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to Flufenoxuron Index Page
Activity: Acaricide,
Insecticide (Benzoylurea)
Structure:
Adverse
Effects:
Blood
Bone
Endocrine:
Adrenal
Endocrine: Ovary
Endocrine:
Testicular
Endocrine: Thyroid
Kidney
Liver
Spleen
Environmental
Registered
use in: Australia,
Hungary, India, Japan, Philippines, Portugal, Tanzania,
South Africa, US, Vietnam
In
US: Apple, Cattle, Goat, Grape,
Horse, Milk, Orange, Pear, Raisin, Sheep (imported
commodities only:
Acute toxicity studies are not required for import tolerance.)
In
Japan
this pesticide is used on the following food commodities:
Apple, Brussel Sprouts, Cabbage, Celery, Cherry, Cotton
seeds, Cucumber, Eggplant, Grape, Grapefruit, Multiplying
onion (inc Shallot), Lemon, Lime, Melons, Mushrooms (other
than Shitake or Button), Natsudaidai (whole), Other Citrus
fruits, Orange, Peach, Pear, Radish (Japanese), Strawberry,
Sugar beet, Tea, Tomato, Unshu orange, Welsh (inc Leek)
METABOLITES & DEGRADATES:
2,6,-difluorobenzoic acid
2,6,-difluorobenzamide
4-(2-chloro,á, á, á trifluoro-p-tolyoxy)-2-fluorophenyl
urea (WL129183)
4-(2-chloro,á, á, á rifluoro-p-tolyoxy)-2-fluoroaniline
(WL15096)
Ref: August 15, 2006. US EPA Human
Health Risk Assessment
• The database is
adequate for establishment of tolerances on the requested
commodities, except for a developmental
toxicity study in rat which was classified as unacceptable/guideline....
Ref: August 15, 2006. US EPA Human
Health Risk Assessment
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Blood
(click on for all fluorinated pesticides)
The critical toxicological effects of flufenoxuron in mammals
are on the hemopoeitic [sic hematopoietic] system. These effects
include shifts in red blood cell parameters (decreased
in hemoglobin, hematocrit, red blood cells and erythroid: myloid
ratio) resulting in mild anemia and enhanced levels of
methemoglobin and sulfhemoglobin in dogs and rats. Dogs appears
to be more susceptible to the hematopoetic effects described above.
It is likely that a metabolite (aniline metabolite (4-[2chloro,
á, á, á-trifluoro-p-tolyoxy]-2-fluoroaniline)
is responsible for the formation of methemoglobin and sulfhemoglobin.
Two oncogenicity studies in mice and one in rat; were conducted
at doses exceeding 4 - 7.5x limit dose.
Reference: August 15, 2006.
US EPA Human Health Risk Assessment for proposed tolerances on
apples, pears, grapes, organges and livestock commodities imported
into US. http://www.fluorideaction.org/pesticides/flufenoxuran.hra.epa.2006.pdf
--
Repeat
dose mammalian studies.
Studies submitted
were 28 d rat, 90 d rat/mouse/dog, 12 and 24 month rat, and 12
month dog. In both the rat and dog there was evidence of regenerative
anaemia and increased methaemoglobin levels
with NELs of 5 mg.kg-1 (rat 28- and 90- day) and 2.5 mg.kg-1.d-1
(dog 12 month). In mice the NEL was 7.5 mg.kg-1.d-1 based on increased
plasma bilirubin. Plasma bilirubin was also increased in rats
(24 month). Evidence of regenerative anaemia (increased methaemoglobin,
decreased erythrocyte parameters, increased reticulocytes, increased
marrow cellularity and increased spleen weight) was
seen in most studies. In addition at higher doses triglycerides
were decreased and heart weight increased in the rat.
-- Repeat
dose studies. Sub-Acute Toxicity.
In an adequately conducted study 7/sex/dose Fischer 344 rats were
administered 0, 50, 500, 5000, 10000 or 50000 ppm flufenoxuron
[in] the diet for 28 days... Haematology parameters were measured
at necropsy. Methaemoglobin concentrations
were increased 100% at and above 500 ppm in males and 5000
ppm in females...
Ref: December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Bone
(click on for all fluorinated pesticides)
--
Mammalian Toxicokinetics. Oral Administration in the rat. Single
high dose. In
an adequately conducted study groups of 5/sec Fischer 344 rats
received a single dose of 350 mg.kg-1 bw of either unlabelled
or [14 C-aniline]-flufenoxuron by gavage... There was a significant
sex difference in the concentration of radioactivity found in
the gonads (7.9 ppm in the males, 52 ppm in the females) and
bone marrow (21.6 ppm in the males and 52.6 ppm in the females)
(approximately 13 ppm).
-- Mammalian
Toxicokinetics. Oral Administration in the rat. Single
low dose. In a preliminary study, 1/sex
Fischer 344 rats received a single dose of 3.5 mg.kg-1 bw [14
C-aniline]-flufenoxuron by gavage... Radioactivity was found to
be extensively distributed throughout the carcass.
Substantial concentrations of radioactivity were associated with
the fat, GI tract, bone marrow and
skin.
Ref:
December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
-- Abstract: Flufenoxuron
(Benzoylphenyl urea derivative) - antimoulting insecticide Ð is
recently used for controlling insect reproduction in cultivated
areas. The study determined the hazardous effects of the applied
dose-treatment during the critical period of rat embryonic development
and the induction of growth retardation. In the present work,
flufenoxuron was intragastrically administered by stomach intubation
to pregnant rats at concentration levels 0 & 20 mg/kg b.wt.
in saline solution every other day on gestation day 7 till parturition.
Experimental and control pregnant rats were sacrificed on days
13 & 16 of gestation and the foetuses were fixed in 10 percent
formol saline. Histological abnormalities
of thyroid, liver and kidneys of mothers as well as of
skeletal axial and appendicular regions of foetuses were
investigated. Foetuses
maternally treated with flufenoxuron exhibited delayed
differentiation of chondrification and ossification of axial and
appendicular regions. The observed defects in foetuses
may be attributed to the histological abnormalities of thyroid,
liver and kidneys of maternal tissues as well as to the
direct effect of the parents as a result of the insecticide or
its metabolites on the affected structures during early morphogenesis
and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
65-81, 1998. PATTERNS OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES
MATERNALLY TREATED WITH AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE
FLUFENOXURON; by Karim,
S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
90-Day oral toxicity in dog: LOAEL = 38 mg/kg/day (M/F), based
on decreased hemoglobin, hematocrit levels, and erythrocyte counts
in males and increased absolute liver weights, bone
marrow hyperplasia and methemoglobinemia in males and females.
Reference: August 15, 2006.
US EPA Human Health Risk Assessment for proposed tolerances on
apples, pears, grapes, organges and livestock commodities imported
into US. http://www.fluorideaction.org/pesticides/flufenoxuran.hra.epa.2006.pdf
Endocrine:
Adrenal (click on
for all fluorinated pesticides)
Carcinogenicity.
Rat. Groups of 50/sex/group Fischer 344 rats were administered
0, 500, 5000 or 50000 ppm flllufenoxuron in the diet for 24 months...
In
males relative spleen weight was reduced in all treatment groups
(respectively 14, 29 and 32 %)...In
the females there was a significant increase in adrenal weight
in all treatment groups (respectively 9, 7 and 15%).
Ref:
December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Endocrine:
Ovary (click on for
all fluorinated pesticides)
-- Abstract: Flufenoxuron
(Benzoylphenylurea derivative)-an environmental antimoulting insecticide-is
recently used for controlling insect production in cultivated
areas. In the present work, the insecticide was administered intragastrically
by stomach tube at a dose of 20 mg/kg b.wt. to the Juvenile female
and male albino rats (Rattus norvegicus) every other day
for three weeks. Histological examination of ovaries revealed
that the flufenoxuron induced massive
degeneration of ovarian follicles with much
cellular debris in the antrum and pyknotic granulosa cells.
On
the other hand,
the testis of flufenoxuron-treated animals exhibited marked decrease
of the thickness of tunica albuginea and atrophy of the seminiferous
tubules. There was a marked increase of desquamated spermatogenic
cells within the lumina of seminiferous tubules. Multinucleated
giant cells and vanishing of sperms were observed in the majority
of tubules of flufenoxuron-treated animals in comparison with
control. Epididymides sperm of experimental group exhibited the
presence of increased number of spermatic precursors as well as
varieties of sperm anomalies. The hepatic tissues toxicated with
the insecticide showed nuclear disintegration, massive breakdown
of hepatocytes and internal haemorrhage. The observed gonadal
dysfunction may be attributed to hepatic damage or decline of
gonadal hormone involved in either processes.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
45-64, 1998. EFFECTS
OF FLUFENOXURON-AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE ON GONAD
FUNCTION OF ALBINO RATS; by EL-Sayyad, H.I. and Karim, S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Endocrine:
Testicular (click
on for all fluorinated pesticides)
-- Abstract: Flufenoxuron
(Benzoylphenylurea derivative)-an environmental antimoulting insecticide-is
recently used for controlling insect production in cultivated
areas. In the present work, the insecticide was administered intragastrically
by stomach tube at a dose of 20 mg/kg b.wt. to the Juvenile female
and male albino rats (Rattus norvegicus) every other day
for three weeks. Histological examination of ovaries revealed
that the flufenoxuron induced massive degeneration
of ovarian follicles with much cellular debris in the antrum and
pyknotic granulosa cells. On
the other hand,
the testis of flufenoxuron-treated animals
exhibited marked decrease of the thickness of tunica albuginea
and atrophy of the seminiferous tubules. There was a marked
increase of desquamated spermatogenic cells within the lumina
of seminiferous tubules. Multinucleated
giant cells and vanishing of sperms were observed in the majority
of tubules of flufenoxuron-treated animals in comparison with
control. Epididymides sperm of experimental group exhibited the
presence of increased number of spermatic precursors as well as
varieties of sperm anomalies. The hepatic tissues toxicated
with the insecticide showed nuclear disintegration, massive breakdown
of hepatocytes and internal haemorrhage. The observed gonadal
dysfunction may be attributed to hepatic damage or decline
of gonadal hormone involved in either processes.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
45-64, 1998. EFFECTS
OF FLUFENOXURON-AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE ON GONAD
FUNCTION OF ALBINO RATS; by EL-Sayyad, H.I. and Karim, S.A.
http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Endocrine:
Thyroid (click
on for all fluorinated pesticides)
-- Abstract: Flufenoxuron
(Benzoylphenyl urea derivative) - antimoulting insecticide Ð is
recently used for controlling insect reproduction in cultivated
areas. The study determined the hazardous effects of the applied
dose-treatment during the critical period of rat embryonic development
and the induction of growth retardation. In the present work,
flufenoxuron was intragastrically administered by stomach intubation
to pregnant rats at concentration levels 0 & 20 mg/kg b.wt.
in saline solution every other day on gestation day 7 till parturition.
Experimental and control pregnant rats were sacrificed on days
13 & 16 of gestation and the foetuses were fixed in 10 percent
formol saline. Histological abnormalities
of thyroid, liver and kidneys of mothers
as well as of skeletal axial and appendicular regions of foetuses
were investigated. Foetuses
maternally treated with flufenoxuron exhibited delayed
differentiation of chondrification and ossification of axial and
appendicular regions. The observed defects in foetuses may be
attributed to the histological abnormalities of thyroid,
liver and kidneys
of maternal tissues as well as to the direct effect of
the parents as a result of the insecticide or its metabolites
on the affected structures during early morphogenesis and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
65-81, 1998. PATTERNS OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES
MATERNALLY TREATED WITH AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE
FLUFENOXURON; by Karim,
S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Kidney
(click on for all
fluorinated pesticides)
Abstract: Flufenoxuron
(Benzoylphenyl urea derivative) - antimoulting insecticide Ð is
recently used for controlling insect reproduction in cultivated
areas. The study determined the hazardous effects of the applied
dose-treatment during the critical period of rat embryonic development
and the induction of growth retardation. In the present work,
flufenoxuron was intragastrically administered by stomach intubation
to pregnant rats at concentration levels 0 & 20 mg/kg b.wt.
in saline solution every other day on gestation day 7 till parturition.
Experimental and control pregnant rats were sacrificed on days
13 & 16 of gestation and the foetuses were fixed in 10 percent
formol saline. Histological abnormalities
of thyroid, liver and kidneys of mothers as well as of skeletal
axial and appendicular regions of foetuses were investigated.
Foetuses
maternally treated with flufenoxuron exhibited delayed differentiation
of chondrification and ossification of axial and appendicular
regions. The observed defects in foetuses may be attributed to
the histological abnormalities of thyroid, liver and kidneys
of maternal tissues as well as to the direct effect of the parents
as a result of the insecticide or its metabolites on the affected
structures during early morphogenesis and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
65-81, 1998. PATTERNS
OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES MATERNALLY TREATED WITH
AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE FLUFENOXURON; by Karim,
S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Liver
(click
on for all fluorinated pesticides)
Carcinogenicity data.
Adequately conducted carcinogenicity studies in the rat and mouse
have been reported. Flufenoxuron was not carcinogenic in the rat.
The NOEL for non-neoplastic effects (body weight and relative
spleen weight changes) was 25 mg-1.kg-1.d-1. In the mouse there
was an increased incidence of haemangiosarcoma
in the liver (males) and spleen (females) at 50000
ppm, and an apparent increase in hepatocellular
carcinoma in males at all dose levels. The apparent increase
in liver tumors was due to an abnormally low control incidence,
and therefore flufenoxuron had no significant carcinogenic activity
in the mouse. No NEL was established in this study.
Ref:
December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
One of the mouse studies conducted at 7.5x limit dose had an
increased incidence of vascular tumors
in males and females. Total incidence of vascular tumors (combined
hemangiosarcomas of the liver and
spleen) among high-dose females (16%) was
significantly increased over controls (0%) and was slightly outside
the published data for historical controls (mean: 3.7%; range:
0%-14%). The overall increase in splenic hemangiosarcomas
in high-dose females (14%, p<0.01) and the increase in total
vascular tumors in the liver of high-dose males (20% vs 12% in
controls) occurred at doses that exceeded the limit dose. The
mouse oncogenicity study was repeated with the high dose exceeding
1.5x limit dose; and there was no increased incidence of any tumors.
Therefore, the increased incidences of vascular tumors are considered
high dose effects only.
Reference: August 15, 2006.
US EPA Human Health Risk Assessment for proposed tolerances on
apples, pears, grapes, organges and livestock commodities imported
into US. http://www.fluorideaction.org/pesticides/flufenoxuran.hra.epa.2006.pdf
Abstract: Flufenoxuron
(Benzoylphenyl urea derivative) - antimoulting insecticide Ð is
recently used for controlling insect reproduction in cultivated
areas. The study determined the hazardous effects of the applied
dose-treatment during the critical period of rat embryonic development
and the induction of growth retardation. In the present work,
flufenoxuron was intragastrically administered by stomach intubation
to pregnant rats at concentration levels 0 & 20 mg/kg b.wt.
in saline solution every other day on gestation day 7 till parturition.
Experimental and control pregnant rats were sacrificed on days
13 & 16 of gestation and the foetuses were fixed in 10 percent
formol saline. Histological abnormalities
of thyroid, liver and
kidneys of mothers as well as of skeletal axial and appendicular
regions of foetuses were investigated.
Foetuses
maternally treated
with flufenoxuron exhibited delayed differentiation
of chondrification and ossification of axial and appendicular
regions. The observed defects in foetuses
may be attributed to the histological abnormalities of thyroid,
liver and kidneys
of maternal tissues as well as to the direct effect of
the parents as a result of the insecticide or its metabolites
on the affected structures during early morphogenesis and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
65-81, 1998. PATTERNS OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES
MATERNALLY TREATED WITH AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE
FLUFENOXURON; by Karim,
S.A.
http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Spleen
(click
on for all fluorinated pesticides)
--
Repeat
dose mammalian studies.
Studies submitted
were 28 d rat, 90 d rat/mouse/dog, 12 and 24 month rat, and 12
month dog. In both the rat and dog there was evidence of regenerative
anaemia and increased methaemoglobin levels
with NELs of 5 mg.kg-1 (rat 28- and 90- day) and 2.5 mg.kg-1.d-1
(dog 12 month). In mice the NEL was 7.5 mg.kg-1.d-1 based on increased
plasma bilirubin. Plasma bilirubin was also increased in rats
(24 month). Evidence of regenerative anaemia (increased methaemoglobin,
decreased erythrocyte parameters, increased reticulocytes,
increased marrow cellularity and increased
spleen weight) was seen in most studies.
In addition at higher doses triglycerides were decreased and heart
weight increased in the rat.
-- Carcinogenicity. Rat. Groups of 50/sex/group Fischer 344 rats
were administered 0, 500, 5000 or 50000 ppm flllufenoxuron in
the diet for 24 months... In
males relative spleen weight was reduced in all treatment groups
(respectively 14, 29 and 32 %)...In
the females there was a significant increase in adrenal weight
in all treatment groups (respectively 9, 7 and 15%).
-- Carcinogenicity
data. Adequately conducted carcinogenicity studies in the rat
and mouse have been reported. Flufenoxuron was not carcinogenic
in the rat. The NOEL for non-neoplastic effects (body weight and
relative spleen weight changes) was 25 mg-1.kg-1.d-1. In the mouse
there was an increased incidence of haemangiosarcoma
in the liver (males) and
spleen (females) at 50000 ppm, and
an apparent increase in hepatocellular carcinoma
in males at all dose levels. The
apparent increase in liver tumors was due to an abnormally low
control incidence, and therefore flufenoxuron had no significant
carcinogenic activity in the mouse. No NEL was established in
this study.
Ref: December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Environmental
(click on for all fluorinated
pesticides)
Environmental
fate, behaviour and toxicology. Flufenoxuron does not readily
break down in the environment. The most rapid form of degradation
reported was aqueous photolysis, with a half-life (T 1/2)
of 11 days. However the solubility of flufenoxuron, in water
is extremely low (0.0040 mg.1-1 at pH7 and 25C). Flufenoxuron
readily adsorbs to organic matter. Consequently it is immobile
and also persists in soil (T
1/2 42 days for clay loam and >6 months for sandy loam)...
Flufenoxuron
is extremely toxic to Daphnia (48
hour EC50 0.065 ug.1-1). This is consistent with
the compound's mode of action against target pests, inhibiting
chitin synthesis/deposition. No fish toxicity could be established
due to flufenoxuron's low water solubility and the failure
to use an appropriate solvent vehicle. Similarly, no accurate
toxicity to freshwater algae was establishsed...Pond
overspray studies indicated that flufenoxuron could have
adverse efects on aquatic invertebrate populations, especially
crustacea zooplankton. Flufenoxuron may
also have the potential to bioaccumulate in fish and aquatic
gastropods although this has not been confirmed in
a laboratory bioaccumulation study. ... due to the acute
toxicity of flufenoxuron to Daphnia and the lack
of any suitable fish toxicity data, products containing
the compound are to be classified 'EXTREMELY DANGEROUS TO
FISH AND OTHER AQUATIC LIFE."
Ref: December
1995. Evaluation
of Flufenoxuron use as a public hygiene insecticide. UK:
Health and Safety Executive, Biocides & Pesticides Assessment
Unit. Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
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