precautions
10. Environmental Fate
11. Exposure Assessment
  1. Biological monitoring
  2. Residues
12. Health Effects
13. Data Gaps
14. Contacts for Additional Information
LEGAL/REGULATORY CONSIDERATIONS
1. Describe FIFRA
2. Implications of Restricted-Use Classification
BIBLIOGRAPHY/SOURCES OF FURTHER INFORMATION

APPENDIX. Provide a list of frequently asked questions and their answers.

February 28, 1989
Prepared by the Subcommittee on Chronic Health Effects
J. Kolcun, Chair; F. Dost; M. Moses; G. Poje