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Upper Midwest Environmental Sciences Center

Determination of the Acute Toxicity of Model-based Candidate Chemical Toxicants to Native and Nonnative Fish Species in Static Exposures

Supervisor - Terrance Hubert
Principal Investigator
– Joel Putnam

Fish Toxicant Database


Invasive fishes are of considerable concern to aquatic resource managers.   For example, the common carp (Cyprinus carpio), originally brought over from Eurasia sometime in the 1800s are now ubiquitous in U.S. waters.  Although they have been around for over 100 years and have become part of U.S. culture, they are still highly detrimental to aquatic ecosystems and a method to eradicate and control of carp is highly desired.   Also originally from Asia, bighead carp (Hypophthalmichthys nobilis) and silver carp (Hypophthalmichthys molitrix) have become established in the United States mainly through their presence in aquaculture ponds and sewage treatment facilities to control plankton (Rach, 2005).  In the early 1970s flooding allowed a route to natural waterways such as the Mississippi River, where the fish were able to thrive and spread further along to parts of the Mississippi River drainage basin (Upper Midwest Environmental Sciences Center, 2007).  Due to the large size and rapid growth of both species, which can reach over 50 pounds, they threaten to outcompete native fish species for food, foul the nets of fishermen, and in the case of the silver carp cause bodily harm by leaping out of the water when disturbed (Indiana Department of Natural Resources, 2009; Upper Midwest Environmental Sciences Center, 2007). In addition to ecological impacts, a fishing industry of nearly $7 billion dollar annually is threatened by the nonnative bighead and silver carp if they were to establish populations in the Great Lakes.

Because of the negative impact that common carp, bighead carp, and silver carp have on aquatic ecosystems, a method of eliminating or controlling them would be highly valued by aquatic resource managers.  Chemical control is one option that is routinely employed to control invasive species.  Currently, there are only four registered fish toxicants that can be used to control aquatic invasive organisms, the larval lampricides TFM and niclosamide, and the general fish toxicants rotenone and antimycin A.  The lampricides are used almost exclusively to control sea lamprey populations in the Great Lake Basin, and in rare cases have been used for the control of aquatic invertebrates in aquaculture ponds.  Because rotenone and antimycin A are non-selective toxicants, they can be used only in circumstances where a complete eradication of all fishes can be tolerated, such as part of a reclamation project. 

Application of a species-specific piscicide is an intuitively appealing approach for controlling invasive fishes, but has rarely been practiced in the U.S. because such selective piscicides are not readily available. Chemical renovation can be expensive, sometimes is logistically difficult, and unfortunately has been associated with collateral damage to non-target organisms and the environment. Chemical renovation has high efficacy, but because it is not 100% effective retreatment is often required for successful control. Other strategies (e.g., selective harvest, regulatory control, physical barriers, and biological controls) are generally not effective in controlling fishes. Thus, effective management of invasive fishes in the U.S., as well as in other ecosystems, probably needs to integrate various methods of control into one management program. The use of piscicides combined with other innovative approaches-such as the use of sterilants, attractants or repellants, or reproductive inhibitors-applied in an integrated manner to manage nonnative fishes may improve the probability of successful renovation of streams and rivers in the U.S.

The selection of new chemicals to test for species selective toxicity must be accomplished in a methodical process.  Quantitative structure activity relationships (QSARs) are one effective method to predict toxicity to families, classes, or individual species (Dearden 2003) by the use of chemical descriptors.  Chemical descriptors transform chemical information into useful numeric values which can be used to predict measurable endpoints (Todeschini 2000).  The U.S. EPA has developed a methodology named Ecological Structure Activity Relationship (ECOSAR), which uses the octanol/water partition coefficient as the major physical-chemical descriptor for correlating toxic effect (LC50) of nonreactive neutral organic chemicals (Konemann 1981, Hermens 1983).  ECOSARs are linear mathematical relationships that correlate the log of the octanol/water partition coefficient and the log of the measured toxicity values (mmol/L).  The ECOSAR models are based on toxicity data for fathead minnow (Pimephales promelas) at 96 hour static conditions.  However, these models predict toxicity for only the fathead minnow.  Expanding the chemicals beyond neutral organic chemicals, compounds such as hexanes and dichloromethane, has been a focus of research at the Upper Midwest Environmental Center (UMESC) and includes models for more than one aquatic species.  One reason for the need for additional fish species-specific toxicity models is that previous toxicity reports indicate that bluegill sunfish (Lepomis machrochirus) and rainbow trout (Oncorhynchus mykiss) are more sensitive to most toxic compounds, specifically rotenone and antimycin A (Rach 2009).  Creating a database that evaluates species selective toxicity structure-activity relationships (SARs) is of great interest for the development of toxicants specific to invasive aquatic species, such as the bighead and silver carp.

The models created at UMESC were used to predict toxicity to three fish species:  rainbow trout, bluegill sunfish, and fathead minnow because data to support these models were both available and provided more extensive statistical analysis. Data on the toxicity of chemicals to the bighead carp and silver carp are lacking so it isn’t possible to develop models to predict chemical toxicity.  Because of the lack of data, bigheaded carps are treated as Cyprinids, which are modeled using the fathead minnow data. 

Five chemicals were selected (see section 2.b.) from the models and represent three chemical classes.  These five chemicals have the minimum chemical structures that indicate selective toxicity to fathead minnow compared to bluegill sunfish and rainbow trout based on the mathematical models.  One additional chemical toxicant has been added (thiram) for comparison to cellular assays.  This project will investigate if the model has adequately predicted chemical toxicity by conducting in vivo assays to determine toxicity.  If one or more of these chemicals indicate selective toxicity, more complex chemical structures will then be investigated. 


  1. Test the models predicted 96-hour and 24-hour LC50 toxicity of the test chemicals to fathead minnow, bighead carp, silver carp, bluegill sunfish and rainbow trout.


American Society for Testing and Materials (ASTM). 2007. Standard Guide for Conducting Acute Toxicity Tests with Fishes, Macroinvertebrates and Amphibians. Annual Book of ASTM Standards. Standard E729-96.

Dearden, J.C.  2003.  In silico prediction of drug toxicity, Journal of Computer-Aided Molecular Design, 17:2-4, 119-127.

Hermens, J; Leeuwangh, P; Musch, A. (1984) Quatative Structure Activity Relationships and Mixture Toxicity Studies of Chloro- and Alkylanilines at an Acute Lethal toxicity Level to the Guppy (Poecilia reticulate). Ecotoxicol Environ Saf 8: 388-394

Konemann, H. (1981) Quatitative Structure Activity Relationships in Fish Toxicity Studies. Part 1: Relationship for 50 Industrial Pollutants. Toxicology 19:209-221.

Lennon, Robert E. and Walker, Charles R.  1964.  Laboratories and methods for screening fish-control chemcials.  U.S. Fish and Wildlife Service. 

Litchfield, J.T. and Wilcoxon, F.A. 1949. A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exper. Therap. 96:99-113.

Marking, L.L. 1974.  Toxicity of the synthetic pyrethroid SBP-1382 to fish.  Prog. Fish culturist.  36:144.

Rach,J.J., Boogaard, M. and Kolar, C. (2009) Toxicity of Rotenone and Antimycin to Silver Carp and Bighead Carp, North American Journal of Fisheries Management, 29:2, 388-395.

Ritz, C. and Streibig, J.C. (2005) Bioassay Analysis using R. J. Statist. Software, Vol.12:5.

Shih, Y. and PM Gschwend. (2009) Evaluating Activated Carbon#Water Sorption Coefficients of Organic Compounds Using Linear Solvation Energy Relationship Approach and Sorbate Chemical Activities. Environmental Science and Technology, 44(3), 851-857.

Todeschini, R and Consonni, V.  Handbook of Molecular Descriptors, Milano Chemometrics, 2000.

U.S. Food and Drug Administration, Center for Veterinary Medicine, Guidance for Industry, Validation of Analytical Procedures:  Methodology, Final Guidance, July 1999.


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