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==Safety==
{{update|reason={{cite journal |vauthors=Lini RS, Scanferla DT, de Oliveira NG, Aguera RG, Santos TD, Teixeira JJ, Kaneshima AM, Mossini SA |title=Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review |journal=Crit Rev Toxicol |volume=54 |issue=1 |pages=35–54 |date=January 2024 |pmid=38288970 |doi=10.1080/10408444.2024.2303481 }}|date=February 2024}}
{{update|reason=https://pubmed.ncbi.nlm.nih.gov/38288970/|date=February 2024}}
Fungicide [[Pesticide#Residue|residues]] have been found on food for human consumption, mostly from post-harvest treatments.<ref>{{cite book |title=Pesticide Chemistry and Bioscience edited by |editor-first=G.T |editor-last=Brooks and |editor2-first=T.R |editor2-last=Roberts. |date=1999. Published by the |publisher=Royal Society of Chemistry |doi=10.1533/9781845698416 |isbn=978-1-84569-841-6 |oclc=849886156}}</ref> Some fungicides are dangerous to human [[health]], such as [[vinclozolin]], which has now been removed from use.<ref>{{cite journal |vauthors=Hrelia ''etP, al.''Fimognari 1996C, -Maffei F, Vigagni F, Mesirca R, Pozzetti L, Paolini M, Cantelli Forti G |title=The genetic and non-genetic toxicity of the fungicide Vinclozolin. |journal=Mutagenesis Volume |volume=11 |issue=5 |pages=445–53 |date=September 1996 |pmid=8921505 |doi=10.1093/mutage/11.5.445-453 }}</ref> [[Ziram]] is also a fungicide that is toxic to humans with long-term exposure, and fatal if ingested.<ref>National Center for Biotechnology Information. PubChem Compound Database; CID=8722, https://pubchem.ncbi.nlm.nih.gov/compound/8722 (accessed Jan. 13, 2019)</ref> A number of fungicides are also used in human health care.
== Types of fungicides==
== Resistance ==
{{See also|Antimicrobial resistance}}
Doses that provide the most control of the disease also provide the largest selection pressure to acquire resistance.<ref>{{cite journal |last=Metcalfe, |first=R.J. ''et|first2=M.W. |last2=Shaw al|first3=P.E.'' (|last3=Russell |date=2000) |title=The effect of dose and mobility on the strength of selection for DMI (sterol demethylation inhibitors) fungicide resistance in inoculated field experiments. ''|journal=Plant Pathology'' '''|volume=49''': |pages=546–557|doi=10.1046/j.1365-3059.2000.00486.x }}</ref>
In some cases, the pathogen evolves resistance to multiple fungicides, a phenomenon known as [[cross resistance]]. These additional fungicides typically belong to the same chemical family, act in the same way, or have a similar mechanism for detoxification. Sometimes negative [[cross-resistance]] occurs, where resistance to one chemical class of fungicides increases sensitivity to a different chemical class of fungicides. This has been seen with [[carbendazim]] and [[diethofencarb]]. Also possible is resistance to two chemically different fungicides by separate mutation events. For example, ''[[Botrytis cinerea]]'' is resistant to both azoles and [[dicarboximide fungicides]].
A common mechanism for acquiring resistance is alteration of the target enzyme. For example, [[Black Sigatoka]], an economically important pathogen of banana, is resistant to the [[QoI]] fungicides, due to a single [[nucleotide]] change resulting in the replacement of one [[amino acid]] (glycine) by another (alanine) in the target protein of the QoI fungicides, [[cytochrome]] b.<ref>Sierotzki,{{cite journal |first=Helge (2000)|last=Sierotzki |title=Mode of resistance to respiration inhibitors at the cytochrome bc1 enzyme complex of ''Mycosphaerella fijiensis'' field isolates ''|journal=Pest Management Science'' '''|volume=56''': |issue= 10|pages=833–841 |date=2000 |doi=10.1002/1526-4998(200010)56:10<833::AID-PS200>3.0.CO;2-Q }}</ref> It is presumed that this disrupts the binding of the fungicide to the protein, rendering the fungicide ineffective. Upregulation of target genes can also render the fungicide ineffective. This is seen in DMI-resistant strains of ''[[Venturia inaequalis]]''.<ref>{{cite journal |vauthors=Schnabel, G., and Jones, A. L. 2001.AL |title=The 14a14alpha-demethylase Demethylasse(CYP51A1) geneGene is overexpressedOverexpressed in ''V.Venturia inaequalis'' strainsStrains resistantResistant to myclobutanil.Myclobutanil ''|journal=Phytopathology'' '''|volume=91''': |issue=1 |pages=102–110 |date=January 2001 |pmid=18944284 |doi=10.1094/PHYTO.2001.91.1.102 |doi-access=free }}</ref>
Resistance to fungicides can also be developed by efficient [[Efflux (microbiology)|efflux]] of the fungicide out of the cell. ''[[Septoria tritici]]'' has developed multiple drug resistance using this mechanism. The pathogen had five [[ATP-binding cassette transporter|ABC-type transporters]] with overlapping [[Substrate (biochemistry)|substrate]] specificities that together work to pump toxic chemicals out of the cell.<ref>{{cite journal |vauthors=Zwiers LH, L.Stergiopoulos H.I, etGielkens al.MM, (2003)Goodall SD, De Waard MA |title=ABC transporters of the wheat pathogen Mycosphaerella graminicola function as protectants against biotic and xenobiotic toxic compounds. ''Molecular|journal=Mol Genetics andGenet Genomics'' '''|volume=269''': |issue=4 |pages=499–507 |date=July 2003 |pmid=12768412 |doi=10.1007/s00438-003-0855-x }}</ref>
In addition to the mechanisms outlined above, fungi may also develop [[metabolic pathway]]s that circumvent the target protein, or acquire [[enzyme]]s that enable the metabolism of the fungicide to a harmless substance.
{{Reflist|30em|refs=
<ref name="Pearson-et-al-2009">{{cite journal | last1=PEARSONPearson | first1=MICHAEL M.N. | last2=BEEVERBeever | first2=ROSS R.E. | last3=BOINEBoine | first3=BARBARAB. | last4=ARTHURArthur | first4=KIERENK. | title=Mycoviruses of filamentous fungi and their relevance to plant pathology (|type=Review) | journal=[[Molecular Plant Pathology]] | publisher=[[British Society for Plant Pathology]] ([[Wiley-Blackwell]]) | volume=10 | issue=1 | year=2009 | issn=1464-6722 | doi=10.1111/j.1364-3703.2008.00503.x | pages=115–128 | s2cid=34331588| pmid=19161358 | pmc=6640375}}</ref>
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