Review, EMF · clUT-.-_(Uc(UL PAGE Chapter 4: Studies of Anin~als arld Plailr:- zng when anrrnals...

Hans Karow Coalition to Reduce Electropollut~on (CORE) 121 5 Poplar Grove Road PENTICTON, BC E-mlaif: Warow@-

Mr. Robert J. Pellatt Cornmission Secretary Britsh Columbia Utilities Commission Sixth Floor, 900 Howe Street, Box 250 Vancouver, BC, V62 2N3 Tel.: (604) 660 4700, Fax: (604) 660 1102 E-mail: Comrnissian.Secrera~@~~c~~~~

Dear Mr, Pellatt,

Re: FortisBC Inc. Order No. G4 14-05 I Proje~t No. 3898407Certlflcate of Public Convenience and Necessity Application "Pot Nk'Mip East Osoyoos Transmission and Substation t 7 t t n . i I w bcuc,comlA~~licatlonVIew as~~?A$pl1cationld=;93

PImse accept a follow up copy of Evidence # I j b ,

Eonncville Power Adrninstration Book "Eiecfricai and Biological Effects of Transmission Lines: A Review", pubiished 1996,

Chapter 4 "Effects of EMF on Animals and Plants'' pages 4-? - 4-26 (Studies of Laboratory Alxmals Behaviour Stress

Growth. Reproduct~on and Development, Melatonin)

The faxed copies of this submission will be sent only to the Commission and the Applicant. Anyone else from the participant's list may receive copies as well (via fax) upon special request

Respectfully submitted,

Hans Karow

C1-27

CNSMITH

Ni'Mip CPCN

Effects of EMF on Animals and Plants

C Since the 1960s large murnl4sre af studleg have been done of animals @xpos&d to EMF in (aboralorfes. These in vjvo studies were mdstiy intended to provide data to help m s w s She poterttial for adverse effects af EMF an psapl6, + Many sf"fal;ts of EMF have btsqn reported oh animals in laboratory studies, but 6eJativlely few have been independently replicatad. Much current interest is kCv$ing on effects on the hormne melatonit?, "and cm cancer promation, The 18boratbry,animaf studies to date have not firmly eststbfist.red the existence of arry hazardous effects from levels of EMF, a? tound typtCrilly in the envitonmeht. + Manv studies hav& also beert done on effects of EMF on eetis ,and tissues. These in vitm studies are often clesigned to expfuke poasibfe mechanisms to explain, how EMF p a y cause bislagical @ffer;ts. Areas of eurrant interest incllrde rnelatoniti, gene expressiun, land oarcino$endsis. + Many scientists believe tbal the cell membrane Is a ba~lc site: for bloIrYglCal Interacttons wlth EMF. Severai possible mechatlisfns,to ,explain biologicat effects of EMF have been proposed. + Studies of plants growing near transmisGion lines gensrally found Rz, adverse effects of EMF on overall growth. Tips of tree bt'an~hss growing close to transmission-line G ~ n t l ~ b t ~ r S can be damaged by corona Sn strong electric fields, Same laboratory studies bund t&at specific, camblnatiohs of AC and DC pagnetic fields rian affed plant growth. + In special studies, honeybee hives were adversely affeetetf by electric currents and shocks induced by electrit; fields from large traflsrnission \~nes. + Some studies have beer! done of witdlik and domestic animals expcprjsed td EMF and rtf;lative!ly few ti!ffectS h a v ~ been reported. Studies are contihuing on a poss~bie effect of EJWFfrorh a 500-kV line an the immune system of sh@@p.

Background

T his chapter provides an overview of the larye body of research on the possible effect\ ui

powel-fsequ e11cy ENIF on animals. cells a13d tissues, CIIIC

plants. This research has been done since the 1960s and ~z~cludes studxes done m iaboratorres and tn ilatur al environments. The laboratory animal studies irn .L wo I span a large number of bxolog~cal axeas. ~ttclud~tlg behavior, stress, growth, reproduct~on. hormones. cardiovascular system, narxrous systcrn. immune aystcm. dnd cancer. Stuaes of EMF and cells and tissues ( rn vttr-o) include carcinogenesis, gene expreszinti, mutagene.ili and cell communicat~on and growtb A pnmary pur - pose of the laboratory studies is to provide infon~~atlon to supplement the hutnan studies described tn Chapter 7 2 and 3 to allow for a hazard assessment of EMF.

A smaller number of szudles has been dot~e of E,lfiF and an~mals and plants 13'1 naturaI environments. These include studies of livestock, wildlif~, uxlsects. a~xdplant~ living near transmission lines Other natural eotrtntr- merit st~rdies have looked at anlmaIs and p1;t~its e x p c t ~ i i to low-frequency EMF from a U,S Navy comtnuotcr tion antenna. In tuTo studies. lrvestock were exposed t*?

slrnulated zrar~srmsslo~i line-fnelbs laslde burld~rlgs This chapter begins with an intxoductrorr to bLislc

exposure consideratioils for laboratory studies of EklF

Laboratory Studies

These studies were done prrmanly to help assess the potential for EMF to cause biological effects in humans, and to invest;rgste posstble meclzan~sxxts for such effects. It is. therefore, important to understand hmi. exposures in the laboratory relate to expnsuxes thai people may receive. This process is cornyllcared by a lack of agreetnent among scientists about what e-ipn-

sures to E m are most biolog~calilly relevant. and 1x Fun- damental. problems In extr-apolafing from results of studies oE animals and cells, to humarts.

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Chapter 4: Studies of Anin~als arld Plailr:-

zng when anrrnals are close together whlch can furthex An an~mal's interactton with an electric fielii 1~ aik reduce elcc~ic-field exposure. In most papers on elec- influenced by the destgn @.I cages at~d feednlg and j7 c wrc f~eld studres, only the unpercurbedelectr~c f~eld level terlng devxces. Unless care IS taken. an1111als can 1.s gmen (~.e., the f ~ e l d wjthout the animals or cages cave shocks Inside the cage, and blolog~cai effcci~ A present) T13e actual exposure may vary gxazltfy arnong tributed to clectric f ields per re may mtunllv bc cau;e: studtes clependtng otl rhe amount of shieldtng that may by shocks Also, the poss~ble pt-oductror-r of noise \

be present. brations, or ozone from .the eleclslc field source tnust iir coi~sidered IVith propex methodology. these factors cal largely be eliminated. These types of cortfounding fai tors may have been present to varylng degrees In somy of the early t esearch 011 power-frequency eJectt tc fieiil

More detailed tnformation 011 proper tecbn~cjucs lcit ti-,

generation and tneasuremenr of 60-Hz elect1 tc frelcls 1

laboratoxy studies can be found in a ieport by \/Iisahr t *

(1984). In vifro studies. Parallel-plate ehposure 5 p t t i

can also be used to expose cells and ilssues tu elect* fields, although there are sorne hm~tntrnns. Ka~ille et z (1 984) calculated that the ?71ax1mum clectt i c field tit,

be induced into cell suspensions through alx fro111 pal; 1 - lel, plates IS about 0 01 V/m. Thrs intel-rlal field strengtri is at least 10-times smaller than the rnaxiinurn electtic f ield mduced III a person standlng In the rnasmnlurrr el r c

tric field beneath a transrnrssion line (Raune and Phi lips 1980). By using dielectric rnarertal S L I C ~ as glass iii golyprogylet~c instead of air, electric 6elds of 0.2 Y / P ~ have been induced into cell suspensjosrs tvlth paialIel plate systems (Kaurle et a; 1984)

5PA Electrical and Biological Eftects Review 4- '

Chapter 4: Studies of Anirnals and Plants

Other researchers have injected current onto electrodes that axe placed dtrectly mto Ble cell suspension med~a to prod~~ce strong mternal electr~c fxelds (Mmoa et a1. 1 986). The eleckxc field strength can be calculated from Ohm's law by drv~ding the current density by the conductlvlty af the culture medium. This approach raises the poss~biUty that metal Ions from electrodes could contamnate the cell media. Some researchers used rnsulated electrodes (Greenebaum et al. 1979), or have used agar bridges to sola ate the electrodes from the rnedia (Reese et al. 1988). Figure 4 3 shows two bas~c type3 of electxic field in v i m exposure syc;tems

Artother approach for producing In vztm electr~c- f~eld exposure is to induce an electr~c freld 1x1 the cul- tule rnediurn with an external AC magnetic field (Kaune et al 1984, Mullins et al. 1993). Wtth this xnerbod, electrodes do not need to bc in contact wtth the expenmen- tal mediura. Researchers have also used RFMW frequencies amplitude modulated at 60-Hz or other low ficqueacies to rnduce electr~c fields in cell and tissue cultures (Blackman et al. 1985a).

Magnetic Fields

In viva studies. As interest in power-frequency magnetic fjelds began to increase, systems ware developed for exposil~g animals to both eelectric and magnetic fields (Miller el al. 1 989, Baum et al. 1991) and to magnetsc fields alone (Wilson et al. 19943. Stuchly et al. 1991, Mitsunx s t al. 1993). These systems were often based on work by Merritt et al. (1983) who described specifications for current-carrying square coils that could

Il In Vltro Expo$ure System (A)

11 Electrode

ulture mediirm

1 Elsctrode plate

, , In VftLo Exposure Sygtr~rn (3)

b2 used ro generate urliforln nlag~letic fields. Figure 4 4 shows one desigu for a s).stem for exposing labora- t o q aninlals to boih elecrrtc and magneuc fields. The ~.errtcal electxic field is produced by parallel-place zlec- trodes as drscribed above. ,4 horizontal magnetic field 1.5 [~roduced I'r'oxrl cuxrexic in the square \fertical coi1.s that jurcoutid the system. Exposure systems can also be de- signed to pr-oduce vertical nt. circularly polarized magnetic Fields (Shigemitsu et al. 1 993, aim et dl. 199 <).

Animals do not penurb the rnqgnetic field, so there i s no need to consider scaling factors for dixect mag- nehc-field effects. However, the irlrernal electric field that is induced by im external. AC magnetic field is influenced greatly by body size and shape. If induced electric fields are of interest, ~t is, therefore, necessary to apply some scaling factor when laboratoty atlinnals are used In st~~dxes to obtain information about possible effects of magnetic fields on h~~maxls. Feero (1 989) suggested that as afirst-order approximation, magnetic field scaltng factors should equal the linear dlrnensions of body srzes.

Stuchly et al. (1991) scaled magnet~c-field el.-,< sure in a laboratory study by aswrn-tdg ltiar the 11ld mum current loop radius js proportional. to the cubc it07 ofthe body mass (volume). If the average \-rumail hr-, - mass i s assumed to be 70 kg (1 54 lb), and the aV23d-

body mass for a mouse is 25 8 (0.9 oz ), then the rcsiir factor is about 14 Thexef01-e In their study, on the n3.

of body mass, exposing mice to a magtletlc tieid of i n (20 G), is sirnllar to exposing people to a field nf a m

0.15 mT (1.5 GI. Welguo et al. ( 3 994) concluded that weight-h~it

scaling for 60-Hz magnedc f~eld erposule is ncrt a< i

curare as scd~ng based on induced curretlts f ~ o r : ~ man and rodent rrlodels For exan~ple. for the Irur!

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Chapter 4: Studies of Animals and Plzntz

mouse cornpartson, the two scalrng methods may vary by 1 7 tunes 01. more assuining homogeneous tissue con- ductivtty F];owever, even bigger diEerences would be expected if heteroge~-tcous conductivity models (which are nloxe realrst~c) were used

In vifro studies, Systems for exposing cells and tissues to power-frequency magnetic fields often use c~rcular wire loops of many turns called Helroholti. coils (Misakian 1984). In a basic system, cell or txssue sarllples are placed wrthrn the magnetic field between two coils. The magnetic field is not perturbed by corn- n ~ o n materials ured lo contam the samples (e,g., glass ot pliasttc). However, the shapc: of the container does affect the c~lxrentr: and electric fieids induced in the medrum wrthlrl the container 04is;rkian et al. 1993).

Kirschvlnk (1 992) discussed desxgn cons~derattot~s for improvrng the uniformity of rnagnetic fields produced by Hefn-rholtz-cox1 exposure systems He a l ~ o ~ecoi~~mended the use: of doublewrapped cot1 syslems. These systems have two sets of wlre wrapping for the co~ls ~nstead of one. When currents rn the two wire$ a1 e parallel, they add together and produce a magnetlc freld

6PA Elecfrical and Bio

When current IS equal and opposxre rn the nrrias tile: cancer and no field is produced, tliis arrangement can be also used for sham control exposurer

The magnelically induced current 111 a crrculai con tainer perpendicular to the field is zero at the cenre, and progressrvely increases in ~trengttt to a msxttnitrn around the outer edge of the container, This pheno:-r~- enon can be used to separate effects from the tn?_ r clt>etlc

field per se, from effects due to tnduced cunent5 ar-iii electric fields. If cell samples are placed I n conccrrtnt circular welIs separated .From each other, ail c-clli ~ i r , exposed to .the same magnetlc flus density, but the! r a

exposed to mduced electric fields of differing 1rltrr1,-t

(Misakian et al. 1993) The type of rnagt~etjc-field polaizatio~l that 1s vss?

also affects the magmtude and osc~llat~on of ~riduced cur-rents and eleclnc l~a lds 113 the cell medium. EC linear and cjrcular polarization t~a%e been uscd to1 :

vitro studles o f power-frequency magnet1 c field< (Misakian 1991).

Studies of Laboratorv Animals

The number of laboratory animal studies t tiat ha." been done on power-frequency EMF IS even I T J O ~ ~ ex tensive than the epidemiologic studies reviewed in Chap ters 3 and 4. It is, therefore, nor feasible ro jtlclucle all known studies. Instead, the most often cited .;tucllc, wil l be described Rel'ei-ences are given to rc\ 1 c1.i. i o-

the laboratory reseatch fox readers wbo wilxir ri~or e I ~ I

formation about studies on a pal-trcr~lai top~c

The laboratory anz~?~al researclt I S grouped I n t o i 1

categorres: I ) betlavior, 22) stress, 3 I growth, 3 , rcprr ductio~l imd developn~ent. 5 ) nlelaton~n. 4 ) otbe~ but mones, 7) cardiovascular system. 8) nervous systc- ln 9) Immune system. and 10) cancer and mutagenesxs Fu. most categories, s t t~d~es are further dlvlded Into elr; ~ i c b field studies, magnetic-field studies. and studies (7- combined electxrc and magnetrc fields As rn prcx 10~1.

chapters, the resezuch is presented in a rough ch~onol ogy reflecting the development of research Issues

Behavior

The bel-tav~or of a~ilmals can be a sensitlye ~ n d i i a tor of effects of exposure to environmental agents Sowc behav~ors are simple predrctable reflexes, and od-ters a1 e influel-tced by past experience (Eckert 1988 r Yla117

bel~av~oraf tests measure locon~otot i l c t~v~ty b! u i c rll such methods as activity wheels, residenttat mzzz. r the open field I n the latter, for example, a n animal

movetnents over a grid-lined floor are recorded

logical Effects Review I e -'?--,

Ch&pfe.er 4: Studies of Animals and Plants

Other antma1 behavioral tests involve condition~ng using posltlve or negative reinforcers For example, an antma1 grven a lnild shock paired with an, audnble tone will cvcntually respond aversely to the tone i m the ab- sence of the sllock (McFarland 1 993).

Operant conditioning is a widely used type of be- iiavtoral test In these tests an ammat is trained to perform a task (e.g., pull a lever, peck a button) to obtarn a food reward ( McFarland 1 993). A wide variety of op- m n t tcsts 1s used i r i whtch aaixnals are trained to respond only under certa~n condittons, for exatq.de only when a cerrarn .;ound or field i s present Tests arc alzo used in which an~mals ate rewarded when they respond In spec~fic tntervals of tnrne. The timing of the response call be studied to determine whether some strmulus lrke EMF affects the tmlng or pattern of the response.

Orher studies exarnil~c the behavior of animals as they perform day-to-day activities as~octared wttb feed- Ing, proornlng, sleeping, 1-eproducing, and carlng for young. Observat~ons may ~nvolve tsolated antmals, or animals that are interacting as part of a social group. As w~tli other research dwcussed m this chapter, behav~oral researcll on EMF rs prlmanly focused on assessing the potential I~azardous effects of these fields. Behavioral effects seen In stud~es of EMF may mean that animal3 are simply aware of the fields and they are respondrng to thexx presence Of more importance holn a potential hazard viewpoint are behavzoral changes that may rep- resent a direct physiological eMect of EMF on the func- ttonlng of the t~eurornuscular system

Electric field One of the earliest studies in the U S of GO-Hz efectrcc Ftelds and laboratory anilnals focused on ammat behaviol (Moos 19641 That study found that ntghurme activity levels were increased when micc were exposed to 60-Hz f~eids of 0 8-11.2 kVlm Sjiwe then, several other laboiatory stud~es of power- frequency elec.tnc fields have also reported changes m behawor of mlce, rats, baboons, and swine Table 4.1 summarizes sevel-a1 of these studies,

Most ofthe studres used stronger fielld strengths than those used in the study by Moos (1964), andit was clear early o n that strong electric fle'xslds could greatly affect behawor because of sl~ocks, d precautions were xlot taken In the study by Knickerbocker et al. (1867) with fields of about 160 kV/m, mlce were shocked'when they attempted to drink from water bottle nipples. The electrlc field had to be turned off for. a time each day to allow the anrmals to drmk. Researchers an that study also repartcd that corona could be heard fiomn the ~nlcc \\/hen they attempted to stand on their bind legs

Soinc studies have attempted to detenmne the lowest 60-Hz electric-field strength that ani~llals cw detect. The cornbilled detection range for rats reported by

two research groups using d~ffel'ent method< -A i

3- 1 3.3 kV/m (Stern et al. 1983. Stern and Latles 1 Cj"

Sagan et al, 1967). T h ~ s 1s very slmi1a1- to thc 60-k7 elcetcic-field detection thrcsbold for bat7oGr (5-15 kV/m) (On et al. 1995a). Tile detection thtc-. old for pigeons was between 10,5 and 21 kV/m i CI per et al 1981)

Detection of electric fields is presuiliahlv nlrrilarc - at least xn part by surface st~rnulatlor~ of fearher< it and vibnssae. Weigel and Lundstrorn ( 1 937 1 found :":I

the vibration of vibrissac 111 1311 c l ~ c t r ~ c field I $ I ~ I ~ ~ I

enced by re1atlt.e hutn~ctlty At least two stud~es found that anlmal derecr:?~

60-Hz elecvrc ijelds ts not caused o ~ l i j h> hair + r \ - tion. StelI et al. (1993) found that b low~t~g air 3% sr 1

(to cause hair rnovexnentl dlci not elznllnate tbc anl*rl- I ability to detect electric fields A cutancous rccrr7t.

was found In the cat's paw that responds to 60-Iiz e - trtc fields (TYeigel ez al. 1957). These studies shoi. t, there may be other biologlcal receptors that ate set1.r dve to 60-Hz electric fields.

1n addihon to detection, some stttdxcs used shurr bux systems to dzter~nine wbetl~er an~inals \-+ould a i ri '

electric fields if given the opportunity to do so Sv 1

tended to avoid 30-kVlm fields (Hjereser-i et al I w2 and rats tended to avoid fields of 40 kV/tn and abo- (Hjeresen et al. 1930) In contra$t, the latter stud) a 1

found that during the ltght period. rats apparent11 r fex~ed to be in 60-Hz electr~c fteids of 25 01 51 1 !,\ Bayel ct al, (1977) f o u ~ ~ d that female rars plefel buildthair~lests outside oTa I@@-kV/m 50-Ha t ie ld

lowest level al whrch fernales \vould 1eax.e tlheir - was about 10-20 kV/rn, Le Bars et al. 11981) 1epii:r that rats dtd not avotd eartnp cn a SO kV/m f i ~ ~ c t c - pared io a area with no fteld,

Strong 60 Hz electrrc f~eldb of up to 65 kY/m 3 t - nor averslve to baboons (Rogers et a1 199%) althou- some stud~es showed that certatn soc~al behavior i v - temporarily affected by electric-field euposule iCne11 et al. 1991, EasZey et aX. 1992). TFtree bcbac~ors rir I

seemed to be affected, although. not always slgn~ficanr:~ were called passive affinity, tension. and stercnti ill Those rescarcl~crs suggested that electric ftelcls of L ( 60 kV/m affected the baboon's central neivolls svrrr i

by unknown mechannsms. They added that there - $ i

insuff~cie~it data to detelminc whether such effects mir1

be deleterxous Magnetic field. Several labor atolq r t ~ i d ~ e i i;

luukcd fur bchaviora] re,pon,se\ of arc~indli to cnnsi fields at or near the frequency oi e lec~r~c pou rt iTL I 4 2) Female pigmented r-atc r Long-Elfans Wontl, appear to be able to detect 60-HL rnagnellc: Flcici a

least 0.22 mT (2.2 G), although Iower flux dei~s~tzz

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Chapter 4: Sz"udj@s of Animals and Plant-.

22 male mtce exposed 70 5 months to Sublectrve observatrons: exposed art~niala 160 kV/tn, 6.5 hr/day. No Water Uunng reacted to the strong electric fielcl and tetldea TL

exposufe 22 controls sleep more tttan cor~ttols

Gavalas-Medicr R Groups of 4-5 monkeys were exposed Exposure to fields at frequenctes of 7 8. 75 W 7 to 7-, 45 , 60-, & 75-Hz horizontal fields but not 60-Hz siyniftcat~tfy ~noclrf~eci a lever- ot up to 56 V/m peak to peak. press response In monkeys.

6 male rars 6-wk oltf exposed to 50-Hz Male actwiry (measured autornat~cally) lower in 100 kV/m for 1 yr; 6 controls. 5 fetnale ~xpossd, but they spent more trine gnawing ni? rats to 1 00 kV/ni tor I -wk. food holdel-s. Females avorded f~elcls 21 0 k V m

Smlrh et at. (19771,

period of conditioned reflexes to bells/huzzers

Babovrch & Kozyann (1 979), Russia

Graves et al. (1 979)' Coopsr et at (1 981),

34 male deerrnice, ungrounded, and Activity (moasurcd automaiicalfy) rnct easecf 21, grounded. exposed to 100-kV/m srgtxficantly durtng the inacttve phase of the over four I-hr perlods st I -hr rntewals. cfrcadran cycle for the first exposure period

Rats, mice, rabbits, and Lliflea pigs exposed fa so-M 10 k ~ h tiefd.

mrn per day for 9 days Controls.

19 male & 5 famale rats were tra~ned lo Threshold of f~eld detection for rnalcs was press food levers, and used 117 tests to gsnorally between 4-1 0 ItV/rn, and foi felnales m@asure detect~on of electrlc Ilelds. the detection thrsshold was about 3-1 0 kV'n?

Groups of 8 male rats were exposed to Consumptron of secchariti rn presence of the fields of 34-133 kVftn i t? taste-avers~an field did not lsad to taste avetsinn Inaitiii~g tfiaiii experirn~nts, did not causo gastrointesiinal drsttessi

20 male mtce were exposed far 30-minl No effects on exploratory behavior or on day far 5 days Icr 90-Hz fleldS of 50-400 emotionality as meastlred by movenient atid Vim peak to peak. 30 eorttr~ls. excretion during 2 min on an open freld arena

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IL) l o t L W W ~ 13; w w ~ t f ~ r l y j t i t f a ~ PWGE 1

Chapter 4: Stud;@$ 0fAnimais and Plants

I I ~tuc iy~~oca t lon 'un~enurbed, vn~ss ' s noted) Selected Behavlor ResuI t s

I Weiysi & Lundstrorn Snouts of 12 rats were exposed to a Tile number of vibrissae that vibrated depen~ti?~ (1 9~71, U.S. 50-kV/m field periodically from spring on OX, reiatlvsl hum~d~ty-abovs 3 g o e no more

through winter, and vibrissae observed. that3 1 vibrated; at 25%, half of them vibrate6 I :?an eta1 ( I 987) 16 male rats were tralned and used tn 2 Threshold of fisld detect~on for rnales was tests to measure their detectton of generally between 7 9-1 3 3 kVIrn Rats wrre electrtc fields of valious strengths. trained to detect tones to teceive water

3 lnale and 2 feniale rats were trained Rats ddid not reliably turn off the oiectt ic iteld o to press a lever to turn off a 90- of 100~ t h e y did turn off an incandescent lamp wiiicn kV/nl I~etd to study avershe stltnt~li, was apparently an aversfve st~rnulcis

Coelho et a!. (1 991), 8 young adult malo baboons were Systematic observat~ot-ts ~nd~cat~ci that b a h x Easley et al. exposed to 30 kV/m, or to 60 kV/m for behavior was significantly affsatcd refloctiti~ a (1991,1992), U S 12 hrlday for 6 wk. 8 controls. stress response to the lleid

6 male rats were trained to detect Mov~ng alr drd not affect fieid detect~on sugges" electric fidrfs, and tested lo see tf rng that movement of hair, vibrissae, or skln IS moving air affected detection. not the main mechanism for field detection

f3 male baboons were trained to push a The average field detection tttreshold ,for tnaie button in the presence of a 60-Hz baboons was 12 kV/m and t h e range arnong electric field to measure field detection, s~rbjects was 5-1 5 kV/m.

et al. (1995a). I2 male baboons pushed a button In 2 stud~es, baboons slgnlflcantly decioased within certarn tlrnes for food. 6 wk at 30 respond~n "work stoppage" to test cucs or1 r!?e 8, 60 kVlm, 12 hrlday. 12 controls. first day o?sxposure N o effects over 6 wi.. ( FJ~;~ers et a 7 995b), 6 male baboons wore trained to obtaln In 7 studles, no st~orig evlclence that baboons a food rewatd In the prsssnce of a lrghr perceived f~elds up to 65-ltV/m f~eld as avers!\ andlor an electnc f~eld and exposure did not affect operant tesponcir

no t tested in the study by Sm~th et al. (19941. A strong 60-Hz field of 3.03 mT (30.3 G) was not found to be aversive to rats (Lovely et al. 1992). This field level was selected by the researchers because it induces currents In a rat that exceed the current induced by a 1 30-kV/m electric Aeld Rats avoid strong electric fields (X-ljexesen et al. 1980). Therefore, the results of the magnetic-field study suggest that field avoidance is me- diated by factors other than induced current, e.g., by sensory stiinulation effects.

Sander et al. (1982) Found no evlderlce that rats avoided sper~d~llg time in a strong 50-Hz magnetic field of 5 mT (50 G), In that smdy, a field-exposed cage and a nonexposed cage were connected by a tube &rough which the rats could move freely

Arlodler study foulld no tvzdence that male alblr~o rars (Sprague-Dawley) could detect a 0 2 m'f (2 G) 35-Hz ~nagnetic field (Marr er al, 1973). There are several differences between this and the s t ~ ~ d y by Smith et al (19941, including sex and type of rat. field frequency, and diffeterlces 1t1 the type of tests used in the studies.

Male rats exposed to 50-Hz; magnetic f ~ e l d s of 0.03 mT (0.3 G) showed increased xea-ing activlty and trends for an increase in atnbulatlon, and lcss defeca-

tion (Rudolph et a1 1985). It i s not known rnii;, these effects were associated wrrb Geld dcrecuot-i. o. other mechanrstns.

Some behavioral studies of rats reyo~tcd xntera between AC magnetic fields and other factors The and pattern of the perforrnat~ce of rats in a brila.1 I(. test was affected only when rats were euyoscd to a c

wetlc 11' 7 cific combination of 60-Hz and DC ma, (Thomas et al. 1986). No effects were seen w ~ t i ~ elit: field alone. The study tvaa a test of a cyclotlon rc. name theory (Liboff 1985); the fields used rn the st^ l-

were selected to correspond to the mass ratio for 11 rirfc* rons. A later study by Stern et a1 (1996) did riot ;cp cate the findings of Thomas et al. (1986) .brr edtlrc* virro study by Blackman et a1 (1 985b) found effe:r\ co~nbmned AC and X3C nlagnetlc fields on calc1u-r flux from ch~ck bran. Eveu ~f cyclotron r e i c i ! ~ ~ ~ not the mechanisn-r respons~ble for effect< seer rat study, zhose autl~ors po~nted nut the lnlpni-t;~r consldexxng the geomagnetic f~eld whcn assess11 c. fects of 60-Hz fields.

S p e c ~ f ~ c cortlblnat~oils of 1.C and DC m fieIds affected the perforrnancc of rats t i1 seek1 , rewards in a radial arm maze (Love1 y et 31 1991 I

BPA E/ectrical and Biological Effects R@v/@w

- - - - - - PAGE I

Chapter 4: Studies of An~rnals and P/a~?is

Mart et al (7 9739, 7 PigeoPs and 4 male rats were trarnod Prgeons: the f~eld did not affoct temporal for behavioral tests and exposed to 0 2 d~scrrntinafion dur~ng tests and it was not mT (2 G) vertlcal fields (rats, 45 Hz) detected Rats a 45-Hz field was not detectezi

2 male & 2 female rhesus inonkeys Field exposure had no consistant offacts an the wele exposed to a 15- or a 45-Hz freld operanr behavlor of lnoitkeys (rates of lever of 0.82-0.93 mT (8.2-9.3 G). presslrlg ro obra~n food).

Stnlth & Ju~tesen 39 male mica (2 strains) in toups of 3 Locomotor activity increased in both strains wete exposed lo a vertical ? 7 mT (17 during field exposure; the pigmented stran mas G) fleld for 2-min perrods over 48 hr more reacrlvs lo the f~ald

Rats were exposed to a 50-Hz 50-mT Rats could freely leave the magnetic field area if (500-Q) field for f wk. they found it aversivts At most, the field caused

only a waak irritation in the rats.

A test of the ablllty oi 4 chlckens to A conditional suppression test suggsstcd that cietect a vertical 60-Hz modulated 2450 chlckens could detect the fleld hut possible ct~cs MHz 1 7 mT (1 7 G) field from vibration or heating could not be ruled out.

Sandet et a! (1982), In B tests with 2 rats each, rats could t~ttie drfference was found between amount of

14 female tnlce were exposed to a 1.65 No effects of f~eid exposure were seen on mT (16 5 G) field for 72 ht 14 controls locomotor activrty, rnemoty of slectzoshock

avotdance task, or rosponse to selzure agent

5 male rats were exposed for 30 r n ~ n Expowre to both 60-Hz and DC f~elcls at iec t~ i l before 1-hr tests to 0.05-,5 mT (.5-5 G) rate & pattern of rats' response In a reinfoicc- fields withfwithout a DC field-0.026 mT, rnent test. No effect seen with erther field aiot~c

Mate mice ware treated with morphine Significant dose-response reduct~on of the pan- and exposed to 0.05-0.1 5 rnT ( 5-1.5 redtrcrng effect of morpt-tfne (behavior on a wal rn G) fields for 80 min. Controls. hotplate) at nlyht. No daytime exposule affect

Male rats were exposed to frelds of Fields of 1-1 5 G signiflcatitly reduced the 0 05-0 185 mT (0.5-1 85 (3) and treated lethal~ty of the drug-~ncfuced seizures Fields of wllth a seizure-lnducrng drug. Controls. 0.5 ancl 1.85 G had no slgnrflcant effects

Lovely el al, (1 QQ2), 32 mala rats. A 3.03-mT (30.3-G) Rats did not avoid that part of the stlutrle box vertical field present in part of the box exposad to the msgnetrc frefd.

Male and female rats were exposed to Both sexes exposed to the freld show6d 50-Hz fields of 8 mT (80 G) 2 hr/day for srgnrflcantly lower levels of irniability and rlo 20 days, and tested at 3 time polnts. effects on exploratory behavlor or locornotrnn

/--

BPA E/ectr/cal and Biologrcal Effects Review 3 . - C i

. .- - .-.---

Chapter 4: Studies of Animals and Piants

rnice exposed to a 0.75-mT (7.5-G) 50-Hz magnetic field tended to make more errors in finding food in a maze compared to the control mice [Sienkiewicz et al. 1996).

Anorher rat stud.y in Table 4.2 reported an intcrac- tion between a 60-Hz magnetic field and nlortality from dtug-induced seizures (Ossenkopp and Cain 1987). The drug was PTZ (yetlt3rlenete2razol.j administered at a dose of 55-60 mglkg. The lethality From seizures was reduced when male rats were exposed to fields of 0.1-0.1.5 rnT (1 -0- 1.5 G), but no reduction was seen with stronger fields. Lovely et al, (1.996) also fout-td a trend for reduced morta,lity from PTZ-induced seizure it1 rats exposed to a 0.1 mT (1 GI GO-Hz magnetic field. In the study by Ossenkopp and Cain (1987), a 0.1 -mT 11 -6) field had no effect on novelty-elicited seizures in Mongolian gerbils. An earlier study with male mice found no effect of a 1.65 mT (16.5 G) 60-Hz tnagiietic field on severity of seizures induced by PTZ at a dose of 75 m g k g (Davis et al. 1984).

A behavioral study with mice also reported an inter'acxion between a drug (morphine) and a 60-Hz magnetic field. (Ossenkopp a ~ d Kavaliers 1987a, 1987b). Another study of mice found that their relative activity levels while exposed to a 60-Hz rna,gnetic field wete highel- foi- a pign.iented strain compared to albino mice (Smith and Justeserx 1976). Those authors suggested, however, that the finding may have been confounded by other variables.

Strong 45-Hz magnetic fields had. no effects on the belxavior or two species of rr~onkeys (Grissett 1971, de Lor&,e 1974), The anirnals were trained to press a lever to obtain food, and Field exposure had no significant etiects on the monkeys' performance of this task.

Combined fields. Some of the earliest behavioral studies of combined AC electric and magnetic fields were done for frequencies of 45 and 75 Hz, instead of the electric power frequencies (50/60 Hz). The fowmer %.ere associated with frequencies of a planned U.S. Navy submarine communication project (at various times the project was called Sanguine, Seafarer, and ELF'). Sev- eral species were srudied that were exposed to electric fields of 10-20 Vlm and magnetic fields of 0.2 mT (2 GI (Coate et al. 1 970). In somc of thr: tests, bluegill finger- ling fish and 1Easrer.n painted turtles reacted to the onset of the fields i n water. Reactions were not observed for youi-~g and adult rats. or for mallard ducklings. Adult tats and their offspring conceived and. raised in the cotn- bined f3eld.s did not di.ffer from controls in their performance in avoidance and escape learning tests,

In other Navy-sponsored studies, rhcsus monkeys were exposed to 1 1x1T (10 Gj magnetic fields and weak electric fielids of up to a few 10s of V/m at frequencies

of 10,45, and 60 Hz (de Lorge 1973a. 1973b). Eur,r sure to these fields produced no consistent eI;Tec~\ IT the monkeys' performance 111 vatlous behav~oral reit,

Adult rats that were exposcd perinatally to 60-* f fields of 30 kV/n~ (vertical), and 0 1 rriT (1 G I ic,r larly polartzedf showed altered beha'i'tor rn tesponnr to tests CSalzitiger et a1 1990) Forty--one male - two expextrnents wele cxposed to EMF rt~rou,"hnu mother s pregnancy, and for the first 8 daqs were born- The rats wete tra~ned tu prcss a a$ adults they gradua11y began to nesporld at Ion r compared to unexposed con tro1c No effec~s 1% ere t(?* a

on general actrvlty levels of the expobed rals Perfornlance on a s~mple nlotot task was 5:udit-c

six monkeys (pigtatled macaques) exposed to hi1 1 I

EMF of 3 kV/m and 0.01 rn7: (0 J. G). XU hV/m 3:

0.03 mT (0 3 G), and 30 kV/m and 0.09 1-177 (0 0 r

(Wolpaw et al. 1989). Exposure occurred tfur~rrg i i i ~ t - 21-day periods. Compared to four cotltrol rnnnkccx exposure to cotnblned EMF had no effects on the trl b r #

keys7 performance of arask to obtain watet. Thei e 1; also no indicatlorls chat the fields were d~sturbma tr, 'I animals.

Another study found 110 ecfecrs on the t 2 e i l i m

rhythm of twn cquirrel mookeys exposed to h( )-HI F \ I

of 2 6 kV1m and 0.1 mT I 1 G) (Sulztnati and \Iu i

1936). A slight ieligtt~ening of the feeding period I- i seen in three of rune crionkeys exposed to 36 kL!rt - 1 8

0.1 n1T (1 GI, and 111 three of four ~notikevs exposat' 39 kV/m and 0.1 113371 ( 1 6). It1 these ' i ~ u d ~ c s t h e . M ~ I S served as their own contxols dur~ng the ficla- periods. The researchel-s suggested that the .results TI--) their laboratory study might not occm i n tlat?ttal i.1

door environments where numerous cues are avati: I- to time biologrcd rhythms.

As sunlxnar~zed in Table 4.2 rats exposed tcr \ w r i i , r

AC and a DC magnetic field showed a change 1t1 ;.z formance nn a behavtoral test (Thomas et al. 198h, such effects were found whcn the sarrie reseatc'iler c r posed rats to combrned 60-Hz EMF of 1 kVi111 and i, 1-

0 5 tnT (0.5-5 G) (Thomas el; al, 1984) Orr et al, (1995b) studied operant behavior ni

boons exposed For 6 weeks to 60-117 FKIF of 6 FJ and 50 pT (0.5 G), and 30 kV/11~ and 100 pT t I I

(Fg, 4.5). No sigrlificar~f effects of either nf tl1 birled exposures wete found on the perfor TTI arlc boons in selecting the correct butt011 to nnatch cl

lug light (match TO sa11ple test), Thcie was also r ~ t

dcncc oC a "work stoppage" whrch was found blV Rc >-c

et al. (1895a) in a previo~xs stud) of baboons expo<-cr - a17 electric field

4- 10 BPA EIecfrical and Biological Effects Review

Chapter 4; Studies of Animals and Plants

The soctal behavior of male baboons was also studied by the same research group using the same combined EMF as in the above study (Coelho et al. 1995). Neither of the combined EMF exposwcs resulted it1 clear eEects on passive affinity, tension, or stereotypy behav- iors found in an earlier studies of electric fields (Coelkro et al, 1991). However, exposure to combined 6 kV/m and 50 CLT (0.5 6 ) EMF did result in overall decreased behavtoral pe~t-fonnance rates compared to pre- and post- exposure pefiods. Exposure at the bigher colnbrned field Incenstaes. 30 kV/m and 100 pT ( I G), dld not produce the same elTecls seen with the lower intensities, or ef-

fects seen in sarlicr studies with electric fields or~ly, The researchers %aid that it was not clear whether the ab- sence of effects at thz higher levels were due to prlor exposure to the lower levels, or to an inhibitory effect of the 100-wT ( I -G) magnetic field on the effects from the 30-kV/m electric field (CoeXho et al 1995).

Observations were made of the general bchavjor of sheep raised in the 60-Hz EMF beneath a 500-W transmission line (Lee 1992). The observations were made at 15-m~r~ute mtervals during 24-hour periods once a

--+*w

BPA Electrical and

month Cor 9 months. Compared to sheep raised IT) a control area, there were no noticeable effects of exposure on the percentage of time spent by the sheep t i i

resting, feeding, srandlng, wallung, or drinkir~g

Stress

Stre?? has been defined by Sel y e 11 97 J 13) as the nonspectltc response of the body to any derrili3il placed upon ~ t . " He added that it makes TIO dlfferencc whether the stsass-productng ageat IS pleasant nl i r ~ i

pleasant Selye (19741 refelx-ed to darnagtr~g 01 ~inpicac- ant stress as "distress " By t lwx~. def~nttions stress c a n - not be avoided. brrt excegslve stress (dtst1-eqq1 zhoulci hi- avoided ~f possxble

Response of anrnlals to env~rgnniental stressot-s car1 be divided into two general. kinds nC pbysiolog~cal reac- ttons (Dantzer and Momede 1983). First at- the sholi- tern1 emergency reactions characterized hy release of hor~mnes such as epinephrine (adtet~aht~e) from the adrenal medulla. Secotid rs the long-term reaction uiigt- nally refened to as the "general ada~jeatiorl syndrome by Selye (1936) In this syndrome, deletcrlous e f f c ~ r i including death occur when an an~mal 19 no 1011ger A ~ I C

to adapt to chronic strew Hornlones invoix ed rn the shess reaction ~nc iuJc

ACTH from the gltuttary which causes ille adrenal cot tex to secrete corficos"croids--cortisol and cortlcostsi- one. Sheep, moxtkevs, and humaas pnniarr I! sect e:r cortisol. whereas brrds, rats. and n ~ l c c sect ele rnarnb~ cortjcosterone (Ganong 193 11, R/leasurerner~t of- the so- called stress hoxrnones tderttified abovc, as miell as otili-t possible stress indicators have all been used In stud$?? to determine whether exposure to EMF cau ses euceb- sive stress in laboratory animals

Electric field The early studles of behamor of animals exposcd to strong electric fields described abox E (e.g., Kn~ckerbocker et a1 1967) reported adver .ie teac- tzons of animals to the fields Marrno et al. 1197hh 1977) were axnong the first to specifically prolrtosc thar exposure to power-frequency electr~c field5 causrd ;1

stress response ln laborato~y animals, Thew research however, Found that lath evywsed to 15-k\'/rn cleztr-c fields had lower levels of col-ticolds cot~lpaxed in ct t r~

trnlx This i s opposlte to the tiottn I ' a mcrease i n tile-L

lrlorrnones expected in anjnzalc r.ergondiag to stle5.5

There have now been several labotatoi? s~udrei ti-ini have measured corticosterone 117 a~ltrnals exposed 10

power-frequency electric fields (Table 4.3). One of t hew

also found a decrease ttl the level of the Iiolrnotie t r

rats, but a decrease was not found in a replicate cxuer 2

ment (Free et al. 198 1 ). Those authors suggested that the inconsistent results of their two studies, r n a j lla\r

Biological Efficts Review 4-1 1

- - - ---- -- PAGE A

Chapter 4: Studies of Animals and P/ants

I I SpeciesIExposure (GO-Hz vertical, Study/Location unperturbed, unless noted) Selected 6~t-ravior Results

Marlrlo et al. (1976b. 354 male tats rn 10 expertments were In some experrments, exposed animals snow- I@??), U.S caxpossd to I 5 kV/m for 1 month. 179 depressed body welght, water cot~surnption z-

controls cortico~ds-~nteiproted as stress resjjollse

1 Mailno st at. (197921, Flbula bone fractured in 80 male rats Fracture heal~ng was slower tot 5 kV/m a1 13

1 1979b). and rats were then exposed to fields of days but no1 for 1 kV/ni, Authots conciuded 1 or 5 kVlm for 14 days 78 controls result is evidonc~ that electr~c field 1s a st~esscr

Graves et at. (3979), Male mice (351‘group) exposed to 25 Or Exposed mice had sign~ftcatltl higher WBCs Hackman & Graves 50 kV/m for 6 wk and 35 controls. 220 ConICoBferone was significantyy increased 5 IT 1 . (1981), U.S mice (0.25, & 50 kV/rn) taxposed 2 hr. after start of exposure, but not over 6-wk

Male rats were exposed for 30 days In one 7 20-day study body and adtenal nleigI?+- (1 study) and 120 days (2 studies) to a and conicosterone were significantly decreusec4 a

98-kV/m fietd. Controls. Adrenal weight significantly h~ghet in the other 120-day study. No effects in tho 30-day st~~ctv ,

Set0 et al. (1 982a, 3 generations of male rats (more than Exposed rats h8d lhcreased adrenal welghts, 1982b), Hs~eh el al. 300 ~ndividuals) were exposed to a 80 and :, 25% rncreased levels of coriicosterone (1983). U.S. kV/m field. Controls. Aurhors sugaested the field is 3 mild stressor I

I McGlanahan and Fibula bone was fractured in male rats Fracture healing was slowet at 74 days for Phillips (1 9831, U.S and rats were exposed to a 100 I<V/tn exposed rats as found by Marino et al isoe 9

field for 14-26 days Controls above). No effect on bone strength at 26 days

Portet et a!. (1 984), 50-Hz 50-kV/ms 20 male rats exposed Rats; corticoslerone 8, ACTH h~gher in oxri~?s;. Portsl & Cabanes for 4 Wk; 28 pregnant rabbits sxposed rats, but not slynlflcantly. Mothers & yourg (1988), France during andfor after pregnancy Controls rabb~ts no effects O n corticosfetono ol AGTI;

Qurnlan et at (1985), Male rats were exposed for I or 3 hr to No s~gn~f~cant effects of oxpasure were foi~nci r U.S a 100-kV/m constant or intermittent (1 6 corticasterone levels

see on/ 18 sec off) field. Controls

Beharr el al. (1986). 20 male fats were ex osed to a Ex osed aninials ate and drank less and had lndla hofizonai 50-Hz 5 k& field for 2-3 dlfPerences in elsctracam~ograms compared ro

months. 20 controls. cantfols-interpreted as stress responses

Quinlan st al (1987), Blood samples were tak~n from male No significant effects of exposure were focrnd 3 1

rats every 14 sec during 1 -hr exposures corticosterone Isvals. to a Eo &Vim fleld. Controls.

Study 7 : female rat$ exposed to a 40- Fernales exposed to 40-1 30 kV/m had rn- kV/m field from gestation to adulthood. creased deposits of brown matetiat (possibiy

I Study 2: female rats exposed in utero to from Hardsrian gland) on nose and ears. The 74 wk to 70-736 kV/m. Controls. depos~rs may reflect a response to stress,

I Coelho et a! (1991), 8 young adult mala baboons were Systematic observations lndrcatcd that ttie Easley et al exposed to 30 kV/m, ot to 60 kV/m for baboons' behavior was stgnrf~cantly affecleci (1 991,1992), U.S. 12 hrlday for 6 wk. 8 controls. reflecting a stress response to the frelrts.

6 generations of mice were exposed to Adult males had sign~ficantly higher daytime a 50-Hz 1 0-kVlm field from cOrtce~ZIon cortlcosterone levels, and stgn~f~cantiy increasen

trntil deatl-t, mean adrenal lipids, suggesting chronic stilrsss

been because the exposed and cot~crol anlrnals showed diffet'ent conicostexone cyclic patterns, whlch would affect Ievcls rncasured at a single time point.

Of the three stridics in Table 4.3 that showed in- c

r

eased corcrcoscerone, one found that the increase in male mice only occurred for a few minutes after the electric field had been curned on (Graves et al. 1979, Hackman and Graves 1981). In another study, adult

male mice showed it~creased levels of da? tlnic costcrone during long-ten11 exyosur e to rlcctr~c t I - I

(de Bmyn and de Jager 1994). Levels were not elel ;;r at night, but autt~ors ofrbe s~udy collcluded that the c!. tric f ield acted as a chronic stressor. No effect.; on c ~ - costerone were Eoui~cX irt tbat study fox female mice

fox young male mlce. Male rats exposed lorig-tet7.1 electric fields had mcreased corticoscexot~e level\. ,ir

4- 12 BPA Electrical and Biological Effects Rewsw

- -.+- , ..P-....,w&. PAGE

increased adrenal gland weights, which led tl-te researchers to conclude that electric fields are a mild stressot (Hsleh et aI. 1981).

No effects on corticosterone were found with shoi-t- Ketrn eIcctr~c-field exposures on rats In t h e studies by Qviiilan et a1 (1 985. 1987). Those authorss pottlred out the rtnporrance ofconsrdertng the many extraneous factors that can cause stress in laboratory amrnals. If not controlled for, such factors can confound the effect that may be attributed to electric field esposure.

In? add~txon to hormones, other measures have been cited by some xesearct~ers as evidence that electric fields can cause stress rn laboratory animals. These include slowing of body growdl and bone fracture repair (Matlao ex a1 1977, 1979a. 1979bj, food and water consurnp- tion (Behai-i et al. 1986). changes in anitnal behav~or (Easlej et all 199 1, 1982 j, and secx.etion of material that has been assoc~ateci with response to stress (Leung et a1 1990) Although two studies found that fracture re- pax ts slowed 111 rats exposed to 60-Hz electnc fields (Manno et ai. 1979a. 1979b. McClanahan and Mtjllips 1983). oorrnal bone growch 1s not affected (McCXanaIlan and Phlll~gs 1981) or may even be shghtly increased (?Valker et al. 1982)

All of the studres ctted above that reported a stress response rn rats were conducted with electric-field strengths that were within or above tbres2lolds for field derecaon (Table 4 1) Some were also done with field strertgths above levels shown in other studres to be aversrve to rats (Table 4.1). If eleceic-field srress responses tn rats and other species are due primarily to detection of an unpleasant stimulus, this i s of interest for human exposure Most people are seldom erposed to pocver-frequency electric fields that are detectable.

Magnetic field Few laboratory studies have looked for indications of stress In an~rnals esposed to power-frequency rnagnetlc fields. Plcazo et a1 (1996') found that rhytlxmicity of the daily cort~sol plasnia con- centratlon tn m ~ c e was altered w ~ t h chronic exposure to a 50-Hz 15-WT (150-mG) maglietic field, This, alorlg w ~ t h h~stologrcdl changes xn the adrenal gland, suggested to the researchers a possible response of the mice GO stress A long-term study of shccp raised beneath a 500-kV traosrnlsslon llne found no evidence that col-tl- col secret1or-1 was affected by exporure to 60-H7 EMF (Thompson et al. 1995).

Growth

Growth is lnfluenced by many factors, including genetics, food and water cor~sumpdon, food content, age, health. and a wide variety of envixonrxrental factors includ~r~g telnperatrlte. Controlling and accountixlg fo~:

C h a ~ f e r 4: Sfudies of Animals and Plants

these factors in studies of EMF rs challengrng ISot a1 stud~es report sufficient details to allow ari asseqsrneTl1 of whether these factors infiirex~ced studv tcsults T'I? PI-esenca of induced cunrcuts on m arer and f e e d ~ n g d i

vices in. aolrnal cages can greatly affect food and .ii at t .~

I ntakke. In some studies, exposure sy sterns wesc des~giiet? to minimize rnduced currents: ~n other studies, f ~ c l d - wet-e turned off at tilnes to allow anrrnalr clrne to & ~ n k

EleCtrCc field Several studies that looked at grow& of Xaboratorv an~ntals exposed to electr~c frrlci,\ are summarized in Table 4 4. Most of the stud~es re ported some changes in growth m field-exposed an1

rnals, but results often appear to be inconsls~erlt u T t t l ~ t i

and among studies. Marino et al. ( 1 976a) reported that at least some of the effects on growth of mice 111 the11 pilot study may have beex1 'elated to induccd cuwettt. on food and water devices. Steps were taken to red~lce pxoblems from itlduced currents in tbe~r later <tud\ (Marino et a1. 1980). and there was a trend for tncreased weight of exposed ilntmals con~pax-ed to controls

Margonato et al. (1 993) suggested tJ~ai their ear 1. stitdies tliat found decreased growtt-, of xats evposed r 100-kVlr.11 fields, may also have been d r ~ e to indilc;.{ cutTer1t.s on $rinkmg devicec In theil Inter siudy wstc ,

was provided to anirnals only whet1 the zlectrlc fxeiz was turned off. atid tlo effects on growth wele f n u i ~ i (&Wargonato et al. 1993). Sikov et al. (1 984'1 cicc~gntltl their exposure system so that rats exposed to a 100-E;L 1111 field did not recelve shocks while eatmg or dnnk~n? No effects on growth wcrc reported in that study.

Exposure in the large four-generation Itvwse ~ t u d ~ ,

by Smith et 4. (198 1 ) was assunlcd to be at 700 kV/tr-, However, after the study was publ~sbed. the resear chei s

discovered that, because of a problem with a trax)qfor~ner the field was only 120-250 V/m (Ph~lhps 1982). T h s study points out the high variability 1x1 growth rates thar typically occur in ar11rna.l populations Thc 125 Izttzl 112 the study were consistentlv diffetetlt IT> wcigi-tt born for exposed and control groups Tbe studv also zhnv - the d ~ ~ c u l t y of detecting a possible small zffecr of ci-i tric-field exposure when growth rates ala changing dad.

Statistical tests car1 be used to deternlrrle lhe pml' ability that diffelences between cxpo>cd and coritrci groups are due to chance. However, ~t 1s a matter u- subjectrve judg111ent by the researchers about how interpret statistically sigxlifican t dtffetences that appear to be mcons~stent. As an example, Marina 11990) dr 1 a Xyzed results of eight ~~lultigenerat~on studies o f t n~z r exposed to 60452 elecrsic fields, includ~ng ~hosc conducted in his laboratory and those conducted by S f t l ~ t h et al. (1981). The study by Marino et al. (1975ar Wac not included because of problexns assoctated w ~ t h 111

duced cuxxnts on drinking devices.

- -

BPA Elecfr~caf and Biological Effects Review 4- 1

Chapter 4: Studies of Animals and Plants

22 male rnice wete exposed to a 760- Average weigtits of mate offspring of expnsecl kV/m field for 10.5 months and mated males were consistetitly lower than controls with unexposed females. Controls. The effect was small but statistrcally slgniflcani

315 young chickens were exposed to No sigttrficant effects of sxposure were fout?o 1 -, lo-, or 3600-Vlm fields for up to 10 the growth of young chlckens wk of age. 283 controls.

Rabbits Were exp~ssd to a 50-Hz The first F4 wk after birth; no effect of exposuie $0-kV/m field for I 00 days on weight galn. After a disease outbreak,

exposed rabbits grew slower than controls.

Dumanskiy et al. 100 male rats exposed for 4 months to Exposed rats showed a trend for inctsased (7 976), Russia 50-Hz fields of 0.1 -5 kV/m. 20 controls. growlh rates

Marrno et al {'I 97Ba), 3 snerations of mice were exposed to At 35 d ~ y s old, vertical fteld, lower weights for fieyds of l D kV/rn (honronlal) or all 3 @nerrttions-may have been shock relaiea 15 kV/m (vertical). Confrols. hot-~zonfaf fieirf. lower weights for 2 generat~oils

up to 100 Vim. 48 controls

Mat rno et a1 (7 976b, 154 male rats ln 10 expetlments were l t i 3 of the 70 experiments f~nal body weight rn exposed to 7 5 kVlm far 1 month. 179 exposed rats was si nificantly towel than ~n controls. controls+ tt.e~id for iower weqht in ail enposu[l

6 male rats 6-wk old were exposed to Qrowth decreased slightly but s~gnifrcantlv 1 1 1 50-Hz 100 kV/m for 1 yr. rats exposed to 25 8 100 kV/m but not 10 kV r i

Cerretelli et al. jl979), 50 male rats exposed in grou s to 50- fn 33 Studies, exposed rats (but not ni~cs) had Hz fields of 10, 25, and $00 kbim b r 35 lower body wefghts than controls N o effects on or 48 days (8 hrlday). 50 controls. weight for sc3Cond series of 120-day exnosirres

Maifno et al. (1980). Three generations of mice were There was a trend for ex osecl i-t~ice ~n tho tha ii exposed to 3.5-kVIm fields, both generation to be slightly teavier ih3n ~ o n l i o r horizontal and vertical. Controls.

Rats anrl mice were exbased t0 t 00- Exposecl rats shbwed a sniall but s~gnificant 120 kVJm fields far 311-1 20 days in slowing of growth af 4-8 wk but there was no more than 31 experiments. Controls. overaft effact of exposure of growth.

Smith st al (1 ga l ) , 1400 mice from 4 generations ware Effects of exposure on growth, if arty, weie conce~ved born and raised ~n a transrent. not readily reproducrble, and oas~lv 120-250 Vim field masked by other environmental factors

Seto et al (1 983) U.S 176 rats were exposed to 80-kVim There was a slrgl-rt hut significant delay in fields from conceptrZln to about 120 growlit of young exposed rats from 4-8 fvk. > L

days of agn 174 Conrruls. not aftet 8 wk

Le Bars et al. ( 1 983), Male and female rats exposed to SO-Hz The growtl? rates of the exposed rats w e t s 50-kV/m for up to 3 months. Controls slightly but not s~yniticantly less than contio,,

Offspring af female rats exposed to a No significailt effects of exposure wcre foilnci i ; ~

100-kV/m field during estation and for the g~owth of young rats. 8-25 days after birth bntrclis

Portet et al. (1 984). SO-Hz 50 kVirn. 20 male tats exposed No effects of exposure wet-0 seer? on ~ I O V J ~ ~ I 3 Portet & Cabanes for 4 wk; 28 pre nant rabbits exposed young male rats or on newborn tabbits expnse-

dur~ng andior a8er pregnancy Controis from gestation until 6-wk of age

Slkov et al. (I 987b), Female swcne (FO) and offspring CF31 No effects on mothers' growth dur~ny yeslatiof+ exposed to 30-kV/rn. I;a &. F7 brad Birtt-r wei~hta of first female YOUI-I~ of F1 s were twice to zlonexposed males. Gontrb.ls. 75% less than controls. No effr~ct on later grov If-

140 male rats (13-wk old at start) were No effects of exposure were seen on giowtli ot exposed to 50-Hz fields of 25 or 100 tnale rats. kV/m for 280-1 240 hr. 80 controls

BPA Electric~l and Biological Effects Review

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C h a ~ k r 4: Studies of Animals and P~anfs

Togethex, the studies reported 5 1 lout of 168) 5ra- tist~cally sign~ficant dsfferet~cec rn we~ght. Of these. I n

29 cases the exposed animals were heavier than the control mlce. and in 22 the exposed mjce were Ilghter than the controls, Thuc the results do not show a cons~ster.it dose-response patte~n. Some researchers would vlew the results as evidence of no effect of electrlc field cx- posure on the growth of rnlce Mmno (1990), however, suggested that both rncreases and decreases In weight ale possible, depending on conditions present 111 each experiment Overall, Marlno cancluded that the ~esults of hss analyses provide evidence for an effect of electric field exposure on growth of mice of about 6.6 percent.

Magnetic field. The growth of 374 young chickens e~poscd to GO-Hz lllagnetlc fields of 0 8 or 3 0 mT (8 or 30 G) was cornpared to that o f 361 cotltrol chickens (Durfee et al. 1975) Through 7.0 weeks o f age theze we1 e no sratksttcally significant differences m growth bztwcen the two groups TFtrey-days of exposure to a 1 02-mT ( I 0 2-G) 60-Hz vertlcal rnagnetlc field bad no efiec~ on body OX bone gtowrh I n 14 male ~ a t s (Sirnn-ions et a1 1986). The rats were exposcd fol 12 houi 3 pel day ( halt were exposed during the dark phase, and half wele exposed dunng the light phase). Their growth was compared to six control rats. There were also ilo effects 011 the growth or 20 pregnant rats exposed for 24 hours per day for 20 days to a 50-HZ magnetlc fxeld of 30 mT 1300 6) (Mevissen et al. 1994).

Njtie inale tntce exposed 1 week for 23 hours per day to a -very strong 60-Hz magnetic field of 0.1 1 T ( 1 100 G) losc an average of 3.77 percent of their body weight lFam 198 1). Dunng the same time 9 control mrce gartied an averagc o f 4.76 percent m body welgfit.

Growth rhrough 30-day s of age was studled for 184 young male and fe t~~a lc mice exposed during gestation to a 50-HT 20-xnT (200-G) magnetic field (Sienkicu.icz et af. 1994). Cornpared to 166 control mice, there were no overail effects of magnetic-field exposore on giowtl~. Fol exposed males. then. average wezgt~t at 30 days of age %as 5lrghtly Ie?$ than that for the controls, and the diffetencc was statrsttcalXy sign~ficanc. Picazo ert a1 (1 996) found that g1-owth increased signzficatitly in rnale rnice chionic,iIly exposed to a 50-Hz 1 5-yT (150-n1C) field

Two fiundred and fifty-SIX rnale rats in two expen- ments were exposed 22 hours per day fox 32 weeks to a 50-Hz, 5-pT (SO-mG) nlagrnetlc field (Margonato et al. 1995) Compared to 256 controls, there were no cffccts on growtl~ rate. or on the final weights for the exposed rats.

Combined fields As part of teseafc'rl for t i le L ".1

Navy's submarine communicat~o~~ project. 30 r h e s ~ ~ s monkeys were exposed torig-term to conlbrned EMF 0,

0 2 rnT (2 G) and 20 V/m at fi equencres that kar~cd ran domly between 72 and SO Hz (Gr~ssett et al. 1977) Tlli most ngn~fxcat~t frndrng of the first year of thc stud^.

was that exposed males gained weight Inote raprdl:! that control males At the end of I year, the ra-tale rnonkevs exposed to EMF were about 1 1 percent beavrex rtlari rile controls. The weight gain appeared to be ynrnal~l! :I?

the form of increased mass of upper back and pccrol a1

muscles. At the end o f the study EMF exposure taraIed nearly 3 years. At that time the growth rates for ei- posed and control. males was no longer ~tgnrfrcanti> cii f- ferenc from each other (Lotz and Saxton 1987)

A follow~rp studv was condx~cted by Lorz and Sarlcin f 1987), in which 30 mol~keys were exposed to the bane

levels of EMF as used in the study by G~issert et RL ( 1977). In the second study, nrale tnonheys had a sligkiti. h~gher growth rate during puberty compared to co~~tso l i but it was not srat~sncally slgnjficanrt Authois of t l ~ r study suggested that possible effects on growth sctulii be related to increased testocobterone sscretror-i caused i? i current s t~inul~hot~ of the scrotuxn while a motlkrv -A

w i n g on the cage floor.

Reproduction and Development

Possible effects of power-Frequency EllvlF on I C ~ ~ O -

duction and development have bee11 of prttnaq Intersir since the earliest studies of EMF were C O ~ C ~ L J C ~ ~ ~ . 14 large number o f such studies has now been conducted by researchers in several countries. Animals are gener - ally considered to be more sensitive to effects of en\ I -

rorlmental agents during early stages of developmci~r especrally before birth. The term developmental toxr c- ~ t y has been used to descnbe affcctr durii~g the earl) stages of developmellt (Rornmere1111 1989) Such t'- fects, which include abnorlnal cl-tangez 117 s t iuc tu le of

f~~nction, are caIIed reratoiogles

Laboratory at~imals are studied to provrde data foi

assessing whether sorrle agent like ENIF rnay cause I r-

productivf: or dcvclopniental effects rn humans In gcn- era], however, there are nlany lirnjtatlons to applyl!lg results of animal. stuclres to assess reproductive risks m hutnans (Brent et al. 1993). Also agents that cause dtt- velopmental toxrcity In animals at very high closes llza\ not be relevant to human exposures to tbe agent

TI1t studies of EMF described below were done \& I:~I

a wide range of Field i~~tensities, and looked at m a n y end points, Posstble effects of exposure ro EMF we3.e

studied fox. tirne periods that included breeding, gesta-

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Ch&Wfer 4.- Studies of Animals and Plants

tion and early development of the young. Several of the studies included nlultrple generations of animals exposed to EMF

Electric field. Table 4 5 summarizes several studies of xcproductio~x and development 1x1 animals exposed to electric fields in labol-atory experiments One of the earlrest studies to report effects on reproduct~on from a powel--frequency electric field was done In Russ~a (P*n&xex~ko 1977). That sttrdy reported a vxxety of ad- kerse reproductrve effects xn male and female rats exposed to a tx~oderare stre~lgtl~ 50-Hz electric field of 5-kVlm. Howevex, the pager gave no information about the electric-field exposure system, or about how the ar~i- mals were fed and watered. Tfic reproductwe effects reported by the Russian researchers were generally not found by the other studxes of rats m Table 4.5 Tbese rtxclude three large multlgeneration rat stud~es (Seto et al. 1954; Rommcrcil-ct et al. 1989, 1990).

Manno er a1 (1980) reported that sui'vival rate.; decreased m the offspring of mice exposed to 3.5 kV/m 60-Hz fields. This effect was not reported in three other studies of mxce (fCnrckerbocker er al. 1967, Smxtb et al. 198 1 , Sav~n and Sokolova 1985). About the only cort- slstent effect foul~d i11 the large rnultxgeneration study by Smjrh et al. (1951) was a delay in the age at which inclsoi teeth erupted in young mice At 10 days of age, the number of tnice with erupted incisors was about 19-25 percent less for exposed antmaXs co.ly?ased to controls (colllbjtllng all. data for both sexes).

When two generations of female miniatuxe swine were exposed to a 30-kVlm 60-Hz electr~c field fox 20 houi s pel- day, and bred to unexposed boars, significant increases In fetal malfor~nations and birth defects xn offspring were found (Fig. 4,6) (S~kov et al. 1987a, 1957b). The results, fiowevex, were not consisterlt among breed- ings. or among generations. To obtain data on fetal malformations, some swinc were sacrificed at 100 days of geytation. and others were allowed to give birth to provide breedlng anlxnals for the next generatxon Tl~ele were no consistent dlffereaces between exposed and control groups for I~tter size, fetal mass. or mass of fetal organs. Sorne of the terarology results from this com- plex mutzigenexation study are surnrnanzed in Tablc 4.6.

At the fir% breedmg of thc second generatton fe- nlale swxne (Fl) that were born and raised zn the electric field, most of the animals refused to mare w~tli the unexposed boar lSikov et al. 1987a). Breeding had to be temporarily suspended There were no such prob- letns wrtb the control females at first breeding. Because of tnconslstelxcres rn the lesults of the study, the scscarch- err; could not conclude that the electric field was the cause of the irrmous xeproductive effects that were fo~~zid,

The researchers that conducted the $~\ltte 7ti - conducted a followup multiger~eratrot~ studv 1% 1tl-r 1 r

In an attempt to see Wether s1rn11a.1 I-epldoducri~- I hcts would occur" 111 anotllex specles (Rotnmcietrn c* 1989). So~ne teratology results of the rat stud! are .;he in comparison with the swxne ~ t u d y 111 Table 4 6 sults of the f~rs t rat experimnerit produced result5 - I -

were very similar to dle swine study. Fol the i i r q t btrr ing, there was no s~gn~ftcant differerlce 1t.i fetal malt-* mations between csposed and control rats. I11 tile 4:: ond breeding, tha proportlot1 of lltters xq it11 malfor--I tions was threefold higher in the exposed gtoup c a v * -

pared to controls. although rt was not statistlcall~ -1

nificant. Also, as m the swltle study, ttte first brzei,! of the second-generation rats produced a srgn~fica:l: crease In malformations m the exposed atllrridli 1X I -

the rat study was tegeated (experiment 2 ) . tttc reaulr- the first rat experxment were trot repltcated i Tqb1~ -

Rarnmereim et a1 ( 1967) suggested that r he L ~ I T I - ences in the results of the two rat experrments rnav i been fxom random or biologxcal varratior~. Thci 7 8 %

also indicate that the threshold fo~' the eftects 15 n s a field strength of 100-kVlm The researcher, concl u;lr that rats are not a good tnodel for asseqsinp rbe racrt 7

that may have been ~nvolved in produclt~g the efti:" found rn the swine study. No further elect1 ~c-field li~i

les of miniature swine were done. Rommere~nl et al. (1990) did conduct anotilel + x

tenswe electric-field reproduction s t u d ts iih -i a t \ Groups of 68 fernale rats each (FO generation I err t posed to vast~cal 60-Hz fields of 10, 65, a3 I30 kl r and mated with unexposed males. Some of 1he1r -- male offsprrng iFl generation,, after bettig exposzc t 3 months, were mated wtrh a new gi-oup of vi>ew?i.- males, After 20-days of gestation. the F i females . * I killed and their fetuses exam! ned

On a per-fetus basis. there cvas a slgnrfrcantl\ h - number of ~t~alfoxmed fetuses 111 the F1 ferndies 8.

to 65 kV/nt con~pared to the conltols No such e z was seen in the fernales exposed to 10, or to 13" lh 8

The researchers said that one could wgue that till- sult is a "w~ndow elfect." but tfiev could ~ d t l r i ~ T ~ biologncal explanatioxr. for such a possibilltv The ~ i l - i i

bers of young born per litter, and ttle~r mortality i -it.. were not affected by exposure The vveights nF iiw -. posedF0 mothers were slightly depressecl durjnp g e y - don, and d ~ i r ~ n g the lactation yenod

Effects on reprod~~ctxon and developrnct~r seen r some studies of anlmals exposed to clectrlc fields 17 7

have been lilfluenced by the amrnals' pelceptxon OT r: field by skin, hair, or feather stimulation CJtaies rr A

t 1985) attempted to ellrn~nate cornpl~catrons frorll SD 4 1

4- 16 BPA Electrical and Biological Effects Review

Chaptef 4: Studies of Animals and Plants

Breeding ageftirne Litters with malformations (%) LRters with birth defects (46) 1 Anlmalslbreedtng exposed (months) Elposed Control Exposed Control I

-----,?.---

I Swine First generation (FO) 1 First breeding 22/4 2/7 (28.6 YO] 4/7 (57.1 %) 18D (38 9 %) 10/2 (20 i) ' -

I Second breading 3617 8 12/16 (75.0 %*) 2/7 (28.6 Oh) - -- - - Second generatlon (F?)

First breeding 18/18 - - - - 20125 (71.4 %*) 4/12 (33.3 a < I Second breeding 28132 79/27 (70.3 %) 811 1 (72.7 %) - - - -

-------------_.---------i_l__.-_I----------

Rats, Experiment 1 First generation (FO)

First breeding Ui 1/22 (4.6 % 0/21 (0.0 O h )

Second breeding 7.214.2 6/20 (30.0 %] 2/20 (10.0 %)

Second generation (Fl) First breeding 3/3 6/37 (16.2 %*1 1/42 (2.4 %f

Rats, Experiment 2 First generation (Fa)

Second breeding 7.2f4.2 1/27 (3.7 %) 2/24 (8.3 %)

Second generatton (FY) Flrst breeding 313 1/37 (2.7 Qh) 3/37 (8'1 %)

" The higher parcantage of litters with fetal malformations or birth defects in exposed animals cornpared to control anitnals is statistically significant.

4- 1.8 BPA Electrical and Biological Effects Review

Chapter 4.- Studies of Aninlals and Piants

dtscharges and per~pheral stirnulatxon by studying chicken embryos. Large numbers of eggs were exposed to 60-Hz electr~c fxelds of up to 100 kV/m through the 2 1-day ixrcubat~on per~od (Fig. 4.7). No effects of f~eld exposure on developing embryos were seen in this study.

Magnetic field. Chicken embryos were also iunong the several species used In studies of power-fie- quency magnetic fields (Table 4.7). F~nnls l~ researchers found that in thelr ~tudles, the threshold for adverse develupn~ental efkcts froin 50-Hz magnetrc fields was around 1. 2 pT (12 m C ) (Juut~laxnen 1986, Juut~lanr?er~ et al. 1937). There was no inclrcalion of a dose-response effect, with fields of 1.25 LLT (12.5 mG) and 12.5 RT (1 25 mG ) producing about the same percetltage of ab- r~orillalltles Most of the abnormalteies involved the neural tube. and both lnlnor and severe abnormalities were elevated In cxposed embiyos

Martin (1 992) found no increases in abnormalities when cb~ckerl embryos were exposed to a 60-Hz magnetlc field of t ,05 pT (10.5 mG). This level is slightly below the threshold for effects not& in the above Pxnn- ish studies. MuAn (2988) had previously found ~11at a I -pT (10-mG) (peak) pulsed magnetic Weld did cause a s~gnrficank increase In abnormalities in develop~ng chick ernbryos (pulse characteristics. 2-rns (millisecond) rise and fall. ntnes, 500-ms durat~on, and a 100-Hz reperi- t1on rate).

Interest rn pulsed rnaznetlc fieldh and chicken embryos developed after Spanrsl? researchers first reported adverse effects of 0 5 - m ~ puIsed fields of 100 and 1000 Hz (Delgado ct al. 1982) Six independent research laboratories used den tical equipment and methods HI an at-

BPA Electrical a f~d

tempt to provide deftn~t~ve iiiforniat~or~ of the effect (Bei-man et a1 1990). They used a pulsed nlagnetlc field with the chal-acterrsttcs as defined above ITI Ihe I-esea~ch by Martin (J988). Only two of the sxx laboratories touriri statistically significant ltlcreaseb 213 develop~nlentdl anomalies Together, however, the cornhlrled t e6ul t i

showed that the incidence o f anonlalies wa\ ahour 25 percent greater than in the controls

Although the researchers concluded that the11 over all results appeared to conf~rm earlier reports of effects on developing embryos, they could not esplaio rhe i r i -

constrtent results among the six lilborato~ ~ c s , 111 a .r analysis of the studv Handcock and Kolasba i 19L~2 i

found that the inter-laboraton variation rn thc sxpct , i~l

effect from unmeasured factors was at least ac larg,.e ac

the exposure effect Martjn. (19921 also po~rlted nut [list the one laboratory that found no effect on anomal~ei had used a chicken stram different from tlioqe used bi the ottm- laboratories.

Of the seven studtes In Table 4.7 that used mice four reported vanous effects on developrr~ent In one study, on1 y one of several measures of phystcal postnatal development ofnllce was affected by preriarai exposure to a 60-Hz magnetic aeId (Sienkrewicz et ai. 1994) Compared to controls, exposed male rnicc (but not fe - males) were s~gnihcantly ligl-tter in wergtlt at 30-dai 5

of age. Exposed nlilce also performed the atr I l,ob ling reflex earher. arid stayed 011 a rota-rod treadnull. fol lesr tinlie tliaxl controls. No s~gntKicant differences \sere wcii XII e~ght other behavroral tests. Authotss of the scud- concluded that a 60-Hz Inagnetlc field 15 ~ i o t a bchal ioral tetafogetl

Plrcazo et al, f 1995b) repolted that. tn n~ale mlce c\ posed to a 50-Hz nlagtletlc field, testlcu1a.1 weight drici

testosterone levels %irere increased De Vi ta et al. I 1905 i reported an effect on sperm otrn~ce exposed to a 50-Hz n~agnctic field, but the effect occurred 111 o n ] \ one ot the six tune-points that were studied

Picazo et a1 (1995a) found chanpec 1r1 skeletal muscle in female rnlce exposed to a 50-Hz magnetic field. Two studies of rats also reported t ha t the ma- dence of minor fetal skeXetal anomalies was increased xn animals exposed to SO-Hz magnetic r ~ e l d c (Huuskonen et al. 1993, Mevissen et al. 1994 ) In borh studies, the skeletal tmalfonnat~or~s pximar~l y i ~~vo l sed the ribs, and they were of a type that would probabi~ not mpatr later deveIopnnent of the fe t~~ses (Rle? l s s f i

er al. 7 994) The jr~cidence of skeletal and o t k a fetal malfor'mat~ons was not lncteased in rats exposcci rr\

60-Hz rnagnctrc fields (Rornrnercltn. et a1 1 996 1

Lloyd et a1 (1993) found some star~stlcally ~ i ~ n ~ f i

cant differences In xeproducrion of ~heep~head it11 nnov fish reared xn an aquarium In a 60-Hz magnetic fteic

Biolo&ricaf Effects Revrew


I SpecieslExposure I StudylL~cation (GO-Hz horizontal unless noted) Selected ReproductionlDevelopment Rosults.

8 I

Fam (1 981), I Caneda

1 male mouse exposed ,6500 hr In an There were no srgn~f~cant differences between I electromagnet to 0.1 1 7 ( 7 100 G) and exposed and control progenies for mean f

bred to 7 unexposed females. 1 control. weights, numbers born, or numbers sulvrveci. Z

Ramirez at at. (1 983), Drosophrla flles and eggs were Flies showed a srgnificant avo~dance of the f~elri Spaln exposed to a 50-Hz fleld of 1 mT fore g laying, Moitality of exposad eggs was

(1 0 G). Controls. signi 7 icantly h~gher than rhat for controts

Cameron et a1 (1 985), 27 fertiirzed Medaka fish eggs were By 51 hr after exposure there was an average U.S. ex osed to a 0.1 -mT (I -Gf clrc~rlariy 18-1-rr delay in embtyo dovrvioprnent cornpareci

porarized fieid for 48 hr 26 controls. to conti-01s. No developtnentnl abnormsl~ties

Juut~lalnen & Saall 20 chicken srnbtyos were exposed to For fields of 12 5 mG & 1 25 G the numbei s r +

1 (1986), Finland 50-Hz vertical fields of up to 0 125 niT abnormal embryos were about twice as ti iyi i

(I .25 G) for 48 hr. 20 controls. for controls and stat~stically signif~cant

Juutllalnen et al. 365 chicken ernbtyos were exposed to Significant increases in abnormal etnbryo (1 987). Finland 50-Hz vertical fields of up to 0.125 mT development fourid above a thteshold of abolir 1

(1.25 G ) for 48 hr. 77 cantrabs. 11.3-12.5 mG. No effect on development rare : 1

, Zrrnmerman et al. ' (1990), U.S.

Martin (1 992), Canada

Sea urchin eggs were exposed 4 mln Compared to controls, sxpossd eggs had a 1 -hr after insemination to a rotating 0.1-mT delay in emb onic developtnent betvrreen l a - b (1-0) field for 23 hr. Controls. 23-hr KO developmental defects forln0

40 chtcken embryos were exposeci to a Nelther b~polar nor unipolar sinewave fields 1.05 pT (10.5 mG) fleld parallel to long Mbsed an ~ncreaso In rnalfortnatrotis 11-1 deve lo~ axis of the egg for 48 hr. 40 controls. iw embryos during 48 hr.

Huuskonan ot al. (1 993), Finland

Llo d et al. (7 993). i t &

70 pregnant rats were exposed to a The incidences of minor fetal skeletal anonia- 50-Hz 12.46-pT (T24.6-mG) field for 20 lies, and of llve fetuses per litter were stgriifi- days. 70 controls. ~antly higher in the exposed rats

Reproduction of shsepshead minnow Survival of QrWp I1 embryos redirced 7 . 7 ' o , fksh ln a 60-Hz 1-1.25 mT (110:12,5 G) group I 1 fish at 26-56 days 4-6% longer eyq field. Group 1 started as juvenrles, produdt~bn low~tr it? 'I of 3 triais, lower embryo group II as embryos. Controls. survival of 1 hatch froin group II (Soo toxt )

YRSLI~ et RI, (1993), 70 male & female nirce. 50-Hz field of No s~gnrficant exposure effects on feral s u t ~ l \ ? Japan 0.5 or 5 mT (5, 50 G) during develop- rnter~~al abnormalitias, or sex ratio Exl~osecj

rnent, matlng, gestation. Controls. fetuses had fewer external abr?orrnal~ties.

Kowalczuk et al. 90 pregnant mice were exposed to a. No effects of exposure weie found on mating (1994), U.K. 50-Hz vert~cal field of 20 mT (200 G ) for fertility, or on htusee: weight, ex ratio, n u m b s

17 days. 86 controls. alive, number bf external anomalies,

Lazetlc S, Pa-Nadj 2 getIerations of rats were exposeci to a Slgnifrcant exposure effects. postnatal rn~r ta l i t '~ i (1 994), Yugosiavla 50-Hz field of 100-500 pT (1-5 G) and welyht were sltghtly rncreassd, the nurriofi- 8

7 hrlday 5 days/wk. Conttols of young born peta mother was decreased 1

Mevtssen et a! (1 $94, 12 pregnant rats were exposed The number 6 f tnlnor fetal skeletal anomal~es 1 Gerinany 24 hrfday fof 20 days ro a 50-hi! field of was more than twrcs as high in exposed rats

30 mT (do0 G). 12 conrrol~. compared to controls. No effects on mothers I Sienkiewiz et al. 184 offspring of fetnale rnice exposed No significant effects on eat attachment, toott- (1994), U.K during geatarion to a vertical 50-Hz field eruption, eye opening, hair coat, or sexual

of 20 mT (200 G). 168 controls. rnatunty. Effects ~n 2 out of 10 behavioral tests

De Vita et a1 (1 993, 30 male mice 8.1 0 wk d d weris Sperm assessed by flow ~ytometry at 7, 14 21 Italy exposed for 2 or 4 hr to a 50-kz 1 7-mT 28, 35. & 42 days after exposure. A significant

(1 7-G) field. 30 controls. effect found only at 28 days after 4-hr ewposiiie

Picazo et al. Second-generation male R female mice Exposed females. calc~um in skeletal n-tuscle (1 995a, l995b), Spain 30/group) exposed to a 5Q-Hz 15-pT significantly decreased. Exposed males

150-mG) field, 30 controls/group. testicular wetqht & testosterone rncieascd -

Rornmereirn et at. 96 female rats exposed 20 hr/day to 20 Malformat~on incidcrrrce did not differ among (I 996). U .S . days gestation to 1 niT ( I 0 (3) or 0.61 gtb~ips. Mean l~ve nutnber of ferusos siqi?ifi-

GT (6.1 rnG1 iq 2 mplicattes 96 controls. cantly lower in 1 m i group In replicate A or-dy

4-20 BPA EkPcfrical and Biological Effects Review

Chapter 4: Studies of Animals ancl Plants

coll-tpared to a those m a control aquarium (Table 4.7). However, the researchers said that because the effects were ~zot sccn consistently, the elfecls could not be pos1- t n ely atmbuted to field exposure.

Combined fields, Part of the early research for the U S Navy's submarine comlxlunication project included a smdy of fertility of rats exposed to electnc fields of 10 or 20V/m, comblned with magnetic fields of 0.1 or 0.2 mT [ 1 or 2 G ) at frequencies of45 ox 75 Hz (Coate and Rcno 1970) The study included first aod second generations, witl;~ a total of about 300 rat3 exposed to EMF artd 90 conkofs No consxstent dtfferences be- tweet1 exposed and control rats were found for mating behawor. conceptlot1 rates, or the number and appear- ance of llve fetuses. For all data cornbzned, exposed aruinals had a lower fertility index, but ~t was not statis- tjcally sigmficant. The young of the second-generation exposed group had a significantly h~gher survival, rate compared to controls.

In another Navy-sponsored study, thee male beagle dogs were exposed at night, 5 days per week for 3 weeks to 45 or 75-Hz fields of the same intensities as in the above study (Teeters and Coate 1970). In addjtion to field exposure. the dogs received a 0 5 mA current (45 or 75 Hz) injected th.rougX~ two electrodes (one in a front leg and orie in a hind leg). Sperm count was qmte van- able, but there were no apparent effects related to exposure on spenn morphology or xnot~l~ty.

Berrz et a1 (1987) conducted sevelal reproducttve tox~cology studles wit11 mice exposed to coxnblned 60-Hz EMF of I I ~ T ( 1 0 G ) and 50 kV/m, and O 3 mT (3 G) and 15 kV/tn. In studies of possible dornznant lethal mutations, no s~gnlficant consxstent d~@erences between exposed and conu-01s were found for ~~npreg- nation, vlable embryos, early or late deaths, corpora lutea, or l?re~mpXantation losses. There were also no such drfferences for several endpoints in n~ulageneration studies, and ISI cytogenehc studtes (including sister chro- tnaud exchanges),

In a study w ~ t b two types of experiments, female rafs and their young were exposed to combined 60-Hz vertical electric fields of 1 or 3 00 kV/m, and ellipt~cally poiaj xed magnetlc fields of 0,1 or 1 0 mT (I. or 10 G). 1x1 one experiment, young rats were exposed for 7-8 hours per day for 1 , 2, or 3 weeks (Gona et al. 1993) Rats exposed to 1 kV/w and 1.0 1117' (10 G) had a small but statistxcally s~gntf~cant decrease in cerebellas mass, but overall body growth was not affected. The lats exposed to these held levels also had cexebellurn DNA at~d RNA levels significantly higher than In the con- t~ols at ages 6 and 13 days, but not at 20 days. For rats cxp~sed to 100 kV/nl and 1 mT (1 G) , DNA and protein

levels were lower than for cor~trols at 8 days of age. and were higher at 22 days of age. There were no rnor-pho- logical differences in the developing cerebellutn bei\%ecti exposed and control rats at any field cornbinatlon.

In the second expeiirnent, pregnant female rats were exposed 23-hours per day from days 5 to 19 of y r e g xzancy, arid their young were examined at 0, 5. 1 1 . and 19 days postnatally (Mang et al. 1993). There were rlo

slgmficant d~fferences between exposed and cont~ o i young rats for overall 31-owtl-r, or for physlcal abnolmali- tles. There was a srnaIl decrease in comcal w e t ~ h t fix rats exposed to 1 kV/m and 1 mT (10 G). a7d a sniail

mcrease in cortical weight f fo rats exposed to 100 kVfri; and 1 mT (1 G). For rats exposed to 1 kX71xn and I tr;-T

(10 G) there were small reductions in DNA, RKA. anc: protein levels from the neopdliurn (the cortical gray anri underlying whrte matter). There were tlo morpholrrgr- cal diflerences in the developing neopal lium bet\v,een exposed and cox~trol rats at m y field ~0mbinali0~1.

The developing brain was examined in another study of EMIF, but the experimental subjects were chicken

~ g s wete ernbqos (Blackman et a]. 1988). Fenilized e,_ exposed continuously during incubabon to e ~ t h m 50- 01

60-Hz vertical electric fields of 15 9 V/m ( 7 2 eggs ar each frequency for each of two expel-lrnentsj Brain t~ 7-

sue from 1.5-day-old chicks was then exposed for 20 minutes to 50- or 60-Hz combined EMF of 15 9 Virri and 0,073 pT (0.73 mG). For brat11 tlssue fro113 chicl.:5 incubated in a 60-Hz clectrjc field and then exposrcl i n

50-Hz EMF in virm, there ivns about 3 40 percent In-

crease in calcium ion efflux fro111 bra~n tissue. This e+- fect occurred rn both experrtnents, and was 11ot founc for the other frequency combraat~ons A th~rd expc~t -

merit was conducted .ctl which egg positions in the expa- sure system were reversed and the same results u7ers found.

Melatonln Endocrinology is the study of certain glatlds and ttien~.

secreted chemical messengers called hormones that xegu- late physiology and behavior (Norris 1985). Endocrine glands seczete hormones directly ~nto the blood strean FIom~urncs produce effects at extremely low concentl-a- tions. The etldocrine sysrenl is essential for an organ- ism to function and to adapt to rts environment

Mellatonio is a hormone found in vertebrates, In-\Iei -

tebrates. and even in plants (Balzer and Hardclancl 199 I Rexter and Robmson 1995), I I ~ ~liarnrnals meiatontn I \

produced primarily bv the pineal gland in t h e brrui: tho~gkl sruallcr amounts rnay be produced eisewhc~r: includirig the Harderian and lacrimal glands 111 sonlr: specxes (Rerter 1989a ) In birds rnelatonin is produced in the eye and in the pineal (Underwood et al. 1951)

BPA Electrical and Biologicffl Effects Revic'w 4-2 1

Chapter 4: Studi@s of Animals and Plart fs

Circadian rhythm Brain

gland

Melatonin iovel in the blood

I Noon Midnight Noot-i Midnight Noon klldi

The nigrttly secretion ot the hormone melatanin by the Melatonrn levels are very low during t h e day pineal gland is driven by a: circadian rhythm generator and Increase rapidly at n~ght TIm secretion

In the brain. Light regulate$ the gensiator sb that; mela-, dortesponds to the length of the night This tonin secretion by the pineal rnafc%esl the day-night cytle., otovides biological information about the tit-le

(Melatonin Is also found in many species without a pineal, of day, atxi the t1tii8 of year such as Insects, plants, and even one-celled organisms.)

The pineal secretes xnelatonin into the blood on a cycl~c basis that typrcally cox~csponds to the cycle of darkneqs (Figs. 4.8, 4.91 Howevex, the secretion 1s drrverl bq a crrcadtan rhythm generato1 called the suptach~asrnattc nuclle~ CSCN) ('XBmarba et al 1985) Even rn constant darkness, the generator causes melatontn to be secreted for a period of time about every 24- hours (thrs 1s called free ~xinnmg) (Taxnark11 et al. 1965). Normally, the SCN is regulated by the daily light-dark cycle though neural stxxnulatxon from the retma, so that n~elatonir, secretion occurs during the daily dark period.

In rile plxlcal. gland, melaton~n IS syn.thes~zed from selotonln thiough a cotnplex serres of steps that occur In structures called pinealocytes (Reiter 1989b). Mela- tonln and serotonrn are classified as indoleamines because they are der~ved from the m n o acid tryptopllan. The melatonin synthesis process is shown i ~ z a simpli- fied ibrm in F~gui-e 4.9. Thls rnfoxmatxon IS prov~ded because some EMF research cbscussed below has examined some of the key enzymes (K4T and HIOMT) in thxs process,

Secretion of ~nelatonin provides biological inforrna- t~on about the Xet~gtl,. of the night Thrs can also be In-

terpreted by orga~lisms' physiology to provide informa- uon about the season of the year Tlzus the metatorrrn slgnal provldes cilttcal tnforrnatton to specres rl?ar breed only a t certain times of the year, so that thex young are born durqtn_a Favorable environmental conditions (Tarnark~n et al, 1985). Sheep and other seasonal breed-

4-22 SPA Electrical and Biologic&l Effects Review

ii, IUI L U U ~ LS; ww L 3 W Y Y J l j 3 U L PAGE - -

Chapter 4: Studies of Ar~irnals and Planr,~

ers car1 be "tri.cked9 into breeding at atypical times of year by artificially manipulating the melatonin signal (Kennaway et al. 1987, Paterson and Foldes 1: 994).

Melatonin ha,s many other influ.etlcas on biologicali functions and processes, in addition to regulating seasonal breeding, In humans, rnelatonin rnay a,ffect the sleep-wake cycle, mood and behavior; contribute to ' jet lag'': help fight cancer; and may help slow the effects of aging (Reiter and Robinson 1995). Recent books, ar- ticles, and news about mclatonin'a purported be~wficial effects, have led to a rapid growth in the sale of melatonin as an over the counter "wonder drug" (Reiter and Robinson 1995, Cowley 19951. Some scientists, however. believe rbae some of the claims about the benefi- cial health effects of rnelatonin misrepresent the scien- tific research that has been done to date (Turek 1996).

Several factors are reported to contribute to the pat- ten1 of nocturnal tnelatonin secretion (Reiter 1989c, 1993). These include age, genetics, m d several external environmental factors. Included among the latter are light, stl-ess, alcohoI, and EMF- Light at night can have tile m o s ~ dramatic effects on suppressing melatonin levels at night, However, there is considerable val-ia- tiort among species as to the light intertsiry requi

r

ed to suppress tnelatonin (Reiter 1985). Laboratory rats re- qu.ire only a brief exposure to very weak white light for tnelatotiin to be suppressed. 111 comparison, hurr~ans require I I I L . C ~ sh-anger light it~ter~sities for melatonin suppression (Lewy et al. 1980, Laakso ct al. 1993).

The continued interest in EMF and 1nelatorlir-i is largely due to suggestions by some scientists that mela- totlit1 rnay be one mechanism for explaining how EMF could affect carcinogenesis in humans (Stevens 1987, 1 993; Wilson et al. 1 989, 1.990). There is evidence that 60-Hz magnetic fields can lower melatonin's natural ability to slow thc growth of breast cancer cells (Llburdy X 99%). Reports that power frequency EMIF could af-

fect rnelatonin secretion were first made in the early 1980s. Since then, many more studies have been conducted. The studies with animals are sunxmarized in Table 4.5 and in the sections below. Later se.ctions in this chapter afso describe cellular studies uf EMF and melatanitl. Studies of E.MF and melatonin in humans are described in Chapter 2: DC field studies are described in Chapter 6 ,

Electric field. Wilson et aX. (1981. 1983) first reported that noctur~lal pinaaI ri~elatonin was reduced significantly by about 53-75 percent in ad.uIt ]male rats exposed to 60-Hz clcctric fields. Similar effects were seen i'ot.fields of 1.7 and 65 kVhn, with no indication of dose response. The efFect appeared after about 3 weeks of continuous exposure, and recovery occurred within

about 3 days after exposure ended, In these stud~es jlevels of the melatonln rate- lttntting enzyme NAT (hip. 4.9) were also decreased. and there was a trend fot an increasc in the pineal hornlone 5-inethoxytn~propttcf~ (5-MTOL). Synthesxs of both melatortin at id 5-i19TciTa requires the enzyme MIOMT (Fig 4 9). but only melatonrn requires SAT. Tlle researchcrs. therefwe, sug gested that the effect on melatomil seen~eci ro irlr olx r 2 "biochemical lesroa" m the actrvlty of the SAT enz) ti;e

The ab0-r.e ~cstrucb gloup extended ~l-reti Cindrlir> in adult rats, a11d showed that nocturnal pjr~eai melak- nrn was also decreased in youtlg male tats expored tri 60-Hz electrlc fields of as low a.s 10-kV/m iReiter ci a1 J 988). In this study. however, statisttcally s~gn~fical-it reductions (55-65 %) In melatonin o c c u ~ ~ e d at oill? one of three hme-poznts during dark (4 br after lights our)

In later studies the researchers Miere unable to repll- catc thew earlter findings of a large decrease 11-i pineal melatonin in adult male rats (Sassex et al. 1991 1 4 n - other research group also found no effects of a GO-Hz electric field on pineal melatown. NAT, or HTOR4T 111

male rats (Grota et al. 1994). However. t~octur rial se- rL1m illelatollin levels wcrc rcduc~d sign1ficnntl> h? about 20 percent In that study. The researchers said that t h ~ s i ~ n d ~ n g suggested that tissue uptake 01 degr adatloi-i of melaton~n was affected by 60-Hz electr~c field elpo sure.

Magnetic field Several research ~ ~ o u p s il;.,>r studled rnelatontn In laboratory anrmals esposeii i t -

power-frequency rnagnetlc fields CTable 4.8). Nlost stud Ies of tneIatontti atid EMF included long-term ctpnsilre of animals in the dark penod. Yellon (1991 ). h o w e ~ c i reported tllzit tn D~lmgarian hamsters, an accute I 5-rxlinu te exposure to a 60-Hz magtletlc field xt~ the light per.lcoii led to delays tn the onset and a reductron In the peak. pineal and serum melatonin in the subsequelit d a ~ k pe riod, Serum melaton111 levels in the exposed tlarllster ,i were about 40-60 percent less than in the controls.

Yellon (1996) was unable eo consrsrently repllcaiz the effects on rnelatonin from acute magnetzc-field ex,- posures (during long-day llght exposures effec-t.5 KJt. le

found in three of f ~ v e stud~es; w ~ t h short day eyposutcs effects were found in both o f two studres). Yellon ( 1996 r also found that a datly 15-minute ntagnerjc-ficld exposure for 3 weeks d ~ d not affect aoctux~~al mclarortin pa! terns. or sexual maturation In hamsters.

Matt et al. (1 994) aIso fouizd that an acute 1 5-mi-11,rc exposurs to a O.l-mT (1-G) 60-Hz field slgnihc,?ntI-\ seduced plrzled melatonin Icvcls irt tnale haliistet s / \ ~ u t e

exposures of inale rats to the satne fteld IeveI fat. 15 or 60 minutes did not affect either pineal or S ~ I - L ~ T L ~ ~ I ~ melatonin concentrations (Rexier et a1 1996)

BPA EIectrical and Biological Effects Review 4-2-;

A.CI I-t A.UU4 I.3s urn L3UL-1=J5rj3WL PAGE -r


Study/Location SpeciesfExposure/NZght Samples Selected ~ssults

Electric Field Studies (60-Hz vertical)

I Wilson et al (I 981, 40 male rats (2 studies) exposed for 30 Nocturnai p~neal melatonin and NAT s~gnrf!car?*!, 1983), U.S. days to 1.7-'1.9 kV/rn, or to 60 kV/m. decreased after exposure, and 5-MTOL signtfi

Samples 4 hr after dark. 40 controls cantiy increased after exposure. I F p n "1 a (1986), 40 adult male rats wefe e osed for 1 ! A significant depression In t'locturnal pineal 2,3, or 4 wk to a 65-kVimTeld. melatonin after 3 wk of exposure. Levels Samples 4 hr after dark. 46 controls. recovered in <; 3 days after ~xposure ended

Male rats exposed from conce tion to Noctitrnal pineal melatonrn was sryn~ficantly 23 days; 10, 65, 01 $30 kV/m. gamplea reduced at all field strengths at one iln?a-pe~:-d 4, 6, & 8 hr after dark. Controls, (4 hr after dark), Phase delayed by about 1 4 ni

Anderson st al. (1988), Young adult rats were exposed ro a Exposure did not cause a depress~on ~n fleld of 200 V/m. Controls. nocturnal melatonin, suygestrng ttireshoid for

60-132 elsaric field effect between 0.2-2 liV/tn

( ",PI". et a"lWV, 23 male & 23 female rats exposed to a No slgnlflcant exposure effects on pineal 65-kV/m field for 30 days. Samples 3, melatonin in mate rats. Pineal melatonin in 5, & 7 hr after dark. 46 controls, females significantly increased 7 hr after dark

Grota et al. (1 994), Male rats (in 3 studies) were exposed No exposure effects on nocturnal pineal U.S. to a 65-kV/m field for 30 days. Samples rnelatonln, NAT, or HIOMT. A significant redirc-

4 hr after dark. Controls. tion in nocturnal serum melatonin.

Msgnet l~ FCeld Studies (60-Hz vertical unless noted)

11 ?$" fl"l), Adult hamsters exposed to a 0.1 -mT After exposure durlng tight petiod, a s~gnificani 7-Q) fisld for 15 min. 2 hr before dark. decrease In nocturnal serum melatonin ancl a b arnples 6 times after dark. Controls. reduced duratlon of nocturnal prneal melalonri?

Kato et al. (7897,1993), Male rats, crrcularly polarized 50-Hz Compared to coritrols, plasrna & pinoal melars- fields 1-250 .LLT (7 0-2500 mG) for 6 Wk. nin reduced sigtliflcanrly at all field levels d~ir ina Samples 6 hr after dark. Controls. day & nlght. No diff~rances among field ieveis

d8 male rats exposed 6 wk to circularly Noct~rrnal plasma melatonin was significsntlv polarized 50-Hi! field of 1 p,T (1 0 mG). reduced by exposure, and returned to conirol Samples 8 ht' after dark. 48 controls, levels w~thin 1 wk after exposure ended

Kato et a1 (1 994b), 48 male pigtnented rats, 50-Hz Nocturnal plneal K plasma melatotlrn signifi- Japan circularly polarized 1 pT (1 0 mG), B wk. cantly reduced 15-1 6% tn exposed vs shams

48 shams (.OZEiT), 60 controls (.014pT). Exposed &. shams also less than controls

Kato et al (1 994c), Male rats exposed f3 wk 40 horizontal or There were no significant effects of exposure or Japan vt3rtticaI 50-Hz flelds of t p,T (1 0 ma). either plasma ur pineal melatonin In contiast t t ,

Samples 6 tir after dark. Controls. effocts from circularly polarized fields

Yellon (1 994). U.S.

Yellon et al. (1994), U.S

Adult hameters exposed to a 0 1 -mT Exposure significantly decreased nocturnal a n d (I -G) field for 15 mln 2 hr before dark serum melatonin in 2 of 3 studies. Effects at Samples 5 times after dark. Conttols. specific trmes of night were not consistent.

Juvenile hafnsters expossd to a 0.1-mT The nocturnai melatonrn rhythm of juvenkie (1 "-0) field for 15 m n 2 hr before dark, hamsters on long-day photoperlocls was dally for 7 days, Controls, affected by daily 75-min exposures,

Matt et al. ( 1 994), Male banisters exposed to a 0.7 mT Pineal rnelatot~in was significantly rediiced r ? ? Wilson et a!. (1994&), (I-G) field for 15 min, 2 hr before dark. hamsters In short-day photo periocis arid ttiai

Samples 3 & 5 hr after dark. Controls. were not photorafrsctory.

Abbreviations: 5-MTOL= 5-methoxytryptophol (a pineal hormone). HIOMT= hydroxyindole-0-mefl?yltrar~sferase enzyme in synthesis process for melatonin and 5-MTOL), NAT (also called SNAT) serotonin N-acetyltransferase rate-limiting enzyme in melatonin synthesis).

BPA Electrical and Biological Effects Review

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CITapter 4; Studies of Animals and Pjanis

Magnetic Field Studies (Cont 60-Hz ve~t~cal unless noted)

Rats & mice (12!sex/group) exposed to 0.2 pT (2 mG) to 1 -rnT(t 0-Q) fields continuaus or onlofl for 10 wk. Controls.

Loscher et al. (1 994), 36 female rats exposecl9 wk to 50-Hz Nocturnal serum melatonin levels were signlft- horizontal field of 0.3-1 pT (3-10 mG). cantly reduced In rats e~posed to the graclferrt Samples 4 hr after dark. 36 controls. magnetic field.

54 male tats 1,10,T00 ~Tf10,100, 1000 ma) 50-Hz horl2Qnta1, 12 hr or 30 days. Samples 6 hr after dark. 18 controls.

10 male and 10 female rats exposed to Comparsd to pre- and post-exposure times, 50-Hz fields of 5 or 500 pT (50 mG or 5 there were no significant effects of sxposure on 6) for 24 hr, Self controls. a melatonin metabolite (aMT13s) irl urine,

Adult hamsters exposed to a 0,l-mT (l-G) field Rr 15 min 2 hr befoie dark, daily far 3 wk. Controls.

Mafe rats exposed to a horizot~tal No effects of exposure were seen for ris~rjg (3 0.1 mT ( I G) field for 15 or 60 mrn 2 hr after dark) or peak (5 hr after dark) p~neal or hefore dark, or 3 hr d~irrng dark. serum rnslaton~n levels

Bakos et al. (1 996), 5 male rats exposed for 24 h i to a 50- Nd slgniflcant difterence was found in the Hz 7 00-gT (I -G) horrzontal fretd, and 5 amount of nocturnal 0-sulphatoxyn~eiatonrn IP rats exposed to a I-pT (10-n7G) field urine betwean the two groups of rats

For 100 tnG field- signrficant 30°h dcct-ease i n

& 12 wk to a SO yT (500 rnG) fleld. Prneal: 9 rats, freld only; 9 raIs field .t DMBA Sham controls.

Studies of Combined Electric and Magnetic Fields (60 Hz)

f 0 female shee exposed 10 months ta No significarit effects of 24 hrlday EMF on 500-IcV line, 4 p% (40 n?G & ti kV/rn, nocturnal serum melatontn amplittide, duratrori Samples every 0.5-1 hr 10 sontrois. or phase as measured over ergtit 49-f~r portods

15 femafa sheep exposed 10 months to No sign~ficant effects of 24 hriday EMF or1 500-kV line, 3.8 pT (38 mG) & G . 3 kVini, nocturnal serum melatotiln amplittlde, dulatiat? Samples every 0.5-1 hr 15 controls or phase as nteasured over elgM 48-hr period

No significant effects of 12 hrlday EMF during 50-1tT (~OO-MG), & vertical 6 kV/m, or light period on nocturnal tnelatonin lsvsls with 100 pT (1 Q) & 30 kV!rn. 3 controls. fields turned on cZ off slowly to avoid transients

W~th variablo exposittes 0 5-23.5 hrlday ana 50 FT (500 mG), & venlcat6 kV/rn, or rapid on-off field swrtchtng mostly clutlng the 100 KT (1 G) & 30 kV/m No controls lrght phase, srgntflcant day R nrght mslatonin

suppression cot~lp~rbd to pre-exposure levels

-

BPA Electrical and B~ological Ef&cts Review


Kato et al. ( 1 991. 1993) found that 1-250 pT (0.01- 2 5 GI crrcularly polarized 50-Hz magnet~c fields depressed pXasn~a and pineal melatonzn levels in male aI- bino (Wister-King) rats during night and day. Tn the studies, the conu-of, tesrs were not done concurrently wtth the fieid-exposure tests, The xesearclxers d ~ d not say wliether comparing exposed/canttol data collected at dlffexent tlrnes of the year rnxght have affected their results. No effects were seen when the researchers used l-pT (IO-mG) horizontal. or vertical magnetic fields {Kato et al. 1994~). Kato et al. (1994b) also fou~ld that nocturnal plasma and pineal. rnelatot~in were significantly reduced when pigmented rats (Long-Evans) were used. In that study, both the exposed and sham-exposed rats had significantly lower nocturnal and dayame melatonln levels compared to controls, 'The shams were exp03ed to a stray field of 0.02 p'T (0.2 mG) when the exposure facility was energized. The cot~txols were tested about 1 month before the exposed/sham tests were done. and without the facility energized in an arnbienr field of 0 014 p,T (0 14 mG). The researchers drd not say whether by comparing the exposed and sham rats to tbe controls tX7at were tested at a d~ffel'e?~t time perrod, their results could have been affected.

Setrnaoui and Touitou (1995) also found that a 1-pT ( I O-mG) 50-Hz honzonral magnetic fidd had no cffect on nocturnal serum melatonzn levels in male rats. When they used stronger horizontal fields of 10 or 100 pT (100 or 1000 mG), both serum melatonjn and pineal NAT levels were significantly reduced by 30-40 per- cem. Serum xnelatonin levels were also reduced sig- n~frcantly by 20 percent xn female rats exposed to horizontal 50-Hz magnetic fields of 0.3-1 MT (3-10 mG) (Loscfier et al. (1 994). In a later study, these researchers found a 30 percent reduction in semm melatonin in female rate exposed to a 10 )1Tr (100 mG ) 50-Hz magnetic field; no effect was seen on prneal nlelalonin (Mevi5sen et a1 1996a)

Exposure of maIe and female mts and mice to 60-Hz magnetic fields of 2 pT-l nlT (20 1nG -10 G) had no effects on nocturnal serum or p~neal melaton~z~. or on p~rieal NAT (McCorrnick et al. 1994a). Exposure included continuous j 1 8 5 hours/day ), and rmex~nrttex3t (1 hour on, 1 hour off).

nvo studtes measured the excre$on of a melatonin metabolite in the urine of rats exposed to 50-Hz tnag- netxc fields (Bakos et a.1. 1995, 19915)~ With this tech- nique, small laboratory animals do not have to be k~lled at a single time-pomt, as IS requlred when melatonin is measured 111 serum or in the pineal. Illstead, urine can be collected tvithout disturbing the animals. add melatontn production over the whole night or day can be estimated. There was no indication in the study that the

amount of excrecxon OF lhe tnelatorl~n metzl~oi~te in

was affected by 24-hour expo~ure to a 50-Hz mar-1.: I

field. Combined fields Two research gloups

melaton~n In animals exposed to coinblned 6Cl- tnc and magnetic fields. One group stuct~cd In,

in baboons expoqed to 60-?Tz EMF 111 a spec~all., - - strutted exposuie facility (Fig 4 5 I The baboo~i.; L - fitted with a special jacket and catheter appalatus sc th i blood samples for lnelatoniil rneasurernerltc, cnu + 1

taken automatically It1 three studies, three baboon.; exposed to dtfferent levels of EIVF (Table 4 i. 12 hours per day during the light period for 6 (Rogers et al. 1995~). The fields were turned 011 ar slowly to prevent trans~ents. Undel these con61 ' c i there wereno statistically sigotficatlt drffere~ices In turnal rnelatoaln between exposed a11d COLI~J ni t)abni>~

In another study two baboons were expnscd to EA'' on a variable schedule, and rile frelds \were turned and off raptdly, therefore, trans~ents were p loat : -~ (Rogers et af. 1995d). Exposure occuned tt~osti\ i ing dayatne over a 21-day per~od. The baboons st-- as their own controls. h4elatorlrn levels wcje ; between pre-exposure. and exposure cond~tions trast to the previous srudles with EMF turncd on

slowly, in th i s study nearly cornplere suppresslo., nocturnal melatonin occurred with babootls eipncec? raprdly switched fields. The supyressjon ,% n c r i i i ~ .

after 9 days of daytime exposure The researci~et c I-%

sidered their results as preiimlilary because the! TIC-

to be replicated 111 a cnoi-e e~tens jvc cxpc~iinerit Ilu a replicated study, female lambs wele expoc.- -

for 10 tnonths to (50-Hz EMF heneath a 500-k1' r C:

mission line (Lee el al. 1993, 1995). Rlrlatonln -i

measured In blood samples taken at 0.5-3-f~~)ur 'rti

vals during eight 48-hour penods Figure 3 I17 r - 3 example of the rx~elatonixt pattern 111 the sheep ciua:~: 48-hour period In May {for clarity, val iarlon arno1.r i

sheep at each measurerncli t point 13 not sholvn I 4; ~ I I

time the sheep had beeo exposed to the 500-kX- lilic 4 weeks, As is typical for spec~es i n ~enc t a l . n~elcri 3

secretion irtcreased raprdly 111. the evenilig. and ~ a r i r decl-eased near sunrise, No statlst~cally ~ i g r i i f i ~ ~ i i i ~ ferences were Found In melatonin patter 11s b e ~ ~ v e e ~ l ? . raised beneath the 500-kV line, a l ~ d sheep ralced

control area.

Other Hormones

This section revJews studrcs of EMF and other r t

mones that were not already covered in I ) T ? ~ ~ C ) I I \ \

tions on stress and melatonin. Table 4 9 sufnrnailri- some basic information about the specjfic hot m o ~ i e s it 8.3

are mentioned in thls section.

4-26 BPA El@ctrical and Biological Effects Review

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Review, EMF · clUT-.-_(Uc(UL PAGE Chapter 4: Studies of Anin~als arld Plailr:- zng when anrrnals...

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