Atrazine (/ˈætrəziːn/A-trə-zeen) is achlorinatedherbicide of thetriazine class.[2] It is used to prevent pre-emergence broadleafweeds in crops such asmaize (corn),[3]soybean[3] andsugarcane and on turf, such as golf courses and residential lawns. Atrazine's primary manufacturer isSyngenta and it is one of the most widely used herbicides in the United States,[2] Canadian,[4] and Australian agriculture.[5] Its use was banned in theEuropean 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.[6][7]
At least two significant Canadian farm well studies showed that atrazine was the most common contaminant found.[4] As of 2001[update], atrazine was the most commonly detected pesticide contaminating drinking water in the U.S.[8]: 44 Studies suggest it is anendocrine disruptor, an agent that can alter the natural hormonal system.[9] However, in 2006 theU.S. Environmental Protection Agency (EPA) had stated that under theFood Quality Protection Act "the risks associated with the pesticide residues pose a reasonable certainty of no harm",[10] and in 2007, the EPA said that atrazine does not adversely affect amphibian sexual development and that no additional testing was warranted.[11] The EPA's 2009 review[12] 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".[13] 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."[14] EPA started a registration review in 2013.[15]
The EPA's review has been criticized, and the safety of atrazine remains controversial.[16][17][18] 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."[2]
In theUnited States as of 2014, atrazine was the second-most widely used herbicide afterglyphosate,[16] with 76 million pounds (34 thousand metric tons) of it applied each year,[19][20] nearly identical to its usage in 1974, of 76.8 million pounds.[21] Atrazine continues to be one of the most widely used herbicides in Australian agriculture.[5] Its effect on corn yields has been estimated from 1% to 8%, with 3–4% being the conclusion of one economics review.[22][23] In another study looking at combined data from 236 university corn field trials from 1986 to 2005, atrazine treatments showed an average increase of 5.7 US bushels per acre (0.50 m3/ha) (~400 kilograms per hectare (360 lb/acre)) than alternative herbicide treatments.[24] 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.[25]
Atrazine was invented in 1958 in theGeigy laboratories as the second of a series of1,3,5-triazines.[26]
Atrazine is prepared fromcyanuric chloride, which is treated sequentially withethylamine andisopropylamine. Like other triazine herbicides, atrazine functions by binding to theplastoquinone-bindingprotein inphotosystem II, which animals lack. Plant death results from starvation and oxidative damage caused by breakdown in theelectron transport process. Oxidative damage is accelerated at high light intensity.[27]
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.[30] 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.[31] 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.[citation needed]
Atrazine remains in soil for a matter of months (although in some soils can persist to at least four years)[9] and can migrate from soil togroundwater; 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).[9]
Atrazine degrades insoil primarily by the action ofmicrobes. Thehalf-life of atrazine in soil ranges from 13 to 261 days.[32] Atrazinebiodegradation can occur by two known pathways:
Hydrolysis of the C-Cl bond is followed by theethyl andisopropyl groups, catalyzed by thehydrolaseenzymes called AtzA, AtzB, and AtzC. The end product of this process iscyanuric acid, itself unstable with respect to ammonia and carbon dioxide. The best characterized organisms that use this pathway are ofPseudomonas sp. strain ADP.
Dealkylation of theamino groups gives 2-chloro-4-hydroxy-6-amino-1,3,5-triazine, the degradation of which is unknown. This path also occurs inPseudomonas species, as well as a number of bacteria.[33][34]
Rates of biodegradation are affected by atrazine's low solubility; thussurfactants 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 becatabolized 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,[35] a process referred to as adenitrification. 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.[36] Low concentrations ofglucose can decrease the bioavailability, whereas higher concentrations promote the catabolism of atrazine.[37]
Thegenes for enzymesAtzA-C have been found to be highly conserved in atrazine-degrading organisms worldwide. InPseudomonas sp. ADP[clarification needed], the Atz genes are located noncontiguously on aplasmid with the genes formercury catabolism. AtzA-C genes have also been found in aGram-positive bacterium, but are chromosomally located.[38] The insertion elements flanking each gene suggest that they are involved in the assembly of this specialized catabolic pathway.[34] Two options exist for degradation of atrazine using microbes,bioaugmentation orbiostimulation.[34] Like the herbicidestrifluralin andalachlor, atrazine is susceptible to rapid transformation in the presence of reduced iron-bearing soil clays, such as ferruginoussmectites. 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".[39]
In 2016, photolytic degradation with 254 nmultraviolet 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.[40]
According to Extension Toxicology Network in the U.S., "The oral median Lethal Dose orLD50 for atrazine is 3090 mg/kg inrats, 1750 mg/kg inmice, 750 mg/kg inrabbits, 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." Themaximum contaminant level is 0.003 mg/L and thereference dose is 0.035 mg/kg/day.[41]
A September 2003 review by theAgency 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".[42] Incidence of a birth defect known asgastroschisis 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.[43]
The EPA determined in 2003 "that atrazine is not likely to cause cancer in humans".[45]
In 2006, the EPA stated, "the risks associated with the pesticide residues pose a reasonable certainty of no harm".[10][11]
In 2007, the EPA said, "studies thus far suggest that atrazine is anendocrine 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 inpubertal 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.[9] EPA opened a new review in 2009[12] 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."[13] 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."[16]
ANatural Resources Defense Council report from 2009 said that the EPA is ignoring atrazine contamination in surface and drinking water in the central United States.[46]
"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.[47]
A 2011 review of the mammalian reproductive toxicology of atrazine jointly conducted by theWorld Health Organization and theFood and Agriculture Organization of the United Nations concluded that atrazine was notteratogenic. Reproductive effects in rats and rabbits were only seen at doses that were toxic to the mother. Observed adverse effects in rats includedfetal resorption in rates (at doses ≥50 mg/kg per day), delays in sexual development in female rats (at doses ≥30 mg/kg per day), and decreased birth weight (at doses ≥3.6 mg/kg per day).[48]
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.[49]
Atrazine has been a suspectedteratogen, with some studies reporting causing demasculinization in malenorthern leopard frogs even at low concentrations.[50] A 2002 study byTyrone Hayes, of the University of California, Berkeley, found that exposure caused maletadpoles to turn intohermaphrodites – frogs with both male and female sexual characteristics.[51][52] However, this study has not been able to bereplicated,[53] 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.[53][54] A 2005 study, requested by EPA and conducted under EPA guidance and inspection, was unable to reproduce Hayes' results.[55]
In 2010, theAustralian 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.[56] APVMA responded to Hayes' 2010 published paper,[57] that his findings "do not provide sufficient evidence to justify a reconsideration of current regulations which are based on a very extensive dataset."[56]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".[11] 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 larvalX. laevis to atrazine at concentrations ranging from 0.01 to 100 μg/L does not affect growth, larval development, or sexual differentiation".[58] 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 invitellogenin, another marker of feminization."[59]The Atrazine Saga has been chronicled.[60]
In 2012, Syngenta, an atrazine manufacturer, 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.[16][61][62]
Prompted by the EU's 2004 ban, a regulatory review of the product in Canada by thePMRA was begun in 2015. On 31 March 2017 the review result was published and the PMRA decided to leave the product's registration unchanged. This was done because while the EU's ban was based on a legislated pollutant level of 0.1 μg/L, the Canadian regulations call for a home-grown "risk-based scientific approach in determining the risk to human health from pesticides in drinking water." The U.S. drinking water standard of 3 μg/L is 40% lower than the Canadian standard of 5 μg/L. Both maximum pollutant levels in North America were not exceeded by the maximum pollutant level in Canadian data of 2.32 μg/L.[63]
^abc"Chemical Review: Atrazine". Australian Pesticides and Veterinary Medicines Authority. 2014-05-28.Archived from the original on 2015-02-11. Retrieved2015-02-11.
^European Commission.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)Archived 15 March 2022 at theWayback Machine 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."
^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
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^Dooley, G. P.; Reardon, K. F.; Prenni, J. E.; Tjalkens, R. B.; Legare, M. E.; Foradori, C. D.; Tessari, J. E.; Hanneman, W. H. (April 2008). "Proteomic Analysis of Diaminochlorotriazine Adducts in Wister Rat Pituitary Glands and LβT2 Rat Pituitary Cells".Chemical Research in Toxicology.21 (4):844–851.doi:10.1021/tx700386f.PMID18370413.
^Zeng Y, Sweeney CL, Stephens S, Kotharu P. (2004). Atrazine Pathway Map. Wackett LP. Biodegredation Database.
^abcWackett, L. P.; Sadowsky, M. J.; Martinez, B.; Shapir, N. (January 2002). "Biodegradation of atrazine and related s-triazine compounds: from enzymes to field studies".Applied Microbiology and Biotechnology.58 (1):39–45.doi:10.1007/s00253-001-0862-y.PMID11831474.S2CID2998290.
^Crawford JJ, Sims GK, Mulvaney RL, Radosevich M (1998). "Biodegradation of atrazine under denitrifying conditions".Appl. Microbiol. Biotechnol.49 (5):618–623.doi:10.1007/s002530051223.PMID9650260.S2CID5126687.
^Pesticide Information Profile: AtrazineArchived 2022-04-01 at theWayback Machine, 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.
^"Public Health Statement for Atrazine".Toxic Substances Portal - Atrazine. Center for Disease Control, Agency for Toxic Substances and Disease Registry, Division of Toxicology and Human Health Sciences. September 2003. Archived fromthe original on March 15, 2022. RetrievedMay 2, 2015.
^"www.epa.gov"(PDF).EPA Scientific Advisory Panel. June 2003. Archived fromthe original(PDF) on 2022-03-15. Retrieved2014-10-24.
^Jooste, Alarik M.; Du Preez, Louis H.; Carr, James A.; Giesy, John P.; Gross, Timothy S.; Kendall, Ronald J.; Smith, Ernest E.; Van Der Kraak, Glen L.; Solomon, Keith R. (July 2005). "Gonadal Development of Larval Male Xenopus laevis Exposed to Atrazine in Outdoor Microcosms".Environmental Science & Technology.39 (14):5255–5261.Bibcode:2005EnST...39.5255J.doi:10.1021/es048134q.PMID16082954.
