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'''Brodifacoum''' is a highly lethal [[4-Hydroxycoumarins|4-hydroxycoumarin]] [[vitamin K antagonist]] [[anticoagulant]] [[poison]]. In recent years, it has become one of the world's most widely used [[pesticides]]. It is typically used as a [[rodenticide]], but is also used to control larger pests such as [[common brushtail possum|
Brodifacoum has an especially long half-life in the body, which ranges up to nine months, requiring prolonged treatment with antidotal [[vitamin K]] for both human and pet poisonings.
==Chemical synthesis==
Brodifacoum is a derivative of the 4-hydroxy-coumarin group. Compounds numbers are found next to their respective compounds in the image below. Compound 1 is the starting ester needed to synthesize brodifacoum. To obtain this starting
[[File:Synthesis of Brodifacoum.png|thumb|left|Stereospecific formation of Brodifacoum using an asymmetric organocopper compound.]]
==Toxicology==
Brodifacoum is a [[4-hydroxycoumarin]] anticoagulant, with a similar mode of action to its historical predecessors [[dicoumarol]] and [[warfarin]]. However, due to very high potency and long duration of action (elimination [[half-life]] of 20 – 130 days), it is characterised as a "second-generation" or "[[superwarfarin]]" anticoagulant.<ref name=autogenerated1>{{cite web|url=http://www.inchem.org/documents/hsg/hsg/hsg093.htm |title=Brodifacoum (HSG 93, 1995) |publisher=Inchem.org |
Brodifacoum inhibits the [[enzyme]] [[vitamin K epoxide reductase]], which is needed for the reconstitution of the vitamin K in its cycle from vitamin K-epoxide,
In addition, brodifacoum (as with other anticoagulants in toxic doses) increases [[Vascular permeability|permeability]] of blood capillaries; the blood plasma and blood itself begin to leak from the smallest blood vessels. A poisoned animal suffers progressively worsening internal bleeding, leading to [[Shock (circulatory)|shock]], loss of consciousness, and eventually [[death]].{{citation needed|date=July 2019}}
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| * rats (oral)|| 0.27 mg/kg b.w.<ref name="who#57"/>
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| * mice (oral) || 0.40 mg/kg b.w.<ref name="who#57">{{cite web|url=http://www.inchem.org/documents/pims/chemical/pim077.htm |title=Brodifacoum (PDS) |publisher=Inchem.org |
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| * rabbits (oral) ||0.30 mg/kg b.w.<ref name="who#57"/>
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| * fish — LC<sub>50</sub> for fish:
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| ** trout (96 hours exposure)|| 0.04 ppm<ref>{{cite web|url=http://www.wil-kil.com/public/2005-06_labels-msds/WeatherBlok%20XT%20M.pdf#search=%22LC50%2Bbrodifacoum%22 |title=Pest Control Product Labels And MSDS |publisher=Wil-kil.com |
|-
|}
As brodifacoum is not selective and can cause secondary poisoning of predators,<ref>{{cite web | url=http://npic.orst.edu/factsheets/rodenticides.html | title=Rodenticides }}</ref> its outdoor use is either banned or not recommended; the only exception is use for rodent eradication from islands (where it is feasible), because invasive rodents can be destructive for seabirds.<ref>{{cite journal | url=https://escholarship.org/uc/item/20k063g1 | doi=10.5070/V424110625 | title=New Zealand's Use of Brodifacoum in Eradication Efforts and Current Investigation of New Baits and Toxins | date=2010 | last1=Broome | first1=Keith | last2=Murphy | first2=Elaine | last3=Cunningham | first3=Celia | last4=Eason | first4=Charles , T. | journal=Proceedings of the Vertebrate Pest Conference | volume=24 }}</ref> Biological resistance to Brodifacoum has been indicated in some species of rats in sample studies <ref>{{cite journal | url=https://bioone.org/journals/wildlife-research/volume-50/issue-1/WR21064/Apparent-resistance-to-brodifacoum-in-Rattus-rattus-in-a-New/10.1071/WR21064.full | doi=10.1071/WR21064 | title=Apparent resistance to brodifacoum in | date=2022 | last1=Sran | first1=Suman P. K. | last2=Gartrell | first2=Brett G. | last3=Fisher | first3=Penny | last4=Armstrong | first4=Doug P. | journal=Wildlife Research | volume=50 | pages=28–38 | doi-access=free }}</ref>
== Brand names ==
[[File:Brodifacoum notice.jpg|thumb|Notice about laying of brodifacoum baits in New Zealand]]
[[File:Ratpoison Bait Box.JPG|thumb|Baitbox containing brodifacoum in Finland]]
Brodifacoum is marketed under many trade names, including Arakus (Advansia), Biosnap, [[d-CON]], Finale, Fologorat, Havoc, Jaguar, Klerat, Matikus, Mouser, Pestoff,
==Human poisoning==
=== Treatment ===
The primary antidote to brodifacoum poisoning is immediate administration of [[vitamin K|vitamin K<sub>1</sub>]] (dosage for humans: initially slow intravenous injections of 10–25 mg repeated at 3–6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before excessive bleeding ensues.
If unabsorbed poison is still in the digestive system, [[gastric lavage]] followed by administration of [[activated charcoal]] may be required.
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Cases of brodifacoum intoxication have been reported in the human medical literature.
In one report, a woman deliberately consumed over 1.5 kg (3 lb) of rat bait, constituting about 75 mg brodifacoum, but made a full recovery after receiving conventional medical treatment.<ref name="LiptonKlass">{{cite journal |author1=Lipton R.A. |author2=Klass E.M. | year = 1984 | title = Human ingestion of a 'superwarfarin' rodenticide resulting in a prolonged anticoagulant effect | journal = [[Journal of the American Medical Association|JAMA]] | volume = 252 | issue = 21| pages = 3004–3005 | doi=10.1001/jama.252.21.3004|pmid=6502864 }}</ref>
In another case reported in 2013, a 48-year-old female patient reported 4 days of mild [[dyspnea]], dry cough, bilateral popliteal fossae pain, and diffuse upper abdominal pain. She had no history of liver disease or [[alcohol (drug)|alcohol]] or [[narcotic|illicit substance]] [[drug abuse|abuse]]. Initial physical examination was remarkable only for mildly pale [[conjunctivae]] and mild abdominal tenderness and pain in the left [[popliteal fossa]]. A complete blood count and complete metabolic panel were normal. [[Prothrombin]] time (PT) was above 100 s, partial [[thromboplastin]] time (PTT) was above 200 s and international normalized ratio (INR) was reported as above 12.0. Urinalysis revealed [[hematuria]] (blood in the urine). Venous [[Doppler ultrasound]] of lower extremities demonstrated left popliteal vein [[thrombosis]]. Computed tomography scan of the abdomen demonstrated transmural hematoma, and a [[fecal occult blood test]] was positive. A full anticoagulant work-up showed critical reduction of vitamin K-dependent factors II, VII, IX, and X. PT and PTT corrected with mixing studies proving factor deficiency as the cause of the [[coagulopathy]]. [[Lupus anticoagulant]] studies were negative. Superwarfarin toxicity was suspected and confirmed with an anticoagulant poison panel positive for brodifacoum. The patient was hospitalized and successfully treated with fresh frozen plasma, [[cryoprecipitate]], and vitamin K. In conclusion, paradoxical thrombosis and hemorrhage should raise the suspicion for superwarfarin toxicity in the appropriate clinical setting. Concomitant presentation for thrombosis and hemorrhage with remarkably abnormal PT and PTT should raise the suspicion for brodifacoum poisoning.<ref>{{Cite journal|title = I smell a rat|journal = Blood Coagulation & Fibrinolysis|doi = 10.1097/mbc.0b013e328358e959|
In 2015, 19 [[inmate]]s in [[New York City]]'s [[Rikers Island]] jail claimed that they had been poisoned with the chemical. The inmates had noticed "what appeared to be blue and green pellets in the [[meatloaf]]" they were eating on March 3, and felt ill afterwards. A sample was analyzed and tested positive for brodifacoum; the [[New York City Department of
In another report, a 17-year-old boy presented to the hospital with a severe bleeding disorder. He was found to have habitually smoked a mixture of brodifacoum and [[marijuana]]. Despite treatment with vitamin K, the bleeding disorder persisted for several months. He eventually recovered.<ref name="LaRosaEtAl">{{cite journal |author1=La Rosa F |author2=Clarke S |author3=Lefkowitz J B | year = 1997 | title = Brodifacoum intoxication with marijuana smoking | journal = Archives of Pathology & Laboratory Medicine | volume = 121 | pages = 67–69 }}</ref>▼
A 20-year-old female college student presented with abdominal pain and blood in urine. She was tested for [[warfarin]], a common anticoagulant also used in some rodenticides, which returned a negative result. Vitamin K and fresh [[Blood plasma|plasma]] were administered to treat symptoms. Three weeks later, she returned with bleeding into her calf, and was subsequently tested for superwarfarin chemicals. The test showed that brodifacoum was in her bloodstream. She later admitted to consuming seven packets of [[rodenticide]].<ref name="WeitzelEtAl">{{citation |author=Weitzel, J. N.|journal=[[Blood (journal)|Blood]]|title=Surreptitious Ingestion of a Long-Acting Vitamin K Antagonist/Rodenticide, Brodifacoum: Clinical and Metabolic Studies of Three Cases |year=1990|volume=76|issue=12|pages=2555–2559|doi=10.1182/blood.V76.12.2555.2555|pmid=2265249|doi-access=free}}</ref>▼
▲In 2015, 19 [[inmate]]s in [[New York City]]'s [[Rikers Island]] jail claimed that they had been poisoned with the chemical. The inmates had noticed "what appeared to be blue and green pellets in the [[meatloaf]]" they were eating on March 3, and felt ill afterwards. A sample was analyzed and tested positive for brodifacoum; the [[New York City Department of Corrections|NYC Department of Corrections]] stated it was investigating the incident.<ref>{{cite news|last1=Marzulli|first1=John|title=EXCLUSIVE: Rikers Island meatloaf that left 19 inmates sick did have rat poison, lab tests confirm|url=http://www.nydailynews.com/new-york/nyc-crime/rikers-island-meatloaf-rat-poison-lab-tests-article-1.2201479|accessdate=28 April 2015|work=[[New York Daily News]]}}</ref><ref>Sydney Lupkin, [https://abcnews.go.com/Health/22-rikers-island-prisoners-sickened-rat-poison-meatloaf/story?id=30676137 "22 Rikers Island Prisoners Sickened By Rat Poison in Meatloaf, Lawyer Says], Daily News April 29, 2015</ref>
▲A 20-year-old female college student presented with abdominal pain and blood in urine. She was tested for [[warfarin]], a common anticoagulant also used in some rodenticides, which returned a negative result. Vitamin K and fresh [[Blood plasma|plasma]] were administered to treat symptoms. Three weeks later, she returned with bleeding into her calf, and was subsequently tested for superwarfarin chemicals. The test showed that brodifacoum was in her bloodstream. She later admitted to consuming seven packets of [[rodenticide]].<ref name="WeitzelEtAl">{{citation |author=Weitzel, J. N.|journal=[[Blood (journal)|Blood]]|title=Surreptitious Ingestion of a Long-Acting Vitamin K Antagonist/Rodenticide, Brodifacoum: Clinical and Metabolic Studies of Three Cases |year=1990|volume=76|issue=12|pages=2555–2559|doi=10.1182/blood.V76.12.2555.2555|doi-access=free}}</ref>
A 48-year-old businessman was admitted with a severe nosebleed and abnormal coagulation parameters. Standard treatment of vitamin K and fresh plasma was administered to stem the nosebleed. Two weeks later, he presented again with bleeding into the calf. Continual doses of vitamin K were necessary to counteract the brodifacoum. He denied taking any of the brodifacoum found in his home contained within packages of Contrac.<ref name="WeitzelEtAl"/>
====Recreational drug use====
As of November 26, 2018, at least eight fatalities and 320 cases of severe coagulopathy and bleeding associated with [[synthetic cannabinoid]] use had been reported in Illinois, Wisconsin, Maryland, Missouri, Florida, North Carolina, Indiana, Pennsylvania, Kentucky, Virginia, and West Virginia.<ref>{{cite news|date=2018-11-26|title=COCA Clinical Action: Outbreak Alert Update: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated With Synthetic Cannabinoids Use|url=https://content.govdelivery.com/accounts/USCDC/bulletins/21e1a0f|newspaper=Centers for Disease Control and Prevention (CDC)}}</ref><ref>{{cite news|first1=Robert|last1=McCoppin|title=Illinois gets donation of nearly 800,000 vitamin K tablets to treat poisoning from synthetic marijuana|url=http://www.chicagotribune.com/news/local/breaking/ct-met-synthetic-pot-illinois-vitamin-k-donation-20180423-story.html|newspaper=chicagotribune.com}}</ref><ref>{{cite web|title=Synthetic Marijuana Expands to Florida - Florida Department of Health in Hillsborough|url=http://hillsborough.floridahealth.gov/newsroom/2018/08/synthetic-marijuana.html|website=hillsborough.floridahealth.gov}}</ref> The first case occurred in Illinois on March 7, 2018.<ref>Center for Acute Disease Epidemiology, Iowa Department of Public Health [https://idph.iowa.gov/Portals/1/Publishing/Files/7/3d4dd310-685d-410f-b312-186715a61cf0.pdf Coagulopathies Associated with Contaminated Synthetic Cannabinoids] April 6, 2018</ref> Brodifacoum was suspected to be present in these products in Illinois. Products named '''Matrix''' and '''Blue Giant''' from a convenience store in Chicago have tested positive for brodifacoum and [[AMB-FUBINACA]] (FUB-AMB).<ref>{{cite news|first1=Jacqueline Howard and Marlena Baldacci|last1=CNN|title=Fake weed leaves two dead, 54 with severe bleeding|url=https://edition.cnn.com/2018/04/02/health/fake-weed-illinois-death-bn/index.html|newspaper=CNN}}</ref><ref>{{cite news|title=3 arrested in Chicago in connection to synthetic pot; 2 deaths, 54 others cases of severe bleeding|url=http://wgntv.com/2018/04/02/2-deaths-54-other-cases-of-severe-bleeding-tied-to-fake-weed-in-illinois/|newspaper=WGN-TV|date=2 April 2018}}</ref><ref>{{cite web|title=Masoud et al complaint - Department of Justice|url=https://www.justice.gov/usao-ndil/press-release/file/1048041|website=www.justice.gov}}</ref>▼
Brodifacoum has been mixed with [[synthetic cannabinoid]]s such as K2 and Spice, reportedly "to extend the duration of the drug euphoria".<ref>{{cite web |last1=Gottlieb |first1=Scott |title=Statement from FDA warning about significant health risks of contaminated illegal synthetic cannabinoid products that are being encountered by FDA |url=https://www.fda.gov/news-events/press-announcements/statement-fda-warning-about-significant-health-risks-contaminated-illegal-synthetic-cannabinoid |publisher=U.S. Food and Drug Administration |access-date=3 August 2024 |date=July 19, 2018}}</ref>
▲As of November 26, 2018, at least eight fatalities and 320 cases of severe coagulopathy and bleeding associated with
▲In another report, a 17-year-old boy presented to the hospital with a severe bleeding disorder. He was found to have habitually smoked a mixture of brodifacoum and [[marijuana]]. Despite treatment with vitamin K, the bleeding disorder persisted for several months. He eventually recovered.<ref name="LaRosaEtAl">{{cite journal |author1=La Rosa F |author2=Clarke S |author3=Lefkowitz J B | year = 1997 | title = Brodifacoum intoxication with marijuana smoking | journal = Archives of Pathology & Laboratory Medicine | volume = 121 | pages = 67–69 }}</ref>
==References==
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{{rodenticides}}
{{Authority control}}
[[Category:Anticoagulant rodenticides]]
[[Category:Coumarin drugs]]
[[Category:Tetralins]]
[[Category:
[[Category:Vitamin K antagonists]]
[[Category:4-Hydroxycoumarins]]
[[Category:Biphenyls]]
[[Category:Rodenticides]]
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