Revised Cumulative Risk Assessment Questions & Answers
Note: This information is provided for reference purposes only. Although the information provided here was accurate and current when first created, it is now outdated.
EPA has released its revised cumulative risk assessment for the organophosphate pesticides. This assessment is based on evaluation of the potential for people to be exposed to more than one member of this group of pesticides at a time and considers exposures from food, drinking water, and residential sources. The assessment incorporates regional exposures from residential and drinking water sources, as the most appropriate way to account for the considerable variation in potential exposures across the country. EPA has developed an overview of the various aspects of the assessment, as well as detailed regional evaluations. Appendices to the risk assessment provide detailed views of the results.
A cumulative risk assessment is the process of combining exposure (the amount of a pesticide to which an individual is exposed) and hazard (the health effects a pesticide could cause) from all substances that share a common mechanism of toxicity. The Food Quality Protection Act (FQPA) directs EPA to consider the combined effects to human health that can result from exposure to such pesticides and other substances.
The potential risk presented by a pesticide depends on the toxicity of the pesticide and the amount of the pesticide to which a person is exposed. It is important to note that a pesticide having low toxicity but the potential for high exposure can present a risk similar to that of a pesticide having high toxicity but very little potential for exposure. Since people can be exposed to several pesticides that act the same way in the body at the same time through various foods, drinking water, and from uses in and around the home, school, or recreational areas, it is also necessary to assess the effects of cumulative exposure.
Organophosphates affect the nervous system by reducing the ability of cholinesterase, an enzyme, to function properly in regulating a neurotransmitter called acetylcholine. Acetylcholine helps transfer nerve impulses from a nerve cell to a muscle cell or another nerve cell. If acetylcholine is not properly controlled by cholinesterase, the nerve impulses or neurons remain active longer than they should, overstimulating the nerves and muscles and causing symptoms such as weakness or paralysis of the muscles.
The assessment shows that most organophosphate pesticides degrade rapidly and that people are exposed to levels that are not toxic or dangerous.
This scientific assessment of organophosphate pesticide food safety contains good news for American consumers. After years of rigorous scientific work, it strongly supports our confidence that the U.S. has one of the safest food supplies in the world. Specifically, with this groundbreaking work, EPA has evaluated over 1,000 organophosphate pesticide tolerances (legal residue limits), and virtually all of them are now consistent with the highest levels of safety. (EPA is still evaluating the tolerances for a few of the pesticides.) This finding comes after years of scientific work, countless scientific and public meetings, and an existing regulatory process to ensure these pesticide tolerances meet the tough food safety standard in the Food Quality Protection Act. In the last several years, EPA has taken a variety of regulatory actions on the organophosphates, ranging from lowering application rates to complete cancellations on specific uses. These actions have substantially reduced the risks and have contributed to the high level of safety found in the cumulative risk assessment.
Overall, this revised organophosphate cumulative risk assessment presents results showing a range of estimated risks depending on the exposure period considered (one-day or seven-day average) and the percentile of exposure. EPA is evaluating the appropriateness of consideration of these estimates throughout the full scope of the range.
It appears that one of the major factors influencing the results at the highest portion of the range for dietary and residential exposures derives from the fact that a few individual organophosphate risk assessments have not been finalized and resulting risk management actions have not been completed. This is particularly true for DDVP and dimethoate. In the next several weeks, EPA will continue the scientific and regulatory work to evaluate and address these potential risks.
EPA has confidence in the continued safety of our food supply and emphasizes the importance of eating a varied diet rich in fruits and vegetables. Regulatory actions taken over the last six years have considerably reduced the risks posed to Americans by exposure to organophosphate pesticide residues that may be found in food and in and around the home. After years of rigorous scientific work, the Revised Organophosphate Cumulative Risk Assessment strongly supports our confidence that the U.S. has one of the safest food supplies in the world.
This assessment supports the high level of regulatory confidence in the safety of the food supply. By evaluating the potential for combined exposures to two or more organophosphate pesticides, the assessment moves beyond the already high level of protection of public health provided by the individual aggregate assessments. Looking at exposure over time helps take into account the potential effects of additional exposure before complete recovery from any given exposure. It also evaluates variation in exposure from drinking water and residential uses in different areas of the country. The assessment includes the FQPA safety factor for protecting sensitive populations, e.g., infants and children.
EPA's approach to cumulative risk assessment relies on a careful review of the data on toxicity of individual pesticides and information on potential for exposure. The process generally follows these steps:
Before beginning the cumulative assessment process, EPA generally assesses risks associated with individual pesticides. For each individual pesticide, EPA performs an aggregate risk assessment (considering all combined sources of exposure). In the aggregate assessment, EPA considers exposures to the individual pesticide from food, drinking water, and residential uses. At this stage, if risks exceed EPA's level of concern, the Agency would take steps to reduce risks associated with the chemical to acceptable levels. EPA's revised guidance on aggregate risk assessment ("General Principles for Performing Aggregate Exposure and Risk Assessment") is available on the web at http://www.epa.gov/pesticides/trac/science/.
Identify Pesticides with a Common Mechanism
EPA identifies pesticides that have a common mechanism of toxicity. Once identified, these pesticides are called a "common mechanism group." Such a group consists of pesticides for which scientifically reliable data demonstrate that the same toxic effect occurs in or at the same organ or tissue by essentially the same sequence of major biochemical events. EPA guidance on the process for identifying whether pesticides have a common mechanism ("Guidance for Identifying Pesticides and Other Substances that Have a Common Mechanism of Toxicity") is available on the web at http://www.epa.gov/pesticides/trac/science/.
Perform a Cumulative Assessment
After establishing the common mechanism group, EPA performs the cumulative risk assessment in four steps:
- Hazard Assessment and Characterization-This step identifies the potential health effects that can be caused by a pesticide. For the cumulative assessment, this includes the potential for health effects from exposure to multiple pesticides with a common mechanism of toxicity, including consideration of conditions that will allow the effects to cumulate and whether specific subgroups might have increased sensitivity to the common toxic effect.
- Dose-Response Assessment and Characterization-This step determines the relative toxic strength of each pesticide included in the assessment and establishes a dose that is used to estimate the potential combined risk.
- Exposure Assessment and Characterization-This step assesses who is potentially exposed, how they might be exposed, and how much of the pesticide people could be exposed to through food, drinking water, and various non-agricultural uses, such as use in and around the home. For the cumulative assessment, EPA will assess the potential for humans to be exposed to multiple members of the common mechanism group at the same time and whether there are regional or subpopulation concerns.
- Risk Characterization-This step identifies the strengths and weaknesses of the analysis, potential sources of risk, and any subpopulations that are at increased risk. It describes the Agency's confidence in the results as well as assumptions used and uncertainties in the analysis.
The first two steps include use of a weight-of-the-evidence approach to determine the harmful effect that occurs through a common mechanism of toxicity and to establish a common measure of toxic potency. A weight-of-the-evidence approach involves reviewing all pertinent data and information, assessing the strengths and weaknesses of the data, and reaching conclusions based on the overall picture provided by the data, rather than based on any one specific study. One way of comparing toxic potency is by selecting one pesticide as the "index" pesticide (generally the one for which the Agency has the best information on effects at a variety of doses) and comparing the other pesticides to it to determine their relative potency (e.g., one might be half as toxic as the index pesticide, while another might be twice as toxic).
Steps 3 and 4 include estimating exposure and risks for the food, drinking water, and residential/non-occupational pathways. EPA combines these exposures using a calendar-based software modeling tool that allows the user to develop exposure estimates for a period of time, such as a day, a week, or a month.
EPA has published guidance on conducting cumulative risk assessments. This guidance has been reviewed by the FIFRA Scientific Advisory Panel. The revised guidance is available on EPA's Web site at http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf (PDF, 90 pp., 490 KB, about PDF)
The revised assessment includes consideration of the Food Quality Protection Act (FQPA) safety factor as it relates to the organophosphate cumulative risk assessment. The available data support differences among the pesticides, which led the Agency to incorporate the safety factor determination into the relative potency factor process.
Specific information on dimethoate, omethoate (a metabolite of dimethoate), chlorpyrifos, and methamidophos showed no age-dependent sensitivity, allowing the FQPA factor to be removed.
For the pesticides for which such a conclusion could not be reached, EPA retained a 3X FQPA uncertainty factor in calculating the relative potencies of the pesticides.
Any harmful neurodevelopmental effects from exposure to organophosphate pesticides from a mechanism other than cholinesterase inhibition are examined and dealt with in the individual chemical assessments.
The Agency's consideration of the FQPA safety factor as it relates to the organophosphate cumulative risk assessment will be the subject of a June 25/26 meeting of the FIFRA Scientific Advisory Panel. This meeting will cover certain science issues including the role of cholinesterase in development, interpretation of animal data and factors underlying age-dependent sensitivity, and relevance of animal data to protect children.
The revised assessment being released for public review incorporates, as appropriate, public comments received on the preliminary assessment as well as advice provided by the SAP. The major differences in this assessment and the preliminary assessment include:
- The revised assessment includes consideration of the FQPA safety factor as it relates to the organophosphate cumulative risk assessment.
- The revised assessment includes an analysis of the upper tail of the exposure distribution, which determined that specific high-end consumption and/or residue values are not responsible for the exposure estimates at the higher percentiles of the exposure distribution.
- The assessment presents a range of margins of exposure at various percentiles of exposure, including the percentiles at which the margins of exposure approach 100. This information provides the basis for setting upper and lower limits or bounds on the risk estimates.
- The assessment includes risk estimates for two time periods of exposure: one-day exposures and seven-day rolling average exposures.
- Revised relative potency factors for several chemicals have been used.
- EPA has calculated relative potency factors for four additional chemicals (chlorethoxyphos, phostebupirim, profenofos, and omethoate, a metabolite of dimethoate).
- New data on exposure from the pet uses of tetrachlorvinphos have been used to include tetrachlorvinphos in the residential assessment.
- The residential assessment for the indoor uses of DDVP has been revised to account for the size of the pest strip.
- Chlorpyrifos methyl has been removed from the assessment to reflect the phase-out agreements with the registrants of those chemicals. (Fenamiphos is included in the residential assessment, with use only on golf courses. However, the Agency has concluded a phase-out agreement with the registrant.) Other use pattern changes are reflected in the assessment either as the result of corrections or additional risk mitigation actions.
- New information provided in the comment period has been incorporated, as appropriate, in the assessment. This includes revisions to processing factors used in the dietary assessment.
- The number of regions used in the regional assessment for water and residential exposure has been reduced to seven, based on similarities in climate, soils, and geography.
EPA is undertaking regional risk assessments for potential exposures from drinking water and residential pesticide uses. These regional assessments will allow the Agency to take into account the variation in uses of pesticides across the country, as well as the differences both in sources of drinking water and in the potential for presence of pesticide residues in water sources.
The Agency's food risk assessment for the organophosphate pesticides is based on residues reported in the U.S. Department of Agriculture's Pesticide Data Program. The estimate of food exposure is conducted on a national basis, since most food commodities are available in all areas of the country. EPA will combine this national food assessment with the regional drinking water and residential results.
The currently registered organophosphate pesticides are included in the revised cumulative assessment unless they:
- are being phased out according to specific legal agreements or
- pose negligible, if any, potential for exposure, based on results of their individual risk assessments
The assessment includes 30 pesticides. The full risk assessment provides details about the pesticides included and excluded.
FQPA requires EPA to consider the cumulative effects of substances that share a common mechanism of toxicity in making decisions about the safety of pesticide residues in food. EPA has determined that virtually all of the organophosphate tolerances are expected to meet the safety standard; some are still being evaluated. EPA has already taken significant actions and continues to act on risks associated with individual pesticides, based on the risk assessments for those pesticides.
This risk assessment is rich in data. EPA has gone to great lengths to obtain data to use in conducting this risk assessment. Each component of the risk assessment uses the best-available data. The sources of data vary for the food, water, and residential components of the risk assessment.
The sources of data for the food component include:
- USDA's Pesticide Data Program
- USDA's Continuing Survey of Food Intake by Individuals
- The Food and Drug Administration Center for Food Safety and Applied Nutrition monitoring data
For the water component of the assessment:
- USDA Agricultural Chemical Usage Reports for Field Crops, Fruits, and Vegetables
- USDA Typical Planting and Harvesting Dates for Field Crops and Fresh Market and Processing Vegetables
- Local sources for refinements
- Monitoring studies from USGS and other sources
For the residential/non-occupational component:
- National Home and Garden Pesticide Use Survey
- Outdoor Residential Exposure Task Force
- State Cooperative Extension Service
- Commercial Pesticide Applicators
- Choreographed Activities of Adults Measured Using Biomonitoring (Vacarro, 1996)
- Non-Scripted Activities of Children Measured Using Fluorescent Tracers (Black, 1993)
- Hand-to-Mouth Frequency of Events (Reed, 1999)
- Lawn Residue Data to Account for Saliva-Wetted Hands (Clothier, 2000)
- Pesticide Handlers Exposure Database
- Exposure Factors Handbook
EPA used an open process in developing cumulative risk assessment methods and approaches, beginning shortly after the 1996 enactment of the Food Quality Protection Act. EPA held numerous public meetings on various components of the methods used in the risk assessment:
- Technical briefings on methods and on the preliminary assessment
- More than 30 consultations with the FIFRA Scientific Advisory Panel on various issues related to scientific methods used in the assessment.
- The International Life Sciences Institute (ILSI) held workshops with EPA and other scientists on topics related to cumulative risk assessment.
- In addition, EPA released for public comment 10 science policy papers related to the cumulative process over the past several years, including the draft guidance on cumulative risk assessment for comment on June 30, 2000.
- EPA released the preliminary cumulative assessment in December 2001 and accepted public comments until March 8, 2002; the Agency is considering these comments in the development of the revised assessment.
EPA has provided opportunities for public comment on the preliminary assessment leading up to this revised assessment and has conducted technical briefings to explain the methods being used in the assessment. Continuing in this effort to ensure transparency of our decision processes, we are implementing several steps:
- EPA will open a public comment period, which will close mid-July, 2002 (see the Federal Register notice for information on submitting comments).
- On June 18, 2002, EPA will hold a technical briefing on the revised assessment.
- On June 25-27, 2002, the FIFRA Scientific Advisory Panel:
- will review the Agency's consideration of the FQPA safety factor as it relates to the organophosphate cumulative risk assessment, including certain science issues such as the role of cholinesterase in development, interpretation of animal data and factors underlying age-dependent sensitivity, and relevance of animal data to children and
- will be consulted on the status of preliminary results from cumulative risk estimates for the organophosphate pesticides using alternative models (CalendexTM , LifelineTM , and CARESTM ).
- EPA will evaluate SAP comments as well as other comments or data received and will modify this assessment as appropriate. As existing analyses are revised or new information becomes available, EPA will review this assessment and make further changes as appropriate.
The revised organophosphate cumulative risk assessment and summary documents are available on EPA's web site: www.epa.gov/pesticides/cumulative/rra-op/index.htm. It also is available from the Office of Pesticide Programs docket. Call the docket at 703-305-5805 for information.