Current ecotoxicity testing needs among selected U.S. federal agencies.

U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives. These data are used to conduct hazard assessments and evaluate potential risks to aquatic life (e.g., invertebrates, fish), birds, wildlife species, or the environment. To identify opportunities for regulatory uses of non-animal replacements for ecotoxicity tests, the needs and uses for data from tests utilizing animals must first be clarified. Accordingly, the objective of this review was to identify the ecotoxicity test data relied upon by U.S. federal agencies. The standards, test guidelines, guidance documents, and/or endpoints that are used to address each of the agencies' regulatory and research needs regarding ecotoxicity testing are described in the context of their application to decision-making. Testing and information use, needs, and/or requirements relevant to the regulatory or programmatic mandates of the agencies taking part in the Interagency Coordinating Committee on the Validation of Alternative Methods Ecotoxicology Workgroup are captured. This information will be useful for coordinating efforts to develop and implement alternative test methods to reduce, refine, or replace animal use in chemical safety evaluations.

Evaluation of the avian acute oral and sub-acute dietary toxicity test for pesticide registration.

The United States Environmental Protection Agency (USEPA), as well as other international regulatory agencies, require pesticide registrants to submit toxicity data that are used to conduct ecological risk assessments. While the USEPA has required both an acute oral and sub-acute dietary test in birds, trends in the use of data from these tests over the past 20 years have suggested that the avian sub-acute dietary test generally does not contribute to risk assessment conclusions. To address this question, a retrospective analysis was conducted to evaluate 119 pesticides with publicly available ecological risk assessments that were registered into commerce between 1998 and 2017. New pesticides (i.e., registered in the United States within the past 20 years) were chosen for the retrospective analysis to show utility of these tests for modern pesticide chemistries. Risk quotient (RQ) values (a point estimate of exposure divided by a deterministic toxicity endpoint) from the avian acute oral and dietary tests, as well as risk assessment conclusions, were compared to determine which test(s) drove the risk assessment findings. The RQ values were chosen as the data point for comparison in order to assess total risk (i.e., exposure and toxicity). After comparing RQ values from avian acute oral versus sub-acute dietary tests, there was only one case in which an avian sub-acute dietary RQ was greater than the acute oral RQ. Thus, the sub-acute dietary test did not identify risk in greater than 99% (118 out of 119) of chemicals based on results that either the acute oral RQ was higher than the sub-acute dietary RQ, or both the acute oral and the subacute dietary tests did not generate an RQ value of concern. For the one exception, both the oral and sub-acute RQ values were greater than the USEPA's level of concern for endangered species. Based on the results of the retrospective analysis, it is concluded that in most cases avian risk can confidently be assessed without conducting the sub-acute dietary test.

Mechanistic modeling of insecticide risks to breeding birds in North American agroecosystems.

Insecticide usage in the United States is ubiquitous in urban, suburban, and rural environments. There is accumulating evidence that insecticides adversely affect non-target wildlife species, including birds, causing mortality, reproductive impairment, and indirect effects through loss of prey base, and the type and magnitude of such effects differs by chemical class, or mode of action. In evaluating data for an insecticide registration application and for registration review, scientists at the United States Environmental Protection Agency (USEPA) assess the fate of the insecticide and the risk the insecticide poses to the environment and non-target wildlife. Current USEPA risk assessments for pesticides generally rely on endpoints from laboratory based toxicity studies focused on groups of individuals and do not directly assess population-level endpoints. In this paper, we present a mechanistic model, which allows risk assessors to estimate the effects of insecticide exposure on the survival and seasonal productivity of birds known to forage in agricultural fields during their breeding season. This model relies on individual-based toxicity data and translates effects into endpoints meaningful at the population level (i.e., magnitude of mortality and reproductive impairment). The model was created from two existing USEPA avian risk assessment models, the Terrestrial Investigation Model (TIM v.3.0) and the Markov Chain Nest Productivity model (MCnest). The integrated TIM/MCnest model was used to assess the relative risk of 12 insecticides applied via aerial spray to control corn pests on a suite of 31 avian species known to forage in cornfields in agroecosystems of the Midwest, USA. We found extensive differences in risk to birds among insecticides, with chlorpyrifos and malathion (organophosphates) generally posing the greatest risk, and bifenthrin and λ-cyhalothrin (pyrethroids) posing the least risk. Comparative sensitivity analysis across the 31 species showed that ecological trait parameters related to the timing of breeding and reproductive output per nest attempt offered the greatest explanatory power for predicting the magnitude of risk. An important advantage of TIM/MCnest is that it allows risk assessors to rationally combine both acute (lethal) and chronic (reproductive) effects into a single unified measure of risk.