Invited Perspective: Pesticide Adjuvants and Inert Ingredients — A Missing Piece of the Puzzle

Pesticides encompass a wide variety of chemicals. The active ingredients in pesticides are designed to kill or repel pests, including invasive and unwanted plants, insects, fungi, rodents, and nematodes. Human exposure is widespread and not limited to those who apply pesticides themselves, making the potential health effects of these chemicals an important public health concern. In the United States, it is estimated that $>90\%$ of the population has detectable concentrations of pesticide biomarkers in their blood or urine.¹

Despite the ubiquity of these chemicals, the assessment of pesticide exposure is particularly challenging owing to often intermittent exposures, the short half-lives of most pesticides in use today, and the fact that even occupationally exposed workers may not know what pesticides they are using.² Although a recent literature review reported $>\mathrm{1,250}$ articles published in the previous 25 y that evaluated pesticides and chronic disease effects, many studies were limited to crude estimates of exposure, focusing on broad classifications of “pesticides.”³ This makes the identification of etiologic agents difficult given that there are hundreds of active ingredients available for agricultural use around the world.⁴

Studies with more detailed exposure assessments have typically focused on active ingredients either singly or in combination, rather than on large classes such as herbicides or insecticides. Epidemiologic studies of specific pesticide active ingredients and disease outcomes, and studies designed to support biological plausibility of these pesticide–disease associations, have greatly improved our understanding of the potential impacts of these chemicals on health. Examples include associations between permethrin and multiple myeloma^5,6 and between some organophosphates and Parkinson’s disease.^7,8

Although we still have much to understand about the potential effects of the hundreds of pesticide active ingredients being used currently, in their recent commentary, Cox and Zeiss highlight another important issue that thus far has not been addressed in most epidemiologic studies of chronic diseases and pesticides: inert ingredients and adjuvants.⁹ An inert ingredient is defined as any substance other than the active ingredient that is included in a pesticide product; notably, it does not imply that the chemical is nontoxic.¹⁰ Adjuvants are chemicals that are added to a pesticide mixture to improve the efficacy of the active ingredient.

The exclusion of these chemicals in epidemiologic studies of pesticides is largely because exposure data are not widely available. Although the active ingredients in a pesticide are reported on the product label, the components of the pesticide mixture that are not the active ingredient are not included and are not generally included in publicly available databases. An exception is California’s Pesticide Use Reporting System, which requires that use of adjuvants, but not inert ingredients, be reported.¹¹ Using this database, Cox and Zeiss demonstrated that the adjuvant $\mathrm{\alpha }\text{-}\left(p\text{-nonylphenyl}\right)\text{-}\mathrm{\omega }$-hydroxypoly(oxyethylene) (APNOHO) was applied to the largest number of acres of any chemical in the system in 2019.⁹ APNOHO is used as both an inert ingredient and an adjuvant; because only its use as an adjuvant was reported in the system, the presumed actual application would be even greater.

Pesticide use has increased dramatically in the last several decades, with an estimated growth of 11% per year from 1950 to 2003.¹² In 2012, the last year for which data are available, $>6\text{\hspace{0.17em}billion}$ pounds (>2.7 billion kg) of pesticide active ingredients were applied worldwide.¹³ In some formulations, active ingredients make up only 1% of the pesticide mixture.¹⁴ This highlights the potential for extensive exposures to constituent chemicals other than active ingredients. In addition, inert and adjuvant ingredients may in some cases increase the potential for human exposures to active ingredients through inhalation and dermal pathways.¹⁵

Incorporating information on inert ingredients and adjuvants in epidemiologic studies of pesticides could enhance our understanding of the health effects of active ingredients. Components of pesticide mixtures may act synergistically.¹⁶ Cox and Zeiss focused on the endocrine-disrupting properties of APNOHO,⁹ effects which are also common in many active ingredients¹⁷ However, with the limited information available, evaluations of such potential synergy are not possible.

Our understanding of the health effects of pesticides is continuing to grow; advances in pesticide exposure assessment and in the incorporation of multipollutant models in epidemiologic studies should increase our knowledge of how these chemicals influence health. However, we will have an incomplete picture of potential impacts as long as we can evaluate only the active ingredient component of the pesticide mixture.

Refers to https://doi.org.10.1289/EHP10634