Atrazine: Difference between revisions

| verifiedrevid = 443663905

| ImageFile_Ref = {{chemboximage|correct|??}}

| ImageFile = AtrazineVector.svg

| ImageName = Atrazine

| ImageFile1 = Atrazine-3D-balls.png

| ImageName1 = Atrazine

| PIN = 6-Chloro-''N''²-ethyl-''N''⁴-(propan-2-yl)-1,3,5-triazine-2,4-diamine

| OtherNames = Atrazine<br/>1-Chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine<br/>2-Chloro-4-ethylamino-6-isopropylamino-''s''-triazine<br/>6-Chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine

|Section1={{Chembox Identifiers

| ChEBI_Ref = {{ebicite|correct|EBI}}

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| RTECS =

|Section2={{Chembox Properties

| C=8 | H=14 | Cl=1 | N=5

| Appearance = colorless solid

| Density = 1.187 g/cm³

| Solubility = 7 mg/100 mL

| MeltingPtC = 175

| BoilingPtC = 200

| BoilingPt_notes = decomposes<ref name=PGCH/>

| pKa =

| pKb =

| Viscosity =

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|Section7={{Chembox Hazards

| ExternalSDS =

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| FlashPt = noncombustible

| FlashPt_notes = <ref name=PGCH/>

| PEL = none<ref name=PGCH>{{PGCH|0043}}</ref>

| REL = TWA 5 mg/m³<ref name=PGCH/>

| IDLH = N.D.<ref name=PGCH/>

|Section8={{Chembox Related

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'''Atrazine '''is a [[herbicide]] of the [[triazine]] class. It is used to prevent pre-emergence broadleaf [[weed]]s in crops such as [[maize]] (corn) and [[sugarcane]] and on turf, such as golf courses and residential lawns. Atrazine's primary manufacturer is [[Syngenta]] and it is one of the most widely used herbicides in the United States<ref name=EPAatrazine /> and Australian agriculture.<ref name="APVMAmain">{{cite web|url=http://apvma.gov.au/node/12371|title=Chemical Review: Atrazine|publisher=Australian Pesticides and Veterinary Medicines Authority|access-date=2015-02-11|date=2014-05-28}}</ref>

{{As of|2001}}, atrazine was the most commonly detected pesticide contaminating drinking water in the U.S.<ref name=USGS>Gilliom RJ et al. US Geological Survey [http://pubs.usgs.gov/circ/2005/1291/pdf/circ1291_chapter4.pdf The Quality of Our Nation’s Waters: Pesticides in the Nation’s Streams and Ground Water, 1992–2001] March 2006, Revised February 15, 2007</ref>{{rp|44}} Studies suggest it is an [[endocrine disruptor]], an agent that can alter the natural hormonal system.<ref name=AtrazineChemSummEPA>{{Cite report|date=2007-04-24 |title=Atrazine: Chemical Summary. Toxicity and Exposure Assessment for Children's Health |url=http://www.epa.gov/teach/chem_summ/Atrazine_summary.pdf |publisher=U.S. Environmental Protection Agency |url-status=dead |archive-url=https://web.archive.org/web/20120316130312/http://www.epa.gov/teach/chem_summ/Atrazine_summary.pdf |archive-date=2012-03-16 }}</ref> However, in 2006 the [[United States Environmental Protection Agency|U.S. Environmental Protection Agency]] (EPA) had stated that under the [[Food Quality Protection Act]] "the risks associated with the pesticide residues pose a reasonable certainty of no harm",<ref name="EPATriazine">[http://www.epa.gov/oppsrrd1/cumulative/triazine_fs.htm Triazine Cumulative Risk Assessment and Atrazine, Simazine, and Propazine Decisions] {{webarchive |url=https://web.archive.org/web/20130601222524/http://www.epa.gov/oppsrrd1/cumulative/triazine_fs.htm |date=June 1, 2013 }}, June 22, 2006, EPA.</ref> and in 2007, the EPA said that atrazine does not adversely affect amphibian sexual development and that no additional testing was warranted.<ref name=EPAUpdateAmphib>[http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm#amphibian Atrazine Updates: Amphibians], April 2010, EPA.</ref> EPA's 2009 review<ref name="EPAPress">[http://yosemite.epa.gov/opa/admpress.nsf/d0cf6618525a9efb85257359003fb69d/554b6abea9d0672f85257648004a88c1!OpenDocument EPA Begins New Scientific Evaluation of Atrazine], October 7, 2009, EPA.</ref> concluded that "the agency's scientific bases for its regulation of atrazine are robust and ensure prevention of exposure levels that could lead to reproductive effects in humans".<ref name="AtraUpdateHealth">EPA [http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm#atrazine Atrazine Updates: Scientific Peer Review—Human Health] Current as of January 2013. Accessed March 15, 2014</ref> However, in their 2016 Refined Ecological Risk Assessment for Atrazine, it was stated that "it is difficult to make definitive conclusions about the impact of atrazine at a given concentration but multiple studies have reported effects to various endpoints at environmentally-relevant concentrations."<ref>{{cite web |title=Refined Ecological Risk Assessment for Atrazine |url=https://www.regulations.gov/document?D=EPA-HQ-OPP-2013-0266-0315 |publisher=EPA |access-date=12 October 2020 |page=184}}</ref> EPA started a registration review in 2013.<ref name="AtraUpdateHealthB">EPA [ww.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm#amphibian Atrazine Updates: Scientific Peer Review—Amphibians] Current as of January 2013. Accessed March 15, 2014</ref>

The EPA's review has been criticized, and the safety of atrazine remains controversial.<ref name=yorker>[http://www.newyorker.com/reporting/2014/02/10/140210fa_fact_aviv?currentPage=all "A Valuable Reputation: Tyrone Hayes said that a chemical was harmful, its maker pursued him"] by Rachel Aviv, ''[[The New Yorker]]'', 10 February 2014</ref><ref name="NYT">{{cite news|url=https://www.nytimes.com/2009/08/23/us/23water.html?_r=1&hp=&pagewanted=all|title=Debating How Much Weed Killer Is Safe in Your Water Glass |last=Duhigg|first=Charles|date=August 22, 2009|work=The New York Times|access-date=2015-05-02}}</ref><ref name=TillittFish>{{cite journal |vauthors=Tillitt DE, Papoulias DM, Whyte JJ, Richter CA |title=Atrazine reduces reproduction in fathead minnow (Pimephales promelas) |journal=Aquat. Toxicol. |volume=99 |issue=2 |pages=149–59 |year=2010 |pmid=20471700 |doi=10.1016/j.aquatox.2010.04.011 |url=https://zenodo.org/record/1258744 }}</ref> EPA has however stated that "If at any time EPA determines there are urgent human or environmental risks from atrazine exposure that require prompt attention, we will take appropriate regulatory action, regardless of the status of the registration review process."<ref name=EPAatrazine>{{cite news|url=https://www.epa.gov/ingredients-used-pesticide-products/atrazine| title= Ingredients Used in Pesticide Products-Atrazine | work= US Environmental Protection Agency}}</ref>

Its use was banned in the [[European Union]] in 2004, when the EU found groundwater levels exceeding the limits set by regulators, and Syngenta could not show that this could be prevented nor that these levels were safe.<ref name=EUban>European Commission. [http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv:OJ.L_.2004.078.01.0053.01.ENG 2004/248/EC: Commission Decision of 10 March 2004 concerning the non-inclusion of atrazine in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance (Text with EEA relevance) (notified under document number C(2004) 731)] Decision 2004/248/EC - Official Journal L 078, Decision 2004/248/EC. March 16, 2004: Quote: "(9)Assessments made on the basis of the information submitted have not demonstrated that it may be expected that, under the proposed conditions of use, plant protection products containing atrazine satisfy in general the requirements laid down in Article 5(1)(a) and (b) of Directive 91/414/EEC. In particular, available monitoring data were insufficient to demonstrate that in large areas concentrations of the active substance and its breakdown products will not exceed 0,1 μg/l in groundwater. Moreover, it cannot be assured that continued use in other areas will permit a satisfactory recovery of groundwater quality where concentrations already exceed 0,1 μg/l in groundwater. These levels of the active substance exceed the limits in Annex VI to Directive 91/414/EEC and would have an unacceptable effect on groundwater." (10) Atrazine should therefore not be included in Annex I to Directive 91/414/EEC. (11) Measures should be taken to ensure that existing authorisations for plant protection products containing atrazine are withdrawn within a prescribed period and are not renewed and that no new authorisations for such products are granted."</ref><ref name=NYT2004>Danny Hakimfeb for the New York Times. February 23, 2015. [https://www.nytimes.com/2015/02/24/business/international/a-pesticide-banned-or-not-underscores-trans-atlantic-trade-sensitivities.html?_r=0 A Pesticide Banned, or Not, Underscores Trans-Atlantic Trade Sensitivities]</ref>

Atrazine is a [[herbicide]] that is used to stop pre- and post-emergence broadleaf and grassy [[weed]]s in crops such as [[sorghum]], [[maize]], [[sugarcane]], [[lupins]], [[pine]], and [[eucalypt]] plantations, and triazine-tolerant [[canola]].<ref name="APVMAmain"/>

In the [[United States]] as of 2014, atrazine was the second-most widely used herbicide after [[glyphosate]],<ref name=yorker/> with {{convert|76|e6lb|e3MT|abbr=off}} of it applied each year.<ref>{{cite news | last = Walsh | first = Edward | title = EPA Stops Short of Banning Herbicide | url = http://www.waterconserve.org/shared/reader/welcome.aspx?linkid=19803 | pages = A14 | newspaper = Washington Post | date = 2003-02-01 | access-date = 2007-04-27 }}</ref><ref name=rupr>{{cite web|title=Restricted Use Products (RUP) Report: Six Month Summary List |publisher=[[Environmental Protection Agency]] |url=http://www.epa.gov/opprd001/rup/rup6mols.htm |access-date=1 December 2009 |archive-url=https://web.archive.org/web/20100111030314/http://www.epa.gov/opprd001/rup/rup6mols.htm |archive-date=11 January 2010 |url-status=dead }}</ref> Atrazine continues to be one of the most widely used herbicides in Australian agriculture.<ref name="APVMAmain"/> Its effect on corn yields has been estimated from 1% to 8%, with 3–4% being the conclusion of one economics review.<ref name=Ackerman2007>{{Cite journal

| author = Ackerman, Frank

| title = The economics of atrazine

| journal = International Journal of Occupational and Environmental Health

| volume = 13

| issue = 4

| pages = 437–445

| year = 2007

| pmid = 18085057

| url = http://ase.tufts.edu/gdae/Pubs/rp/EconAtrazine.pdf

| doi=10.1179/oeh.2007.13.4.437

| s2cid = 2655422

| author-link = Frank Ackerman

}}</ref><ref>{{cite journal |title=BioOne Online Journals - A Rationale for Atrazine Stewardship in Corn |doi=10.1614/WS-06-104.1 |volume=55 |journal=Weed Science |pages=75–81|year = 2017|last1 = Swanton|first1 = Clarence J|last2= Gulden|first2= Robert H|last3= Chandler|first3= Kevin|s2cid=86209323 }}</ref> In another study looking at combined data from 236 university corn field trials from 1986 to 2005, atrazine treatments showed an average of 5.7 bushels more per acre (~400&nbsp;kg per hectare) than alternative herbicide treatments.<ref name=NCWSS>Fawcett, Richard S. "[http://www.ncwss.org/proceed/2008/abstracts/137.pdf Twenty Years of University Corn Yield Data: With and Without Atrazine]", [http://www.ncwss.org/about.php North Central Weed Science Society] {{webarchive |url=https://web.archive.org/web/20140305163756/http://www.ncwss.org/about.php |date=March 5, 2014 }}, 2008</ref> Effects on sorghum yields have been estimated to be as high as 20%, owing in part to the absence of alternative weed control products that can be used on sorghum.<ref>{{cite journal |title=Market-level assessment of the economic benefits of atrazine in the United States | doi=10.1002/ps.3703 | pmid=24318916 |volume=70 | issue=11 |journal=Pest Management Science |pages=1684–1696|pmc=4282455|year = 2014|last1 = Mitchell|first1 = P. D}}</ref>

Atrazine was invented in 1958 in the [[Geigy]] laboratories as the second of a series of 1,3,5-triazines.<ref>{{cite book|url=https://books.google.com/books?id=CdBpwokWL08C&pg=PA360|title=Modern Crop Protection Compounds, Volume 1|author=Wolfgang Krämer|year=2007|publisher=Wiley-VCH|isbn=9783527314966}}</ref>

Atrazine is prepared from [[cyanuric chloride]], which is treated sequentially with [[ethylamine]] and [[isopropylamine]]. Like other triazine herbicides, atrazine functions by binding to the [[plastoquinone]]-binding [[protein]] in [[photosystem II]], which animals lack. Plant death results from starvation and oxidative damage caused by breakdown in the [[electron transport]] process. Oxidative damage is accelerated at high light intensity.<ref>{{Cite encyclopedia

| last1 = Appleby | first1 = Arnold P.

| last2 = Müller | first2 = Franz

| last3 = Carpy | first3 = Serge

| doi = 10.1002/14356007.a28_165

| encyclopedia = Ullmann's Encyclopedia of Industrial Chemistry

| year = 2001

| isbn = 978-3-527-30673-2

| chapter = Weed Control

}}</ref>

Atrazine's effects in humans and animals primarily involve the [[endocrine system]]. Studies suggest that atrazine is an [[endocrine disruptor]] that can cause [[hormone imbalance]].<ref name="AtrazineChemSummEPA"/>

Atrazine has been found to act as an [[agonist]] of the [[G protein-coupled estrogen receptor 1]].<ref name="ProssnitzBarton2014">{{cite journal |last1=Prossnitz |first1=Eric R. |last2=Barton |first2=Matthias |title=Estrogen biology: New insights into GPER function and clinical opportunities |journal=Molecular and Cellular Endocrinology |date=May 2014 |volume=389 |issue=1–2 |pages=71–83 |doi=10.1016/j.mce.2014.02.002 |pmid=24530924 |pmc=4040308 }}</ref> Atrazine has been shown to covalently bind to (chemically react with) a large number of mammalian proteins.<ref>{{cite journal |last1=Dooley |first1=G. P. |last2=Reardon |first2=K. F. |last3=Prenni |first3=J. E. |last4=Tjalkens |first4=R. B. |last5=Legare |first5=M. E. |last6=Foradori |first6=C. D. |last7=Tessari |first7=J. E. |last8=Hanneman |first8=W. H. |title=Proteomic Analysis of Diaminochlorotriazine Adducts in Wister Rat Pituitary Glands and LβT2 Rat Pituitary Cells |journal=Chemical Research in Toxicology |date=April 2008 |volume=21 |issue=4 |pages=844–851 |doi=10.1021/tx700386f |pmid=18370413 }}</ref>

==Environment==

===Levels===

Atrazine contamination of surface water (lakes, rivers, and streams) in the U.S. has been monitored by the EPA and has consistently exceeded levels of concern in two Missouri watersheds and one in Nebraska.<ref>{{cite web|url=http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm |title=Atrazine Updates &#124; Pesticides &#124; US EPA |publisher=Epa.gov |access-date=2015-02-08}}</ref> Monitoring of atrazine levels in community water systems in 31 high-use states found that levels exceeded levels of concern for infant exposure during at least one year between 1993 and 2001 in 34 of 3670 community water systems using surface water, and in none of 14,500 community water systems using groundwater.<ref>{{cite web|url=http://www.epa.gov/oppsrrd1/REDs/atrazine_combined_docs.pdf |title=www.epa.gov |url-status=dead |archive-url=https://web.archive.org/web/20080625030339/http://www.epa.gov/oppsrrd1/REDs/atrazine_combined_docs.pdf |archive-date=2008-06-25 }}</ref> Surface water monitoring data from 20 high atrazine use watersheds found peak atrazine levels up to 147 parts per billion, with daily averages in all cases below 10 parts per billion.

[[File:Pathway Atrazine degradation.svg|thumb|right|300px|Atrazine biodegradation - [[atrazine chlorohydrolase]] pathway]]

Atrazine remains in soil for a matter of months (although in some soils can persist to at least 4 years)<ref name=AtrazineChemSummEPA/> and can migrate from soil to [[groundwater]]; once in groundwater, it degrades slowly. It has been detected in groundwater at high levels in some regions of the U.S. where it is used on some crops and turf. The U.S. Environmental Protection Agency expresses concern regarding contamination of surface waters (lakes, rivers, and streams).<ref name=AtrazineChemSummEPA />

Atrazine degrades in [[soil]] primarily by the action of [[microbe]]s. <!--there's probably also a non-bio route-->The [[half-life]] of atrazine in soil ranges from 13 to 261 days.<ref>[http://www.epa.gov/oppsrrd1/REDs/atrazine_combined_docs.pdf Interim Reregistration Eligibility Decision for Atrazine] {{webarchive |url=https://web.archive.org/web/20080625030339/http://www.epa.gov/oppsrrd1/REDs/atrazine_combined_docs.pdf |date=June 25, 2008 }}, U.S. EPA, January, 2003.</ref> Atrazine [[biodegradation]] can occur by two known pathways:

#[[Hydrolysis]] of the C-Cl bond is followed by the [[Ethyl group|ethyl]] and [[isopropyl]] groups, catalyzed by the [[hydrolase]] [[enzyme]]s called AtzA, AtzB, and AtzC. The end product of this process is [[cyanuric acid]], itself unstable with respect to ammonia and carbon dioxide. The best characterized organisms that use this pathway are of ''[[Pseudomonas]]'' sp. strain ADP.

#Dealkylation of the [[amino group]]s gives 2-chloro-4-hydroxy-6-amino-1,3,5-triazine, the degradation of which is unknown. This path also occurs in ''Pseudomonas'' species, as well as a number of bacteria.<ref>Zeng Y, Sweeney CL, Stephens S, Kotharu P. (2004). Atrazine Pathway Map. Wackett LP. Biodegredation Database.</ref><ref name="wackett">{{cite journal |last1=Wackett |first1=L. P. |last2=Sadowsky |first2=M. J. |last3=Martinez |first3=B. |last4=Shapir |title=Biodegradation of atrazine and related s-triazine compounds: from enzymes to field studies |journal=Applied Microbiology and Biotechnology |volume=58 |issue=1 |pages=39–45 |date=January 2002 |pmid=11831474 |doi= 10.1007/s00253-001-0862-y |first4=N.|s2cid=2998290 }}</ref>

Rates of biodegradation are affected by atrazine's low solubility; thus [[surfactant]]s may increase the degradation rate. Though the two alkyl moieties readily support growth of certain microorganisms, the atrazine ring is a poor energy source due to the oxidized state of ring carbon. In fact, the most common pathway for atrazine degradation involves the intermediate, cyanuric acid, in which carbon is fully oxidized, thus the ring is primarily a nitrogen source for aerobic microorganisms. Atrazine may be [[catabolism|catabolized]] as a carbon and nitrogen source in reducing environments, and some aerobic atrazine degraders have been shown to use the compound for growth under anoxia in the presence of nitrate as an electron acceptor,<ref>{{cite journal | authors = Crawford, J. J., G.K. Sims, R.L. Mulvaney, and M. Radosevich | year = 1998 | title = Biodegradation of atrazine under denitrifying conditions | journal = Appl. Microbiol. Biotechnol. | volume = 49 | pages = 618–623 | doi = 10.1007/s002530051223 | pmid = 9650260 | issue = 5| s2cid = 5126687 }}</ref> a process referred to as a [[denitrification]]. When atrazine is used as a nitrogen source for bacterial growth, degradation may be regulated by the presence of alternative sources of nitrogen. In pure cultures of atrazine-degrading bacteria, as well as active soil communities, atrazine ring nitrogen, but not carbon are assimilated into microbial biomass.<ref>{{cite journal | authors = Bichat, F., G.K. Sims, and R.L. Mulvaney | year = 1999 | title = Microbial utilization of heterocyclic nitrogen from atrazine | journal = Soil Science Society of America Journal | volume = 63 | issue = 1 | pages = 100–110 | doi = 10.2136/sssaj1999.03615995006300010016x| bibcode = 1999SSASJ..63..100B }}</ref> Low concentrations of [[glucose]] can decrease the bioavailability, whereas higher concentrations promote the catabolism of atrazine.<ref>{{cite journal |vauthors=Ralebitso TK, Senior E, van Verseveld HW | year = 2002 | title = Microbial aspects of atrazine degradation in natural environments | journal = [[Biodegradation (journal)|Biodegradation]] | volume = 13 | issue = 1 | pages = 11–19 | doi = 10.1023/A:1016329628618| pmid = 12222950 | s2cid = 21098999 | url = https://research.tees.ac.uk/en/publications/c8197257-2338-4626-8ca5-73f70b276b73 }}</ref>

The [[gene]]s for enzymes AtzA-C have been found to be highly conserved in atrazine-degrading organisms worldwide. In ''Pseudomonas'' sp. ADP, the Atz genes are located noncontiguously on a [[plasmid]] with the genes for [[mercury (element)|mercury]] catabolism. AtzA-C genes have also been found in a [[Gram-positive bacteria|Gram-positive bacterium]], but are chromosomally located.<ref>{{cite journal |vauthors=Cai B, Han Y, Liu B, Ren Y, Jiang S | year = 2003 | title = Isolation and characterization of an atrazine-degrading bacterium from industrial wastewater in China | journal = [[Letters in Applied Microbiology]] | volume = 36 | pages = 272–276 | doi = 10.1046/j.1472-765X.2003.01307.x | pmid=12680937 | issue = 5| s2cid = 8003165 }}</ref> The insertion elements flanking each gene suggest that they are involved in the assembly of this specialized catabolic pathway.<ref name="wackett"/> Two options exist for degradation of atrazine using microbes, [[bioaugmentation]] or [[biostimulation]].<ref name="wackett"/> Recent research suggests that microbial adaptation to atrazine has occurred in some fields where the herbicide is used repetitively, resulting in more rapid biodegradation.<ref>{{cite journal | authors = Krutz, L.J., D.L. Shaner, C. Accinelli, R.M. Zablotowicz, and W.B. Henry | year = 2008 | title = Atrazine dissipation in s-triazine-adapted and non-adapted soil from Colorado and Mississippi: Implications of enhanced degradation on atrazine fate and transport parameters | journal = Journal of Environmental Quality | volume = 37 | pages = 848–857 | doi = 10.2134/jeq2007.0448 | pmid = 18453406 | issue = 3}}</ref> Like the herbicides [[trifluralin]] and [[alachlor]], atrazine is susceptible to rapid transformation in the presence of reduced iron-bearing soil clays, such as ferruginous [[smectite]]s. In natural environments, some iron-bearing minerals are reduced by specific bacteria in the absence of oxygen, thus the abiotic transformation of herbicides by reduced minerals is viewed as "microbially induced".<ref>{{cite journal | authors = Xu, J., J. W. Stucki, J. Wu, J. Kostka, and G. K. Sims | year = 2001 | title = Fate of atrazine and alachlor in redox-treated ferruginous smectite | journal = Environmental Toxicology and Chemistry | volume = 20 | pages = 2717–2724 | doi = 10.1002/etc.5620201210 | issue = 12| pmid = 11764154 }}</ref>

===Photolysis===

In 2016, photolytic degradation with 254&nbsp;nm [[ultraviolet]] was seen by the authors of a particular study as an efficient process, which could be used in pilot plants to reduce or eliminate compounds of the atrazine class or similar emerging contaminants, in effluents.<ref name=fdel>[https://www.researchgate.net/profile/Francisco_Pereira20/publication/310843049_Photolytic_Degradation_of_Herbicide_Atrazine_by_Radiation_Ultraviolet_UVC_An_Application_of_Green_Chemistry/links/5839959a08aef00f3bfbba30/Photolytic-Degradation-of-Herbicide-Atrazine-by-Radiation-Ultraviolet-UVC-An-Application-of-Green-Chemistry.pdf Felix de Lima et al, "Photolytic Degradation of Herbicide Atrazine by Radiation Ultraviolet (UVC): An Application of Green Chemistry"], Chemical Science International Journal 17(3): 1-10, 2016</ref>

==Health effects==

According to Extension Toxicology Network in the U.S., "The oral median Lethal Dose or {{LD50}} for atrazine is 3090 mg/kg in [[rat]]s, 1750 mg/kg in [[mouse|mice]], 750 mg/kg in [[rabbit]]s, and 1000 mg/kg in hamsters. The dermal LD₅₀ in rabbits is 7500 mg/kg and greater than 3000 mg/kg in rats. The 1-hour inhalation LC₅₀ is greater than 0.7 mg/L in rats. The 4-hour inhalation LC₅₀ is 5.2 mg/L in rats." The [[maximum contaminant level]] is 0.003&nbsp;mg/L and the [[reference dose]] is 0.035&nbsp;mg/kg/day.<ref>[http://extoxnet.orst.edu/pips/atrazine.htm Pesticide Information Profile: Atrazine], Extension Toxicology Network (Cooperative Extension Offices of Cornell University, Oregon State University, the University of Idaho, and the University of California at Davis and the Institute for Environmental Toxicology, Michigan State University), June 1996.</ref>

[[File:Atrazine USA 2011.png|thumb|376px|Atrazine use in pounds per square mile by county. Atrazine is one of the most commonly used herbicides in the United States.<ref>{{Cite web|url=https://water.usgs.gov/nawqa/pnsp/usage/maps/|title=USGS NAWQA: The Pesticide National Synthesis Project|website=water.usgs.gov}}</ref>]]

===Mammals===

A September 2003 review by the [[Agency for Toxic Substances and Disease Registry]] (ATSDR) stated that atrazine is "currently under review for pesticide re-registration by the EPA because of concerns that atrazine may cause cancer", but not enough information was available to "definitely state whether it causes cancer in humans." According to the ATSDR, one of the primary ways that atrazine can affect a person's health is "by altering the way that the reproductive system works. Studies of couples living on farms that use atrazine for weed control found an increase in the risk of preterm delivery, but these studies are difficult to interpret because most of the farmers were men who may have been exposed to several types of pesticides. Little information is available regarding the risks to children, however "[m]aternal exposure to atrazine in drinking water has been associated with low fetal weight and heart, urinary, and limb defects in humans".<ref name=ATSDR>{{cite web | url=http://www.atsdr.cdc.gov/phs/phs.asp?id=336&tid=59 | publisher = Center for Disease Control, Agency for Toxic Substances and Disease Registry, Division of Toxicology and Human Health Sciences | title= Public Health Statement for Atrazine | website = Toxic Substances Portal - Atrazine | date = September 2003 | access-date = May 2, 2015}}</ref> Incidence of a birth defect known as [[gastroschisis]] appears to be higher in areas where surface water atrazine levels are elevated especially when conception occurs in the spring, the time when atrazine is commonly applied.<ref>{{Cite journal | title= Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State | journal =American Journal of Obstetrics and Gynecology | volume=202 | issue= 3 | pages= 241.e1–241.e6 | date = March 2010 | doi=10.1016/j.ajog.2010.01.023| pmid= 20207240 | last1 =Waller | first1 =Sarah A | last2 =Paul | first2 =Kathleen | last3 =Peterson | first3 =Suzanne E | last4 =Hitti | first4 =Jane E }}</ref>

The [[World Health Organization]]'s [[International Agency for Research on Cancer]] has classified atrazine as "not classifiable as to its carcinogenicity to humans" ([[List of IARC Group 3 Agents - Not classifiable as to its carcinogenicity to humans|Group 3]]).<ref>{{cite journal | url=https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono73.pdf | volume=73 | journal = IARC Monographs on the Evaluation of Carcinogenic Risks to Humans | title= IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS | publisher=[[International Agency for Research on Cancer]]}}</ref>

The EPA determined in 2003 "that atrazine is not likely to cause cancer in humans".<ref>[http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm#cancer Interim Reregistration Eligibility Decision for Atrazine], U.S. EPA, January, 2003.</ref>

In 2006, the EPA stated, "the risks associated with the pesticide residues pose a reasonable certainty of no harm".<ref name="EPATriazine" /><ref name="EPAUpdateAmphib" />

In 2007, the EPA said, "studies thus far suggest that atrazine is an [[endocrine disruptor]]". The implications for children's health are related to effects during pregnancy and during sexual development, though few studies are available. In people, risks for preterm delivery and intrauterine growth retardation have been associated with exposure. Atrazine exposure has been shown to result in delays or changes in [[pubertal]] development in female rats; conflicting results have been observed in males. Male rats exposed via milk from orally exposed mothers exhibited higher levels of prostate inflammation as adults; immune effects have also been seen in male rats exposed in utero or while nursing.<ref name="AtrazineChemSummEPA" /> EPA opened a new review in 2009<ref name="EPAPress" /> that concluded that "the agency's scientific bases for its regulation of atrazine are robust and ensure prevention of exposure levels that could lead to reproductive effects in humans."<ref name="AtraUpdateHealth" /> Deborah A. Cory-Slechta, a professor at the University of Rochester in New York has said in 2014, "The way the E.P.A. tests chemicals can vastly underestimate risks." She has studied atrazine's effects on the brain and serves on the E.P.A.'s science advisory board. She further stated, "There's still a huge amount we don't know about atrazine."<ref name=yorker/>

A [[Natural Resources Defense Council]] report from 2009 said that the EPA is ignoring atrazine contamination in surface and drinking water in the central United States.<ref name="NRDC, Poisoning the Well">{{cite news| url=http://graphics8.nytimes.com/packages/pdf/us/NRDC-Atrazine-report.pdf?scp=2&sq=atrazine&st=cse | work=[[Natural Resources Defense Council]] |publisher=The New York Times | title=How the EPA is Ignoring Atrazine Contamination in Surface and Drinking Water in the Central United States |date=August 2009}}</ref>

Research results from the U.S. [[National Cancer Institute]]'s 2011 Agricultural Health Study concluded, "there was no consistent evidence of an association between atrazine use and any cancer site". The study tracked 57,310 licensed pesticide applicators over 13 years.<ref name=EHP2011>Beane Freeman, Laura E. (2011) ''[http://ehp03.niehs.nih.gov/article/fetchArticle.action;jsessionid=16CAEF820312206AF426693F83851464?articleURI=info:doi/10.1289/ehp.1103561 Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007)] {{Webarchive|url=https://web.archive.org/web/20120328114218/http://ehp03.niehs.nih.gov/article/fetchArticle.action;jsessionid=16CAEF820312206AF426693F83851464?articleURI=info%3Adoi%2F10.1289%2Fehp.1103561 |date=2012-03-28 }}.'' Environmental Health Perspectives.</ref>

A 2011 review of the mammalian reproductive toxicology of atrazine jointly conducted by the [[World Health Organization]] and the [[Food and Agriculture Organization]] of the United Nations concluded that atrazine was not [[teratogenic]]. Reproductive effects in rats and rabbits were only seen at doses that were toxic to the mother. Observed adverse effects in rats included [[fetal resorption]] in rates (at doses <u>></u> 50&nbsp;mg/kg per day), delays in sexual development in female rats (at doses <u>></u>30&nbsp;mg/kg per day), and decreased birth weight (at doses <u>></u>3.6&nbsp;mg/kg per day).<ref>{{cite web |url=https://www.who.int/water_sanitation_health/dwq/chemicals/antrazine.pdf?ua=1 |title=Chemical Hazards in Drinking Water - Atrazine |access-date=2015-02-08 }}</ref>

A 2014 systematic review, funded by atrazine manufacturer Syngenta, assessed its relation to reproductive health problems. The authors concluded that the quality of most studies was poor and without good quality data, the results were difficult to assess, though it was noted that no single category of negative pregnancy outcome was found consistently across studies. The authors concluded that a causal link between atrazine and adverse pregnancy outcomes was not warranted due to the poor quality of the data and the lack of robust findings across studies. Syngenta was not involved in the design, collection, management, analysis, or interpretation of the data and did not participate in the preparation of the manuscript.<ref>{{Cite journal

| pmid = 24797711

| pmc = 4265844

| year = 2014

| last1 = Goodman

| first1 = M

| title = Atrazine and pregnancy outcomes: A systematic review of epidemiologic evidence

| journal = Birth Defects Research Part B: Developmental and Reproductive Toxicology

| volume = 101

| issue = 3

| pages = 215–36

| last2 = Mandel

| first2 = J. S.

| last3 = Desesso

| first3 = J. M.

| last4 = Scialli

| first4 = A. R.

| doi = 10.1002/bdrb.21101

}}</ref>

===Amphibians===

Atrazine has been a suspected [[teratogen]], with some studies reporting causing demasculinization in male [[northern leopard frog]]s even at low concentrations,<ref name="EU">{{cite news | author = Jennifer Lee | title = Popular Pesticide Faulted for Frogs' Sexual Abnormalities | date = 2003-06-19 | work = The New York Times | url = https://www.nytimes.com/2003/06/19/us/popular-pesticide-faulted-for-frogs-sexual-abnormalities.html}}</ref> and an [[Endocrine system|endocrine]] disruptor.<ref>{{cite journal |author1=Mizota, K. |author2=Ueda, H. | year = 2006 | doi = 10.1093/toxsci/kfj087 | journal = [[Toxicological Sciences]] | title = Endocrine Disrupting Chemical Atrazine Causes Degranulation through Gq/11 Protein-Coupled Neurosteroid Receptor in Mast Cells | volume = 90 | pmid = 16381660 | issue = 2 | pages = 362–8| doi-access = free }}</ref> A 2002 study by Tyrone Hayes, of the University of California, Berkeley, found that exposure caused male [[tadpole]]s to turn into [[hermaphrodites]] – frogs with both male and female sexual characteristics.<ref name="Briggs">Briggs, Helen. (April 15, 2002), [http://news.bbc.co.uk/1/hi/sci/tech/1930658.stm Pesticide 'causes frogs to change sex']. ''BBC News''. Retrieved on 2007-10-16.</ref> However, this study has not been able to be [[reproducibility|replicated]],<ref name=eparesp>{{cite news | url = https://www.epa.gov/sites/default/files/2019-04/documents/5001-response.pdf | title = Summary of Atrazine Reregistration Activities }}</ref> and a 2003 EPA review of this study concluded that overcrowding, questionable sample handling techniques, and the failure of the authors to disclose key details including sample sizes, dose-response effects, and the variability of observed effects made it difficult to assess the study's credibility and ecological relevance.<ref name=eparesp /><ref>{{cite web |url=http://www.epa.gov/scipoly/sap/meetings/2003/june/dereporthdemasculinizedfrogsafterexposureherbicideatrazineatlowecologicallyhayes2.pdf |title=www.epa.gov |website=EPA Scientific Advisory Panel|date=June 2003 }}</ref> A 2005 study, requested by EPA and conducted under EPA guidance and inspection, was unable to reproduce Hayes´ results.<ref name="Jooste-et-al-2005">{{cite journal |last1=Jooste |first1=Alarik M. |last2=Du Preez |first2=Louis H. |last3=Carr |first3=James A. |last4=Giesy |first4=John P. |last5=Gross |first5=Timothy S. |last6=Kendall |first6=Ronald J. |last7=Smith |first7=Ernest E. |last8=Van Der Kraak |first8=Glen L. |last9=Solomon |first9=Keith R. |title=Gonadal Development of Larval Male Xenopus laevis Exposed to Atrazine in Outdoor Microcosms |journal=Environmental Science & Technology |date=July 2005 |volume=39 |issue=14 |pages=5255–5261 |doi=10.1021/es048134q |pmid=16082954 |bibcode=2005EnST...39.5255J }}</ref>

The EPA's Scientific Advisory Panel examined relevant studies and concluded in 2010, "atrazine does not adversely affect amphibian gonadal development based on a review of laboratory and field studies".<ref name=EPAUpdateAmphib/> It recommended proper study design for further investigation. As required by the EPA, two experiments were conducted under Good Laboratory Practices (GLP) and were inspected by EPA and German regulatory authorities, concluding 2009 that "long-term exposure of larval ''X. laevis'' to atrazine at concentrations ranging from 0.01 to 100 μg/l does not affect growth, larval development, or sexual differentiation".<ref>{{cite journal |last1=Kloas |first1=Werner |last2=Lutz |first2=Ilka |last3=Springer |first3=Timothy |last4=Krueger |first4=Henry |last5=Wolf |first5=Jeff |last6=Holden |first6=Larry |last7=Hosmer |first7=Alan |title=Does Atrazine Influence Larval Development and Sexual Differentiation in Xenopus laevis? |journal=Toxicological Sciences |date=February 2009 |volume=107 |issue=2 |pages=376–384 |doi=10.1093/toxsci/kfn232 |pmid=19008211 |pmc=2639758 }}</ref> A 2008 report cited the independent work of researchers in Japan, who were unable to replicate Hayes' work. "The scientists found no hermaphrodite frogs; no increase in aromatase as measured by aromatase mRNA induction; and no increase in [[vitellogenin]], another marker of feminization."<ref>{{cite journal |last1=Renner |first1=Rebecca |title=Atrazine Effects in Xenopus Aren't Reproducible |journal=Environmental Science & Technology |date=May 2008 |volume=42 |issue=10 |pages=3491–3493 |doi=10.1021/es087113j |pmid=18546678 |bibcode=2008EnST...42.3491R |doi-access=free }}</ref>

A 2007 study examined the relative importance of environmentally relevant concentrations of atrazine on [[Trematode lifecycle stages|trematode cercariae]] versus tadpole defense against infection. Its principal finding was that susceptibility of [[wood frog]] tadpoles to infection by ''E. trivolvis'' is increased only when hosts were exposed to an atrazine concentration of 30&nbsp;mg/L and not to 3&nbsp;mg/L.<ref>{{cite journal |last1=Koprivnikar |first1=Janet |last2=Forbes |first2=Mark R. |last3=Baker |first3=Robert L. |title=Contaminant Effects on Host–Parasite Interactions: Atrazine, Frogs, and Trematodes |journal=Environmental Toxicology and Chemistry |date=2007 |volume=26 |issue=10 |pages=2166–70 |doi=10.1897/07-220.1 |pmid=17867892 }}</ref>

A 2008 study reported that tadpoles developed deformed hearts and impaired kidneys and digestive systems when chronically exposed to atrazine concentrations of 10 ppm in their early stages of life. Tissue malformation may have been induced by ectopic [[programmed cell death]], although a mechanism was not identified.<ref name=Tufts2008>{{cite journal |vauthors=Lenkowski JR, Reed JM, Deininger L, McLaughlin KA |title=Perturbation of organogenesis by the herbicide atrazine in the amphibian Xenopus laevis |journal=Environ. Health Perspect. |volume=116 |issue=2 |pages=223–30 |year=2008 |pmid=18288322 |pmc=2235211 |doi=10.1289/ehp.10742 }}</ref>

In 2010, the [[Australian Pesticides and Veterinary Medicines Authority]] (APVMA) tentatively concluded that environmental atrazine "at existing levels of exposure" was not affecting amphibian populations in Australia consistent with the 2007 EPA findings.<ref name="apvma2010">[https://web.archive.org/web/20100704154517/http://www.apvma.gov.au/news_media/chemicals/atrazine.php Chemicals in the News: Atrazine], [[Minister for Agriculture, Fisheries and Forestry (Australia)|Australian Pesticides and Veterinary Medicines Authority]], Original June 30, 2010, Archived by Internet Archive July 4, 2010</ref> APVMA responded to Hayes' 2010 published paper,<ref>{{cite journal | pmid = 20194757 | year = 2010 | last1 = Hayes | first1 = TB | last2 = Khoury | first2 = V | last3 = Narayan | first3 = A | last4 = Nazir | first4 = M | last5 = Park | first5 = A | last6 = Brown | first6 = T | last7 = Adame | first7 = L | last8 = Chan | first8 = E | last9 = Buchholz | first9 = D | last10 = Stueve | first10 = T. | last11 = Gallipeau | first11 = S. | title = Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis) | volume = 107 | issue = 10 | pages = 4612–7 | doi = 10.1073/pnas.0909519107 | pmc = 2842049 | journal = Proceedings of the National Academy of Sciences of the United States of America| display-authors = 8 | bibcode = 2010PNAS..107.4612H | doi-access = free }}</ref> that his findings "do not provide sufficient evidence to justify a reconsideration of current regulations which are based on a very extensive dataset."<ref name="apvma2010" />

A 2015 EPA article discussed the Hayes/Syngenta conflict to illustrate both financial and nonfinancial conflicts of interest. The authors concluded, "Statements by Hayes and Syngenta suggest that their scientific differences have developed a personal aspect that casts doubt on their scientific objectivity".<ref>{{cite journal |title=The problem of biased data and potential solutions for health and environmental assessments |journal=Human and Ecological Risk Assessment |year=2015 |last1=Suter |first1=Glenn |last2=Cormier |first2=Susan |volume=21 |issue=7 |doi=10.1080/10807039.2014.974499 |pages=1–17|s2cid=84723794 }}</ref>

===Class action lawsuit===

In 2012, Syngenta, manufacturer of atrazine, was the defendant in a class-action lawsuit concerning the levels of atrazine in human water supplies. Syngenta agreed to pay $105 million to reimburse more than one thousand water systems for "the cost of filtering atrazine from drinking water". The company denied all wrongdoing.<ref name=yorker/>

<ref>[http://www.atrazinesettlement.com/ City of Greenville v. Syngenta Crop Protection, Inc., and Syngenta AG Case No. 3:10-cv-00188-JPG-PMF], accessed August 23, 2013</ref><ref>Clare Howard

for Environmental Health News. June 17, 2013 [http://www.environmentalhealthnews.org/ehs/news/2013/atrazine Special Report: Syngenta's campaign to protect atrazine, discredit critics.]</ref>

* [[Pesticides in the United States#Atrazine|Pesticides in the United States – Atrazine]]

{{Reflist|colwidth=35em}}

*[https://pubchem.ncbi.nlm.nih.gov/compound/Atrazine Atrazine]- PubChem(National library of medicine) - atrazine

*[http://npic.orst.edu/factsheets/atrazine.html Atrazine Fact Sheet] - National Pesticide Information Center - Atrazine Fact Sheet

*[https://www.cdc.gov/niosh/npg/npgd0043.html Atrazine] - CDC - NIOSH Pocket Guide to Chemical Hazards

*{{PPDB|43}}

{{Estrogen receptor modulators}}

{{Authority control}}

[[Category:GPER agonists]]

[[Category:Chloroarenes]]

[[Category:Suspected teratogens]]

[[Category:Xenoestrogens]]

[[Category:Isopropyl compounds]]