F ood Q uality P rotection A ct of 1996

Chapter 31 - Risk Assessment and Risk Management: The Regulatory Process

Chapter 62 - Risk Assessment and Risk Management: The Regulatory Process

In Response: A Government perspective.

The U.S. Environmental Protection Agency's Office of Pesticide Programs (OPP) is a licensing program that regulates pesticides in the U.S under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). As part of this program, OPP has a regulatory mandate to evaluate a substantial body of health effect and exposure data in order to assess the effects of pesticides on human health. Through this evaluation, OPP plays a critical role in translating observational research into regulatory science and aims to ensure that pesticide risk assessments incorporate epidemiologic evidence on the potential adverse effects on people that may result from pesticide exposure through dietary, environmental, and occupational exposure pathways. The thematic poster will provide background on OPP's regulatory requirements and then describe the systematic review methodology used to evaluate epidemiologic evidence based on a scientifically robust and transparent approach. This description will emphasize key regulatory considerations and outline elements of OPP's 2016 framework for incorporating epidemiological data into risk assessments for pesticides. The 2016 framework may be of interest to a range of stakeholders in the scientific community and characterizes OPP's "fit-for-purpose" approach to systematic review. OPP uses this approach to define to the scope and complexity of reviews and integrate epidemiologic findings into OPP's overall risk assessment process.

The US Environmental Protection Agency (EPA) regulates pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). Under FIFRA, the EPA is authorized to regulate pesticides to ensure that their use does not cause unreasonable adverse effects to humans and the environment. Under FFDCA, EPA has the responsibility to establish tolerances for pesticide residues on food crops. A tolerance is the maximum allowable residue of a pesticide on food. Such regulatory oversight is designed to minimize risks while allowing the public to benefit from pesticide use. Prior to lawful use in commerce, a pesticide must be registered by the EPA, unless specifically exempted by regulation. Registrants of pesticides are responsible for submitting specific data to the agency to support the conclusion that the pesticide will not significantly increase the risk of adverse effects to humans or to the environment. Once a pesticide is registered by the EPA, it may be sold and distributed in the United States and used as specified on the approved label.

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), enacted in 1947 and amended in 1972, 1978, and 1988, established federal regulation of pesticides in order to protect human and environmental health. FIFRA has been under the jurisdiction of the U.S. Environmental Protection Agency (EPA) since the EPA’s inception in 1970. Although FIFRA requires EPA to consider the benefits of a pesticide’s use, EPA must ensure that the pesticide is used without posing unreasonable adverse effects to human health or the environment. Furthermore, the Endangered Species Act (ESA), enacted in 1973, requires federal agencies to protect species vulnerable to extinction without consideration of costs. The amendments to FIFRA in 1972, 1978, 1988, and 1996 mandated the EPA review and reevaluate the eligibility of older pesticide products for reregistration under the updated FIFRA standard, while also complying with the new environmental laws of the 1970s. Today EPA’s goal is to review existing pesticide product registrations at least every 15 years under “Registration Review.” To meet their responsibilities under the ESA, EPA is initiating consultations with the U.S. Fish and Wildlife Service (USFWS) during the Registration Review process. The first pesticide active ingredients to advance to consultations under Registration Review are those in gas cartridge products. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) holds two gas cartridge product registrations. As a federal agency, APHIS also must comply with the ESA and consults with the USFWS on wildlife damage management activities, including tools such as pesticide products. This discussion presents APHIS’ unique ground view as a federal agency navigating the EPA’s ESA consultations during the Registration Review process, and describes the mitigation measures and their impacts on APHIS Wildlife Services’ activities.

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) is the predominant statute for regulating economic poisons commonly referred to as pesticides. FIFRA is arguably the most forceful environmental statute, and deservedly so, for regulating toxic releases expected to kill or deter pest organisms and potentially other nontarget organisms. National pesticide control was first attempted by the Insecticide Act of 1910, a limited law whose essence was to prevent the sale of any adulterated or mis-branded fungicide or insecticide. The Office of Pesticide Programs within Environmental Protection Agency administers the statutory requirements under FIFRA. Ecological risk assessments are required to determine whether use of a pesticide will present an unreasonable risk to the environment. The potential aquatic risks of a proposed pesticide to nontarget finfish and invertebrates in freshwater and estuarine environments are examined by comparing toxicological and exposure data using regulatory risk criteria.

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.

<h3>Introduction</h3> The U.S. Environmental Protection Agency’s Office of Pesticide Programs (OPP) is a licensing program that regulates pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). As part of this program, OPP has a regulatory mandate to evaluate research on the health effects of pesticides and plays a critical role in translating epidemiologic research into regulatory science and policy. <h3>Objectives</h3> OPP has developed a framework to ensure that pesticide risk assessments include systematic evaluation of epidemiologic research on the potential adverse effects of pesticide exposure. The objective of the presentation is to raise awareness about how epidemiologic research on pesticides can inform risk assessment and occupational health policy by: (1) Providing background on OPP’s risk assessment process, (2) Describing how OPP evaluates epidemiologic research using an approach that is scientifically robust and transparent; and (3) Highlighting opportunities for collaboration between researchers and risk assessors on the translation of epidemiologic research into risk assessment. <h3>Methods</h3> OPP has extensive experience evaluating epidemiology studies on pesticides and is required to review all registered pesticides according to a 15-year registration review schedule. Building off of this experience, OPP will provide a survey of its evaluation approach and explore challenges that may be promising areas for future collaboration between researchers and risk assessors. <h3>Results and Conclusions</h3> EPA/OPP routinely evaluates epidemiology research on pesticides and is guided by a systematic review framework that is scientifically robust and transparent. While epidemiologic research increasingly plays important role in the risk assessment process, there are important regulatory challenges that often limit the ability of OPP to translate research findings into policy. Therefore, there is a critical need to strengthen collaboration between researchers and risk assessors to better understand the scientific capabilities and data needs across occupational health disciplines.

Summary:The purpose of this symposium was to create an awareness of pesticide regulation research and not to discuss the positive and negative aspects of regulation. In this respect three topics of interest were discussed; federal, biological, and economic issues of regulation.Pesticide usage has been regulated in some form by the Federal Government since the 1930s. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1972 gave the Environmental Protection Agency (EPA) explicit authority to regulate these pesticides. The primary criterion for decision making under the statute is “unreasonable adverse effects on the environment” which is defined in FIFRA as “any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of any pesticide.”Once it is determined a pesticide does have adverse effects, then it enters the Rebuttable Presumption Against Registration (RPAR) process. The RPAR process determines the risks, costs, and benefits associated with the suspect chemical. This process is a coordinated effort between EPA, the United States Department of Agriculture, and the states. When the analysis is completed, the EPA administrator weighs the risks and benefits and determines whether regulatory action is required. Legal mitigation may then follow.Government regulation affects the discovery and development of pesticides and redirects research programs and production practices. Extensive regulation may encumber the research and development programs of chemical companies, increase the cost of chemicals reaching the market place, and decrease the number available to the producer, forcing him to revert to older or less effective chemicals. Both industry and producers must adapt to a constantly changing environment.On the other hand, regulating the use of chemicals may extend the life of a chemical because pest populations will be less apt to build up genetic resistance. Research programs may be redirected into areas of alternative pest control measures such as biological control and host plant resistance. This ultimately leads to integrated pest management strategies. Inherent in this redirection is the need for researchers and producers alike to understand the basic interactions of animals and plants which would spawn new non-chemical control measures and prompt more judicious use of chemical controls.EPA has tended to define benefits in a cost sense. In the economic analysis of pesticide regulation (primarily cancelling the registration of the pesticide) to date, benefits are synonymous with changes in production cost (per acre) for the affected producer and the industry (by commodity) as a whole. For this reason, the two methods of analysis have been partial budgeting and budgeting. There are two serious drawbacks in these approaches. Both problems originate from the short-run nature of the approaches. No supply response is considered in the analyses. This implies no consumer price effects and ignores the relevance of the concept of economic threshold in pesticide usage. Secondly, there has been little effort directed at regionalizing the producer impacts of the regulatory act. These problems must be overcome to perform adequate analysis. This requires increased research in the area pesticide productivity for supply response and regionalizing economic supply utilization, and price data.

11 - Federal Insecticide, Fungicide and Rodenticide Act

Use of Bacteriocins in Food: Regulatory Considerations

The Environmental Protection Agency (EPA) is committed to encouraging the development and use of biopesticides and considers them inherently reduced-risk pesticides. Biopesticides (microbial pesticides, biochemical pesticides, and plant-incorporated protectants) are required to be evaluated by EPA. The Agency must make findings of “no unreasonable adverse effects” to man and the environment to support its registration decision to permit sale and distribution under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as well as a “reasonable certainty of no harm” under the Federal Food, Drug, and Cosmetic Act (FFDCA) to permit residues in food and/or feed. This chapter will review areas including how EPA views the benefits of biopesticides, related laws and legal requirements, biopesticide registration, and biopesticide data requirements. EPA’s commitment to low risk biological pesticides as alternatives to conventional chemical pesticides will also be emphasized.

This chapter outlines the regulatory frameworks for agricultural chemicals and veterinary medicines in Australia, China, India, Japan, the United States, and the European Union, each operating under distinct legislative structures. It Australia’s Agricultural and Veterinary Chemicals Code 1994 and the role of the Australian Pesticides and Veterinary Medicines Authority (APVMA) under the National Registration Scheme. It also describes how China requires Ministry of Agriculture approval under the Administrative Regulations on Pesticides and Chemical Fertilizer, while India operates under the Insecticides Act, 1968 with various registration types. The chapter examines Japan’s Pharmaceutical Affairs Law and the US system, where the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) share oversight under the Federal Food, Drug, and Cosmetic Act (FDC Act) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). It includes the EU process for the Inclusion of an Active Substance in Annex I of Directive 91/414/EEC.

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.