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?
4. Flutriafol IS EXTREMELY PERSISTENT
IN SOIL AND WILL LIKELY BE A GROUNDWATER CONTAMINANT.
Flusilazole is also persistent in soil.
(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.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf
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.
http://www.pesticides.gov.uk/PSD_PDFs/Evaluations/158_flutriafol.pdf
BONE:
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.
EYE:
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.
LIVER:
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.
