Fipronil

from Wikipedia, the free encyclopedia
Structural formula
Structure of Fipronil
1: 1 enantiomer mixture (racemate) from ( S ) form (top) and ( R ) form (bottom)
General
Non-proprietary name Fipronil
other names
  • ( RS ) -5-amino-1- (2,6-dichloro-α, α, α-trifluoro p -tolyl) -4-trifluoromethylsulfinyl-1 H -pyrazole-3-carbonitrile
  • regent
Molecular formula C 12 H 4 Cl 2 F 6 N 4 OS
Brief description

white to yellowish powder

External identifiers / databases
CAS number 120068-37-3
EC number 424-610-5
ECHA InfoCard 100.102.312
PubChem 3352
Wikidata Q415933
Drug information
ATC code

Q P53AX15

properties
Molar mass 437.15 g mol −1
Physical state

firmly

density

1.55 g cm −3 (20 ° C)

Melting point

200-201 ° C

boiling point

decomposes before boiling at 230 ° C

Vapor pressure

2 · 10 −6  Pa (20 ° C)

solubility
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
06 - Toxic or very toxic 08 - Dangerous to health 09 - Dangerous for the environment

danger

H and P phrases H: 330-311-301-372-410
P: 261-273-280-301 + 310-311-501
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fipronil is an active ingredient from the phenylpyrazole group used in many countries as a biocide and "systemic pesticide " (" insecticide ") . It acts as a contact poison fast and long lasting against agricultural pests and ectoparasites such as fleas , lice , louse , ticks , fur mites , harvest mites and mange mites .

history

The active ingredient was developed in 1987 by the French chemical company Rhône-Poulenc and first launched on the market in 1993. In the course of the merger of Rhône-Poulenc with Hoechst , Aventis was created , which Fipronil sold to Bayer AG in 2002 . Bayer sold the rights to Fipronil and some acaricides / fungicides on to BASF in 2003 ; the total value of the acquisition was put at 1.33 billion euros. Fipronil's active ingredient patent has now expired, which is why the active ingredient can now be produced generically worldwide .

Manufacturing

Fipronil can be synthesized by a multi-stage reaction starting from 2,6-dichloro-4-trifluoromethylaniline by reaction with ethyl-2,3-dicyanopropionate , sulfuric acid , sodium nitrite , trifluoromethylsulfenyl chloride and meta- chloroperbenzoic acid.

properties

Fipronil is a white to yellowish solid that is practically insoluble in water . It is chemically stable in the pH value range from 5 to 7 and slowly decomposes at a pH value of 9 ( DT 50 = 28 days) to form the amide . Fipronil is chiral , which means that it has a stereocenter . The active ingredient is used as a racemate [1: 1 mixture of the ( R ) form and the ( S ) form].

Fipronil is suspected of causing cancer (" carcinogenic ") and being an endocrine disruptor . According to the current state of scientific knowledge, however, Fipronil is not officially classified as mutagenic or carcinogenic.

Mechanism of action

In parasites, fipronil reaches the central nervous system as a contact poison via the exoskeleton . There it inhibits the ligand-controlled GABA receptor and thus the influx of chloride ions . As a result, nerve stimuli can no longer be passed on. The GABA receptor is only inhibited in invertebrates ; In mammals, birds and reptiles, the agent does not develop a comparably strong effect in this regard. However, it can be fatal for them even in relatively high doses. Bitter substances added to certain products are intended to prevent poisoning of children and pets.

use

Veterinary medicine

In veterinary medicine, the agent is usually applied to the skin (as a spray or spot-on ). It is not absorbed through the intact skin, but instead accumulates in the epidermis and the hair follicles . As it accumulates in the patient's sebum glands , it is distributed to the skin and hair via their secretion and over the entire surface of the skin via diffusion.

It takes effect within 24 hours. The remedy is effective against fleas for at least seven weeks in domestic dogs , and only about five weeks in domestic cats due to the more frequent grooming and faster elimination. The agent works against ticks in dogs for up to four weeks, and in cats only for two weeks, after which the effectiveness drops. However, the agent does not protect against tick bites because it requires a longer exposure time before the tick dies. In dogs, therefore, tick active ingredients that act faster are to be preferred for reliable protection against tick-borne diseases ( babesiosis , ehrlichiosis , anaplasmosis , borreliosis ). In addition, the brown dog tick, for example, already has resistances and tolerances to the active ingredient. In reptiles , the agent is mainly used against mites.

The use of Fipronil in food-producing animals is not allowed.

Contraindications

The product should not be used on very young and severely weakened animals. Also, rabbits , hedgehogs and chicken birds are very sensitive. Application to mucous membranes and oral intake should generally be avoided.

Plant protection

Regulation in Europe

In the European Union, Fipronil has been approved exclusively for seed treatment since 2007 and expires on July 31, 2018. At the national level, Fipronil is approved in Belgium and the Netherlands. The permitted daily dose is 0.0002, the acute reference dose 0.009 and the acceptable user exposure 0.0035 milligrams per kilogram of body weight and day.

In Germany, Fipronil is not generally approved as a plant protection product. From 2009 to 2015, however, the Federal Office for Consumer Protection and Food Safety (BVL) repeatedly issued special permits, according to which the active ingredient according to Section 11 (2) of the Plant Protection Act could be used in potatoes in the pickling preparation Goldor Bait against wireworms . No such emergency license has been issued since 2016.

In Switzerland, Fipronil was an active ingredient in the Regent dressing agent used to treat grain seeds against wireworms. The permit has now been terminated; Fipronil is no longer contained in any pesticides in Switzerland. In 2019, pirimicarb contaminated with fipronil , which was sold in Landi agricultural markets, led to bee deaths in Switzerland.

A preparation against wireworms in potatoes was approved in Austria, but is no longer approved there.

In France, in February 2004, a sales freeze for pesticides containing the active ingredient fipronil, which has not yet been lifted, was imposed in France due to the possible risk to honey bees. BASF then stated that all scientific studies had shown that fipronil in crop protection products posed no risk to humans, animals or the environment if it was used according to the instructions.

Several beekeeping associations filed a lawsuit against the approval of Fipronil in 2007, which was dismissed as inadmissible in 2008.

In March 2010, the European Commission tightened the regulations on the use of fipronil after its accidental release had led to considerable losses of honey bee colonies in several member states. Seed dressing with Fipronil is only permitted in professional seed treatment facilities and drill seeding is only permitted with appropriate equipment in order to reduce the release of dust.

On the basis of new information about the risks of fipronil for honey bees, the EU Commission asked the European Food Safety Authority (EFSA) in August 2012 for a risk assessment, which was presented at the end of May 2013. The EFSA came to the conclusion that the dressing of maize seeds with fipronil and especially the dust posed a high acute risk for bees. The EU Commission then proposed a partial ban, which was adopted on July 16 in the Standing Committee on the Food Chain and Animal Health. Since March 2014, seeds treated with Fipronil may no longer be placed on the market or used. Excluded from the ban are seeds for cultivation in the greenhouse, as well as leek, onion, shallot and cabbage plants that are cultivated outdoors and harvested before flowering. The ban concerns corn and sunflowers. At the time of the ban, Fipronil was approved for use in corn and sunflowers in Spain, Hungary, Bulgaria, the Czech Republic and Slovakia. In November 2013, BASF filed a lawsuit against the restriction and accused the EU Commission of improperly applying the precautionary principle , which did not include all available scientific findings in its decision and also violated European plant protection law.

Regulation in the USA

Uses of Fipronil in the US

In the US in 2004 the use of fipronil was the dressing of rice set Seeds. American rice farmers had sued the manufacturers because they saw a connection with the sharp decline in freshwater crabs . These crabs live on the flooded fields and are also of economic importance. In a settlement, the manufacturers agreed to pay damages of $ 45 million.

Pest Control

Fipronil is used as a pesticide. It is contained as an active ingredient in bait granules and casting agents against ants as well as in bait gels against cockroaches and in New Zealand in several baits against wasps , which have spread strongly there.

The bait granules consist mainly of sugar or meat, mixed with the toxin fipronil and a bitter substance that is supposed to prevent children, pets and birds from ingesting them. The insecticidal effect of Fipronil occurs with a delay. Before they die, the animals pass on part of the ingested substance to other members of their own species. Ants in particular also feed their brood with the poison and eat the carcasses of their poisoned conspecifics, which can exterminate the entire colony. Fipronil is also used in the United States to protect wooden structures from termites .

Various derivatives are also examined for their suitability.

Fipronil in eggs and egg products

In June, July and August 2017, fipronil was found in chicken eggs, chicken meat and chicken droppings from the Netherlands, Belgium, Germany and Austria, although the use of the insecticide is prohibited in animals used for food production. In 2018, the maximum levels for organic eggs from the Netherlands were exceeded.

Analytics

Enzyme immunoassays are available for the detection of fipronil . The forensically reliable qualitative and quantitative determination succeeds after adequate sample preparation by coupling gas chromatography or HPLC with mass spectrometry . This procedure can be used for various examination materials such as eggs, blood plasma or even when growing rice.

Trade names

Plant protection and pesticides

Adonis, Agenda, Ascend, Celaflor, Chipco Choice, Combat, Goliath, Icon, Maxforce, Regent, Termidor

Veterinary drugs

Monopreparations

Amflee, Effipro, Eliminall (excluding trade), Fipralone, Fiprocat, Fiprodog, Fiproline, Frontline

Combination preparations
  • with S-methoprene [(2 E , 4 E , 7 S ) -stereoisomer of methoprene ; CAS no. 65733-16-6]: Frontline Combo, Frontline Top Spot, Strectis
  • with S-methoprene and eprinomectin : Broadline
  • with S-methoprene and Amitraz : Certifect
  • with permethrin : Frontect

Web links

Commons : Fipronil  - collection of images, videos and audio files
  • Entry on Fipronil at Vetpharm, accessed July 29, 2012.

Individual evidence

  1. ↑ a b c d e f g Entry on Fipronil in the GESTIS substance database of the IFA , accessed on August 4, 2017(JavaScript required) .
  2. ↑ a b Entry on Fipronil in the Pesticide Properties DataBase (PPDB) of the University of Hertfordshire , accessed on April 15, 2020.
  3. ↑ FAO (Rome): Pesticide Residues in Food - 2001 Evaluations. Residuals . Food & Agriculture Org., 2002, ISBN 978-92-5104795-8 , pp. 191 ( limited preview in Google Book search).
  4. ↑ Entry on (±) -5-amino-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -4 - [(trifluoromethyl) sulfinyl] -1H-pyrazole-3-carbonitrile Template: Linktext-Check / Escaped in the Classification and Labeling Inventory of European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  5. ↑ Fipronil data sheet from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).
  6. ^ S. Gangolli, Royal Society of Chemistry (Great Britain): The Dictionary of Substances and Their Effects . Royal Society of Chemistry, 1999, ISBN 0-85404-818-9 , pp. 323 ( limited preview in Google Book search).
  7. ↑ Registration dossier on fipronil (section Toxicity to aquatic algae and cyanobacteria ) at the European Chemicals Agency (ECHA), accessed on August 8, 2017.
  8. ↑ a b Sonja and Joachim Budde: Plant protection poison affects fertility. In: Deutschlandfunk , research current . December 8, 2016, accessed August 5, 2017.
  9. ↑ a b A little background on the geneology and events of the insecticide Icon. In: Fluoride Action Network. Retrieved November 6, 2013.
  10. ↑ BASF Agro completes acquisition of the insecticide Fipronil. Press release BASF from March 24, 2003.
  11. ↑ Thomas A. Unger: Pesticide Synthesis Handbook . William Andrew, 1996, ISBN 0-8155-1853-6 , pp. 511 ( limited preview in Google Book search).
  12. ↑ Google patent search: Patent US8507693 - Process for synthesis of fipronil - Google patent search , accessed on August 4, 2017.
  13. ↑ Terry R. Roberts, David H. Hutson, Philip W. Lee, Peter H. Nicholls, Jack R. Plimmer: Metabolic Pathways of Agrochemicals Part 2: Insecticides and Fungicides . Royal Society of Chemistry, 2007, ISBN 978-1-84755-137-5 , pp. 1475 ( limited preview in Google Book Search).
  14. ↑ Richard P. Pohanish: Sittig's Handbook of Pesticides and Agricultural Chemicals . William Andrew, 2014, ISBN 978-1-4557-3157-2 , pp. 412 ( limited preview in Google Book search).
  15. ↑ Federal Institute for Risk Assessment : Questions and answers on fipronil content in foods of animal origin .
  16. ↑ Valérie Raymond-Delpech, Kazuhiko Matsuda, Benedict M. Sattelle, James J. Rauh, David B. Sattelle: Ion Channels: Molecular Targets of Neuroactive Insecticides . In: Invertebrate Neuroscience . tape 5 , no. 3-4 , November 1, 2005, pp. 119-133 , doi : 10.1007 / s10158-005-0004-9 , PMID 16172884 .
  17. ↑ AL Eiden et al .: Determination of metabolic resistance mechanisms in pyrethroid-resistant and fipronil-tolerant brown dog ticks. In: Medical and veterinary entomology. Volume 31, number 3, 09 2017, pp. 243-251, doi : 10.1111 / mve.12240 , PMID 28639697 .
  18. ↑ a b c Directorate-General for Health and Food Safety of the European Commission: Entry on Fipronil in the EU pesticide database; Entry in the national registers of plant protection products in Switzerland , Austria and Germany ; accessed on March 13, 2016.
  19. ↑ a b EFSA: Conclusion on the peer review of the pesticide risk assessment for bees for the active substance fipronil . In: EFSA Journal . tape 11 , no. 5 , 2013, p. 3158 , doi : 10.2903 / j.efsa.2013.3158 .
  20. ↑ Approvals for emergency situations (last change: March 7, 2016) ( Memento of January 7, 2015 in the Internet Archive ), accessed on March 13, 2016.
  21. ↑ Potato growers fear for their harvest . In: agrarheute . March 3, 2016 ( agrarheute.com [accessed November 7, 2018]).
  22. ↑ Illegal material: bee deaths in Aargau. In: schweizerbauer.ch . October 20, 2019, accessed October 20, 2019 .
  23. ↑ Statement from BASF on the ban on sales as a crop protection product in France
  24. ↑ Official Journal of the European Union: Case T-403/07: Union Nationale de l'Apiculture Française and Others v Commission . January 12, 2008.
  25. ↑ General Court of the European Union : Order of the General Court (Fourth Chamber) of November 3, 2008 - Union nationale de l'apiculture française et al. V Commission , Case T-403/07.
  26. ↑ Directive 2010/21 / EU of the Commission of March 12, 2010 amending Annex I of Directive 91/414 / EEC of the Council with regard to special provisions for clothianidin, thiamethoxam, fipronil and imidacloprid .
  27. ↑ EFSA assesses risks for bees from fipronil. EFSA, May 27, 2013.
  28. ↑ EU Commission: Implementing Regulation (EU) No. 781/2013 of August 14, 2013 .
  29. ↑ Bee Health: EU takes additional measures on pesticides to better protect Europe's bees. EU Commission, July 16, 2013.
  30. ↑ BASF files a lawsuit against the restriction of the use of insecticides by the EU Commission.  ( Page no longer available , search in web archives ) BASF, press release P-13-502, November 5, 2013.@1@ 2Template: Dead Link / www.basf.com
  31. ↑ Link to the procedure at the ECJ
  32. ↑ Regulation (EC) No. 1048/2005 of the Commission of 13 June 2005 amending Regulation (EC) No. 2032/2003 on the second phase of the ten-year work program in accordance with Article 16 (2) of Directive 98/8 / EC of the European Parliament and of the Council on placing biocidal products on the market . Contains: List of biocides in the EU review program.
  33. ↑ Entry on Fipronil in the Pesticide Properties DataBase (PPDB) of the University of Hertfordshire , accessed on May 24, 2019.
  34. ↑ To control wasps over a large area with several nests - use Vespex , Department of Conservation / New Zealand Government, accessed April 18, 2020
  35. ↑ Zheng Xiaohua, Jiang Dingxin, Liu Zhicheng, Xu Hanhong: Synthesis, characterization and bioactivity of Fipronil derivatives as a lead for new insecticide. In: Indian Journal of Chemical Technology , Vol. 17, May 2010, pp. 215–219 (PDF)
  36. ↑ Jan Grossarth: How an insecticide got into chicken eggs. In: FAZ.net , August 2, 2017.
  37. ↑ Maximum values ​​exceeded again: State office finds Fipronil in eggs In: n-tv.de, June 8, 2018, accessed on June 9, 2018.
  38. ↑ N. Vasylieva, KC Ahn, B. Barnych, SJ Gee, BD Hammock: Development of an Immunoassay for the Detection of the Phenylpyrazole Insecticide Fipronil. In: Environmental Science & Technology . 49 (16), Aug. 18, 2015, pp. 10038-10047. PMID 26196357 ; doi: 10.1021 / acs.est.5b01005 ; PMC 4605820 (free full text).
  39. ↑ M. Zhang, K. Bian, T. Zhou, X. Song, Q. Liu, C. Meng, L. He: Determination of Residual Fipronil in Chicken Egg and Muscle by LC-MS / MS. In: Journal of Chromatography B . 1014, Mar 1, 2016, pp. 31-36. PMID 26871280 ; doi: 10.1016 / j.jchromb.2016.01.041 .
  40. ↑ MZ Lacroix, S. Puel, PL Toutain, C. Viguié: Quantification of Fipronil and Its Metabolite Fipronil Sulfone in Rat Plasma Over a Wide Range of Concentrations by LC / UV / MS. In: Journal of Chromatography B . 878 (22), Jul 15, 2010, pp. 1934-1938. PMID 20599175 ; doi: 10.1016 / j.jchromb.2010.05.018 .
  41. ↑ JJ Pérez, MK Williams, G. Weerasekera, K. Smith, RM Whyatt, LL Needham, DB Barr: Measurement of Pyrethroid, Organophosphorus, and Carbamate Insecticides in Human Plasma using Isotope Dilution Gas Chromatography-High Resolution Mass Spectrometry. In: Journal of Chromatography B . 878 (27), Oct 1, 2010, pp. 2554-2562. PMID 20434413 ; doi: 10.1016 / j.jchromb.2010.03.015 ; PMC 3024141 (free full text).
  42. ^ R. Kumar, B. Singh: Persistence and Metabolism of Fipronil in Rice (Oryza sativa Linnaeus) Field. In: Bulletin of Environmental Contamination and Toxicology . 90 (4), Apr 2013, pp. 482-488. PMID 23238826 ; doi: 10.1007 / s00128-012-0926-y .
  43. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X , p. 1034.