U.S. EPA releases updated draft risk assessment for pesticide malathion

On March 1, 2024, the U.S. Environmental Protection Agency (EPA) released an updated draft human health risk assessment (HH DRA) for the pesticide malathion. The updated HH DRA amends the 2016 malathion dietary, occupational, and residential risk assessments using updated information and techniques. The updated HH DRA finds no human health risks of concern for malathion when used in accordance with label instructions. EPA is also proposing several food tolerance changes, based on commodity definition revisions and to harmonize tolerance levels with those of other countries.

Malathion is an organophosphate pesticide that is registered for agricultural and non-agricultural uses, including controlling pests on fruits, vegetables, landscaping plants, and shrubs, as well as for controlling mosquitos. Mosquito-borne diseases, such as those caused by the West Nile and Zika viruses, are among the world's leading causes of illness and death and pose a significant risk to people in the United States. Climate change also increases the risk of human exposure to mosquito-borne diseases, as studies show that warmer temperatures associated with climate change can expand the range and breeding season of mosquitos, as well as accelerate mosquito development, biting rates, and the incubation of the disease within a mosquito. Using pesticides like malathion to control mosquito populations is important to maintaining public health, particularly in densely populated areas in overburdened communities.

The human health risk assessment for malathion includes an assessment of malaoxon, its breakdown product that is formed through metabolism and degradation. Malaoxon is the active form of malathion that is responsible for interacting with the nervous system through inhibition of the acetylcholinesterase (AChE) enzyme. This process is what makes the pesticide effective against insects, but the process can also occur in mammals, including humans, depending on the level of malathion exposure. AChE inhibition has been found to be the most sensitive effect for malathion, and EPA has a long-standing history of using a 10% change in AChE levels as the basis for its organophosphate human health risk assessments.

In the previous 2016 HH DRA for malathion, traditional approaches that rely solely on animal data and default uncertainty factors were used to evaluate exposure to malathion and malaoxon and identified potential risks of concern. The updated malathion HH DRA released today incorporated modernized scientific techniques and new data that provided a more refined assessment compared to traditional approaches and found no human health risks of concern.

• The updated HH DRA: Incorporated a physiologically based pharmacokinetic-pharmacodynamic (PBPK) model to obtain a more realistic estimate of human toxicity associated with AChE inhibition for different age groups and routes of exposure (oral, dermal, and inhalation). A PBPK model simulates how quickly and how much of a chemical enters the body, where it distributes in the body, how it breaks down, and how it eventually exits the body using human-specific data and information.

• Updated the Food Quality Protection Act safety factor (FQPA SF) taking into consideration a weight of evidence analysis (WOE) of developmental neurotoxicity (DNT) potential using chemical-specific data. The FQPA SF is intended to provide a 10X additional margin of safety to account for any additional risk to pregnant women and children in the absence of scientific information demonstrating that no such additional risk exists. EPA concluded there is reliable chemical-specific data to support reducing the FQPA SF from 10X to 1X.

• Incorporated updated dietary, residential, and non-occupational bystander exposure data.

• Utilized updated guidance for evaluating exposures and potential risk from the public health use to control mosquitos.

As noted above, a WOE analysis of DNT potential was used to inform the malathion FQPA SF determination, where all relevant evidence is looked at, taking into consideration the strengths and limitations of each line of evidence. EPA’s ″Approach for Evaluating Developmental Neurotoxicity Potential for the Organophosphate Pesticides″ outlines the Agency’s strategy to assess the DNT potential of organophosphates in women and children. The approach uses three primary lines of evidence—epidemiological studies, animal toxicity studies, and a battery of in vitro assays—to evaluate pesticides on a chemical-by-chemical basis using high quality, chemical-specific data. Using the WOE approach, EPA concluded that a reduction of the FQPA SF to 1X was supported by the evidence. For further information, the WOE analysis can be found in the document entitled ″Evaluation of the Developmental Neurotoxicity Potential of Malathion/Malaoxon to Inform the FQPA Safety Factor.″

This revised assessment covers the human health risks of malathion, while the ecological risks to non-target species will be described in a separate assessment that is expected to be released next month. EPA has completed its Endangered Species Act (ESA) consultations on malathion. Malathion is one of 18 organophosphates currently in registration review, with many scheduled to have decisions between 2024-2026.

The Agency is still assessing the risks, benefits, and alternatives of malathion through the ongoing registration review process. These assessments, as well as the updated HH DRA, will inform the malathion proposed final decision (PFD) and final decision (FD) which are expected to be completed later this year. The PFD may propose risk mitigation to address any risks identified in the human health and/or ecological risk assessments, and the FD will finalize the requirements for any mitigation. A PFD and FD address all aspects of the registration review, as necessary, including considerations under the ESA and for the Endocrine Disruptor Screening Program (EDSP) under the Federal Food, Drug and Cosmetic Act as amended by the FQPA.

For malathion, the Agency is planning to issue a PFD and FD, rather than a Proposed Interim Decision and an Interim Decision, because the Agency has already completed ESA consultation for malathion and addressed the EDSP’s requirements.

The Agency will accept public comment on the updated HH DRA and the ecological DRA at the same time that it accepts public comment on the PFD, later this year. For more information on the registration review of malathion, including the updated HH DRA and supporting documents, please visit the malathion docket on at docket ID EPA-HQ-OPP-2009-0317 on www.regulations.gov.

Read the Updated Draft Risk Assessment