CAS No. 42874-03-3

For more abstracts search PubMed or Toxnet

Return to
Index Page
Adverse Effects

ACTIVITY: Herbicide (Diphenyl ether)

CAS Name: 2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene


Reports available from
The National Technical Information Service

Order from NTIS by: phone at 1-800-553-NTIS (U.S. customers); (703)605-6000 (other countries); fax at (703)605-6900; and email at orders@ntis.gov. NTIS is located at 5285 Port Royal Road, Springfield, VA, 22161, USA.
Order No. Title Abstract / Keywords



Available online

See background support papers at FAN's Index on Oxyfluorfen

2002 - Reregistration Eligibility Decision (RED) Oxyfluorfen. (Includes RED Facts: Oxyfluorfen.).

Environmental Protection Agency, Washington, DC. Office of Prevention, Pesticides and Toxic Substances.

In evaluating pesticides for reregistration, EPA obtains and reviews a complete set of studies from pesticide producers, describing the human health and environmental effects of each pesticide. To implement provisions of the Food Quality Protection Act of 1996, EPA considers the special sensitivity of infants and children to pesticides, as well as aggregate exposure of the public to pesticide residues from all sources, and the cumulative effects of pesticides and other compounds with common mechanisms of toxicity. The Agency develops any mitigation measures or regulatory controls needed to effectively reduce each pesticide's risks. EPA then reregisters pesticides that meet the safety standard of the FQPA and can be used without posing unreasonable risks to human health or the environment. When a pesticide is eligible for reregistration, EPA explains the basis for its decision in a Reregistration Eligibility Decision (RED) document. This fact sheet summarizes the information in the RED document for reregistration case 2490, [abstract truncated]



1989 - Pesticides Research and Monitoring: Annual report 1987-88.

Environment Canada, Ottawa (Ontario).

This is the second annual report on Environment Canada's pesticides program, summarizing the results of projects undertaken by the department's regional and district offices, research institutes and centres, branches and services. The report is organized into 6 sections based on the location (Atlantic region, Quebec region, Ontario region, Western and Northern region, Pacific and Yukon region, and the National Wildlife Research Centre in Hull, Quebec) where each project was conducted. Also included are discussion documents summarizing the environmental effects of oxyfluorfen, pentachlorophenol, triadimefon, metsulfuron-methyl and propiconizole. An index is included. Text in English and French (Bilingual). French ed.: 90-02247/2.



1989 - Oxyfluorfen (Goal) trials with bareroot forest seedlings in British Columbia, 1987.

Authors: Trotter DB, Shrimpton GM

British Columbia Ministry of Forests, Victoria.
Forest Resource Development Agreement (Canada).

Herbaceous weeds are a serious problem in forest nurseries, affecting the growth and survival of seedlings by reducing the efficiency of fertilizers and irrigation, and harbouring tree-damaging insects and pathogens. A promising herbicide which has been registered for use in U.S. forest nurseries since 1979 is oxyfluorfen (Goal). On the basis of its potential and extensive use in nurseries in the U.S., oxyfluorfen was chosen by the Canadian Forest Nursery Weed Management Assoc. as a candidate for registration. A standardized oxyfluorfen trial was designed by the Association to facilitate and coordinate weed control and crop tolerance data from different regions of Canada. The trials were conducted across the country, and provided information on the tolerance of 1 plus 0 and 2 plus 0 bareroot Douglas-fir and lodgepole pine to oxyfluorfen, and the degree of herbicide efficacy in controlling weeds commonly found in B.C. forest nurseries. FRDA report no. 092.

NTIS/PB89-237218 18p

1988 - Biological and Abiotic Degradation of Xenobiotic Compounds in Vitro Estaurine Water and Sedimentater Systems.

Authors: Walker WW, Cripe CR, Pritchard PH
Bourquin AW

Battelle Columbus Labs., OH.
Gulf Coast Research Lab., Ocean Springs, MS.
Georgia State Univ., Atlanta.

First-order biotic degradation rate constants of 14 pesticides were determined in estuarine water and sediment/water slurry systems. Test systems used environmentally realistic concentrations of pesticides in sterile and nonsterile samples of water and sediment taken directly from the field. Thiobencarb, sulprofos, chlorothalonil, diclofop-methyl, fenthion, oxyfluorfen, methoxychlor, phorate, and trifluralin all showed significantly (p < = 0.01) more degradation in the presence of nonsterile sediment than in the presence of sterile sediment. Most of these nine pesticides biodegraded significantly faster in flasks containing sediment than in those with water alone. Endosulfan and PCNB, however, biodegraded faster in the absence of sediment. EPN and chlorpyrifos were degraded primarily by abiotic processes. Methomyl did not significantly degrade under any test conditions. Oxyfluorfen and chlorpyrifos were also slow to degrade, with half-lives of generally over two weeks in nonsterile sediment.



1980 - Oxyfluorfen, herbicide.

Plant Industry Directorate. Pesticide Information Division, Ottawa (Ontario).
Canada. Pesticides Directorate, Ottawa (Ontario).

The registration status of oxyfluorfen represents an important ongoing regulatory issue concerning onion production in Canada. Because onions do not compete well with weeds, production without appropriate weed control is not practical. The purpose of this document is to provide a summary of the data reviewed and outline the regulatory action on the active ingredient oxyfluorfen. Discussion document no. D87-01. Text in English and French (Bilingual). French ed. (Oxyfluorfene, herbicide) on the same fiche. At head of title: Agriculture Canada, Food Production and Inspection Branch, Pesticides Directorate.



1987 - Pesticide Background Statements. Volume 3. Nursery Pesticides.

Authors: Sczerzenie PJ, Weeks JA, Vigerstad TJ, Drendel GH, Crouch CP

NOXSO Corp., Library, PA.

The document is a compendium of pesticide background statements that review the available information on the chemistry, toxicology, environmental fate properties, and methods of application of 14 pesticides used in USDA Forest Service nurseries. The following nursery pesticides are reviewed in the 14 background statements. Herbicides: bifenox, DCPA, diphenamid, napropamide, oxyfluorfen, sethoxydim, sulfometuron methyl. Fungicides: DCNA, metalaxyl, thiram, triadimefon. Fumigants: dazomet, 1,3-dichloropropene, Vorlex. Each nursery pesticide background statement contains (1) a description of the chemical and physical properties of the pesticide, (2) a discussion of the results of laboratory animal studies that indicate how toxic the pesticide may be to humans, wildlife, aquatic species, and other nontarget organisms, and (3) a description of the pesticide's normal use patterns and application rates, its specific use in nursery operations, and its likely fate in the environment in the immediate area



1982 - Oxyfluorfen (Goal 2E): Position Document No 4

Environmental Protection Agency, Washington, DC. Office of Pesticides and Toxic Substances.

This document details the final determination regarding the Rebuttable Presumption Against Registration (RPAR) of products containing the above chemical. The responses by the EPA to comments on the preliminary determination by the Scientific Advisory Panel and the United States Department of Agriculture are contained in the document. A bibliography of citations used in this final determination is also provided.



1982 - Oxyfluorfen (Goal 2E(Trade Name)) Position Document Number 1-2-3. Pesticide Rebuttable Presumption Against Registration

Environmental Protection Agency, Washington, DC. Office of Pesticides and Toxic Substances.

This document details the Rebuttable Presumption Against Registration (RPAR) regarding products containing the above chemical. The bases for EPA's concern are contained in this document. It also contains a bibliography of citations used in this preliminary determination. Errata sheet inserted.



1982 - Oxyfluorfen (Goal 2E(Trade Name)) Position Document Number 1-2-3. Pesticide Rebuttable Presumption Against Registration

Environmental Protection Agency, Washington, DC. Office of Pesticides and Toxic Substances.

This document details the Rebuttable Presumption Against Registration (RPAR) regarding products containing the above chemical. The bases for EPA's concern are contained in this document. It also contains a bibliography of citations used in this preliminary determination. Errata sheet inserted.


EPA/OTS; Doc #878220827



CAS Registry Numbers:


Pesticide Biochemistry and Physiology; Volume 80, Issue 2 , October 2004, Pages 65-74

Expression of human protoporphyrinogen oxidase in transgenic rice induces both a photodynamic response and oxyfluorfen resistance

Y. Lee, S. Jung and K. Back,

Department of Biotechnology, Agricultural Plant Stress Research Center, Biotechnology Research Institute, Chonnam National University, Gwangju, 500-757, Republic of Korea

A human protoporphyrinogen oxidase (Protox) coding sequence under the control of a ubiquitin promoter was introduced into rice to determine whether transgenic rice overexpressing the human Protox gene exhibits resistance against a peroxidizing herbicide. The transgenic rice lines (H3, H4, H5, H6, H9, and H10) transcribed the human Protox mRNA, whereas hybridizing RNA band was not detected in wild-type rice, indicating that the human Protox gene had been successfully transmitted into transgenic rice plants. The transgenic lines H9 and H10 showed growth retardation and light-dependent formation of necrotic lesions. Compared with wild-type rice plants, rice with a human Protox gene had increased Protox activity and content of the photosensitizer protoporphyrin IX, and reduced chlorophyll. The photosynthetic efficiency in lines H9 and H10, as indicated by Fv/Fm, was not different from that of wild type. The two transgenic lines had decreased levels of antheraxanthin, lutein, and ?-carotene and similar levels of neoxanthin and violaxanthin as compared with wild-type plants. The staining activities of catalase, peroxidase, superoxide dismutase, and glutathione reductase were higher in transgenic lines than in wild type. Line H9 germinated in the presence of 20 ?M oxyfluorfen, whereas 2 ?M oxyfluorfen inhibited the germination of wild-type seeds. Thus, the transgenic rice plants exhibited enhanced resistance to oxyfluorfen.


J Environ Qual. 2004 Mar-Apr;33(2):605-11.
Surface retention and photochemical reactivity of the diphenylether herbicide oxyfluorfen.

Scrano L, Bufo SA, Cataldi TR, Albanis TA.

Dipartimento di Produzione Vegetale, Universita della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy.

The photochemical behavior of oxyfluorfen [2-chloro-1-(3-etoxy-4-nitrophenoxy)-4-(trifluoromethyl) benzene] on two Greek soils was investigated. Soils were sampled from Nea Malgara and Preveza regions, characterized by a different organic matter content. Soils were spiked with the diphenyl-ether herbicide and irradiation experiments were performed either in the laboratory with a solar simulator (xenon lamp) or outside, under natural sunlight irradiation; other soil samples were kept in the dark to control the retention reaction. Kinetic parameters of both retention and photochemical reactions were calculated using zero-, first- and second- (Langmuir-Hinshelwood) order equations, and best fit was checked through statistical analysis. The soil behaviors were qualitatively similar but quantitatively different, with the soil sampled from the Nea Malgara region much more sorbent as compared with Preveza soil. All studied reactions followed second-order kinetics and photochemical reactions were influenced by retaining capability of the soils. The contributions of the photochemical processes to the global dissipation rates were also calculated. Two main metabolites were identified as 2-chloro-1-(3-ethoxy-4-hydroxyphenoxy)-4-(trifluoromethyl)benzene and 2-chloro-1- (3-hydroxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene.

PMID: 15074812 [PubMed - indexed for MEDLINE]


Chemosphere. 2003 Oct;53(3):217-21.
Effect of the herbicides oxadiazon and oxyfluorfen on phosphates solubilizing microorganisms and their persistence in rice fields.

Das AC, Debnath A, Mukherjee D.

Department of Agricultural Chemistry and Soil Science, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur 741 252, India. acdas2@rediffmail.com

A field experiment has been conducted with two herbicides viz. oxadiazon [5-terbutyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-one] and oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenyl)-4-(trifluoromethyl) benzene] at rates of 0.4 and 0.12 kg a.i. ha(-1), respectively, to investigate their effect on the growth and activities of phosphate solubilizing microorganisms in relation to availability of phosphorus as well as persistence of the herbicides in the rhizosphere soil of wetland rice (Oryza sativa L. variety IR-36). Application of herbicides stimulated the population and activities of phosphate solubilizing microorganisms and also the availability of phosphorus in the rhizosphere soil. Oxyfluorfen provided greater microbial stimulation than oxadiazon. Dissipation of oxyfluorfen and oxadiazon followed first order reaction kinetics with half-life (T(1/2)) of 8.8 and 12 days, respectively. Sixty days after application 0.5% and 3% of the applied oxadiazon and oxyfluorfen residues persisted, respectively, in the rhizosphere soil of rice.

PMID: 12919781 [PubMed - indexed for MEDLINE]


Arch Environ Contam Toxicol. 2003 Nov;45(4):445-52.

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

Geoffroy L, Dewez D, Vernet G, Popovic R.

Laboratoire d'Eco-Toxicologie, Unite de Recherche "Vignes et Vins de Champagne," UPRES-EA 2069, Universite de Reims Champagne-Ardenne, BP 1039, F51687 Reims 2, France.

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

PMID: 14708660 [PubMed - indexed for MEDLINE]


Ecotoxicol Environ Saf. 2003 Feb;54(2):151-6.

Dissipation of the herbicide oxyfluorfen in subtropical soils and its potential to contaminate groundwater.

Yen JH, Sheu WS, Wang YS.

Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan.

The dissipation and mobility of the herbicide oxyfluorfen (2-chloro-alpha,alpha,alpha-trifluoro-p-tolyl 3-ethoxy-4-nitrophenyl ether) in field soil of Taiwan were investigated in the laboratory with six tea garden soils. The dissipation coefficients of oxyfluorfen in soils of different moisture content (30%, 60%, and 90% of soil field capacity) and soil temperature (10 degrees C, 25 degrees C, and 40 degrees C) were studied. Results indicate that the half-life of oxyfluorfen ranged from 72 to 160 days for six tea garden soils. It was found that if the temperature is high, the dissipation rate is rapid, and there is almost no dissipation at 10 degrees C. Possible contamination of groundwater by the herbicide oxyfluorfen was assessed using the behavior assessment model and the groundwater pollution-potential (GWP) model. The results obtained after evaluating the residue and travel time using the GWP model illustrated that oxyfluorfen is not very mobile in soil and may not contaminate groundwater under normal conditions. But in the case of soil of extremely low organic carbon content and coarse texture, oxyfluorfen has the potential to contaminate groundwater less than 3m deep.

PMID: 12550092 [PubMed - indexed for MEDLINE]


J Environ Sci Health Part A Tox Hazard Subst Environ Eng. 2002;37(4):521-7.

Toxicological effects of the herbicide oxyfluorfen on acetylcholinesterase in two fish species: Oreochromis niloticus and Gambusia affinis.

Hassanein HM.

Zoology Department, Faculty of Science at Sohag, South Valley University, Egypt. hamada10@mailcity.com

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.

PMID: 12046652 [PubMed - indexed for MEDLINE]


Pest Manag Sci. 2001 Aug;57(8):743-8.

Resistance of a soybean cell line to oxyfluorfen by overproduction of mitochondrial protoporphyrinogen oxidase.

Warabi E, Usui K, Tanaka Y, Matsumoto H.

Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.

The diphenyl ether herbicide oxyfluorfen (2-chloro-4-trifluoromethylphenyl 3-ethoxy-4-nitrophenyl ether) inhibits protoporphyrinogen oxidase (Protox) which catalyzes the oxidation of protoporphyrinogen IX (Protogen) to protoporphyrin IX (Proto IX), the last step of the common pathway to chlorophyll and haeme biosynthesis. We have selected an oxyfluorfen-resistant soybean cell line by stepwise selection methods, and the resistance mechanism has been investigated. No growth inhibition was observed in resistant cells at a concentration of 10(-7) M oxyfluorfen, a concentration at which normal cells did not survive. While the degree of inhibition of total extractable Protox by oxyfluorfen was the same in both cell types, the enzyme activity in the mitochondrial fraction from non-treated resistant cells was about nine-fold higher than that from normal cells. Northern analysis of mitochondrial Protox revealed that the concentration of mitochondrial Protox mRNA was much higher in resistant cells than that in normal cells. There were no differences in the absorption and metabolic breakdown of oxyfluorfen. The growth of resistant cells was also insensitive to oxadiazon [5-tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-(3H)- one], the other chemical class of Protox inhibitor. Therefore, the resistance of the selected soybean cell line to oxyfluorfen is probably mainly due to the overproduction of mitochondrial Protox.

PMID: 11517729 [PubMed - indexed for MEDLINE]


J Environ Sci Health B. 2000 Mar;35(2):121-41.

Laboratory study on leachability of five herbicides in South Australian soils.

Ying GG, Williams B.

Department of Environmental Science & Management, University of Adelaide, Roseworthy, Australia.

Norflurazon, oxadiazon, oxyfluorfen, trifluralin and simazine are herbicides widely used in the vineyards of the Barossa Valley, South Australia. The leaching behaviour of norflurazon, oxadiazon, oxyfluorfen and trifluralin was investigated on four key soils in the Barossa Valley. Leaching potential on packed soil columns and actual mobility using intact soil columns were investigated. On the packed soil columns, norflurazon was the most leachable herbicide. More of the herbicides were detected in the leachates from the sandy soils (Mountadam and Nuriootpa) than from the clayey soils (Lyndoch and Tanunda). Organic matter is generally low in soils in the Barossa region. Porosity and saturated conductivity significantly affect herbicide movement and in the sandy Mountadam and Nuriootpa soils, the water flux is greater than for the higher clay content Lyndoch and Tanunda soils. Increasing the time interval between herbicide application and the incidence of "rainfall" reduced the amounts of herbicides found in the leachates. The use of intact soil columns and including simazine for comparison showed that both norflurazon and simazine were present in the leachates. Simazine was the first herbicide to appear in leachates. Sectioning of the intact soil columns after leaching clearly demonstrated that norflurazon and simazine reached the bottom of the soil columns for all soils studied. Greater amounts of norflurazon were retained in the soil columns compared with simazine. The other herbicides were mostly retained in the initial sections of the soil columns.

PMID: 10736764 [PubMed - indexed for MEDLINE]


Arch Environ Contam Toxicol. 1999 Jul;37(1):78-84.

Induction of hsp70 by the herbicide oxyfluorfen (Goal) in the Egyptian Nile fish, Oreochromis niloticus.

Hassanein HM, Banhawy MA, Soliman FM, Abdel-Rehim SA, Muller WE, Schroder HC.

Institut fur Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universitat Mainz, Duesbergweg 6, D-55099 Mainz, Germany.

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.

PMID: 10341045 [PubMed - indexed for MEDLINE]


J Environ Sci Health B. 1999 May;34(3):397-411.

Herbicide residues in grapes and wine.

Ying GG, Williams B.

Department of Environmental Science and Management, University of Adelaide, Australia.

The persistence of several common herbicides from grapes to wine has been studied. Shiraz, Tarrango and Doradillo grapes were separately sprayed with either norflurazon, oxyfluorfen, oxadiazon or trifluralin-persistent herbicides commonly used for weed control in vineyards. The dissipation of the herbicides from the grapes was followed for 28 days following treatment. Results showed that norflurazon was the most persist herbicide although there were detectable residues of all the herbicides on both red and white grapes at the end of the study period. The penetration of herbicides into the flesh of the grapes was found to be significantly greater for white grapes than for red grapes. Small-lot winemaking experiments showed that norflurazon persisted at levels close to the initial concentration through vinification and into the finished wine. The other herbicides degraded, essentially via first-order kinetics, within the period of "first fermentation" and had largely disappeared after 28 days. The use of charcoal together with filter pads, or with diatomaceous earth was shown to be very effective in removing herbicide residues from the wine. A 5% charcoal filter removed more than 96% of the norflurazon persisting in the treated wine.

PMID: 10227191 [PubMed - indexed for MEDLINE]


Can J Physiol Pharmacol. 1997 Oct-Nov;75(10-11):1181-7.

Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs.

Krijt J, Stranska P, Maruna P, Vokurka M, Sanitrak J.

Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Administration of oxadiazon or oxyfluorfen (1000 ppm in the diet) to male BALB/c mice for 9 days resulted in experimental porphyria, resembling the acute phase of human variegate porphyria. Urinary concentrations of 5-aminolevulinic acid and porphobilinogen reached 1500 and 3000 mumol/L, respectively. Both herbicides caused a decrease of protoporphyrinogen oxidase activity in liver and kidney. Brain protoporphyrinogen oxidase activity was not altered. Liver and kidney porphyrin content increased to 11 and 17 nmol/g, respectively (control mice, 2 nmol/g). Over 50% of liver and kidney porphyrins were in the reduced (porphyrinogen) form. Bile of oxadiazon-treated mice contained 700 nmol/mL of protoporphyrinogen (control mice, 15 nmol/mL). Porphyrin content of the trigeminal nerve increased from 1 nmol/g in control animals to 11 nmol/g in oxadiazon-treated animals, suggesting a possible contribution of peripheral nerve porphyrins to porphyric neuropathy. Mice treated with 125 ppm of oxadiazon in the diet for 9 days excreted moderately elevated levels of porphobilinogen in urine (control mice, less than 50 mumol/L; treated mice, 330 mumol/L). Administration of phenobarbital or phenytoin (single injections on days 7, 8, and 9) increased the urinary porphobilinogen concentration to 3500 mumol/L. This response to porphyrogenic drugs resembles the response observed in human acute porphyrias.

PMID: 9431441 [PubMed - indexed for MEDLINE]


Hum Exp Toxicol. 1997 Feb;16(2):115-22.

Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis.

Rio B, Parent-Massin D, Lautraite S, Hoellinger H.

Laboratoire de Microbiologie et Securite Alimentaire, Ecole Superieure de Microbiologie et Securite Alimentaire de Brest, ISAMOR, Technopole Brest-Iroise, Plouzane, France.

The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis. The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Erythroid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the development of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentiation showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10(-4) M) that have no adverse effect on cellular proliferation.

PMID: 9051416 [PubMed - indexed for MEDLINE]


Chem Res Toxicol. 1996 Oct-Nov;9(7):1135-9.

Protoporphyrinogen oxidase: high affinity tetrahydrophthalimide radioligand for the inhibitor/herbicide-binding site in mouse liver mitochondria.

Birchfield NB, Casida JE.

Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.

Protoporphyrinogen oxidase (protox), the last common enzyme in heme and chlorophyll biosynthesis, is the target of several classes of herbicides acting as inhibitors in both plants and mammals. N-(4-Chloro-2-fluoro-5-(propargyloxy)phenyl)-3,4,5,6-tetrahydro phthalimide (a potent protox inhibitor referred to as THP) was synthesized as a candidate radioligand ([3H]-THP) by selective catalytic reduction of 3,6-dihydrophthalic anhydride (DHPA) with tritium gas followed by condensation in 45% yield with 4-chloro-2-fluoro-5-(propargyloxy)aniline. Insertion of tritium at the 3 and 6 carbons of DHPA as well as the expected 4 and 5 carbons resulted in high specific activity [3H]THP (92 Ci/mmol). This radioligand undergoes rapid, specific, saturable, and reversible binding to the inhibitor/herbicide binding site of the protox component of cholate-solubilized mouse liver mitochondria with an apparent Kd of 0.41 nM and Bmax of 0.40 pmol/mg of protein. In the standard assay, mouse preparation (150 micrograms of protein) and [3H]THP (0.5 nM) are incubated in 500 microL of phosphate buffer at pH 7.2 for 15 min at 25 degrees C followed by addition of ammonium sulfate and filtration with glass fiber filters. The potencies of five nitrodiphenyl ethers and two other herbicides as inhibitors of [3H]THP binding correlate well with those for inhibition of protox activity (r2 = 0.97, n = 7), thus validating the binding assay as relevant to enzyme inhibition. It is also suitable to determine in vivo block as illustrated by an approximately 50% decrease in [3H]THP binding in liver mitochondria from mice treated ip with oxyfluorfen at 4 mg/kg. This is the first report of a binding assay for protox in mammals. The high affinity and specific activity of [3H]THP facilitate quantitation of protox and therefore research on a sensitive inhibition site for porphyrin biosynthesis.

PMID: 8902268 [PubMed - indexed for MEDLINE]


Arch Toxicol. 1993;67(4):255-61.

Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells.

Krijt J, van Holsteijn I, Hassing I, Vokurka M, Blaauboer BJ.

Research Institute of Toxicology, University of Utrecht, The Netherlands.

The effects of the herbicides fomesafen, oxyfluorfen, oxadiazon and fluazifop-butyl on porphyrin accumulation in mouse liver, rat primary hepatocyte culture and HepG2 cells were investigated. Ten days of herbicide feeding (0.25% in the diet) increased the liver porphyrins in male C57B1/6J mice from 1.4 +/- 0.6 to 4.8 +/- 2.1 (fomesafen) 16.9 +2- 2.9 (oxyfluorfen) and 25.9 +/- 3.1 (oxadiazon) nmol/g wet weight, respectively. Fluazifop-butyl had no effect on liver porphyrin metabolism. Fomesafen, oxyfluorfen and oxadiazon increased the cellular porphyrin content of rat hepatocytes after 24 h of incubation (control, 3.2 pmol/mg protein, fomesafen, oxyfluorfen and oxadiazon at 0.125 mM concentration 51.5, 54.3 and 44.0 pmol/mg protein, respectively). The porphyrin content of HepG2 cells increased from 1.6 to 18.2, 10.6 and 9.2 pmol/mg protein after 24 h incubation with the three herbicides. Fluazifop-butyl increased hepatic cytochrome P450 levels and ethoxy- and pentoxyresorufin O-dealkylase (EROD and PROD) activity, oxyfluorfen increased PROD activity. Peroxisomal palmitoyl CoA oxidation increased after fomesafen and fluazifop treatment to about 500% of control values both in mouse liver and rat hepatocytes. Both rat hepatocytes and HepG2 cells can be used as a test system for the porphyrogenic potential of photobleaching herbicides.

PMID: 8517781 [PubMed - indexed for MEDLINE]


Bull Environ Contam Toxicol. 1991 Apr;46(4):485-91.

No Abstract available

Disappearance of oxyfluorfen (goal) from onions and organic soils.

Frank R, Clegg BS, Ritcey G.

Agricultural Laboratory Services Branch, University of Guelph, Ontario, Canada.

PMID: 1854991 [PubMed - indexed for MEDLINE]

Return to Oxyfluorfen Index Page

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