January 12, 1994. Federal Register.

US EPA's proposal to add 23 fluorine and organofluorine pesticides to the Toxic Release Inventory
The proposed addition of these chemicals and chemical categories is based on their acute human health effects, carcinogenicity or other chronic human health effects, and/or their environmental effects. EPA believes that these chemicals and chemical categories meet the EPCRA section 313(d)(2) criteria for addition to the list of toxic chemicals.
-- References below

Notes from FAN:

Pesticide activity as of May 2003

and CAS No.

Acifluorfen, sodium

Acifluorfen sodium salt (FIFRA AI) (Ref. 3). Acifluorfen is classified as a Group B2 compound, i.e., the chemical is a probable human carcinogen. Acifluorfen produced an increased incidence of combined malignant and benign liver tumors in two different strains of mice. The compound also displayed positive mutagenic activity in several non-mammalian test systems, and is structurally similar to four other diphenyl ether herbicide compounds which caused increased incidences of liver tumors in two different strains of mice. EPA believes that there is sufficient evidence for listing acifluorfen sodium salt on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available carcinogenicity data.

Herbicide

US: Cattle, Eggs, Goat, Hogs, Horse, Milk, Peanut, Poultry, Rice, Sheep, Soybean, Strawberry

062476-59-9

Benfluralin

Benfluralin (FIFRA AI) (Ref. 3). Increased relative liver weights, decreased red blood cell counts and decreased hematocrit and hemoglobin levels were observed in dogs orally administered benfluralin at a dose of 125 mg/kg/day for 2 years. The NOAEL was 25 mg/kg/day. Based on the NOAEL, EPA has established an oral RfD of 0.003 mg/kg/day. EPA believes that there is sufficient evidence for listing benfluralin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hematological toxicity data for this chemical.

Herbicide

US: Alfalfa, Clover, Lettuce, Peanut, Trefoil (Birdsfoot)

001861-40-1

Bifenthrin

Bifenthrin (FIFRA AI) (Ref. 3). Tremors or head and forelimb twitching were noted in dogs, rats and rabbits exposed to various doses. NOEL values based on the appearance of tremors (often transient) ranged from 1 to 2.67 mg/kg/day. The oral RfD for bifenthrin was based on a 1year beagle dog feeding study, in which the LOEL, based on tremors observed during weeks 15 to 29, was 3.0 mg/ kg/day and the NOEL was 1.5 mg/kg/day. The RfD based on this NOEL was 0.015 mg/kg/day.

In a rat teratology study, an increased incidence of hydroureter (without hydronephrosis) was noted in fetuses at 2 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day.

EPA believes that there is sufficient evidence for listing bifenthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological and developmental toxicity data.

Aquatic acute toxicity values for bifenthrin include a bluegill 96- hour LC50 of 0.35 ppb, a rainbow trout 96-hour LC50 of 0.15 ppb, a sheepshead minnow LC50 of 17.5 ppb, and a daphnid 48-hour EC50 of 1.6 ppb. EPA believes that there is sufficient evidence for listing bifenthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data.

Acaracide,
Insecticide,
Wood Preservative

US: Artichoke, Brassica, Cabbage, Caneberry, Cattle, Citrus Fruit & Oil, Corn, Cotton, Egg, Eggplant, Goat, Grape, Hogs, Horse, Lettuce, Milk, Peanut meat (hulls removed), Pepper (bell and non-bell), Poultry, Potato, Rapeseed, Sheep, Strawberry, Sweet Potato, Legumes, Cattle, Goat, Hog, Horse, Poultry, Sheep

082657-04-3

Boron trifluoride

Boron trifluoride (EPCRA EHS) (Ref. 8). Boron trifluoride is a colorless gas that is corrosive to tissues due to its rapid hydrolysis to hydrofluoric acid and boric acid. The principal acute effect in animals is irritation of the mucous membranes of the respiratory tract and eyes; post mortem examination also revealed pneumonia and degenerative changes in renal tubules. The kidneys are most severely affected because boric acid concentrates in this organ. Exposure of six animal species to 0.28 mg/L of boron trifluoride for 4 to 7 hours a day, 5 days a week killed all animals within 30 days. Rats, rabbits, and guinea pigs were exposed to boron trifluoride via inhalation. Guinea pigs died of respiratory failure after being exposed to 0.036 mg/L for 19 days; rats experienced fluorosis of the teeth at this concentration. All three species were minimally affected at 0.004 mg/L. In a 2-week rat inhalation study, all animals died after 6 daily exposures to 0.18 mg/L. Rats exposed to 0.024 mg/L showed signs of respiratory irritation, increased lung weights, and depressed liver weights. Rats exposed to 0.17 mg/L of boron trifluoride 6 hours/day, 5 days a week for 13 weeks developed necrosis of the proximal tubular epithelium of the kidneys. Guinea pigs exposed to 0.035 mg/L, 7 hours/day, 5 days a week for 3 months developed severe pneumonitis and pulmonary changes indicating chemical irritation.

EPA believes that there is sufficient evidence for listing boron trifluoride on EPCRA section 313 pursuant to section 313(d)(2)(B) based on the available chronic toxicity data for this chemical.

Fumigant

Not registered for pesticidal use in the US

007637-07-2

Cyfluthrin

Cyfluthrin (FIFRA AI) (Ref. 3). In a 14-day rat study, oral administration of 60 mg/kg/day produced tremors, uncoordinated gait, salivation, slight brain hemorrhages, necrosis of the skeletal muscle fibers, and death. The NOEL was not defined. In another study, salivation, straddled gait, axonal degeneration of sciatic nerve, microtubular dilation, and mitochondria degeneration in the sciatic and femoral nerves were observed in rats administered 80 mg/kg/day orally for 5 days and 40 mg/kg/day for the following 9 days. No NOEL was established.

Liver and adrenal weight increases were observed in rats orally administered 40 to 80 mg/kg/day for 28 days. The highest dose of 80 mg/ kg/day was reduced to 40 mg/kg/day. The NOEL was 20 mg/kg/day. Liver weight changes and urobilinogen and ketone bodies in the urine were observed in rats fed 15 mg/kg/day for 28 days. No NOEL was established. In a 28-day mouse feeding study, increased liver weight was observed at 50 mg/kg/day (LOEL). The NOEL was 15 mg/kg/day. Inflammatory foci in the kidneys of females were observed at 7.5 mg/kg/day in a 2-year rat feeding study. The NOEL was 2.5 mg/kg/day. Based on the NOEL of the study, an oral RfD of 0.025 mg/kg/day was determined. Increased alkaline phosphatase activity was observed in males at 7.5 mg/kg/day in a 23-month mouse feeding study. EPA believes that there is sufficient evidence for listing cyfluthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, hepatic, and renal toxicity data.

Aquatic acute toxicity values for cyfluthrin include a rainbow trout 96-hour LC 50 of 0.68 ppb, a bluegill 96-hour LC 50 of 1.5 ppb, and a daphnid 48-hour EC 50 of 0.14 ppb. EPA believes that there is sufficient evidence for listing cyfluthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data.

Insecticide

US: Alfalfa, Animal feed, Aspirated grain, Barley, Carrot, Cattle, Citrus fruit, Corn, Cotton, Processed foods, Egg, Goat, Grape, Raisin, Hog, Hop, Horse, Milk, Oat (grain), Pepper, Potato, Poultry, Radishe, Sheep, Sorghum, Sugarcane (Cane), Sugarcane (Molasses), Sunflower seeds, Tomato, Wheat (grain)

068359-37-5

Cyhalothrin

Cyhalothrin (FIFRA AI) (Ref. 3). Cyhalothrin administered orally (in capsules) to dogs at 10 mg/kg/day for 26 weeks produced occasional disturbances of the nervous system (unsteadiness and/or muscular trembling). The NOEL for these effects was not defined. In a 1-year dog study, ataxia, muscle tremors, and convulsions were observed following oral administration at 3.5 mg/kg/day. Abnormal gait and convulsions were observed at 0.5 mg/kg/day. The LOEL of the study was 0.5 mg/kg/day and the NOEL was 0.1 mg/kg/day. EPA believes that there is sufficient evidence for listing cyhalothrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological toxicity data.

Acaracide, Insecticide

US EPA: registration pending.

EPA has approved emergency use on Rice and Sugarcane

068085-85-8

Dichlorofluoromethane

Hydrochlorofluorocarbons (CAA OD) (Ref. 8). Hydrochlorofluorocarbons are known to release chlorine radicals into the stratosphere. Chlorine radicals act as catalysts to reduce the net amount of stratospheric ozone.

Stratospheric ozone shields the earth from ultraviolet-B (UV-B) radiation (i.e., 290 to 320 nanometers). Decreases in total column ozone will increase the percentage of UV-B radiation, especially at its most harmful wavelengths, reaching the earth's surface.

Exposure to UV-B radiation has been implicated by laboratory and epidemiologic studies as a cause of two types of nonmelanoma skin cancers: squamous cell cancer and basal cell cancer. Studies predict that for every 1 percent increase in UV-B radiation, nonmelanoma skin cancer cases would increase by about 1 to 3 percent.

Recent epidemiological studies, including large case control studies, suggest that UV-B radiation plays an important role in causing malignant melanoma skin cancer. Recent studies predict that for each 1 percent change in UV-B intensity, the incidence of melanoma could increase from 0.5 to 1 percent.

Studies have demonstrated that UV-B radiation can suppress the immune response system in animals, and, possibly, in humans. Increases in exposure to UV-B radiation are likely to increase the incidence of cataracts and could adversely affect the retina.

Aquatic organisms, particularly phytoplankton, zooplankton, and the larvae of many fishes, appear to be susceptible to harm from increased exposure to UV-B radiation because they spend at least part of their time at or near the surface of waters they inhabit.

Increased UV-B penetration has been shown to result in adverse impacts on plants. Field studies on soybeans suggest that yield reductions could occur in some cultivars of soybeans, while evidence from laboratory studies suggest that two out of three cultivars are sensitive to UV-B.

Because this increased UV-B radiation can be reasonably anticipated to lead to cancer and other chronic human health effects and significant adverse environmental effects, EPA believes there is sufficient evidence for listing the following HCFCs that are commercially viable on EPCRA section 313 pursuant to EPCRA sections 313(d)(2)(B) and (C). Dichlorofluoromethane is included in the HCFCs that EPA is proposing be added individually to EPCRA section 313.

Dichloropentafluoropropane (CAS No. 127564-92-5)
1,3-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225ea) (CAS No. 136013-79-1)
2,2-Dichloro-1,1,1,3,3-pentafluoropropane (HCFC-225aa) (CAS No. 128903-21-9)
1,1-Dichloro-1,2,3,3,3-pentafluoropropane (HCFC-225eb) (CAS No. 111512-56-2)
1,1-Dichloro-1,2,2,3,3-pentafluoropropane (HCFC-225cc) (CAS No. 13474-88-9)
1,3-Dichloro-1,1,2,2,3-pentafluoropropane (HCFC-225cb) (CAS No. 000507-55-1)
1,2-Dichloro-1,1,3,3,3-pentafluoropropane (HCFC-225da) (CAS No. 000431-86-7)
3,3-Dichloro-1,1,1,2,2-pentafluoropropane (HCFC-225ca) (CAS No. 000422-56-0)
2,3-Dichloro-1,1,1,2,3-pentafluoropropane (HCFC-225ba) (CAS No. 000422-48-0)
1,2-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225bb) (CAS No. 000422-44-6)
Dichlorofluoromethane (HCFC-21) (CAS No. 000075-43-4)
1,1,1,2-Tetrachloro-2-fluoroethane (HCFC-121a) (CAS No. 000354-11- 0)
1,1,2,2-Tetrachloro-1-fluoroethane (HCFC-121) (CAS No. 000354-14-3)
1,2-Dichloro-1,1-difluoroethane (HCFC-132b) (CAS No. 001649-08-7)
2-Chloro-1,1,1-trifluoroethane (HCFC-133a) (CAS No. 000075-88-7)
3-Chloro-1,1,1-trifluoropropane (HCFC-253fb) (CAS No. 000460-35-5).

US EPA List 2 Inert

currently used in pesticide products

127564-92-5

Diflubenzuron

Diflubenzuron (FIFRA SR) (Ref. 8). In a 2-year study in which beagle dogs received diflubenzuron daily in gelatin capsules, the LOAEL for increases in sulfhemoglobin and methemoglobin was 10 mg/kg/day and the NOAEL was 2 mg/kg/day. EPA has derived an oral RfD of 0.02 mg/kg/day for this chemical from this study. Similar effects were noted in two separate 2-year rat feeding studies (the LOAEL was 7.8 to 8 mg/kg/day; the NOAEL was 2 mg/kg/day), and in a lifetime oral study in mice (the LOAEL was 12 mg/kg/day; the NOAEL was 2.4 mg/kg/day). EPA believes that there is sufficient evidence for listing diflubenzuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hematological toxicity data.

Measured aquatic acute toxicity data for diflubenzuron include a 48-hour LC50 of 4.55 ppb for daphnids. EPA believes that there is sufficient evidence for listing diflubenzuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental toxicity data for this chemical.

Insecticide, Chemosterilant

US: Artichoke, Egg, Grapefruit, Grass (pasture, range, rangeland), Milk, Mushroom, Orange, Pear, Rice, Soybean, Tangerine, Walnut, Cattle, Goat, Horse, Hog, Poultry, Sheep

035367-38-5

Dithiopyr

Dithiopyr (FIFRA AI) (Ref. 3). In a 2-generation rat reproduction study, decreased body weight, diffuse hepatocellular swelling, and ``white spots'' on the livers were observed in the offspring of rats administered greater than or equal to 16.4 mg/kg/day. The NOEL values were 1.7 mg/kg/day. In a 13-week rat feeding study, the LOEL of 6.62 mg/kg/day produced diffuse hepatocellular swelling. The NOEL was 0.662 mg/kg/day. In a 13-week dog feeding study, increased alkaline phosphatase, discolored livers, and cholestasis was observed at 10 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. In addition, at 30 mg/kg/day, increased serum glutamic-pyruvic transaminase and serum glutamic oxaloacetic transaminase, increased liver and kidney weights, and decreased cholesterol and albumin were observed. EPA believes that there is sufficient evidence for listing dithiopyr on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic and renal toxicity data.

Herbicide

registered for use in the US

097886-45-8

Fluazifop butyl

Fluazifop butyl (FIFRA AI) (Ref. 3). A 3-month rat feeding study demonstrated hepatocyte hypertrophy in males (the LOEL was 5 mg/kg/day; the NOEL was 0.5 mg/kg/ day). In a 1-year feeding study, dogs had changes in serum alkaline phosphatase and alanine aminotransferase and/or alanine sulfatransferase (the LOEL was 25 mg/kg/day; the NOEL was 5 mg/kg/day). Similar changes were also reported in dogs following 3 months exposure in their diet (the LOEL was 125 mg/kg/day). In a carcinogenicity study, male mice fed 20 ppm (2.6 mg/kg/day, the LOEL) had an increased incidence of hepatocyte hypertrophy. The NOEL was 5 ppm or 0.65 mg/kg/ day. Male and female mice exposed to a higher dose of 80 ppm (10.4 mg/ kg/day) had increased liver weight (relative and absolute) and hypertrophy of periacinal hepatocytes. Males in this dose group also had increased pigmentation in hepatocytes and Kupffer cells.

In a teratogenicity study in Sprague-Dawley rats exposed via oral gavage, delayed ossification and an increased incidence of hydroureter were observed in fetuses (the fetotoxic LOEL was 5 mg/kg/day; the NOEL 1 mg/kg/day) and a teratogenic LOEL of 200 mg/kg/day (the NOEL was 10 mg/kg/day) was determined based on the incidence of diaphragmatic hernia. Maternal toxicity was observed in this study at doses higher than those causing fetotoxicity and included reduced body weight gain and decreased gravid uterus (the maternal LOEL was 200 mg/kg/day; the NOEL was 10 mg/kg/day). In a 2-generation reproductive toxicity dietary study in Wistar rats, the reproductive LOEL of 250 ppm (12.5 mg/kg/day; the NOEL was 80 ppm or 4 mg/kg/day) was based on reduced litter sizes, reduced viability, reduced testis and epididymis weights and tubular atrophy in offspring. Fetotoxicity (delayed ossification and eye opacities) was also demonstrated in New Zealand White rabbits (the LOEL was 30 mg/kg/day; the NOEL was 10 mg/kg/day). EPA believes that there is sufficient evidence for listing fluazifop butyl on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic and developmental toxicity data for this chemical.

Herbicide

US: Asparagus, Carrots, Coffee beans, Cotton seed / oil, Eggs, Endive, Stone fruits, Cattle, Goats, Hogs, Horse, Milk, Macadamia nuts, Onions (dry bulb), Pecans, Peppers (tabasco), Poultry, Rhubarb, Sheep, Soybeans, Spinach, Sweet potatoes

069806-50-4

Flumetralin

Flumetralin (FIFRA AI) (Ref. 3). Aquatic acute toxicity values for flumetralin include a daphnid 48-hour EC50 of greater than 2.8 ppb, a bluegill sunfish 96-hour LC50 of greater than 3.2 ppb, and a rainbow trout 96-hour LC50 of greater than 3.2 ppb. EPA believes that there is sufficient evidence for listing flumetralin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data for this chemical.

Plant Growth Regulator Herbiciide

registered for use in the US

062924-70-3

Fluorine

Fluorine (CERCLA; EPCRA EHS; RCRA APP8; RCRA P) (Ref. 8). Inhalation of fluorine causes initial coughing, choking and chills, which is followed 1 or 2 days later with pulmonary edema. Fluorine has a strong caustic action on mucous membranes, eyes and skin. In human volunteers exposed to 100 ppm (0.16 mg/L) for 30 seconds, much irritation to the nose and eyes was reported. In acute inhalation studies in animals, lethality occurs at a fairly uniform level and is the result of pulmonary edema. Following 1 hour exposures in mice, rats or guinea pigs, the inhalation LC

50 values ranged from 150 to 185 ppm (0.23 to 0.29 mg/L). The LC50 for rabbits following a 30-minute exposure was 270 ppm (0.42 mg/L). EPA's exposure analysis indicates that fluorine concentrations are likely to exist beyond facility site boundaries, as a result of continuous, or frequently recurring releases, at levels that can reasonably be anticipated to cause significant adverse acute human health effects. EPA believes that there is sufficient evidence for listing fluorine on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(A) based on the available acute toxicity and exposure data for this chemical.

Intermedate in the manufacture of fluorine and organofluorine pesticide formulations

007782-41-4

Fluorouracil

Fluorouracil (5-Fluorouracil) (CAL; EPCRA EHS) (Ref. 8). A major use of fluorouracil is in the palliative treatment of carcinoma of the colon, rectum, breast, stomach, and pancreas that is not amenable to surgery or irradiation. The major toxic effects of fluorouracil are on the normal, rapidly proliferating tissues particularly of the bone marrow and lining of the gastrointestinal tract. Leukopenia, predominantly of the granulocytopenic type, thrombocytopenia, and anemia occur commonly with intravenous fluorouracil therapy at doses ranging from 6 to 12 mg/kg. Pancytopenia and agranulocytosis also have occurred.

Developmental abnormalities or other effects on newborns were reported in offspring of women receiving 150 or 240 mg/kg fluorouracil intravenously during weeks 11 to 14 or 20 to 31 of pregnancy. In addition, maternal toxicity to the reproductive organs, toxicity to the fetus, and developmental abnormalities have been reported in mice, rats, and hamsters receiving oral, intraperitoneal, or intramuscular doses of fluorouracil ranging from 10 to 700 mg/kg.

Chronic neurotoxic effects were noted in dogs fed fluorouracil at a dietary dose of 2 mg/kg/day for 6 months. In this study, animals were examined at the end of 3 months and 6 months. At the end of the experiment, or at death, the brain was removed and examined (only one dog survived the entire 6-month period). Histological sections of the brain showed the presence large multiple monolocular vacuoles in the wall of the fornix of the third ventricle.

EPA believes that there is sufficient evidence for listing fluorouracil on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the toxicity of this substance to bone marrow, and on the developmental and chronic neurotoxicity data for this chemical.

Former insect chemosterilant

000051-21-8

Fluvalinate

Fluvalinate (FIFRA AI) (Ref. 3). Delayed ossification and decreased weight and length of fetuses were observed in offspring of rats orally administered 50 mg/kg/day (LOEL) on days 6 to 15 of gestation. The NOEL was 10 mg/kg/day. These effects were observed at doses that produced maternal toxicity. Curved tibia and fibula were observed in the offspring of rabbits orally administered 125 mg/kg/day (LOEL). The NOEL was 25 mg/kg/day. In a 2-generation reproduction study, a decrease in pup weight and growth were observed in offspring of rats orally administered 5 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. Significantly decreased weight and survival were observed in offspring of rats orally administered 25 mg/kg/day.

In a range finding study, dietary administration of 50 mg/kg/day for 30 days produced skin lesions in rats. The NOEL was not determined. A 2-year rat feeding study was terminated at 64 weeks due to dermal lesions produced in animals at 15 mg/kg/day. The NOEL was 2 mg/kg/day. Dietary administration of 10 mg/kg/day (LOEL for effect) to mice for 2 years produced scabbing and dermal abrasion. No NOEL for these effects was established. An increase in plantar ulcers was observed in rats fed 2.5 mg/kg/day (LOEL) for 2 years. The NOEL was 1 mg/kg/day. Decreases in body weight gain were also observed in this study. Based on the NOEL of the study, an oral RfD of 0.01 mg/kg/day was derived. In a 2- generation rat reproduction study, dietary administration of 5 mg/kg/ day produced decreased body weight gain and skin lesions in parents and offspring.

Dietary administration of 2.5 mg/kg/day to rats for 13 weeks produced anemia in blood parameters (decreased hematocrit, hemaglobin, and red blood cells). The NOEL was 1.0 mg/kg/day. Dietary administration of 30 mg/kg/day (LOEL) to rats for 3 months produced decreased hemoglobin, hematocrit, and red blood cell count in rats. The NOEL was 3 mg/kg/day.

EPA believes that there is sufficient evidence for listing fluvinate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available developmental, dermal, and hematological toxicity data for this chemical.

Aquatic acute toxicity values for fluvalinate include a daphnid 48- hour EC50 of 0.40 ppb, a bluegill sunfish 96-hour LC50 of 0.9 ppb, a rainbow trout 96-hour LC50 of 2.9 ppb, and a sheepshead minnow 96-hour LC50 of 10.8 ppb. EPA believes that there is sufficient evidence for listing fluvinate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data for this chemical.

Acaracide, Insecticide

US: Cattle, Coffee bean, Cotton, Egg, Goat, Hog, Honey, Horse, Milk, Poultry, Sheep

069409-94-5

Fomesafen

Fomesafen (FIFRA AI) (Ref. 3). Decreased plasma cholesterol and triglycerides and increased liver weights (reversible at 7 days post-treatment) were observed at 50 mg/kg/day (only dose tested) when administered in the diet of rats for 4 weeks. In a 90-day rat study, dietary administration of 5 mg/kg/day (LOEL) produced alterations in lipid metabolism and increases in liver weight. The NOEL was 0.25 mg/kg/day. In a 26-week dog study, dietary administration of 25 mg/kg/day (LOEL) produced alterations in lipid metabolism and liver changes (changes not defined). The NOEL was 1 mg/ kg/day. Liver toxicity (increased liver masses, discolored hepatocytes, and pigmented Kupffer cells) was observed in a 2-year rat feeding study at 50 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day. Metabolism studies have shown that fomesafen accumulates in the liver. EPA believes that there is sufficient evidence for listing fomesafen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic toxicity data for this chemical.

Herbicide

US: Soybean

072178-02-0

Hydramethylnon

Hydramethylnon (FIFRA AI) (Ref. 3). In a 90-day dog feeding study, testicular atrophy was observed at 6 mg/ kg/day (LOEL). The NOEL was 3 mg/kg/day. In a 90-day rat study, dietary administration of 5 mg/kg/day (LOEL) produced testicular atrophy. The NOEL was 2.5 mg/kg/day. Dietary administration of 6.5 mg/kg/day for 18 months produced testicular lesions in mice. The NOEL was 2.75 mg/kg/ day. In a 2-year rat study, dietary administration of 5 mg/kg/day produced decreased testicular weight and testicular atrophy. The NOEL was 2.5 mg/kg/day. In a 3-generation rat reproduction study, oral administration of 5 mg/kg/day produced male infertility. The NOEL was 2.5 mg/kg/day.

Decreased fetal weight was observed in the offspring of rats administered 30 mg/kg/day (LOEL). The NOEL was 10 mg/kg/day. Increased post implantation loss and decreased fetal viability were observed in the offspring of rabbits administered 15 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day. Vertebral anomalies were seen in the offspring of rabbits administered 10 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day.

Dietary administration of 1 mg/kg/day (LOEL) for 6 months to dogs produced increased absolute and relative liver weights. The NOEL was 0.33 mg/kg/day. Based on the NOEL of the study, an oral RfD of 0.0003 mg/kg/day was derived.

EPA believes that there is sufficient evidence for listing hydramethylnon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available reproductive, developmental, and hepatic toxicity data for this chemical.

The 96-hour LC50 in the Chanel Catfish was 90 ppb. Bioaccumulation factors in bluegill sunfish are 1300 for the whole fish, 780 for the fillet, and 1900 for viscera. EPA believes that there is sufficient evidence for listing hydramethylon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data and the potential for bioaccumulation.

Insecticide

US: Grass - Pasture, Grass - Pasture/Hay, Grass - Rangeland, Pineapple

067485-29-4

Lactofen

Lactofen (FIFRA AI) (Ref. 3). Lactofen meets the criteria of an EPA Group B2 compound, i.e., a probable human carcinogen. This conclusion was based on an increased incidence of hepatocellular carcinomas in males and combined incidence of hepatocellular adenomas and carcinomas in both sexes of CD-1 mice following dietary administration of lactofen. In CD rats, there was increased incidence of liver neoplastic nodules in both sexes. Four structurally similar chemicals, acifluorfen, nitrofen, oxyfluorfen, and fomesafen, all produced hepatocellular tumors in rodents.

Results of several subchronic and chronic studies indicated the liver and kidney as target organs for lactofen. Increased absolute and relative liver weight and hepatocytomegaly (the LOEL was 1.5 mg/kg/day; the NOEL was not determined) were observed in male mice fed lactofen for 78 weeks. At 37.5 mg/kg/day, there was also an increased incidence of cataracts and renal pigmentation. Based on the LOEL, an oral RfD of 0.002 mg/kg/day was derived. Renal dysfunction and decreased hemoglobin and hematocrit levels and red blood cell counts (the LOEL was 25/75 mg/ kg/day; the NOEL was 5 mg/kg/day) were observed in a 1-year feeding study in dogs. Increased renal and hepatic pigmentation (the LOEL was 50 mg/kg/day; the NOEL was 25 mg/kg/day) were noted in a 2-year feeding study in rats. In a 90-day mouse study, increased alkaline phosphatase, serum glutamate oxaloacetate transaminase (SGOT), and serum gleutanic pyruvic transaminase (SGPT) activities, increased liver weight, hepatic necrosis, biliary hyperplasia, decreased hematocrit and hemoglobin levels and red blood cell counts, extramedullary hematopoiesis, and kidney nephrosis and fibrosis (the LOEL was 26 mg/kg/day; the NOEL was not determined) were seen. Decreased hemoglobin and hematocrit levels, decreased red blood cell counts, and brown pigment in the kidney and liver (the LOEL was 50 mg/kg/day) were noted in a 90-day feeding study in rats.

EPA believes that there is sufficient evidence for listing lactofen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available carcinogenicity data and hepatic, renal, and hematological toxicity data for this chemical.

Herbicide

US: Snapbean, Soybean

077501-63-4

Norflurazon

Norflurazon (FIFRA AI) (Ref. 3). Congestion of the liver, hepatocyte swelling and increased liver weights, and increase in colloid vacuole in the thyroid were observed in dogs fed 450 ppm (10.25 mg/kg/day) norflurazon for 6 months. The NOEL was 150 ppm (3.75 mg/kg/day). An oral RfD of 0.04 mg/ kg/day has been determined. Increased relative liver weight and hypertrophy of the thyroid with depletion of colloid were seen in rats fed 2,500 ppm (125 mg/kg/day) norflurazon for 90 days. The NOEL was 500 ppm (25 mg/kg/day). Hepatic hyperplasia and hypertrophy and increased relative liver weight were noted in a 28-day feeding study in rats. The LOEL was 1,000 ppm (50 mg/kg/day) and the NOEL was 500 ppm (25 mg/kg/ day). Increased relative liver weight and diffuse and smooth granular livers were seen in a 28-day feeding study in mice. The LOEL was 2,520 ppm (328 mg/kg/day) and the NOEL was 420 ppm (55 mg/kg/day). EPA believes that there is sufficient evidence for listing norflurazon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic and thyroid toxicity data.

Herbicide

US: Alfalfa, Almond, Apple, Apricot, Asparagus, Avocado, Blackberry, Blueberry, Cattle, Cherry, Citrus Fruit, , Cotton, Filbert, Goat, Grape, Grass, Hog, Hop (fresh), Horse, Milk, Nectarine, Peach, Peanut, Pear, Pecan, Plum, Poultry, Raspberry, Sheep, Soybean, Walnut

027314-13-2

Oxyfluorfen

Oxyfluorfen (FIFRA SR) (Ref. 8). Oxyfluorfen is a phenoxyphenyl-type herbicide. Several chronic oral toxicity studies suggest that oxyfluorfen may be hepatotoxic. Hepatic effects (e.g. increased absolute liver weight, necrosis, regeneration, and hyperplastic nodules) were observed in mice fed diets containing greater than 3 mg/kg/day oxyfluorfen for 20 months (the NOEL was 0.3 mg/kg/day). Based on these findings, an oral RfD value of 0.003 mg/kg/ day was derived. This study was supported by other chronic feeding studies that demonstrated increases in liver weight, alkaline phosphatase activity, and bile pigmented hepatocytes (the LOEL was 15 mg/kg/day; the NOEL was 2.5 mg/kg/day) in dogs, and minimal hypertrophy of centrilobular hepatocytes (the LOEL was 40 mg/kg/day; the NOEL was 2 mg/kg/day) in rats. EPA believes that there is sufficient evidence for listing oxyfluorfen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the hepatotoxic effects of this chemical.

The estimated chronic MATC values for fish and daphnids are 9 ppb and 20 ppb oxyfluorfen, respectively. The estimated log Kow is 6.1. EPA believes that there is sufficient evidence for listing oxyfluorfen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental toxicity data and potential for bioaccumulation for this chemical

Herbicide

US: Almond, Artichoke, Avocado, Banana (inc Plantains), Blackberry, Broccoli, Cabbage, Cattle, Cauliflower, Chickpea seed, Cocoa bean, Coffee bean, Corn, Cotton, Dates, Egg, Feijjoa, Fig, Fruit (Pome & Stone group), Goat, Grape, Guava, Hog, Horse, Horseradish, Kiwifruit, Milk, Peppermint, Spearmint, Nuts (tree), Olive, Onion, Papaya, Persimmon, Pistachio, Pomegranate, Poultry,Raspberry, Sheep, Soybean, Strawberry, Taro, Walnut

042874-03-3

Primisulfuron methyl

Primisulfuron (FIFRA AI) (Ref. 3). In a 90-day dog feeding study, reduced thyroid weights accompanied by colloid depletion and parafollicular hyperplasia and anemia were observed at the LOEL of 25 mg/kg/day. The NOEL was 0.625 mg/kg/day. In a 1-year dog study, dietary administration of 250/125 mg/kg/day (LOEL: the dose was changed after week 10 in the study) produced thyroid hyperplasia, anemia, increased platelet levels, vacuolar changes, and increased absolute and relative liver weights. The NOEL was 25 mg/kg/day. In an 18-month study in mice, dietary administration of 1.7 mg/kg/day produced increased absolute and relative liver weights in females. No NOEL was established. Based on this study, an oral RfD of 0.006 mg/kg/day was derived. In a 2-year mouse study, increases in absolute and relative liver weights were observed at 408 mg/kg/day in males and 1.7 mg/kg/day in females. The systemic LOEL and NOEL in males was 408 mg/kg/day and 40.2 mg/kg/day, respectively. The systemic LOEL in females was 1.7 mg/kg/day and a NOEL could not be established. EPA believes that there is sufficient evidence for listing primisulfuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available thyroid and liver toxicity data for this chemical.

Plant toxicity values include a duckweed 14-day EC50 of 0.27 ppb and an algae 7-day EC50 of 24 ppb. EPA believes that there is sufficient evidence for listing primisulfuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data for this chemical.

Fungicide, Herbicide

US: Cattle, Corn, Egg, Goat, Hog, Horse, Milk, Poultry, Sheep

086209-51-0

Sodium fluoroacetate

Sodium fluoroacetate (CERCLA; EPCRA EHS; FIFRA SR; RCRA APP8; RCRA P) (Ref. 8). In a 13-week oral study in rats, gavage administration of sodium fluoroacetate (0.02 mg/kg/day) resulted in decreased testis weight and altered spermatogenesis in males (the NOAEL was 0.05 mg/kg/day). In addition, increased heart weight was noted in females and males administered 0.20 mg/kg/day of sodium fluoroacetate. The increase in heart weight, however, was only accompanied by subacute, minimal inflammation (not dose-related). Also, fluorocitrate levels were significantly increased after 4 weeks in males administered 0.50 mg/kg/day and after 13 weeks in both male and female rats administered 0.20 or 0.50 mg/kg/day. The testicular and cardiac effects were reported to be consistent with those noted in the literature.

A case study reported a deliberate ingestion of an unspecified dose of sodium fluroacetate by a healthy female. The woman experienced nausea, vomiting, and abdominal pain 30 minutes after ingestion, with subsequent seizures occurring 60 minutes after the initial onset of symptoms. Neurological examination after 2 weeks revealed severe cerebellar dysfunction. By 18 months, memory disturbances and depressive behavior persisted. Inhalation exposure to unspecified levels of sodium fluoroacetate caused salivation, loss of speech, violent convulsions, and coma in a male worker. The patient ultimately recovered. Neurological effects have also been reported in rats in a 13-week oral study. Four of 20 female rats treated with 0.50 mg/kg/day (the highest dose tested) exhibited convulsions at day 79, with no recurrences for the remainder of the study. An estimated lethal dose of sodium fluoroacetate in humans ranges from 5 to 10 mg/kg.

EPA believes that there is sufficient evidence for listing sodium fluoroacetate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the neurologic, reproductive, and myocardial toxicity data for this chemical.

Measured oral LD50 values of fluoroacetate in the house sparrow, redwinged blackbird, starling and golden eagle are 3.0, 4.22, 2.37, and 1.25 to 5 mg/kg, respectively. In addition, measured acute toxicity data for mammalian wildlife include an oral LD50 of 0.22 to 0.44 mg/kg for mule deer, an oral LD50 of 1.41 mg/kg for male ferrets, and an oral LD50 of 0.5 to 1.0 mg/kg for bears. EPA believes that there is sufficient evidence for listing sodium fluoroacetate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental toxicity data for this chemical.

Insecticide, Rodenticide

Registered for use in the US

000062-74-8

Sulfuryl fluoride

Sulfuryl fluoride (Vikane) (FIFRA AI) (Ref. 3). The primary effects of sulfuryl fluoride in humans are respiratory irritation and central nervous system depression, followed by excitation and possibly convulsions. Rabbits exposed via inhalation (6 hours/day, 5 days/week, for 2 weeks) to sulfuryl fluoride showed hyperactivity, convulsions and vacuolation of the cerebrum at 600 ppm (2.5 mg/L). Renal lesions were present in all rats exposed by inhalation (6 hours/day, 5 days/week, for 2 weeks) to 600 ppm (2.5 mg/ L) sulfuryl fluoride. Minimal renal changes were noted in rats exposed to 300 ppm (1252 mg/L), whereas no effects occurred at 100 ppm (4.2 mg/ L). Convulsions at near lethal concentrations were reported in rabbits, mice, and rats. In a 30-day inhalation study, loss of control, tremors of the hind quarters, and histopathological changes in the lung, liver, and kidney were reported in rabbits exposed to 400 ppm (1.6 mg/L) for 7 hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm (0.83 mg/L). Cerebral vacuolation and/or malacia and inflammation of nasal tissues were observed in rabbits exposed by inhalation to 100 or 300 ppm (0.4 or 1.25 mg/L) for 13 weeks. The NOEL was 30 ppm (0.125 mg/L). Rats exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed mottled teeth (indicative of fluoride toxicity), renal and respiratory effects, and cerebral vacuolation. EPA believes that there is sufficient evidence for listing sulfuryl fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, renal, and respiratory toxicity data for this chemical. .

Fumigant, Insecticide

US: registration pending as a fumigant on food.

002699-79-8

Tefluthrin

Tefluthrin (FIFRA AI) (Ref. 3). Delayed ossification was seen in the offspring of rats administered 5 mg/kg/day (LOEL) orally on days 7 through 16 of gestation. The NOEL was 3 mg/kg/ day.

In a 3-month rat study, dietary administration of 10 mg/kg/day produced plasma, red blood cell, and brain cholinesterase inhibition. The NOEL was 5 mg/kg/day. In a 6-month dog study, dietary administration of 10 mg/kg/day (LOEL) produced plasma cholinesterase inhibition. The NOEL was 1 mg/kg/day.

n a 21-day rat dietary study, administration of 20 mg/kg/day (LOEL for females) produced decreased platelet counts, increased white blood cell, lymphocyte, and neutrophil counts in males and females. The NOEL for females was 5 mg/kg/day. Increased absolute and relative liver weights were observed at 5 mg/kg/day in males, thus no NOEL could be established for males. Dietary administration of 10 mg/kg/day (LOEL) for 3 months to rats produced increased absolute liver weights, decreased bilirubin levels, and hepatocellular hypertrophy. The NOEL was 5 mg/kg/day. In a 6-month dog study, dietary administration of 10 mg/kg/day (LOEL) produced hepatotoxicity (effects not reported). The NOEL was 1 mg/kg/day. In a 2-year mouse study, dietary administration of 13.5 mg/kg/day produced liver necrosis. The NOEL was 3.4 mg/kg/day.

EPA believes that there is sufficient evidence for listing tefluthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available developmental, neurological, hepatic, and hematological toxicity data for this chemical.

Aquatic acute toxicity values for tefluthrin include a rainbow trout 96-hour LC50 of 0.06 ppb, a bluegill 96-hour LC50 of 0.13 ppb, a sheepshead minnow 96-hour LC50 of 0.13 ppb, a daphnid 48-hour EC50 of 0.07 ppb, and a mysid 96-hour EC50 of 0.053 ppb. EPA believes that there is sufficient evidence for listing teflurin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data for this chemical.

Insecticide

US: Corn

079538-32-2

Tributyltin fluoride

Tributyltin fluoride (FIFRA AI) (Ref. 3). Aquatic acute toxicity values for tributyltin fluoride include a bleak fish 96-hour LC50 of 2.3 ppb, an algae 72-hour EC50 of 9.3 ppb, and a Harpacticoid copepod 96-hour LC50 of 0.8 ppb. EPA believes that there is sufficient evidence for listing tributyltin fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data.

Antifoulant, Fungicide, Microbiocide

Prohibited from use in the US

001983-10-4