Federal Insecticide, Fungicide, And Rodenticide Act Research Articles

U.S. EPA Regulation of Plant-Incorporated Protectants: Assessment of Impacts of Gene Flow from Pest-Resistant Plants

The U.S. Environmental Protection Agency licenses pesticide-expressing plants under the authority of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). Transgenes and their pesticidal products represent pesticides under FIFRA and are referred to as plant-incorporated protectants (PIPs). When sexually compatible wild relatives (SCWR) are sympatric with PIP crops, there is a need to assess the potential for adverse effects to man and the environment resulting from transgene introgression in accord with FIFRA requirements. Genetic compatibility, introgression, weediness of SCWR × PIP hybrids, seed dispersal, and dormancy, among other parameters, as well as effects on other species (herbivores and beneficial insects), all need to be considered as part of the risk assessment for experimental use under Section 5 or registration under Section 3 of FIFRA. EPA is currently developing data requirements and guidance toward addressing potential gene flow impacts from PIPs.

Quantitative analysis of over 20 years of golf course monitoring studies

The purpose of the present study was to comprehensively evaluate available golf course water quality data and assess the extent of impacts, as determined by comparisons with toxicologic and ecologic reference points. Most water quality monitoring studies for pesticides have focused on agriculture and often the legacy chemicals. There has been increased focus on turf pesticides since the early 1990s, due to the intense public scrutiny proposed golf courses receive during the local permitting process, as well as pesticide registration evaluations by the U.S. Environmental Protection Agency under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Results from permit-driven studies are frequently not published and knowledge about them is usually not widespread. Forty-four studies involving 80 courses from a 20-year period passed our quality control and other review criteria. A total of 38,827 data entries (where one analysis for one substance in one sample equals a data entry) from pesticide, pesticide metabolite, total phosphorus, and nitrate analyses of surface water and groundwater were evaluated. Analytes included 161 turf-related pesticides and pesticide metabolites. Widespread and/or repeated water quality impacts by golf courses had not occurred at the sites studied, although concerns are raised herein about phosphorus. Individual pesticide database entries that exceed toxicity reference points for groundwater and surface water are 0.15 and 0.56%, respectively. These percentages would be higher if they could be expressed in terms of samples collected rather than chemicals analyzed. The maximum contaminant level ([MCL]; 10 mg/L) for nitrate-nitrogen was exceeded in 16/1,683 (0.95%) of the groundwater samples. There were 1,236 exceedances of the total phosphorus ecoregional criteria in five ecoregions for 1,429 (86.5%) data entries. (This comparison is conservative because many of the results in the database are derived from storm flow events.) Thus, phosphorus appears to present the greatest water quality problem in these studies. Pesticides detected in wells had longer soil metabolism half-lives (49 d) compared with those not detected (22 d), although the means were not significantly different.

Panel Discussion – Regulatory and Policy Issues around Non-Target Mortality and Environmental Fate of Rodenticides

Author(s): Eisemann, John D.; Swift, Catherine E.; Dunlevy, Peter A.; Pitt, William C.; Witmer, Gary W. | Abstract: One of the goals of this Symposium was to bring together agricultural and conservation users of rodenticides to discuss the impacts of rodenticides on the environment, examine the current regulatory climate governing their use, and identify ways that users can reduce or eliminate these impacts. Some of the presentations in today’s symposium highlighted specific impacts, and the preceding talk described the scenario of what can happen if an issue related to pesticide impacts ends up in the courts. The three agencies that were represented on this panel (USDA, USFWS, and EPA) have regulatory oversight and enforcement authority for the use of rodenticides and/or the adverse effects resulting from the use of rodenticides. In addition, USDA and FWS are the primary federal users of rodenticides for agriculture and conservation. USDA holds the registrations for a number of rodenticide products for agricultural and conservation purposes. Panelists were asked to describe how Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), Migratory Bird Treaty Act (MBTA), Endangered Species Act (ESA), National Environmental Policy Act (NEPA), the Animal Damage Control Act, and the administration of USDA’s pesticide labels apply to rodenticide adverse effects. Panelists were then asked to bring up an issue within the scope of their agency that they view as problematic for conducting eradication projects. Panelists were also asked to suggest proactive measures that the rodent eradication community can undertake to improve future rodent eradication efforts. Finally, the floor was opened to audience members for questions and comments.

Florida Agricultural Handbook of Solid and Hazardous Waste Regulation: Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

Revised! Circular 1139, a multi-part handbook by Michael T. Olexa and Ian Goldfarb, helps Floridians recognize which agricultural and household activities may involve solid and hazardous wastes. It also provides an introduction to the agencies and statutes that govern solid and hazardous waste disposal. Published by the UF Department of Food and Resource Economics, November 2008. Ask IFAS: Florida Agricultural Handbook of Solid and Hazardous Waste (2008) (ufl.edu)

Organophosphates, Friend and Foe: The Promise of Medical Monitoring for Farm Workers and Their Families

ABSTRACT Millions of farm workers nation-wide who load, mix and/or apply pesticides are exposed to incredible amounts of pesticides on a daily basis. Various inefficiencies and inconsistencies in the system--including insufficient illness reporting data systems, lack of compliance and enforcement, and inadequate data and information on the chronic effects of exposure and overexposure to various pesticides--increase the likelihood that these workers will continue to be exposed to dangerous amounts of pesticides. This Article assesses the existing mechanisms designed to protect farm workers from occupational exposure to pesticides and identifies and analyzes some of the shortcomings of the system. It focuses on the class of pesticides known as organophosphates and examines the impact that such pesticides can have on farm workers as well as on their families. It then evaluates the State of Washington's medical monitoring rule, and recommends implementation of a federal medical monitoring program as a means of protecting all American farm workers from the dangers of pesticide overexposure. I. INTRODUCTION II. ORGANOPHOSPHATE BACKGROUND A. Importance of Organophosphates B. Concerns Over Organophosphates III. EXPOSURE BY SENSITIVE SUBPOPULATIONS A. Concern for Farm Worker Exposure B. Exposure by Children of Farm Workers IV. THE WASHINGTON STATE MEDICAL MONITORING CASE A. Medical Monitoring Rule B. Opponents of the Rule C. Initial Results V. IMPROVING FARM WORKER PROTECTIONS A. Determining Risks B. The Pesticide Industry C. History of Legislation D. Recommendations for a National Medical Monitoring Rule E. Additional Protection Outside the Medical Monitoring Rule VI. CONCLUSION I. INTRODUCTION In 1999, a healthy fifteen-year-old migrant farm worker named Jose Casillas left his home in Mexico for the orchards of central Utah hoping to earn enough to support his family in Mexico. (1) A few months after his arrival, Casillas was sprayed by an applicator-tractor Guthion Solupak, a pesticide similar to Sarin. (2) Earlier that same week, Casillas had been sprayed other pesticides--which he believed to be only water--while he was working in the field. (3) After the first field exposure, Casillas suffered intense headaches. After the second exposure, Casillas began to vomit, sweat excessively and suffer diarrhea. (4) Despite being ill, Casillas attempted to ride his bike to work the next morning but lost consciousness and collapsed. By the time medical help arrived, he was dead, with foam streaming from his nose. (5) There are legal protections that are supposed to prevent tragedies like this. For instance, it is illegal to spray pesticides when workers are in fields, and farmers are supposed to be informed about, and take preventative steps to protect against, pesticide poisoning. (6) Moreover, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7) requires states to certify pesticide applicators who use restricted-use pesticides and anyone who commercially sells, distributes, or applies pesticide products. (8) Additionally, FIFRA standards require that an individual be deemed competent before they can be formally certified to use or handle pesticides. (9) Sadly for Casillas, and many other farm workers across the United States, these regulatory guarantees are not enough. Despite such protections, millions of farm workers nationwide who load, mix and apply pesticides are exposed to incredible amounts of pesticides every day. They can be exposed through direct handling of pesticide products, daily work around recently treated areas, contaminated and often inadequate clothing, and inhalation of airborne pesticides drifting in the winds. Occasionally, farm workers, like Casillas, suffer direct exposure. …

Test substance characterization for the EPA: what you've always wanted to know but were afraid to ask

AbstractThe Society of Quality Assurance (SQA) GLP Specialty Section, a member of the SQA Regulatory Forum, is a group of participants from the regulated community which provides insight and guidance to our membership and the regulated community. The Specialty Section has encountered several participants who want to know what types of information and data are needed during an inspection by the US EPA's Office of Enforcement and Compliance Assurance (OECA). The OECA is responsible for monitoring studies submitted to the Office of Pesticide Programs in support of pesticide registrations as defined under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). All submitted studies are to be conducted according to the FIFRA US Good Laboratory Practice Standards (GLPS). The GLPS contain specific language concerning the characterization of test, control and reference substances used in these studies. This article clarifies those requirements and provides perspective on the EPA expectations on meeting those requirements. The topics of discussion include: regulatory requirements responsibilities of the testing facility management, study director, Quality Assurance Unit and the sponsor preparing for an inspection overview of data to be made available at the time of inspection composition of a Certificate of Analysis. Copyright © 2008 John Wiley & Sons, Ltd.

REGULATORY CONSIDERATIONS WITH BIOLOGICAL CONTROL OF PUBLIC HEALTH PESTS

Laws and regulations specifically focused on biological control of public health pests are rare, so public health staff that implement biocontrol programs for mosquitoes must be familiar with a large number of more general statutory and regulatory requirements that do apply, and that have become increasingly demanding in recent years. These requirements can be divided into two basic categories. First, numerous laws and regulations directly govern introductions or relocations of living organisms; while most focus on ‘‘pest’’ or ‘‘nuisance’’ species and how to minimize their potential negative impacts, some specifically address biological control activities. Second, a wide range of general-purpose environmental statutes, including laws protecting endangered species, regulating pesticide use, protecting water quality, and requiring evaluation of environmental impacts, regulate biological control programs indirectly. Compliance with all the relevant laws and regulations can be challenging, in part because of the sheer number and variety of requirements, but also because the requirements of different laws, agencies, or levels of government are frequently ambiguous or contradictory, and finally because they vary dramatically depending on the site and the species used. In some jurisdictions such as California, Hawaii, or New Zealand, which have large numbers of rare or endemic organisms and well-developed agricultural sectors, the regulatory requirements for releasing novel biological control agents can be quite stringent. In other places and/ or with more familiar or established organisms such as Gambusia affinis, specific rules may be nonexistent or straight-forward, though general environmental laws can still demand considerable attention and care. This chapter is divided into five sections, starting with an introduction to essential legal and regulatory concepts and terms. The second section reviews governmental oversight over the release or relocation of living organisms in general, while the third more narrowly focuses on regulation of biological control in particular. Next is an introduction to general environmental statutes, including the National Environmental Policy Act (NEPA), the Endangered Species Act (ESA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Clean Water Act (CWA), and equivalent statutes in other jurisdictions. Finally, a case study of fish stocking for mosquito control in California illustrates many of the regulatory principles and challenges associated with biological control of public health pests. This chapter emphasizes U.S. and, even more specifically, California laws and regulations; though the principles are broadly applicable, some laws and regulations from other jurisdictions are also used to illustrate variations.

Uncalibrated modelling of conservative tracer and pesticide leaching to groundwater: comparison of potential Tier II exposure assessment models

The Root Zone Water Quality Model (RZWQM) and Pesticide Root Zone Model (PRZM) are currently being considered by the Office of Pesticide Programs (OPP) in the United States Environmental Protection Agency (US EPA) for Tier II screening of pesticide leaching to groundwater (November 2005). The objective of the present research was to compare RZWQM and PRZM based on observed conservative tracer and pesticide pore water and soil concentrations collected in two unique groundwater leaching studies in North Carolina and Georgia. These two sites had been used previously by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Environmental Model Validation Task Force (EMVTF) in the validation of PRZM. As in the FIFRA EMVTF PRZM validation, 'cold' modelling using input parameters based on EPA guidelines/databases and 'site-specific' modelling using field-measured soil and hydraulic parameters were performed with a recently released version of RZWQM called RZWQM-NAWQA (National Water Quality Assessment). Model calibration was not performed for either the 'cold' or 'site-specific' modelling. The models were compared based on predicted pore water and soil concentrations of bromide and pesticides throughout the soil profile. Both models tended to predict faster movement through the soil profile than observed. Based on a quantitative normalised objective function (NOF), RZWQM-NAWQA generally outperformed or was equivalent to PRZM in simulating pore water and soil concentrations. Both models were more successful in predicting soil concentrations (i.e. NOF < 1.0 for site-specific data, which satisfies site-specific applicability) than they were at predicting pore water concentrations.

Embracing Uncertainty, Complexity and Change: An Eco-Pragmatic Reinvention of a First Generation Environmental Law

Recent scientific reports demonstrate that despite more than thirty years of environmental regulation, we are experiencing unprecedented declines in bird and wildlife species, as well as ecosystem services. Pesticides are at least in part to blame for these profound declines. U.S. pesticide law has failed to carryout its mission. Moreover, a number of lawsuits have been filed recently asserting that the registration of certain pesticides is in violation of the federal endangered species act. One of the great ironies of environmental law is that the ecological consequences of pesticide use, such as the devastating impacts DDT had on predatory bird populations, which fueled the environmental movement of the late 1960's and early 1970's, largely have been ignored for the past 30 years. Only very recently has there been renewed interest in the ecological (as opposed to human health) risks posed by pesticides. Moreover, the explosion of pesticidal genetically modified organisms (GMOs) in agriculture has raised concerns regarding the novel risks to biodiversity posed by these new pesticides. Surprisingly, however, the primary federal statute governing pesticides, the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), has not changed significantly with regard to ecological matters since 1972 and remains primarily a consumer protection statute not well suited for ecological protection. Moreover, the manner in which the Environmental Protection Agency (EPA) has implemented FIFRA has not kept pace with developments in our understanding of the uncertainty, complexity, and changing nature of ecological systems. This Article breaks new ground by being the first to use the new legal discipline of to analyze, and then reinvent, U.S. pesticide law to better protect ecological resources. For years, environmental legal scholars have sought a middle ground between absolutist risk-based approaches to environmental regulation and cost/benefit analysis approaches. In the past several years, scholars have begun exploring the emerging field of eco-pragmatism - a dramatic new framework for environmental decision-making developed by Professor Daniel Farber - as a way to achieve a workable middle ground. Although a number of prominent legal scholars have analyzed eco-pragmatism in a general sense, none have attempted to apply an eco-pragmatic framework to any environmental pollution control law. This Article is the first to do so. This Article builds on Farber's work and the works of a number of other prominent legal scholars by first bolstering eco-pragmatism through consciously incorporating into it principles of ecological science, and then applying the strengthened eco-pragmatism to a long overlooked area - pesticide law. As the first attempt to actually apply eco-pragmatism to a field of environmental pollution control law, this Article represents an important step in the development of this area of legal theory. By analyzing current pesticide law as well as EPA's implementation of such law through an eco-pragmatic lens, this Article identifies areas of the law that are in need of revision and proposes revisions based on eco-pragmatic principles, which if implemented would greatly enhance our ability to protect critical ecological resources.

Application of GMOs in the U.S.: EPA research &amp; regulatory considerations related to soil systems

During the last 20 years recombinant biotechnology has resulted in the development of organisms with unique genetic compositions, some of which are for intentional release to the environment. While concerns have been raised that such organisms may be capable of inducing transient unintended environmental effects, longer-term perturbations to soil processes and non-target species effects have yet to be demonstrated. In parallel with the growth of the commercial biotechnology industry has come a significant growth in regulatory review processes intended to evaluate the risks of these GMO products. Under the Toxic Substances Control Act (TSCA), certain new microbial products that undergo pre-manufacture review are examined for human and environmental risks using data and other information received in accordance with the U.S. Environmental Protection Agency’s (EPA’s) “Points to Consider” guidance document. In the risk assessment process, carried out under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA) authorities, EPA evaluates both microbial pesticide products and plants with pesticidal properties to determine if Federal safety standards are met. For all pesticide products, including genetically engineered pesticides, EPA receives testing of product composition and chemical properties, human health effects, environmental effects on non-target pests, and the fate of the pesticide in the environment. The EPA’s Office of Research and Development supports risk assessment research related to such GMO products. This paper focuses on relevant EPA research and regulatory examples related to soil effects considerations for GMOs.

Comparative Analysis of Passive Dosimetry and Biomonitoring for Assessing Chlorpyrifos Exposure in Pesticide Workers

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreasonable adverse human health effects associated with pesticide exposure. Accordingly, the EPA requires pesticide registrants to perform studies evaluating the potential for pesticide handler exposure. Data from five such studies that included exposure measurements based on both external measurements and biological monitoring were used to examine methods of assessment, routes and determinants of exposure and dose to the pesticide chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders (M/L, n = 24), mixer/loader/applicators (M/L/A, n = 37), applicators (A, n = 9) and re-entry scouts (RS, n = 10). Results showed that doses were highly variable and differed by job class (P < 0.05) with median total (inhalation and dermal combined) exposure-derived absorbed doses (EDADtot) of 129, 88, 85 and 45 microg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the measurement of 3,5,6-trichloro- 2-pyridinol (3,5,6-TCP) in urine were similar in magnitude but differed in rank with median values of 275, 189, 122 and 97 microg/application for A, M/L, RS, and M/L/A, respectively. The relative contribution of dermal to inhalation exposure was examined by their ratio. The median ratios of exposure-derived absorbed dermal dose (EDADderm) (assuming 3% absorption) to exposure-derived absorbed inhalation dose (EDADinh) (assuming 100% absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%), this ratio exceeded 1.0, indicating the significance of the dermal exposure pathway. Different dermal absorption factor (DAF) assumptions were examined by comparing EDADtot to the biomarker-derived absorbed dose (BDAD) as a ratio where EDADtot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45, 0.71 and 1.28, respectively, were determined suggesting the DAF is within the range of 3-10%. A simple linear regression of urinary 3,5,6-TCP against EDADtot indicates a positive association explaining 29% of the variability in the 3,5,6-TCP derived estimate of dose. A multiple linear regression model including the variables EDADderm, EDADinh and application type explained 46% of the variability (R2 = 0.46) in the urinary dose estimate. EDADderm was marginally significant (P = 0.066) while EDADinh was not (P = 0.57). The EDADderm regression coefficient (0.0007) exceeded the coefficient for EDADinh (0.00002) by a factor of 35. This study demonstrates the value of the pesticide registrant database for the purpose of evaluating pesticide worker exposure. It highlights the significance of the dermal exposure pathway, and identifies the need for methods and research to close the gap between external and internal exposure measures.

Citizen Lawsuit Involving Chemical Spraying Can Proceed Under the CWA

The US Court of Appeals for the Second Circuit has determined that a citizen enforcement suit brought under the Clean Water Act (CWA) that was based on the use of chemicals regulated by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) could proceed regardless of whether the alleged violation of the CWA was also a substantial violation of FIFRA.

Registration of disinfectants based on relative microbicidal activity.

Along with proper hand hygiene, disinfection of contaminated surfaces and medical instruments has been a key method of preventing patient-to-environment-to-patient transmission of infectious agents via the hands of healthcare workers.1-3 However, there is growing concern regarding the increase in antibiotic-resistant pathogens for which environmental and device contamination may play a role in disease transmission, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Clostridium difficile, and multidrugresistant aerobic gram-negative bacilli (eg, Pseudomonas aeruginosa and Acinetobacter).1 Proper use of disinfectants plays an important role in reducing person-to-person transmission of these pathogens. For decades, the medical community in the United States has relied on the federal government’s disinfectant testing and registration program for assurance that registered disinfectants meet their label claims. However, recognized flaws in test methodologies could result in registration of ineffective disinfectants.4 Control measures should be instituted at the federal level to improve the test methodology and reduce the frequency of contaminated or ineffective disinfectants and the threat of serious healthcare-associated infections related to disinfectant use. We have previously reviewed the issues surrounding the selection and registration of high-level disinfectants and chemical sterilants.5 However, there are several unique aspects of testing and registration of low-level and intermediate-level disinfectants (eg, microbicidal testing methods) that warrant separate discussion. This article proposes a scheme for testing and registration of low-level and intermediate-level disinfectants that could be used by the U.S. Environmental Protection Agency (EPA). BACKGROUND Chemicals formulated as disinfectants in the United States are registered and regulated in interstate commerce by the Antimicrobial Division, Office of Pesticides Program, EPA. The authority for this activity was mandated by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) in 1947. In June 1993, the U.S. Food and Drug Administration (FDA) and the EPA issued a “Memorandum of Understanding” that divided responsibility for review and surveillance of chemical disinfectants between the two agencies. Under the agreement, the FDA regulates disinfectants used on critical or semicritical medical devices and antiseptics and the EPA regulates disinfectants used on noncritical surfaces. In 1996, Congress passed the Food Quality Protection Act (FQPA). The Act amended FIFRA regarding several products regulated by both the EPA and the FDA. One provision of FQPA is that regulation of disinfectants used on critical and semicritical medical devices (the EPA continues to regulate non-medical disinfectants) was removed from the jurisdiction of the EPA and now rests solely with the FDA.1,6 Examples of disinfectants that are registered by the EPA with the intent of providing a public health benefit, therefore requiring efficacy data as a condition of their registration, include disinfectants used in hospitals and other healthcare settings on floors, walls, and medical equipment surfaces and household products claiming to have disinfectant activity. There are three types of disinfectant products that the EPA registers based on submitted efficacy data: limited, general or broad-spectrum, and hospital disinfectants. When a disinfectant is represented in its labeling for use in hospitals, medical clinics, dental offices, or any other medical-related facility, it must show

Comparative organ system development: introduction.

It is well known that development continues postna-tally in both humans and animals. There has also beenrecent concern in the scientific and regulatory arenas thatimproved safety assessments for pediatric populationsare needed. The need for the evaluation of potentialtoxicity in immature animals has been raised (WHO,1986; Guzelian et al., 1992; EPA, 1999). Regulatoryrequirements for hazard and risk assessment specific tothe immature individual have received a lot moreattention within the past several years (Kimmel andMakris, 2001). For pesticides, regulatory attention hasincluded the 1996 Food Quality Protection Act (FQPA),an amendment to the Federal Insecticide, Fungicide, andRodenticide Act (FIFRA) and the Federal Food, Drug,and Cosmetic Act (FFDCA), which specifically mandatesa focus on children’s health risks from pesticideexposure. For pharmaceuticals, the FDA Center for DrugEvaluation and Research (CDER) developed regulationsrequiring the assessment for use in pediatric patients(FDA, 1998a,b), including functional evaluations depend-ing on the intended use, pharmacologic activity of thedrug, and expected target organ or system. In order tocomply with the FDA’s and EPA’s regulations, studies injuvenile animals are being initiated. However, as theincrease in studies in young animals continues, it hasbecome clear that there are many challenges to thedesign, conduct, and interpretation of these new data.The Developmental and Reproductive ToxicologyTechnical Committee of the ILSI Health and Environ-mental Sciences Institute (HESI) has undertaken a projectto address the need for developing information oncomparative postnatal development in animal modelsand humans. Overall, the project is focused around 4objectives. First, a focused review of current knowledgeof comparative postnatal development (functional and/or physiological) identifying stage marks for organsystem development and key physiologic developmentallandmarks was undertaken. This information wasdeemed a critical component in the design and conductof studies in young animals. Second, a review of theclinical experience for pediatric toxicity was undertaken.The intent was to evaluate the differences in sensitivitybetween children and adults, reviewing relevant casestudies focusing on the key endpoints of significance andtheir relationships to endpoints used in animal models.The third objective is to define the decision process(es)to determine when juvenile animal studies are needed toprovide safety assessments; and the fourth objective is topropose effective study designs and testing strategies.The following series of mini-reviews on the malereproductive system, the female reproductive system, thelung, kidney, and bone, is the result of efforts to addressthe first objective. Additional reviews on the heart,central nervous system, and immune system will followand complete this objective. Activity is ongoing on theadditional objectives and a workshop is being plannedfor summer/fall 2003, to address the overall project andspecifically objectives three and four. The reviews serveas the basis for identifying information to guide animalmodel selection for pediatric safety assessments.

Using Monte Carlo techniques to judge model prediction accuracy: Validation of the pesticide root zone model 3.12

Individuals from the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force (FEMVTF) Statistics Committee periodically met to discuss the mechanism for conducting an uncertainty analysis of Version 3.12 of the pesticide root zone model (PRZM 3.12) and to identify those model input parameters that most contribute to model prediction error. This activity was part of a larger project evaluating PRZM 3.12. The goal of the uncertainty analysis was to compare site-specific model predictions and field measurements using the variability in each as a basis of comparison. Monte Carlo analysis was used as an integral tool for judging the model's ability to predict accurately. The model was judged on how well it predicts measured values, taking into account the uncertainty in the model predictions. Monte Carlo analysis provides the tool for inferring model prediction uncertainty. We argue that this is a fairer test of the model than a simple one-to-one comparison between predictions and measurements. Because models are known to be imperfect predictors prior to running the model, the inaccuracy in model predictions should be considered when models are judged for their predictive ability. Otherwise, complex models can easily fail a validation test. Few complex models, such as PRZM 3.12, would pass a typical model validation exercise. This paper describes the approaches to the validation of PRZM 3.12 used by the committee and discusses issues in sampling distribution selection and appropriate statistics for interpreting the model validation results.

Review of the validation of models used in Federal Insecticide, Fungicide, and Rodenticide Act Environmental exposure assessments

The first activity of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force, established to increase confidence in the use of environmental models used in regulatory assessments, was to review the literature information on validation of the pesticide root zone model (PRZM) and the groundwater loading effects of agricultural management systems (GLEAMS). This literature information indicates that these models generally predict the same or greater leaching than observed in actual field measurements, suggesting that these models are suitable for use in regulatory assessments. However, additional validation research conducted using the newest versions of the models would help improve confidence in runoff and leaching predictions because significant revisions have been made in models over the years, few of the literature studies focused on runoff losses, the number of studies having quantitative validation results is minimal, and modelers were aware of the field results in most of the literature studies. Areas for special consideration in conducting model validation research include improving the process for selecting input parameters, developing recommendations for performing calibration simulations, devising appropriate procedures for keeping results of field studies from modelers performing simulations to validate model predictions while providing access for calibration simulations, and developing quantitative statistical procedures for comparing model predictions with experimental results.

Development of a Monte Carlo sampling shell for the pesticide root zone model and its application by the Federal Insecticide, Fungicide, and Rodenticide Act Environmental modeling validation Task Force

A user interface to the U.S. Environmental Protection Agency pesticide root zone model (PRZM) was constructed to allow Monte Carlo sampling of input parameter distributions. The interface was constructed employing the Visual Basic for Applications development environment, along with the functionality of the Crystal Ball Professional forecasting and risk analysis package. The tool has been utilized by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force to perform detailed statistical analyses of model input parameter uncertainty and the propagation of this uncertainty on the model outputs as well as comparisons of modeled and field-measured data.

Guidelines and Resources for Conducting an Environmental Crime Investigation in the United States

Abstract Common environmental crimes in the United States include the illegal disposal of hazardous waste, unpermitted discharges to sewer systems or surface water, discharge of oil by vessels to waters within United States jurisdiction, the misapplication of pesticides, the illegal importation of ozone-depleting substances, data falsification, and laboratory fraud. Federal, state, and sometimes local statutes and regulations are in place to protect the water, air, land, and human health. From a federal perspective, these include the Resource Conservation and Recovery Act (RCRA) for hazardous wastes, the Toxic Substances Control Act (TSCA) for toxic substances, the Clean Air Act (CAA), the Clean Water Act (CWA), the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) for abandoned waste sites, and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) for pesticides. Each of these laws contains some standard methods for sampling and analyses to prove environmental crimes. The Code of Federal Regulations (CFR) contains the specific requirements of the laws. Within the United States Environmental Protection Agency (USEPA), the Criminal Investigation Division (CID) of the Office of Criminal Enforcement, Forensics and Training (OCEFT) has the responsibility to investigate criminal offenses. Criminal offenses are more serious in nature than civil violations in the United States. To successfully prosecute an environmental criminal case, the government has to prove, beyond a reasonable doubt, that a corporation or person knowingly violated an environmental statute containing criminal sanctions. The same environmental forensic techniques used to provide scientifically defensible data prevail in both civil and criminal cases; the only distinction between the two types of cases is legal.

Guest Editorial

Common environmental crimes in the United States include the illegal disposal of hazardous waste, unpermitted discharges to sewer systems or surface water, discharge of oil by vessels to waters within United States jurisdiction, the misapplication of pesticides, the illegal importation of ozone-depleting substances, data falsification, and laboratory fraud. Federal, state, and sometimes local statutes and regulations are in place to protect the water, air, land, and human health. From a federal perspective, these include the Resource Conservation and Recovery Act (RCRA) for hazardous wastes, the Toxic Substances Control Act (TSCA) for toxic substances, the Clean Air Act (CAA), the Clean Water Act (CWA), the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) for abandoned waste sites, and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) for pesticides. Each of these laws contains some standard methods for sampling and analyses to prove environmental crimes. The Code of Federal Regulations (CFR) contains the specific requirements of the laws. Within the United States Environmental Protection Agency (USEPA), the Criminal Investigation Division (CID) of the Office of Criminal Enforcement, Forensics and Training (OCEFT) has the responsibility to investigate criminal offenses. Criminal offenses are more serious in nature than civil violations in the United States. To successfully prosecute an environmental criminal case, the government has to prove, beyond a reasonable doubt, that a corporation or person knowingly violated an environmental statute containing criminal sanctions. The same environmental forensic techniques used to provide scientifically defensible data prevail in both civil and criminal cases; the only distinction between the two types of cases is legal.

An Evaluation of the Common Mechanism Approach to the Food Quality Protection Act: Captan and Four Related Fungicides, a Practical Example

Under the Food Quality Protection Act (FQPA) of 1996 (Act), the United States Environmental Protection Agency (EPA) is mandated to conduct cumulative risk assessment on pesticides that act through a common mechanism of toxicity. Incumbent on the Agency is the development of sound scientific principles upon which to evaluate compounds for the presence of a common mechanism. Using the currently available draft guidance criteria, this paper employs five fungicides of the same general class, typified by captan, to evaluate both the criteria and the available scientific data.Captan and folpet are two chloroalkylthio fungicides currently registered with EPA under Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) for agricultural use. As such, these compounds are subject to the provisions of FQPA. Three additional fungicidal compounds—dichlofluanid, tolylfluanid, and captafol—are not registered for use in the United States; however, these five compounds have chemical structure and biological toxicity similarities and differences that permit their utility as test cases to determine what the EPA would conclude, with regard to common mechanism, if these draft guidelines were applied to these compounds.The results of the analyses are consistent and support the conclusion that captan and folpet share a common mode of toxicity for mouse duodenal tumors as defined in the Act. This common mode of toxicity is not shared by dichlofluanid, tolylfluanid, or captafol.The basis for concluding a common mechanism exists between captan and folpet. They include 1. Structural Similarity—The compounds are structural analogs having the identical biologically active moiety (i.e., the-SCCl3side chain). 2. Mechanisms of Pesticidal Action—The compounds have the same mechanism of action. The overwhelming body of evidence suggests they are active because of their reactions with thiols. Both compounds, in reacting with thiols, produce similar degradates. Differences in rates of reaction are attributable to physical-chemical properties of the two compounds. 3. General Mechanisms of Mammalian Toxicity—The compounds induce mammalian toxicity through the same mechanism that is responsible for their pesticidal action, reactions with thiols. Another, albeit less likely, mechanism (for both compounds) is cross-Unking of proteins with DNA, although the extremely short half-lives of these compounds (seconds) argues against this possibility. 4. Sites of Action—Both compounds express their primary toxicity as local rather than systemic effects. 5. Common Toxic Endpoint—These two compounds induce gastrointestinal tumors (in mice only). 6. Mode of Action—Both compounds express their common toxic endpoint through a nongenotoxic, compensatory proliferation mechanism. 7. Specificity of Action—For both compounds, the majority of tumors appear in the duodenum. Furthermore, these tumors are induced only in mice. Repeated carcinogenicity testing suggests that rats are refractive to the effects of captan and folpet. The significantly faster hydrolytic rate for folpet at the lower pH values (e.g., increased 8-fold at pH 5) encountered in the stomach is believed to account for the tumors of the stomach observed with folpet and not captan. 8. Other Toxic Endpoints—For other toxic endpoints where comparative data are available, captan and folpet show similar patterns of toxicity (e.g., mutagenicity, skin sensitization, and acute toxicity).