Adverse Effects
Oxyfluorfen
CAS No. 42874-03-3

 
 

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 ØBR 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 ØBR 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 ØBR 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 Š 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 Š2;1.4,28.3,or 565.6 ppm for week 3 Š4;2.0,40.0,or 800.0 ppm for weeks 5 Š56 (800 ppm was actually 686 ppm for weeks 6-48);and 2.0,40.0,or 1600 ppm for weeks 57 Š104. 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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