INVESTIGATIONS IN FISH CONTROL

86. Registration of Thirty-three Fishery Chemicals: Status 

of Research and Estimated Costs of Required 

Contract Studies

UNITED STATES DEPARTMENT OF THE INTERIOR

FISH AND WILDLIFE SERVICE
Investigations in Fish Control, published by the Fish and Wildlife Service, include reports 

on the results of work at the Service's Fish Control Laboratories at La Crosse, Wis., and 

Warm Springs, Ga., and reports of other studies related to that work. Though each report is 

regarded as a separate publication, several may be issued under a single cover, for economy. 

[See Investigations in Fish Control 47-50 (in one cover) for list of issues published prior to 

1970.]

(Reports 47 through 50 are in one cover.)

47. Preparation and Properties of Quinaldine Sulfate, an Improved Fish Anesthetic, by 

John L. Alien and Joe B. Sills. 1973. 7 pp.

48. Toxicity of Quinaldine Sulfate to Fish, by Leif L. Marking and Verdel K. Dawson. 1973. 

8pp.

49. The Efficacy of Quinaldine Sulfate as an Anesthetic for Freshwater Fish, by Philip A. 

Gilderhus, Bernard L. Berger, Joe B. Sills, and Paul D. Harman. 1973. 9 pp.

50. Residue of Quinaldine in Ten Species of Fish Following Anesthesia with Quinaldine Sulfate, by Joe B. Sills, John L. Alien, Paul D. Harman, and Charles W. Luhning. 1973. 

9pp.

(Reports 51 and 52 are in one cover.)

51. Methods for Simultaneous Determination and Identification of MS-222 and Metabolites in Fish Tissues, by Charles W. Luhning. 1973.10 pp.

52. Residues of MS-222, Benzocaine, and Their Metabolites in Striped Bass Following 

Anesthesia, by Charles W. Luhning. 1973.11 pp.

(Reports 53 through 55 are in one cover.)

53. Toxicity of Mixtures of Quinaldine Sulfate and MS-222 to Fish, by Verdel K. Dawson 

and Leif L. Marking. 1973.11 pp.

54. The Efficacy of Quinaldine Sulfate:MS-222 Mixtures for the Anesthetization of Freshwater Fish, by Philip A. Gilderhus, Bernard L. Berger, Joe B. Sills, and Paul D. Harman. 1973. 9 pp.

55. Residues of Quinaldine and MS-222 in Fish Following Anesthesia with Mixtures of 

Quinaldine Sulfate:MS-222, by Joe B. Sills, John L. Alien, Paul D. Harman, and 

Charles W. Luhning. 1973.12 pp.

(Reports 56 through 59 are in one cover.)

56. Toxicity of the Lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) to 10 Species of 

Algae, by A. A. Maki, L. D. Geissel, and H. E. Johnson. 1975.17 pp.

57. Acute Toxicites of 3-Trifluoromethyl-4-nitrophenol (TFM) and 2 ',5-Dichloro-4 '-nitrosalicylanilide (Bayer 73) to Larvae of the Midge Chironomus tentans, by J. A. Kawatski, 

M. M. Ledvina, and C. R. Hansen. 1975. 7 pp.

58. Acute Toxicity of the Lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) to Nymphs of 

Mayflies (Hexagenia sp.), by C. R. Fremling. 1975. 8 pp.

59. Toxicity and Residue Dynamics of the Lampricide 3-Trifluoromethyl-4-nitrophenol 

(TFM) in Aquatic Invertebrates, by H. O. Sanders and D. F. Walsh. 1975. 9 pp.

(Reports 60 through 62 are in one cover.)

60. Toxicity of the Lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) to Nontarget Fish in 

Static Tests, by L. L. Marking and L. E. Olson. 1975. 27 pp.

61. Toxicity of the Lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) to Nontarget Fish in 

Flow-Through Tests, by L. L. Marking, T. D. Bills, and J. H. Chandler Jr.. 1975. 9 pp.

62. Toxicity of the Lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) to Selected Aquatic

Invertebrates and Frog Larvae, by J. H. Chandler, Jr. and L. L. Marking. 1975. 7 pp. 

(Reports 63 through 66 are in one cover.)

63. Laboratory Efficacy of 3-Trifluoromethyl-4-nitrophenol (TFM) as a Lampricide, by 

V. K. Dawson, K. B. Cumming, and P. A. Gilderhus. 1975.13 pp.

64. Effects of 3-Trifluorornethyl-4-nitrophenol (TFM) on Developmental Stages of the Sea 

Lamprey, by G. W. Piavis and J. H. Howell. 1975. 8 pp.
INVESTIGATIONS IN FISH CONTROL

86. Registration of Thirty-three Fishery Chemicals: Status 

of Research and Estimated Costs of Required 

Contract Studies

By R. A. Schnick and F. P. Meyer

UNITED STATES DEPARTMENT OF THE INTERIOR

FISH AND WILDLIFE SERVICE 

Washington, D.C. 1978
Contents

Page

Abstract............................................................... 1

Piscicides, Lampricides, and Collecting Aids.................................. 2

Antimycin .......................................................... 2

Bayer 73, and the Combination of TFM and Bayer 73 ....................... 3

GD-174............................................................. 3

Rotenone ........................................................... 4

Squoxin ............................................................ 4

TFM............................................................... 5

Thanite............................................................. 5

Therapeutants, Disinfectants, Pond Sterilants, 

Oxidizing Agents, and Osmoregulatory Enhancers........................... 6

Betadine............................................................ 6

Calcium hypochlorite (HTH) ........................................... 6

Formalin ........................................................... 6

Furanace ........................................................... 7

Furazolidone ........................................................ 7

Hyamine 1622 ....................................................... 8

Lime (Calcium Carbonate, Calcium Hydroxide, and 

Calcium Oxide)..................................................... 8

Malachite Green, and the Combination of 

Malachite Green and Formalin........................................ 8

Masoten (Trichlorfon)................................................. 9

Nitrofurazone (Furacin) .............................................. 10

Potassium Permanganate ............................................ 10

R05-0037 (Sulfadimethoxine and Ormetroprim)........................... 11

Sodium Chloride .................................................... 11

Sulfamerazine ...................................................... 11

Terramycin ........................................................ 11

Herbicides and Algicides................................................. 12

Copper Sulfate. ..................................................... 12

2,4-D. ..;..........................................................12

Dichlobenil......................................................... 12

Diquat ............................................................ 13

Diuron ............................................................ 13

Endothall.......................................................... 13

Fenac............................................................. 14

Silvex............................................................. 14

Simazine .......................................................... 15

Anesthetics ........................................................... 15

MS-222 (Tricaine Methanesulfonate).................................... 15

Quinaldine Sulfate, and the Combination 

of MS-222 and Quinaldine Sulfate .................................... 15

References ............................................................16

Appendix 1............................................................ 17

Appendix 2............................................................ 18
Registration of Thirty-three Fishery Chemicals: 

Status of Research and Estimated Costs of Required Contract Studies

by

Rosalie A. Schnick and Fred P. Meyer

U.S. Fish and Wildlife Service

Fish Control Laboratory, P.O. Box 818

La Crosse, Wisconsin 54601

Abstract

An estimated $8.8 million for contract studies is needed to meet registration requirements for 

33 chemicals now used or being considered for use in fish culture and management. Information 

given for each chemical includes its sponsor, current registration status, research situation in six 

categories (toxicity to target and nontarget organisms, field testing, physiological studies, 

analytical methods development, counteraction, and mammalian safety determination), costs of 

required contract studies, and the prognosis for registration of the use of each compound.

Since Lennon (1967) first issued a warning about the 

need to register chemicals for fishery use, regulations 

and guidelines have been developed that require extensive and costly safety evaluation studies (Gumming 

1975; U.S. Environmental Protection Agency 1975a, 

19756). Without these studies, many compounds now 

being used by fish culturists and fishery managers 

could become unavailable. If this occurred, the impact 

on fisheries would be far-reaching: The Great Lakes 

Fishery Commission estimated that 3.5 million angler 

days spent each year fishing for lake trout (Salvelinus 

namaycush) and Pacific salmon (Oncorhynchus sp.) 

would be lost if the sea lamprey (Petromyzon marinus) 

were not being controlled by lampricide applications; 

an estimated 4 million hatchery fish intended for 

stocking in lakes and streams would be lost if chemicals used for disease treatment were unavailable; and 

it is anticipated that the $200 million bait and commercial fish culture industry would suffer a 50% or $100 

million loss if chemicals were not available for use.

When the U.S. Fish and Wildlife Service (FWS) assigned primary responsibility for facilitating registration of fishery compounds to the Fish Control Laboratory in 1972, the Deputy Associate Director for Research and Environment requested, for each priority 

compound, a summary of current information regarding its use patterns in fisheries, patent position, status 

of current registration, and cost estimates of research

needed to obtain registration for fishery uses. This information was first presented in status reports on 22 

compounds in 1973. Literature reviews on 20 of these 

compounds were prepared in 1974. Since then, two 

articles on the registration status of fishery chemicals 

(Meyer et al. 1976) and on the approaching crisis in the 

registration of fishery chemicals (Meyer and Schnick 

1978) have emphasized the need for mammalian safety 

data to support registration or reregistration of fishery chemicals. Development of these data requires specialized facilities that are not available within FWS.

We summarize here the research known to have been 

completed, or yet to be done, on 33 fishery chemicals, 

based on our interpretation of the requirements and 

guidelines of regulatory agencies as of January 1978. 

Information is included on the sponsor of each compound, its current registration status, the research situation in six categories (toxicity to target and nontarget organisms, field testing, physiological studies, 

analytical methods development, counteraction, and 

mammalian safety determination), costs for required 

contract studies, and the prognosis for achieving registration. Requirements for safety evaluation studies on 

various domestic animals, fish, and wildlife were excerpted from the Federal Register (U.S. Environmental Protection Agency 1975a). Costs for required 

work to be done outside FWS are based on January 

1978 prices, but will vary among testing facilities. New
rules by FDA governing the laboratory evaluation of 

the safety of chemicals will probably increase the costs 

of testing (Smith 1977).

The sequence of the registration procedure is shown 

in Appendix 1, and the status of research on the 

various fishery chemicals is summarized in Appendix 2.

Information on each compound was gathered from 

sponsors, regulatory notices, chemical reference 

works, literature reviews, and status reports prepared 

by FWS.

Our estimates of the costs of the contract studies 

needed to meet registration requirements are 

$8,839,800, divided as follows:

7 piscicides, lampricides, and

collecting aids ................... $2,954,000

15 therapeutants, disinfectants, pond

sterilants, oxidizing agents,

and osmoregulatory enhancers ...... 4,239,650

9 herbicides and algicides. ............ 1,010,000

2 anesthetics ........................ 636,150

Total33compounds. ............... $8,839,800

Costs of registering or reregistering chemicals have 

increased as much as 20-fold in the past 10 years. 

Under current regulations, registration costs are relatively fixed, whether a product is likely to be widely 

used and highly profitable or of such limited use that 

profitability is questionable. FWS encourages industry to accept and bear the major costs of compounds 

needed in conservation programs, but most chemical 

companies cannot afford the costs of developing 

"minor-use" products under present requirements, 

without outside support.

The Environmental Protection Agency (EPA) recently established a separate committee to give attention to problems concerning registration of minor-use 

compounds, and the Food and Drug Administration 

(FDA) is revising the criteria for registration of drugs 

and biologies needed for minor uses in the production 

of food animals.

Even though some progress is being made in clarifying procedures and guidelines for registering minoruse compounds, funding has been inadequate to meet 

the complete research need. In the absence of increased funding for registration research, FWS has 

had to limit its effort to a few selected priority chemicals at the expense of others. Lack of funds has also 

made it necessary for FWS to forego the development 

of new techniques and chemicals.

The following sections provide a synopsis of the 

current status of the registration for fishery uses of 33 

priority chemicals, and the cost of fulfilling existing requirements for safety testing.

Piscicides, Lampricides, and 

Collecting Aids

Antimycin

Use

Piscicide.

Sponsor

Sold by Aquabiotics Corporation, Northbrook, 111., 

under license from the Wisconsin Alumni Research 

Foundation; Aquabiotics Corp. will not assist in the 

registration effort.

Registration Status

Registered for nonfood fish use as a piscicide. 

Studies on antimycin are not being actively pursued 

by industry. Major studies are needed on mammalian 

safety, methodology, and residues.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

 most requirements met; invertebrates and 

birds requirements met; plants requirements partly met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements partly 

met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

partly met.

5. Counteraction: removal and inactivation most 

requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); acute dermal, eye, and inhalation studies (rat and rabbit); and 90-day subacute oral (rat) requirements met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) ................$ 35,000

2. Metabolism (cow).................. 100,000

3. Metabolism (rat or dog)............. 25,000

4. 2-year oncogenicity (rat) ............ 100,000

5. 2-year oncogenicity (hamster)........ 100,000

6. 6-month feeding (dog) .............. 35,000

7. Mutagenicity Ames test or

equivalent...................... 1,500

8. Residues methodology ........... 120,000

9. Residues use pattern............. 40,000

10. Residues metabolites ............ 60,000

Total. ........................ $616,500
Prognosis

Reregistration uncertain. Low concentrations (<10 

parts per billion) ordinarily are used and the material 

degrades so rapidly under most conditions that sensitive analytical methods with detection limits in parts 

per trillion are required. Technology for such sensitivity is not now available. Entire registration cost will 

have to be borne by FWS.

is scheduled to be prepared in fiscal year 1978. Further 

studies may be needed on the TFM:Bayer 73 mixture.

GD-174

Bayer 73, and the Combination of 

TFM and Bayer 73

Use

Lampricide; survey tool.

Sponsor

FWS and Great Lakes Fishery Commission. Manufactured by Mobay Chemical Corporation, Kansas 

City, Mo. (formerly Chemagro), specifically for use as a 

lampricide. Mobay Chemical Corp. cooperates by allowing FWS to use data in its files.

Registration Status

Registered for nonfood fish use in surveys for larval 

lampreys and for use as a lampricide in combination 

with 3-trifluoromethyl-4-nitrophenol (TFM) in the 

Great Lakes.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and degradation requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal and inactivation requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); intravenous (iv) or intraperitoneal (ip) injections (rat and mouse); 90-day 

subacute (rat and hamster); metabolism (cow); 

and 6-month feeding (dog) requirements 

met.

b. Carcinogenicity and teratology requirements met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Reregistration promising. A petition for an exemption from tolerance and an amendment of registration

Use 

Piscicide.

Sponsor

FWS; owned by McLaughlin Gormley King Co., 

Minneapolis, Minn. Some technical studies and research are being done by the company.

Registration Status

Not registered for fishery use. GD-174 [2-(digeranylamino)-ethanol] is an experimental compound being 

tested by FWS as a possible selective control for carp, 

or as a general piscicide.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements partly met.

2. Field testing: geographic areas, ecotypes, and efficacy requirements partly met; delivery systems no work done.

3. Physiological studies: mode of action, biotransformation, and excretion no work done.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

partly met.

5. Counteraction: removal and inactivation requirements partly met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); acute dermal and eye studies 

(rabbit); 90-day subacute oral (rat and hamster) requirements met.

b. Carcinogenicity and teratology -* no work 

done.

Costs for Required Work to be Done Outside FWS

1. Acute inhalation (rat). .............$ 500

2. 21-day subacute dermal (rabbit) ..... 3,000

3. Teratology (rabbit). ............... 35,000

4. Metabolism (cow)................. 100,000

5. Metabolism (rat or dog)............ 25,000

6. 2-year oncogenicity (rat) ........... 100,000

7. 2-year oncogenicity (hamster)....... 100,000

8. 6-month feeding (dog). ............. 35,000

9. Avian acute oral (three species)...... 5,000

10. 1-generation reproduction (bobwhite

quail or mallard) ................ 20,000

11. Residues methodology........... 60,000

12. Residues use pattern ............ 40,000

13. Residues metabolites. ........... 60,000

Total. ....................... $583,500
Prognosis

Registration uncertain. Field studies have indicated 

that GD-174 is an excellent piscicide but have failed to 

duplicate the selective action against carp noted in laboratory studies. GD-174 has phytotoxic properties but 

these should not be a serious obstacle to registration. 

Should either rotenone or antimycin be lost to fishery 

use, GD-174 is an excellent candidate replacement.

Rotenone

Use 

Piscicide.

Sponsor 

S. B. Penick & Co., Lyndhurst, N.J., and others.

Registration Status

Registered for nonfood fish use as a piscicide. S. B. 

Penick & Co. is negotiating with EPA to resolve the 

problem of a Rebuttable Presumption Against Registration listing caused by a Spanish report which supposedly showed that rotenone is carcinogenic when injected into rats. A study was initiated by EPA to determine whether the Spanish results could be duplicated. Available results to date show no carcinogenicity. A hamster study was terminated because high 

mortality of control animals made the test results statistically invalid. The master study is being repeated.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements partly 

met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

partly met.

5. Counteraction: removal and inactivation requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); 2-year feeding (rat); and acute 

dermal, eye, and inhalation studies requirements met.

b. Carcinogenicity and teratology; 2-year oncogenicity (hamster) in progress.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. Metabolism (cow) .................. 100,000

3. Metabolism (rat)................... 25,000

4. 2-year oncogenicity (rat)............. 100,000

5. 6-month feeding (dog)............... 35,000

6. Mutagenicity Ames test

or equivalent .................... 1,500

7. Residues methodology............ 120,000

8. Residues use pattern ............. 40,000

9. Residues metabolites ............. 180,000

Total......................... $636,500

Prognosis

Reregistration uncertain. S. B. Penick & Co. is 

highly interested in maintaining the registration of 

rotenone as a piscicide, and is willing to perform some 

of the needed residue and safety studies.

Squoxin

Use 

Piscicide.

Sponsor

American Cyanamid Co., Princeton, N.J.; assisted 

by the National Marine Fisheries Service.

Registration Status

Not registered for fishery use. EPA has granted a 

yearly renewable permit for field tests for use as a selective toxicant for squawfish.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements partly met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action and excretion requirements partly met; biotransformation no work done.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

partly met.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); dermal toxicity (rabbit); and 

31-day subacute oral (rat) requirements 

met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. 90-day subacute oral (rat)............ 25,000

2. 90-day subacute oral (dog)........... 25,000

3. Teratology (rabbit)................. 35,000

4. Metabolism (cow) .................. 100,000
5. Metabolism (rat)................... 25,000

6. 2-year oncogenicity (rat)............. 100,000

7. 2-year oncogenicity (hamster) ........ 100,000

8. 6-month feeding (dog)............... 35,000

9. Mutagenicity Ames test

or equivalent .................... 1,500

10. Avian acute oral (mallard or quail) .... 1,500

11. 8-day avian subacute

dietary (bobwhite quail

or pheasant)..................... 1,000

12. Residues methodology............ 15,000

13. Residues use pattern ............. 10,000

14. Residues metabolites ............. 60,000

Total......................... $534,000

Prognosis

Registration uncertain. Currently completed studies 

are not adequate to meet EPA requirements for registration. Safety evaluation and residue data must be 

developed before the compound can be registered.

TFM

Use 

Lampricide.

Sponsor

FWS and Great Lakes Fishery Commission; manufactured by American Hoechst Corp., Somerville, N. J.

Registration Status

Registered for nonfood fish use as a lampricide.

In February 1976 FWS submitted petitions for an 

exemption from tolerance and an amendment of registration for use of the sodium salt of TFM (3-trifluoromethyl-4-nitrophenol) as a lampricide. EPA provided 

preliminary comments on 22 October 1976, to which 

FWS responded. Further comments from EPA were 

received in March and April 1977.

Data provided were adequate to support negotiations that eliminated the need for further studies in 

several categories: acute oral toxicity tests; 2-year 

hamster feeding study; characterization of residues in 

milk, cattle kidney, and other edible products of cultured mammals; and an indication of the distribution, 

retention, or elimination of TFM and its metabolites.

Points still being negotiated include an exemption 

for the application of dimethylformamide in streams 

as a part of TFM formulations, residue information in 

potable waters, possible restrictions on use in irrigation waters, and possible soil binding effects. An Ames 

test to evaluate potential mutagenicity of TFM was 

completed and found negative by Wisconsin Alumni 

Research Foundation. Progress continues toward registration.

Research Situation

All research studies originally required have been 

completed.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Reregistration highly promising. Outlook is excellent for continued and amended registration and for 

exemption from tolerance.

Thanite

Use 

Collecting aid; piscicide.

Sponsor

FWS; owned by McLaughlin Gormley King Co., 

Minneapolis, Minn.

Registration Status

Not registered for fishery use. Thanite is an experimental fish collecting aid. EPA will require additional 

oncogenic data for reregistration of its current label as 

an insecticide.

Research Situation

1. Toxicity to target and nontarget organisms: fish

 most requirements met; invertebrates and 

birds requirements partly met; plants no 

work done.

2. Field testing: geographic areas and ecotypes 

requirements met; efficacy and delivery systems

 requirements partly met.

3. Physiological studies: mode of action requirements met; biotransformation and excretion 

no work done.

4. Analytical methods development: residues and 

metabolites requirements partly met; degradation no work done.

5. Counteraction: removal and inactivation requirements partly met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat, rabbit, and guinea pig); 6- 

month subacute oral (rat and guinea pig); and 

acute dermal and inhalation studies requirements met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. 90-day subacute oral (hamster) .......$ 25,000

2. Teratology (rabbit)................. 35,000

3. Metabolism (cow) .................. 100,000
4. Metabolism (rat)................... 25,000

5. 2-year oncogenicity (rat)............. 100,000

6. 2-year oncogenicity (hamster) ........ 100,000

7. 6-month feeding (dog)............... 35,000

8. Mutagenicity Ames test

or equivalent ..................... 1,500

9. 8-day avian subacute (mallard) ........ 1,000

10. 8-day avian subacute (quail or

pheasant)....................... 1,000

11. Residues methodology............ 60,000

12. Residues use pattern ............. 40,000

13. Residues metabolites ............. 60,000

Total......................... $583,500

Prognosis

Registration unlikely. Research has been halted. 

McLaughlin Gormley King Co. has expressed concern 

over the cost of the mammalian safety tests that will 

be required and has decided not to continue efforts 

toward obtaining a registration for fishery use at this 

time.

Therapeutants, Disinfectants, Pond

Sterilants, Oxidizing Agents, 

and Osmoregulatory Enhancers

Betadine

Use 

Therapeutant.

Sponsor 

Purdue Frederick Company, Norwalk, Conn.

Registration Status

Not registered for fishery use. National Institute for 

Occupational Safety and Health has expressed concern because a portion of the molecule (poly[l-vinyl-2- 

pyrrolidinone], polymer no. 1) has produced tumors in 

rats in experimental studies.

Research Situation

Requirements are considered to have been met, except perhaps for bird toxicity.

Costs for Required Work to be Done Outside FWS

1. Mutagenicity Ames test or

equivalent ........................ $1,500

2. 8-day avian subacute dietary

(mallard).......................... 1,000

3. 8-day avian subacute dietary

(quail or pheasant). ................. 1,000

Total. .......................... $3,500

Prognosis

Registration highly promising. Betadine is registered as a disinfectant for human and animal skin. 

Purdue Frederick Co., in conjunction with Tavolek, 

Inc., is preparing a New Animal Drug Application on 

Betadine for use as a fish egg disinfectant. Most of the 

required research is considered complete on Betadine.

Calcium Hypochlorite (HTH)

Use

Disinfectant.

Sponsor 

Olin Corporation, Stamford, Conn.

Registration Status

Registered for fishery use as a disinfectant; for sanitizing fish tanks, raceways, and utensils; and for controlling algae and bacteria in fish ponds.

Research Situation 

No additional research needed.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis 

Desired registration has been achieved.

Formalin

Use 

Therapeutant.

Sponsor 

FWS; manufactured and sold by many companies.

Registration Status

Not registered for fishery use. Formalin is used extensively by fish culturists as a therapeutant for external parasites on fish and fungus on fish eggs. National Institute for Occupational Safety and Health 

has expressed concern because neoplastic effects were 

observed in rats.

Research Situation

Required studies completed to date are considered to 

be adequate. FDA may require that further tests be 

done.

Costs for Required Work to be Done Outside FWS 

1. Teratology (rabbit).................. $35,000

Prognosis 

Registration highly promising. A Not New Drug
Monograph was submitted to FDA in 1973. On the 

basis of the review of this document, FDA ruled that 

residue studies based on the use pattern would have to 

be carried out. The Fish Control Laboratory completed 

such studies and submitted the information to FDA in 

1977.

Furanace

Use 

Therapeutant.

Sponsor

Abbott Laboratories, North Chicago, 111. The company has expressed a willingness to help support some 

of the required research. Zodiac Pet Products, Inc., 

Dallas, Texas, currently markets the compound for 

aquarium use.

Registration Status

Registered for nonfood fish use. Abbott Laboratories obtained an aquarium use registration for Furanace in December 1975. A petition for food fish use 

submitted by Abbott to FDA in 1976 was denied, 

pending submission of additional data.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

and invertebrates requirements met; birds 

and plants not needed.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: host responses and mode 

of action requirements met; biotransformation and excretion no work done.

4. Analytical methods development: residues 

most requirements met; metabolites and degradation no work done.

5. Counteraction: removal and inactivation requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute

oral LD50 (rat); and 120-day subacute oral

(mice) requirements met. 

b. Carcinogenicity and teratology no work

done.

Costs for Required Work to be Done Outside FWS

1. Acute dermal (rabbit) ...............$ 300

2. Acute dermal irritation (rabbit)....... 150

3. Acute eye irritation (rabbit).......... 200

4. Acute inhalation (rat)............... 500

5. 90-day subacute oral (dog)........... 25,000

6. Teratology (rabbit)................. 35,000

7. 2-year oncogenicity (rat). ............ 100,000

8. 2-year oncogenicity (hamster) ........ 100,000

9. 6-month feeding (dog)............... 35,000

10. Mutagenicity Ames test or

equivalent ...................... 1,500

11. Residues methodology. ........... 40,000

12. Residues use pattern ............. 40,000

13. Residues metabolites ............. 60,000

Total........... ...... ........$437,650

Prognosis

Food use registration uncertain. Many of the above 

tests may not be needed if FDA accepts the removal of 

Furanace by filtration of treated water through 

carbon, or establishes new minor-use requirements. 

Current label for use on aquarium fishes could easily 

be expanded to include nonfood fishes. Inclusion of 

food fishes will require completion of listed research or 

changes in FDA position, as indicated above.

Furazolidone

Use 

Therapeutant.

Sponsor

Hess stnd Clark, Division of Rhodia, Inc., Ashland, 

Ohio.

Registration Status 

Not registered for fishery use.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

 requirements partly met; invertebrates and 

plants no work done; birds requirements 

met.

2. Field testing; geographic areas, ecotypes no 

work done; efficacy requirements partly met; 

delivery systems no work done.

3. Physiological studies: host responses, mode of 

action, biotransformation, and excretion no 

work done.

4. Analytical methods development: residues and 

metabolites requirements partly met; degradation no work done.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic ,toxicity: acute 

oral LD50 (rat); 53-week feeding (rat); and ip 

injection studies requirements met. 

b. Carcinogenicity and teratology: 2-year oncogenicity (rat and mouse) requirements met.
Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit). ................$ 35,000

2. Metabolism (cow).................. 100,000

3. Metabolism (rat). .................. 25,000

4. 6-month feeding (dog) .............. 35,000

5. Residues methodology ........... 40,000

6. Residues use pattern. ............ 40,000

7. Residues metabolites. ............ 40,000

Total......................... $315,000

Prognosis

Registration highly unlikely. A notice of intent by 

FDA to cancel registrations for furazolidone appeared 

13 May 1976 in the Federal Register. This course of 

action is being considered because of the potential carcinogenic or mutagenic action of the compound. 

Chances of having the compound approved for fishery 

use are nil.

Hyamine 1622

Use 

Therapeutant; disinfectant.

Sponsor 

Rohm and Haas Co., Philadelphia Pa.

Registration Status

Not registered for fishery use. Hyamine 1622 has potential use as a disinfectant and as a treatment for bacterial gill disease. The compound was dropped from 

consideration in 1973 because the product is a mixture 

of compounds, and complex residue studies would be 

required. Also, Furanace was considered to be a better 

choice as a control for bacterial gill disease. Research 

was resumed on the product in 1978 because of renewed interest in the compound by fish culturists.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

 requirements partly met; invertebrates, birds, 

and plants no work done.

2. Field testing: geographic areas and ecotypes 

no work done; efficacy and delivery systems 

requirements partly met.

3. Physiological studies: host responses, mode of 

action, biotransformation and excretion no 

work done.

4. Analytical methods development: residues requirements partly met; metabolites and degradation no work done.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat and mouse); 1-year feeding

(dog); 2-year feeding (rat); and acute dermal 

and eye studies; iv or ip injections requirements met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. Metabolism (cow) .................. 100,000

3. Metabolism (rat)................... 25,000

4. 2-year oncogenicity (rat)............. 100,000

5. 2-year oncogenicity (hamster) ........ 100,000

6. Residues methodology............ 100,000

7. Residues use pattern ............. 40,000

8. Residues metabolites ............. 60,000

Total......................... $560,000

Prognosis

Registration uncertain. Too few data are available to 

evaluate potential problems in registering Hyamine 

1622. The fact that the product is a mixture of compounds may complicate registration efforts.

Lime (Calcium Carbonate, Calcium 

Hydroxide, and Calcium Oxide)

Use 

Pond sterilant.

Sponsor 

FWS.

Registration Status

Registered for fishery use as a pond sterilant under 

the Generally Recognized As Safe classification.

Research Situation 

Requirements met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis 

Desired registration has been achieved.

Malachite Green,

and the Combination of Malachite

Green and Formalin

Use 

Therapeutant.

Sponsor

FWS; produced by American Cyanamid Co., Princeton, N.J., and others.
Registration Status

Not registered for fishery use. Malachite green is 

used extensively to control fungi and protozoans. In 

combination with formalin it is very effective against 

Ichthyophthirius infections.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

and invertebrates requirements met; birds 

not needed; plants requirements partly met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: host responses and excretion requirements partly met; mode of action 

 requirements met; biotransformation no 

work done.

4. Analytical methods development: residues requirements partly met; metabolites and degradation no work done.

5. Counteraction: removal requirements met; inactivation no work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); iv or ip injections requirements met.

b. Carcinogenicity and teratology: teratology 

(rabbit) requirements met.

Costs for Required Work to be Done Outside FWS

1. 90-day subacute oral (rat). ...........$ 25,000

2. 90-day subacute oral (dog) ........... 25,500

3. Teratology (F3 generation rat)........ 100,000

4. Metabolism (cow) .................. 100,000

5. Metabolism (rat)................... 25,000

6. 2-year oncogenicity, parent

compound (rat) .................. 100,000

7. 2-year oncogenicity, parent

compound (mouse)................ 100,000

8. 3-generation reproduction,

parent compound (rat)............. 100,000

9. 2-year oncogenicity, metabolites

(rat)............................ 100,000

10. 2-year oncogenicity, metabolites

(mouse)......................... 100,000

11. 3-generation reproduction,

metabolites (rat) ................. 100,000

12. 6-month feeding (dog)............... 35,000

13. Mutagenicity Ames test

or equivalent .................... 1,500

14. Residues methodology............ 200,000

15. Residues use pattern ............. 40,000

16. Residues metabolites ............. 400,000

Total ....................... $1,552,000

Prognosis

Registration highly unlikely. Malachite green has 

been implicated as a possible teratogen and carcinogen

in fish, and a study in rabbits showed some teratology. 

Discussions with FDA officials indicated that the full 

complement of safety tests would be required. Even if 

all the studies were performed, no guarantee could be 

given that malachite green could be registered. FWS 

has halted its efforts to register it.

Masoten (Trichlorfon) 

Use 

Therapeutant.

Sponsor

Bayvet Division of Mobay Chemical Corp., Kansas 

City, Mo.

Registration Status

Registered for nonfood fish use. Masoten is used in 

fisheries as a control for a variety of ectoparasites, especially the anchor parasite, Lernaea. National Institute for Occupational Safety and Health has expressed 

concern because it has produced carcinogenic effects 

on animals in two studies and teratogenic effects in another.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: host responses, mode of 

action, excretion, and biotransformation requirements partly met.

4. Analytical methods development: residues and 

degradation requirements met; metabolites 

no work done.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); ip injections; 90-day subacute 

(rat); and 2-year feeding (rat and dog) requirements met.

b. Carcinogenicity and teratology requirements met.

Costs for Required Work to be Done Outside FWS 

1. Residues metabolites.............. $75,000

Prognosis

Registration for use on food fish unlikely. Masoten is 

subject to Rebuttable Presumption Against Registration and its status is uncertain. If it is not canceled for 

other uses and if a food use is desired, the listed tests 

will probably be required. The company has shown 

little interest in extending the label to food fish use.
10

Nitrofurazone (Furacin)

Use 

Therapeutant.

Sponsor 

FWS; sold by Norwich Pharmacal Co., Norwich,

N.Y.

Registration Status

Not registered for fishery use. Nitrofurazone was 

listed as a drug of concern in an PDA notice of intent 

to cancel registration of furazolidone because of its 

possible carcinogenicity or mutagenicity. Nitrofurazone is considered a close analog of furazolidone.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

and birds requirements partly met; invertebrates and plants no work done.

2. Field testing: geographic areas and ecotypes 

no work done; efficacy and delivery systems 

requirements partly met.

3. Physiological studies: host responses, mode of 

action, biotransformation, and excretion no 

work done.

4. Analytical methods development: residues and 

degradation requirements partly met; metabolites no work done.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); 53-week feeding (rat); skin 

tests; and ip injections requirements met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. 90-day subacute (dog). ..............$ 25,000

2. Teratology (rabbit)................. 35,000

3. Metabolism (cow) .................. 100,000

4. Metabolism (rat)................... 25,000

5. 2-year oncogenicity (hamster) ........ 100,000

6. 2-year oncogenicity (rat). ............ 100,000

7. 6-month feeding (dog)............... 35,000

8. Residues methodology............ 40,000

9. Residues use pattern ............. 40,000

10. Residues metabolites ............. 40,000

Total......................... $540,000

Prognosis

Registration highly unlikely. Because of the concern 

over the possible carcinogenicity of nitrofurans, it is 

unlikely that any fishery uses of nitrofurazone could 

be registered unless such concern is favorably resolved.

Potassium, Permanganate

Use 

Oxidizing agent.

Sponsor

FWS; sold by Carus Chemical Company, Inc., La 

Salle, 111.

Registration Status 

Not registered for fishery use.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

 requirements met; invertebrates and plants 

requirements partly met; birds no work done.

2. Field testing: geographic areas and ecotypes 

requirements partly met; efficacy requirements met; delivery systems requirements 

partly met.

3. Physiological studies: host responses and mode 

of action requirements partly met; biotransformation and excretion no work done.

4. Analytical methods development: residues requirements partly met; metabolites no work 

done; degradation requirements met.

5. Counteraction: removal and inactivation requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); acute subcutaneous (mouse); 

and acute dermal and eye studies requirements met.

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. 90-day subacute oral (rat). ...........$ 25,000

2. 90-day subacute oral (dog)........... 25,000

3. Teratology (rabbit)................. 35,000

4. Metabolism (cow) .................. 100,000

5. Metabolism (rat)................... 25,000

6. 2-year oncogenicity (rat). ............ 100,000

7. 2-year oncogenicity (hamster) ........ 100,000

8. 6-month feeding (dog)............... 35,000

9. Residues methodology............ 40,000

10. Residues use pattern ............. 40,000

11. Residues metabolites ............. 60,000

Total......................... $585,000

Prognosis

Registration promising. Since certain fishery uses of 

potassium permanganate are not considered to be 

pesticidal, a petition for exemption from registration 

has been requested. If the exemption is not allowed, 

many of the above tests will be required.
11

R05-0037 (Sulfadimethoxine 

and Ormetoprim)

Use 

Therapeutant.

Sponsor 

Hoffmann-La Roche, Inc., Nutley, N.J.

Registration Status

Not registered for fishery use. A decision was made 

to drop this sulfa drug in 1974 because the potentiator 

leaves residues in fish skin. A nitrofuran such as furazolidone or nitrofurazone was suggested as a suitable 

substitute, but these have been dropped because they 

are considered to be potential carcinogens. R05-0037 

was reconsidered for registration in 1977.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

and birds requirements met; invertebrates 

and plants requirements partly met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements 

partly met.

3. Physiological studies: host responses and excretion requirements partly met; mode of action 

 requirements met; biotransformation no 

work done.

4. Analytical methods development: residues and 

metabolites requirements partly met; degradation no work done.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (mouse); 13-week subacute oral (rat 

and dog); and 9-week subacute oral (pig) requirements met.

b. Carcinogenicity and teratology: teratology 

(dog) requirements met.

Costs for Required Work to be Done Outside FWS

1. Metabolism (cow) .................. $100,000

2. Metabolism (rat)................... 25,000

3. Mutagenicity Ames test

or equivalent .................... 1,500

4. Residues use pattern ............. 10,000

Total......................... $136,500

Prognosis

Registration promising. The sponsoring company 

apparently is interested in the compound and will 

pursue its registration. Potential problems exist because skin tissues may retain residues of the drug for 

extended periods. Withdrawal requirements could be 

as long as 6 months after use. Efficacy studies are

under way to determine if a shorter treatment period 

would result in a shorter residue retention period.

Sodium Chloride

Use 

Osmoregulatory enhancer.

Sponsor 

FWS.

Registration Status

Registered for fishery use as an osmoregulatory enhancer under the Generally Recognized as Safe registration.

Research Situation 

Requirements met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis 

Desired registration has been achieved.

Sulfamerazine

Use 

Therapeutant.

Sponsor 

FWS and American Cyanamid Co., Princeton, N.J.

Registration Status

Registered for food fish use. Sulfamerazine is registered for the treatment of furunculosis in trout and 

salmon only.

Research Situation

No research is under way to extend the use label. 

Known research needs have been met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Reregistration promising. No problems are anticipated when reregistration is required.

Terramycin

Use 

Therapeutant.

Sponsor 

FWS and Pfizer, Inc., New York, N.Y.
12

Registration Status

Registered for food fish use. Terramycin is registered for treatment of bacterial infections in trout, 

salmon, and catfish and for marking bones or scales of 

fish in age or identification studies.

Research Situation

No research is under way to extend the label. Known 

research needs have been met.

Costs for Required Work to be Done Outside FWS 

None; requirements met,

Prognosis

Reregistration promising. No problems are anticipated when reregistration is required unless Terramycin is restricted to human uses only. Such a restriction has been rumored because of the possible transfer 

of resistance factors between pathogenic and nonpathogenic bacteria. Current FDA concerns relate 

only to subtherapeutic uses. Since fishery uses involve 

only therapeutic levels, it appears that the compound 

will remain available.

Herbicides and Algicides

Copper Sulfate

Use 

Herbicide and algicide.

Sponsor

Cities Service Co., Atlanta, Ga.; Phelps Dodge Refining Corp., New York, N.Y.; 3M Company, St. Paul, 

Minn.; and others.

Registration Status

Registered for food fish use. Two types of tolerances 

exist for copper as an active component of algicides: 

exemptions from tolerance exist for CuSO4 :5H2O and 

basic copper carbamate, and finite tolerances of 1 ppm 

have been established for copper complexes.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal requirements met; inactivation requirements partly met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity requirements met.

b. Carcinogenicity and teratology requirements met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Desired registration has been achieved. Manufacturers of copper sulfate (Kennecot Chemical, 3M Company, and Phelps Dodge Refining Corp.) indicated to 

the Fish Control Laboratory that they were not interested in attempting to register copper sulfate for other 

uses.

2,4-D

Use 

Herbicide.

Sponsor

AmChem Products, Inc., Ambler, Pa.; 

Chemical USA, Midland, Midi.; and others.

Dow

Registration Status

Registered for food fish use. It can be used as an herbicide only by Federal, State, or local public agencies.

Research Situation

All requirements are considered met, except counteraction.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Extended registration uncertain. Efforts are being 

made by AmChem Products, Inc. to extend the use of 

2,4-D to other than public agencies. Contract studies 

have been started by the company.

Dichlobenil

Use 

Herbicide.

Sponsor

Thompson-Hay ward Chemical Co., Kansas City, 

Kans.

Registration Status 

Registered for nonfood fish use. Dichlobenil can be
13

used in ponds, lakes, and reservoirs with nonflowing 

waters, but the fish cannot be used for food or feed for 

90 days after application. The herbicide cannot be used 

in waters open to commercial fishing for fish or shellfish. EPA will require additional data on oncogenic 

properties for reregistration.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues requirements met; metabolites and degradation 

requirements partly met.

5. Counteraction: removal and inactivation most 

requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity requirements met.

b. Carcinogenicity and teratology: 2-year oncogenicity (rat) requirements met.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. 2-year oncogenicity (hamster) ........ 100,000

Total.... .....................$135,000

Prognosis

Registration for food fish use unlikely. No known 

effort is under way to extend the label for food fish use.

Diquat

Use 

Herbicide.

Sponsor 

Chevron Chemical Co., San Francisco, Calif.

Registration Status

Registered for food fish use. EPA allows residues of 

diquat in potable water during the review of the petition for tolerance. EPA will require additional oncogenic data for reregistration.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal and inactivation requirements met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute 

oral LD50 (rat); 2-year feeding (rat and dog); 

and acute dermal, eye, and inhalation studies 

 requirements met.

b. Carcinogenicity and teratology: teratology 

(rat); and histopathological and neuropathological studies on chronic test animals requirements met.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. 2-year oncogenicity (rat). ............ 100,000

3. 2-year oncogenicity (hamster) ........ 100,000

Total......................... $235,000

Prognosis

Reregistration promising. No problems are anticipated when reregistration is required.

Diuron

Use 

Herbicide.

Sponsor

AmChem Products, Inc., Ambler, Pa.; E. I. Dupont 

De Nemours & Co., Inc., Wilmington, Del.

Registration Status

Not registered for fishery use. It is registered in the 

United States for treating irrigation ditches only and 

has an aquatic use registration in Canada. EPA will require additional oncogenic data for reregistration.

Research Situation

All research has been completed except for counteraction and teratology studies.

Costs for Required Work to be Done Outside FWS 

1. Teratology (rabbit).................. $35,000

Prognosis

Registration unlikely. There is a tolerance in meat of 

mammals, but diuron accumulates in fish tissues.

Endothall

Use 

Herbicide.
14

Sponsor 

Pennwalt Corp., Fresno, Calif.

Registration Status

Registered for food fish use. Endothall was given an 

interim food additive tolerance covering use in canals, 

lakes, ponds, or other potential sources of potable 

water in 1973.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, birds, invertebrates, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal requirements met; inactivation requirements partly met.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity requirements met.

b. Carcinogenicity and teratology: life-time oncogenicity (mouse); teratology (rat) requirements met.

Costs for Required Work to be Done Outside FWS 

None; requirements met.

Prognosis

Reregistration promising. No problems are anticipated when reregistration is required.

Fenac

Use 

Herbicide.

Sponsor

AmChem Products, Inc., Ambler, Pa.; and others. 

Registration Status

Registered for nonfood fish use. Fenac is registered 

for use in lakes, drainage ditches, ponds, and reservoirs where the water is not used for irrigation or domestic purposes or for livestock. EPA will require additional oncogenic data for reregistration.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity: acute

oral LD50 (rat); chronic feeding (rat and dog);

and acute dermal, eye, and inhalation studies

 requirements met. 

b. Carcinogenicity and teratology no work

done.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. 2-year oncogenicity (rat). ............ 100,000

3. 2-year oncogenicity (hamster) ........ 100,000

Total......................... $235,000

Prognosis

Extended registration uncertain. AmChem 

Products, Inc. would like to obtain a label for more 

generalized use, but is pursuing an extension of 2,4-D 

labels first.

Silvex

Use 

Herbicide.

Sponsor 

Dow Chemical USA, Midland, Midi.; and others.

Registration Status

Registered for nonfood fish use. Silvex can be used 

in lakes and ponds to control emergent or submersed 

vegetation, but cannot be used where it could contaminate water intended for domestic use, irrigation, or 

crop spraying.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal most requirements 

met; inactivation no work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity requirements met.
15

b. Carcinogenicity and teratology no work 

done.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. 2-year oncogenicity (rat)............. 100,000

3. 2-year oncogenicity (hamster) ........ 100,000

Total......................... $235,000

Prognosis

Food use registration uncertain. No known research 

is under way to extend the label for food use. Silvex is 

a candidate for the Rebuttable Presumption Against 

Registration list.

Prognosis

Extended registration uncertain. The compound 

may require more research.

Simazine

Use 

Herbicide.

Sponsor 

Ciba-Geigy Corp., Greensboro, N.C.

Registration Status

Registered for food fish use. Simazine has a 

tolerance of 0.1 ppm in potable water and 12 ppm in 

agricultural commodity fish. The registration allows 

use of simazine in ponds (single owner and little or no 

outflow). An experimental use permit was granted for 

experiments on algae in lakes in 1975. EPA will require 

additional oncogenic data for reregistration.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal most requirements 

met; inactivation requirements partly met,

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity requirements met.

b. Carcinogenicity and teratology: 2-year oncogenicity (rat) requirements met.

Costs for Required Work to be Done Outside FWS

1. Teratology (rabbit) .................$ 35,000

2. 2-year oncogenicity (hamster) ........ 100,000

Total....... ....... ...........$135,000

Anesthetics

MS-222 (Tricaine Methane sulfonate)

Use 

Anesthetic.

Sponsor 

Ayerst Laboratories, New York, N.Y., and others.

Registration Status

Registered for food fish use as an anesthetic; 21-day 

withdrawal period required after use on food fish.

Research Situation

1. Toxicity to target and nontarget organisms: 

fish, invertebrates, birds, and plants requirements met.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal requirements met; inactivation not needed.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity not

needed, 

b. Carcinogenicity and teratology not needed.

Costs for Required Work to be Done Outside FWS 

1. Mutagenicity Ames test

or equivalent ...................... $1,500

Prognosis

Desired registration has been achieved. Further research will be directed toward reducing the 21-day 

withdrawal time.

Quinaldine Sulfate, and the 

Combination of MS-222 

and Quinaldine Sulfate

Use 

Anesthetic.
16

Sponsor

FWS; a possible producer is McLaughlin Gormley 

King Co., Minneapolis, Minn.

Registration Status 

Not registered for fishery use.

Research Situation

1. Toxicity to target and nontarget organisms: fish 

 requirements met; invertebrates and plants 

not needed; birds no work done.

2. Field testing: geographic areas, ecotypes, efficacy, and delivery systems requirements met.

3. Physiological studies: mode of action, biotransformation, and excretion requirements met.

4. Analytical methods development: residues, 

metabolites, and degradation requirements 

met.

5. Counteraction: removal and inactivation no 

work done.

6. Mammalian safety determination:

a. Acute, subacute, and chronic toxicity; acute

oral LD50 (rat) requirements met. 

b. Carcinogenicity and teratology no work

done.

Costs for Required Work to be Done Outside FWS

1. Acute dermal (rabbit) .......,.......$ 300

2. Acute primary dermal irritation (rabbit) 150

3. Acute primary eye irritation

(rabbit)......................... 200

4. Acute inhalation (rat)............... 500

5. 90-day subacute oral (rat). ........... 25,000

6. 90-day subacute oral (dog) ........... 25,000

7. Teratology (rabbit)................. 35,000

8. Metabolism (cow) .................. 100,000

9. Metabolism (rat)................... 25,000

10. 2-year oncogenicity (rat). ............ 100,000

11. 2-year oncogenicity (hamster) ........ 100,000

12. 6-month feeding (dog)............... 35,000

13. Mutagenicity Ames test

or equivalent .................... 1,500

14. Avian acute oral (three

species)......................... 5,000

15. 8-day avian subacute

dietary (mallard) ................. 1,000

16. 8-day avian subacute 

dietary (quail or 

pheasant)....................... 1,000

17. 1-generation reproduction 

(bobwhite quail or 

mallard) ........................ 20,000

18. Residues methodology............ 60,000

19. Residues use pattern ............. 40,000

20. Residues metabolites ............. 60,000

Total......................... $634,650

Prognosis

Registration promising. McLaughlin Gormley King 

Co. has expressed interest in supporting a limited 

amount of the needed research. After reviewing New 

Animal Drug Applications for quinaldine sulfate and 

the combination of quinaldine sulfate and MS-222 submitted by FWS in 1974, FDA required additional research for consideration of a registration for food 

fish use. Some contract studies on this compound may 

not be needed if FDA waives certain of its requirements.

References

Gumming, K. B. 1975. History of fish toxicants of the United 

States. Pages 5-21 in P. H. Eschmeyer, ed. Rehabilitation 

of fish populations with toxicants: a symposium. N. Cen. 

Div., Am. Fish Soc., Spec. Publ. No. 4.

Lennon, R. L. 1967. Clearance and registration of chemical 

tools for fisheries. Prog. Fish-Cult. 29(4): 187-193.

Meyer, F. P., and R. A. Schnick. 1978. The approaching crisis 

in the registration of fishery chemicals. Proc. Annu. Conf. 

Southeast. Assoc. Fish Wildl. Agencies 30(1976):5-14.

Meyer, F. P., R. A. Schnick, K. B. Cumming, and B. L. 

Berger. 1976, Registration status of fishery chemicals, 

February 1976. Prog. Fish-Cult. 38(l):3-7.

Smith, R. J. 1977. Creative penmanship in animal testing 

prompts FDA controls. Science 198 (4323):1227-1229.

U.S. Environmental Protection Agency. 1975a. Pesticide program: guidelines for registering pesticides in United 

States. Fed. Regist. 40(123):26801-26928.

U.S. Environmental Protection Agency. 19756. Pesticide 

progress: registration, reregistration, and classification 

procedures. Fed. Regist. 40(129);28241-28286.
screening Preliminary 

review Literature 

screening Delineative 

fish selected of 

invertebrates and 

Preliminary

mutagenicity

tests

S'fr 

x a 

1 1 

S-P I 

S£I

1 1 

5- » 

3 5' 

3

subacute Acute,chronic toxicity Carcinogenicity 

teratology

i i 

Countera

n-

§

Removal and

inactivation

> a CL 

3 i 3 

£,£2- 

*< o 'o 

£T. CL 0 

o en a 

~ § 

Residues, an metabolites, degradation

a

CO & 

5] 8 

o

(K5

O

' '

Host responses mode ofaction, 

biotransformat excretion and 

o

s-£

CK5

are Geographic 

ecotypes, and efficacy, delivery systerr

8 5 

2. S- » a 

IIP

4r' p w'oq 

g- ^ S- § 

Fish, 

invertebrates, and birds,plants

1 1 -i- 1 1 1

FDA or EPA to Submission 

registration for 

.

St.

comment and review Agency 

FDA or EPA to Response 

required comments 

studies further 

e a a- a 

comment and review Agency 

or EPA to Response 

comments FDA 

REGISTRATION 

action Jinal or 

I__.

years 5 in Reregistration 

LI
18

Appendix 2. Status of research on fishery chemicals, January 1978 (c = complete, pc = partly complete; o = no

work done).

Research and development categories

08 I "o £ <B >>

s I » » .S 42 -3 --a 

g e " ~ g '3 -S » c««.H >/| £s § 8. s a § | s^ g

§ » §£ i! 1 'Is ll 2 111 a s l-s -fa " 33 ii 3 e 3 §

| £ 1 g -g | 2 £3 -S^ § 6 3J3 £ .5 ghcg-w .93 Js to S « o « « «

OH PH E-" &H 0* < O S

1

-4J |

13 3 o < 

" § » ^ Comment

** { S 1 el* 1 H "! § *S Q or or

g "i 3 -2 < situation8

1 & S !g 

« T3 a 3 ^

S 0)

Piscicides, lampricides, or collecting aids

Antimycin

Bayer 73

GD-174

Rotenone

Squoxin

TFM

Thanite

c o pc

c c c

c c pc

c c c

c o pc

c c c

c o pc

c pc pc pc pc

c c c c c

pc o pc pc pc

c pc pc c pc

c pc pc o pc

c c c c c

pc pc pc pc pc

o c Registered by

EPA

c o Ready for submission to EPA

o o Experimental

use only

pc c On RPAR list

o o Being sponsored

by NMFS

c c Awaiting final

action by EPA

o o Research discontinued

Therapeutants, disinfectants, pond sterilants,

Betadine

Calcium hypochlorite

Formalin

Furanace

Furazolidone

Hyamine 1622

Lime

Malachite green

Masoten

Nitrofurazone

Potassium permanganate

R05-0037

oxidizing agents,

c o pc

c c c

c c c

c o c

c c pc

c c pc

c c c

c o pc

c c c

c c pc

c c pc

c o pc

and osmoregulatory enhancers

c c c c c

c c c c c

c c c c c

c pc pc c pc

pc o pc o pc

pc o pc o pc

c c c c c

c pc pc pc pc

c pc pc o pc

pc o pc o pc

pc pc pc pc pc

pc pc pc o pc

c o Ready for submission to FDA

c c Registered by

EPA

pc c Awaiting final

action by FDA

o o Responding to

FDA comments

for use on food

fish

pc o Notice to cancel

filed by FDA

o o Research renewed in 1977

c c GRAS

pc o Research terminated

c c Nonfood use

only, on RPAR

list

o o FDA may cancel

o c Awaiting ruling

by EPA

c o Experimental

use only
19

Appendix 2. Continued. Status of research on fishery chemicals, January 1978 (c = complete, pc = partly complete; o = no work done).

Research and development categories

Sodium chloride

Sulfamerazine

Terramycin

Preliminary 

investigations Preliminary mutac c

c c

c c

genicity tests Toxicity to nonc

c

c

organisms target 

Field tests

c

c

c

Physiological 

studies

c

c

c

Analytical methods 

residues and 

c

c

c

Counteraction

c

c

c

1 1

>> ,-. >> -U O> >> 4J __ . O> -t> -u o> ^

111 if 1 C -D 0 G e a, C

« =5 -" S % a o ^3 w _y S g< G « 

CO CO W CO ^ O< 3

S S da

c c c

c c c

c c c

FDA EP aor

Comment 

or 

situation8

GRAS

Registered for

food fish

Registered for

food fish

Herbicides and algicides

Copper sulfate

2,4-D

Dichlobenil

Diquat

Diuron

Endothall

Fenac

Silvex

Simazine

c c

c c

c c

c c

c c

c c

c c

c c

c c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

c

pc

c

c

c

c

c

c

pc

pc

pc

c

pc

pc

o

pc

pc

c c c

c c c

c pc c

c pc c

c pc o

c c c

c o c

c o c

c pc c

Registered for

food fish

Restricted registration

Nonfood use

only

Registered for

food fish

Registered for irrigation ditches

only

Registered for

food fish

Nonfood use

only

Nonfood use

only

Registered for

food fish

Anesthetics

MS-222

Quinaldine sulfate

c o

c o

c

pc

c

c

c

c

c

c

c

o

c c c

pc o c

Registered by

FDA

Awaiting final

action by FDA

aAbbreviations: EPA = 

ognized as Safe; NMFS

Environmental Protection Agency; FDA = Food and Drug Administration; GRAS = Generally Rec- 

= National Marine Fisheries Service; RPAR = Rebuttable Presumption Against Registration.

GPO 847 -293



65. Accumulation and Loss of Residues of 3-Trifluoromethyl-4-nitrophenol (TFM) in Fish 

Muscle Tissue: Laboratory Studies, by J. B. Sills and J. L. Alien. 1975.10 pp.

66. Residues of 3-Trifluoromethyl-4-nitrophenol (TFM) in a Stream Ecosystem after Treatment for Control of Sea Lampreys, by P. A. Gilderhus, J. B. Sills, and J. L. Alien. 1975. 

7pp.

67. Method for Assessment of Toxicity or Efficacy of Mixtures of Chemicals, by L. L. 

Marking and V. K. Dawson. 1975. 7 pp.

68. Development and Evaluation of On-site Toxicity Test Procedures for Fishery Investigations, by R. M. Burress. 1975. 8 pp. 

(Reports 69 and 70 are in one cover.)

69. Toxicity of 3-trifluoromethyl-4-nitrophenol (TFM), 2'5,-dichloro-4'-nitrosalicylanilide 

(Bayer 73), and a 98:2 Mixture to Fingerlings of Seven Fish Species and to Eggs and 

Fry of Coho Salmon, by T. D. Bills and L. L. Marking. 1976. 9 pp.

70. The Freshwater Mussel (Anodonta sp.) as an Indicator of Environmental Levels of 3- 

trifluoromethyl-4-nitrophenol (TFM), by A. W. Maki and H. E. Johnson. 1976. 5 pp.

71. Field Tests of Isobornyl Thiocyanoacetate (Thanite) for Live Collection of Fishes, by 

R. M. Burress, P. A. Gilderhus, and K. B. Gumming. 1976.13 pp.

72. Toxicity of Rotenone to Fish in Standardized Laboratory Tests, by L. L. Marking and

T.D.Bills. 1976. llpp. 

(Reports 73 through 76 are in one cover.)

73. Formalin: Its Toxicity to Nontarget Aquatic Organisms, Persistence, and Counteraction, by T. D. Bills, L. L. Marking, and J. H. Chandler, Jr. 1977. 7 pp.

74. Chlorine: Its Toxicity to Fish and Detoxification of Antimycin, by L. L. Marking and 

T. D. Bills. 1977. 5 pp.

75. Malachite Green: Its Toxicity to Aquatic Organisms, Persistence, and Removal with 

Activated Carbon, by T. D. Bills, L. L. Marking, and J. H. Chandler, Jr. 1977. 6 pp.

76. Toxicity of Furanace to Fish, Aquatic Invertebrates, and Frog Eggs and Larvae, by

L. L. Marking, T. D. Bills, and J. H. Chandler, Jr. 1977. 6 pp. 

(Reports 77 through 79 are in one cover.)

77. Efficacy of 3-Trifluoromethyl-4-nitrophenol (TFM), 2',5-Dichloro-4'-nitrosalicylanilide 

(Bayer 73), and a 98:2 Mixture as Lampricides in Laboratory Studies, by V. K. Dawson, 

K. B. Gumming, and P. A. Gilderhus. 1977.11 pp.

78. Toxicity of the Molluscicide Bayer 73 and Residue Dynamics of Bayer 2353 in Aquatic 

Invertebrates, by H. O. Sanders. 1977. 7 pp.

79. Accumulation, Elimination, and Biotransformation of the Lampricide 2',5-Dichloro-4'- 

nitrosalicylanilide by Chironomus teutons, by J. A. Kawatski and A. E. Zittel. 1977. 

8pp.

(Reports 80 and 81 are in one cover.)

80. Effects of Antimycin A and Rotenone on Macrobenthos in Ponds, by L. J. Houf and 

R. S. Campbell. 1977. 29 pp.

81. Aquatic Macroinvertebrates in a Small Wisconsin Trout Stream Before, During, and 

Two Years After Treatment with the Fish Toxicant Antimycin, by G. Z. Jacobi and 

D. J. Degan. 1977. 24 pp.

82. Investigations in Fish Control: Index to Numbers 1-72, 1964-76, by R. A. Schnick and

K. A. Graves. 1977.19 pp. 

(Reports 83 through 85 are in one cover.)

83. Survival of Two Species of Freshwater Clams, Corbicula leana and Magnonaias boykiniana, After Exposure to Antimycin, by L. L. Marking and J. H. Chandler, Jr. 1978. 

5pp.

84. Chronic and Simulated Use-Pattern Exposures of Brook Trout (Salvelinus fontinalis) to 

3-Trifluoromethyl-4-nitrophenol (TFM), by W. P. Dwyer, F. L. Mayer, J. L. Alien, and 

D. R. Buckler. 1978. 6 pp.

85. Hydrolysis and Photolysis of the Lampricide 2',5-Dichloro-4'-nitrosalicylanilide (Bayer 

73), by D. P. Schultz and P. D. Harman. 1978. 5 pp.

Use of trade names does not imply U.S. Government endorsement of commercial products.
As the Nation's principal conservation agency, the Department of the 

Interior has responsibility for most of our nationally owned public 

lands and natural resources. This includes fostering the wisest use of 

our land and water resources, protecting our fish and wildlife, preserving the environmental and cultural values of our national parks and 

historical places, and providing for the enjoyment of life through outdoor recreation. The Department assesses our energy and mineral 

resources and works to assure that their development is in the best 

interests of all our people. The Department also has a major responsibility for American Indian reservation communities and for people who 

live in island territories under U.S. administration.

Fish Control Laboratories

Fish and Wildlife Service

U.S. Department of the Interior

P.O. Box 818 

La Crosse, Wisconsin 54601

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U.S. DEPARTMENT OF THE INTERIOR

INT 423