Fluoride in Drinking Water A Scientific Review of EPA's Standards (2006) / Chapter Skim
Currently Skimming:
10 Genotoxicity and Carcinogenicity
10 Genotoxicity and Carcinogenicity
Pages 304-339
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 304... ...
10 Genotoxicity and Carcinogenicity This chapter reviews research publications and relevant review articles published since the earlier NRC (1993) report and other relevant papers not included in that review, and also considers salient earlier papers.
|
From page 305... ...
, and cultured human lymphocytes. Positive results in the human lymphocytes were seen at fluoride concentrations above 65 micrograms per milliliter (µg/mL)
|
From page 306... ...
306 secnerefeR .lateiL.Y 5991 htehS 4991.late gne M ;5991.late dnagne M gnahZ 7991 dnau 5991u W W skrameR edirouflenirudnaamsalP ;derusaemoslasnoitartnecnoc retawotlanoitroporpereweseht .snoitartnecnoc fonoitatnemucodtneicfifusnI lortnocrotnemniatrecsatcejbus cihpargomedlaitnetoprof .gnidnuofnoc fonoitatnemucodtneicfifusnI lortnocrotnemniatrecsatcejbus cihpargomedlaitnetoprof .gnidnuofnoc dahnoiger ediroulFfoseidutSyticixotoneGtneceRfoyrammuS sgnidniF L/gm-8.4ehtnistcejbuS .llecrepsECSegarevarewol retaergyltnacfiingissawetar tub,tarajuGhtroN ECS morfstcejbusni llecehtniecnereffidonsawereht .xednievitarefilorpelcyc ninoitaveledahsrekrowdesopxE .detsetsemoctuocitenegotyclla niycneuqerfrehgih:ECS %78(sisorouflhtiwslaudividni sisorouflonnaht,) sECSniesaercni htiwderapmoc)
|
From page 307... ...
30 noskcaJ 7991.late netsAnaV 8991.late hpesoJ dna aihdaG 0002 hsemaR 1002.late deunitnoc noitatnemucodtneicfifusnI dnatnemniatrecsatcejbusfo .scitsiretcarahccihpargomed gniogrednustneitapylnO latipsohenotagnittfisisehtsorp saibnoitceles;detceleserew detacilperfI.elbissopsaw ,tnemniatrecsacitametsyshtiw aetacidnidluocngisedsiht cinegonicracrof msinahcem .edirouflybytivitca L/gm-0.4nirehgihsECS ydutspu-wolloF.ytinummoc ytinummoc L/gm-0.4ehtni llewgnisustnedisergnirapmoc retawyticdna) L/gm3.0(retaw niecnereffidondnuof)
|
From page 308... ...
308 secnerefeR regieZ 4991.late ecapinuD 6991.late oriebiR .late a4002 amedraA dna iustusT 5991 orugO 5991.late skrameR ehtfoemossesserddadohte M dnaortivnisuoiverpnistciflnoc noitibihnifo .seidutsovivni msinahcemsesoporP .riaperdnasisehtnys ANDfo sgnidniF niesaercniielcunorcimoN ondna,sllecdoolbderlarehpirep niesaercninoitarrebaemosomorhc snoitartnecnocenoB.worramenob otesodhtiwdesaercniedirouflfo .mpp000,7> desopxeynaninoitavele ECSoN .puorgbus ANDdnarts-elgnisniesaercnioN .egamad tsewolsiFaN mpp05 .snoitarrebagnicudninoitartnecnoc oN.mpp5>tacinegotsalcediroulF .ydiolpnotceffe ni deunitnoC yassAdnadohte .shtnom6rof 1-01 ELBAT M/metsySronoitalupoP seidutslaminaoinI .skeew6rofretawgniknirdaivdesopxe) F3C6B(eci 1 .enobnisnoitartnecnocedirouflderusae M M ,sllecdoolbderlarehpirepniielcunorcim:yassA .worramenobnisnoitarrebaemosomorhc .selamcitebaidnondnacitebaid,starrekcuZruoF L/gm05ot5taretawniediroulF .ECS:yassA L/gm001dna,7,0taFaNotdesopxestarratsi W retawgniknird )
|
From page 309... ...
30 iustusT 5991.late aihdaG dna hpesoJ 7991 gna W 4002.late dnaihsiK adihsI 3991 swehtta M 3991.late dnalilahK arad'aD 4991 deunitnoc egnarnisnoitartnecnocediroulF .seilppusretawfo niesaercnidetaler-esoD niesaerced,esadixorepdipil ehtniesaercnidna,enoihtahtulg .slleccitotpopafoegatnecrep yassanoitamrofsnartdradnatS .ytivitisnesesaercniotdefiidom .yticinegotsalcoN %32:noitarrebalamosomorhC foycneuqerfdesaercni %8dna ,mpp03dna02tasnoitarrebalatot .mpp01tatontub,ylevitcepser .detroperstceffeon:ECS -elgnisniesaercnidetaler-esoD .egamad ANDdnarts taergniedirouflfoyticinegotsalC ot24taylnosllecnamuhdnasepa ) mpp391ot91( .FaN mpp252 Mm6.4ot2.1 .noitamrofsnartrofevitagenFaN rofdevresboesnopser-esoD llecfonoitibihnioN.yticixototyc .ECSnotceffeoN.noitarefilorp htiwdetaertegatstnecseiuqtastsalborbfidiolpidnamuH 1,)
|
From page 310... ...
310 secnerefeR lilahK 5991 oriebiR .late b4002 ihsahi M dna iustusT 6991 rof skrameR fonagrotegratlaitnetoP seidutsyticinegonicracPTN .samocrasoetsodedleiytaht msinahcemelbissopsedivorP .earbetrevfosisenegonicrac dnaFaN, sgnidniF Mµ0.1tastceffekae W FKrofretaergylthgilsstceffE.FK .FaNnaht ANDdnarts-elgnisniesaercnioN .egamad fosesaercnidetaler-esoD dna5.0tasnoitarrebaemosomorhc .sruoh84dna42rof Mm0.1 .sllec ro,42,21rof .sruoh3rof deunitnoC yassAdnadohte 1-01 ELBAT M/metsySronoitalupoP worramenobderutluc) yelwaD-eugarpS(taR Mµ001ot1.0FKdnaFaNhtiwdetaerT .sruoh63 .kaerbdnanoitarrebalamosomorhc:yassA .sllecyravoretsmahesenihC Lm/gµ001dna,65,82.7taFaNhtiwdetaerT )
|
From page 311... ...
(1995) applied sodium fluoride (NaF)
|
From page 312... ...
reported that in vitro exposure of oocytes to NaF disrupted meiotic anaphase of ewes and cows but not of mice. The effective doses were the same order of magnitude as those reported by NRC in 1993 to cause chromosome aberrations in human lymphocytes.
|
From page 313... ...
(1997) compared SCE occurrence in lymphocytes of residents of communities with water fluoride concentrations of 0.2, 1, and 4 mg/L.
|
From page 314... ...
The following three less-well-documented studies reported associations between cytogenetic effects and residence in areas with high natural fluoride concentrations in drinking water. Sheth et al.
|
From page 315... ...
2001) described a case series of 20 osteosarcoma patients of which the two with the highest fluoride concentrations in their tumor tissue had mutations of the tumor-suppressor gene p3 and the others did not.
|
From page 316... ...
. The review concluded that "the collective data from the rodent fluoride toxicological studies do not present convincing evidence of an association between fluoride and increased occurrence of bone cancer in animals" (NRC 1993)
|
From page 317... ...
(1985) that were used for the evaluation in the fluoride drinking water study.
|
From page 318... ...
Fluoride intake for the control mice was 0.9 mg of NaF/kg/day (0.4 mg of fluoride/kg/day) for the males and 1.1 mg of NaF/kg/day (0.5 mg of fluoride/kg/day)
|
From page 319... ...
Among the other tumor sites and types highlighted in the NTP report as not statistically and biologically significant was the hepatocellular neoplasm (adenoma, carcinoma, hepatoblastoma, and hepatocholangiocarcinoma) in male and female mice (NTP 1990)
|
From page 320... ...
The earlier NRC (1993) review considered the impact of the infection and concluded that the fluoride exposure was the most obvious cause for the increase in osteoma.
|
From page 321... ...
GENOTOXICITY AND CARCINOGENICITY 321 The basic criteria for evaluating studies are appropriate methodology, potential selection and information biases, statistical power to detect real associations, appropriate time windows for assessing exposures and potential effects, and control for potential confounding by sociodemographic and other factors. In addition, sufficiently specific end points (types of cancer)
|
From page 322... ...
. However, the authors concluded that an association of fluoridation and osteosarcoma was not supported by the data because there was no linear trend of increased rate of osteosarcoma with the duration of fluoridation of the pertinent water supplies.
|
From page 323... ...
323 secnerefeR .lategrebleG 5991 naejdnarG ;2991.late dnanaejdnarG 4002neslO .latesso M 5991 deunitnoc skrameR tonenolanoitsegnireta W atadoN.srohtuaybdessucsid lacitircelbissopfosisylanaro repaP.ycnetalro wodniwemit atadfolasreveremosdeniatnoc selbatcfiiceps-rednegnisnmuloc gnidragerstnemetatssimemosdna selamefdnaselamfosnoitroporp ehtno,revewoH.amocrasoetsohtiw ehtotelbaliavanoitamrofnifosisab odsrorrecfiicepsesoht,eettimmoc fonoitaterpretnitceffaotraeppaton .ydutssiht .atadretawgniknirdrognikomsoN aivyrotsihlaitnediserfokcaL stnereferrecnacfoesudna weivretni .snoitatimilera recnaCdnaediroulFfoseidutStneceRfoyrammuS sgnidniF sddo:denibmocatadllA ediroufllatotrof) sRO(soitar rofsRO.desaercednoitsegni .detaveleerewnoitsegniretaw rofevitcetorpediroufllatoT rofataddecudeR.selam :ylno)
|
From page 324... ...
324 secnerefeR 1002nissaB 2002renietS ihsahakaT 1002.late amayhoT 6991 skrameR elpitlum,noitatressidyrotarolpxE dna,sisylana,ngisednisnoitatimil .sgnidnfifonoitatneserp dna,setarelamefdnaelamdegarevA .srecnaclladenibmoc .snosirapmocforebmunegraL etaR.nwohstonsetarrecnaC .nossioPebotdetatsnoitubirtsid .ylevitcelesdetneserpstluseR .dewaflsdohtemlacitsitatS ataderusopxefosraey31otpU detarenegsisehtopyH.denibmoc emasnirehtrufdezylanaataddna .noitalupop sgnidniF serusopxefosnoitaicossA yletamixorppataedirouflot htiwretawni L/gm1 6segagnirudamocrasoetso .selamrofylralucitrap,8ot neewtebpihsnoitaleresrevnI noitadiroufldnasetarrecnac edutitaL.57.0-= Rdetroper oslaerutarepmetdna sarehtegottontub,dezylana .setairavoc tneicfifeocnoissergeR 0991'selamefroftsehgih enobelamdnaevitsegid/laro .srecnac fonoitalerrocevitisoP ytilatromhtiwnoitadiroufl gnomasetarytilatro M.setar retfadegrevnocsnwoteht .detanimretnoitadiroufl deunitnoC snoitavresbO ,slortnoc881,sesac19 ycnedisernodeweivretni edirouflrehtodnayrotsih .desab-latipsoH.serusopxe noseirtnuocroseitic94 defiissalc,stnenitnoc5 recnac wolrohgihsa edirouflereh W.ecnedicni erewsnoitartnecnoc morfataddesu,elbaliavanu .aeragnirobhgien fosetistnereffid63,saera9 .sdoirepraey-5eerht,recnac nehw(sraey5rosraey51 dnastneicfifeoc) tnereffid .soitarecnedicnirecnac fonoitamrofsnart-goldesU dnanoitartnecnocediroufl .setarrecnac snwot35ehtfo02 rofdellortnoC.dedulcni .scihpargomedoicos snoitartnecnocedirouflllA .L/gm4.0 woleb noitacoL 3-01 ELBAT &ngiseDydutS folortnocesaC 02 |
From page 325... ...
32 .lategnaY 0002 sinnaiyuomaiY 3991 -sisehtopyH.snosirapmocelpitlu M rofdellortnoC.gnitareneg noitcefnisiddnanoitazinabru tonsamocrasoetsO.stcudorp-yb enobrehto morfdehsiugnitsid .srecnac rednegenotcartbusotetairporppanI .rehto morf .ytilasuacnogninosaerralucricsesU %59htiwgnidnfiylnoehT gnidulcxelavretniecnedfinoc recnacreddalbfossecxe=0.1 etarrehgihoslA.selamefni ,enobrofselamnisoitar lla,noloc,sureturofselamef .sredneghtob;setis ecnereffidehttahtdedulcnoC elamefdnaelamneewteb dnadetadirouflneewtebsetar setacidnisaeradetadirouflnon .snoitaicossarecnac wol01dnahgih01 .derapmocsnwotdehctam dedeecxesnoitalupoplatoT soitaretaR.noillim1 .detareneg) sR MS( ,setarJNdna.S.UdesU .srehtognoma recnacfonosirapmoC snwotrofsetarytilatrom larutan wol.svhgihhtiw .snoitartnecnocediroufl .nawiaT ytilatromdnaecnedicnI detcartbus;scitsitats elam morfelamef .setaramocrasoetso .ediwdlro W
|
From page 326... ...
(2000) 1 conducted an ecologic analysis of cancer mortality in 20 municipalities in Taiwan, half with measurable naturally occurring fluoride concentrations.
|
From page 327... ...
To date, this study is the closest to fulfilling the recommendation of the 1993 NRC report regarding conducting one or more analytic studies of osteosarcoma and fluoride exposure. However, no bone fluoride concentrations could be assessed through this design.
|
From page 328... ...
Lack of such information can be problematic if socioeconomic status, or factors for which it is a surrogate, introduce confounding. The primary exposure metrics for fluoride in drinking water were based on a combination of data from the Centers for Disease Control and Prevention, states, locales, and purveyors on year-specific water system fluoride concentrations expressed as proportions of the recommended fluoride
|
From page 329... ...
A relatively large hospital-based case-control study of osteosarcoma and fluoride exposure is under way (Douglass 2004) and is expected to be reported in the summer of 2006 (C.
|
From page 330... ...
The ultimate analysis and validity of this study will depend partly on the degree to which control selection is not biased in such a way as to artificially increase or decrease the likelihood of fluoride exposure compared with the general population to which this study is intended to apply. A preliminary retrospective recruitment phase of this investigation, including telephone interviews, residential history reconstruction, and an attempt to estimate dietary fluoride intakes, reported ORs of 1.2 to 1.4 that were not statistically significant (Douglass 2004)
|
From page 331... ...
In Iowa, one of the two cancer registries they analyzed, the authors observed a trend among males in the incidence rates of oropharyngeal cancer with duration of fluoridation, but mortality analyses did not indicate an association with fluoridation. However, in an earlier study in England, oral-pharyngeal cancers among females constituted the only site-gender category for which standardized mortality ratios in England were found to be significantly elevated in areas with naturally occurring high fluoride concentrations, defined as more than 1.0 mg/L.
|
From page 332... ...
(1991) observed a few suggestive increases among some subgroups for soft tissue sarcoma, non-Hodgkin's lymphoma, colorectal cancer, and lip cancer, but those cancers were not a priori of concern as related to fluoride exposure based on biologic plausibility.
|
From page 333... ...
conducted an ecologic analysis of latitude, temperature, and fluoridated water in 49 cities worldwide. When fluoride concentrations were unavailable for these cities, he substituted data from neighboring areas.
|
From page 334... ...
. "Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (2000)
|
From page 335... ...
GENOTOXICITY AND CARCINOGENICITY 33 "1 and 10" to an RfD derived from noncancer health effects (EPA 2000d)
|
From page 336... ...
animal results described above, and (4) pre-1993 publication of some positive, as well as negative, epidemiologic reports on associations of fluoride exposure with osteosarcoma risk.
|
From page 337... ...
comprehensive hospital- Male F344 rats: based case-control study inconclusive including bone fluoride measurements is under way)
|
From page 338... ...
could add important data to the current body of literature on fluoride risks for osteosarcoma because the study includes bone fluoride concentrations for cases and controls. When this study is published, it should be considered in context with the existing body of evidence to help determine what follow-up studies are needed.
|
From page 339... ...
Documentation of subject enrollment with different fluoride concentrations would be useful for addressing the potential genotoxic hazards of fluoridated water in this country.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.