12 regulatory assessment II Flashcards
what are human health study requirements?
-to protect human health, evaluations focus on the prevention of adverse effects like cancer, genetic mutation, and birth/reproductive effects
-an extensive battery of toxicity studies using surrogate species is required to determine the nature and extent of the hazard that pest control products pose
what are the assessments included in human health study requirements?
assessments include:
-different lengths of exposure: single vs. multiple vs. lifetime
-different routes of exposure: dermal vs. oral vs. inhalation
-different animal species: to evaluate consistency of effects
-metabolic and toxicokinetic information
what are the major studies in human health study requirements?
-acute
-short-term
-long-term and carcinogenicity
what is the major studies: acute?
objective: provide information on adverse effects that may result within = or < 2 weeks of exposure to high doses (single or multiple) of pesticides
-routes of exposure: oral, dermal, inhalation, skin sensitization, eye irritation
-endpoint of interest: lethality
-outcome: how bad (toxic) is it?
studies provide information for:
-safe handling practives
-doses for longer-term studies
-MSDS sheets
-product label information: prevent poisoning
how do we set up a toxicity test?
what is the major studies: short-term?
objective: determine the effects of repeated exposure to a pesticide over a short period of time, usually 3 weeks to 3 months. Focus on non-lethal effects
-doses: moderate concentrations (range)
-exposure route: dermal, oral, inhalation
-outcome: how does it cause toxicity?
studies provide information that:
-identifies tissues and organs most susceptible to damage from a range of doses
-establishes doses tolerated by test animals
-determine suitable doses for use in long-term studies
what is the major studies: long-term and carcinogenicity?
objective: determine the effects of exposure to a pesticide over most of the test animal’s lifetime (18-24 months for mice and rats)
-doses: lower concentrations (with a range of sub-lethal responses)
-exposure route: oral
-outcome: what is the safe level (NOAEL)?
studies provide information on systemic toxicity and carcinogenicity through:
-examination of organs and tissues
-biochemical and pathological analysis of blood and urine
-must include at least one dose that results in no observable adverse effects and at least one that causes toxicity
what are the special studies?
-reproductive and developmental toxicity
-teratology
-neurotoxicity
-genetic toxicity (genotoxicity)
-metabolism and toxicokinetics
what are reproductive and developmental toxicity studies?
objective: designed to generate information on possible effects of chemicals on growth and reproduction, and are conducted over at least two generations
-doses: sublethal concentrations
-exposure route: oral
-the dosing period includes pre-treatment of males through the period of sperm development and of females through at least one ovulatory cycle
-offspring are also exposed through maternal milk during weaning and subsequently through the diet
-outcome: is reproduction or development the most sensitive endpoint (NOAEL)?
what are teratology studies?
objective: designed to determine whether chemicals can cause adverse effects on the developing fetus
-doses: sublethal concentrations
-exposure route: oral
-test substance is administered to pregnant animals during the most sensitive stages of development
-outcome: is fetal development the most sensitive endpoint (NOAEL)?
what are neurotoxicity studies?
objective: designed to determine whether chemicals can cause adverse effects on the nervous system or nerve tissue
-doses: sublethal concentrations
-exposure route: oral
-only for some pesticides, but required for all insecticides with a neurotoxic mode of action
-outcome: is neurotoxicity or development neurotoxicity the most sensitive endpoint (NOAEL)?
what are genotoxicity studies?
-genotoxicity: to determine possible interference of a compound with genetic material, causing mutations or other damage (e.g., chromosome breaks), or interference with normal genetic processes (e.g., genetic damage potential)
-an Ames test is one example of how we test for genotoxicity
-used in conjunction with information from a carcinogenicity assessment to help determine the mechanism of action of a carcinogenic response
what are metabolism and toxicokinetics studies?
objective: provide information about the relative amount of pesticide that is likely to be absorbed into the body, the relative distribution of the absorbed dose among tissues, and the rates and routes of excretion (urine, feces, bile, expired air)
-toxicokinetics: the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compounds once it is in the body
-pesticide metabolites are also identified, as is the relative proportion of each metabolite
-outcome: toxicological understanding and clearance rates in food animals
what are some other endpoints?
these endpoints are evaluated as part of other studies. They are not investigated separately, unless endpoint-specific effects are seen
-immunotoxicity
-endocrine disruptor potential
what is the immunotoxicity endpoint?
-evaluated in the short-term and long-term studies
-organ weights (e.g., thymus, spleen) and/or white blood cell counts provide an indication of potential interference with normal immune function
what is the endocrine disruptor potential endpoint?
Interference with the production and function of hormones
-evaluated in the course of examining information from reproductive, teratology, short-term and long-term studies
what are the environmental risk study requirements?
what is environmental fate?
-information on what happens to a pesticide once it enters the environment, including expected environmental concentrations (EECs) to which non-target organisms may be exposed
-goal: determine the potential behavior of a pesticide in soil, water and air, the potential for its uptake by plants and animals (bioaccumulation), and the potential for food-chain transfer
what is data used includes (use pattern) of environmental fate?
-rates and methods of application
-number of applications/season
-timing of application
-target pests
-targets crops and resources
-geographic area and climate
to determine/model environmental fate, the following data for a pesticide if required:
- physical and chemical properties
- transformation processes
- mobility
- field study results
what are physical and chemical properties?
obtained from laboratory studies and are essential for the prediction of environmental behavior of a pesticide. the following properties are key:
-water solubility: good for evaluating pesticide mobility in soil and deposition into sediments in aquatic environments
-vapour pressure: indicator of the potential of a compound to volatilize
-octanol/water partitioning coefficient (Kow): indicates the likelihood of a compound to move from soil or water into organisms, and its bioaccumulation potential. If the Kow indicates that the pesticide is likely to bioaccumulate, a lab bioaccumulation study is necessary
what are the transformation processes?
indicates what pesticides are likely to transform into in the environment and how (pathways)
pesticides can be transformed or degraded by:
-light (sunlight): phototransformation
-chemical reactions: e.g. hydrolysis, oxidation
-biological reactions: biodegradation
-provides information on the persistence of a particular compound under both aerobic and anaerobic conditions
-aids in the design of field studies (used to confirm lab-based predictions)
what are mobility studies?
provides information on the ability of terrestrial-use pesticides and their major transformation products to move through soils, and their potential to contaminate nearby surface and ground waters
common ways that pesticides move from area of application:
-leaching
-runoff
-drainage
-dust
-soil erosion
-snowmelt
-this is evaluated through laboratory studies with a range of soil types, and is validated in field studies
what are field studies?
required to demonstrate fate in Canadian Environments and to substantiate results from lab studies, especially regarding persistence and mobility
studies have to consider:
-colder climates
-regional precipitation patterns
-specific soil types
-use patterns (planting seasons, etc.)
-studies completed in the United States in areas similar to Canada (e.g. North Dakota vs. southern MB or SK) are also acceptable
-aquatic field studies: required where there is high product mobility into aquatic systems
what is environmental toxicology?
-information on the hazards that pesticides pose to non-target plants and animals
-information on effects in both aquatic and terrestrial settings is mandatory
-this mainly involves evaluating the lethal and sublethal effects of acute and chronic exposure to a range of standard test species
-key outcome: no observed effect concentrations (NOECs)
what is environmental toxicology of terrestrial organisms?
manufacturers have to provide toxicological information on effects on birds terrestrial invertebrates and plants
birds: typically, studies are done with bobwhite quail and mallard duck
-involves: acute and chronic, oral, dietary and reproductive
-reproductive studies: mortality of adults and chicks and sublethal effects (egg production, egg shell thinning)
-invertebrates: studies need to be conducted on earthworms, pollinators, and predatory/parasitic insects/mites
-plants: studies need to be completed on non-target, vascular plants
-mammals: effects on wild mammals are predicted from the mammalian toxicology risk assessment (human health data)
what is environmental toxicology of aquatic organisms?
manufacturers are required to provide toxicological information on the effects on algae, non-target invertebrates and fish
-algae: freshwater algae required; marine species conditional
-invertebrates: acute and chronic toxicity tests on aquatic arthropods (e.g. daphnids- Daphnia magna or Ceriodaphnia dubia)
-fish: acute and chronic tests with both cold-water and warm-water fish species (e.g. rainbow trout, bluegill sunfish)
-acute and chronic effects on marine molluscs (shellfish) and marine fish are only required when pesticide can enter estuarine or marine ecosystems
-no required testing on sensitive aquatic insect species
