Adverse Effects
TFM (3-Trifluoromethyl-4-nitrophenol)
CAS No. 88-30-2
 
 

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Activity: Lampricide, Piscicide
Structure:

Adverse Effects:
Body Weight Decrease
Endocrine: Altered Sex Ratio
Endocrine: Disruptor
Genotoxic
Environmental

TFM is the main chemical used to kill sea lamprey larvae in tributaries to the Great Lakes, the Finger Lakes, and Lake Champlain. Since 1958, TFM has been used in the tributaries of the Great Lakes on a rotational basis. The Sea Lamprey Control Program is the responsibility of the Great Lakes Fishery Commission, but it is delivered by Fisheries and Oceans in Canada and the Fish and Wildlife Service in the United States. Since March 1990 the U.S. Fish and Wildlife Services are the only "approved company" to use this lamprecide.

Food Tolerances: From the Table below, approximately 400,000 pounds of TFM were put into streams, creeks, and lakes in the Great Lakes Basin between 1993-1997. Many of these areas are prime fishing areas. Yet, there are no tolerances for TFM in the US because EPA considers the use of this compound to be non-food. According to EPA: "Based on current use pattens and exposure profiles, residues in and on food and/or feed or in drinking water are not expected to occur. Therefore, a dietary risk assessment is not required."
Ref: Nov 1999 EPA RED

Table 1: Summary of TFM use by the USFWS in the Great Lakes Region (1993-1997)
Ref: US EPA RED, November 1999
Lake 1993 1994 1995 1996 1997
pounds active ingredient used
Superior 6,717 19,991 15,997 12,083 18,768
Michigan 18,150 31,219 25,507 29,811 22,959
Huron 40,371 26,953 24,065 14,605 27,926
Erie 0 9,561 414 5,981 2,815
Ontario 9,438 7,026 10,307 11,001 6,442
Total 74,676 94,750 76,290 73,481 78,910

Effects on fish TFM became a concern in 1992, when Fisheries and Oceans staff identified previously undetected metabolic effects in fish at sites that had been treated. The Commission responded quickly, helping to fund research by Fisheries and Oceans. The research found that the TFM batches contained trace amounts of dioxin. Though it was not the most toxic form, fish are known to be sensitive to dioxins, especially in their developmental stages. The source of the dioxin was traced to a by-product of the chemical's production, and concentrations varied widely from one batch to another. The research led to a change in the manufacturing process, and the Commission now requires manufacturers to produce TFM without dioxins.
Ref: The importance of maintaining up-to-date information on the environmental impacts of pesticide use for sea lamprey control


Body Weight Decrease (click on for all fluorinated pesticides)

In a second 90-day feeding study in rats (MRID 00112727), groups of weanling SD rats (10/sex/group) were fed diets containing TFM (90%) at concentrations of 500, 900, 1620, 2916, or 5248 ppm for 90 days. The control groups (20/sex) received the untreated diet. The results showed that body weights of the 2916 and 5248 ppm groups were consistently decreased (10-13%) in males from week 3 to the end of the study. The decrease was statistically significant (8)
Ref: Reregistration Eligibility Decision (RED) 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide. US EPA, Office of Prevention, Pesticides And Toxic Substances (7508C). Report No. EPA 738-R-99-007. November 1999.
http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

... The sensitivity of mudpuppies, frog tadpoles, and adult frogs to use of 3-trifluoromethyl-4- nitrophenol (TFM) in the Great Lakes has been noted on many occasions. TFM has been used annually since 1958 for the control of sea lampreys throughout the Great Lakes. Amphibians regularly have been found dead in creeks immediately after TFM treatment (Gilderhus and Johnson 1980, Matson 1990). Laboratory tests have confirmed that species native to the Great Lakes Basin, such as the grey tree frog, northern leopard frog, and bullfrog, are sensitive to levels of TFM used for sea lamprey control (Chandler and Marking 1975). Mudpuppy population size decreased by a minimum of 29 per cent after a spray event in the Grand River of Ohio (Matson 1990)...
Ref: Conservation Priorities for the Amphibians and Reptiles of Canada. Sept 2000 report published by World Wildlife Fund Canada and Canadian Amphibian and Reptile Conservation Network. Prepared by David Seburn and Carolyn Seburn.

Endocrine: Altered Sex Ratio (click on for all fluorinated pesticides)

• Note from FAN: The use of TFM in the Great Lakes began at the end of the 1950's. Since that time there has been a dramatic shift from male to female sea lampreys. A confounding factor may be that TFM was found to be contaminated with dioxin in the early 1990s. It is unclear to me whether dioxin influenced this alteration, or TFM alone, or the combination of TFM and dioxin. If someone can clarify, please contact me. [EC, Sept. 2003]

-- TFM treatments have been associated with induction of hepatic mixed function oxyganase activity and altered levels of circulating steroids in fish and induced hepatic vitellogenesis in primary cultures of rainbow trout hepatocytes (Hewitt et al. 1997). As such, TFM acts as an estradiol agonist and has a demonstrated endocrine disrupting effect...
-- Abundance of sea lamprey peaked in several Great Lakes before chemical control began. The sex ratio in these peak populations were predominately males (68-71%). Following a decade of lampricide treatments, populations of sea lampreys showed marked declines and the sex ratios in these populations shifted toward a predominance of females accounting for 72% of the population (Henrich, et al, 1979). This publication by Henrich concludes that lampricides reduced the populations of sea lampreys in the Great Lakes and contributed to the sequential shifting of the sex composition from a predominance of males to a predominance of females. There are no data to support that the endocrine mediated effect associated with TFM is related to the observed sex-ratio shifts among TFM-treated populations of sea lamprey [page 23].

Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide). http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

Abstract: HEEP COPYRIGHT: BIOL ABS. Growth and age at metamorphosis were determined for populations of larval sea lampreys that became reestablished after chemical treatments of tributaries of Lakes Superior and Michigan (USA) with the selected lampricide, 3-trifluoromethyl-4-nitrophenol. Age at metamorphosis varied from 3-7 yr. Growth of ammocetes varied considerably from stream to stream and within streams. Mean lengths of ammocetes of age group III in late summer or early fall in different streams ranged from 65-144 mm. Ammocetes of the 1st yr class established after a chemical treatment grew faster than those of succeeding year classes. Transformation at an early age usually occurred only among fast-growing larvae in large streams. A reversal of the sex ratio, from predominately male to predominately female, followed the reduction of the adult sea lamprey population. Sex ratios of larval and recently metamorphosed sea lampreys reestablished after chemical treatments rapidly shifted from an excess of males to an excess of females. The shift in sex ratio was related to decreased densities of sea lampreys resulting from treatments.
Ref: PURVIS HA (1979). Variations in growth, age at transformation, and sex ratio of sea lampreys (Petromyzon marinus) reestablished in chemically treated tributaries of the upper Great Lakes (USA). GREAT LAKES FISH COMM TECH REP; 0 (35). 1-36.

Endocrine: Disruptor (click on for all fluorinated pesticides)

-- TFM treatments have been associated with induction of hepatic mixed function oxyganase activity and altered levels of circulating steroids in fish and induced hepatic vitellogenesis in primary cultures of rainbow trout hepatocytes (Hewitt et al. 1997). As such, TFM acts as an estradiol agonist and has a demonstrated endocrine disrupting effect...
-- Abundance of sea lamprey peaked in several Great Lakes before chemical control began. The sex ratio in these peak populations were predominately males (68-71%). Following a decade of lampricide treatments, populations of sea lampreys showed marked declines and the sex ratios in these populations shifted toward a predominance of females accounting for 72% of the population (Henrich, et al, 1979). This publication by Henrich concludes that lampricides reduced the populations of sea lampreys in the Great Lakes and contributed to the sequential shifting of the sex composition from a predominance of males to a predominance of females. There are no data to support that the endocrine mediated effect associated with TFM is related to the observed sex-ratio shifts among TFM-treated populations of sea lamprey [page 23].
Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide).
http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

Abstract: BIOSIS COPYRIGHT: BIOL ABS. Recent laboratory studies with nontarget fish species have shown that the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) exhibits estrogenic activity through binding to rainbow trout (Oncorhynchus mykiss) hepatic estrogen receptors and induction of vitellogenin in hepatocyte cultures. In addition, mixed function oxygenase (MFO) activity associated with exposure to field formulations has been attributed in part to the presence of chloro-nitrotrifluoromethyl-dibenzo-p-dioxin impurities. To investigate the environmental effects associated with these findings, the temporal and spatial patterns of MFO activity and vitellogenin induction were monitored in three nontarget fish species following a TFM field treatment. Elevated MFO activity was detected as early as 1 day in caged rainbow trout and activity in trout, wild white sucker (Catostomus commersoni), and longnose dace (Rhinichthys cataractae) peaked 2 or 3 days after treatment. Highest activities were observed in fish
Ref: HEWITT LM et al. (1998). Hepatic mixed function oxygenase activity and vitellogenin induction in fish following a treatment of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM). CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES; 55 (9). 1998. 2078-2086.

Genotoxic (click on for all fluorinated pesticides)

Mutagenicity. In an in vitro cytogenetic assay (MRID 40999201), cultured CHO cells were exposed to TFM (86%) at concentrations of 49.6, 99.2, 149, or 198 Fg/ml for 17.25 hrs. in absence of the S9 metabolic activation. In the presence of the S9 activation, the CHO cells were exposed to TFM at concentrations of 115, 384, 769, 1150, or 1540 Fg/ml for 2 hrs. After exposure to TFM, the treated cells were washed with buffered saline, and complete McCoy’s a medium containing 0.1 Fg/ml Colcemid was added to the washed cells. The cells were then incubated for 2.5 hrs (without S9) or 7.5 hrs (with S9). The metaphase cells were then harvested, and slides prepared for analysis. The results showed that, without S9 activation, TFM at concentrations of 149 and 198 Fg/ml induced chromosomal aberrations, consisting mainly of simple chromatid breaks. In the presence of S9 activation, 1150 and 1540 Fg/ml of TFM caused a statistically significant and dose-related increase in chromosomal aberrations, consisting of simple chromatid and chromosome breaks. (pp 10--11)
Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide).
http://www.fluoridealert.org/pesticides/tfm.red.19
99.pdf

Environmental (click on for all fluorinated pesticides)

Abstract: Toxicity testing with fish began early in this century, but standardized methods have been developed only within the last three decades. Standardized test procedures promote reproducibility of results; healthy fish properly handled and acclimated to test conditions are a given prerequisite. The principles of acute toxicity testing are important in the design of chronic tests for suspected carcinogens because certain factors influence the activity of chemicals or contaminants. The pH of test water is a critical factor in governing the uptake of chemicals by fish. Buffering is required so that uniform pH in waters of different hardnesses and different pHs in water of a given hardness are maintained. The importance of water quality control is graphically demonstrated by the lampricide 3-trifluoromethyl-4-nitrophenol; the toxicant is over 50 times more toxic in water at pH 6.5 than at pH 9.5. Results of laboratory tests on toxicity or carcinogenicity of single compounds in a clean environment represent an oversimplification of the real world because organisms are actually exposed to multiple chemicals or stresses. Because the environment is a complex interaction of physical, chemical, and biological factors that are extremely variable and dynamic, simulation of these systems in the laboratory is, at best, artificial; therefore, results developed must be considered to be predictive.
Ref: Marking LL (1984). Procedures for use of freshwater fishes in the development of reproducible toxicological information. Natl Cancer Inst Monogr 1984 May;65:195-9

-- TFM is chemically and biologically very stable. The compound possesses many of the chemical features known to impart persistence to organic compounds... TFM was converted to reduced-TFM with a half-life of less than one week under both aerobic and anaerobic aquatic metabolism conditions. It must be stressed that when reduced-TFM is reported as a reaction product, degradation has not occurred. TFM has just undergone a chemical reduction and under appropriate conditions, reduced-TFM may be re-oxidized to TFM... TFM is expected to remain in solution in the lake system and persist for long periods of time... TFM (C7 H4 F3 NO3 ; M.W. 207.11) is chemically and biologically very stable. An examination of its structure, i.e., aromatic, fluoro-containing, m-substituted phenol, shows that the compound possesses many of the chemical features known to impart persistence to organic compounds. Its pKa is 6.07 and the effect of pH on the toxicity appears to follow closely to the concentration of the lipid-soluble, free phenol form of TFM. This pH sensitivity is used to maximize effectiveness. As pH increases, toxicity, bioaccumulation, and adsorption to sediment decrease. Aqueous solubility of the sodium salt is 5 g/L.[P 24-25].
Ref: Reregistration Eligibility Decision (RED) 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide. US EPA, Office of Prevention, Pesticides And Toxic Substances (7508C). Report No. EPA 738-R-99-007. November 1999.
http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

Note from FAN: The use of TFM in the Great Lakes began at the end of the 1950's. Since that time there has been a dramatic shift from male to female sea lampreys. A confounding factor may be that TFM was found to be contaminated with dioxin in the early 1990s. It is unclear to me whether dioxin influenced this alteration, or TFM alone, or the combination of TFM and dioxin. [EC, Sept. 2003]

-- TFM treatments have been associated with induction of hepatic mixed function oxyganase activity and altered levels of circulating steroids in fish and induced hepatic vitellogenesis in primary cultures of rainbow trout hepatocytes (Hewitt et al. 1997). As such, TFM acts as an estradiol agonist and has a demonstrated endocrine disrupting effect...
-- Abundance of sea lamprey peaked in several Great Lakes before chemical control began. The sex ratio in these peak populations were predominately males (68-71%). Following a decade of lampricide treatments, populations of sea lampreys showed marked declines and the sex ratios in these populations shifted toward a predominance of females accounting for 72% of the population (Henrich, et al, 1979). This publication by Henrich concludes that lampricides reduced the populations of sea lampreys in the Great Lakes and contributed to the sequential shifting of the sex composition from a predominance of males to a predominance of females. There are no data to support that the endocrine mediated effect associated with TFM is related to the observed sex-ratio shifts among TFM-treated populations of sea lamprey [page 23].

Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide).
http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

... The sensitivity of mudpuppies, frog tadpoles, and adult frogs to use of 3-trifluoromethyl-4- nitrophenol (TFM) in the Great Lakes has been noted on many occasions. TFM has been used annually since 1958 for the control of sea lampreys throughout the Great Lakes. Amphibians regularly have been found dead in creeks immediately after TFM treatment (Gilderhus and Johnson 1980, Matson 1990). Laboratory tests have confirmed that species native to the Great Lakes Basin, such as the grey tree frog, northern leopard frog, and bullfrog, are sensitive to levels of TFM used for sea lamprey control (Chandler and Marking 1975). Mudpuppy population size decreased by a minimum of 29 per cent after a spray event in the Grand River of Ohio (Matson 1990)...
Ref: Conservation Priorities for the Amphibians and Reptiles of Canada. Sept 2000 report published by World Wildlife Fund Canada and Canadian Amphibian and Reptile Conservation Network. Prepared by David Seburn and Carolyn Seburn.

HEEP COPYRIGHT: BIOL ABS. Since 1958, 3-(trifluoromethyl)-4-nitrophenol (TFM) has been used to control the sea lamprey (Petromyzon marinus) in the USA-Canadian Great Lakes Superior, Michigan, Huron and Ontario. A study was conducted to determine the degradability of TFM under laboratory conditions in aqueous (sediment-free) systems. No evidence of microbial degradation of TFM was found up to 80 days. TFM may persist for extended periods of time in the Great Lakes. On the basis of past and present levels of usage of TFM, it was estimated that the concentration of TFM in Lake Superior water could approach, if TFM were a completely conservative chemical, 0.015 mug/l. This concentration was considerably less than the concentrations found to be acutely and chronically toxic to aquatic life. The use of TFM as a sea lamprey larvicide did not represent a hazard to fish and other nontarget aquatic life in the Great Lakes.
Ref: THINGVOLD DA et al. (1981). Persistence of 3-(trifluoromethyl)-4-nitrophenol in aquatic environments. ENVIRON SCI TECHNOL; 15 (11). 1335-1340.


Excerpts from Technical Report 7. April 2000. Animal Deformities or Reproduction Problems. Prepared for the Lake Erie LaMP Preliminary Beneficial Use Impairment Assessment. Keith A. Grasman, Lead Author. Co-Authors: Christine A. Bishop, William W. Bowerman, James P. Ludwig, Pamela A. Martin. http://www.epa.gov/glnpo/lakeerie/buia/lamp7.pdf

(page 13): The sensitivity of mudpuppies, frog tadpoles and adult frogs to TFM use in the Great Lakes has been noted (Gilderhus and Johnson, 1980). TFM is intended to control larval sea lamprey and has been used historically in 19 (8 in U.S./11 in Canada) of the 842 tributaries to Lake Erie for sea lamprey (Petromyzon marinus) control. Since 1995, TFM has been applied in Conneaut Creek and the Grand River in Ohio and Big Creek and Big Otter Creek in Ontario. Only four Lake Erie tributaries (Big Creek Ontario, and 3 U.S. tributaries) are currently scheduled for future regular treatments every 4 to 6 years.

When TFM is used, amphibians have regularly been found dead in creeks immediately after treatment in Lake Erie watersheds and elsewhere in the Great Lakes (Gilderhus and Johnson, 1980; Matson, 1990). Laboratory tests have confirmed that species native to the Great Lakes basin such as gray tree frog, leopard frog, and bullfrog are sensitive to field applied rates of TFM (Chandler and Marking, 1975). In the Grand River, Ohio, Matson (1990) found that in the year following TFM application (1997), mudpuppy population size decreased by a minimum of 29% in the segment treated. In 1999, the Grand River was treated with TFM and dead mudpuppies were found downstream of the application zone within twenty-fours hours.

Because TFM is not bioaccumulative and is only applied periodically in closely controlled and monitored conditions, the associated mudpuppy mortality is often perceived to be insignificant. However, mudpuppies do not become sexually mature until 4 to 6 years of age. Given the past and projected future schedule for TFM applications, there is the potential for the TFM applications to match periods when large numbers of mudpuppy are reaching an age when they can reproduce. In addition, TFM is generally applied in the spring when stream flows are higher. Therefore, TFM has the potential to kill a portion of the existing females before they lay their eggs in May and June. For these reasons, future study is needed to determine the significance of the mortality and the life stages most affected (see section 7.5).

(page 16) • There are conflicting opinions about the significance of non-target species sensitivity, particularly mudpuppy, to TFM (when used for sea lamprey eradication), and its implications for potential impairment. Therefore, the impact of TFM on amphibian populations needs to be assessed by monitoring populations of mudpuppies and other amphibians pre- and postapplication. From a reproductive standpoint, it is particularly important to determine if TFM has greater impacts on certain age classes and/or egg-bearing females.

 
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