Return to Fluquinconazole Index Page

Activity: Fungicide (conazole)
Structure:

Adverse Effects:
Ataxia
Blood
Body Weight Decrease (emaciation)
Bone
Endocrine: Breast
Endocrine: Pituitary
Endocrine: Thyroid
Fetotoxicity
Kidney
Liver
Environmental: Highly toxic to fish and algae

Ataxia (click on for all fluorinated pesticides)

-- Acute oral toxicity. Rat. Groups of 5 male and 5 female COBS CD Sprague-Dawley rats were each administered by gavage fluquinconazole (99.6% purity) suspended in a 1% w/v aqueous methyl-cellulose solution at dose levels of 10, 50 or 250 mg/kg bw. Animals were killes and necropsied after a 14-day observation period. Five males and 5 females at the 250 mg/kg bw dose were killed in a moribund condition one day after treatment. There were no mortalities in either sex at dose levels of ² 50 mg/kg bw. The signs of intoxication prior to death were very severely reduced activity and reduced muscle tone, severe hunched posture and slight to moderate ataxia... The acute oral LD 50 of fluquinconazole in the rat was 112 mg/kg bw in both sexes. Fluquinconazole is classified with R25 Toxic if swallowed under current EC criteria.
-- -- Acute oral toxicity. Mouse. Groups of 5 male and 5 female CRLL:CD (ICR) BR mice were each administered by gavage fluqinconazole (99.6% purity) dissolved in a 1% aqueous methyl cellulose solution at nominal dose levels of 0, 100, 200 or 400 mg/kg bw. The test animals were killed and necropsied after a 14-day observation period... Signs of intoxication were observed from 5 h after treatment for up to 5 days in males at dose levels of ³ 200 mg/kg bw and in females at dose levels of ³ 100 mg/kg bw. The severity of the signs was dose related and included reduced activity, laboured respiration, reduced muscle tone (females only), ataxia, piloerection, hunched posture, pale extreminities, urogenital soiling (females). Slight (200 mg/kg bw) to significantly marked (400 mg/kg bw) loss of body weight was recorded in surviving females after week one. Body weight gain was normal in males throughout the study and in females after week one. The acute oral LD 50 of fluquinconazole in the mouse was 325 mg/kg bw in males and 180 mg/kg bw in females.
-- Acute inhalation toxicity. Groups of 5 male and 5 female Crl:CD (SD)BR Spraque-Dawley rats were exposed head-only to a dust aerosol of fluquinconzole (98.7% purity), at mean analytical concentrations of 0, 0.082, 0.24, 1.08 or 4.56 mg/l for four hours. All surviving animals were killed and necropsied after a 14-day observation period... signs of toxicity inclding ataxia, hunched posture and respiratory distress were observed at the 0.24 mg/l dose for up to 4 days and at the higher dose levels until death... The acute inhalation LC50 of fluquinconazole in the rat was 0.75 mg/l (0.83 mg/l in males and 0.51 mg/l in females). Fluquinconazole is classified under current EC criteria with R23 Toxic by inhalation.
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... At the 200 ppm dose level 2 males and 5 females were killed in a moribund condition after 9 and 7 days respectively of treatment. The signs of toxicity observed showed dose-related severity. The signs at dose levels of 100 ppm and above included hunched posture, hypoactivity, ataxia, reduced mucle tone, piloerection, twitches, urogenital staining, ptosis and emaciation...
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Slight signs of intoxication were observed after 2 weeks in both sexes at the 100 ppm dose level. The signs included unsteady gait, tremors, hunched posture, and reduced muscle tone. Lower incidence of reduced activity and twitches in males, and muscular fibrillation and ataxia in females were also observed. Body weight gain was significantly reduced (9%) in males only at the 100 ppm dose level compared with controls during the treatment period and transient significantly lower body weights were recorded...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Blood (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... There was a very slight reduction in red blood cells, haemoglobin and haematocrit in females during the first 12 months. At 24 months, the mean cell volume, mean corpuscular haemoglobin (MCH) and haemoglobin values were statistically significantly lower at the 100 ppm dose level than in controls. In males, the mean cell volume, mean corpuscular haemoglobin (MCH) and haemoglobin values were statistically significantly lower than controls at 12 months only. The main changes in clinical chemistry were related to serum protein content...
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... Minimal statistically non-significant differences were noted in surving male rats at the 200 ppm were reduction in white blood cells, reduction in lymphocytes and increased mean cell haemoglobin concentration. Changes in clinical chemistry parameters were related primarly to plasma proteins...
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Haematology, clinical chemistry and urinalysis parameters showed incidences of statistically significant changes which were considred to be of limited toxicological significance because they were either not dose-related or were reported to be withing the range of historical data.
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... Mortalities over the 24-month period were 24/50, 28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and 39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations showed the most probable cause of deaths in males to be pituitary tumors followed by chronic progressive nephropathy and urinary tract infections. In females mammmary tumors followed by pituitary tumors were considered the most probable cause of morbidity... Feed consumption was very slightly increased at the 100 ppm dose level (7% in males and 15% in females over weeks 1-104) compared to controls. Body weight gain was during weeks 0-55 reduced in treated females (9-12%) compared with controls but was significantly reduced during weeks 55-103 in males (13% at 10 ppm and 68% at 100 ppm) and in females (40% at 100 ppm dose level)...
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... At the 200 ppm dose level 2 males and 5 females were killed in a moribund condition after 9 and 7 days respectively of treatment. The signs of toxicity observed showed dose-related severity. The signs at dose levels of 100 ppm and above included hunched posture, hypoactivity, ataxia, reduced mucle tone, piloerection, twitches, urogenital staining, ptosis and emaciation... Reductions in body weight gain occurred in males only at 100 ppm (17%) and 10 mg/kg bw/day (16%) ppm compared to controls. The reduction in body weight gain in the surviving males at the 200 ppm dose level was 39% compared with that of the control over the treatment period...
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Slight signs of intoxication were observed after 2 weeks in both sexes at the 100 ppm dose level. The signs included unsteady gait, tremors, hunched posture, and reduced muscle tone. Lower incidence of reduced activity and twitches in males, and muscular fibrillation and ataxia in females were also observed. Body weight gain was significantly reduced (9%) in males only at the 100 ppm dose level compared with controls during the treatment period and transient significantly lower body weights were recorded...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Bone (click on for all fluorinated pesticides)

-- Developmental toxicity studies. (a) Oral teratology study in rats. In a study (1992), groups of 30 mated outbred albino Sprague-Dawley CRL:COBS CD(SD)BR rats were administered by gavage fluqinconazole (96% purity) in a 1% w/v aqueous methylcellulose solution at concentrations of 0, 0.4, 2 and 20 mg/kg bw/day (based on a range-finding study) from day 6 to 15 of presumed gestation... An increase in abnormal sternebrae was seen in the low dose group (27%) and the high dose group (31%, p<0.05) but not at the mid dose group (15%) when compared to controls (13%) - as the incidence, of this relatively common anomaly, in the low dose group is not statistically significant and not party of a dose response it is considered to be of no biological significance. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 9 mg/kg bw/day. The NOAEL for maternal and fetotoxicity was 2 mg/kg bw/day based on increased incidence of abortions in dams and increased mortality.
-- In the rabbit the NOEL for maternal and fetal toxicity was 2 mg/kg bw/day. Fluquinconazole was not teratogenic in the rabbit in the presence of maternal toxicity. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 8 mg/kg bw/day.
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Endocrine: Breast (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... Mortalities over the 24-month period were 24/50, 28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and 39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations showed the most probable cause of deaths in males to be pituitary tumors followed by chronic progressive nephropathy and urinary tract infections. In females mammmary tumors followed by pituitary tumors were considered the most probable cause of morbidity... In the thyroid gland a significantly higher incidence in follicular cell tumors were noted in the 100 ppm dose level in both sexes. Historical tumor incidences provided showed that the slight statistically non-significant increase in thyroid follicular cell tumors at the lowest and intermediate dose levels were at the upper limit of the historical control range and therefore in the absence of a dose response they were considered to be not of toxicological significance...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Endocrine: Pituitary (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... Mortalities over the 24-month period were 24/50, 28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and 39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations showed the most probable cause of deaths in males to be pituitary tumors followed by chronic progressive nephropathy and urinary tract infections. In females mammmary tumors followed by pituitary tumors were considered the most probable cause of morbidity... In the thyroid gland a significantly higher incidence in follicular cell tumors were noted in the 100 ppm dose level in both sexes. Historical tumor incidences provided showed that the slight statistically non-significant increase in thyroid follicular cell tumors at the lowest and intermediate dose levels were at the upper limit of the historical control range and therefore in the absence of a dose response they were considered to be not of toxicological significance...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK.Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Endocrine: Thyroid (click on for all fluorinated pesticides)

-- Groups of 40 male Sprague Dawley rats were fed a diet containing fluquinaconazole at concentrations of 0 (control) or 100 ppm for 14 days. Twenty rats per dose group were killed and necropsied on day 15. The remaining animals were kept for a further 14 days on a treatment-free diet then killed and necropsied... Hormone assays for thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH) and reverse triiodothyronine (RT3) were conducted but the details of the assay methods were not provided... Histopathology of the thyroid was reported and focussed on 3 parameters; colloid depletion, follicular cell hypertrophy and follicular cell hyperplasia... Histopathology of the thyroid showed the most distinctive finding to be the increased incidences of follicular epithelial hyperplasia of the thyroid (11/20) compared with 0/20 in controls at day 15). An increase in the incidence of severe folicular hypertrophy and severe or very severe colloid depletion was considered to be also indicative of increase in thryoidtoxicity in fluquinconazole-treated animals. Severe to very severe colloidal depletion (5/20 animals compared with 1/20 in controls), severe follicular cell hypertrophy (3/20 compared wtih 0/20 in controls) and slight to moderate follicular epithelial hyperplasia (4/20 compared with 1/20 in controls) was present in the thyroid at the end of the recovery period. In conclusion, administration of fluquinconazole to male rats resulted in changes in thyroid hormone homeostasis manifested by histopathological changes int he thyroid... (DP 47301)
-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... In the thyroid gland a significantly higher incidence in follicular cell tumors were noted in the 100 ppm dose level in both sexes. Historical tumor incidences provided showed that the slight statistically non-significant increase in thyroid follicular cell tumors at the lowest and intermediate dose levels were at the upper limit of the historical control range and therefore in the absence of a dose response they were considered to be not of toxicological significance.
-- The rat was the most sensitive species to fluquinconazole compared with the dog and mouse. The main target organs were the liver, kidney and thyroid... For the thyroid tumors in the rat, a correlation between induction of liver UDGPT and imbalances in thyroid hormone (increase in TSH and reduction in T4) and histopathological changes in the thyroid was demonstrated. Disturbance of thyroid hormone homeostasis is a well recognised mechanism for the induction of thyroid tumours. Futher this is considered to be secondary to the observed liver enzme induction. A clear NOEL for thyroid tumors and the induction of thryoid effects was established.
-- Acute inhalation toxicity. Groups of 5 male and 5 female Crl:CD (SD)BR Spraque-Dawley rats were exposed head-only to a dust aerosol of fluquinconzole (98.7% purity), at mean analytical concentrations of 0, 0.082, 0.24, 1.08 or 4.56 mg/l for four hours. All surviving animals were killed and necropsied after a 14-day observation period... signs of toxicity inclding ataxia, hunched posture and respiratory distress were observed at the 0.24 mg/l dose for up to 4 days and at the higher dose levels until death... In the thyroid, the incidence and severity of thyroid effects including colloid depletion, follicular cell hyperplasia and hypertrophy did not show a clear treatment-relationship (statistically significant compared with controls at 100 and 200 ppm but not at 400 ppm and 10 mg/kg bw/day dose levels). The NOEl was 5 ppm (0.45 mg/kg bw/day) based on increased liver and kidney weights and histopathological changes in the liver, kidney and thyroid at the higher dose level of 20 ppm... The liver, thyroid and kidneys were noted to be the target organs of the test compound and significant changes in these organs indicative of significant hepatic enzyme induction were considered to be relevant for risk assessment.
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Fetotoxicity (click on for all fluorinated pesticides)

- Developmental toxicity studies. (a) Oral teratology study in rats. In a study (1992), groups of 30 mated outbred albino Sprague-Dawley CRL:COBS CD(SD)BR rats were administered by gavage fluqinconazole (96% purity) in a 1% w/v aqueous methylcellulose solution at concentrations of 0, 0.4, 2 and 20 mg/kg bw/day (based on a range-finding study) from day 6 to 15 of presumed gestation... An increase in abnormal sternebrae was seen in the low dose group (27%) and the high dose group (31%, p<0.05) but not at the mid dose group (15%) when compared to controls (13%) - as the incidence, of this relatively common anomaly, in the low dose group is not statistically significant and not party of a dose response it is considered to be of no biological significance. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 9 mg/kg bw/day. The NOAEL for maternal and fetotoxicity was 2 mg/kg bw/day based on increased incidence of abortions in dams and increased mortality.
-- In the rabbit the NOEL for maternal and fetal toxicity was 2 mg/kg bw/day. Fluquinconazole was not teratogenic in the rabbit in the presence of maternal toxicity. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 8 mg/kg bw/day.
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Kidney (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... At the interim-kill, organ weights showed moderate significant treatment-realted increase in the absolute liver and kidney weights in males and females at the 100 ppm dose level compared with controls. The relative liver and kidney weights were significantly increased in males at the 100 ppm dose level and in females at ³ 10 ppm. A significant increase in the incidence of hyaline droplet deposition in the proximal tubular epithelium occurred in the kidneys of males (15/20 compared with 6/20 controls) at the 100 ppm dose level. Minimal to moderate hypertrophy of centrilobular hepatocytes was observed in the liver of all top dose animals and at the 10 ppm dose level (10/20 males and 3/20 females). In the thyroid, an increase in the follicular epithelial height in both sexes was noted at the 100 ppm dose level. At the terminal-kill, the absoloute and relative liver and kidney weights of males and females were slightly to moderately increased at 100 ppm dose level...
-- Kidney effects were observed in the rat and mouse and consisted of increases in organ weight and histopathological changes including hyaline droplet nephropathy, focal tubular hyperplasia, increases in the incidence of small and large eosinophilic inclusions, and increase in the incidence and severity of chronic progressive nephropathy. There is no conclusive mechanism for the observed kidney effects.
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... Organ weights showed a dose-related increase in the relative liver weight at dose levels of ³ 20 ppm in males (15-44%) and at 100 ppm and 10 mg/kg bw/day dose levels (25-27%). The relative kidney weight was increased in males only (11-21%) compared with controls at dose levels of ³ 20 ppm. Gross examination at necropsy revealed accentuation of the lobular pattern of the liver at dose levels of ³ 5 ppm in females and at ³ 20 ppm in males. Pale kidneys were observed in males at dose levels of ² 5 ppm... Histopathology showed significant treatment-related centrilobular hepatocyte hypertrophy in males and females at dose levels of ³ 100 ppm. In the kidney, slight to moderate hyaline droplet mephropathy was observed in males at ³ 20 ppm... The liver, thyroid and kidneys were noted to be the target organs of the test compound and significant changes in these organs indicative of significant hepatic enzyme induction were considered to be relevant for risk assessment.
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Slight signs of intoxication were observed after 2 weeks in both sexes at the 100 ppm dose level. The signs included unsteady gait, tremors, hunched posture, and reduced muscle tone. Lower incidence of reduced activity and twitches in males, and muscular fibrillation and ataxia in females were also observed. Body weight gain was significantly reduced (9%) in males only at the 100 ppm dose level compared with controls during the treatment period and transient significantly lower body weights were recorded... Haematology, clinical chemistry and urinalysis parameters showed incidences of statistically significant changes which were considred to be of limited toxicological significance because they were either not dose-related or were reported to be withing the range of historical data. There was an increase in the absolute liver (35%) and adrenal (36.4%) weights in females at the 100 ppm dose level. The relative kidney (14%) and liver (21%) weights in males and the relative kidney (6.9%) and adrenal (30%) weights in females were significantly increased at the 100 ppm dose level. In females, the relative liver weight was increased at dose levels of 15 ppm (14%) and 100 ppm (32%). At the end of the withdrawal period, the relative kidney weight in males and the relative liver weight in females were still siginficantly elevated compared with controls...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Liver (click on for all fluorinated pesticides)

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... Mortalities over the 24-month period were 24/50, 28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and 39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations showed the most probable cause of deaths in males to be pituitary tumors followed by chronic progressive nephropathy and urinary tract infections. In females mammmary tumors followed by pituitary tumors were considered the most probable cause of morbidity... At the interim-kill, organ weights showed moderate significant treatment-related increase in the absolute liver and kidney weights in males and females at the 100 ppm dose level compared with controls. The relative liver and kidney weights were significantly increased in males at the 100 ppm dose level and in females at ³ 10 ppm. A significant increase in the incidence of hyaline droplet deposition in the proximal tubular epithelium occurred in the kidneys of males (15/20 compared with 6/20 controls) at the 100 ppm dose level. Minimal to moderate hypertrophy of centrilobular hepatocytes was observed in the liver of all top dose animals and at the 10 ppm dose level (10/20 males and 3/20 females). In the thyroid, an increase int he follicular epithelial height in both sexes was noted at the 100 ppm dose level. At the terminal-kill, the absoloute and relative liver and kidney weights of males and females were slightly to moderately increased at 100 ppm dose level. Necropsy revealed slightly increased incidence of liver masses in top dose females (0/50, 0/50 and 6/50 at dose levels of 0. 1, 10 and 100 ppm respectively). Microscopic findings at 24 months were slight increases in the incidence and severity of chronic progressive nephropathy in males and females at the 100 ppm dose level. Slight to severe centrilobular cellular hypertrophy, bile duct hyperplasia (51/100 compared with 21/100 for controls in both sexes) and significant increase in the incidence of malignant liver tumors (8/50 compared with 0/50 in males) in females occurred at the top dose level...
-- For liver tumours, no clearcut identifiable preneoplastic lesions were identified (No data requirement for this to be demonstrated has previously been requested). Liver tumors in both sexes at 100 ppm were associated with increased liver weight, increased incidence and severity of hepatocyte hypertrophy (both of which were observed in shorter term studies and responded to changes in dose), and bile duct hyperplasia and a slight increase in eosinophilic foci in females seen in the chronic study of the rat at 24 months only. Clear NOELs for liver tumors and the induction of associated liver effects were determined in rats and mice.
-- Acute inhalation toxicity. Groups of 5 male and 5 female Crl:CD (SD)BR Spraque-Dawley rats were exposed head-only to a dust aerosol of fluquinconzole (98.7% purity), at mean analytical concentrations of 0, 0.082, 0.24, 1.08 or 4.56 mg/l for four hours. All surviving animals were killed and necropsied after a 14-day observation period... signs of toxicity inclding ataxia, hunched posture and respiratory distress were observed at the 0.24 mg/l dose for up to 4 days and at the higher dose levels until death... The acute inhalation LC50 of fluquinconazole in the rat was 0.75 mg/l (0.83 mg/l in males and 0.51 mg/l in females). Fluquinconazole is classified under current EC criteria with R23 Toxic by inhalation.
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbred albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm...Organ weights showed a dose-related increase in the relative liver weight at dose levels of ³ 20 ppm in males (15-44%) and at 100 ppm and 10 mg/kg bw/day dose levels (25-27%). The relative kidney weight was increased in males only (11-21%) compared with controls at dose levels of ³ 20 ppm. Gross examination at necropsy revealed accentuation of the lobular pattern of the liver at dose levels of ³ 5 ppm in females and at ³ 20 ppm in males. Pale kidneys were observed in males at dose levels of ² 5 ppm... Histopathology showed significant treatment-related centrilobular hepatocyte hypertrophy in males and females at dose levels of ³ 100 ppm. In the kidney, slight to moderate hyaline droplet mephropathy was observed in males at ³ 20 ppm. In the thyroid, the incidence and severity of thyroid effects including colloid depletion, follicular cell hyperplasia and hypertrophy did not show a clear treatment-relationship (statistically significant compared with controls at 100 and 200 ppm but not at 400 ppm and 10 mg/kg bw/day dose levels). The NOEl was 5 ppm (0.45 mg/kg bw/day) based on increased liver and kidney weights and histopathological changes in the liver, kidney and thyroid at the higher dose level of 20 ppm... The liver, thyroid and kidneys were noted to be the target organs of the test compound and significant changes in these organs indicative of significant hepatic enzyme induction were considered to be relevant for risk assessment.
-- Haematology, clinical chemistry and urinalysis parameters showed incidences of statistically significant changes which were considred to be of limited toxicological significance because they were eithe not dose-related or were reported to be withing the range of historical data. There was an increase in the absolute liver (35%) and adrenal (36.4%) weights in females at the 100 ppm dose level. The relative kidney (14%) and liver (21%) weights in males and the relative kidney (6.9%) and adrenal (30%) weights in females were significantly increased at the 100 ppm dose level. In females, the relative liver weight was increased at dose levels of 15 ppm (14%) and 100 ppm (32%). At the end of the withdrawal period, the relative kidney weight in males and the relative liver weight in females were still siginficantly elevated compared with controls. Gross examination of organs revealed accentuated lobular pattern of the liver in males and females at the 15 ppm (on male only) and 100 ppm (3 males and 6 females) dose levels but a significant reduction in the incidence of lobulation of the liver (1 male only) was observed at the end of the withdrawal period.
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:
http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm