Return
to Oxyfluorfen Index Page
Activity:
Herbicide
(diphenyl
ether)
Structure:
Adverse
Effects:
Anemia
Blood
Body Weight Decrease
Bone
Brain
Cancer: Possible Human Carcinogen -
LIVER
Endocrine: Adrenal
Endocrine: Pituitary
Endocrine: Thymus
Endocrine: Thyroid
Kidney
Liver
Spleen
Contamination Incidents
Environmental
•
As of October 8, 2003, this herbicide is permitted in
or on 91 food commodities
in the United States - click
here to see list.
•
Oxyfluorfen is used for broad spectrum pre- and post-emergent
control of annual broadleaf and grassy weeds in a variety
of tree fruit, nut, vine, and field crops. The
largest agricultural markets in terms of total pounds active
ingedient are wine grapes and
almonds. There are also non-agricultural
ornamental and forestry uses. Oxyfluorfen is also used for
weed control in landscapes, patios, driveways, and similar
areas in residential sites.
Ref: Oct 30, 2002 - RED
Fact Sheet. US EPA.
|
HAZARD
CHARACTERIZATION
Oxyfluorfen
is a diphenyl ether herbicide structurally related to lactofen
and acifluorfen.
The diphenyl ether herbicides act by inhibiting protoporphyrinogen
oxidase, which is the second-to-last enzyme in chlorophyll
biosynthesis.This enzyme is the second-to-last enzyme in
heme synthesis, as well (Birchfield and Casida, Pesticide
Biochemistry and Physiology,1997).
The
older toxicity studies with oxyfluorfen used technical material
of approximately 71% or 85% purity.
The newer toxicity studies used a technical material of
approximately 98% purity, which is
the basis for the current registrations of oxyfluorfen (97.4%
or 99% on labels for the 2 registrations). The newer
technical material has similar impurities to the older technical
material, but in reduced concentrations.
New
studies with the current 98% product were submitted: subchronic
toxicity in rats, developmental toxicity in rats and rabbits,
a battery of mutatagenicity studies, and a battery of acute
studies. Toxicity was less
severe for studies with the 98% product than for the 71%
product.
When
there were studies with both the new and old technical material,
consideration for an endpoint for risk assessment purposes
was given to the newer, 98% technical material which is
the basis of the current registrations. The
studies described in this document had doses adjusted for
per cent a.i. [active ingredient] and/or for analytical
concentrations determined in the diet...
Developmental
studies with the current 98% technical material found no
developmental toxicity in rats whereas an increase in late
resorptions occurred in the rabbit study (principally in
1 litter).
A developmental study in rats with
the older 71% technical material found increased early resorptions,
decreased fetal weight, and increased incidence of fetal
visceral and skeletal variations and malformations.
A developmental study in rabbits with
formulation manufactured from the older technical material
found increased early resorptions and decreased litter size.
A reproduction study with 71%technical material reported
decreased live pups per litter and decreased pup body weights.
The
current technical material was tested in 12 genetic toxicology
studies, all of which were negative, except for one Ames
assay which was positive. A second Ames assay with 96% material
was negative.
The older 71%technical material and a polar fraction were
tested in 8 genetic toxicology studies, of which 3 Ames
assays were positive, as was a mouse lymphoma study.
DATA
GAPS - There are datagaps for subchronic dermal and inhalation
exposure studies.The HIARC determined that the dermal and
inhalation studies were both classified unacceptable.
Ref: August 8,2001.
OXYFLUORFEN. Toxicology Chapter for RED. Submission No.S549936.
P.C.Code:111601. Tox.Chem.No.188AAA. US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Note
from FAN:
The older formulation produced severe bone defects. If
you know what the impurities were in the older formulation,
attributed to these defects, please contact us. Thanks,
EC.
|
Anemia
(click
on for all fluorinated pesticides)
Human
Health Assessment. Toxicity, Oxyfluorfen is of low acute oral,
dermal, and inhalation toxicity. The primary toxic effects are
alterations in blood parameters (anemia)
and in the liver. Oxyfluorfen is classified as a possible human
carcinogen based on combined hepatocellular adenomas/carcinomas
in the mouse carcinogenicity study. A cancer potency factor (Q1*)
was used to estimate human risk. The FQPA Safety Factor for protection
of infants and children was reduced to 1X for all population subgroups
as there was no increased susceptibility in animals due to pre-
or post-natal exposure to oxyfluorfen.
-- Toxicity was similar for subchronic and
chronic rat, mouse, and dog studies in both sexes. Oxyfluorfen
inhibits heme production, which
results in a variety of anemias. Heme is the part of the
hemoglobin molecule that contains iron and binds oxygen. In the
1997 subchronic rat study which used the current 98% a.i. formulation,
the red blood cell count was normal, but the red blood cell mass
was decreased due to the small size of the red blood cells, presumably
because of inhibition of the protoporphyrinogen oxidase enzyme.
The anemia was generally mild in other studies, with varying
hematologic abnormalities described in the rat, mouse, and dog
studies.
-- It should be noted that older
toxicity studies with oxyfluorfen used technical material of approximately
71% or 85% purity. The newer toxicity studies used a technical
material of approximately 98% purity, which is the basis for the
current registrations of oxyfluorfen. The newer technical material
has similar impurities to the older technical material, but in
reduced concentrations. Toxicity was less severe for studies with
the 98% product than for the 71% product; however,
one mammal developmental study with the 98% technical was submitted
in which animals experienced the most severe anemia and related
hematologic effects of any of the mammalian studies. When
there were studies with both the new and old technical material,
preference for an endpoint for risk assessment purposes was generally
given to the newer, 98% technical material (current registrations).
Ref: US EPA Reregistration Eligibility Decision (RED) OXYFLUORFEN.
EPA738-R-02-014 October 2002.
http://www.epa.gov/oppsrrd1/REDs/oxyfluorfen_red.pdf
Blood
(click
on for all fluorinated pesticides)
Human
Health Assessment. Toxicity, Oxyfluorfen is of low acute oral,
dermal, and inhalation toxicity. The primary toxic effects are
alterations in blood parameters (anemia)
and in the liver. Oxyfluorfen is classified as a possible human
carcinogen based on combined hepatocellular adenomas/carcinomas
in the mouse carcinogenicity study. A cancer potency factor (Q1*)
was used to estimate human risk. The FQPA Safety Factor for protection
of infants and children was reduced to 1X for all population subgroups
as there was no increased susceptibility in animals due to pre-
or post-natal exposure to oxyfluorfen.
-- Toxicity was similar for subchronic and
chronic rat, mouse, and dog studies in both sexes. Oxyfluorfen
inhibits heme production, which
results in a variety of anemias. Heme is the part of the
hemoglobin molecule that contains iron and binds oxygen. In the
1997 subchronic rat study which used the current 98% a.i. formulation,
the red blood cell count was normal, but the red
blood cell mass was decreased due to the small size of the red
blood cells, presumably because of inhibition of the protoporphyrinogen
oxidase enzyme. The anemia was generally mild in other
studies, with varying hematologic abnormalities described in the
rat, mouse, and dog studies.
-- It should be noted that older
toxicity studies with oxyfluorfen used technical material of approximately
71% or 85% purity. The newer toxicity studies used a technical
material of approximately 98% purity, which is the basis for the
current registrations of oxyfluorfen. The newer technical material
has similar impurities to the older technical material, but in
reduced concentrations. Toxicity was less severe for studies with
the 98% product than for the 71% product; however,
one mammal developmental study with the 98% technical was submitted
in which animals experienced the most severe anemia and related
hematologic effects of any of the mammalian studies. When
there were studies with both the new and old technical material,
preference for an endpoint for risk assessment purposes was generally
given to the newer, 98% technical material (current registrations).
Ref: US EPA Reregistration Eligibility Decision (RED) OXYFLUORFEN.
EPA738-R-02-014 October 2002.
http://www.epa.gov/oppsrrd1/REDs/oxyfluorfen_red.pdf
--
Phototoxicity. Oxyfluorfen may pose risks to animals not conveyed
by standard guideline toxicity studies because oxyfluorfenÕs mode
of action suggests it may be more toxic in the presence of light
(phototoxic). Oxyfluorfen, and other light-dependent peroxidizing
herbicides, act in plants by producing phototoxic compounds. Toxicity
studies with
oxyfluorfen and other similar herbicides suggest the same phototoxic
compounds may occur in animals as a result of herbicide exposure.
Because guideline toxicity studies are normally conducted under
relatively low, artificial light conditions, the effects of being
exposed simultaneously to oxyfluorfen and sunlight are not known.
To provide information on the magnitude of this effect, EFED is
currently requesting fish phototoxicity studies be conducted for
light-dependent peroxidizing herbicides (Appendix D).
-- Phototoxicity is a concern for terrestrial organisms as well.
Although oxyfluorfen inhibits heme synthesis, the anemia described
in all but one of the mammalian sub-chronic studies was generally
mild, with varying hematologic abnormalities. The anemia described
one subchronic study with rats (MRID 449331-01) was more severe.
The red blood cell count was normal, but the red blood cell mass
was decreased because of the small size of the red blood cells,
presumably because of inhibition of the protoporphyrinogen oxidase
enzyme. In wild mammal populations, these
hematologic effects have the potential to magnify since the lack
of natural sunlight in the laboratory does reduce the likelihood
of activating the phototoxic effects of oxyfluorfen.
-- US EPA identified the herbicides Acifluorfen,
Azafenidin, Carfentrazone-ethyl, Flumiclorac-penty, Flumioxazin,
Fluthiacet-methyl, Fomesafen, Lactofen, Oxadiargyl, Oxadiazon,
Oxyfluorfen, Sulfentrazone,
Thidiazimin as phototoxic
pesticides [10 out of the 13 pesticides
that EPA identified are organofluorines].
SEE http://www.fluoridealert.org/pesticides/PHOTOTOXICITY.PAGE.htm
Ref: December 11, 2001 - US EPA. Revised
Environmental Fate and Effects Division Preliminary Risk Assessment
for the Oxyfluorfen Reregistration Eligibility Decision Document
-- also at: http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxyefedchap.pdf
Body
Weight Decrease (click
on for all fluorinated pesticides)
-- In a developmental
toxicity study (MRID 44933102),oxyfluorfen (98.0%a.i.)in 1%(w/v)methylcellulose
was administered to pregnant New Zealand White rabbits (15/dose)at
dose levels of 0,10,30,or 90 mg/kg/day by gavage on gestation
days (GDs)6 through 19. Does were sacrificed on GD 29. Two premature
deaths occurred in the control group; one female was sacrificed
in extremis on GD 20 due to an ulceration on the ventral neck
area and a second female aborted on GD 21. At 90 mg/kg,one female
was found dead on GD 28,and two other females aborted on GD 27
or GD 29; all three females displayed reduced food consumption
and fecal output from mid-gestation resulting in decreased
body weight and general thin appearance prior to death.
No treatment-related changes in body weight were noted at any
dose level tested.
-- In a developmental toxicity study (MRID 00094052),19 presumed
pregnant New Zealand White rabbits per group were administered
oxyfluorfen (26.9%ai ;Lot No.CDP 0482- 1) by gavage at dose levels
of 0 (negative control),0 (vehicle control),10,30,or 90 mg/kg/day,
on gestation days (GD)6-18,inclusive. Doses were adjusted for
per cent active ingredient. The vehicle control consisted of all
ingredients of the 25 WP formulation without the active ingredient
administered at the equivalent of a 90 mg/kg/day dose of 25 WP.
Five premature deaths and 4 abortions occurred in the 90 mg/kg/day
treatment group. Treatment related clinical signs of toxicity
consisted of anorexia and red exudate
in the cage pan at 30 and 90 mg/kg/day and hematuria and decreased
motor activity at 90 mg/kg/day of oxyfluorfen. Ulceration, erosions,
and/or petechial hemorrhages were observed at necropsy in the
stomach mucosa of 3 high-dose does which died. Body
weight gain was decreased during GD 13-18 at 30 mg/kg/day
and throughout the dosing at 90 mg/kg/day; terminal body weights
were not significantly affected at any dose level. The maternal
NOAEL is 10 mg/kg/day. The maternal LOAEL is 30 mg/kg/day based
on clinical signs of toxicity and decreased
body weight gain during treatment. Decreased
litter size and an increase in early resorptions occurred
at 90 mg/kg/day. The small number of litters (5/11 pregnant does)evaluated
precluded adequate statistical evaluation of cesarean section
data. There were no treatment-related external, visceral,or skeletal
malformations or variations observed at any treatment level. There
was no evidence for delayed fetal growth at any treatment level
compared to controls. The developmental NOAEL is 30 mg/kg/day.
The developmental LOAEL is 90 mg/kg/day
based on decreased litter size and increased early resorptions.
This study is classified acceptable/guideline and satisfies the
guideline requirements for a developmental toxicity study in rabbits.
-- Reproductive Toxicity Adequacy of data base for Reproductive
Toxicity: There is an acceptable reproductive study with 71%technical
material.The data base for reproductive toxicity is complete and
no additional studies are required at this time. Parental toxicity
included mortality, body weight decrements,
and microscopic liver and kidney lesions. The kidney lesion was
microscopic mineralization, which was not observed in other rat
feeding studies. Reproductive/offspring effects included smaller
litter size and body weight decrements on day 0 of lactation.
-- 870.3800 Reproduction and Fertility Effects -Rat Goal Herbicide
(71.4%a.i.) was administered to groups
of 25 male and 25 female Crl:CD ¨BR rats in the diet at concentrations
of 0,100,400,or 1600 ppm of active ingredient for two generations
(MRID 42014901). One litter was produced in each generation. Premating
doses for the adult F0 males were 0,7.8,30.9,and 120.0 mg/kg/day
and for the F0 females were 0,8.5,32.8,and 131.2 mg/kg/day,respectively.
Premating doses for the adult F1 males were 0, 8.9,36.4,and 146.3
mg/kg/day and for the F1 females were 0,8.9,35.7,and 151.3 mg/kg/day,
respectively. F1 pups chosen to produce the F2 litters were weaned
onto the same diets as their parents. Animals were given test
or control diet for 10 (F0)or 14 (F1) weeks then mated within
the same dose group. One high-dose F1 male was sacrificed moribund
during week 9 of treatment;treatment- related chronic pyelonephritis
secondary to pelvic mineralization was described at necropsy;
this death was attributed to treatment. No treatment-related clinical
signs of toxicity were observed in parental animals of either
generation. Several intercurrent deaths of F0 females and F1 males
and females were considered incidental to treatment. Mean body
weights,body weight gains,and food consumption by the low-and
mid-dose males and females of both generations were comparable
to their respective controls. Body weights of the high-dose F0
males were slightly (n.s.)lower than the controls throughout premating
with overall body weight gains 92%of the control level .Absolute
body weights of the high-dose F0 females were significantly (p
#0.05)less than the controls during weeks 4-7, with overall body
weight gain 88% of controls. Food consumption by the high-dose
F0 males was significantly (89-92%of control;p #0.05)less than
the controls during weeks 0,2,and 4-8 of the premating interval.
Food consumption by the high-dose F0 females was 85-94%of the
control levels during the premating period with statistical significance
(p #0.05) reached during weeks 0-6 and 8.
High-dose F1 males and females had significantly (p #0.05) lower
body weights than the controls throughout the premating
interval (84-89%and 79-93%,respectively of the controls). Overall
body weight gains were 89% and 97%, respectively, of control levels.
Food consumption was significantly (p #0.05 )less than the controls
by the high-dose F1 males during treatment weeks 0-9 and 12 and
by high-dose F1 females during weeks 0-3,5,and 8. High-dose
F0 dams had significantly (p #0.05) lower body weights than the
controls on GD 21 and on lactation day 14. Body
weights of the high-dose F1 dams were significantly (p #0.05)
less than the controls throughout gestation and on lactation
days 0,7,and 14. Body weights of the high-dose
F1 pups were significantly (78-89%of controls;p #0.05) less than
the controls throughout lactation. High-dose
F2 pups had significantly (82-89%;p #0.05)lower body weights than
the controls on lactation days 0,14,and 21.Body weight
gains by the high-dose pups of both generations were 81-85% of
the control level for lactation days 0- 14 and were 73-77%of the
control level for lactation days 14-21.Because the most pronounced
effect on pup body weight gain was after they started to eat the
test diets, the lower pup body weights are
considered a systemic effect and not a lactational effect.
-- The NOAEL for parental toxicity is 400 ppm (males:30.9 mg/kg/day;females:32.8
mg/kg/day). The LOAEL for parental toxicity is 1600 ppm (males:120.0
mg/kg/day; females:131.2 mg/kg/day) based on mortality,
body weight decrements, and microscopic kidney and liver
lesions.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
-- Risks
to Terrestrial Organisms. The results of the risk assessment
do not suggest concern for acute risks to birds or mammals. Sub-chronic
and chronic risks to terrestrial birds and mammals present a serious
concern. These toxic effects may be manifested as reproductive,
developmental, and hemolytic consequences. The chronic LOC was
exceeded for birds in all crop scenarios and for mammals in scenarios
with the highest application rate (2 lbs ai/application). In the
bobwhite quail reproduction study, reduced chick weights were
observed, which would reduce fitness if experienced in the wild.
In the 2-generation rat reproduction study, toxic effects in adults
were mortality, decreased body weight, and liver and kidney histopathology,
and toxic effects observed in the pups were decreased body weight
and a decreased number of live pups/litter.
In three of the four developmental toxicity studies, increases
in spontaneous abortions, fetal resorptions, and fetal bone deformities
as well as decreases in litter size
were observed. Any of these effects would have an effect on the
fitness of individuals, and may have an effect on the overall
fitness of wild mammal populations exposed to oxyfluorfen.
Ref: December 11, 2001. Environmental Fate
and Effects DivisionÕs Preliminary Risk Assessment for the Reregistration
Eligibility Document for Oxyfluorfen
http://www.fluoridealert.org/pesticides/Oxyfluorfen.EnvEffects.2001.pdf
Bone
(click on for all fluorinated pesticides)
-- Renal
toxicity was most severe in the 2-generation reproduction
study in rats,in which pelvic mineralization
occurred.Other studies had indications of renal toxicity:increases
in organ weight and occasional histopathological observations.
-- In a developmental toxicity study (MRID 41806501),oxyfluorfen
(71.4%), was administered by gavage
to pregnant Crl:CD BR rats from gestation days 6-15.There were
27 rats/group.Doses were 0,18,183,or 848 mg/kg/day (adjusted for
analytical results).... There were 12 litters
in the mid-dose group with skeletal malformations which included
bent scapula,fused sternebrae,and bent bones in hindlimbs and
forelimbs compared to 0 litters in the control group with skeletal
malformations. The NOAEL for maternal toxicity is 18 mg/kg/day;the
maternal LOAEL is 183 mg/kg/day based on clinical signs (red vaginal
discharge,soft feces,scant feces). The NOAEL for developmental
toxicity is 18 mg/kg/day.The LOAEL for developmental toxicity
is 183 mg/kg/day based on increased early resorptions,decreased
fetal weight,and increased incidence of
fetal visceral and skeletal variations and malformations.
-- Goal Herbicide (71.4%a.i.) was
administered to groups of 25 male and 25 female Crl:CD ¨BR rats
in the diet at concentrations of 0,100,400,or 1600 ppm of active
ingredient for two generations (MRID 42014901).One litter was
produced in each generation.Premating doses for the adult F0 males
were 0,7.8,30.9,and 120.0 mg/kg/day and for the F0 females were
0,8.5,32.8,and 131.2 mg/kg/day,respectively.Premating doses for
the adult F1 males were 0, 8.9,36.4,and 146.3 mg/kg/day and for
the F1 females were 0,8.9,35.7,and 151.3 mg/kg/day, respectively.F1
pups chosen to produce the F2 litters were weaned onto the same
diets as their parents. Animals were given test or control diet
for 10 (F0) or 14 (F1)weeks then mated within the same dose group.
One high-dose F1 male was sacrificed moribund during week 9 of
treatment;treatment- related chronic pyelonephritis secondary
to pelvic mineralization was described
at necropsy;this death was attributed to treatment.No treatment-related
clinical signs of toxicity were observed in parental animals of
either generation.Several intercurrent deaths of F0 females and
F1 males and females were considered incidental to treatment.
Study which would not meet current guideline requirements.The
study was,however,adequate to determine a NOAEL value.
... 90-Day Oral Toxicity -Mouse In a 3-month dietary toxicity
study (MRID 00117602),Goal (72.5%
) was administered to Charles River CD-1 mice (15/sex/group)at
dietary concentrations of 0,200,800,or 3200 ppm for 13 weeks.Doses
were equivalent to 0,32.0,134.5,or 490.5 mg/kg/day in males and
0,44.4, 166.6,or 520.9 mg/kg/day in females... Bone
marrow hyperplasia was present in low-dose males and mid-and high-dose
males and females.Vacuolation of the adrenal cortex was
present in high-dose females.Thymic atrophy occurred in high-dose
males and females.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
-- Risks
to Terrestrial Organisms. The results of the risk assessment
do not suggest concern for acute risks to birds or mammals. Sub-chronic
and chronic risks to terrestrial birds and mammals present a serious
concern. These toxic effects may be manifested as reproductive,
developmental, and hemolytic consequences. The chronic LOC was
exceeded for birds in all crop scenarios and for mammals in scenarios
with the highest application rate (2 lbs ai/application). In the
bobwhite quail reproduction study, reduced chick weights were
observed, which would reduce fitness if experienced in the wild.
In the 2-generation rat reproduction study, toxic effects in adults
were mortality, decreased body weight, and liver and kidney histopathology,
and toxic effects observed in the pups were decreased body weight
and a decreased number of live pups/litter. In
three of the four developmental toxicity studies, increases
in spontaneous abortions, fetal resorptions, and fetal
bone deformities as well as decreases
in litter size were observed. Any of these effects would
have an effect on the fitness of individuals, and may have an
effect on the overall fitness of wild mammal populations exposed
to oxyfluorfen.
Ref: December 11, 2001. Environmental Fate
and Effects DivisionÕs Preliminary Risk Assessment for the Reregistration
Eligibility Document for Oxyfluorfen
http://www.fluoridealert.org/pesticides/Oxyfluorfen.EnvEffects.2001.pdf
Brain
(click on for all fluorinated pesticides)
Absolute and relative
thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the adrenal cortex
was present in high-dose females. Thymic atrophy occurred in high-dose
males and females.... Fine vacuolation of adrenal glands (slight)and
cortical atrophy of the thymus (slight) were increased in high-dose
males... Absolute and/or relative organ weights in the high-dose
groups that showed statistically significant
changes relative to control weights (thyroid gland in both
sexes and kidney in females at 12 months and brain,
pituitary, and spleen in females sacrificed at 24 months) had
no microscopic correlates and are not considered toxicologically
significant.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Cancer:
Possible Human Carcinogen - LIVER (click
on for all fluorinated pesticides)
Group
C -- Possible Human Carcinogen. Liver (adenomas,
carcinomas 7 combined adenomas and/or carcinomas); CD-1 mice (M).
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
Group C--Possible Human Carcinogen.
Reviewed 9/ 29/ 89.
Ref: List of Chemicals Evaluated
for Carcinogenic Potential. Science Information Management Branch,
Health Effects Division, Office of Pesticide Programs, U. S. Environmental
Protection Agency. March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
There are eight diphenyl ethers that are structurally similar
to diclofop-methyl. Of the chemicals, fomesafen
sodium, haloxyfop-methyl (Verdict), oxyfluorfen,
acifluorfen sodium, nitrofen, and
lactofen were reviewed in the initial CPRC report. All of these
chemicals induced liver adenomas and carcinomas
in rats and/or mice. Except for haloxyfop-methyl, all
of the other chemicals produced positive results in at least one
of the mutagenicity assays...
May
24, 2000 - Cancer
Assessment Document. Evaluation of the
Carcinogenic Potential of Diclofop-Methyl. (Second Review). Final
Report. Cancer Assessment Review Committee, Health Effects Division,
US EPA Office of Pesticide Programs.
Note:
Except for Nitrofen, all the pesticides cited above are fluorinated.
Oxyfluorfen is classified
as a possible human carcinogen based on
combined hepatocellular adenomas/carcinomas in the mouse carcinogenicity
study... Dow AgroSciences has committed to undertake mechanistic
studies to determine whether or not oxyfluorfen acts via a mechanism
involving peroxisome proliferation. If oxyfluorfen is shown to
be a peroxisome proliferator, an MOE approach (indicative of a
non-linear dose response), rather than a Q* approach would be
more appropriate to quantify cancer risks. If oxyfluorfen is determined
to be a peroxisome proliferator, EPA will re-evaluate cancer risks
and risk mitigation decisions for oxyfluorfen... The cancer dietary
risk from food alone is 3.8 x 10 -7 for the general U.S. population,
and is not a concern for the Agency (< 1 x 10 -6 ). The drinking
water risk estimates for chronic (non-cancer) exposures are below
EPAÕs level of concern for ground or surface waters. However,
cancer risk estimates from modeling for surface water sources
of drinking water indicate a concern based on conservative assumptions
for model inputs. Residential risks are below EPAÕs level of concern,
however, there is a concern for aggregate risk when considering
exposures from food, drinking water, and residential uses. There
are cancer risk concerns for workers who mix, load, and apply
oxyfluorfen to agricultural sites, as well as workers who re-enter
treated sites.
Ref: US EPA Reregistration Eligibility Decision
(RED) OXYFLUORFEN. EPA738-R-02-014 October 2002.
http://www.epa.gov/oppsrrd1/REDs/oxyfluorfen_red.pdf
Subchronic and chronic
toxicity. Adverse effects on the liver marked the LOEL in all
three chronic toxicity studies with NOELs of 2.5, 2.0, and 0.3
mg/kg/day seen
in the dog, rat, and mouse studies respectively. A statistically
significant positive dose-related trend for liver adenomas and
carcinomas was observed in the chronic mouse study and
oxyfluorfen is classified as a Group C chemical
by EPA. A reference dose of 0.003 mg/kg/day and a Q1*
of 0.128 (mg/kg/ day) -1 has been set by the Agency.
Ref: Federal Register: January 9, 1998 [Page
1456-1464]. Notice of Filing of Pesticide Petitions. http://www.fluoridealert.org/pesticides/Oxyfluorfen.FR.Jan.9.1998.htm
Endocrine:
Adrenal (click
on for all fluorinated pesticides)
-- Absolute and relative
thymus weights were decreased in mid-dose males (-14%/-10%) and
high-dose males (-32%/- 18%)...Vacuolation of the
adrenal cortex was present in high-dose
females. Thymic atrophy occurred in high-dose
males and females.... Fine vacuolation of adrenal glands (slight)and
cortical atrophy of the thymus (slight)
were increased in high-dose males...
-- In a second
subchronic dietary toxicity study (MRID 00117601),15 Long Evans
rats/group received oxyfluorfen (72.5%)in the diet for 13 weeks.Dietary
concentrations of 0, 400,800 or 1600 ppm in weeks 1 and 2 were
increased to 0,560,1120,or 2240 ppm in weeks 3 and 4 and were
increased to 0,800,1600,or 3200 ppm for weeks 5-13.Dietary concentrations
were reportedly increased to maintain a constant compound intake
and were adjusted for per cent active ingredient. Microscopic
lesions of the liver included diffuse hepatocellular
hypertrophy and eosinophilia in all male treatment groups
and in high- dose females; hepatic necrosis was seen in 3 high-dose
males. Hypertrophy of cells in the zona
glomerulosa of the adrenals was seen in all male and female
treatment groups...
Ref: August 8, 2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Endocrine-
Pituitary (click
on for all fluorinated pesticides)
...
Absolute and/or relative organ weights in the high-dose groups
that showed statistically significant changes
relative to control weights (thyroid gland in both sexes
and kidney in females at 12 months and brain, pituitary,
and spleen in females sacrificed at 24 months) had no microscopic
correlates and are not considered toxicologically significant.
Ref:
August 8,2001. OXYFLUORFEN. Toxicology Chapter for RED. Submission
No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA. US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Endocrine:
Thymus (click
on for all fluorinated pesticides)
Absolute and relative
thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the
adrenal cortex was present in high-dose
females. Thymic atrophy
occurred in high-dose males and females.... Fine vacuolation
of adrenal glands (slight)and cortical
atrophy of the thymus (slight)
were increased in high-dose males...
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Endocrine:
Thyroid (click
on for all fluorinated pesticides)
Absolute and relative
thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the
adrenal cortex was present in high-dose females. Thymic atrophy
occurred in high-dose males and females.... Fine vacuolation of
adrenal glands (slight)and cortical atrophy of the thymus (slight)
were increased in high-dose males... Absolute and/or relative
organ weights in the high-dose groups that showed statistically
significant changes relative to
control weights (thyroid gland in
both sexes and kidney in females at 12 months and brain, pituitary,
and spleen in females sacrificed at 24 months) had no microscopic
correlates and are not considered toxicologically significant.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Kidney
(click on for all fluorinated pesticides)
--
Renal toxicity was most severe in the 2-generation reproduction
study in rats,in
which pelvic mineralization occurred.Other studies had indications
of renal toxicity:increases in organ weight and occasional histopathological
observations.
-- In a third subchronic dietary toxicity study (MRID 00117603),oxyfluorfen
(72%) was administered to 10 CRJ-CDF rats/group at dietary concentrations
of 0,200,1000,or 5000 ppm for 13 weeks.Doses corresponded to
0,14,71,or 361 mg/kg/day in males and 0,18,75,or 396 mg/kg/day
in females... At necropsy,dark-brown livers and/or kidneys
in mid-and high-dose males and females were noted... Microscopic
kidney lesions in high-dose males and mid-and high-dose females
included calcium deposition,vacuolar degeneration of distal tubules,hypertrophy/hyperplasia
of transitional epithelium,and yellow pigment in renal tubular
epithelium.The microscopic liver and kidney lesions were
generally classified slight in mid-dose animals and slight
to moderate in high-dose animals... The NOAEL is 200 ppm
(males:14 mg/kg/day; females:18 mg/kg/day).The
LOAEL is 1000 ppm (males:71 mg/kg/day);females:75 mg/kg/day)based
upon brown livers and kidneys in
males and females, increased relative liver weights in males,
decreased absolute and relative thymus weights in males, and microscopic
liver and kidney lesions in males
and females (classified slight).
-- Reproductive Toxicity. Adequacy of data base for Reproductive
Toxicity: There is an acceptable reproductive study with 71%technical
material. The data base for reproductive toxicity is complete
and no additional studies are required at this time. Parental
toxicity included mortality, body weight decrements, and microscopic
liver and kidney lesions. The kidney
lesion was microscopic mineralization, which was not observed
in other rat feeding studies.
-- Reproduction and Fertility Effects -Rat Goal Herbicide (71.4%a.i.)was
administered to groups of 25 male and 25 female Crl:CD ¨BR rats
in the diet at concentrations of 0,100,400,or
1600 ppm of active ingredient for two generations (MRID
42014901).One litter was produced in each generation. Premating
doses for the adult F0 males were 0,7.8,30.9,and 120.0 mg/kg/day
and for the F0 females were 0,8.5,32.8,and 131.2 mg/kg/day,respectively.
Premating doses for the adult F1 males were 0, 8.9,36.4,and 146.3
mg/kg/day and for the F1 females were 0,8.9,35.7,and 151.3 mg/kg/day,
respectively.F1 pups chosen to produce the F2 litters were weaned
onto the same diets as their parents .Animals were given test
or control diet for 10 (F0)or 14 (F1)weeks then mated within the
same dose group... Gritty material was observed in the renal
pelvis of 2/25 high-dose F0 males and in 1/25 and 5/25 mid- and
high-dose F1 males, respectively. This was not observed
in any control or low-dose males. Dose-related increases in the
incidence rates of liver and kidney lesions
were observed in males and females of both generations...
The incidence rates of mineralization of
the renal pelvis were 0/25,1/25,3/25,7/25 (p #0.01)in F0
males;4/25,2/25,3/25,7/25 in F0 females; 1/25,1/25,5/25,11/25
(p #0.01)in F1 males; and 3/25,2/25,8/25,13/25 (p #0.01)in F1
females, respectively. In the kidney of high-dose F1 animals,
there were increased incidences of dilatation
of the collecting ducts (0/25,0/25,2/25,11/25 [p #0.01
] males and 1//25,0/25,0/25, 9/25 [p #0.01 ] females)) and hyperplasia
of the pelvic/papillary epithelium (4/25,5/25,6/25, 11/25 [p #0.05
] males and 1//25,3/25,2/25,8/25 [p #0.05 ] females)). The NOAEL
for parental toxicity is 400 ppm (males:30.9 mg/kg/day;females:32.8
mg/kg/day).The LOAEL for parental toxicity is 1600 ppm (males:120.0
mg/kg/day; females:131.2 mg/kg/day) based on mortality, body weight
decrements, and microscopic kidney and
liver lesions.
-- 870.4100a (870.4300)Chronic Toxicity
Ð Rat In a chronic toxicity/carcinogenicity study (MRID
00083445,00135072,92136061),RH- 2915 technical (82.2%and 85.7%a.i.)was
administered in the diet to groups of 50 male and 50 female Long
Evans rats at concentrations of 1.0,20.0,or 400.0 ppm for weeks
1 Ð2;1.4,28.3,or 565.6 ppm for week 3 Ð4;2.0,40.0,or 800.0 ppm
for weeks 5 Ð56 (800 ppm was actually 686 ppm for weeks 6-48);and
2.0,40.0,or 1600 ppm for weeks 57 Ð104. Based on %active ingredient,doses
in males were approximately equivalent to 0,0.10,1.94,and 56.96
mg/kg/day, and in females were 0,0.12,2.43,and 72.57 mg/kg/day,in
the respective dose groups. The mortality rate at study termination
was 54,48,52,and 40%for male and 22,40,26, and 20%for females
administered the control ,low,mid,and high doses,respectively;no
treatment-related effect was observed... Absolute and/or relative
organ weights in the high-dose groups that showed
statistically significant changes relative to control weights
(thyroid gland in both sexes and kidney
in females at 12 months and brain, pituitary, and spleen
in females sacrificed at 24 months) had no microscopic correlates
and are not considered toxicologically significant. Gross lesions
were not observed in animals sacrificed at 12 or 24 months...
The changes that were statistically increased
in the 24-month group were polypoid hyperplasia of the papillary
epithelium in the kidney of high dose females (20/40 vs
13/45 controls,p<0.05) and cortical cysts
in the kidney of mid-and high-dose males (6/25 (p<0.01)
and 4/40 (p<0.05)vs 0/45 for controls). The lack of a dose-response
relationship for the changes in males and the high background
for the finding in females suggest that the microscopic findings
were not treatment related.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Liver
(click on for all fluorinated pesticides)
Group
C -- Possible Human Carcinogen. Liver (adenomas,
carcinomas 7 combined adenomas and/or carcinomas); CD-1 mice (M).
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
Oxyfluorfen is a phenoxyphenyl-type
herbicide. Several chronic oral toxicity studies suggest that
oxyfluorfen may be hepatotoxic. Hepatic effects (e.g. increased
absolute liver weight, necrosis, regeneration, and hyperplastic
nodules) were observed in mice fed diets containing greater
than 3 mg/kg/day oxyfluorfen for 20 months (the NOEL was 0.3 mg/kg/day).
Based on these findings, an oral RfD value of 0.003 mg/kg/ day
was derived. This study was supported by other chronic feeding
studies that demonstrated increases in liver
weight, alkaline phosphatase activity, and bile pigmented hepatocytes
(the LOEL was 15 mg/kg/day; the NOEL was 2.5 mg/kg/day) in dogs,
and minimal hypertrophy of centrilobular hepatocytes (the LOEL
was 40 mg/kg/day; the NOEL was 2 mg/kg/day) in rats. EPA believes
that there is sufficient evidence for listing oxyfluorfen on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
hepatotoxic effects of this chemical.
Ref: USEPA/OPPT. Support Document for the
Health and Ecological Toxicity Review of TRI Expansion Chemicals.
U. S. Environmental Protection Agency, Washington, DC (1993).
As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
Microscopic changes
observed at 12 months included binucleate hepatocytes (6/10),
central lobular hepatocyte hypertrophy
(7/10), and enlarged hepatocyte nuclei (6/10) in high dose females
compared to 0/5 for controls. Similar changes were not seen at
the terminal sacrifice, despite the fact that the animals received
higher doses during the last 12 months of the study. Therefore
the findings at 12 months may be an adaptive effect... The microscopic
liver and kidney lesions were generally
classified slight in mid-dose animals and slight to moderate in
high-dose animals... The only treatment-related histopathological
lesion in the liver was slight to
moderate bile
pigmented hepatocytes in both sexes after 104 weeks (n.s.) and
hepatocellular vacuolization was seen in high-dose females.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Spleen
(click on for
all fluorinated pesticides)
Absolute
and relative thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the adrenal cortex
was present in high-dose females. Thymic atrophy occurred in high-dose
males and females.... Fine vacuolation of adrenal glands (slight)and
cortical atrophy of the thymus (slight) were increased in high-dose
males... Absolute and/or relative organ weights in the high-dose
groups that showed statistically significant changes relative
to control weights (thyroid gland in both sexes and kidney in
females at 12 months and brain, pituitary, and spleen
in females sacrificed
at 24 months) had no microscopic correlates and are not considered
toxicologically significant.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Contamination
incidents (click on
for all fluorinated pesticides)
--
Reported Aquatic Incidents.
There is one reported incident in the EIIS database with
an aquatic organism effect. On 22
August 2000, Fifteen Mile Creek
near the Dalles Dam in Oregon was the site of an
oxyfluorfen spill (Incident# I010844-01,
I010949-001). A truck carrying formulated oxyfluorfen
(Goal 2XL) crashed on a bridge spilling
approximately 20,000 pounds (2600 gallons) of herbicide
into the creek yards from where the creek enters the Columbia
River. Two weeks after the spill, samples of filtered
(8-micron filter) and unfiltered water near the spill site
contained an average of 32 µg/L and 340 µg/L, respectively.
This spill was estimated to cause
a 35% decrease in the numbers of adult chinook salmon and
a 26% decrease in the numbers of steelhead passing over
the Dalles Dam the day immediately following the spill,
relative to the day prior to the spill. The spill was also
reported to kill thousands of young lampreys. An
extensive cleanup operation (removal of water and sediment)
removed a majority of the chemical, and the estimated
quantity of oxyfluorfen not recovered was less than 1000
gallons... As a result of the Goal 2XL spill in the
Columbia River Basin (Fifteen Mile Creek) on 22 August 2000
(Incident# I010844- 01, I010949-001 and Appendix C), a focused
sediment and water sampling was conducted. Water and sediment
samples were collected as background measures from areas
thought not to be impacted by the spill. The few background
water samples did not have detectable amounts of oxyfluorfen,
but 2 of the 35 background sediment
samples did have detectible amounts of oxyfluorfen (the
highest was 541 ppb). It is
important to note that these background samples were collected
seven months after most oxyfluorfen applications would have
occurred (oxyfluorfen is primarily applied during the dormant
winter season). As a result of the Goal spill in
Fifteen Mile Creek near the Columbia River, fish samples
in the Columbia were collected for oxyfluorfen measurements.
The fish were collected from fishermen several miles up
and downstream of the spill site during a three month period
after the spill. Of 108 fin fish tissue
samples collected from the Columbia River, 57 had quantifiable
levels of oxyfluorfen, 20 had trace levels, 31 had
undetectable levels. The average quantified
fish tissue concentration was 48 ppb (range of 10 to 370
ppb). Given the containment efforts at the spill
site and the enormous dilution from Fifteen Mile Creek into
the Columbia River, it is likely that residues measured
in many of these fish were a result of background levels
of oxyfluorfen from registered uses. Some
of the fish collected upstream would not be expected to
have contacted contaminated water from the spill site, yet
they still had significant levels of oxyfluorfen in their
tissues.
Ref:
Revised Environmental Fate and Effects Division Preliminary
Risk Assessment for the Oxyfluorfen Reregistration Eligibility
Decision Document. Date:11 December 2001.
http://www.fluorideaction.org/pesticides/oxyfluorfen.enveffects.2001.pdf
--
Reported Incidents. There
are several reported incidents in the Environmental Incident
Information System (EIIS) database with a terrestrial organism
effect. One incident occurred on 7
March 1996, when a pest control operator in Madera
County, California, applied Roundup (glyphosate)
and Goal (oxyfluorfen) to an unspecified site (Incident#
I003377-003). These herbicides drifted
to 40 acres of plums and 90-100 acres of almonds with total
damage estimated at $520,000 to $760,000. Either
of these compounds may have contributed to the damage of
these crops. A similar incident (#I005625-012)
occurred in May 1996 in Desha County,
Arkansas. A grower stated that aerial
drift of Roundup Ultra and Goal damaged 160 acres of rice,
and 80 acres had to be replanted. Either of these
compounds may have contributed to the damage of these crops.
Another aerial drift incident (#I005625-016)
occurred in March 1996 in Kern County,
California. A grower stated that aerial
drift of Roundup Ultra and Goal damaged 10 acres of oranges.
Investigation by Monsanto representatives revealed that
adequate buffer zones had not been employed. Either of these
compounds may have contributed to the damage of these crops.
One incident (# I001734-001)
involved repeated applications of Goal to
8 acres of fir trees in Idaho. Trees exhibited one
or more of the following symptoms: death, loss of turgidity,
some woody tissue above base of tree was enlarged with necrosis
and darkening of internal tissue, and stem brittleness and
fissures. There are 2 reported incidents
(#I003268-050 and #I010800-098) of damage attributed
to a home use product (Ortho GroundClear Triox).
Both incidents involved damage and
death to small numbers of ornamentals and juniper trees.
The damage may have been caused by oxyfluorfen and/or
the other active ingredient in Triox, isopropylamine salt.
Ref: Revised Environmental Fate and
Effects Division Preliminary Risk Assessment for the Oxyfluorfen
Reregistration Eligibility Decision Document. Date:11 December
2001.
http://www.fluorideaction.org/pesticides/oxyfluorfen.enveffects.2001.pdf
|
Environmental
(click
on for all fluorinated pesticides)
Highly
toxic to fish.
Ref: PAN Summary of Acute Toxicity
for Organism Group
http://www.pesticideinfo.org/PCW/Detail_Chemical.jsp?Rec_Id=PC33601
The
estimated chronic MATC values for fish
and daphnids are 9 ppb and 20 ppb oxyfluorfen, respectively.
The estimated log Kow is 6.1. EPA believes that there is
sufficient evidence for listing oxyfluorfen on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data and potential for bioaccumulation
for this chemical.
Ref: USEPA/OPPT. Support
Document for the Health and Ecological Toxicity Review of
TRI Expansion Chemicals. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372.
Addition of Certain Chemicals; Toxic Chemical Release Reporting;
Community Right-to-Know; Proposed Rule.
Also see EPA on enviro ! J Environ Sci Health Part A Tox
Hazard Subst Environ Eng 2002;37(4):521-7
--
Phototoxicity. Oxyfluorfen may pose risks to animals not
conveyed by standard guideline toxicity studies because
oxyfluorfen's mode of action suggests it may be more toxic
in the presence of light (phototoxic). Oxyfluorfen,
and other light-dependent peroxidizing herbicides, act in
plants by producing phototoxic compounds. Toxicity studies
with oxyfluorfen and other similar herbicides suggest the
same phototoxic compounds may occur in animals as a result
of herbicide exposure. Because guideline toxicity studies
are normally conducted under relatively low, artificial
light conditions, the effects of being exposed simultaneously
to oxyfluorfen and sunlight are not known. To provide information
on the magnitude of this effect, EFED is currently requesting
fish phototoxicity studies be conducted for light-dependent
peroxidizing herbicides (Appendix D).
-- Phototoxicity is a concern for
terrestrial organisms as well. Although oxyfluorfen
inhibits heme synthesis, the anemia described in all but
one of the mammalian sub-chronic studies was generally mild,
with varying hematologic abnormalities. The anemia described
one subchronic study with rats (MRID 449331-01) was more
severe. The red blood cell count was normal, but the red
blood cell mass was decreased because of the small size
of the red blood cells, presumably because of inhibition
of the protoporphyrinogen oxidase enzyme. In wild mammal
populations, these hematologic effects
have the potential to magnify since the lack of natural
sunlight in the laboratory does reduce the likelihood of
activating the phototoxic effects of oxyfluorfen.
-- US EPA identified the herbicides Acifluorfen,
Azafenidin, Carfentrazone-ethyl, Flumiclorac-penty, Flumioxazin,
Fluthiacet-methyl, Fomesafen, Lactofen, Oxadiargyl, Oxadiazon,
Oxyfluorfen, Sulfentrazone,
Thidiazimin as phototoxic
pesticides [10 out of the 13
pesticides that EPA identified are organofluorines].
SEE http://www.fluoridealert.org/pesticides/PHOTOTOXICITY.PAGE.htm
Ref: December 11, 2001 - US EPA. Revised
Environmental Fate and Effects Division Preliminary Risk
Assessment for the Oxyfluorfen Reregistration Eligibility
Decision Document -- also at: http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxyefedchap.pdf
Phototoxicity:
Oxyfluorfen and other herbicidal inhibitors of protoporphyrinogen
oxidase are being evaluated by EFED and ORD for
possible phototoxicity based on reports of porphyrin accumulation
in test animals.Since the biosynthesis of heme is
inhibited by oxyfluorfen, there is
the possibility that porphyrin precursors of heme could
accumulate in the skin and be activated by light and cause
toxicity. There have so far been no indications that
oxyfluorfen does cause phototoxicity.
Ref: August 8,2001. OXYFLUORFEN.
Toxicology Chapter for RED. Submission No.S549936. P.C.Code:111601.
Tox.Chem.No.188AAA. US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
-- Risks to Terrestrial Organisms. The results of the risk
assessment do not suggest concern for acute risks to birds
or mammals. Sub-chronic and chronic
risks to terrestrial birds and mammals present a serious
concern. These toxic effects may be manifested as reproductive,
developmental, and hemolytic consequences. The
chronic LOC was exceeded for birds in all crop scenarios
and for mammals in scenarios with the highest application
rate (2 lbs ai/application). In the bobwhite quail reproduction
study, reduced chick weights were
observed, which would reduce fitness if experienced in the
wild. In the 2-generation rat reproduction study,
toxic effects in adults were mortality, decreased body weight,
and liver and kidney histopathology, and toxic effects observed
in the pups were decreased body weight and a decreased number
of live pups/litter. In three of the four developmental
toxicity studies, increases in spontaneous abortions, fetal
resorptions, and fetal bone deformities
as well as decreases in litter size were observed. Any of
these effects would have an effect on the fitness of individuals,
and may have an effect on the overall fitness of wild mammal
populations exposed to oxyfluorfen.
Ref: December 11, 2001. Environmental
Fate and Effects DivisionÕs Preliminary Risk Assessment
for the Reregistration Eligibility Document for Oxyfluorfen
http://www.fluoridealert.org/pesticides/Oxyfluorfen.EnvEffects.2001.pdf
Abstract:
The alterations of the AChE activity in the brains of two
fresh water fishes; Oreochromis niloticus and Gambusia affinis
were measured after exposure to acute, sub-acute and chronic
concentrations from the widely used herbicide; oxyfluorfen.
Bioassays were conducted under controlled laboratory conditions.
The used concentrations were acute: LC50 for 6 days, sub-acute
1/3 LC50 for 15 days and chronic 1/10 LC50 for 30 days.
The obtained results showed marked
inhibitory effects of the herbicide on the activity of AChE
in both fishes. However, these effects were more
pronounced in O. niloticus where the decline in the enzyme
activity ranged from 19.7 to 81.28% while in case of G.
affinis it ranged from 5.7 to 36.7%. These findings demonstrate
that G. affinis is most tolerant to oxyfluorfen toxicity
compared with O. niloticus.
Ref: Toxicological
effects of the herbicide oxyfluorfen on acetylcholinesterase
in two fish species: Oreochromis niloticus and Gambusia
affinis; by HM Hassanein. J Environ Sci Health Part
A Tox Hazard Subst Environ Eng 2002;37(4):521-7
Abstract:
This paper deals with the expression of the biomarker hsp70
in the liver and kidney of the freshwater fish Oreochromis
niloticus following exposure to the herbicide oxyfluorfen
(Goal). Fishes were exposed to three concentrations, the
96-h LC50 (3 mg/L), the 96-h (1/2)LC50 (1.5 mg/L), and the
96-h (1/4)LC50 (0.75 mg/L) of oxyfluorfen for 6, 15, and
24 days, respectively, and samples were taken at three different
time periods for each concentration. The livers responded
to the herbicide by an induction of the expression of both
the constitutive (hsp75; Mr 75 kDa) and the inducible (hsp73;
Mr 73 kDa) hsp70 proteins. In kidney, the herbicide induced
a time-dependent increase in the expression of the constitutive
hsp70 (hsp75) as well, but the inducible hsp70 (hsp73) required
much longer incubation periods to reach maximal levels (15
and 24 days). Our results suggest
that expression of hsp70 in fish is a sensitive indicator
of cellular responses to herbicide exposure in the aquatic
environment.
Ref:
Induction of hsp70 by the herbicide oxyfluorfen (Goal) in
the Egyptian Nile fish, Oreochromis niloticus; by HM
Hassanein et al. Arch Environ Contam Toxicol 1999 Jul;37(1):78-84.
-- Endangered
Species Assessment. The preliminary
risk assessment for endangered species indicates that oxyfluorfen
exceeds the endangered species LOCs for the following combinations
of analyzed uses and species:
• terrestrial plants for all uses;
•
avian chronic for non-bearing citrus and all applications
with rates greater than 0.5 lb ai/acre/application (such
as rights-of-way, apples, walnuts and grapes) based on both
maximum and mean residue levels;
• mammalian chronic for non-bearing citrus, and applications
with rates of 2 lbs ai/acre (such as rights-of-way, apples,
walnuts and grapes) based on maximum residues;
• freshwater fish for non-bearing citrus and grapes
(of those scenarios modeled); and
• freshwater invertebrates for non-bearing citrus,
apples, grapes and cotton (of those scenarios modeled).
Based on the available data, oxyfluorfen acute toxicity,
RQs, and LOC exceedences for estuarine/marine fish were
assumed to be similar to that of freshwater fish. Although
the endangered species LOC for estuarine invertebrates has
been exceeded, there are no federally listed species in
this group. Risks to endangered aquatic vascular plants
cannot be assessed at this time since no acceptable toxicity
test for Lemna gibba has been submitted to the Agency. Further
analysis regarding the overlap of individual species and
their behavior with each use site is required prior to determining
the likelihood of potential impact to listed species. The
Agency had a consultation in 1985 (amended in 1986) with
the US Fish and Wildlife Service (FWS or the Service) on
oxyfluorfen (Goal 1.6E and Goal 2E) regarding its use on
noncrop areas including rights-of ways, fence rows, roadsides,
levee banks. The Service found jeopardy
to 76 species of endangered plants, 54 species of endangered
fish, 23 species of endangered mussels (clams), two species
of snails, eleven species of endangered insects, four endangered
amphibians and one endangered bird (piping plover). The
Service proposed a Reasonable and Prudent Alternatives (RPA)
to avoid jeopardy to these species. The RPA prohibited the
application of Goal within a quarter mile of the habitat
of the listed plants and terrestrial invertebrates and within
a quarter mile of the streams or bodies of water where the
aquatic species occur.
Ref:
December 11, 2001 - US EPA. Revised
Environmental Fate and Effects Division Preliminary Risk
Assessment for the Oxyfluorfen Reregistration Eligibility
Decision Document
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