Adverse Effects
Flutriafol
CAS No.
76674-21-0
 
 

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Abstracts

Activity: Fungicide (azole)
Structure:



Adverse Effects:
Body Weight Decrease
Bone
Eye
Liver
Environmental

Although flutriafol is a triazole, the UK Scientific Subcommittee on Pesticides (April 1983) noted that its chemical structure closely resembles triarimol, fenarimol and nuarimol. Triarimol was found to induce hepatocarinomas at high doses and was subsequently withdrawn. Both fenarimol and nuarimol were suspected of inducing adverse effects on rodent fertility.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf


Flutriafol ranked number 20 for "Most Widely used pesticides in the UK (by Area Treated)" and "Chlorothalonil/flutriafol" ranked no. 48 in the same category.
Rank Formulation Method Area treated (ha) Weight applied (kg ai)
20 Flutriafol Spray 496,556 37,357
48 Chlorothalonil/flutriafol Spray 226,595 126,289
Ref: April 29, 2000. UK Department for Environment, Food & Rural Affairs in the online report, "Design of a Tax or Charge Scheme for Pesticides. " Annex C3: Overview of Pesticide Industry
http://www.fluorideaction.org/pesticides/pesticides.ranks.uk.2000.htm

 

Body Weight Decrease (click on for all fluorinated pesticides)

-- 7.2 Subacute toxicity. a) In a 90-day feeding study, rats were fed diet containing 0, 20, 200 or 2,000 ppm flutriafol. At the highest does, reduced body weight and food intake, haemotological and biochemical changes, increased liver weight, centrilobular hypertrophy, proliferation of SER, elevated hepatic aminopyrine-N-demethylase (APDM) activity were noted. In females fed 200 ppm, only adaptive responses (liver enlargement and elevated APDM) were seen, whereas minimal fatty change was evident in some males. A NEL of 20 ppm (approx. 1 mg/kg bw/day) was established by the SSC (April 1983).
--b) In a 90-day study, dogs were administered oral doses (capsules) of 0, 1, 5 or 15 mg flutriafol/kg bw/day. Reduced body weight gain, increased liver weight, elevated hepatic APDM and plasma ALP activity, were observed in the 15 mg/kg bw/ dosage group. At the 5 mg/kg dosage level, APDM activity was elevated in both sexes. Slight increases in liver weight were seen in females at the low and intermediate dosage levels. A NEL of 5 mg/kg bw/day was established by the SSC [Scientific Subcommittee on Pesticides] (April 1983).
-- 7.5 Two year feeding study in the rat (1982-84). Wistar derived Alpk: AP rats (52/sex/dose) were fed diet containing flutriafol (purity 93%) at a concentration of 9, 20, 200 or 2,000 for at least 104 weeks. Additional animals (12/sex/dose) were given identical treatment and sacrified at 52-54 weeks... Apart from non-specific clinical observations, the only treatment-related clinical findings were an increased number of thin rats and reduction in the number with distended abdomens in the dop dosage group. A significant reduction in bodyweight gain was observed in the top dosage group throughout the study. On termination, the mean bodyweight of males in the high dosage group was reduced by about 10% compared to controls, in females the reduction was about 20%.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm

Bone (click on for all fluorinated pesticides)

7.3 Reproductive toxicity. Pregnant rats were administered 0, 10, 50 or 125 mg/kg bw/day from day 5 to 15 of gestation. Maternal toxicity was apparent at the highest dose level. Significant dose-related reductions in fetal ossification were observed in all treatment groups. At the 10 mg/kg bw dosage level, incomplete ossification of the odontoid, calcaneum and occipital bones were noted. In the 50 and 125 mg/kg bw dosage groups, the incidence of fetuses with extra ribs was increased. In a rabbit teratology study, the dams were administered (orally) 9, 2.3, 7.5 or 15 mg/bw from day 6 to 18 of gestation. Reduced maternal body weight gain, increased post implantation loss, and a reduction in viable fetuses were seen at the 15 mg/kg bw dose level. There was a small increase in the number of fetuses with extra ribs in the lumber region in all treatment groups. The NEL in the rabbit study was considered to be 7.5 mg/kg bw/day. Although a NEL was not established for the rat study, it was considered to be in the order of 10 mg/kg bw/day.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf

Definitions:
Odontoid
- Having the form of a tooth; toothlike. Of or pertaining to the odontoid bone or to the odontoid process. Odontoid bone, the anterior process of the centrum of the second vertebra, or axis, in birds and mammals. See Axis. Origin: Gr., a tooth + form: cf.F. Odontoide. Source: Websters Dictionary
Calcaneum - Synonym: calcaneus. Origin: L. The heel
Occipital - Of or pertaining to the occiput, or back part of the head, or to the occipital bone. Occipital bone, the point of the occiput in the mesial plane farthest from the ophryon. Origin: Cf. F. Occipital. The occipital bone. Source: Websters Dictionary

Eye (click on for all fluorinated pesticides)

Ophthalmoscopic examinations, performed on 20 males and 20 femals from the control and top dosage groups after 52 and 104 weeks of the study, found a variety of ocular changes. Apart from retinal pallor, changes were regarded as age-related (or the incidence of the changes was within the historical data). At 52 weeks, very pale to pale retinal pallor was found in 3/20 male and 2/20 female animals in the hgh dosage group compared to nil in the control animals. On termination, slightly pale to pale retinal pallor was seen in 6/19 male and 5/18 female rats from the high dosage group compared to 1/18 males in the control group. No opthalmoscopic examinations were carried out on the low and intermediate dosage groups. In the absence of abnormalities in the retinal vessels and hyper-reflection of the retina, the study authros concluded that the retinal pallor was not toxicologically significant. No treatment-related histopathological abnormalities were detected in eyes at termination in any dosage group... Data requirements: To be submitted within 6 months of the date of issue of approval: The applicant must address the increased retinal pallor seen in the two chronic two year feeding study in rats or provide a reasoned argument as to why it is not of toxicological significance.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf

Liver (click on for all fluorinated pesticides)

-- 7.2 Subacute toxicity. a) In a 90-day feeding study, rats were fed diet containing 0, 20, 200 or 2,000 ppm flutriafol. At the highest does, reduced body weight and food intake, haemotological and biochemical changes, increased liver weight, centrilobular hypertrophy, proliferation of SER, elevated hepatic aminopyrine-N-demethylase (APDM) activity were noted. In females fed 200 ppm, only adaptive responses (liver enlargement and elevated APDM) were seen, whereas minimal fatty change was evident in some males. A NEL of 20 ppm (approx. 1 mg/kg bw/day) was established by the SSC (April 1983).
--b) In a 90-day study, dogs were administered oral doses (capsules) of 0, 1, 5 or 15 mg flutriafol/kg bw/day. Reduced body weight gain, increased liver weight, elevated hepatic APDM and plasma ALP activity, were observed in the 15 mg/kg bw/ dosage group. At the 5 mg/kg dosage level, APDM activity was elevated in both sexes. Slight increases in liver weight were seen in females at the low and intermediate dosage levels. A NEL of 5 mg/kg bw/day was established by the SSC [Scientific Subcommittee on Pesticides] (April 1983).
-- 7.7 Assessment a)... Although the incidence of hepatocellular tumours was higher than the historical control data predicted, the increased incidence of individual tumours was not significant, only the combined incidence of hepatocellular carcinoma and adenoma achieved statistical significance. The available evidence suggested that the increase in hepatocellular tumors involved an epigenetic mechanism, all in vitro and in vivo mutagenicity assays were negative and changes in clinical chemistry suggested altered liver metabolism and liver injury. In addition, adaptive responses (increased liver weight, centrilobular hypertrophy, proliferatin of SER and enzyme induction) were evident at low doses in the subacutre rat and dog studies. This evidence suggested that flutriafol was possibly a weak tumour promoter at high dose levels and this effect was possibly secondary to the liver injury. The NOEL for the study was determined to be 20 ppm flutriafol (about 1 mg/kg bw/day). (b) In the multigeneration study, dietary administration of 1,000 ppm flutriafol during the premating period induced a reduction in bodyweight gain and food consumption in F0 parents, and reduced bodyweight gain in F1 females. Increased liver weight, centrilobular hypertrophy (males only) and fatty change were found in F0 and F1 parents fed 1,000 ppm flutriafol. Fatty change in the liver was also evident in F1 males fed 240 ppm flutriafol.... In the high dosage group, the proportion of pups born alive in the second generation litters was significantly reduced. Mean litter size was significantly reduced in F1B and F2A litters. In the high dosage groups, fatty change of the liver was evident in F1B, F2A and F2B pups.. The NEL for reproductive performance in rats was 240 ppm flutriafol (equivalent to approx 12 mg/kg bw/day).
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf

Environmental (click on for all fluorinated pesticides)

Recommendations (page 51): [Flutriafol] is extremely persistent in soil and will accumulate following repeated annual applications. Soil residues also demonstrate the potential to be mobile. Although the fate and behaviour of flutriafol in water has not been evaluated and no data are available from natural water monitoring, the high spray application rate and the use on cereals, indicated that water contamination is likely.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf


The Svalbard archipelago in arctic Norway receives considerable semivolatile organic contaminant (SOC) inputs from the atmosphere... The surface sample also had highest concentrations of pendimethalin (herbicide, 18.6 ng L-1) and flutriafol, the lone observed fungicide (9.6 ng L-1).
Reference: Current-Use and Legacy Pesticide History in the Austfonna Ice Cap, Svalbard, Norway. By Mark H. Hermanson et al. Environ. Sci. Technol., 39 (21), 8163 -8169, 2005. See Abstracts
 
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