1、Humans have altered the nitrogen cycledramatically over the last half-century,and as aresult,nitrate is steadily accumulating in ourwater resources.Globally,human nitrogenproduction has increased rapidly since 1950and currently exceeds nitrogen fixed by naturalsources by about 30%(Fields 2004).This
2、fig-ure compares with pre-1950 human inputs,which were a small fraction of the input fromnatural sources(Lambert and Driscoll 2003).Fertilizer is the largest contributor to anthro-pogenic nitrogen worldwide;other majorsources include animal and human waste,nitrogen oxides from utilities and automobi
3、les,and leguminous crops that fix atmosphericnitrogen(Fields 2004).These organic andinorganic sources of nitrogen are transformedto nitrate by mineralization,hydrolysis,andbacterial nitrification.Under reducing condi-tions,nitrate can be biologically transformedto nitrogen gas through denitrificatio
4、n.Nitratenot taken up by plants or denitrified migratesto streams and groundwater.The U.S.Environmental ProtectionAgency(EPA)maximum contaminant level(MCL)for nitrate in drinking water of10 mg/L nitrate-nitrogen(nitrate-N)(equiva-lent to 45 mg/L as nitrate)and the WorldHealth Organization(WHO)guidel
5、ine(WHO2004b)of 50 mg/L as nitrate(equivalent to11 mg/L as nitrate-N)were promulgated toprotect against methemoglobinemia,or“bluebaby syndrome,”to which infants are especiallysusceptible.The regulatory level is usually metfor public water supplies,which are routinelymonitored.Much less is known abou
6、t privatewells,which in the United States are usuallyrequired to be tested only when the well is con-structed or when the property is sold.Somehave suggested recently that the regulatory levelfor nitrate in drinking water is overly conserva-tive(Avery 1999;Lhirondel and Lhirondel2002).However,this d
7、iscussion of the regula-tory level has not thoroughly considered studiesof other chronic health effects including cancer,adverse reproductive outcomes,and diabetes.Although a causal role for nitrate in these otherhealth outcomes is not conclusive,recent studiesthat indicate possible adverse effects
8、at nitratelevels below the MCL are of concern(Brenderet al.2004b;DeRoos et al.2003;Ward et al.1996;Weyer etal.2001).In recognition of the widespread contam-ination of drinking-water sources by nitrateand the potential for health effects in additionto methemoglobinemia,a symposium titled“Drinking Wat
9、er Nitrate and Health:RecentFindings and Research Needs”took place atthe annual meeting of the InternationalSociety for Environmental Epidemiology(14 August 2004,New York,New York,USA).Invited experts presented results fromrecent unpublished studies and summarizedthe state of knowledge on exposure a
10、ndhealth effects of drinking-water nitrate,with afocus on cancer and adverse reproductive out-comes.This article summarizes the sympo-sium discussions and recommends promisingareas for future research.Specifically,we dis-cuss the epidemiologic evidence for drinking-water nitrate and risk of specific
11、 cancers,adverse reproductive outcomes,and otherhealth outcomes in the context of the currentregulatory limit for nitrate in drinking water.Nitrate Levels in Groundwaterand Water SuppliesNitrate is the most common chemical contami-nant in the worlds groundwater aquifers(Spalding and Exner 1993).An e
12、stimated 42%of the U.S.population uses groundwater as theirdrinking-water supply(Hutson et al.2004).Inthe United States,total nitrogen in streams andnitrate in groundwater are highest in agricul-tural areas,followed by urban areas and areaswith mixed land use(Figure 1).The mostrecent data indicate t
13、hat about 22%of domesticwells in agricultural areas of the United Statesexceeded the MCL(U.S.Geological Survey,unpublished data).In contrast,3%of publicsupply wells in major aquifers(typical sourcesfor public water supplies)exceed the MCL(U.S.Geological Survey,unpublished data).Environmental Health
14、PerspectivesVOLUME113|NUMBER11|November 20051607ResearchAddress correspondence to M.H.Ward,Occupationaland Environmental Epidemiology Branch,Division ofCancer Epidemiology and Genetics,National CancerInstitute,6120 Executive Blvd.,EPS 8104,Bethesda,MD 20892 USA.Telephone:(301)435-4713.Fax:(301)402-1
15、819.E-mail:wardmmail.nih.govWe thank K.Cantor of the National Cancer Institutefor his review of the manuscript.The authors declare they have no competingfinancial interests.Received 25 February 2005;accepted 23 June 2005.Workgroup Report:Drinking-Water Nitrate and HealthRecent Findings andResearch N
16、eedsMary H.Ward,1Theo M.deKok,2Patrick Levallois,3Jean Brender,4Gabriel Gulis,5Bernard T.Nolan,6and James VanDerslice71Division of Cancer Epidemiology and Genetics,National Cancer Institute,National Institutes of Health,Department of Health andHuman Services,Bethesda,Maryland,USA;2Department of Health Risk Analysis and Toxicology,University of Maastricht,theNetherlands;3Institut National de Sant Publique du Qubec and Unit de recherche en sant publique,Centre Hospitalier Universitairede Qubec,Qub
