Flutriafol - CAS No. 76674-21-0
Comments submitted to US EPA on flutriafol for exemption use on soybean
Docket No. OPP-2005-0243. October 6, 2005.

Return to Index Page

October 6, 2005

Comments on Flutriafol submitted to US EPA

Via email: opp-docket@epa.gov

Docket No. OPP-2005-0243

Ellen Connett
Fluoride Action Network Pesticide Project
82 Judson Street, Canton NY 13617
Email: pesticides@fluoridealert.org

The Minnesota and South Dakota Departments of Agriculture have requested a quarantine exemption for the use of flutriafol (Impact 125SC) on soybeans to control Asian soybean rust (Federal Register, September 21, 2005).

1. EPA should have presented information in the docket on the available animal and human studies conducted with flutriafol for this exemption request. Without this information, the public is left uninformed of the potential consequences of using flutriafol.

2. Flutriafol and flusilazole are fluorinated triazole (or azole) fungicides that have been requested for exemption use on soybean. These fungicides present too many risks for an exemption use. Please see my comments on flusilazole submitted to Docket OPP-2005-0242.

3. Can the public expect adverse effects from flutriafol and flusilazole to be additive when both are applied to soybean? Will the risks be additive when other foods treated with triazole pesticides are consumed?


(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.
Reference: 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.

5. Is flutriafol toxic to Honey Bees? In a Material Safety Data Sheet for flutriafol, the Oral LD50 for honey bees is reported to be >0.005 mg/bee
Reference: Material Safety Data Sheet. Crop Care. Product Name: Impact ® In-Furror, Impact 250.
Available at: http://dkt.net.au/msdsfiles/impact.pdf

6. In animal studies, adverse effects from flutriafol were the eye, bone, liver, and body weight decrease. The seriousness of these effects need clarification; as well as the potential for additive effects from flusilazole on these same parameters.

The Reference for the following citations: 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.


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.


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.


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, proliferation 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).

Note: This comment is listed in the Federal Register as Docket No. OPP-2005-0243-0005.

Fluoride Action Network | Pesticide Project | 315-379-9200 | pesticides@fluoridealert.org