Adverse Effects
Fluazinam
CAS No.
79622-59-6
 
 

Return to Fluazinam Index Page

Activity: Fungicide (2,6-Dinitroaniline)
Structure:


Adverse Effects:
Body Weight Decrease
Bone (including Cleft Palate)
Brain
Cancer- Suggestive evidence: THYROID, LIVER
Cholesterol
Dermal
Endocrine: Testicular
Endocrine: Thymus
Endocrine: Thyroid
Endocrine: Uterus
Eye
Liver
Lung
Pancreas
Spinal Cord
Stomach

Thyroid
Environmental

• As of February 16, 2005, this fungicide is permitted in or on 3 food commodities in the United States - see list at bottom of page.

• In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain. Generalized toxicity was observed in rats, mice and dogs as decreases in body weight, body-weight gain, food consumption and/or food efficiency. Liver toxicity was evident in most studies including increased size and weight, fatty changes, pallor, as well as hepatocyte hypertrophy, necrosis and apoptosis. Thyroid toxicity was less common, but included follicular hyperplasia and cystic thyroid follicles. Endocrine-related effects included small and/or flaccid testes, testicular tubular atrophy, pancreatic exocrine atrophy and thymic hyperplasia.
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf


Body Weight Decrease (click on for all fluorinated pesticides)

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain. Generalized toxicity was observed in rats, mice and dogs as decreases in body weight, body-weight gain, food consumption and/or food efficiency.
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Prenatal developmental toxicity -rats. LOAEL = 250 mg/kg/day based on decreased fetal body weights and placental weights, increased facial/cleft palates, diaphragmatic hernia, and delayed ossification in several bone types, greenish amniotic fluid and possible increased late resorptions and postimplantation loss...
Prenatal developmental toxicity -rabbits. LOAEL = 12 mg/kg/day based on an increase in total litter resorptions and possible fetal skeletal abnormalities.

Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

-- Prenatal developmental toxicity rats Maternal. NOAEL = 50 mg/kg/day LOAEL = 250 mg/kg/day based on decreased body weight gain and food consumption and increased water consumption and urogenital staining Developmental NOAEL = 50 mg/kg/day LOAEL = 250 mg/kg/day based on decreased fetal body weights and placental weights, increased facial/cleft palates, diaphragmatic hernia, and delayed ossification in several bone types, greenish amniotic fluid and possible increased late resorptions and postimplantation loss
-- Reproduction and fertility effects rats. Parental/Systemic NOAEL = 1.9 mg/kg/day LOAEL = 9.7 mg/kg/day based on liver pathology in F1 males Reproductive NOAEL = 10.6 mg/kg/day LOAEL = 53.6 mg/kg/day based on decreased number of implantation sites and decreased litter sizes to day 4 post-partum for F1 females (F2 litters). Offspring NOAEL = 8.4 mg/kg/day LOAEL = 42.1 mg/kg/day based on reduced F1 and F2 pup body weight gains during lactation.
-- Specicial study. 4-Week dietary (range-finding) rats. NOAEL = M: 5.1 mg/kg/day; F: 5.3 mg/kg/day LOAEL = M: 26.4 mg/kg/day; F: 25.9 mg/kg/day based on decreased body weight gain and food consumption, increased serum phospholipids, increased total cholesterol, increased relative liver weights, and liver histopathology.
-- Specicial study. 4-Week dietary (Range-finding) mice NOAEL = M: 7.6 mg/kg/day; F: 8.2 mg/kg/day LOAEL = M: 36 mg/kg/day; F: 43 mg/kg/day based on decreased body weight gain, increased serum glucose, increased kidney weights.
Ecological Effects
-- a. Aquatic (Acute/Chronic Hazard Summary) Fluazinam is considered to be very highly toxic to highly toxic to fish (freshwater and estuarine/marine) on an acute basis (LC50 = 0.036 - 0.11 ppm). Chronic freshwater NOAEC/LOAEC values were calculated at 0.0053 - 0.00069 ppm and 0.010 - 0.014 ppm, respectively, with larval survival, reduced number of spawns, and growth as the endpoints affected. Acute toxicity values for aquatic invertebrates suggest that fluazinam is highly toxic to freshwater invertebrates (Daphnia EC50 = 0.18 - 0.22 ppm) and very highly toxic to estuarine/marine invertebrates (oyster EC50 = 0.0047 and mysid shrimp EC50 = 0.039 ppm ). Chronic toxicity to invertebrates are only represented through the Daphnia magna life cycle where the NOAEC was calculated at 0.068 ppm and the LOAEC at 0.140 ppm.. The endpoints affected for this study were reproductive (reduced number of young per female) and growth effects. No acceptable data have been submitted to assess the chronic effects of fluazinam to estuarine/marine fish or invertebrates. An estuarine/marine fish life-stage toxicity test (Guideline 72-4a) and an estuarine/marine invertebrate life-cycle toxicity test (Guideline 72-4b) are required to fulfill these requirements.
-- d. Risk to Avian Species (Acute/Chronic) Although acute exposure should result in minimal toxic effects to birds, the risk assessment suggests that the proposed uses can cause chronic (reduced growth in young) effects in birds. RQ values were calculated for exposure to peanuts (maximum EECs RQ = 1.0 - 1.8 and 56 day average EECs RQ = 1.1 ppm) and potatoes (maximum EECs RQ = 1.0 - 1.5 and 56 day average(RQ = 1).
Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001.

http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

Bone (including Cleft Palate) (click on for all fluorinated pesticides)

-- Prenatal developmental toxicity rats. Maternal NOAEL = 50 mg/kg/day LOAEL = 250 mg/kg/ day based on decreased body weight gain and food consumption and increased water consumption and urogenital staining Developmental NOAEL = 50 mg/kg/ day LOAEL = 250 mg/kg/ day based on decreased fetal body weights and placental weights, increased facial/ cleft palates, diaphragmatic hernia, and delayed ossification in several bone types, greenish amniotic fluid and possible increased late resorptions and postimplant
-- Prenatal developmental toxicity rabbits. Maternal NOAEL = 4 mg/kg/day LOAEL = 7 mg/kg/ day based on decreased food consumption and increased liver histopathology. Developmental NOAEL = 7 mg/kg/ day LOAEL = 12 mg/kg/ day based on an increase in total litter resorptions and possible fetal skeletal abnormalities

Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Developmental. 98.5%, NZW Rabbits, 0, 2, 4, 7, 12 mg/kg/d, 16–18 pregnant females/dose Maternal NOAEL 4 mg/kg/d Maternal LOAEL 7 mg/kg/d Developmental NOAEL 7 mg/kg/d Developmental LOAEL 12 mg/kg/d Qualitative sensitivity of young. 7 mg/kg/d 9 Food consumption. 8 Liver histopath (cellular hypertrophy, single cell necrosis, binucleate hepatocytes, brown pigment deposition, apoptosis). 12 mg/kg/d 9 bwg, food consumption. 8 Liver histopath (cellular hypertrophy, single cell necrosis, binucleate hepatocytes, brown pigment deposition, apoptosis). 8 Incidence total litter resorptions. 8 Incidence placental anomalies. 8 Skeletal abnormalities (slight) (kinked tail tip, fused or incompletely ossified sternebrae, abnormalities of head bones).
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Brain (click on for all fluorinated pesticides)

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
-- In acute and subchronic neurotoxicity studies, treatment with fluazinam resulted in marked neuropathology in the form of vacuolation of the white matter of the brain.
Special studies have been submitted that show this effect is not due to fluazinam itself, but rather to a manufacturing impurity. In the subchronic study, generalized toxicity was observed as decreased body weight and food efficiency. A developmental neurotoxicity study was suggested upon preliminary review of the data and the applicant submitted a rationale. Upon full review of the dataset, a developmental neurotoxicity study is a requirement for full registration. Special studies were generated to determine the cause of the white matter vacuolation. All nine impurities were tested at doses that reflected their relative content in the technical product. Only one impurity was found to produce the vacuolation effects and all subsequent special studies focus on this chemical. The vacuolation was determined to be in the myelin sheaths surrounding axons in the white matter. Dogs, mice and rats were found to have comparable results when tested in similar manners. Older animals were found to be more susceptible than the young. All vacuolation effects were found to be reversible. Neurotoxic findings were common at high doses and included decreased motor activity, partial paralysis and ataxia. This effect was observed at high doses (LOAEL was 50 mg/kg/d) when the dose level of impurity no. 5 was sufficiently high to cause these effects. Therefore, the presence of this impurity will be limited to 0.1% of the technical active.
-- Determination of acceptable daily intake (ADI). The recommended ADI for fluazinam is 0.0011 mg/kg bw/day. The chronic toxicity and oncogenicity study in mice was considered the most appropriate study to assess chronic dietary exposure. The no observed adverse effect level (NOAEL) was 1.1 mg/kg bw/day, based on increased incidences of brown pigmented macrophages in the liver, increased incidences of eosinophilic vacuolated hepatocytes in males and increased liver weights relative to body weights. The standard uncertainty factor of 100-fold is applied to account for intraspecies and interspecies variability, an additional 10-fold safety factor is recommended to firstly, protect for endocrine-related effects and secondly, to account for the lack of a developmental neurotoxicity (DNT) study. This provides margins of safety of 9100 to the NOEL for white matter vacuolation and 6350 to the NOEL for developmental effects in the rabbit developmental study.
-- The USEPA has chosen an ADI of 0.00367 mg/kg bw/d based on a 2-year carcinogenicity study in mice (1.1 mg/kg bw/d with 100-fold uncertainty factor (UF) and three-fold Food Quality Protection Act (FQPA) safety factor.) They have also requested a developmental neurotoxicity study.

Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

90-Day oral toxicity dogs NOAEL = 10 mg/kg/day LOAEL = 100 mg/kg/day based on retinal effects, increased relative liver weight, liver histopathology and possible increased serum alkaline phosphatase in females and possible marginal vacuolation of the cerebral white matter (equivocal)...
Carcinogenicity mice NOAEL = Males:<126 mg/kg/day, Females: <162 mg/kg/day LOAEL = Males: 126 mg/kg/day; Females: 162 mg/kg/day based on increased liver weights and liver and brain histopathology in both sexes
Special study: 4-Week dietary (Range-finding) mice NOAEL = not identified (Males; <555 mg/kg/day; Females: <658 mg/ kg/day) LOAEL = Males: 555 mg/kg/day; Females: 658 mg/kg/day based on vacuolation of white matter in brain, increased liver weights, histopathology in liver...
Eight special mechanistic studies to assess the CNS white matter vacuolation: White matter vacuolation in the CNS of mice, rats, and dogs was found to be due to Impurity-5.
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

A second oncogenicity study in mice was conducted at 1,000, 3,000 and 7,000 ppm to ensure that an maximum tolerance dose (MTD) was studied. Findings included increased female mortality, reduced body weight gains, increased brain weights and/or liver weights. An impurity in the test material used in this study resulted in vacuolation of the white matter of the brain and cervical spinal cord in treated animals. A statistically significant higher incidence of hepatocellular adenomas was observed in the 3,000 ppm dose males. Hepatocellular adenomas are common tumors in male mice. There was no dose relationship in the induction of the adenoma and no increase in hepatocellular carcinomas. It was concluded that fluazinam is not carcinogenic in the mouse.
Ref: Federal Register: December 6, 2000 [Page 76253-76258].
http://www.fluoridealert.org/pesticides/Fluazinam.FR.December.2000.htm

Of particular concern was a neurotoxic lesion described as vacuolation of the white matter of the brain and sometimes cervical spinal cord which was initially observed in long-term (1-2 year) chronic studies in mice and dogs and later, upon careful re-examination of the central nervous system (CNS), also in shorter-term (4-week to 90-day) subchronic studies. Although this lesion was also observed in control animals, the increased incidence and/or severity of the lesion in test animals was clearly treatment-related and dose-related. Further investigation of this finding in a series of special studies demonstrated the same lesion could also be induced in rats. In the special studies, the following were also determined.
• Fluazinam, per se, was not responsible for the induction of this lesion. Evaluation of the effects of impurities present in technical grade fluazinam revealed that one single impurity, Impurity-5, was solely responsible for the induction of this lesion.
• No significant differences in susceptibility or in incidence or severity of vacuolation of the white matter of the CNS were observed between species (mice, dogs, or rats). Similarly, no significant differences were attributed to sex.
Electron microscopy of the white matter (cerebellum) of mice treated with technical grade fluazinam indicated that treatment-related effects were confined to the myelin sheaths. Large vacuoles were observed in the intramyelin sheaths due to the accumulation of fluid between the sheaths. The nucleus and mitochondria in the oligodendroglia were observed to remain intact, suggesting no damage to these cells.
• White matter vacuolation in the CNS was reversible. The myelin sheaths appeared to recover completely during a recovery period of up to 56 days.
• There appears to be a non-linear dose-response with a clear threshold below which no effect occurs. It was concluded that a LOAEL of 0.1 mg/kg/day and a NOAEL of 0.02 mg/kg/day for CNS effects could be established for Impurity-5.
-- At the current maximum concentration of Impurity-5 in technical grade fluazinam of 0.1%, the NOAEL for CNS effects of 0.02 mg/kg/day for Impurity-5 is equivalent to a NOAEL for CNS effects of 20 mg/kg/day for technical grade fluazinam. The NOAEL of 20 mg/kg/day for CNS effects for technical grade fluazinam is comparable to the NOAEL for chronic effects for technical grade fluazinam of 1.1 mg/kg/day used to establish the chronic RfD for fluazinam. Therefore, based on a consideration of all the available data and information relating to this treatment-related neurotoxic lesion, it was concluded that the chronic dietary RfD of 0.011 mg/kg/day for “all populations”, including infants and children, is protective of the CNS effects caused by the presence of Impurity-5 in technical-grade fluazinam.
Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001.
http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

SPECIAL/IMPURITIES
-- Comparative— susceptibility to neurotoxicity. 97.0% Impurity-5, 2.0 mg/kg/d, 5 Crj:CD (ICR) mice, 5 Crj:CD (SD) rats, 3 beagles, all male 9 Spontaneous motor activity in rats and mice. 9 Mean body weight in mice and rats. 8 Brain weights in mice and rats. Vacuolation of white matter and swelling of the brain in all treated animals. Dogs appear to be slightly less susceptible.
-- Comparative— brain sensitivity rats and mice. 99.5% Impurity-5, 0, 0.5 mg/kg, 5 Crj:CD-1 mice, 5 Crj:CD(SD) SPF/VAF rats, all female. Incidence and severity of white matter vacuolation in brains of mice and rats were similar. Brain weights were comparable to controls.
-- Comparative— brain sensitivity 3- and 10-week old rats and mice—14 days. 99.5% Impurity-5, 0, 0.5 mg/kg/d, 10 Crj:CD-1 (ICR) SPF/VAF mice and Crj:CD(SD) SPF/VAF rats, all male, half 3 weeks old, the other half 10 weeks old Edema in brains of 1 rat and 2 mice (10 weeks old). Vacuolation in white matter of brains similar between species of same age, but more severe in older animals compared to younger.
-- Effect on brain/optic nerves 99.5%. Impurity-5, 2.5 mg/kg, Crj:CD-1(ICR) mice, 5 males/group, aged 3, 5, 8, 10, 12, 16, 20, 24 weeks All treated mice except 3 week olds had vacuolation of the optic nerve. The effect was less severe than in the brain. The eyes themselves were normal. Ages 3, 5, 8 weeks. Trace vacuolation of white matter in brains Ages 10, 12, 16, 20, 24 weeks Trace to minimal vacuolation of white matter in brains.
-- Various impurities— effect on brains. 96–100% Impurities 1 through 9, doses correspond to 5000 mg/kg dose of technical, 5 male Crj:CD-1 mice (Impurity-5 was dosed at 5 mg/kg) Only Impurity-5 was toxic. Coarse fur, paralysis of hind legs, staggering gait, sedation, moribund. 9 Mean body weight. 8 Brain weight, edema. Vacuolation of white matter.

-- Recommended ADI. 0.0011 mg/kg bw/d based on 2 year carcinogenicity in mice (1.1 mg/kg/d with 100- fold UF, three-fold SF for endocrine-related effects (testicular atrophy, pancreatic exocrine atrophy), and three-fold for lack of DNT). MOS for other critical endpoint(s) White matter vacuolation/Neurotox NOEL for white matter vacuolation was 10 mg/kg/d in chronic dog study (equivalent to 0.02 mg/kg/d Impurity-5). MOS = 9100. Tumours NOEL for tumours was 3.8 mg/kg bw/d in 2-year rat study. MOS = 3450. Developmental effects NOAEL for developmental effects was 7 mg/kg bw/d in developmental rabbit study. MOS = 6350
[ MOS = Margin of Safety ]
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.

http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Cancer: LIVER, THYROID (click on for all fluorinated pesticides)

Suggestive Evidence of Carcinogenicity to Humans. An increase in thyroid gland follicular cell tumors in male rats, and an increased incidence of hepatocellular tumors observed in the male mice was treatment-related.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

-- Carcinogenicity mice NOAEL = Males:1.1 mg/kg/day; Females: 1.2 mg/kg/day [[Page 46732]] LOAEL = Males: 10.7 mg/kg/day; Females: 11.7 mg/kg/day based on increased incidences of brown macrophages in the liver of both sexes, eosinophilic vacuolated hepatocytes in males, and increased liver weight in females. Clear evidence of carcinogenicity (hepatocellular tumors) in male mice, but not in females.
-- Combined chronictoxicity/ NOAEL = Males: 0.38 mg/kg/day; carcinogenicity rats Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
-- Carcinogenicity mice NOAEL = Males:<126 mg/kg/day, Females: <162 mg/kg/day LOAEL = Males: 126 mg/kg/day; Females: 162 mg/kg/day based on increased liver weights and liver and brain histopathology in both sexes Equivocal/some evidence of carcinogenicity (hepatocellular tumors) in male mice, but not in females,
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

-- Cancer (oral, dermal, inhalation). `Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential'' 2 . Quantification of human cancer risk not required. 2 Increases in thyroid gland follicular cell tumors in male rats; increases in hepatocellular (liver) tumors in male mice.2 (Ref 2: 2Cancer Assessment Document - Evaluation of the Carcinogenic Potential of Fluazinam, March 29, 2001, HED Doc. No. 014512.)
-- Cancer. Since fluazinam has been classified as ``Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential,'' an exposure assessment was not performed.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Cancer: Some evidence of carcinogenicity in male rats - THYROID (click on for all fluorinated pesticides)

-- Combined chronictoxicity/ NOAEL = Males: 0.38 mg/kg/day; carcinogenicity rats Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

-- Cancer (oral, dermal, inhalation). `Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential'' 2 . Quantification of human cancer risk not required. 2 Increases in thyroid gland follicular cell tumors in male rats; increases in hepatocellular (liver) tumors in male mice.2 (Ref 2: 2Cancer Assessment Document - Evaluation of the Carcinogenic Potential of Fluazinam, March 29, 2001, HED Doc. No. 014512.)
-- Cancer. Since fluazinam has been classified as ``Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential,'' an exposure assessment was not performed.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Cholesterol (click on for all fluorinated pesticides)

-- 21-Day dermal toxicity rats: increased AST and cholesterol levels in clinical chemistry determinations (males).
Special studies: 4-Week dietary (Range-finding) rats- decreased body weight gain and food consumption, increased serum phospholipids, increased total
cholesterol, increased relative liver weights, and liver histopathology.
-- 4-Week dietary (Range-finding) mice- decreased body weight gain, increased serum glucose, increased kidney weights.
-- 4-Week dietary (Range-finding) rats. NOAEL = Males: 5.1 mg/kg/day; Females: 5.3 mg/ kg/day LOAEL = Males: 26.4 mg/kg/day; Females: 25.9 mg/ kg/day based on decreased body weight gain and food consumption, increased serum phospholipids, increased total cholesterol, increased relative liver weights, and liver histopathology.
Ref: Federal Register: April 18, 2002 [Page 19120-19130]. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Dermal (click on for all fluorinated pesticides)

Abstract: In spring 1992, several farmers in the western part of The Netherlands developed dermatitis on their hands, forearms and face. In some, the legs, trunk and genitals were also affected. Complaints ranged from a mildly itchy, papular rash to a painful, weeping and blistering dermatitis. Medical aid was needed by 5/9 of them. Some of the farmers grew seed potatoes, the others cultivated lilies. All of them had in common that their complaints emerged after repeated application of a new fungicide over several weeks. The fungicide was Shirlan, with fluazinam as its active ingredient. 9 farmers were patch tested with a concentration range of the whole formulation (aq.) and of the active ingredient (pet.). In 7 of 9 farmers, positive patch tests were scored with both the whole formulation (down to 0.01% aq.) and fluazinam itself (down to 0.1% pet.). Patch tests in consecutive control patients (n = 10) were all negative. As it was impossible to substitute fluazinam as the active ingredient, farmers are now supplied with detailed information as to how to avoid skin contact as much as feasible.
Ref: Contact Dermatitis 1995 Mar;32(3):160-2;
Allergic contact dermatitis from the newly introduced fungicide fluazinam; by van Ginkel CJ, Sabapathy NN.

Endocrine Pancreas (click on for all fluorinated pesticides)

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain... Endocrine-related effects included small and/or flaccid testes, testicular tubular atrophy, pancreatic exocrine atrophy and thymic hyperplasia.
-- Recommended ADI. 0.0011 mg/kg bw/d based on 2 year carcinogenicity in mice (1.1 mg/kg/d with 100- fold UF, three-fold SF for endocrine-related effects (testicular atrophy, pancreatic exocrine atrophy), and three-fold for lack of DNT). MOS for other critical endpoint(s) White matter vacuolation/Neurotox NOEL for white matter vacuolation was 10 mg/kg/d in chronic dog study (equivalent to 0.02 mg/kg/d Impurity-5). MOS = 9100. Tumours NOEL for tumours was 3.8 mg/kg bw/d in 2-year rat study. MOS = 3450. Developmental effects NOAEL for developmental effects was 7 mg/kg bw/d in developmental rabbit study. MOS = 6350
[ MOS = Margin of Safety ]

Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Combined chronic toxicity/carcinogenicity rats. NOAEL = Males: 0.38 mg/kg/day; Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/ kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Chronic toxicity. Fluazinam was not carcinogenic in rats. A NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on the following effects at 1,000 and/or 100 ppm: lower food consumption and efficiency of food utilization, slight anemia, elevated cholesterol, increased liver weights, an increased number of macroscopic liver and testes lesions and an increased incidence of microscopically observed lung, liver, pancreas, lymph node and testes lesions.
Ref: Federal Register: December 6, 2000 [Page 76253-76258]. Notice of Filing Pesticide Petitions to Establish and to Extend Tolerances for Certain Pesticide Chemicals in or on Food.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.December.2000.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain. Generalized toxicity was observed in rats, mice and dogs as decreases in body weight, body-weight gain, food consumption and/or food efficiency. Liver toxicity was evident in most studies including increased size and weight, fatty changes, pallor, as well as hepatocyte hypertrophy, necrosis and apoptosis. Thyroid toxicity was less common, but included follicular hyperplasia and cystic thyroid follicles. Endocrine-related effects included small and/or flaccid testes, testicular tubular atrophy, pancreatic exocrine atrophy and thymic hyperplasia.
-- Recommended ADI. 0.0011 mg/kg bw/d based on 2 year carcinogenicity in mice (1.1 mg/kg/d with 100- fold UF, three-fold SF for endocrine-related effects (testicular atrophy, pancreatic exocrine atrophy), and three-fold for lack of DNT). MOS for other critical endpoint(s) White matter vacuolation/Neurotox NOEL for white matter vacuolation was 10 mg/kg/d in chronic dog study (equivalent to 0.02 mg/kg/d Impurity-5). MOS = 9100. Tumours NOEL for tumours was 3.8 mg/kg bw/d in 2-year rat study. MOS = 3450. Developmental effects NOAEL for developmental effects was 7 mg/kg bw/d in developmental rabbit study. MOS = 6350
[ MOS = Margin of Safety ]

Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Chronic toxicity. Fluazinam was not carcinogenic in rats. A NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on the following effects at 1,000 and/or 100 ppm: lower food consumption and efficiency of food utilization, slight anemia, elevated cholesterol, increased liver weights, an increased number of macroscopic liver and testes lesions and an increased incidence of microscopically observed lung, liver, pancreas, lymph node and testes lesions. An additional study was conducted to further define the NOAEL for long-term effects in the rat. In the second study, a NOAEL of 50 ppm (2.2 mg/kg/day) was established based on liver and testes effects.
Ref: Federal Register. December 6, 2000. [PF-983; FRL-6573-7]

http://www.fluoridealert.org/pesticides/Fluazinam.FR.December.2000.htm

-- Combined chronic toxicity/carcinogenicity rats. NOAEL = Males: 0.38 mg/kg/day; Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/ kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
-- 7-Day inhalation toxicity rats. Test Material: Frowncide WP (51.9% a.i.). NOAEL = Males: 1.38 mg/kg/day; Females: 1.49 mg/ kg/day LOAEL = Males: 3.97 mg/kg/day; Females: 4.25 mg/ kg/day based on increased testes weight (males) and increased liver weight (females)
.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Endocrine: Thymus (click on for all fluorinated pesticides)

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Endocrine: Thyroid (click on for all fluorinated pesticides)

Suggestive Evidence of Carcinogenicity to Humans. An increase in thyroid gland follicular cell tumors in male rats, and an increased incidence of hepatocellular tumors observed in the male mice was treatment-related.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Suggestive Evidence of Carcinogenicity to Humans. An increase in thyroid gland follicular cell tumors in male rats, and an increased incidence of hepatocellular tumors observed in the male mice was treatment-related.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

-- Combined chronic toxicity/carcinogenicity rats. NOAEL = Males: 0.38 mg/kg/day; Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/ kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

-- In a carcinogenicity study in rats, an increased incidence of thyroid gland follicular cell tumors was observed in males. In this study, there were statistically significant positive trends for thyroid gland follicular cell adenocarcinomas and combined follicular cell adenomas/adenocarcinomas. There was also a statistically significant increase by pair-wise comparison of the high dose group (40 mg/kg/day) with the control group for combined follicular cell adenomas/adenocarcinomas. There was no treatment-related increase in tumor incidence in female rats. The highest dose level tested in this study was considered to be adequate but not excessive. It was concluded that there was some evidence that the thyroid tumors observed in the male rats in this study were treatment-related. There were insufficient data to determine whether the thyroid gland tumors may have been due to disruption of thyroid-pituitary homeostasis.
Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001.

http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

-- Cancer (oral, dermal, inhalation). Increases in thyroid gland follicular cell tumors in male rats; increases in hepatocellular (liver) tumors in male mice.\2\
-- iii. Cancer. Since fluazinam has been classified as Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential, an exposure assessment was not performed.
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain... Thyroid toxicity was less common, but included follicular hyperplasia and cystic thyroid follicles. Endocrine-related effects included small and/or flaccid testes, testicular tubular atrophy, pancreatic exocrine atrophy and thymic hyperplasia.
-- Long-term studies in both rats and mice provided some evidence of treatment-induced oncogenicity of the thyroid (follicular cell adenomas and adenocarcinomas) and liver (hepatocellular adenomas and carcinomas). Although tumours of this type may be the result of a non-genotoxic and non-linear mode of action, no data was provided on potential modes of action (e.g., enzyme induction, thyroid hormone levels). There was insufficient mechanistic data to determine the mode of action. A Q was generated at 5.40 • 10 -2 in the absence of a demonstrated mode of action.
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Endocrine: Uterus (click on for all fluorinated pesticides)

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

-- 90-Day oral toxicity rats NOAEL: Males = 3.8 mg/kg/day; Females = 4.3 mg/kg/day [[Page 46731]] LOAEL Males = 38 mg/kg/day; Females = 44 mg/kg/day based on increased liver weights and liver histopathology in males, and increased lung and uterus weights in females.
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

Eye (click on for all fluorinated pesticides)

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Acute eye irritation rabbits. Technical grade fluazinam. Extremely irritating. Corneal opacity did NOT reverse in 21 days. Toxicity Category I.
Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001
.
http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

Liver (click on for all fluorinated pesticides)

Suggestive Evidence of Carcinogenicity to Humans. An increase in thyroid gland follicular cell tumors in male rats, and an increased incidence of hepatocellular tumors observed in the male mice was treatment-related.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain... Liver toxicity was evident in most studies including increased size and weight, fatty changes, pallor, as well as hepatocyte hypertrophy, necrosis and apoptosis...
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

-- Carcinogenicity mice NOAEL = Males:1.1 mg/kg/day; Females: 1.2 mg/kg/day [[Page 46732]] LOAEL = Males: 10.7 mg/kg/day; Females: 11.7 mg/kg/day based on increased incidences of brown macrophages in the liver of both sexes, eosinophilic vacuolated hepatocytes in males, and increased liver weight in females. Clear evidence of carcinogenicity (hepatocellular tumors) in male mice, but not in females.
-- 90-Day oral toxicity rats NOAEL: Males = 3.8 mg/kg/day; Females = 4.3 mg/kg/day [[Page 46731]] LOAEL Males = 38 mg/kg/day; Females = 44 mg/kg/day based on increased liver weights and liver histopathology in males, and increased lung and uterus weights in females.
-- 90-Day oral toxicity dogs NOAEL = 10 mg/kg/day LOAEL = 100 mg/kg/day based on retinal effects, increased relative liver weight, liver histopathology and possible increased serum alkaline phosphatase in females and possible marginal vacuolation of the cerebral white matter (equivocal).
-- Prenatal developmental toxicity Maternal NOAEL = 4 mg/kg/day rabbits LOAEL = 7 mg/kg/day based on decreased food consumption and increased liver histopathology...
-- Reproduction and fertility effects Parental/Systemic NOAEL = 1.9 mg/ rats kg/day LOAEL = 9.7 mg/kg/day based on liver pathology in F1 males...
-- Combined chronictoxicity/ NOAEL = Males: 0.38 mg/kg/day; carcinogenicity rats Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females: 4.9 mg/kg/day based on liver toxicity in both sexes, pancreatic exocrine atrophy in females and testicular atrophy in males. Some evidence of carcinogenicity (thyroid gland follicular cell tumors) in male rats, but not in females.
-- Carcinogenicity mice NOAEL = Males:<126 mg/kg/day, Females: <162 mg/kg/day LOAEL = Males: 126 mg/kg/day; Females: 162 mg/kg/day based on increased liver weights and liver and brain histopathology in both sexes Equivocal/some evidence of carcinogenicity (hepatocellular tumors) in male mice, but not in females,
-- Special studies: 4-Week dietary (Range-finding) rats NOAEL = Males: 5.1 mg/kg/day; Females: 5.3 mg/kg/day LOAEL = Males: 26.4 mg/kg/day; Females: 25.9 mg/kg/day based on decreased body weight gain and food consumption, increased serum phospholipids, increased total cholesterol, increased relative liver weights, and liver histopathology.
-- 4-Week dietary (Range-finding) mice NOAEL = not identified (Males; <555 mg/kg/day; Females: <658 mg/ kg/day) LOAEL = Males: 555 mg/kg/day; Females: 658 mg/kg/day based on vacuolation of white matter in brain, increased liver weights, histopathology in liver.
-- 90-Day dietary (Special liver study) rats NOAEL = not determined (Males: <37.6 mg/kg/day, Females: <44.7 mg/kg/day) LOAEL = Males: 37.6 mg/kg/day, Females: 44.7 mg/kg/day based on increased relative liver weights and liver histopathology...
Ref: Federal Register. September 7, 2001. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm

-- Metabolism and pharmacokinetics rats. Only 33-40% of the administered dose was absorbed. Most of the administered dose was recovered in the feces (>89%). Excretion via the urine was minor (<4%). Total biliary radioactivity, however, represented 25- 34% of the administered dose, indicating considerable enterohepatic circulation [Recycling of certain compounds between the small intestine and the liver].
-- Cancer (oral, dermal, inhalation). `Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential'' 2 . Quantification of human cancer risk not required. 2 Increases in thyroid gland follicular cell tumors in male rats; increases in hepatocellular (liver) tumors in male mice.2 (Ref 2: 2Cancer Assessment Document - Evaluation of the Carcinogenic Potential of Fluazinam, March 29, 2001, HED Doc. No. 014512.)
-- Cancer. Since fluazinam has been classified as ``Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential,'' an exposure assessment was not performed.
Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluazinam.FR.Apr.18.2002.htm

Lung (click on for all fluorinated pesticides)

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

PubMed Abstract: We report two cases of occupational asthma caused by sensitisation to powdered fungicides fluazinam and chlorothalonil, from the same fungicide formulation plant. Both developed work related lower respiratory symptoms after a latent interval of asymptomatic exposure. The diagnosis in each case was confirmed with a serial peak flow record in the workplace followed by specific inhalation tests. These fungicides are known to cause dermatitis; this report indicates that these compounds can induce specific immunological reactions in the airways as well as skin.
Ref: Occup Environ Med 2003 Jan;60(1):76-7. Occupational asthma from fungicides fluazinam and chlorothalonil; by Draper A, Cullinan P, Campbell C, Jones M, Newman Taylor A.

-- Subchronic toxicity. The NOAEL for the 13 week feeding study in rats was 50 ppm (4.1 mg/kg/day). The LOAEL was 500 ppm (41 mg/kg/day), based on periacinar hepatocellular hypertrophy and sinusoidal chronic inflammation in males, increased liver weights in males and increased lung weights in females.
-- Chronic toxicity. Fluazinam was not carcinogenic in rats. A NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on the following effects at 1,000 and/or 100 ppm: lower food consumption and efficiency of food utilization, slight anemia, elevated cholesterol, increased liver weights, an increased number of macroscopic liver and testes lesions and an increased incidence of microscopically observed lung, liver, pancreas, lymph node and testes lesions.
Ref: Federal Register: December 6, 2000 [Page 76253-76258]. Notice of Filing Pesticide Petitions to Establish and to Extend Tolerances for Certain Pesticide Chemicals in or on Food.
http://www.fluoridealert.org/pesticides/Fluazinam.FR.December.2000.htm

Spinal Cord (click on for all fluorinated pesticides)

Oral 1 year 95.3%, Beagles, 0, 1, 10, 50 mg/kg/d, 6/sex/dose NOAEL 1 mg/kg/d LOAEL 10 mg/kg/d 10 mg/kg/d 8 Nasal dryness &. 8 Incidence and severity of gastric lymphoid hyperplasia. 9 Myeloid to erythroid ratios in bone &. 50 mg/kg/d 8 Nasal dryness and salivation % and &. 9 bwg in both sexes, but only significant in &. 9 Myeloid to erythroid ratios in bone &. 9 Hematocrit, hemoglobin, RBC % and . 8 WBC mid and high doses % and &. 8 Alk phos, cholesterol % and &. 8 Abs and rel liver weight % and 8 Incidence and severity of white matter vacuolation in brain and spinal cord 8 Incidence and severity of gastric lymphoid hyperplasia.
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Stomach  (click on for all fluorinated pesticides)

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Environmental (click on for all fluorinated pesticides)

-- Ecological Effects Summary:
a. Aquatic (Acute/Chronic Hazard Summary) Fluazinam is considered to be very highly toxic to highly toxic to fish (freshwater and estuarine/marine) on an acute basis (LC50 = 0.036 - 0.11 ppm). Chronic freshwater NOAEC/LOAEC values were calculated at 0.0053 - 0.00069 ppm and 0.010 - 0.014 ppm, respectively, with larval survival, reduced number of spawns, and growth as the endpoints affected. Acute toxicity values for aquatic invertebrates suggest that fluazinam is highly toxic to freshwater invertebrates (Daphnia EC50 = 0.18 - 0.22 ppm) and very highly toxic to estuarine/marine invertebrates (oyster EC50 = 0.0047 and mysid shrimp EC50 = 0.039 ppm ). Chronic toxicity to invertebrates are only represented through the Daphnia magna life cycle where the NOAEC was calculated at 0.068 ppm and the LOAEC at 0.140 ppm.. The endpoints affected for this study were reproductive (reduced number of young per female) and growth effects. No acceptable data have been submitted to assess the chronic effects of fluazinam to estuarine/marine fish or invertebrates. An estuarine/marine fish life-stage toxicity test (Guideline 72-4a) and an estuarine/marine invertebrate life-cycle toxicity test (Guideline 72-4b) are required to fulfill these requirements.
-- b. Risk to Aquatic Organisms (Acute/Chronic) The risk assessment suggests that exposure of this compound to fish (freshwater and estuarine/marine) through the proposed use patterns (peanuts and potatoes) can result in acute (restricted use and endangered species concern category) and chronic risk. Exposure to aquatic invertebrates (freshwater and estuarine/marine) from peanut use can result in acute risk (restricted use and endangered species concern category). No acute or chronic exceedences are expected for freshwater invertebrates from the potato use. Chronic exposure to estuarine/marine fish and invertebrates could not be calculated at this time because of a lack of appropriate data.
-- d. Risk to Avian Species (Acute/Chronic) Although acute exposure should result in minimal toxic effects to birds, the risk assessment suggests that the proposed uses can cause chronic (reduced growth in young) effects in birds. RQ values were calculated for exposure to peanuts (maximum EECs RQ = 1.0 - 1.8 and 56 day average EECs RQ = 1.1 ppm) and potatoes (maximum EECs RQ = 1.0 - 1.5 and 56 day average(RQ = 1).
-- e. Risk to Mammalians (Acute, Chronic) The risk assessment suggests that the proposed uses can result in chronic risk to mammalians (herbivores and insectivores). RQ values were calculated for exposure to peanuts (maximum EECs RQ = 1.6 - 3.5 and 56 day average EECs RQ = 1.0 - 2.2) and potatoes (maximum EECs RQ = 1.0 - 1.9 and 56 day average EECs RQ = 1.4 - 3.0). Acute concerns appear to be focused on grass eating endangered mammals (RQ = 0.1)

Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001.
http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

-- Risk mitigation. Fluazinam is of very high toxic risk to freshwater aquatic organisms, of high toxic risk to marine aquatic organisms, and of high dietary and reproductive risk to wild mammals.
--
Results of terrestrial field studies of dissipation and accumulation conducted in Canada indicated that fluazinam was moderately persistent in soil, with DT50 values of 81.5 and 95 days with significant carryover of residues to the next season. The major transformation product, HYPA, was formed at one of the Canadian field sites reaching a maximum of 15%. HYPA was a minor transformation product at the other Canadian site. There was no evidence of leaching of fluazinam or HYPA through the soil layers. Field dissipation studies conducted in the U.S. yielded DT50 values of 19 and 33, indicating slight persistence. HYPA was formed as a major transformation product at one of the U.S. sites reaching 15% HYPA was a minor transformation product at the other U.S. site. Both field and laboratory studies indicate that fluazinam will be moderately persistent and have low potential to leach.

Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf


A February 16, 2005, check at the Code of Federal Regulations for Fluazinam (and its metabolite in or on grape): this fungicide is permitted in or on 3 food commodities in the United States. The following list identifies these crops for which EPA has set pesticide tolerances. 

Note: On April 18, 2002, US EPA established an import tolerance for residues of fluazinam and its metabolite AMGT3 in or on wine grapes at 3.0 ppm. ISK BioSciences Corporation requested this tolerance under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996.

[Code of Federal Regulations]
[Title 40, Volume 22]
[Revised as of July 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR180.574]
[Page 510-511]

TITLE 40--PROTECTION OF ENVIRONMENT

CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)

PART 180_TOLERANCES AND EXEMPTIONS FROM TOLERANCES FOR PESTICIDE CHEMICALS
IN FOOD--Table of Contents

Subpart C_Specific Tolerances

Sec. 180.574 Fluazinam; tolerances for residues.
(a)(1) General. Tolerances are established for residues of
fluazinam, (3-
chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl) phenyl]-5-
(trifluoromethyl)-2-pyridinamine) in or on the following commodities:
Commodity Parts per million
Peanut
0.02
Potato 0.02
(a)(2) Tolerances are established for residues of fluazinam and its
metabolite AMGT 3-
[[4-amino-3-[[3-chloro-5-(trifloromethyl)-2-
pyridinyl]amino]-2-nitro-6-(trifluoromethyl) phenyl] thio]-2-(beta-D-
glucopyranosyloxy) propionic acid) in or on the following commodity:
Wine grape /1/ 3.0
/1/ No US registration as of March 15, 2002.
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
 
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