Acute Toxicity of the Lampricide 4-Nitro-3-(trifluoromethyl)phenol to the Mussel (Obovaria subrotunda), Its Host (Percina maculata), and a Surrogate Mussel Species (Obovaria olivaria).

The risk of lampricide applications (such as 4-nitro-3-[trifluoromethyl]phenol [TFM]) to nontarget fauna continues to be a concern within the Great Lakes Fishery Commission Sea Lamprey Control Program, especially among imperiled aquatic species-such as native freshwater mussels. The Grand River (Ohio, USA) is routinely treated for larval sea lampreys (Petromyzon marinus), and this river contains populations of the federally threatened mussel Obovaria subrotunda. Given this spatial overlap, information on the sensitivity of O. subrotunda to TFM is needed. Our objectives were to assess the toxicity of TFM to (1) adult Obovaria olivaria (a surrogate for O. subrotunda), (2) glochidial larvae of O. olivaria and O. subrotunda, (3) juveniles of O. olivaria and O. subrotunda, and (4) adult Percina maculata (host for O. subrotunda glochidia). In acute toxicity tests, TFM was not toxic to glochidia and adult mussels at exposure concentrations that exceed typical treatment rates. Although significant dose-response relationships were observed in hosts and juveniles, survival was ≥95% (Percina maculata), ≥93% (O. olivaria), and ≥74% (O. subrotunda) at typical treatment rates. However, the steep slope of these dose-response relationships indicates that an approximately 20% difference in the treatment level can result in nearly an order of magnitude difference in survival. Collectively, these data indicate that routine sea lamprey control operations are unlikely to acutely affect these species or their host. However, given that many mussel species are long-lived (30-100 years), the risks posed by lampricide treatments in the Great Lakes would be further informed by research on the potential long-term effects of lampricides on imperiled species. Environ Toxicol Chem 2024;43:1423-1430. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Control of invasive sea lampreys using the piscicides TFM and niclosamide: Toxicology, successes & future prospects.

The invasion of the Laurentian Great Lakes of North America by sea lampreys (Petromyzon marinus) in the early 20th century contributed to the depletion of commercial, recreational and culturally important fish populations, devastating the economies of communities that relied on the fishery. Sea lamprey populations were subsequently controlled using an aggressive integrated pest-management program which employed barriers and traps to prevent sea lamprey from migrating to their spawning grounds and the use of the piscicides (lampricides) 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide to eliminate larval sea lampreys from their nursery streams. Although sea lampreys have not been eradicated from the Great Lakes, populations have been suppressed to less than 10% of their peak numbers in the mid-1900s. The ongoing use of lampricides provides the foundation for sea lamprey control in the Great Lakes, one of the most successful invasive species control programs in the world. Yet, significant gaps remain in our understanding of how lampricides are taken-up and handled by sea lampreys, how lampricides exert their toxic effects, and how they adversely affect non-target invertebrate and vertebrates species. In this review we examine what has been learned about the uptake, handling and elimination, and the mode of TFM and niclosamide toxicity in lampreys and in non-target animals, particularly in the last 10 years. It is now clear that the mode of TFM toxicity is the same in non-target fishes and lampreys, in which TFM interferes with oxidative phosphorylation by the mitochondria leading to decreased ATP production. Vulnerability to TFM is related to abiotic factors such as water pH and alkalinity, which we propose changes the relative amounts of the bioavailable un-ionized form of TFM in the gill microenvironment. Niclosamide, which is also a molluscicide used to control snails in areas prone to schistosomiasis infections of humans, also likely works by uncoupling oxidative phosphorylation, but less is known about other aspects of its toxicology. The effects of TFM include reductions in energy stores, particularly glycogen and high energy phosphagens. However, non-target fishes readily recover from sub-lethal TFM exposure as demonstrated by the rapid restoration of energy stores and clearance of TFM. Although both TFM and niclosamide are non-persistent in the environment and critical for sea lamprey control, increasing public and institutional concerns about pesticides in the environment makes it imperative to explore other means of sea lamprey control. Accordingly, we also address possible "next-generation" strategies of sea lamprey control including genetic tools such as RNA interference and CRISPR-Cas9 to impair critical physiological processes (e.g. reproduction, digestion, metamorphosis) in lamprey, and the use of green chemistry to develop more environmentally benign chemical methods of sea lamprey control.

An automated approach to Litchfield and Wilcoxon's evaluation of dose-effect experiments using the R package LW1949.

The authors developed a package, LW1949, for use with the statistical software R to automatically carry out the manual steps of Litchfield and Wilcoxon's method of evaluating dose-effect experiments. The LW1949 package consistently finds the best fitting dose-effect relation by minimizing the chi-squared statistic of the observed and expected number of affected individuals and substantially speeds up the line-fitting process and other calculations that Litchfield and Wilcoxon originally carried out by hand. Environ Toxicol Chem 2016;35:3058-3061. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

Evaluation of the short term 12 hour toxicity of 3-trifluoromethyl-4-nitrophenol (TFM) to multiple life stages of Venustaconcha ellipsiformis and Epioblasma triquetra and its host fish (Percina caprodes).

The present study evaluated the risk of 12-h exposures of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) to multiple life stages of the federally endangered snuffbox (Epioblasma triquetra) and its primary host fish the common logperch (Percina caprodes) as well as a surrogate to the snuffbox, the ellipse (Venustaconcha ellipsiformis). Life stages examined included free glochidia, 1-wk juveniles, and adults of the ellipse; free glochidia, glochidia on host fish, and 1-wk juveniles of the snuffbox; and adult logperch. Larval sea lampreys were also tested alongside adult ellipse and logperch for direct comparison. Survival exceeded 82% among all life stages in both mussel species at levels up to 1.8 times what would be applied during treatments, suggesting that routine sea lamprey control operations would not adversely affect mussels. However, substantial mortality of adult logperch was observed at TFM concentrations typically applied to streams, and loss of host fish could adversely affect snuffbox reproduction. In addition, TFM had no significant effect on the number of glochidia that metamorphosed on adult logperch. Although the snuffbox is not likely to be acutely affected from sea lamprey control operations, mitigation efforts to minimize impacts to the host fish should be considered.

Multilevel empirical bayes modeling for improved estimation of toxicant formulations to suppress parasitic sea lamprey in the upper great lakes.

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data.

Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance.

Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/ concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2',5'-dichloro-4'-nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4-nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software.

Residues of the lampricides 3-trifluoromethyl-4-nitrophenol and niclosamide in muscle tissue of rainbow trout.

Rainbow trout (Oncorhyncus mykiss) were exposed to the (14)C-labeled lampricide 3-trifluoromethyl-4-nitrophenol (TFM) (2.1 mg/L) or niclosamide (0.055 mg/L) in an aerated static water bath for 24 h. Fish were sacrificed immediately after exposure. Subsamples of skin-on muscle tissue were analyzed for residues of the lampricides. The primary residues in muscle tissue from fish exposed to TFM were parent TFM (1.08 +/- 0.82 nmol/g) and TFM-glucuronide (0.44 +/- 0.24 nmol/g). Muscle tissue from fish exposed to niclosamide contained niclosamide (1.42 +/- 0.51 nmol/g), niclosamide-glucuronide (0.0644 +/- 0.0276 nmol/g), and a metabolite not previously reported, niclosamide sulfate ester (1.12 +/- 0.33 nmol/g).