Fluoride in Drinking Water A Scientific Review of EPA's Standards (2006) / Chapter Skim
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6 Reproductive and Developmental Effects of Fluoride
6 Reproductive and Developmental Effects of Fluoride
Pages 181-204
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From page 181... ...
Animal Studies The large number of studies gleaned from a search of the literature since 1990 that evaluated reproductive tract structure or function in animal models are outlined in Table 6-1, listing the fluoride dosing regimens and main observations. Most of the studies were conducted for the purpose of hazard identification and involved high doses of fluoride to reveal potentially sensitive reproductive-tract targets and pathways.
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From page 182... ...
182 ecnerefeR yonihC 4991.late dnayonihC 8991letaP dnayonihC 1002letaP stceffE erewenitsetnillamsdna,elcsum,revilninietorpdesaerceD suimencortsagninegocylgfonoitalumuccatnacfiingiS.devresbo niytivitcaesanegordyhedetaniccusnienilceD.revildnaelcsum dicacibrocsafonoitartsinimdA.ecimdetaertfoelcsumsilarotcep morfyrevocertnacfiingisdesuacecimdetaert-FaNot devresboerew dewohs muidosdna muiclac dewohssyad54rofFaNfolawardhti .suretuninegocylgfonoitalumuccA.detceted muiclacdna .yticixotediroufl dna,mures,eniruehtnidesaercnierewsnoitartnecnocediroulF deriapmisawereht,yravoehtnI.slortnochtiwderapmocyravo evitcetorpehtfonoitcnufderiapmidnaenoihtahtulgfonoitcudorp ,esatumsidedixorepus,esadixorepenoihtahtulg,yleman -- semyzne .noitadixorepdipilnairavodesaercnisawerehT.esalatacdna muissatopfosnoitartnecnocdecnahnE muresfosnoitartnecnocehT.muresehtni W.noitelpedtnacfiingis cibrocsahtiwtnemtaertybdecnahnesawyrevoceR.yrevocerlaitrap .Dnimativdna,Enimativ,muiclac,dica -71dna-3dnanietorpnairavofoenilcedtnacfiingiS cimeloretselohcopyH.seitivitcaesanegordyheddioretsyxordyh muresnitceffe seidutSyticixoTevitcudorpeR erusopxE noitaruD syad03 syad54 syad03 Concentration/ esoD yad/gk/gm01 )
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From page 183... ...
183 dnayonihC arieuqeS 9891 dnayonihC arieuqeS 2991 dnayonihC amrahS 8991 deunitnoc erew mrepslanimulfoecnesbadnasisonkypllec-lailehtipE foslleclailehtipelanimregfonoitazinagrosiD.devresbo .animulehtni mrepsfoecnesbahtiwselubutsuorefinimes raelcun,thgiehlleclailehtipe,sllecfonoitadunedninoitcudeR .simydidipeaduacehtnidevresbo mrepsfoecnesbadna,sisonkyp raelcun,ailicoretsdepmulcdewohs nadnanemulehtni ,ytilitom mreps,tnuoc muilehtipesnerefedsavehT mrepsontubsirbedllecdna,sisonkyp htiwdevresbosawyrevocerdekra M.airporpanimalehtniesaercni dnalgetatsorpehtnidevresbostceffeoN.tnemtaertfolawardhtiw .selcisevlanimesro elamefgnilcyclamronnehwetarytilitrefdenesseldesuacFaN detallegafledfosrebmunegraL.ecimdetaerthtiwdetamerewecim seitilamronbaliatdna,eceipdim,lamosorcahtiwaozotamreps mrepsniyrevocertnacfiingiS.devresboerew 2roftnemtaertfolawardhtiwretfadevresbosawetarytilitrefdna .shtnom tnacfiingisehtybdetadiculesaueilimlamydidipenisnoitaretlA sallewsanietorpdnadicacilaisfosnoitartnecnocniesaerced ydobniesaercedtnacfiingiS.sedimydidipeniesaPTAfoytivitca elcisevlanimesdnasnerefedsavfothgie gnidael,detceffasawssecorpnoitarutam .ytilibaivdnaytilitom W.thgiewsimydidipedna mrepS.detceffatonerew mrepslamydidipeaduacnienilcedot mrepslamydidipeaduacdnaetarytilitrefninoitcudertnacfiingiS ehtnisnoitaretlacilobatemlaitnatsbusdecudnitnemtaerT.tnuoc stnemelppuS.ecimfoselcisevlanimesdna,snerefedsav,sedimydipe decnahnedoireplawardhtiwehtgnirud Edna Dnimativfo .stceffedecudni-FaNllafoyrevocer syad03 syad03 syad03 /gk/gm02,01 )
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From page 184... ...
184 ecnerefeR dnayonihC amrahS 0002 aheiteblE 0002.late .esadinorulayhdnanisorcalamosorca raelcun dnayrevocerdecnahne 01retfa evitaleR.skeew01rof skeew4rof stceffE mrepsnienilcedtnacfiingiS mrepS.devresbonoitallegafleddnaegamadlamosorcA dnasnoitaretlacilobatemdnalarutcurtS.detceffatonytirgetni tnacfiingisanidetluser mrepsnisemyzneehtfoytivitcadecuder FaNfonoitasseC.etarytilitrefroopdnatnuoc mrepsniesaerced .yrevoceretelpmoctuobagnirbtondidsyad03roftnemtaert muiclacrodicacibrocsafonoitartsinimdA dicacibrocsahtobhtiwdetaertspuorgnidecnuonorperomsaw .muiclacdna L/gm003dna,002,001tayltnacfiingisdecuderytilitreF sesutefelbaivdnasetisnoitatnalpmI.skeew4retfatontubskeew dahtahtselamhtiwdetamselamefnidecuderyltnacfiingiserew L/gm002fonoitartnecnocataFaNdetsegni yltnacfiingiserewsdnalglaituperpdnaselcisevlanimesfosthgiew L/gm003dna002FaNotdesopxeslaminanidesaercni .skeew01rofdesopxeslaminanitontub erusopxE noitaruD syad03 01dna4 skeew Concentration/ esoD yad/gk/gm01 )
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From page 185... ...
18 .latenauY 4991 snilloC 5991.late tasayiH-lA 0002.late amreV anuGdna nilrehS 1002 deunitnoc sa,sisorouflcinorhchtiwstarninoitatcalfonoitibihnisawerehT rewoldnaspupniniagthgiewydobfosetarrewolsybderusaem .spuplortnochtiwderapmocsetunim03nidelkcusklimfotnuoma ehtnidesaercnitub muresnidesaercedsawnoitartnecnocnitcalorP fonoitalumuccadewohsnoitanimaxecipocsorci M.dnalgyratiutip egralylemertxefoecnaraeppadnaselunargyroterceserutamegral .amsalpotychportotcalniselunargyroterceslamronba owtehtninoitpmusnocretawlanretamnisnoitcudertnacfiingiS deeflanretamninoitcudertnacfiingisadnaspuorgesodtsehgih erewsmadfosthgiewydoB.puorgesod-hgihehtninoitpmusnoc ynanotceffetnacfiingisoN.spuorgesod-rehgihehtnidecuder .stniopdneevitcudorper L/gm052htiw,laminimerewedirouflfostceffelatnempoleveD oteudleveltceffedevresbotsewolehtgniebyad/gk/gm1.52( .) snoitairavlateleks ydutsehtdevivruspuorgyad/gk/gm30.82ehtnistarehtfoenoN .puorgyad/gk/gm53.81eht morfdevivruseerhtylnodna,doirep )
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From page 186... ...
186 ecnerefeR yonihC a1991.late yonihC 2991.late akswosarK dna ikswotsol W 2991 stceffE ehtniaozotamrepsfoecnesbadnasisenegotamrepsfotserrA anidetlusersihT.setsetehtfoselubutsuorefinimesehtfoanimul dnanoitallegafleD.sedimydidipeeaduacnitnuoc mrepsnienilced .devresboerewseitilamronbaliat enisoneda,setsetehtniytivitcaesanegordyhedetaniccuS nisnoitartnecnocdicacilaisdna,ytivitcaesatahpsohpirt tceffedecnuonorperom A.detibihnierewsetsetnisedimydidipe dnaloretselohcralucitseT.simydidipeaduacehtnodevresbosaw tnacfiingiS.detceffatonerewsnoitartnecnocenoretsotset .tnuocdnaytilitom mures mrepsdesaercedotdetubirttaytilitrefnienilced enobdnasetsetehtnisnoitartnecnocedirouflniesaercnidloflareveS tnecrepytfiF.slortnochtiwderapmocsnoitartnecnoctsethtobta cigolohtapotsihdetibihxespuorgtnemtaerthtobnistarehtfo .skeew61retfasetsetehtfo muilehtipelanimregehtnisegnahc dna,revil,setsetehtniesenagnamdnareppocfosnoitartnecnoC dnasetsetehtnisnoitartnecnocnorI.degnahctonerewsyendik ,revilehtnidesaercnierewtubedirouflybdetceffatonerewamsalp ,amsalp,setsetehtnicnizfosnoitartnecnoC.enobdna,syendik -61ehtniylralucitrap,yltnacfiingisdesaercedsyendikdna,revil .enobehtniesaercniotdednetcniZ.spuorgkeew erusopxE noitaruD esodelgniS noitcejni syad03 61dna6 skeew Concentration/ esoD Lµ05/gµ05 )
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From page 187... ...
18 anayaraN yonihCdna a4991 anayaraN yonihCdna b4991 yonihC 5991.late .lateoahZ 5991 odnarpS 6991.late deunitnoc dnaesadinorulayhlamosorca mreps,tnemtaertfosyad05retfA lamosorcadedulcnisnoitavresborehtO.decudererewnisorca ,ytilitom mrepsnienilced,mrepsfonoitallegafleddnaegamad .ytilitrefdecuderdna,tnuoc tnemtaerT.muiclac .sdipilohpsohpenarbmem mrepslamydidipeaduacdesaerced roftnemtaertFaNfolawardhtiwtadevresboyrevoceretelpmocnI foyrevocertnacfiingisdecudorp muiclacdnadicacibrocsA.syad07 .stceffedecudni-FaN .snoitartnecnocloretselohcralucitsetniegnahctnacfiingisoN desaercedyltsedomerewseitivitca ,xedniytivitcalairdnohcotim DSH-71dna DSH-3ralucitseT adetacidnisesylanacirtemohpromotsiH.noitsegniFaNyb htiwnoitalerrocniretemaidllecgidyeLehtniegnahctnacfiingis ±6.3(snoitartnecnocediroufl .snoitartnecnocnegordna muresninoitaveletnacfiingiS mrepsniesirsuoenatlumisahtiw) mpp11.0 gnidael,mrepsnisnoitaretlacilobatemdnalarutcurtsnidetluser mreps wol,ytilitom mreps wolot mrepsnisegnahcdna,ytilibaivdecuder mrepsfosnoitartnecnocetylortceleninoitcudertnacfiingis A mrepslamydidipeaduacnisnoitartnecnocnietorP.devresbosaw yltnacfiingisetatsorpdna,elcisevlanimes,snerefedsav,noisnepsus snerefedsavnidetalumuccanegocylG.tnemtaertretfadesaerced .snerefedsavdnaselcisevlanimesnidesaercedesotcurfdna desopxeniemithtiwdesaercednoitartnecnocenoretsotset mureS nidesaercedyltnacfiingissawnoitartnecnocloretselohcsitseT.star .skeew6dna4desopxestarforevileht lortnocdetcejni-elcihevnidevresboegamadelubutsuorefinimeS .setsetdetcejninonnidevresbosawegamadon;setsetdesopxedna noitcejnitadevresbosawnoitartlfinietycokuelraelcunohpromyloP oN.sruoh42retfaspuorgdetcejni-ediroufldna-elcihevhtobnietis .sllecgidyeLnotceffe syad05 syad05 05dna03 syad skeew6,4,2 elgniS noitcejni yad/gk/gm01 )
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From page 188... ...
188 ecnerefeR odnarpS 7991.late odnarpS 8991.late snilloC a1002.late stceffE FehtdnaselamnoitarenegPehtnihtiwdevresboerewstceffeoN 1 ,sthgiewelcisevlanimes/etatsorp,sthgiewsitsetnispuorgnoitareneg mreps,stnuocditamrepsralucitset,sthgiewnagroevitcudorpernon margrepnoitcudorp mreps,yadrepsitsetfo margrepnoitcudorp muresro,enomrohgnitalumits-elcillof,enomrohgnizinetul,sitsetfo devresboerewsegnahclacigolotsihoN.snoitartnecnocenoretsotset .noitareneg FehtroPehtrehtie 1 morfseussitralucitsetni suorefinimesehtfoemulovetulosbanotceffetnacfiingisoN yradnuoblessevdoolb,sllecgidyeL,ecapslaititsretni,selubut etulosbaronemulralubut,segahporcam,ecapscitahpmyl,reyal ilotreSnaem,aeraecafrusralubutetulosbadnahtgnelralubut suorefinimesnaem,noitces-ssorcralubutreprebmuniloelcunllec .muilehtipesuorefinimesehtfothgiehnaemdna,retemaidelubut emulovdnaemulovetulosbaehtniesaercedtnacfiingisyllacitsitatS detaert-FaNnidevresbosaw muilehtodnecitahpmylehtfotnecrep -FaNehtnieluspacralucitsetehtnidna) L/gm052dna571(spuorg .)
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From page 189... ...
18 .latehsohG 2002 amreV anuGdna nilrehS a2002 ihsahS a2991 yonihC b1991.late deunitnoc desaercederewseitivitca DSH-71dna DSH-3ralucitseT fosnoitartnecnocamsalpninoitcuderlaitnatsbuS.yltnacfiingis mrepslamydidipedesaerceD.puorgdesopxeehtnienoretsoretset .puorgdesopxeehtniaozotamrepslanimulerutamrewefdnatnuoc detacidnisa,ssertsevitadixohtiwdetaicossasawtnemtaertFaN ,sitsetehtniseneiddetagujnocfonoitartnecnocdesaercninayb ninoitcudertnacfiingiS.tellep desopxenitellep desuac ) 100.0< mrepslamydidipedna,simydidipe mrepsehtniseitivitcaesalatacdnaesadixorep .slortnochtiwderapmocsapuorg ydobnisnoitcudertnacfiingishtiwdetaicossatnemtaertFaN nietorpdna,esoculgfonoitartnecnoc,noitpmusnocdeef,thgiew otdepleh Edna,D,CsnimativfonoitartsinimdA.muresehtni dna,muidos,nietorp,esoculgsallewsassolthgiewydoberotser lawardhti W.stardesopxefo tnuocdnaytilitom fonoitartsinimdahti muresehtnisnoitartnecnoc muissatop noitaroilematnacfiingisdesuacnoitatcalgnirudtnemtaertFaNfo dna,esoculg,muissatop,muidos muresnidnanoitpmusnocdeefni EnimativhtiwtnemtaertlanoitiddA.snoitartnecnocnietorp muresnidnasnoitcuderthgiewydobnistnemevorpmilaitnatsbus .nietorpdna,esoculg,muissatop,muidosfonoitartnecnoc detaertnidevresbosetsetnisdipilfonoitalumuccalamronbA dna,aimedirecylgirtrepyh,aimedipilohpsohprepyH.stibbar sawsisehtnysoibdipildecnahnedetacidniaimeloretselohcrepyh P(tnacfiingiS.sisocixotedirouflotesnopsernidevresbo detaertfosetsetnidevresbosdicayttafeerffotnuomaniesaercni .slamina mrepsdecuderotdetalerytilitrefnienilceD retfayrevoceroN.msilobatemdnaygolohpromnisegnahcdna W.tnemtaert morfsyad03roflawardhtiw .derruccoyrevocerdekram,muiclacdnadicacibrocsa syad92 fo6yaD otnoitatseg fo12yad noitatcal syad001 syad03 yad/gk/gm02 )
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From page 190... ...
10 ecnerefeR aleehsuS ramuKdna 1991 dnaramuK aleehsuS 4991 dnaramuK aleehsuS 5991 stceffE ilutcudehtfonemulehtgninilslleclailehtipeehtnoailicfossoL ehtnoailicoeretsfodnasidimydidipetupacehtfosetnereffe .devresbosawsnerefedsavehtfonemulehtgninilslleclailehtipe emosniraelctonerewdnaffodeleepsllecfoseiradnuobehT setnereffeilutcudehtfonemulehtfogninillailehtipeehtfosnoiger niylnodetonsawsisenegotamrepsfonoitasseC.snerefedsavdna .shtnom92rofdetaertstibbar fosuelcunehtdna,emosorcaeht,mullegaflehtnistcefedlarutcurtS ehtnidevresboerewaozotamrepslamydidipednasditamrepseht ecnesbaetelpmoc,selubutorcimretuofoecnesbA.stibbardetaert esnedretuofosnoitarrebaciremundnalarutcurts,semenoxafo ehtnistcefedlarutcurts,htaehssuorbfiehtfonwodkaerb,srebfi tnemhcateddna,mullegaflehtfoeceipelddimehtfoairdnohcotim suelcunehtfosecafrustafleht morfemosorcaehtfognileepdna .devresbosaw erewslaminadetaertfoaresehtnisnoitartnecnocediroulF ehtniesaercedtnacfiingis,ailicoeretsfossoL.desaercniyltnacfiingis tnacfiingisdna,muilehtiperanmulocdefiitartsoduespehtfothgieh simydidipesutcudaduacdnatupacehtforetemaidehtniesaercni aduacehtfosthgie W.puorgtnemtaerthtnom-32ehtnidevresbo -htnom-32ehtnidecuderyltnacfiingiserewtupacdnasimydidipe snagroesohtniselunargyrotercesforebmuneht;slaminadetaert .decudersaw erusopxE noitaruD 92ro81 shtnom shtnom81 32dna02 shtnom Concentration/ esoD yad/gk/gm01 )
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From page 191... ...
11 aleehsuS ramuKdna 7991 yonihC 7991.late grebnellehcS 0991.late desaercniyltnacfiingiserewaresehtnisnoitartnecnocediroulF htoomsehtfonoitalidsawerehT.) 100.0< gidyeLehtfoeatsirclairdnohcotimdna P(stibbardetaertni mulucitercimsalpodne htoomsdnastelporddipilfosrebmunrewoldahsllecgidyeL.sllec desopxenufosllecgidyeLhtiwderapmoc mulucitercimsalpodne detaertnidevresbosnoisulcnisuotnemalfiraelcunartnI.stibbar .detarenegedsawsitsetehtfoeussitlaititsretnI.stibbar lamydidipeaduacehtfosnoitaretlacilobatemdnalarutcurtS lairdnohcotim mrepsnisesaercedlaitnatsbusotdelaozotamreps mrepsnisesaercnI.oitardaed/evil,ytilitom,xedniytivitca etaniccus,esaPTA.devresboerewsdipilohpsohpenarbmem nidesaercederewsnoitartnecnocenoihtatulgdna,esanegordyhed otdeldicacibrocsafonoitartsinimdA.slaminadetaertfositset .sretemarapesehtniyrevocer ynoB.tnemtaertotelbatubirttanoitcudorpernotceffeesrevdaoN .sgoddetaert01fo4nidevresbosawsesotsoxe .elam, 32dna81 shtnom syad03 sraey2 yad/gk/gm01 )
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From page 192... ...
In an ecological study of U.S. counties with drinking-water systems reporting fluoride concentrations of at least 3 mg/L (Freni 1994)
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From page 193... ...
That has the potential advantage of not assuming an effect at lower fluoride concentrations (as does the mean fluoride concentration, the other exposure measure) , but it has the disadvantage that, unlike individual-level studies, nondifferential misclassification of dichotomous exposures within groups tend to bias ecologic results away from the null (Brenner et al.
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From page 194... ...
states Pregnant women (n = 22) Drinking water Maternal serum fluoride concentrations ranging from 0.003-0.041µg/ml Men with skeletal fluorosis Drinking water 1.5-14.5 mg/L (fluoride)
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From page 195... ...
Cord serum fluoride concentrations ranged from 0.003-0.078 µg/ml, Shimonovitz and neonatal serum concentrations ranged from 0.017-0.078 µg/ml.
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From page 196... ...
. Those high-quality studies evaluated fluoride concentrations in drinking water of 0-300 mg/L in rats and 0-400 mg/L in rabbits.
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From page 197... ...
suggests that Down's syndrome is a biologically plausible outcome of exposure. There are other indications in the literature that environmental exposures could contribute to an increased incidence of Down's syndrome births among younger mothers (Read 1982; Yang et al.
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From page 198... ...
18 FLUORIDE IN DRINKING WATER TABLE 6-3 Developmental Toxicity Studies Species, Sex, Exposure Number Route Concentration/ Dose Exposure Duration Rat, F, 33-35/group Drinking 0, 10, 25, 100, 175, 250 From day of sperm water mg/L (NaF) detection to gestation Mean doses: day 20 0, 1.4, 3.9, 15.6, 24.7, and 25.1 mg/kg/day (NaF)
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From page 199... ...
No dose-related feed consumption or mean body weight gain in either F0 or F1 Collins females. Statistically significant decreases in fluid consumption for F0 at 250 et al.
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From page 200... ...
200 ecnerefeR aredlaC 8891.late artohla M 3991.late .lateatpuG 4991 ztivonomihS 5991.late seidutSlatnempoleveDnamuH stluseR nisnrobwenfosnoitartnecnocedirouflamsalpdrocneewtebecnereffidtnacfiingiS naem(spuorgdetnemelppusdenibmocfodna) L/gµ8.72naem(puorgdetaertnu .Lm001/gµ8.14ot fo Lm001/gµ00.21 %8;Lm001/gµ8.83ot .)
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From page 201... ...
201 iksnyzrko M dna yohca M 4991 .lateatpuG 5991 ihsahakaT 8991 deunitnoc ehtfotraplaesyhpaidehtnidesolcsiderewPdna,g M,aCfostnetnocrehgiH nahtsisyhpatemehtnidedrocererewedirouflfosnoitartnecnocrehgiH.senob fotnetnocdnaegalatefneewtebsnoitalerroctnacfiingisyllacitsitatS.tfahsehtni ehtnidnatfahsehtnistnetnocediroufleht;senobehtnisurohpsohpdna muiclac .eussitynoblateffonoitacfiiclacnoedirouflfoecneuflnioN.traplaesyhpatem ehtfo) %21(6dna,puorgydutsehtninerdlihc05ehtfo)
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From page 202... ...
202 ecnerefeR gnitih W 1002.late llehcti M 1991.late .latekciD 9991 stluseR degnarksirevitaleredurC.noitaulaveehtnidedulcnierewseidutslacigolocexiS s'nwoDneewtebnoitaicossatnacfiingisondnuofseidutsruoF.0.3ot48.0 morf desaercnidewohsseidutsowT.noitartnecnocedirouflretawdnaemordnys snoitartnecnocedirouflretawdesaercnihtiwemordnyss'nwoDfoecnedicni owtylnO.tnemssessaytidilavehtnoylroopderocsseidutsehtllA.) 50.0< P( yrammusdetneserphcihwfoenoylno,srotcafgnidnuofnocrofdellortnocseiduts .serusaememoctuo P(38.0-foerutarepmetyliadnaemdnaSDISneewtebnoitalerrocevitagengnortS P(noitadirouflegarevadnaSDISneewtebnoitalerroctnacfiingisnoN.)
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From page 203... ...
Berry (1958) found little difference in rates of Down's syndrome between communities with relatively high and low water fluoride concentrations; however, the populations evaluated were small, and maternal age was not considered in the analysis.
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From page 204... ...
found an association between high fluoride concentrations (3 mg/L or more) in drinking water and decreased total fertility rate.
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