Return to Fluopicolide Index Page

ACTIVITY:Fungicide (acylpicolide)

CAS Name: 2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzamide

Structure:

Adverse Effects:
Boby weight decrease
Bone
Developmental: Decreased crown-rump length in fetuses
Kidney
Liver

Boby weight decrease (click on for all fluorinated pesticides)

Reproductive and developmental toxicity (page 3)
• In a developmental toxicity study in rats gavage dosed from gestation days 7 to 20 at levels of 0, 5, 60 or700 mg/kg/day, evidence of maternal and fetal toxicity was observed at 700 mg/kg/day, the highest dose tested. The maternal and fetal NOAEL was 60 mg/kg/day based on statistically lower body weights in dams an fetuses, and skeletal findings in fetuses that included delayed ossification of some bones and slight increases in the incidences of various rib and thoracic vertebrae anomalies.
• In a 2-generation reproductive toxicity study, fluopicolide was administered to rats at dietary levels of 0, 100, 500, or 2000 ppm. The NOAEL was 500 ppm (equivalent to 26 and 33 mg/kg/day for males and females respectively) for developing offspring and for parental/systemic toxicity. The LOAEL was 2000 ppm based on decreased body weight and organ weight changes in both F0 anb F1 and F2 pups. The reproductive NOAEL was 2000 ppm.
Chronic toxicity (page 4)
i. Lower body weight gain at the limit dose of 1000 mg/kg/day was the only treatment-related effect noted in a 52-week dog study performed at 70, 300, and 1000 mg/kg/day by gavage.
iii. The oncogenic potential of fluopicolide was investigated in C57BL/6 mice at dietary levels of 0, 50, 400, or 3200 ppm. Significantly lower body weight gain was seen at 3200 ppm in conjunction with a slight decrease in food consumption....
Reference: January 1, 2005, submission to US EPA from Valent U.S.A. Company. Federal Register Docket EPA-HQ-OPP-2006-0481-0002.
http://www.fluorideaction.org/pesticides/fluocopicolide.valent.june.2005.pdf

Bone (click on for all fluorinated pesticides)

Reproductive and developmental toxicity (page 3)
• In a developmental toxicity study in rats gavage dosed from gestation days 7 to 20 at levels of 0, 5, 60 or700 mg/kg/day, evidence of maternal and fetal toxicity was observed at 700 mg/kg/day, the highest dose tested. The maternal and fetal NOAEL was 60 mg/kg/day based on statistically lower body weights in dams an fetuses, and skeletal findings in fetuses that included delayed ossification of some bones and slight increases in the incidences of various rib and thoracic vertebrae anomalies.
Reference: January 1, 2005, submission to US EPA from Valent U.S.A. Company. Federal Register Docket EPA-HQ-OPP-2006-0481-0002.
http://www.fluorideaction.org/pesticides/fluocopicolide.valent.june.2005.pdf

• Twenty three mated Sprague-Dawley female rats/group were dosed orally by gavage with 0, 5, 60 or 700 mg/kg/day from gestation day 7 through gestation day 20. The mean body weight gain of the 700 mg/kg dams was less than that of the control between days 7 and 21. The mean fetal body weight of the 700 mg/kg offspring was less than the control value (p<0.05). The mean crown-rump length of the 700 mg/kg fetuses was less than the control value (p<0.05). No adverse effect indicated. Maternal NOEL: 60 mg/kg/day (based on the lower body weight gain of the 700 mg/kg group); Developmental NOEL: 60 mg/kg/day (based on the lower mean body weight and crown-rump length of the fetuses in the 1000 mg/kg group).
• Four mated female SpragueDawley rats/group were dosed orally by gavage with 500 or 1000 mg/kg/day from day 7 through day 20 of gestation. The vehicle was aqueous 1% (w/v) methyl cellulose. The number of live fetuses/litter was inversely affected with 13.0 for the 500 mg/kg group and 9.3 for the 1000 mg/kg group. The mean fetal weight and crown-rump length for the 1000 mg/kg offspring were 2.78 g and 32.6 cm as compared to 3.12 g and 34.1 cm for the 500 mg/kg group. There was an apparent treatment-related effect upon both the dams and the development of the fetuses in the 1000 mg/kg group.
• Rabbit Oral Developmental Toxicity (Teratogenicity) Study (Including Addendum). Twenty three mated female Himalayan rabbits/group were dosed orally by gavage with 0, 5, 20 or 60 mg/kg/day from day 6 through day 28 of gestation. Three does in the 60 mg/kg group died during the study. Fifteen does in the 60 mg/kg group and 1 doe in the 20 mg/kg group delivered their offspring prematurely. The mean food consumption of the 5 does in the 60 mg/kg group which delivered live fetuses was less than that of the control during the last 6 days of the treatment (p<0.05). The mean body weight and crown-rump length of the fetuses in the 60 mg/kg group were less than the respective control values (p<0.05). Developmental NOEL: 20 mg/kg/day (based upon the lower mean body weight and the crownrump length of the fetuses in the 60 mg/kg/day group).
Ref: Fluopicolide: summary of toxicology data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. May 2, 2007.
http://www.fluoridealert.org/pesticides/fluopicolide.ca.epa.2007.pdf

Developmental (click on for all fluorinated pesticides)

• Twenty three mated Sprague-Dawley female rats/group were dosed orally by gavage with 0, 5, 60 or 700 mg/kg/day from gestation day 7 through gestation day 20. The mean body weight gain of the 700 mg/kg dams was less than that of the control between days 7 and 21. The mean fetal body weight of the 700 mg/kg offspring was less than the control value (p<0.05). The mean crown-rump length of the 700 mg/kg fetuses was less than the control value (p<0.05). No adverse effect indicated. Maternal NOEL: 60 mg/kg/day (based on the lower body weight gain of the 700 mg/kg group); Developmental NOEL: 60 mg/kg/day (based on the lower mean body weight and crown-rump length of the fetuses in the 1000 mg/kg group).
• Four mated female SpragueDawley rats/group were dosed orally by gavage with 500 or 1000 mg/kg/day from day 7 through day 20 of gestation. The vehicle was aqueous 1% (w/v) methyl cellulose. The number of live fetuses/litter was inversely affected with 13.0 for the 500 mg/kg group and 9.3 for the 1000 mg/kg group. The mean fetal weight and crown-rump length for the 1000 mg/kg offspring were 2.78 g and 32.6 cm as compared to 3.12 g and 34.1 cm for the 500 mg/kg group. There was an apparent treatment-related effect upon both the dams and the development of the fetuses in the 1000 mg/kg group.
• Rabbit Oral Developmental Toxicity (Teratogenicity) Study (Including Addendum). Twenty three mated female Himalayan rabbits/group were dosed orally by gavage with 0, 5, 20 or 60 mg/kg/day from day 6 through day 28 of gestation. Three does in the 60 mg/kg group died during the study. Fifteen does in the 60 mg/kg group and 1 doe in the 20 mg/kg group delivered their offspring prematurely. The mean food consumption of the 5 does in the 60 mg/kg group which delivered live fetuses was less than that of the control during the last 6 days of the treatment (p<0.05). The mean body weight and crown-rump length of the fetuses in the 60 mg/kg group were less than the respective control values (p<0.05). Developmental NOEL: 20 mg/kg/day (based upon the lower mean body weight and the crownrump length of the fetuses in the 60 mg/kg/day group).
Ref: Fluopicolide: summary of toxicology data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. May 2, 2007.
http://www.fluoridealert.org/pesticides/fluopicolide.ca.epa.2007.pdf

Kidney (click on for all fluorinated pesticides)

Chronic toxicity (page 4)
ii. Chronic toxicity/carcinogenicity was assessed in rats at dietary levels of 50, 200, 750 and 2500 ppm. The NOAEL was 200 ppm (8.4 mg/kg/day in males and 10.8 mg/kg/day in females) based on microscopic changes in the liver and kidneys similar to those observed in the 90-day rat study. No evidence of carcinogenicity was observed in rats up to 2500 ppm.
Subchronic toxicity (pages 3-4)
Ninety-day feeding studies were conducted in dogs, mice and rats.
iii. In a 90-day rat study with dietary levels of 100, 1400 and 20,000 ppm, the maximum tolerated dose (MTD) was exceeded at 20,000 ppm based on body weight gain of 30 to 40% below control. The target organs identified in rats were the liver (centrilobular hypertrophy) in both sexes and the kidneys in males (accumulation of hyaline droplets, single cell death at the proximal tubule epithelium, slight foci of basophilic tubules and granular casts) at 1400 ppm and 20,000 ppm. The NOAEL was 100 ppm, equivalent to 7.4 and 8.4 mg/kg/day, in males and females, respectively.
Reference: January 1, 2005, submission to US EPA from Valent U.S.A. Company. Federal Register Docket EPA-HQ-OPP-2006-0481-0002.
http://www.fluorideaction.org/pesticides/fluocopicolide.valent.june.2005.pdf

Liver (click on for all fluorinated pesticides)

Chronic toxicity (page 4)
ii. Chronic toxicity/carcinogenicity was assessed in rats at dietary levels of 50, 200, 750 and 2500 ppm. The NOAEL was 200 ppm (8.4 mg/kg/day in males and 10.8 mg/kg/day in females) based on microscopic changes in the liver and kidneys similar to those observed in the 90-day rat study. No evidence of carcinogenicity was observed in rats up to 2500 ppm.
iii. The oncogenic potential of fluopicolide was investigated in C57BL/6 mice at dietary levels of 0, 50, 400, or 3200 ppm. Significantly lower body weight gain was seen at 3200 ppm in conjunction with a slight decrease in food consumption. Increased liver weight and centrilobular hepatocellular hypertrophy were observed at 400 and 3200 ppm in both sexes. In addition at 3200 ppm, an increased incidence of hepatocellular adenomas was noted in both sexes, but the incidence of hepatocellular carcinomas was not affected. The NOAEL was 50 ppm (equivalent to 7.9 and 11.5 mg/kg/day in males and females, respectively). Subsequent mechanistic work demonstrated a marked transient hepatocellular profileration, whch returned to control levels after 28 days of treatment. This was accompanied by a clear induction of total cytochrome P-450 and related enzymes. These results parallel findings with Phenobarbital, which has a well understood threshold-based mechanism of roden tumor formation commonly known to be of no relevance to humans.
Subchronic toxicity (pages 3-4)
Ninety-day feeding studies were conducted in dogs, mice and rats.
ii. In 90-day feeding studies in both CD-1 and C57BL/6 mice, liver was the only target organ identified with hepatocellular hypertrophy seen at dietary levels of 320 ppm and higher. The NOAEL in C57BL/6 mice was 200 ppm (equivalent to 37.8 and 52.8 mg/kg/day in males and females, respectively.)
iii. In a 90-day rat study with dietary levels of 100, 1400 and 20,000 ppm, the maximum tolerated dose (MTD) was exceeded at 20,000 ppm based on body weight gain of 30 to 40% below control. The target organs identified in rats were the liver (centrilobular hypertrophy) in both sexes and the kidneys in males (accumulation of hyaline droplets, single cell death at the proximal tubule epithelium, slight foci of basophilic tubules and granular casts) at 1400 ppm and 20,000 ppm. The NOAEL was 100 ppm, equivalent to 7.4 and 8.4 mg/kg/day, in males and females, respectively.
Reference: January 1, 2005, submission to US EPA from Valent U.S.A. Company. Federal Register Docket EPA-HQ-OPP-2006-0481-0002.
http://www.fluorideaction.org/pesticides/fluocopicolide.valent.june.2005.pdf