Editing Rodenticide (section)

==Classes of rodenticides==
[[File:Rat Poison.jpg|thumb|Poison baits infused with peanuts to attract rodents]]

=== Anticoagulants ===

[[Anticoagulant]]s are defined as chronic (death occurs one to two weeks after ingestion of the lethal dose, rarely sooner), single-dose (second generation) or multiple-dose (first generation) rodenticides, acting by effective blocking of the [[Vitamin-K|vitamin-K cycle]], resulting in inability to produce essential blood-clotting factors—mainly coagulation factors II ([[prothrombin]]) and VII ([[proconvertin]]).<ref name=":0" /><ref>{{Cite journal |last1=Regnery |first1=Julia |last2=Rohner |first2=Simon |last3=Bachtin |first3=Julia |last4=Möhlenkamp |first4=Christel |last5=Zinke |first5=Olaf |last6=Jacob |first6=Stefanie |last7=Wohlsein |first7=Peter |last8=Siebert |first8=Ursula |last9=Reifferscheid |first9=Georg |last10=Friesen |first10=Anton |date=2024-01-10 |title=First evidence of widespread anticoagulant rodenticide exposure of the Eurasian otter (Lutra lutra) in Germany |journal=Science of the Total Environment |volume=907 |pages=167938 |doi=10.1016/j.scitotenv.2023.167938 |pmid=37866608 |bibcode=2024ScTEn.90767938R |issn=0048-9697|doi-access=free }}</ref>

In addition to this specific metabolic disruption, massive toxic doses of [[4-Hydroxycoumarins|4-hydroxycoumarin]], 4-thiochromenone and [[1,3-indandione]] anticoagulants cause damage to tiny blood vessels ([[capillary|capillaries]]), increasing their permeability, causing internal bleeding. These effects are gradual, developing over several days. In the final phase of the intoxication, the exhausted rodent collapses due to [[hemorrhagic shock]] or severe [[anemia]] and dies. The question of whether the use of these rodenticides can be considered humane has been raised.<ref>{{cite journal |vauthors=Meerburg BG, Brom FW, Kijlstra A |title=The ethics of rodent control |journal=Pest Manag Sci |volume=64 |issue=12 |year=2008 |doi=10.1002/ps.1623 |pmid=18642329 |pages=1205–11}}</ref>

The main benefit of anticoagulants over other poisons is that the time taken for the poison to induce death means that the rats do not associate the damage with their feeding habits.

* First-generation rodenticidal anticoagulants generally have shorter elimination half-lives,<ref name="pmid19000263">{{cite journal |vauthors=Vandenbroucke V, Bousquet-Melou A, De Backer P, Croubels S |title=Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration |journal=J. Vet. Pharmacol. Ther. |volume=31 |issue=5 |pages=437–45 |date=October 2008 |pmid=19000263 |doi=10.1111/j.1365-2885.2008.00979.x }}</ref> require higher concentrations (usually between 0.005% and 0.1%) and consecutive intake over days in order to accumulate the lethal dose, and are less toxic than second-generation agents.
* Second-generation anticoagulant rodenticides (or SGARs)<ref name="CDPR">{{cite web |title=Second-Generation Anticoagulant Rodenticides (SGARs) |url=https://www.cdpr.ca.gov/docs/registration/reevaluation/chemicals/sgars.htm |publisher=California Department of Pesticide Regulation |access-date=29 January 2024}}</ref> are far more toxic than those of the first generation. They are generally applied in lower concentrations in baits—usually on the order of 0.001% to 0.005%—are lethal after a single ingestion of bait and are also effective against strains of rodents that became resistant to first-generation anticoagulants; thus, the second-generation anticoagulants are sometimes referred to as "[[Superwarfarin|superwarfarins]]".<ref name="pmid17655702">{{cite journal |vauthors=Kotsaftis P, Girtovitis F, Boutou A, Ntaios G, Makris PE |title=Haemarthrosis after superwarfarin poisoning |journal=Eur. J. Haematol. |volume=79 |issue=3 |pages=255–7 |date=September 2007 |pmid=17655702 |doi=10.1111/j.1600-0609.2007.00904.x |s2cid=38169953 }}</ref>

{| class="wikitable"
|-
! Class
! Examples
|-
| [[Coumarin]]s/[[4-hydroxycoumarin]]s
|
* First generation: [[warfarin]],<ref name="EPA2023">{{cite web |author1=Office of Pesticide Programs |title=Rodenticides: Draft Biological Evaluation, Effects Determinations, and Mitigation Strategy for Federally Listed and Proposed Endangered, and Threatened Species and Designated and Proposed Critical Habitats |url=https://downloads.regulations.gov/EPA-HQ-OPP-2023-0567-0004/content.pdf |publisher=U.S. Environmental Protection Agency |access-date=8 October 2024 |date=November 28, 2023}}</ref> [[coumatetralyl]]
* Second generation: [[difenacoum]], [[brodifacoum]],<ref name="urlFinal Risk Mitigation Decision for Ten Rodenticides | Pesticides | US EPA">{{cite web |url=http://www.epa.gov/pesticides/reregistration/rodenticides/finalriskdecision.htm |title=Final Risk Mitigation Decision for Ten Rodenticides &#124; Pesticides &#124; US EPA |access-date=24 December 2008}}</ref> [[flocoumafen]] and [[bromadiolone]].
|-
| [[1,3-indandione]]s
| [[diphacinone]], [[chlorophacinone]],<ref name="urlLONG ACTING ANTICOAGULANT RODENTICIDES">{{cite web |url=http://www.addl.purdue.edu/newsletters/1995/rodent.shtml |title=LONG ACTING ANTICOAGULANT RODENTICIDES |access-date=24 December 2008}}</ref> [[pindone]]

These are harder to group by generation. The [[United States Environmental Protection Agency|U.S. Environmental Protection Agency]] considers [[chlorophacinone]] and [[diphacinone]] as first generation agents.<ref name="EPA2023"/> According to some sources, the indandiones are considered second generation.<ref name="urlAnticoagulant Rodenticide Toxicosis in the Dog and Cat">{{cite web|url=http://www.vet.uga.edu/VPP/clerk/Harrell/index.php|title=Anticoagulant Rodenticide Toxicosis in the Dog and Cat|access-date=24 December 2008|archive-url=https://web.archive.org/web/20081229061000/http://www.vet.uga.edu/VPP/clerk/Harrell/index.php|archive-date=29 December 2008|url-status=dead|df=dmy-all}}</ref>
|-
| 4-thiochromenones
| [[Difethialone]] is the only member of this class of compounds.<ref name="pmid15266918">{{cite journal |vauthors=Saravanan K, Kanakasabai R, Thiyagesan K |title=Field evaluation of difethialone, a new second generation anticoagulant rodenticide in the rice fields |journal=Indian J. Exp. Biol. |volume=41 |issue=6 |pages=655–8 |date=June 2003 |pmid=15266918 }}</ref> The EPA and California consider this to be an SGAR.<ref name="EPA2023"/><ref name="CDPR"/>
|-
| Indirect
| Sometimes, anticoagulant rodenticides are potentiated by an [[antibiotic]] or [[bacteriostatic agent]], most commonly [[sulfaquinoxaline]]. The aim of this association is that the antibiotic suppresses intestinal [[symbiosis|symbiotic]] [[microflora]], which are a source of vitamin K. Diminished production of vitamin K by the intestinal microflora contributes to the action of anticoagulants.  Added [[vitamin D]] also has a synergistic effect with anticoagulants.
|}

[[Phylloquinone]] has been suggested, and successfully used, as antidote for [[pet]]s or humans accidentally or intentionally exposed to anticoagulant poisons.  Some of these poisons act by inhibiting [[liver]] functions and in advanced stages of poisoning, several blood-clotting factors are absent, and the volume of circulating blood is diminished, so that a blood transfusion (optionally with the clotting factors present) can save a person who has been poisoned, an advantage over some older poisons. A unique [[enzyme]] produced by the liver enables the body to recycle [[vitamin K]]. To produce the blood clotting factors that prevent excessive bleeding, the body needs vitamin K. Anticoagulants hinder this enzyme's ability to function. Internal bleeding could start if the body's reserve of anticoagulant runs out from exposure to enough of it. Because they bind more closely to the enzyme that produces blood clotting agents, single-dose anticoagulants are more hazardous. They may also obstruct several stages of the recycling of vitamin K. Single-dose or second-generation anticoagulants can be stored in the liver because they are not quickly eliminated from the body.<ref name=":1">{{Cite web |title=Rodenticides |url=http://npic.orst.edu/factsheets/rodenticides.html |access-date=2022-12-01 |website=npic.orst.edu}}</ref>

=== Metal phosphides ===
[[File:5654-Linxia-City-market-rat-poison-vendor.jpg|thumb|Rat poison vendor's stall at a market in [[Linxia City]], China]]
Metal phosphides have been used as a means of killing rodents and are considered single-dose fast acting rodenticides (death occurs commonly within 1–3 days after single bait ingestion). A bait consisting of food and a phosphide (usually [[zinc phosphide]]) is left where the rodents can eat it. The acid in the digestive system of the rodent reacts with the phosphide to generate toxic [[phosphine]] gas. This method of [[vermin]] control has possible use in places where rodents are resistant to some of the anticoagulants, particularly for control of house and field mice; zinc phosphide baits are also cheaper than most second-generation anticoagulants, so that sometimes, in the case of large [[infestation]] by rodents, their population is initially reduced by copious amounts of zinc phosphide bait applied, and the rest of population that survived the initial fast-acting poison is then eradicated by prolonged feeding on anticoagulant bait. Inversely, the individual rodents that survived anticoagulant bait poisoning (rest population) can be eradicated by pre-baiting them with nontoxic bait for a week or two (this is important to overcome bait shyness, and to get rodents used to feeding in specific areas by specific food, especially in eradicating rats) and subsequently applying poisoned bait of the same sort as used for pre-baiting until all consumption of the bait ceases (usually within 2–4 days). These methods of alternating rodenticides with different modes of action gives actual or almost 100% eradications of the rodent population in the area, if the acceptance/palatability of baits are good (i.e., rodents feed on it readily).

Zinc phosphide is typically added to rodent baits in a concentration of 0.75% to 2.0%. The baits have strong, pungent garlic-like odor due to the [[phosphine]] liberated by [[hydrolysis]]. The odor attracts (or, at least, does not repel) rodents, but has a repulsive effect on other mammals. Birds, notably [[wild turkey]]s, are not sensitive to the smell, and might feed on the bait, and thus fall victim to the poison.{{citation needed|date=July 2019}}

The tablets or pellets (usually aluminium, calcium or magnesium phosphide for fumigation/gassing) may also contain other chemicals which evolve [[ammonia]], which helps reduce the potential for spontaneous [[combustion]] or [[explosion]] of the [[phosphine]] gas.{{citation needed|date=July 2019}}

Metal phosphides do not accumulate in the tissues of poisoned animals, so the risk of [[secondary poisoning]] is low.

Before the advent of anticoagulants, phosphides were the favored kind of rat poison. During World War II, they came into use in United States because of shortage of [[strychnine]] due to the Japanese occupation of the territories where the [[strychnine tree]] is grown. Phosphides are rather fast-acting rat poisons, resulting in the rats dying usually in open areas, instead of in the affected buildings.

Phosphides used as rodenticides include:
* [[aluminium phosphide]] ([[fumigant]] and bait)
* [[calcium phosphide]]  ([[fumigant]] only)
* magnesium phosphide ([[fumigant]] only)
* [[zinc phosphide]] (bait only)

=== Hypercalcemia (vitamin D overdose)===
[[Cholecalciferol]] (vitamin D<sub>3</sub>) and [[ergocalciferol]] (vitamin D<sub>2</sub>) are used as [[Cholecalciferol#Use as rodenticide|rodenticides]]. They are toxic to rodents for the same reason they are important to humans: they affect calcium and phosphate [[homeostasis]] in the body. [[Vitamin D|Vitamins D]] are essential in minute quantities (few [[international unit|IU]]s per kilogram body weight daily, only a fraction of a milligram), and like most fat soluble [[vitamin]]s, they are toxic in larger doses, causing [[hypervitaminosis D]]. If the poisoning is severe enough (that is, if the dose of the toxin is high enough), it leads to death. In rodents that consume the rodenticidal bait, it causes [[hypercalcemia]], raising the calcium level, mainly by increasing calcium absorption from food, mobilising bone-matrix-fixed calcium into [[ionised]] form (mainly monohydrogencarbonate calcium cation, partially bound to plasma proteins, [CaHCO<sub>3</sub>]<sup>+</sup>), which circulates dissolved in the [[blood plasma]]. After ingestion of a lethal dose, the free calcium levels are raised sufficiently that [[blood vessel]]s, [[kidney]]s, the [[stomach]] wall and [[lung]]s are mineralised/calcificated (formation of calcificates, crystals of calcium salts/complexes in the tissues, damaging them), leading further to heart problems (myocardial tissue is sensitive to variations of free calcium levels, affecting both myocardial contractibility and action potential propagation between the atria and ventricles), bleeding (due to capillary damage) and possibly kidney failure. It is considered to be single-dose, cumulative (depending on concentration used; the common 0.075% bait concentration is lethal to most rodents after a single intake of larger portions of the bait) or sub-chronic (death occurring usually within days to one week after ingestion of the bait). Applied concentrations are 0.075% cholecalciferol (30,000&nbsp;IU/g)<ref name=vertebratePestProceedings1984>{{cite conference |title=CHOLECALCIFEROL: A UNIQUE TOXICANT FOR RODENT CONTROL |url=https://digitalcommons.unl.edu/vpc11/22/ |conference=Proceedings of the Eleventh Vertebrate Pest Conference (1984) |publisher=University of Nebraska Lincoln |date=March 1984 |quote=''Cholecalciferol is an acute (single-feeding) and/or chronic (multiple-feeding) rodenticide toxicant with unique activity for controlling commensal rodents including anticoagulant-resistant rats. Cholecalciferol differs from conventional acute rodenticides in that no bait shyness is associated with consumption and time to death is delayed, with first dead rodents appearing 3-4 days after treatment.'' }}</ref><ref name=usda2006>{{cite conference |last1=Rizor |first1=Suzanne E. |last2=Arjo |first2=Wendy M. |last3=Bulkin |first3=Stephan |last4=Nolte |first4=Dale L. |title=Efficacy of Cholecalciferol Baits for Pocket Gopher Control and Possible Effects on Non-Target Rodents in Pacific Northwest Forests |url=https://naldc.nal.usda.gov/download/39036/PDF |conference=Vertebrate Pest Conference (2006) |publisher=USDA |quote='' 0.15% cholecalciferol bait appears to have application for pocket gopher control. Cholecalciferol can be a single high-dose toxicant or a cumulative multiple low-dose toxicant.'' |access-date=27 August 2019 |archive-date=14 September 2012 |archive-url=https://web.archive.org/web/20120914083512/http://naldc.nal.usda.gov/download/39036/PDF |url-status=dead }}</ref> and 0.1% ergocalciferol (40,000&nbsp;IU/g) when used alone, which can kill a rodent or a rat.

There is an important feature of calciferols toxicology, that they are [[Synergy#Biological sciences|synergist]]ic with [[anticoagulant]] toxicant. In other words, mixtures of anticoagulants and calciferols in same bait are more toxic than a sum of toxicities of the anticoagulant and the calciferol in the bait, so that a massive hypercalcemic effect can be achieved by a substantially lower calciferol content in the bait, and vice versa, a more pronounced anticoagulant/hemorrhagic effects are observed if the calciferol is present. This synergism is mostly used in calciferol low concentration baits, because effective concentrations of calciferols are more expensive than effective concentrations of most anticoagulants.<ref name=":1" />

The first application of a calciferol in rodenticidal bait was in the Sorex product Sorexa D (with a different formula than today's Sorexa D), back in the early 1970s, which contained 0.025% warfarin and 0.1% ergocalciferol. Today, Sorexa CD contains a 0.0025% difenacoum and 0.075% cholecalciferol combination. Numerous other brand products containing either 0.075-0.1% calciferols (e.g. Quintox) alone or alongside an anticoagulant are marketed.<ref name=":0" />

The Merck Veterinary Manual states the following:
<blockquote>
Although this rodenticide [cholecalciferol] was introduced with claims that it was less toxic to nontarget species than to rodents, clinical experience has shown that rodenticides containing cholecalciferol are a significant health threat to dogs and cats. Cholecalciferol produces hypercalcemia, which results in systemic calcification of soft tissue, leading to [[kidney failure]], cardiac abnormalities, hypertension, CNS depression and GI upset. Signs generally develop within 18-36 hours of ingestion and can include depression, anorexia, polyuria and polydipsia. As serum calcium concentrations increase, clinical signs become more severe. ...&nbsp;GI smooth muscle excitability decreases and is manifest by anorexia, vomiting and constipation. ...&nbsp;Loss of renal concentrating ability is a direct result of hypercalcemia. As hypercalcemia persists, mineralization of the kidneys results in progressive renal insufficiency."<ref name=merckd>{{cite web
| url=https://www.msdvetmanual.com/toxicology/rodenticide-poisoning/cholecalciferol
| title=Merck Veterinary Manual - Cholecalciferol
}}</ref></blockquote>
Additional anticoagulant renders the bait more toxic to pets as well as humans. Upon single ingestion, solely calciferol-based baits are considered generally safer to birds than second generation anticoagulants or acute toxicants. Treatment in pets is mostly supportive, with [[intravenous]] fluids and [[pamidronate]] disodium. The hormone [[calcitonin]] is no longer commonly used.<ref name=merckd/> 

=== Alternatives to Rodenticides ===

Rodenticides have two important drawbacks: 1) they cause a delayed, protracted and painful death for the rodent 2) they bioaccumulate, so that any predator that eats a rodent after it has ingested the poison, will also be poisoned.<ref>Rat Poison’s Long Reach, Science, Vol 385, Issue 6705.https://www.science.org/content/article/really-scary-rat-poisons-wreaking-havoc-raptors-wildlife </ref> The effect is cumulative and can be fatal to the predator.  This decimates owl, raptor, fox and other predators as well as domestic cats and dogs. To address these issues, birth control for rodents has been introduced. The most commonly available, Contraceptol, has been shown to be effective at controlling rodent populations, particularly when coupled with environment modifications to make the area less attractive (remove food sources and minimize potential nesting sites). This form of birth control includes pheromones to attract both male and female rodents. After ingesting the contraceptive, the rodent experiences no discomfort, but cannot effectively breed for a month. If a large predator eats a rodent after it has ingested the contraceptive, it will not be harmed; at most it may experience a few days of infertility.  Therefore, contraception offers an environmentally safe, non-toxic, non-polluting, extremely effective and humane alternative to traditional poisons. 
 
There are a few drawbacks to contraception. Since it doesn't kill the rodent immediately, it takes longer to see results.  Both poisons and contraception need continued application to control the population on an ongoing basis, otherwise the rodent population will quickly rebound.

=== Other ===
[[File:CPS141ratpoison.jpg|thumb|right|[[Civilian Public Service]] worker distributes poisoned bait for [[Endemic typhus|typhus]] control in [[Gulfport, Mississippi]], {{circa|1945}}.]]
Other chemical [[poison]]s include:
*[[ANTU]] (α-naphthylthiourea; specific against [[Brown rat]], ''Rattus norvegicus'')
*[[Arsenic trioxide]]
*[[Barium carbonate]] (sometimes called [[Witherite]])
*[[Chloralose]] (a narcotic [[prodrug]])
*[[Crimidine]] (inhibits metabolism of vitamin B<sub>6</sub>)
*[[1,3-Difluoro-2-propanol]] ("Gliftor")
*[[Endrin]] ([[organochlorine insecticide]], used in the past for extermination of voles in fields)
*[[Fluoroacetamide]] ("1081")
*[[Phosacetim]] (a delayed-action [[acetylcholinesterase inhibitor]])
*[[allotropes of phosphorus|Phosphorus allotropes]]
*[[Pyrinuron]] (a [[urea]] derivative)
*[[Scilliroside]] and other [[cardiac glycosides]] like [[oleandrin]] or [[digoxin]]
*[[Sodium fluoroacetate]] ("1080")
*[[Strychnine]] (A naturally occurring convulsant and stimulant)
*[[Tetramethylenedisulfotetramine]] ("tetramine") - Deadly toxic to humans so use should be avoided
*[[Thallium sulfate]]
*[[Mitochondria]]l toxins like [[bromethalin]] and [[2,4-dinitrophenol]] (cause high fever and brain swelling)
*[[Zyklon B]]/Uragan D2 ([[hydrogen cyanide]] gas absorbed in an inert carrier)

===Combinations===
In some countries, fixed three-component rodenticides, i.e., anticoagulant + antibiotic + vitamin D, are used. Associations of a second-generation anticoagulant with an antibiotic and/or vitamin D are considered to be effective even against most resistant strains of rodents, though some second generation anticoagulants (namely brodifacoum and difethialone), in bait concentrations of 0.0025% to 0.005% are so toxic that resistance is unknown, and even rodents resistant to other rodenticides are reliably exterminated by application of these most toxic anticoagulants.