Date Published: January 21, 2019
Publisher: Oxford University Press
Author(s): William R Reeves, Michelle K McGuire, Milton Stokes, John L Vicini.
Understanding the magnitude and impact of dietary pesticide exposures is a concern for some consumers. However, the ability of consumers to obtain and understand state-of-the-science information about how pesticides are regulated and how dietary exposure limits are set can be limited by the complicated nature of the regulations coupled with an abundance of sources seeking to cast doubt on the reliability of those regulations. Indeed, these regulations are sometimes not well understood within health care professions. As such, the objective of this review is to provide a historical perspective as to how modern pesticides were developed, current trends in pesticide use and regulation, and measures taken to reduce the risk of pesticide use to the consumer. Throughout the review, we provide specific examples for some of the concepts as they apply to glyphosate—a pesticide commonly used by both farmers and consumers. In addition, we describe current efforts to monitor pesticide use. We are confident that this succinct, yet thorough, review of this topic will be of interest to myriad researchers, public health experts, and health practitioners as they help communicate information about making healthful and sustainable food choices to the public.
More than ever before, today’s consumer exhibits a desire to understand where food comes from and how it was grown in a food milieu characterized by the convergence of agriculture, nutrition, and sustainability (1). Although previously separate topics, many health professionals (such as dietitians) are finding that conversations about food, agriculture, and nutrition have coalesced, especially as consumers make food-related decisions in a time of information abundance, and even information inundation leading to increased fear (2).
The EPA defines the term “pesticide” as “Any substance or mixture of substances intended for (1) preventing, destroying, repelling, or mitigating any pest, (2) use as a plant regulator, defoliant, or desiccant, or (3) use as a nitrogen stabilizer” (7). Although this official definition is relatively recent, pesticides have been part of global agricultural production for millennia and have likely been long-essential for controlling insects, weeds, and diseases. For instance, there are reports of sulfur being used to control plant diseases dating back 4500 y to its first use in Sumeria. Mercury and arsenic salts were introduced later, and the insecticidal properties of chrysanthemum flower extracts (pyrethrum) were discovered ∼2000 y ago. Indeed, naturally occurring substances have long been leveraged to help control pests in agriculture (8).
One of the first such laws related to pesticide use was passed by the US Congress in 1947. This was the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) aimed at controlling pesticide quality, and responsibility for overseeing the Act was given to the USDA. In time, regulations were strengthened to ensure that more was known about each chemical before it could be put on the market, and limitations were placed on how much of each active ingredient could remain in or on food products grown with each pesticide product. For instance, in 1972, FIFRA was amended to place a greater emphasis on pesticide safety and give the newly formed EPA authority over pesticide regulation. Today, FIFRA classifies all insecticides, herbicides, fungicides, rodenticides, and plant growth regulators as “pesticides” (7). In addition to synthetic pesticides, this classification also includes pesticides listed in the National Organic Program’s approved substances list (15).
Alongside its responsibilities under FIFRA, the EPA also regulates pesticides under the Federal Food, Drug, and Cosmetic Act (FFDCA). Whereas FIFRA addresses approved uses, rates of usage, and environmental impacts, FFDCA addresses human exposures to pesticides and how the EPA sets allowable limits for pesticides in and on food (17). Before it can establish allowable limits on pesticide exposures—known as tolerances—the EPA must first conduct a risk assessment to determine acceptable levels. The following sections describe this process.
The 1996 Food Quality Protection Act (FQPA) amended FFDCA to increase protections for human health, particularly for at-risk and sensitive subpopulations. Notably, FQPA requires that the EPA may only approve a tolerance if the agency can conclude “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information” (7).
The EPA has standard toxicologic tests that must be submitted for the agency to conduct human health risk assessments. Test durations are acute, subchronic, and chronic. Acute toxicity testing involves short-term tests with a single exposure. These include oral, dermal, and inhalation exposures and endpoints such as frank toxicity, eye irritation, skin irritation, skin sensitization, and neurotoxicity. Subchronic testing involves intermediate-length exposures to multiple doses for periods ranging from 30 to 90 d. As with acute studies, exposure routes may be oral, dermal, and inhalation. Subchronic testing informs assessments of a pesticide’s potential to adversely affect organ systems. Chronic testing considers long-term exposures to consecutive, repeated doses over most of the test animal’s life span. Chronic testing evaluates the potential to cause damage to organs and organ systems and the potential to cause cancer. The EPA also requires a set of tests to assess the potential for a pesticide to damage DNA that also informs assessments of potential carcinogenicity (19).
In addition to reviewing the types of studies described above, the EPA examines the body of toxicologic data to identify an NOAEL for each pesticide. An NOAEL is defined as the highest dose examined in all collective toxicologic studies to date that produced no detectable adverse effect on test animals (23). To translate the NOAEL from the animal toxicity studies to a numeric value protective of human health, the EPA applies a safety factor to the NOAEL. Typically, a value of 10 is used to account for extrapolations from test animals to humans and another safety factor of 10 is used to account for sensitive subpopulations to give a total safety factor of 100 (10 × 10). In other words, the NOAEL is divided by 100 and the resulting value is referred to as the RfD for the compound of interest (23). The EPA can also include additional safety factors (typically 3- to 10-fold) to account for especially sensitive subpopulations (e.g., infants, children, immunocompromised people) if the data warrant additional protection. Such an adjustment may result in dividing the NOAEL by 3 safety margins or as much as 1000 (10 × 10 × 10). RfD values, which are reported in units of milligrams of pesticide per kilogram of body weight per day (mg · kg–1 · d–1), can be interpreted as the amount of a particular compound a person may consume every day without raising concerns for adverse effects. The EPA requires that the sum of all exposures to a pesticide or class of pesticides across all approved uses cannot exceed the RfD. Text Box 2 provides an example of how the NOAEL and RfD were determined for glyphosate.
Once the RfD is calculated, the EPA sets tolerances for individual crops or groups of crops. A tolerance is defined as the legal limit for the level of a given pesticide in each crop or group of crops and is determined by measuring residues of the pesticide in question on a specific crop when the pesticide is applied according to label directions (24). Tolerances thus are not stand-alone safety standards (25). The EPA considers 3 types of data when setting tolerances.
Requests for new tolerances are considered in the context of existing tolerances. To do this, the EPA considers all approved uses of a pesticide to calculate possible exposures to ensure the new tolerance still allows a conclusion of safety. Both acute (short-term) and chronic (long-term) exposures are considered. Acute exposures cover single exposures or exposures lasting a single day. Chronic exposures consider lifetime exposures and rely on food-consumption data, typically obtained from the USDA’s NHANES What We Eat in America survey (28). The EPA uses these residue data to make conservative (i.e., worst-case) estimates of likely exposures for adults, children, and infants (29). The purpose of these estimates is not to provide an exact value for human exposure but rather to provide an upper-limit end estimate of exposures that likely overestimates actual exposures and ensures a protective approach to human health risk assessment.
As part of approving a tolerance level, the EPA determines whether sufficient analytic methods are available to test for the presence of the pesticide in food. Both the USDA (34) and the FDA (35) have programs that rely, in part, on these testing methods to monitor pesticides on and in food. The FDA is responsible for enforcing tolerances. The USDA shares its findings with the FDA to determine whether any violations occurred.
In conclusion, pesticides—along with other nonchemical options—represent an effective and efficient means to control pests in food production, be it conventional or organic in terms of approaches. Advances in agricultural practices have, in fact, kept the total use of pesticides relatively unchanged since the mid-1980s. New pesticidal compounds undergo substantial safety testing and assessment by manufacturers before the data are reviewed by the EPA, and its risk assessments identify the amounts that may be consumed by both adults and children without raising concerns of adverse health impacts. The EPA also sets tolerances on a crop-by-crop basis to ensure that aggregate exposures do not exceed acceptable levels. Both the FDA and USDA monitor pesticides in the US food supply to ensure any pesticides present do not violate tolerances approved by the EPA. The vast majority of the violations the FDA and USDA detect are for pesticides that lack an approved tolerance on a specific commodity rather than an exceedance of an approved tolerance stemming from misapplication (36).