P. 1 

# OAR Box 1128 Prepped by Ollie Stewart



## Document

Number: 

# 76 ) 11-1-25

4 Docket Number: 

# A-83-2 2

Printed 4/21/2008 11:07:13 AM Sheet 76 of 198) n P. 2

Environmental

Health Perspectives Vol. 78. pp. 47-51 1988 

# influence o

f Membran e Sodiu m Transpor t upon th e Relatio n Betwee n Bloo d Lea d an d Bloo d Pressure i n a Genera l Mal e populatio n b y Thierr y Moreau, * Patric k

Hannaert , Geneviev

e Orssaud , Gu y Hue., * Ricard o P . Garay, * jea n R . Claude /

Bernar d Juguet, * Bernar d Festy, 8 

# and Josep h Lellouch *

Fiv e re dbloo dcel l catio n transpor t system s (RBCTS) , togethe r wit h bloo dlea dleve l an dbloo d pressure , wer e measure di n 12 9 mal e adul t subject s wh o wer e no t

occupationall y expose dt o lea do r subsequen t

t o acours e of

treatmen t

for hypertension . Bloo dlea dwa s positivel y relate dwit h systoli c bloo dpressure , an dt o alesse r degre e wit h diastoli c bloo dpressure . Bloo dlea dwa s foun d significantl y negativel y relate dt o on e of th e RBCTS , Na*,K

* cotransport , an di n addition , Na'J C cotranspor t

appeare dnegativel y relate dt o bloo dpressure . Fina l result s showe dtha t bloo dlea dn o longe r account s for

a n increas e i n systoli c bloo dpressur e whe n Na'J C cotranspor t wa s take n int o account ; th e sam e tren dwa s observe dwit h diastoli c bloo dpressure . Thes e finding s sugges t tha t a bloo dlead-relate dNa'^ C cotranspor t impairmen t

coul dexplai n th e bloo dpressur e increas e observe d t o paralle l th e bloo dlea dincrease . 

## Introductio n Th e relationship s o

f bloo dleadt

o bloo dpressur e hav e bee n investigate di

n severa l genera l populations , wit h somewha t divergen t

publishe dresult s (1,2). Non e o f thes e studie s attempte dt o explai n th e mech

anism s possibl y involve di n thes e relationships ; how

ever, several work s hav e show n tha t bloo dleadcoul d inhibi t on e o f th e re dbloo dcel l catio n transpor t sys tems (RBCTS) : th e Na + ,K + pum p (3-5), an dothe r report s sugges t

tha t on e o r mor e RBCTS . includin g Na + ,K + pump , coul db e impaire di n hypertensiv e subject s (6-8). SERM. Unit

e 169 . 1 6 Av

e P.V . Couturier . 94807 . Villejui f Cedex . France . + INSERM . Unit e 7 . 16 1 ru e d e Sevres . 75730 . Pari s Cede x 15 . France . tLaboratoir

e DASES . 8 8 ru e d e L

aJonquiere , 75017 . Paris . France . §Laboratoir

e LHVp . l bi s ru e de s Hospitalieere s St . Gervais . 7.5004 . Paris . France . Therefore , i t wa s logica

l t o tes t th e hypothesi s that

th e increas e o

f bloo dpressur e wit

h bloo dlea

d coul d b e explaine da

t leas t partl y b y RBCTS impairmen t

du e t o a n effec t o f lea dexposur e a s reflecte di

n bloo dlea

d con centration . I

t i s th e ai mo

f th e presen t

stud y t o inin

vestigat e i

n asampl e o

f no t occupationall y lead-expose d me n th e possibl e rol e o l live RBCTS . includin g th e Na + .K + pump , an dth e rol e o f re dbloo dcel l Na + an d K + conten t

i n th e bloo dlead-bloo dpressur e rela

tionship . 

## Material s an d Method s Populatio n Th e stud y populatio n consisie d o f 12 9 adul t me n be

longin g t o th e Pari s Polic e Administration, wh o wer e no t occupationall y expose dt o lead , wh o wer e no t

fol

lowin g acours e o

f treatmen t

fo r hypertension , an d wh o wer e age d2 3 t o 5 7 year s (mean , 36. 2 years) . Eac hP. 3

48 ' MOREAUETAL. subjec t wa s give n astandardize dquestionnair e askin g for detaile dalcoho l an dtobacc o consumption , amon g othe r information . Severa l physica l parameter s wer e recorde dan dafastin g bloo dsampl e wa s take n for biochemica l measurements . 

### Alcoho l Consumptio n an d Smokin g 

## Habit s Fo r eac h subject , th e dail

y consumptio n o

f wine , beer , aperitif , an dspirit s wa s recorde dan dconverte di n gram s o f alcoho l pe r

day . Th e smokin g statu s wa s als o noted : nonsmokers , 4 5 subjects ; exsmokers , 2 4 subjects ; curren t smokers , 5 7 subjects . Fo r curren t smokers , th e quantity o

f tobacc o smoke dpe r

da y wa s expresse di

n grams . 

### Physica l Examinatio n Systoli c an ddiastoli c bloo dpressure s wer e measure d usin g amercur y apparatus . Thre e measurement s wer e performed : th e firs t

afte r 1 0 mi n resting , th e secon d1 0 mi n late r (both in supin e position) , an dth e thir din th e standin g position . Thi s protoco l followe dth e recommendation s fo

r bloo dpressur e measurement s o f th e Britis h Hypertensio n Societ y (9) . Individual bloo d pressur e value s reporte d(systoli c o r diastolic ) ar e th e mean s o f thes e thre e measurements . Heigh t an d weigh t wer e als o recorded . 

## Biochemica l Measurement s Th e followin g parameter s wer e measure do n eac h bloo dsample . Blood Lead. Whol e heparinize dbloo dwa s dilute d (1/10 ) int o an ammoniu mnitrat e solution ; th e dilutio n wa s injecte dint o atantalum-coate dgraphit e furnac e o f aJarrel-As h 85 0 A

A spectromete r

(dr y 100°C , as h 750°C , atomize d2,450°C) . Measurement s wer e performe da t

283. 3 n mwavelengt h wit h backgroun d correctio n an dcalibratio n b y standar dadditions . Special precaution s wer e take n t o avoi dcontaminatio n b y ambien t

lead , reagents , an dmaterial s (heparinize d collectio n tubes , Vacutainer , B D 06527) . RBCTS and

Red Blood Cell Na + and

K + Contents. Fiv e RBCT S wer e considere di n fres h re dcells : Na + ,K + pump ; Na + ,K + cotransport ; Na + ,Li + counter transport ; an dNa + an dK + passiv e permeabilities . Thei r mechanism s o

f actio n ar e outline din Figur e 1 . Method s o

f measuremen t

o f eac h RBCT S ar e describe d i n detai l elsewher e (10) an dca n b e summarize da s fol

lows . Bloo dsample s wer e store da t 4° C an duse dwithi n 3 hr . Afte r removal o

f plasm aan dbuff

y coat , re dcell s wer e washe dfre e o

f Na + . Th e activit

y o f th e different transpor t system s wa s assesse db y spectrophotome

tricall y measurin g Na + efflu x i n four differen t Na +

- fre e medi acontaining : a) K + ; b ) ouabain ; c ) ouabai n an dbumetanide ; an dd ) ouabain , bumetanide , an d Li + . Re dbloo dcel l Na + an dK + content s wer e expresse d »> • pn'coum n i««»Sf0« i NiMii* :

PtKMIOIllI t

Nl ' I T C0t««NSP0I U FIGUR E 1 . Re dbloo dcel l sodium(Na+ ) andpotassiu m(K + ) transpor t system s (RBCTS) . i n nmole/Lcells . Na + an dK + passiv e permeabilitie s wer e expresse di n hr 1

. Activit y o f Na + ,K + pump , Na + ,K + cotransport, ! an dNa + ,Li + countertranspor t wer e expresse din umole/Lcellshr . 

# Results Bloo dLea dan dBloo dPressur e Bloo dlea dlevel s an dsystoli c bloo dpressur e value s ha dlog-norma l distributions , s o tha t lo g transfor

mation s wer e use din statistica l analysis . Amon g informatio n obtaine dfro mth e question

naires , dail y alcoho l consumptio n appeare dt o b e strongl y positivel y relate dt o bloo dlea d(correlatio n coefficien t

r = 0.29 , p < 0.01) ; th e bloo dlea dmean s ± SEM i n nondrinker s (1 9 subjects) , i n subject s wh o dran k betwee n 1 an d5 0 g/da y (64 subjects) , i n subject s wh o dran k

mor e tha n 5 0 g/da y (3 5 subjects ) were , respectively : 142. 1 ± 8. 6 ng/L , 160. 8 ± 5. 2 jig/L , and 188. 3 ± 8. 8 jig/L . Ag e wa s weakl y positivel y associate d wit h bloo diea d( r

= 0.14 , p = 0.13) . Dail y tobacc o consumptio n wa s no t

relate dt o bloo dlea di n curren t smoker s ( r

= 0.01) ; th e bloo dlea dmean s ± SEM in curren t smoker s an di n exsmoker s wer e 175. 4 ± 5. 9 ug/ L an d178. 5 ± 9. 9 |J.g/L , significantl y highe r tha n th e mea n i n nonsmoker s (146. 8 ± 6. 2 ug/L) . Bloo dlea dwa s foun dt o b e significantl y positivel y relate dt o systoli c bloo dpressur e (r = 0.19 , p = 0.05 ) an

d t o alesse r

degre e t o diastoli c bloo dpressur e ( r = 0.17 , p = 0.07 ) Takin g int o accoun t alcoho l consumptio n an

d ag e yielde dth e partia l correlatio n coefficient s 0.1 ? ip = 0.09 ) an d0.1 4 (p = 0.15) , respectively ; takin g furthe r int o accoun t

bod y mas s inde x di dno t chang e thes e latte r results . Th e mean s o

f systoli c bloo dpressur e accordin g t o bloo dlea dlevel s ar e show n i n Tabl e 1 ; the y appea r t o increas e abou t

8 m mH g throug h th e thre e

# r P. 4

SODIUM TRANSPORT, BLOOD LEAD, AND BLOOD PRESSURE 49 lowest bloo dlea dclasse s (lowe

r tha n 12 0 ug/L , betwee n 12 0 to 160 |J.g/L , an dthose-betwee n 16 1 t o 20 0 ug/L ) an d then , a t

> 20 0 (xg/L , t o reac h aplateau in bloo d pressur e values . A s show n in Tabl e 1 , simila r result s we r e obtaine dafte r

adjustin g systoli c bloo dpressur e value s for alcoho l consumption , age , an dbod y mas s index . Tabl e 1 als o show s tha t th e sam e tren di s observe dconcernin g diastoli c bloo dpressure . 

## RBCTS , Re dBloo dCel l Na + 

## an dK + 

## Contents , an dBloo dPressur e Th e distributio n o

f Na + ,K + pum p appeare dlog-nor

mal , s o tha t

statistica l test s wer e performe dafter lo g transformation . Amon g RBCT S an dre dbloo dcel l Na + an dK+ contents , onl y Na + , K + cotranspor t

wa s significantl y inversel y relate dt o eithe r

systoli c o r

diastoli c bloo d pressure ( r

= -0.20 , p < 0.05 ; r

= -0.19 , p < 0.05 , respec tively)

- Figur e 2 show s th e systoli c an ddiastoli c bloo d pressur e mean s accordin g t o Na + ,K + cotranspor t activit y values . Th e systoli c or , respectively , diastoli c bloo dpressur e mea n increas e i s abou t 6 mmH g o r

5 m mHg fro mth e highes t

Na + ,K + cotranspor t

clas s (27 1 nmole/Lcellsh r

an dover ) wher e th e mean s ar e 126.0 m mH g for systoli c (83. 7 mmH g for diastolic ) unti l th e tw o lowes t

classe s (131-20 0 (imole/Lcellsh r an dlower tha n 13 0 nmole/Lcellshr) , i n whic h th e mea n pressure s ar e nearl y equal : 131. 9 m mH g an d 131. 1 m mH g (respectively , diastoli c 88. 6 m mH g an d 88. 1 m mHg) . Afte r adjustmen t

for alcoho l consumption , age , an d bod y mas s inde x (whos e correlation s wit h Na + ,K + co transpor t were : r = -0.20 , p < 0.05 ; r

= -0.21 , p < 0.05 ; r = 0.13 , p = 0.15 ; respectively) , th e partia l correlatio n coefficient s betwee n Na + ,K + cotranspor t an deithe r systoli c o r

diastoli c bloo dpressur e wer e r = -0.2 8 (/xO.Ol) . 

## RBCTS , Re dBloo dCel l Na + 

## an dK+ 

## Contents , an dBloo dLea d The correlatio n coefficient s o f RBCT S an dre dbloo d cel l Na+ an dK+ content s with bloo dlea dar e liste di n Bloo d pressure (mmHg ) 15 0 r 14 0 - 13 0 12 0 11 0 10 0 9 0 8 0 70 

# i I , Systoli c 

# I _ Diastoli c

6 0 \- -13 0 131-20 0 201-27 0 271 *

(23 ) (35 ) (30 ) (26 ) Na+,K + Cotransport (iimole/l.cell s hour ) FIGUR E 2 . Mean s o f

systoli c (• ) ari d diastoli c (• ) bloo dpressur e accordin g t o Na + ,K + cotranspor t activity . Mean s ar e represente d togethe r wit h thei r

95 % confidenc e limits . Number s o f subject s i n eac h Na + ,K + cotranspor t clas s ar e i n parentheses . Tabl e 2 . I t

appear s tha t

onl y adecreas e i n Na + ,K + co transpor t i s significantl y relate dt o an increas e i n bloo dlea d( r

= -0.23 , p < 0.05) . Th e "correspondin g re gressio n coefficien t

indicate s a39. 5 nmole/Lcellsh r Na + ,K + cotranspor t

decreas e fo

r a10 0 (xg/ L bloo dlea d increase . Thi s negativ e relationshi p remain s signifi

can t after allowanc e fo

r alcoho l consumption , age , an d bod y mas s inde x (partia l correlatio n coefficient , r= 0.19 , p< 0.05) . Table 1 . Systoli c an d diastoli c bloo d pressur e mean s accordin g

t o bloo d lea d values . Bloo d lead , K/l Systoli c bloo dpressure ,

mmH g Adjuste d Mea n ± SE M mean 3 Diastoli c bloo dpressure , mmH g Adjuste d Mea n ± SE M mean a < 12 1 124. 7 11. 9 (18) b 121-16 0 126.711. 7 (44 ) 161-20 0 133. 4 ± 2. 2 (31 ) -Jg O 130. 9 ±2. 4 (20 ) 124. 6 (17 ) 82. 9 ± 1. 9 (18 ) 83. 8 (17 ) 126. 3 (40 ) 85. 7 ± 1. 4 (44 ) 86. 4 (40 ) 132.0(27 ) 89. 8 ±2. 0 (31 ) 88.9(27 ) 129. 0 (20 ) 88.012. 8 (20 ) 87. 4 (20 ) 'Systoli c an ddiastoli c bloo dpressur e value s wer e adjuste dfo r alcoho l consumption , age , an dbod y mas s index . Number s o

f subject s ar e i n parentheses . Tabl e 2 . Correlatio n coefficient s o f bloo d lea d level s wit h RBCT S an d re d bloo d cel l Na + an d K + contents . Paramete r Correlatio n coefficien t Significanc e Na*,K * pum p NafK * cotranspor t NafLi * countertranspor t Na * passiv e permeabilit y K * passiv e permeabilit y Re dbloo dcel l Na * conten t Re dbloo dcel l K

* conten t 0.0 5 (124) a

-0.2 3 (124 ) -0.0 4 (124 ) 0.0 1 (124 ) 0.0 9 (119 ) 0.1 1 (124 ) -0.09(124 ) NS b 0.0 2 NS N S N S NS N S a Number s o f

subject s ar e i n parentheses . b NS , no t significan t

a t th e 10 % level .5

0 MOREAUETAL. __•_•_-_-_._- •



# r

Na + 

## ,K + 

## Cotransport , Bloo dLead , an d Bloo dPressur e Th e effec t

o f bloo dlea dupo n bloo dpressur e independen t

o f Na + ,K + cotranspor t

wa s studie db y th e mean s o f multipl e regression s wit h eithe r systoli c o r diastoli c bloo dpressur e a s th e dependen t variable . Result s concernin g systoli c bloo dpressur e ar e sum marize din Tabl e 3 , showin g th e decreas e o f th e bloo d lea dregressio n coefficient s a s a) bloo dlea dalon e con sidere da s a

n independen t

variabl e (regressio n coeffi

cient , 3. 7 mmHg/10 0 u g Pb/L , p = 0.05) ; b ) alcoho l consumption , age , an dbod y mas s inde x adde da s independen t

variable s (regressio n coefficient , 3. 0 m m Hg/10 0 a g Pb/L , p = 0.09) ; c ) Na + ,K + cotranspor t include dfurthe r

in th e regressio n equatio n (regres

sio n coefficient , 2. 1 m

mHg/10 0 u g Pb/L , p = 0.21) . In thi s latte r

case , th e Na + ,K + cotranspor t regressio n coefficien t

i s -3. 5 m

mHg/10 0 nmole/L-cells-hr . O<0.01) . Tabl e 4 show s th e result s o f th e regressio n analyse s performe da s describe dwit h diastoli c bloo dpressur e a s adependen t

variable . Th e bloo dlea dregressio n coeffi

cient s are : 3. 0 m

mHg/10 0 n g Pb/L , (p = 0.07) ; 2. 1 mm Hg/10 0 n g Pb/L , (p = 0.15) ; 1. 4 m mHg/10 0 n g Pb/L , (p = 0.32) . I

n th e latte r

regressio n equation , th e Na + ,K + cotranspor t

regressio n coefficient

i s -3. 2 mmHg/10 0 nmole/Lcellsh r

(p < 0.01) . 

## Discussio n Th e overal l bloo dlea dmea n observe din thi s stud y (165. 8 n g Pb/L ) i s i

n agreemen t

wit h bloo dlea dlevel s foun di n othe r

genera l population s (11-13). Th e factor s contributin g t o variatio n o f bloo dlea dfoun di

n thi s stud y ar e th e sam e a s thos e foundin othe r studies : alcoho l consumptio n i s positivel y relate dt o bloo dlead ; ag e an dbloo dleadar e weakl y positivel y correlated . Th e associatio n betwee n bloo dlea dan dtobacc o consump tion i s o f les s importance, sinc e th e amoun t o f tobacc o smoke dby curren t

smoker s i s no t

correlate dwit

h bloo d lead . Tabl e 3 . Multipl e regression s o f systoli c bloo d pressur e o n bloo d lead , Na + ,K + cotransport , age , bod y mas s index , an d

alcoho l consumption . Tabl e 4 . Multipl e regression s o f diastoli c bloo d pressur e o n bloo d lead , Na + ,K + cotransport , age , bod y mas s index , an d

alcoho l consumption .

Independen t

variables 3 Bloo dlea dalon e (113) c Bloo dlea dandA , B , C (104 ) Bloo dlead , Na+ ,K+ cotransport , andA

, B , C (102 ) Regressio n coefficient s x 10 0 ± SEMb Bloodlea d 3. 7 ± 0.2 2 p = 0.0 5 3. 0 ± 0.2 2 p - 0.0 9 2. 1 ±0.2 2 p = 0.2 1 Na+ ,K+ cotranspor t

-3. 5 ±0.1 3 p < 0.0 1 "Independen t

variables : A , age ; B , bod y mas s index ; C alcoho l consumption . ••Regression coefficien

t x 10 0 indicate s th e systoli c bloo dpressur e increas e i

n m mH g for

a100 u g Pb/ L increas e an dfor a100 umole/Lcellsh r

Na+ ,K+ cotranspor t

increase . c Number s o

f subject s are i

n parentheses . Independen t variables 3 Bloodlea dalon e (113) c Bloodlea dan d A , B, C (104 ) Bloodlead , Na+ ,K+ cotransport , an dA

, B , C (102 ) Regressio n coefficient s x 10 0 ± SEM b Bloo dlea d ' 3. 0 ± 0.2 0 / > = 0.0 7 2. 1 ± 0.2 0 / > = 0.1 5 '. 1. 4 ± 0.2 0

. / > = 0.3 2 Na + ,K + cotranspor t

-3. 2 ± 0.1 2 p < 0.0 1 "Independen t

variables : A , age ; B , bod y mas s index ; C , alcoho l consumption . b Regressio n coefficien

t x 10 0 indicate s th e systoli c bloo dpressur e increas e i n m mH g fo r a10 0 u g Pb/ L increas e an dfo r a10 0 umole/ L cellsh r Na+ ,K+ cotranspor t

increase . c Number s o

f subject s ar e i

n parentheses . Th e associatio n o

f bloo dleadt o systoli c bloo dpressur e wa s foun dt o b e significan t (r = 0.19 , p = 0.05) . Th e correlatio n o

f bloo dlea dwit

h diastoli c bloo dpressur e i s slightl y lowe r

(r = 0.17 , p = 0.07) , a s alread y note di n ou r earlie r stud y (14,15). Takin g int o accoun t alcoho l consumptio n an dag e a s confoundin g variable s slightl y decrease s thes e correlation s (systolic , r = 0.17 , p = 0.09 ; diastolic , r

= 0.14 , p = 0.15) ; adjustin g furthe r fo r bod y mas s inde x doe s no t chang e thes e values . A significan t

negativ e relationshi p wa s observe d betwee n Na + ,K + cotranspor t an dbot h systoli c an d diastoli c bloo dpressur e (r = -0.20 , an dr

= -0.1 9 respectively) . Adjustin g for alcoho l consumption , age , an dbod y mas s inde x appear s t o strengthe n thes e relationship s (r

= -0.28) . Thi s resul t

confirm s thos e obtainedi

n apreviou s stud y wher e hypertensiv e and normotensiv e subject s wer e compare d(16). Althoug h th e interpretatio n o

f Na + ,K + cotranspor t

remain s controversia l a s fa

r a s re dbloo dcell s ar e concerned , i t mus t b e stresse dtha t

th e rol e o

f Na + ,K + cotranspor t

i n regulatin g Na + cel l conten t appear s t o b e o

f greate r importanc e in othe r

cells , includin g vascula r smooth muscl e cell s (17-19). Thus , a n impaire dNa + ,K + cotranspor t

activit y i n thes e cell s coul dincreas e Na+ content . Thi s in tur n ma y increas e Ca 2 + conten t and bloo dpressure , vi aaNa + , Ca 2 + exchang e mechanism . Result s presente dabov e sho w tha t Na + ,K + co transpor t i s significantl y negativel y relate dt o bloo d lead . N o othe r

associatio n wa s foun dbetwee n bloo dlea d an deithe r

othe r RBCT S o r

re dbloo dcel l Na + an dK + contents . In particular , th e lac k o f correlatio n observe d betwee n Na + , K + pump an dbloo dlea dleve l i s no t i n agreemen t

wit h othe r result s (3-5). However , i t mus t b e note dthat , i

n thes e latte r

studies , Na + ,K + ATPas e activit y wa s measure do n re dbloo dcel l hemolysates ; instead , w e measure dNa + ,K + pum p activity . Thi s particula r poin t deserve s furthe r

confirmation . Finally , considerin g th e influenc e o f bot h Na + ,K + cotranspor t

an dbloo dleadupo n systoli c bloo d pressure , afte r adjustmen t

fo r alcoho l consumptio n ag e an dbod y mas s index , th e bloo dlea dregressio n coefficien t i s ver y 

# L

# F P. 6

SODH M TRANSPORT. BLOOD LEAD. AND HLOOD PRESSURE 5 1 fro msignificanc e (p = 0.21) , whil e Na + ,K + ^'transpor t i s highl y significantl y negativ e (p < 0.01 ) /Tabl e 3)

- B y comparison , whe n Na + ,K + cotranspor t i s a longe r take n into account , th e bloo dleadregressio n ".efficien t i s eithe r nearl y significan t

(p = 0.09 ) whe n fo r alcoho l consumption , age . an dbody mas s fa r ,diustin g ndex . or significan t

(p = 0.05 ) withou t

any adjust

I e nt.'Pu t together , thes e result s sho w tha t Na + .K + co I I nS por t impairmen t

explain s th e relationshi p be

1 ee n bloo dlea

dan dsystoli c bloo dpressur e t o agreate r exten t tha n d o th e confounde r

variable s alcoho l con mptio n an dage . Thi s tren di s als o observed , t o a ? eS se r degree , fo r diastoli c bloo dpressur e (Tabl e 4) . I n conclusion , thes e result s ar e i n agreemen t

wit h th e hypothesi s tha t

bloo dlea dcoul dimpai r Na + .K + cotranspor t activity , an dthi s Na + ,K + cotranspor t al

teratio n couldincreas e bloo dpressure . Furthe r studie s ar e neede dt o confir

mthi s finding . Th e author s gratefull y acknowledg e th e wor k o f Josiann e Sahuquill o an d Gisel e Salomo n i n providin g valuabl e technica l assistance . Thi s wor k wa s supporte db y th e Programm e Interdisciplinair e d e Re

- •herch e su r 1'Environmen t

(PIREN ) unde r

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