EPA updates human health, drinking water assessments for acephate

FIFRA registration review

• Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), pesticides must be registered with the Environmental Protection Agency (EPA) before commercial sale or use. A pesticide may only be registered in the U.S. if the EPA can confirm that the pesticide will not pose an unreasonable risk to humans or the environment. Under FIFRA, pesticide registrations must be reviewed at least once every 15 years to ensure that the pesticide can still be used without causing unreasonable adverse effects on humans or the environment.
• The registration review process generally takes at least several years to complete, and involves numerous discrete steps, many with attached public note and comment periods. These include both preliminary and final work plans, public data call-ins, draft and final risk assessments, and finally, interim and final decisions. The risk assessment stage reviews the acute and chronic risk of a pesticide towards humans or the environment. At this stage, the EPA may also consult with the U.S. Fish and Wildlife Service (FWS) and the National Marine Fisheries Service (NMFS, collectively, the Services) for any Endangered Species Act (ESA) requirements the agency may need to fulfill.
• Acephate (CAS RN 30560-19-1) is an organophosphate insecticide that targets sucking and chewing pests. Acephate is used on a variety of agricultural crops, as well as for non-food uses such as ant mound treatment and golf courses. Acephate is characterized as a highly mobile pesticide and can leach into groundwater, however it also has low persistence in soil and a similarly low potential for bioaccumulation in lipids. Methamidophos (CAS RN 10265-92-6) is a major degradant of acephate, and was previously registered as a pesticide, but its registrations were voluntarily cancelled in 2009. Current data on methamidophos indicates that it is not persistent in aerobic environments but may be more persistent in anerobic environments.

Revised draft human health risk assessment

• On August 30, 2023, the EPA published a second draft revised draft human health risk assessment (DRA) for acephate. The DRA was conducted to evaluate all existing registrations of acephate as an active ingredient and methamidophos as a metabolite and degradant. The most recent human health risk assessment was performed in 2018, and the 2023 DRA includes a wide range of updates. The 2023 DRA includes updated toxicological literature and epidemiology and incident reviews.
• In the 2018 review, acephate was determined to have dietary risks of concern for both food and water, however the current assessment finds dietary risks of concern in water alone. Based on water modeling refinements for cotton and soybeans (which make up about 95% of acephate use by reported treated area), dietary exposures result in risks of concern and the inclusion of food and residential exposures would result in even greater risk estimates of concern.
• The DRA determined that humans may be exposed to acephate and methamidophos via food and drinking water. This is mostly from acephate being applied directly to growing crops, and those applications can result in acephate residues on food and residues reaching surface or groundwater. Residential handler exposure is expected with acephate only, specifically for ant mound uses.
• The DRA has no new updates to selected endpoints and points of departure (PODs) from the 2018 risk assessment. The specific endpoint chosen is brain acetylcholinesterase (AChE) inhibition, with a POD based on oral exposure scenarios taken from an acute comparative cholinesterase (CCA) study in rats.
• Dietary risk assessments were presented in both “acute and steady-state” in the assessment, based on both individual daily food consumption as well as daily time series drinking water concentrations. This is because acephate achieves steady-state inhibition of AChE within a day, and therefore both acute and steady-state PODs are the same. However, both acute and stead-state risk estimates for food only do not exceed 100% of the population-adjusted dose (PAD) for all population subgroups at 99.9^th percentile of exposure. However, dietary risks based on estimated drinking water concentrations (EDWCs) for registered acephate uses exceed 100% of the PAD for all population subgroups at 99.9^th percentile of exposure. However, because many acephate labels do not specify a maximum seasonal rate or total number of applications, calculated EDWCs may be overestimated.
• In addition, the EPA found potential residential handler risks of concern, mostly with combinations of dermal and inhalation exposures with certain equipment types. These included garden and turf spot treatments with electric dusters, hand crank dusters, spoons, or shaker cans that resulted in risks of concern. The agency did not conduct a quantitative aggregate risk assessment since there were risks of concern for both dietary and residential exposures, and combining the exposures would result in “even greater risk estimates of concern.”
• For occupational handler exposures, the agency found that inhalation risk drove most combined risk assessments (of dermal and inhalation), which the agency determined were of concern.

Refined drinking water assessment

• On August 30, 2023, the EPA also released a refined drinking water assessment (DWA) for acephate and methamidophos. The assessment focused on the acephate use on cotton and soybeans, only taking into account ground spray applications. The agency explained that although aerial applications are allowed and would likely result in higher EDWCs, the EPA only utilized ground sprays for the purposes of the DWA. The DWA builds on a 2017 DWA released by the agency. Like the DRA, the EPA included several updates and improvements to the 2017 DWA.
• The new DWA incorporated a new formation and decline approach into its assumptions. In the 2017 DWA, the agency had assumed that acephate immediately degraded into methamidophos, which is more toxic. However, the new DWA refined this into new formation and decline methods, which focused on the difference in toxicity between acephate and methamidophos and the differing environmental fates of the substances. In addition, the DWA takes into account a study that suggests that acephate does not degrade into methamidophos in the presence of chlorine.
• Both acephate and methamidophos are considered residues of concern in drinking water. However, the DWA indicates that acephate and methamidophos residues are likely to vary heavily across the country. The areas with the highest potential for exposure are areas with both high use of acephate and runoff-prone watersheds.

Acephate registration review

• Due to the EPA finding risks of concern with drinking water alone, future mitigation measures in the registration review could be increased. However, because acephate labels may not include maximum seasonal rates or total number of applications, this could include label changes to specify maximum seasonal rates or applications that would not pose an unreasonable risk to health or the environment.
• The agency expects to complete the proposed interim decision of acephate “sometime next year,” according to an announcement from the EPA. The agency noted in the email that it had received information from the U.S. Department of Agriculture on the benefits of acephate use on agricultural and non-agricultural applications.

To contact the author of this analysis, please email Walker Livingston.
To contact the editor of this analysis, please email Patricia Iscaro.

Key Documents and Dates

• • Acephate: Second Revised Draft Human Health Risk Assessment (DRA) in Support of Registration Review (August 30, 2023)
  • Acephate Refined Drinking Water Assessment for Registration Review (August 30, 2023)
  • Acephate registration review docket