Introduction
Hydrogen peroxide is commonly used as a disinfectant for cleaning wounds in people. Hydrogen peroxide has also been used in aquaculture as an immersion (bath) treatment against many different disease-causing organisms, including external parasites, bacteria, and fungi, on different species and life-stages of fish. The US Food and Drug Administration (FDA) recently approved a hydrogen-peroxide-based aquaculture product, which has spurred greater interest in its use.
What is hydrogen peroxide?
Hydrogen peroxide is the chemical compound H2O2. Hydrogen peroxide is a highly reactive, strong oxidizing and bleaching (whitening) agent that is classified as corrosive at concentrations higher than 20%. Hydrogen peroxide has numerous non-medical and medical uses because of these properties. When added to water, hydrogen peroxide breaks down into oxygen and water over time, and the formation of these by-products is one reason that hydrogen peroxide is considered to be relatively safe for the environment. Hydrogen peroxide's highly reactive nature, similar in some respects to the reactivity of potassium permanganate, makes it ideal for use in aquaculture against numerous external fish-disease-causing organisms, but with similar concerns regarding toxicity. The FDA-approved product, 35% PEROX-AID® (Western Chemical, Syndel USA, Ferndal, WA), is available at a strength of 35% weight/weight (e.g., 35% active ingredient). Over-the-counter products used for human health are typically sold at 3% active ingredient.
How stable is hydrogen peroxide in water?
A number of different elements, enzymes, and compounds, as well as light, heat, and high pH all accelerate the degradation of hydrogen peroxide. It is important to understand the stability of hydrogen peroxide in water because toxicity can result from improper use and excessive exposure.
At 15°C (~59°F) and 20°C (~68°F), initial hydrogen peroxide concentrations of 10 and 100 mg/L in tank culture water were not measurable after 2–3 days in the presence of aeration and/or organic matter. Under static water conditions with no aeration or organic matter, concentrations were halved by day 6 and undetectable by day 10 (Tort et al. 2003).
Another study tested the stability of hydrogen peroxide during tank trials with ornamental fish and in earthen ponds without fish (Russo et al. 2007). In the tank trials, groups of 17–25 fish were placed into separate, static systems consisting of a glass aquarium containing 32 liters (~8.5 gallons) of water and aeration. Beginning concentrations of hydrogen peroxide ranged from 1.2–26.9 mg/L. The hydrogen peroxide concentration was tested 1 hour and 24 hours after the initial dose was added. After 1 hour, concentrations did not vary significantly from starting concentrations in all tanks. However, after 24 hours, concentrations in all tanks had decreased to 0.4–0.8 mg/L (Russo et al. 2007).
In the same study, two earthen ponds with initial hydrogen peroxide concentrations of 6.46 and 13.60 mg/L, respectively, had concentrations of 1–2 mg/L after 24 hours (Russo et al. 2007).
Hydrogen peroxide appears to degrade relatively rapidly in the presence of organic material and aeration; however, species sensitivities and starting concentrations will also determine its toxicity to fish.
Is hydrogen peroxide legal for use in aquaculture?
In 2007, 35% PEROX-AID® (previously manufactured by Eka Chemicals, Marietta, GA, currently Western Chemical, Syndel USA, Ferndale, WA) was approved by the FDA for control of mortality in (1) freshwater-reared finfish eggs due to saprolegniasis (a common water mold), (2) freshwater-reared salmonids due to bacterial gill disease (Flavobacterium branchiophilum), and (3) freshwater-reared coolwater finfish and channel catfish due to external columnaris (Flavobacterium columnare) disease. No other forms of hydrogen peroxide, including those sold for human use, are approved for use with fish.
What quantities are available?
35% PEROX-AID ® (35%) is currently available in 55-gallon drums and 5-gallon carboys.
What are the approved dosage rates for 35% PEROX-AID® use?
Producers should test any treatment using hydrogen peroxide for safety and efficacy. Test on a small number of fish before treating the entire lot.
A summary of the FDA-approved label dosage rates for hydrogen peroxide is located in Table 1.
How do I calculate the volume of hydrogen peroxide to add to my system?
Use the following formula to calculate how much 35% PEROX-AID® should be added to a system for treatment. NOTE: This formula will not work for hydrogen peroxide products that are not 35% active ingredient. Furthermore, use of non-approved products is illegal. Work with an aquatic veterinarian or other fish health specialist to make sure you are using 35% PEROX-AID® properly.
The following formula can be used to determine the volume (in milliliters [= mL] of 35% PEROX-AID® required for a given treatment concentration and system volume.
NOTE: There are 396,100 mg of hydrogen peroxide per L of 35% PEROX-AID®.
NOTE: There are 1000 mL in 1 L. The liters are converted to milliliters to allow for easier measuring of the 35% PEROX-AID® liquid for treatment.
For example, if you need to use a treatment concentration of 500 mg/L and will treat 150 liters of water in a closed system, then:
Static or closed-system treatments are the most common aquaculture systems used in Florida. If you are treating a raceway type or any other type of system, contact an aquatic veterinarian or other fish health specialist to determine proper dosing protocol.
Can hydrogen peroxide be used on other warm-water finfish species intended for human consumption and for other indications not on the label?
A veterinarian can prescribe 35% PEROX-AID® for an extralabel use provided that all the provisions in Title 21 Code of Federal Regulations Part 530 (21 CFR 530) (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=530) are followed. In brief, the client must be working with a veterinarian within the context of a valid veterinarian-client-patient relationship (see description below), and there must be no residues that pose a public health risk. Research using food fish species is much more common in the literature, and biotests will most likely be required to determine the best dose and treatment time for specific disease problems. A summary of unapproved doses and indications used by researchers in foodfish species is outlined in Table 2. As for approved uses and species, follow label instructions and contact the appropriate regulatory authorities regarding discharge of treated water.
21 CFR 530:
A valid veterinarian-client-patient relationship is one in which:
(1) A veterinarian has assumed the responsibility for making medical judgments regarding the health of (an) animal(s) and the need for medical treatment, and the client (the owner of the animal or animals or other caretaker) has agreed to follow the instructions of the veterinarian;
(2) There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s); and
(3) The practicing veterinarian is readily available for follow-up in case of adverse reactions or failure of the regimen of therapy. Such a relationship can exist only when the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of examination of the animal(s) and/or by medically appropriate and timely visits to the premises where the animal(s) are kept.
Can hydrogen peroxide be used in ornamental finfish species and for other indications?
A veterinarian can prescribe 35% PEROX-AID® for an extralabel use provided that all the provisions in Title 21 Code of Federal Regulations Part 530 (21 CFR 530) (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=530) are followed. Producers should work closely with a veterinarian when considering use of any drugs.
35% PEROX-AID® can also be used under FDA Investigational New Animal Drug (INAD) #11-669 (see: https://www.fws.gov/fisheries/aadap/inads/Hydrogen-peroxide-INAD-11-669.html for more information).
In freshwater ornamental aquaculture, husbandry practices often logistically favor the use of lower doses of drugs for longer time periods. In one study (Russo et al. 2007), results suggested that use of 3.1 mg/L hydrogen peroxide for one hour may be effective for control of external bacteria, and use of 6.5 mg/L or more for one hour may be effective for control of external flagellates, including the parasite Ichthyobodo sp., in swordtails (Xiphophorus hellerii). Trichodina sp. and Gyrodactylus sp., however, did not appear to be controlled with this regimen. As for approved uses and species, follow label instructions and contact the appropriate regulatory authorities regarding discharge of treated water.
Are there any target animal safety concerns with use of hydrogen peroxide?
As with any aquaculture drug or chemical, improper use may potentially lead to ineffectiveness of treatment. Underdosing, toxicity from overdosing, and pathogen tolerance or resistance (the disease-causing organism may become tolerant or resistant to treatment) are some of the potential problems that could render treatment ineffective. Some species of fish have been shown to be very sensitive (see Are any species sensitive to hydrogen peroxide? below). For species not listed on the 35% PEROX-AID® label, test a small subset of fish before treating the entire diseased population. Species differences, differences in fish age and size, as well as differences in water quality parameters and other factors may alter hydrogen peroxide efficacy and fish toxicity.
Reduced growth rate has been reported in fish treated with high doses of hydrogen peroxide (Speare et al. 1999). In addition, damage to the gills has been reported in some species when hydrogen peroxide has been administered at high or lethal concentrations. For instance, at 22°C, there were 50% mortalities after 3 hours in channel catfish exposed to 238 mg/L and bluegill exposed to 460 mg/L (Rach et al. 1997; Speare et al. 1999). Rach et al. (1997) also noted that early life stages of rainbow trout, i.e., sac and swim-up fry, were much more tolerant of high concentrations of hydrogen peroxide (greater than 1132 mg/L) than larger, older fish. This may be due to differences in gill function and gill anatomy among fish of different ages and sizes.
Mansell et al. (2005) observed significant changes in several blood parameters (lactate, osmolality, and pH) in kingfish following hydrogen peroxide treatment, but overall, there were fewer changes after treatment than were observed during peak infection with the monogenean parasite being treated.
Are any species known to be sensitive to hydrogen peroxide?
Several species of fish are known to be sensitive to hydrogen peroxide, and the use of the chemical may be toxic to those species. 35% PEROX-AID® is not recommended for use on northern pike or paddlefish and should be used with caution on walleye because these fish have been shown to be sensitive to the drug (35% PEROX-AID® label).
Tolerances of different concentrations of hydrogen peroxide by five species of ornamental fish, representing five different families, were tested at 1 hour and 24 hours (Russo et al. 2007). Blue gourami (Trichogaster trichopterus) did not tolerate any of the concentrations tested for 1 hour (11.4–15.9 mg/L) or for 24 hours (3.3–6.0 mg/L). Likewise, the suckermouth catfish (Hypostomus plecostomus) did not tolerate even relatively low doses at 1 hour (6.6–21.9 mg/L); no tests were run on suckermouth catfish for 24 hours. Hydrogen peroxide at these concentrations may not be suitable for use in these two species; however, additional testing in different water quality conditions or in different types of systems is warranted.
By contrast, for 1-hour exposure times, serpae tetras (Hyphessobryconis eques) tolerated 17.0 mg/L; tiger barbs (Puntius tetrazona), 10.0 mg/L; and swordtails, 20.2 mg/L. For 24-hour exposure times, serpae tetras tolerated 5.6 mg/L; tiger barbs, 5.0 mg/L; and swordtails, 5.4 mg/L (Russo et al. 2007).
As a general rule, hydrogen peroxide should not be used for treatment in combination with other chemicals.
Are there any human safety concerns with use of hydrogen peroxide?
As with other strong oxidizers, common sense and appropriate precautions, as described on the label and material safety data sheet (MSDS), should be followed, including use of personal protective equipment. Irritation and chemical burns and associated damage may result from eye or skin contact, inhalation, or ingestion. Always read the label and MSDS carefully. (See the following website for links to product information for 35% PEROX-AID®, including MSDS: http://www.wchemical.com/35-perox-aid-131.html).
Summary
Hydrogen peroxide (35% PEROX-AID®) is an aquaculture drug that has recently been approved by FDA for control of mortality in: 1) freshwater-reared finfish eggs due to saprolegniasis (a common water mold), 2) freshwater-reared salmonids due to bacterial gill disease (Flavobacterium branchiophilum), and 3) freshwater-reared coolwater finfish and channel catfish due to external columnaris (Flavobacterium columnare) disease.
35% PEROX-AID® may be used in an extralabel manner, i.e., for other species and for other indications, as long as FDA regulations with regard to extralabel use are followed. Most importantly, a valid veterinary-client-patient relationship is required, and, if used in foodfish, no tissue residues that may be harmful to public health should result. In addition to those listed above, hydrogen peroxide has been used to control a number of other disease-causing organisms, including various protistans and monogenean parasites.
Before use, consultation with a veterinarian or other fish health professional is strongly recommended. Dosages for species or indications other than those on the label may vary. Effectiveness and safety tests should be run on a small group of fish from the affected population (i.e., a biotest) before the entire population is treated.
References
Avendaño-Herrera, R., B Magariños, R. Irgang, and A. E. Toranzo. 2006. Use of hydrogen peroxide against the fish pathogen Tenacibaculum maritimum and its effect on infected turbot (Scophthalmus maximus). Aquaculture 257:104–110.
Crosbie, P. B. B., and B. L. Munday. 1999. Environmental factors and chemical agents affecting the growth of the pathogenic marine ciliate Uronema nigricans. Diseases of Aquatic Organisms 36:213–219.
Mansell, B., M. D. Powell, I. Ernst, and B. F. Nowak. 2005. Effects of the gill monogenean Zeuxapta seriolae (Meserve, 1938) and treatment with hydrogen peroxide on pathophysiology of kingfish, Seriola lalandi Valenciennes, 1833. Journal of Fish Diseases 28:253–262.
Montgomery-Brock, D., V. T. Sato, J. A. Brock, and C. S. Tamaru. 2001. The application of hydrogen peroxide as a treatment for the ectoparasite Amyloodinium ocellatum on the Pacific threadfin Polydactylus sexfilis. Journal of the World Aquaculture Society 32:250–254.
Noga, E. J. 1996. Fish disease: diagnosis and treatment. Mosby Yearbook, St. Louis, Missouri.
Rach, J. J., T. M. Schreier, G. E. Howe, and S. D. Redman. 1997. Effect of species, life stage, and water temperature on the toxicity of hydrogen peroxide to fish. The Progressive Fish Culturist 59:41–46.
Rach, J. J., M. P. Gaikowski, and R. T. Ramsay. 2000. Efficacy of hydrogen peroxide to control parasitic infestations on hatchery-reared fish. Journal of Aquatic Animal Health 12:267–273.
Russo, R., E. W. Curtis, and R. P. E. Yanong. 2007. Preliminary investigations of hydrogen peroxide treatment of selected ornamental fishes and efficacy against external bacteria and parasites in green swordtails. Journal of Aquatic Animal Health 19:121–127.
Speare, D. J., V. Carvajal, and B. S. Horney. 1999. Growth suppression and bronchitis in trout exposed to hydrogen peroxide. Journal of Comparative Pathology 120(4):391–402.
Taylor, N. I., and L. G. Ross. 1988. The use of hydrogen peroxide as a source of oxygen for the transportation of live fish. Aquaculture 70:183–192.
U.S. Food and Drug Administration. 2002. Title 21 Code of Federal Regulations Part 530 (21 CFR 530). Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=530 (May 2018).
Syndel USA. 2006. 35% PEROX-AID®. Available at: https://www.syndel.com/products/fish-egg-treatments/35-perox-aid-hydrogen-peroxide-16/35-perox-aid-89.html (May 2018).
