CAS Nos. 361377-29-9 and 193740-76-0

Return to Fluoxastrobin Adverse Effects

ACTIVITY: Fungicide (strobin)

CAS Name: E-isomer: Methanone, [2-[[6-(2-chloro-phenoxy)-5-fluoro4-pyrimidinyl] oxy]phenyl](5,6-dihydro-1,4,2dioxazin-3-yl)-, O-methyloxime, (1E)-(9CI) (CAS No. 361377-29-9)

Note: This name was provisionally approved for the (EZ)-isomer [193740-76-0] in April 2002. The definition was changed to the (E)-isomer in January 2003 at the request of the sponsor.

Fluoxastrobin is the accepted common name for the pesticidally active E-isomer of (2-[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy phenyl)-5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime.

The Z-isomer of fluoxastrobin is typically present at much lower levels (E:Z ratio of approximately 90:10). Additionally, the Z-isomer of fluoxastrobin is considered to be a metabolite (photo-degradate) of
Z isomer: (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime

The CAS Number Bayer CropScience initially obtained for fluoxastrobin pertained to both isomers combined. After consultation with the EPA, Bayer CropScience requested that fluoxastrobin (the pesticidally active E-isomer only) be designated as the active ingredient.

The tolerances that EPA established on September 16, 2005, include both fluoxastrobin (i.e. the E-isomer) and the Z-isomer and the risk assessment for these tolerances was based on exposures resulting from both isomers.

Note: For milk and meat tolerances, EPA included the phenoxy-hydroxypyrimidine metabolite,

Reference: US EPA. Pesticide tolerances. Final Rule. September 16, 2005. Federal Register.


Adverse Effects:

Body Weight

Endocrine: Adrenal
Endocrine: Testicular
Endocrine: Thyroid
Endocrine: Uterus
Urinary tract

• Moderately to highly persistent in soil
Moderately toxic to estuarine/marine fish;
• Highly toxic to freshwater fish and invertebrates;
• Very highly toxic to estuarine/marine invertebrates.

• Risks to endangered species.
The list of endangered/threatened freshwater fish species where fluoxastrobin is used on potatoes, tomatoes, peppers, and peanuts are grown is comprised of 84 different species representing 36 States. The three States with the largest number of endangered /threatened freshwater fish species include California, Washington, and Oregon.

Regulatory Information
(only comprehensive for the US)
US EPA Registered: Yes
US EPA PC Code: 028869 
US Tolerances: 180.609
UK Temporary MRL's

Applicable from: August 2004

Potato: 0.1 p pm
Wheat (winter), rye (winter: 0.05 ppm

Other Information
Molecular Formula: C21H16Cl F N4O5 (E-Isomer)
Entry Year: 2002  
Inventing Company : Bayer 
Other Names: HEC 480 SC Fungicide 
Of special interest:
PAN Data
November 2005 - US EPA Pesticide Fact Sheet: Fluoxastrobin.

August 10, 2005: Conclusion regarding the peer review of the pesticide risk assessment of the active substance fluoxastrobin. European Food Safety Authority.
Conclusion - 81 pages

Summary - 6 pages
Final addendum to the Draft Assessment Report (July 2005) - 73 pages
Cover page
Comments on the draft assessment report - 39 pages
Reporting Table - 62 pages
Expert Meeting Reports - 42 pages
Evaluation Table - 24 pages

August 17, 2005 - Arysta LifeScience North America has secured exclusive domestic marketing rights for fluoxastrobin, a strobilurin fungicide in development for disease control.
Fluoxastrobin is being tested extensively in university trials across the U.S. to further define the disease control spectrum and performance benefits the product, alone and in combinations, will offer users.
"This investment is a demonstration of our continuing commitment to supply highly effective plant disease control chemistry for turfgrass management and ornamental production," said Elin Miller, Arysta LifeScience president and CEO.
"We expect the activity of these materials will enable us to develop and launch not one, but several new fungicides into turf management and ornamental production," said Doug Houseworth, turf and ornamental technical service representative.
Arysta LifeScience anticipates registrations sometime in late 2005 to early 2006.
Landscape Management

May 11, 2005 - First sales of Fluoxastrobin in Europe.
Fluoxastrobin, the new broad spectrum, leaf systemic strobilurin fungicide of Bayer CropScience is about to make its market debut under the brand name of Fandango® in key markets in Europe this year. The active ingredient Fluoxastrobin gained its first global approval in the UK at the end of 2004, where it will be launched for foliar application in cereals this season. First sales will also take place in Germany and Ireland.
Fandango® is an innovative fungicide, combining two molecules with different modes of action – the new strobilurin Fluoxastrobin and Prothioconazole, the first active ingredient of the triazolinthion class of substances...

April 27, 2005 - Tokyo, Japan-based Arysta LifeScience and Bayer CropScience have announced a package of agreements that further expand their cooperation. Financial terms of the transaction were not disclosed... [Arysta] will be granted an exclusive license for marketing Bayer's fluoxastrobin for crop uses in the US, Canada and Japan as well as an exclusive license for marketing the compound globally for non-crop uses such as on turf and ornamentals. Bayer will supply Arysta with fluoxastrobin for sale in these markets as well as with tebuconazole for in-can mixtures with fluoxastrobin in the US...
Ref: Agriculture Online

2004 - Environmental fate of Fluoxastrobin (HEC5725);
H. Borchers and H.-P. Stupp. Pflanzenschutz-Nachrichten Bayer 57/2004, 3: 337-354

2004 - Fluoxastrobin (HEC5725) – the new dimension in strobilurin fungicides;
by U. Heinemann, J. Benet-Buchholz, W. Etzel and M. Schindler. Pflanzenschutz-Nachrichten Bayer 57/2004, 3: 299-318.

2004 - Behaviour of Fluoxastrobin (HEC 5725) in plants and animals.
by H. Reiner, A. Klempner and J. Koster. Pflanzenschutz-Nachrichten Bayer 57/2004, 3: 391-414.

January 10, 2003 - A dossier for the active substance fluoxastrobin was submitted by Bayer Crop Science,to the authorities of the United Kingdom on 25 March 2002. Official Journal of the European Communities. 
April 2003 - Comment submitted in response to Bayer's petition to establish pesticide tolerances in and on raw agricultural commodities. 

5. First Evaluation for UK Provisional Approval of Fluoxastrobin (HEC 5725), in the products 'Bayer UK831' and 'Bayer UKA 148' and First Consideration of the Inclusion of Fluoxastrobin in Annex I of Directive 91/414/EEC. [ACP 18 (301/2003)]

5.1 Fluoxastrobin is a new strobilurin fungicide, developed by Bayer CropScience. Approval was requested for two formulations, an emulsifiable concentrate (EC) foliar spray and a seed treatment. This is the first application for a seed treatment containing a strobilurin. Fluoxastrobin is also being considered for inclusion in Annex I of Directive 91/414/EEC with the UK acting as Rapporteur.

5.2 The Committee was asked to consider whether Ministers should be advised to grant provisional approval for these formulations. They were also asked to comment on the evaluation and the conclusions reached, ahead of the evaluation being submitted to the EU Commission and the start of the Annex I peer review process.

5.3 Members sought some confirmatory information on the mode of toxicological action of fluoxastrobin, but confirmed that this would not affect the human health risk assessment, which was acceptable

5.4 It was agreed that a risk to aquatic invertebrates from the spray could be addressed by a 15 metre buffer zone. Further data would be required to refine this aspect of the risk assessment. Concerns about risks to non-target arthropods were also discussed. It was thought that there was inconsistency in the data which should be examined outside the meeting. The concerns could be addressed by appropriate labelling.

5.5 The Committee agreed that provisional approval could not be granted for use of the product as a seed treatment at present as this contained prothioconazole (which would not be commercially approved - see minute 4 above). As buffer zones larger than 5m are not acceptable in UK for use on arable crops, the foliar spray could not be recommended for approval in the UK either.
Ref: Final minutes of the 301st meeting of the Advisory Committee on Pesticides held on 10 July 2003.

US Federal Register

•• Note: Due to length, the following is a partial list. Click here to see full list of FR entries.

Date Published Docket Number Details
Sept 16, 2005 OPP-2003-0129

BAYER. Pesticide Tolerances. FINAL RULE.

• Reproduction and fertility - rats. Offspring systemic: decreased body weights, delayed preputial separation, and incomplete ossification in the F1 and/or F2 males and females. Parental systemic: decreased premating body weight gain of the P-generation males and females and decreased premating absolute body weight of the F1 males and females.
• Chronic toxicity-dogs. LOAEL was 8.1 mg/kg/day for males and 7.7 mg/kg/day for females based on body weight reductions and hepatocytomegaly and cytoplasmic changes associated with increased serum liver alkaline phosphatase indicative of cholestasis.
• 90-Day oral toxicity-rats. reduced body weight gain and food intake, vacuolation in the zona fasciculate of the adrenal cortex, calculi in the urethra and kidney, and histological lesions in kidney, urinary bladder, and urethra;
• 90-Day oral toxicity-dogs.
dose-related reductions in net body weight gain and food efficiency in addition to toxicity findings in the liver in both sexes (cholestasis) and in kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).
• 90-Day oral toxicity-mice. There was a dose related increase in liver weight in both sexes and in kidney weight in females, in addition to other effects whose toxicological relevance was considered uncertain. Among these effects were increased hepatocellular hypertrophy with cytoplasmic changes in the high-dose males and minimal to moderate kidney tubular hypertrophy in mid- and high-dose females.
• Combined chronic toxicity / carcinogenicity--rats. decreased body weight, decreased body weight gain, and decreased food efficiency in both sexes; decreased spleen weight in males; and microscopic lesions in the uterus of females. The apparent increase in tumors in the uterus and thyroid were addressed and resolved by an Agency committee, which concluded that no carcinogenic concern exists for fluoxastrobin.
90-Day Subchronic Oral Toxicology-Dog. dose-related reductions in net body weight gain and food efficiency; toxicity findings in the liver (cholestasis) in both sexes; and toxicity findings in the kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males)

• Thyroid. FAN suggested that a 14-week feeding study using dogs showed an effect on the thyroid, which seems to conflict with the statement that ``...There is no evidence to suggest that fluoxastrobin has any primary endocrine disruptive potential.'' FAN stated that a ``discussion or rationale'' addressing this should have been provided. EPA does believe that the thyroid effects seen in the dog study indicated that fluoxastrobin is an endocrine disruptor. An effect on the thyroid gland, even though this gland is part of the endocrine system, does not necessarily mean that endocrine disruption has or will occur. In this case, the effects observed in the thyroid gland were induced by effects fluoxastrobin had on liver enzymes and are therefore considered secondary.

The following conditions are being imposed on Bayer CropScience (the petitioner) for the registration of fluoxastrobin.
1. Submit additional information concerning weather conditions, confirmatory raw data, and soil characteristics data for the crop field trial and field rotational crop studies.
2. Submit additional data concerning the chromatograms and chromatography in the goat metabolism study.
3. The enforcement methods must be rewritten to include instructions for the analysis of all crops, and to specify the
additional ions to be monitored for quantitation.
4. A new peanut processing study must be submitted.
5. Submit reference standard materials for fluoxastrobin and several molecules related to it, including isotopically labeled
internal standard reference materials, to the EPA National Pesticide Standards Repository.
6. Submit additional information concerning the grass forage and hay rotational crop field trials.
7. Submit confirmatory data and additional information concerning the storage stability data.
8. Submit additional information concerning the mouse immunotoxicity subacute feeding study.

Sec. 180.609 Fluoxastrobin; tolerances for residues.
(a) General. (1) Tolerances are established for the combined residues of fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime,
and its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, in or on the following raw agricultural commodities:
Commodity Parts per million

Leaf petioles subgroup 4B

This subgroup includes 8 commodities:
amaranth, leafy • cardoon • celery • celery, chinese • celtuce • fennel, florence • rhubarb • swiss chard

Peanut 0.010
Peanut, hay 20.0
Peanut, refined oil 0.030
Tomato, paste 1.5

Vegetable, fruiting, group 8

This group includes 17 commodities:
chili, postharvest • eggplant • groundcherry • pepino • pepper • pepper, bell • pepper, nonbell • pepper, nonbell, sweet • tomatillo • tomato • tomato, concentrated products • tomato, dried pomace • tomato, paste • tomato, puree • tomato, wet pomace • vegetable, fruiting • vegetable, fruiting, group


Vegetable, tuberous and corm, subgroup 1C

This subgroup includes 22 commodities:
arracacha • arrowroot • artichoke, chinese • artichoke, jerusalem • canna, edible • cassava • chayote root • chufa • dasheen • ginger • leren • potato • potato culls • potato granules flakes • potato peel, wet • potato processed potato waste • potato, specialty • sweet potato • tanier • turmeric • yam bean • yam, true


Tolerances are established for the combined residues of
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime,
its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime,
and its phenoxy-hydroxypyrimidine metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol,
in or on the following raw agricultural commodities:
Commodity Parts per million
Cattle, fat 0.10
Cattle, meat 0.05
Cattle, meat byproducts 0.10
Goat, fat 0.10
Goat, meat 0.05
Goat, meat byproducts 0.10
Horse, fat 0.10
Horse, meat 0.05
Horse, meat byproducts 0.10
Milk 0.02
Milk, fat 0.50
Sheep, fat 0.10
Sheep, meat 0.05
Sheep, meat byproducts 0.10

(d) Indirect or inadvertent residues. Tolerances are established for the indirect or inadvertent combined residues of fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime,
and its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime,
in or on the following raw agricultural commodities when present therein as a result of the application of fluoxastrobin to the growing crops listed in paragraph (a)(1) of this section:
Commodity Parts per million
Alfalfa, forage 0.050
Alfalfa, hay 0.10
Cotton, gin byproducts 0.020

Grain, cereal, forage, fodder, and straw, group 16

This group includes 50 commodities:
barley, hay • barley, straw • corn, field • corn, field, aspirated grain fractions • corn, field, forage • corn, field, hay • corn, field, stover • corn, pod • corn, pod, stover • corn, pop • corn, pop, stover • corn, sweet, cannery waste • corn, sweet, forage • corn, sweet, stover • grain, cereal, forage, fodder and straw, group, for forage, except sweet corn, forage • grain. cereal, group • grass, hay • millet, forage • millet, hay • millet, pearl, forage • millet, pearl, hay • millet, pearl, straw • millet, proso, forage • millet, proso, hay • millet, proso, straw • millet, straw • oat • oat, forage • oat, hay • oat, straw • rice, forage • rice, hulls • rice, straw • rice, wild • ricegrass, indian • rye, forage • rye, straw • sorghum, forage • sorghum, forage, forage • sorghum, forage, hay • sorghum, forage, silage • sorghum, grain • sorghum, grain, forage • sorghum, grain, stover • wheat, forage • wheat, hay • wheat, straw • wheat, vavilovi, straw • wheat, wild einkorn, straw • wheat, wild emmer, straw

Grass, forage 0.10
Grass, hay 0.50

Vegetable, foliage of legume, group 7

This group includes 21 commodities:
bean, dry, forage • bean, dry, hay • bean, forage • bean, hay • bean, lima, forage • bean, lima, hay • bean, snap, forage • bean, straw • cowpea, forage • cowpea, hay • legume, forage • legume, forage, except soybean and peanut • lupin, grain, forage • lupin, grain, hay • pea, field, hay • pea, field, silage • pea, field, vines • pea, pigeon, forage • vegetable, seed and pod, fodder • vegetable, seed and pod, forage • vegetable, seed and pod, hay

•• Note: Due to length, the above is a partial list. Click here to see full list of FR entries.
Fluoride Action Network | Pesticide Project | 315-379-9200 | pesticides@fluoridealert.org