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A B ST R A C T

Ka r e n Le e Ru st:Or al A d

m

inistratio n of Ars e nic : Expe ri me ntatio n and

M

athematic al

M

odel ing

Unde r the d ire ction o f Do ug la s J Cr aw fo rd-Br own

T

h is

w

o r

k d

e s c r

i b

e s a n e x pe r

i m

e nta

l in v e s

t

i g

at

i

o n c a r r

ie

d

o ut to

de

te r

m in e

the

l

e v e

l

o

f

upta

k

e of a r s e n

ic

in t he v

i

ta

l

o rga n s a n

d

tis s u e s of

m i

c e, a n

d

a c o

m

pa rt

m

e n ta

l m

o

d

el

d

e v e

l

o

p

e

d

to s

i m

u

l

ate t

h

e

d

ata o

b

ta

in e

d f

r o

m

t

h

e e xpe r

im

e nt. Du r

in

g t

h

e e xpe r

i m

e nt

de s

i

gn e

d

to

d

ete r

m in e

t

h

e ste a

d

y-state w

h

o

l

e

b

o

d

y

le v e

l

o

f

a r s e n

i

c

i

n

m i

c e, te n B

6 C 3

F

1 m i

c e

we r e

d

o s e

d d

a

i l

y

f

o r n

in e

d

ays

b

y o r a

l

ga v a

g

e

w i

t

h

r a

d io a c

t

i

v e s o

d iu

m

a r s e n ate

in

w

ate r at a

c o n c e ntr atio n

l

e v el o

f 0

.5

m g

o

f

A s

pe r

k

g o

f b

o

d

y wei g

h

t. T

h

e pr e

-

d

o s e a n

d

po st-

d

o s e

ra

d i

o a ct

i

v e a r s e n

ic

le v e

ls

w e r e

m

e a s u r e

d

a n

d

r e c o r

d

e

d f

o r e a c

h

a n

i m

a

l d

a

i l

y u s

i

ng a w

h

o

l

e

-b

o

d y g

a

m m

a c o u nter . T

h

e u r

i

n e a n

d f

ec e s

w

e r e co

l l

e cte

d d

a

i l y f

r o

m

e a c

h

a n

i m

a

l f

o

l l

ow

in

g

the

p

o st-

d

o s e

m

e a s u r e

, a n

d

a n a

l

yz e

d f

or r a

d i

o a ct

i

v e a r s e n

ic

.

A

t t

h

e e n

d

o

f

the te n

d

a y

expe r

i m

e nt,

fi

v e

m i

c e

w

e r e s a c r

i fi

c e

d

a n

d

s e

l

e cte

d

v

i

ta

l

o rga n s a n

d

t

i

s s u e s a

m

p

le s

w

e re

h

a r v e ste

d

a n

d

te ste

d f

o r r a

d i

o a ct

i

v e a r s e n

i

c. T

h

e

fi

v e r e

m

a

in

in

g m i

c e

w

e r e

m

o n

it

o r e

d f

or

n

in e

a

d d i

t

io n a

l d

ays

b

e

f

o r e they w e r e s a c r

i fi

c e

d

a n

d

t

h

e s a

m

e o rga n s a n

d

t

is s u e s a

m

p

l

e s

h

a r v e ste

d

a n

d m

e a s u r e

d

. T he a v e r a

g

e n o r

m

al iz e

d

pe r c e nt of a r s e nic

(

ug

A

s

)

d istr

i b

ute

d i

n

t

h

e

h

a r v e ste

d

o rga n s o

f

a n

i m

a

l

s

6

t

h

r o u

gh 10 w

e r e :

0 0 57 % f

o r

l i

v e r,

0 0 2 6 % f

o r

k i d

n e

y

s,

0

.

0 0

3

%

)

f

o r t

h

e

l

u n

g

s,

0 6 7

5

%)

f

o r t

h

e c a r c a s s, a n

d 0

.2 1 5

%)

f

o r t

h

e s

k i

n

U

s

in

g

t

h

e s e

e x

p

e r

i m

e ntal

d

ata a n

d

the pe r c e nt of c a r

d i

a c o utput fo r the vita

l

o rga n s in

m

ic e, a

m

u lti

-c o

m

pa rtme nta

l

P B P

K m

o

d

e

l

w a s

d

e v elope

d

w ith t

h

e

S

te

l l

a So

f

tw a r e

S y

ste

m

(

H P

S

, 19 97

)

T h

e c o

m p

u tat

i

o n a

l

pa rt o

f

t

h

e

m

o

d

e

l

c o n s

i

sts o

f

a s et o

f fi

r st o r

d

e r equ atio n s t hat a r e a

(2)

fun ctio n of the a ss o ciated b lo od f lo

w

fo r e a ch co

m

partme nt. T he resu ltin

g equatio n s are

s o

l

v e

d

n u

m

e r

i

c al l y

w i

t

h

r e spe ct to t

i m

e. T

h

is

m

o

d

el pr o v

i d

e s c o n c e ntr atio n pr ed ict

i

o n s that

a r e

w i

t

h i

n 1 5 pe r c e nt o

f

t

h

o s e

f

r o

m

t

h

e e x pe r

i m

e nt

f

o r

f

e c e s, u r

i

n e, c a r c a s s, s

k i

n , a n

d

the

(3)

A C

K

N O

W

L E D G E

M

E N

T

S

I

w

o ul

d l i k

e to t

h

a n

k

Dr . Do u

g

la s

C

r a

w f

o r

d

-Br o

wn

f

o r

h i

s a s s

i

sta n c e

w i

t

h

t

h

e

d

e v e

l

o

p m

e nt o

f

the

St

e

l l

a

m

o

d

e

l

, a n

d

t

h

e c o

m

p

l

et

i

on o

f

th is r epo rt. I

w

o u

l d l i k

e to t

h

a n

k

Dr

M

i

c

h

a e

l

Hu g

h

e s

f

o r a

l l

o

w i

n g

m

e to

w

o r

k w i

th h i m du r

i

ng t

h

e e x

p

e r

i m

e nt at t

h

e

U

.

S.

E P

A

, a nd

f

o r h is a s sista n c e

i

n o

b

ta

i

n

i

ng info r

m

at

i

o n

f

o r t

h

is r epo rt. I

w

o u

l d l i k

e to tha nk

D

r.

L

o u

i

s e Ba

l l f

o r

b

e

i

n

g

a r e a

d

e r o

f

t

h i

s r e

p

o rt

I

w o u

l d

a

l

s o

l i k

e to tha n

k D

r.

M

ar

i

n a

E

v an s

f

o r

h

e r a s s

i

sta n c e

i

n o

b

tain

i

n

g

t

h

e

b

lo o

d f l

ow

d

ata. I w o u

l d l

i ke to t

h

a n

k

the c o

m m i

tte e o

f

Dr. Do u

g l

a s

C

r a

w f

o r

d

-

B

r own

(

a

d

v

i

s o r

)

. Dr . L o u

i

s e

B

a

l l

, a n

d

D r.

M

i

c

h

a el

H

ug

h

e s

f

o r t

h

e

i

r

a s s

i

sta n c e

i

n t

h

e r e v isio n a n

d

c o

m

p

l

et

i

o n o

f

t

h i

s r epo rt.

(4)

T A B

L

E O F C O N

T E

N T S

Pa

g

e

L I S T O F F I

G

U R E

S

v

i i

L I S T

O

F T A B L E S v

i i i

C h

a

p

te r

1. Intr o

d

u ctio n 1

2. Pr e v

i

o u s Expe r

i m

e nta

l S

tu

d ie s

In v o

lv

i

n

g

t

h

e D o sin

g

of

M

i

c e w

i

th Ar s e n

i

c 5

3. T he La

b

o r ato ry Expe r

i m

e nt 8

3

1

A

n

i m

a

l

a n

d

A r s e n

ic

S

e

le c

t

i

o n

8

3

.2 Ra

di

o a ct

i

v

i

ty

M

e a s u r e

m

e nt

8

3

.

3

Expe r

i m

e nta

l

Proc e

du r e

9

4

.

A

n a

l y

s

i

s a n

d Su

m m

a r

y

o

f E

x

p

er

i m

enta

l

Data

12

4.1 Expe r

i m

e nta

l

Data R e v

i

ew 1 2

4.2 Do s e

M

e a s u r e

m

e nt

C

a

lc u

l

at

i

o n 1 2

4.

3

Pe r c e nt o

f

A r s e n

i

c

i

n

C

o

m

po n e nts

14

5

M

o

d

e

l

De s

i

gn a n

d D

e v e

l

op

m

e nt 1

8

5

.1

A

r s e n

ic

D

i

stri

b

ut

i

o n 1 9

5.

2 C

o

m

pa r at

iv e

D ata

2 1

5

.

3 C

o n c eptu a

l

M

o

d

e

l

De

fi

n

i

t

i

o n

2 3

5

.4 De s c r

i

pt

i

o n o

f

M

o

d

el

E q

u at

i

o n s 2 5

5

.

5

M

o

d

e

l V

a r

i

a

b l

es

3 3

6

. Re s u

l

ts

3 4

8

.

C

o n c

l

u s

i

o n 4

3

9.

A

p pe n

d ix

1: Data

f

r o

m

the Expe r

i m

e nt

O

r a

l l

y A

d m i

n

i

ste rin

g

A r s e n

i

c 4

6

M

i

c e A n l t

h

r o ug h

A

n 1 0

1 0.

A

p pe n

d i

x 2: Expe r

i m

e nta

l

D ata

Su

m m

a ry Re s u

l

ts

f

r o

m O

r a

l l y

5

6

A dm i

n

i

ste r

in

g

A r s e n

i

c to

M

i

c e

A

n l t

h

r o u

g h A

n

10

.

(5)

T

A B

L

E O

F

C O N

T E

N T S

Page

1

2

. A p pe n

d i

x 4: B lo o

d

F low fo r

M

ic e fr o

m

Sta n

d

a r

d

s

M

a n u al 6 1

13

.

A p p

e n

d i

x

5

:

G l

o s s a ry o

f

T e r

m

s u s e

d i

n t

h

e

M

o

d

e

l

D

i

agr a

m

6 2

1 4. A p pe n

d

ix 6: E qu atio n s of

M

o

d

e

l f

o r Or al D o sing of

M

ic e w ith

A

r s e n ic 6 3

15.

A p p

e n

d i

x 7: Ta

b l

e Re s u

l

ts

f

r o

m

t

h

e

M

o

d

e

l f

o r t

h

e

O

r a

l

6 6

A dm i

n

i

str at

i

o n o

f A

r s e n

i

c

1

6

.

A

p pe n

d i

x

8

:

C

o

m

pa r

i

s o n o

f

M

o

d

e

l

a n

d

Expe r

im

e nta

l

Data fo r

7

2

U

r

i

n e a n

d

Fe c e s

1

7

A

p

p

e n

d i

x

9

:

C

o

m

pa r

i

s o n o

f

M

o

d

e

l

a n

d

Ex

p

e r

i m

e nta

l

Data

i

n

7 9

Ta

b

u la r a n

d G

r a

p

h

i

c a

l

Fo r

m f

o r An

i m

a

l

s 1 t

h

r o u

g h

5

1 8. Re

f

e r e n c e s 9

0

(6)

L I S T

O

F F I

G

U R

E

S

Pa

g

e

F i gu r e 1. P

h

a r

m

a c o

k i

n et

i

c

M

o

d

e

l

I

l l

u str at

i

n g the

M

o v e

m

e nt o

f

A r s e n

i

c 1

8

T

h

r o u

g h

t

h

e Bo

d

y

F

i

gu r e 2.

C

o n c e

p

tu a

l

D

i

agr a

m

o

f

t

h

e

M

o

d

e

l f

o r

O

r a

l

Do sin g o

f

M

ic e 2

3

w ith Ar s e nic

F

i g

u r e 3

M

o

d

e

l

Re s u

l

ts o

f A

r s e n

i

c Pr e s e nt

i

n Fe c e s, Ur

i

n e,

C

a r c a s s,

3 6

Sk i

n, a n

d

L

i

v e r

f

o r

A

n

i m

a

l

s

6

t

h

r o u

g h

1

0

F

i g

u r e 4

M

o

d

e

l

Re s u

l

ts o

f A

r s e n

i

c Pr e s e nt

i

n B la

d d

e r,

K i d

n eys, Lu ngs,

3

7

a n

d

M

u s c

l

e

f

o r

A

ni

m

als

6

thr o ug

h

1 0.

F

i

gu r e 5.

C

o

m

pa r

i

s o n o

f

M

o

d

e

l

a n

d

Expe r

i m

e nta

l D

ata

f

o r t

h

e

U

r

i

n e a n

d

3

8

Fe c e s

f

o r A n

i m

als

6

t

h

r o ug

h

1

0

F i g

u r e

6

.

M

o

d

e

l R

e s ults o

f A

r s e n

i

c Pr e s e nt

i

n Fe c e s,

U

r

i

n e,

C

a r c a s s, 4

0

Sk i

n , a n

d

L

i

v e r

f

o r

A

n

i m

a

l

s

1

t

h

r o ug

h

5.

F

i

gu r e 7.

M

o

d

e

l

Re s u

l

ts o

f A

r s e n

i

c Pr e s e nt

i

n B

l

a

d d

e r,

K i d

n eys,

L

u n

g

s,

4 1

(7)

L I

S

T O F T A B L E S

Page

Ta

b

le

1

D

a

i l

y Data Re a

d i

ngs

f

o r An

i m

al

6

fr o

m

t

h

e Expe r

i m

e nt

O

r a

l l

y 10

A d m i

n

i

ste re

d A

r s e n

ic

.

Ta

b

le 2.

C

a

l

c ulatio n o

f

t

h

e Tota

l

Do s e

M

e a su r e o

f A

r s e n

ic

f

o r

A

n

i m

a

l 6

13

Ta

b l

e 3

C

a

l

c u

l

at

i

o n o

f

the Pe r c e nt o

f

Ar s e n

i

c Pr e s e nt

in

C

o

m

po n e nt 1

5

Pa rts fr o

m

t he Bo

d

y of An

i m

a

l

6.

Ta

b l

e

4

.

C

a

l

c u

l

at

i

o n o

f

the

N

o r

m

a

l i

z e

d

Pe r c e nt o

f A

rse n

ic

Pr e s e nt

in

16

C

o

m

po n e nt Pa rts fr o

m

t

h

e

B

o

d

y o

f

An

i m

al

6

.

Ta

b l

e 5. D

i f f

e r e nt

i

a

l

E qu at

io n s

D e

fi

n e

d b

y V

i

ta

l

Bo

d

y Pa rt to De scr

i b

e the

20

D

is

tr

i b

ut

io n

a n

d A b

s o rp t

i

o n of A r s e n

i

c.

Ta

b

le 6. A v e r age N o r

m

a

l iz e

d

Pe r c e nt of A r s e nic A

b

s o r

b

ed a n

d

Ex c r ete

d

2 2

b

y

A

n i

m

als 6 thr o ug h 1 0.

Ta

b l

e

7

M

o

d

e

l C

o

m p

a rt

m

e nts a n

d C

o r r e spo n

d i

n g

D i f fe r e n

tia

l

E qu at

i

o n 2

5

De s c r

i

p t

i

o n .

Ta

b l

e

8

.

C

o

m

pa r

i

s o n o

f A,

i

n t

h

e

D i

str

i b

ut

i

o n D

i f f

e r e nt

i

a

l

E qu at

i

o n s a n

d

3 1

t

h

e

M

o

d

e

l

.

Ta

b l

e

9

V a r

i

a

b le

In

p

ut Pa r a

m

ete r

Se

t t

in

g

s

f

o r t

h

e

M

o

d

e

l

34

Ta

b l

e 10 Rat

i

o

C

o

m

pa r

i

s o n o

f

Pe r cent o

f A

r s e n

i

c

P

r e s e nt Bet

w

e e n

3

5

M

o

d

el Est

i m

ate s a n

d

t

h

e Expe r

i m

e nt.

(8)

I

n

t

r o

d

u c

t

i

o n

Ar s e nic is a n atu r a

l

l y o c c u r r

in

g m

etal lo

i

d t

h

at

h

a s

b

e e n u s e

d

fo r

m

e

d ic

in al pu rpo s e s,

s u c

h

a s t

h

e tr e at

m

e nt o

f

a c ute pr o

m

ye

l

o cy t

i

c

le u

k

e

m i

a

w i

t

h

a r s e nic tr

io x

i d

e w

h

e n othe r

c o n v e nt io n a

l

tr e at

m

e nts

l i k

e c

h

e

m

othe r ap y a n

d b

o n e

m

a r r ow tr a n sp la ntatio n

f

a

i l

(

So

i g

n et e t

a

l

., 1

9

9

8

)

An othe r

i l l

n e s s t

h

at

m

ay

b

e tr e ate

d

w it

h

a n a r s e n

ic a

l

c o

m

po u n

d

n a

m

e

d

M

ela r s o

p

r o

l

, is A

f

r

i

c a n

Sl

e ep

in

g s

i

c

kn e s s

(

C

D

C

P,

O

n

l i

n e

)

How e v e r, t

h

e u s e o

f

a r s e n

ic

f

or

any pu rpo s e

m

u st

b

e pu r s u e

d w it

h

c a utio n a s

i

t

i

s now c o n s

i d

e r e

d

to

b

e a

h

u

m

a n c a r c

i

n oge n .

Ar s e n

i

c o c c u r s n atu r a

l

l y

i

n 4 v a

l

e n c e

fo r

m

s

(

-

3

,

0

, +3 a n

d

+5

)

. Ho

w

e v e r

, o n

l

y t

w

o o

f

t

h

e s e

v a

l

e n c e

f

o r

m

s, a r s e n ate

(

+

5

)

a n

d

a r s e n

i

te

(

+

3

)

a r e o

f

c o n c e r n

f

o r t

h is

d

o c u

m

e nt A

f

te r

p

e o

p l

e

a r e e xpo s e

d

to a r s e n ate

(

+ 5

)

, t

h

e c

h

e

m i

c a

l i

s r e

du c e

d

to a r s e n

i

te

(

+3

)

,

w h i

c

h m

ay

b

e

m

et

h y l

ate

d

to

m

o n o

m

et

h y l

a r s o n

i

c a c

i d

(

M M

A

)

a n

d d i m

et

h

y

l

a r s

in

i

c a c

i d

(

D

M

A

)

. T

h

e

m

et

h y l

at

i

on o

f i

n o r

g

a n

i

c ar s e n

i

c to

M M

A

a n

d

D

M

A l

o

w

e r s the a c ute to x

ic

i

t

y

o

f

t

h

e a rs en

i

c,

a n

d m

o r e o

f

t

h

e

m

eta

b

o

l i

z e

d

a r s e n

i

c

i

s e x c r ete

d i

n t

h

e u r

in e

.

H

owe v e r

, t

h i

s c

h

a nge

i

n a r s e n

i

c

m

ay v a ry a

m

o n g t

h

e popu

l

atio n a s fa cto r s

l i k

e

g

e n et

i

c s,

m

eta

b

o

l i

s

m

, a n

d h

e a

l

t

h m

ay a

f f

e ct

h

o

w

a

p

e r son r e s

p

o n

d

s t o a r s e n

i

c ex

p

os u r e

(

Fe

d

e r a

l

Re

g i

ste r,

2 0 0 0

)

.

T

h

e e

l

e

m

e nt a r s e n

ic o c c u r s n a

tu r a

l

l y

i

n t

h

e e n v

i

r o n

m

e nt Fo r e x a

m p l

e, a r s e n

i

c c a n

b

e

f

o u n

d

n atu r a

l l

y

i

n s

h

a

l

e a n

d

c

l

ay s o

i l

w

h

ich u s u a

l l

y

h

a s a c o n c e ntr at

io n

of

0

.

3

to 4 9 0

p

a rts

pe r

m i l l i

o n

(

Le v a n

d

e r et a

l

.

, 1

9

7 7

)

. A

d d

i t

io n a

l l

y

, s

m

al l a

m

o u nts o

f

a r s e n

i

c a r e ge n e r a

l l

y

pr e s e nt

in

wate r a n

d f

o o

d

A l

t

h

o ug

h

v a ry

i

ng a

m

o u nts o

f

a r s e n

i

c c a n

b

e

f

o u n

d i

n

w

ate r

w h

e r e

(9)

w

i

t

h i

n

d

u strial

d

e v elop

m

e nt. A r s e nic is u s e

d

in c op pe r s

m

e

l

t in

g

,

m

inin

g

, oi

l

r efi nin g a n

d

ta n n

i

n

g

(

Be n

d

e r

l

y, 1

9 9 3

)

, a n

d i

t

i

s a

b

y

-pr o

d

u ct o

f p

owe r

p l

a nts

b

u r n

i

ng

f

o s s

i l f

u e

l

.

Ho

w

e v e r, a r s e nic in

d

r

i

n

k

i

ng

w

ate r is of gr e ate st c o n c e r n

f

o r r e

g

u

l

ato r s a s

i

t

i

s pr o

b

a

b l y

r e spo n s

i b l

e

f

o r

b

et

w

e e n

2

2 t o

6 3 p

e r c e nt o

f

t

h

e

i

n o r

g

a n

i

c a r s e n

i

c e xpo s u r e

i

n t

h

e

U

n

i

t e

d

S

tate s

(

U

.S. E P A , 1

9 9 8

)

. In a n e

ff

o rt to pr ote ct t

h

e pu

b l i

c

h

e a

l

t

h

, t

h

e

U

.

S

. En v

i

r o n

m

e nta

l

P

r ote ct

i

o n

A

ge n cy

(

U

.

S

.

E P A

)

e sta

b l i

s

h

e

d l i m i

ts

f

o r t

h

e

m

a x

i m

u

m

a c c ep ta

b l

e

l

e v e

l

o

f

c o nta

m i

n a nts,

i

n c

l

u

d i

ng a r s e n

i

c at

5 0

u

g /

L ,

i

n t

h

e

S

a

f

e Dr

i

n

k i

ng

W

ate r

A

ct

i

n 1

9 7 5

, a n

d

c o nt in u e s to e v alu ate t

h

e n e e

d f

o r c

h

a ng in g th is

l i m i

t. In a

d d i

t

i

o n, t

h

e

C l

e a n

W

ate r

A

ct

c r

i

te r

i

o n s et l i

m

its fo r t

h

e

d i

s c

h

a r

g

e of a r s e n

i

c

i

nto s u r

f

a c e-w

ate r at

0

.

0

2

2

ug

/

L

i

n 1 9

8 0

,

b

ut

l

ate r r e v

i

s e

d i

t to

0

.

0

1

8

u

g

/L i

n 1

9 9 2

(

A b

e

m

at

h

y et a

l

.

,

2 0 0 0

)

. T

h

e r e n e

w

e

d i

n te r e st

i

n t

h

e

to x

i

c o

l

o

g

y o

f

a r s e n ic a n

d

t

h

e

m

a x

i m

u

m

le v e

l

t

h

at s

h

o u

l d b

e pe r

m i

t te

d i

n

d

r

i

nk

i

n

g

wate r

h

a s

l

e

d

to a n

i

n c r e a s e

d

n u

m b

e r o

f

s c

i

e nt

i f

i c stu

di

e s. It

h

a s

b

e e n e st

i m

ate

d

t

h

at t

h

e a v e r age pe r s o n

l i

v

i

n

g

in t

h

e

U

n ite

d

State s

h

a s a n

i

ntak e of

4 6

ug o

f

a r s e n

i

c pe r

d

ay

w i

t

h

t

h

e gr e ate st s o u r c e

b

e

i

n g

f

r o

m

wate r a n

d

fo o

d

pr o

d

u cts

(

U S

D H H

S

, 1 9 9 3

)

E p i d

e

m i

o

l

o

g i

c a

l

stu

d i

e s

i

n

d i

c ate t

h

at a r s e n

i

c

i

s a c ar c

i

n o

g

e n

f

or s o

m

e peo

p l

e w

h

o a re

p

r e

d i

spo s e

d

to t

h

e to x

i

c e

f f

e cts o f t

h

e e

l

e

m

e nt a n

d l i

v e

i

n a r e a s w

h

e r e

h i

g

h l

e v e

l

s o

f

a rse n

i

c

are

p

r e s e nt

i

n

d

r

i

n

k i

n

g w

ate r

(

A

b

e

m

at

h

y et al., 1

9 9

7

)

.

A

lt

h

o ug

h

t

h

e

m

e c

h

a n

i

s

m

o

f

act

i

o n

b

et

w

e e n t

h

e to x

i

c e

f f

e cts o

f

a r s e n

i

c a n

d

r e s u

l

t

i

ng

h

a r

m f

u

l h

e a

l

t

h

e

f f

e cts

f

o r

p

e op

l

e

i

s not

k

n o

w

n ,

i

t

h

a s c a u s e

d

a r e n ewe

d i

nte r e st

i

n a r s e n

i

c to x

i

c o

l

og y a

m

o n g s c

i

e nt

i

sts a n

d

g

ov e r n

m

e nt r e

g

u

l

ato r s a n

d

re su

l

te

d i

n a

d d i

t

i

o n a

l

e xpe r

i m

e nta

l i

n v e st

i g

at

i

o n

w i

t

h

s e v e r a

l

spe c

i

e s o

f

la

b

o r ato ry a n

i m

a

l

s s u ch a s

m i

c e, r ats, a n

d h

a

m

ste r s. Ho

w

e v e r

,

m

o st of t

h

e

d

ocu

m

e nte

d

to xic

i

ty stu

d i

e s

h

a v e

b

e e n c o n

d

u cte

d

u s

i

ng a c ute

d

o s

i

n g r at

h

e r t

h

a n c

h

r o n

i

c o r

l

o n

g

-te r

m d

o s

i

n

(10)

l

i m

its

f

o r ap p l ic atio n s

l i k

e s afe

d

r

in

k i

ng w ate r

(

N

e

m

e c et a

l

., 1

9 9 8

)

, s

i

n c e

i

t

do e s n o

t r e

f le c

t

t

h

e

k i

n et

ic s o

f

t

h

e

G I

tr a ct

w h

e r e t

h

e a r s e n

ic

is a

b

s o r

b

e

d i

nto t

h

e

b l

o o

d f

o r

m

o v e

m

e nt a n

d

d i

str

i b

ut

i

o n t

h

r o ug

h

t

h

e

b

o

d

y o r e x c re te

d f

r o

m

t

h

e

b

o

d

y a

f

te r c o nt

i

n u o u s a r s e n

ic e x

p

o s u r e.

T

h

e a

m

o u nt o

f

a r s e n

i

c c o n s u

m

e

d i

n

d

r

i

n

k in

g

w

ate r

i

s u s u a

l l

y v e r>

l

ow , a n

d

c o n s u

m

p t

i

o n

m

ay ta

k

e p

l

a c e o v e r a

lo n

g

p

e r

io

d

o

f

t

i m

e. T

h

e r e

f

o r e

,

i

t

i

s

i m

po rta nt to

h

a v e

l

a

b

o r ato ry

r e s u

l

ts

f

r o

m

e x pe r

i m

e nts

m

o r e

d

ir e ct

l y

r e

l

e v a nt to

lo n

g te r

m i

n

g

e st

i

o n , a n

d

to

d

e v e

l

op

m

athe

m

at

i

c al

m

o

d

e

l

s w h ic

h w i l

l pr o v

i d

e

d

ata to a s s

i

st in

d

e c

i

s

i

o n s r equ

i

r e

d

in e sta

b l is

h i

ng

po

l ic

y r ega r

d in

g

m

a x

i m

u

m

a

l l

o

w

a

b l

e c o nta

m i

n a nt

le v e

l

s.

Re s e a r c

h i

n t

h

e a r e a o

f

t

h

e c a r c

i

n oge n

i

c e

f f

e cts o

f

a r s e n ic

h

a s

b

e e n

h

a

m

pe r e

d b

y t

h

e

a v a

i l

a

b i l i

ty o

f

pr e

d ic

t

iv e

a n

i m

a

l m

o

d

e

ls

. Ho

w

e v e r

,

l

a

b

o r ato ry e x pe r

i m

e nts a n

d

to x

i

c o

lo

g y

stu

d i

es a r e

b

e

in

g c a r r

i

e

d

o ut at t

h

e

U

.

S

. E P

A

s

i

n c e

C

o n

g

r e s s r e

q

u e ste

d

t

h

at n ew

l i m i

ts

f

o r t

h

e

a

m

o u nt o

f

a r s e n

ic

p

e r

m i

t te

d i

n

d

r

i

n

k in

g w ate r

b

e s et

b

y t

h

e ye a r

2 0 0 0

(

A

c ute,

O

n

l i

n e

)

.

Si

n c e

t

h

e

f

a c

i l i

t

i

e s

f

o r

m

a ny c o

m m

u n

i

ty wate r s

y

ste

m

s

m

a

y b

e a

f f

e cte

d b y

a n y r e v

i

s e

d

r e

g

u

la

t

io n s

,

r e s e a r c

h i

s n e c e s s a r

y i

n o r

d

e r to

d

ete r

m i

n e t

h

e n ew

l i m i

ts

(

K

a

i

s e r

,

19 9 8

)

T

h

e U

S E

P A

wo u

l d l i k

e to r e

du c

e t

h

e

l

e v e

l

o

f

a r sen

ic

p

e r

m i

t te

d i

n

d

r

i

n

k in

g

w

ate r

f

r o

m

5

0 m i

c ro

g

r a

m

s pe r

l ite r to a le v el n e a r z e r o, a n

d

in Ju n e of 2 0 0 0 pr opo s e

d

a

l i m i

t o

f

5

m

ic r ogr a

m

s pe r l

i

te r to

b

e

e

f f

e ct

i

v e

i

n 2 0

0

1

(

Fe

d

e r a

l

Re

g i

ste r

,

2 0 0 0

)

.

R

e s e a r c

h i

nto t

h

e e

f f

e cts o

f

a

d m i

n

i

ste r

i

n g a r sen

i

c o r a

l l

y to

la

b

o r ato ry a n

i m

a

l

s

c o nt

i

n u e s. T

h i

s pape r

d

e s c r

i b

e s a n e x pe r

i m

e n ta

l

stu

d

y t

h

at

w

a s c o n

d

u cte

d i

n t

h

e

Expe r

i m

e nta

l

To x

i

c o

lo

g y D

i

v

i

s

i

o n ,

N

at

i

o n a

l H

e a

l

t

h

a n

d

En v

ir o n

m

e nta

l

E

f f

e c ts

R

e s e a r c

h

L a

b

o r ato ry at t

h

e

U S

. En v

i

r o n

m

e nta

l

Pr ote ct

i

o n

A g

e n cy

i

n Re s e a r c

h

T r

ia n

g

l

e Pa r

k

,

N

o rt

h

C

a r o

l i

n a

du r

in

g t

h

e s u

m m

e r o

f

1

9 9 9

. T

h

e

d

ata

f

r o

m

t

h i

s e xpe r

i m

e nt

w

e r e u s e

d f

o r t

h

e

(11)

m

o

d

el

w

a s te sted b y r u n ning the

m

odel to obtain e sti

m

ate s o f a r s e nic c onc e ntr atio n in

v a r

i

o u s o rga n s, t

i

s s u e s a n

d

e x c r eta, w

h ic

h

w e r e t

h

e n c o

m

pa r e

d w

it

h

t

h

e c o r r e spo n

d i

ng v a

l

u e s

c a

lc u

l

ate

d f

r o

m

t

h

e e x pe r

i m

e nta

l d

ata. T h is pape r

d

e s c r

i b

e s t

h

e e x pe r

i m

e nta

l d

ata,

f

itt

i

ng o

f

(12)

P

r e v

i

o u s

E

x

p

e r

i

m

e n

t

a

l S

t

u

d i

e s

I

n v o

l

v

i

n

g

t

h

e

D

o s

i

n

g

o

f

M

i

c e

w i

t

h A

r s e n

i

c

T

h

e

f

o

l

lo

w i

n g syn opsis o

f d

o c u

m

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d

e xpe r

i m

e nta

l

r e s u lts s

h

o

w

s t

h

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l

u

m

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i m

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l i

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e

i

n

g

c a r r

i

e

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n v a r

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l

a

b

o r ato r

i

e s to

i d

e nt

i fy

t

h

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f f

e cts o

f

a r s e n

i

c

i

n t

h

e

b

o

d y

Si

n c e

i

t

i

s

p

r a ct

i

c a

l l

y

i m

po s s

i b l

e to e

l i m i

n ate a r s e n

i

c t

h

at o c c u r s

n atu r a

l l

y

i

n t

h

e

b i

o sp

h

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f

r o

m

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h

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e nt,

i

t

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y

h

ow a r s e n

i

c

af fe cts the

b

o

d

y a nd t he

m

in i

m

u

m

a

m

o u nt r equ

i

r e

d

to af fe ct o n e's he a

l

t

h

. Fo r th is r e a s o n,

i

t

i

s

i m p

o rta nt to

k

n ow

h

o

w

a r s e n

i

c

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s

m

eta

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y,

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ow

f

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h

e

b

o

d

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l i m i

n ates

i

t,

h

o

w m

u c

h i

s a

b

s o r

b

e

d i

n v a r

i

o u s v

i

ta

l

o r

g

a n s, a n

d

a ny to x

i

c e

f f

e cts t

h

at

m

ay o c c u r. T

h

e

f

o

l l

o

w i

n

g

s u

m m

a ry

i d

e nt

i f

i e s t

h

r e e ot

h

e r e x pe r

i m

e nts o r

i

n v e st

i

gat

i

o n s t

h

at we r e pe r

f

o r

m

e

d

w

i

t

h m i

c e to a s s

i

st

i

n a n s

w

er

i

n

g

qu e st

i

o n s r e

l

ate

d

to

h

ow a r s e n

i

c

b

e

h

a v e s

i

n t

h

e

b

o

d y

.

H

. J.

S

a n c

h

e z,

C

. Pe r e z, a n

d

R .

D

. Pe r e z

(

S

a n c

h

e z et a

l

., 1

9 9

7

)

i

n v e st

i

gate

d

t

h

e

l

e v e

l

o

f

a r s e n

i

c

p

r e s e nt

i

n

d i f f

e r e nt

b

o

d

y

f l

u

i d

s a n

d

o r

g

a n s o

f m i

c e a

f

te r t

h

ey

w

e r e g

i

ven wate r a

d

l i b i

tu

m

t

h

at c o nta

i

n e

d

1

0 0

u

g/ m l

o

f

a r s e n

i

c tr

i

o x

i d

e

(

A S 2

O

3

)

. Du r

i

n

g

t

h i

s e x

p

e r

i m

e nt, t

h

e

m i

c e

w

e r e g

i

v e n t

h

e w ate r

f

o r a

p

e r

i

o

d

o

f

o n e

w

e e

k

.

A

s a pa rt o

f

t

h i

s

i

n v e st

i g

at

i

o n

, a n En e rg y D

i

spe r s

i

v e X -

R

a

y F

l

u o r e s c e n c e te c

h

n

i

qu e

w

a s u s e

d

to

m

e a s u r e a n

d

r e c o r

d

t

h

e

pr e s e n c e o

f

a r s e n

i

c

i

n t

h

e a n

i m

a

l

t

i

s s u e T he a v e r age c o n c e ntr atio n o

f

a r s e n

i

c wa s 3.9 ug

A s

/

g

f

o r t

h

e

l i

v e r, 2.

9

u

g A

s

/ m l f

o r t

h

e

b l

o o

d

, a n

d

4 2 u

g

As

/m l f

o r t

h

e u r

i

n e.

T h i

s stu

d y i

s

u s e

f

u

l i

n

d

e

m

o n str at

i

ng t

h

at

m

o st o

f

t

h

e a r s e n

i

c

i

se x c r ete

d i

n t

h

e u r

i

n e; a n

d p

r o v

i d

e s

(13)

pr o vi

d

e in fo r

m

atio n o n the k in etic s of a r s e nic

m

o v e

m

e nt in the

b

o

d

y o r o n c o n c en tr atio n s

i

n

the ful l r a nge o f o rga n s a n

d

tis s u e s.

M

. F.

H

u

g

he s

, L

M

. De

l

Ra z o

, a n

d

E.

M

K

e nyo n

(

Hu

g h

e s et a

l

, 2 0 0 0

)

pe rfo r

m

e

d

a n

e xpe r

i m

e ntal stu

d y w i

th B

6 C

3 F 1

m i

c e to

i

n v e st

i g

ate t

h

e ef fe cts o

f i

ntr a v e n o u s

a

dm i

n

i

str at

i

o n o

f d i m

ethy

l

a r s

i

n

i

c a c

i d

(

D

M

A

)

.

S i

n c e

D

M

A

o c c u r s

i

n

w

ate r n atu r a

l l

y,

i

t

m

ay

b

e e n c o u nte r e

d i

n t

h

e e n v

i

r o n

m

e nt

d

a

i l

y. D

M

A i

s a

l

s o t

h

e pr e

d

o

m

in a nt

m

eta

b

o

l i

te o

f

i

n o r

g

a n

i

c a r s e n

i

c e x c r ete

d i

n u r

i

n e

b

y

m

o st

m

a

m m

a

l

s.

T h i

s stu

d

y s

h

o

w

e

d

t

h

e r e

w

e r e n o

m

et

h

y

l

ate

d

o r

d

e

m

eth y late

d

pr o

d

uc ts o

f

D

M

A in the

b l

o o

d

o r t

i

s s u e e x a

m i

n e

d d

u r

i

n

g

a n

8

h

o u r

m

o n

i

to r

i

n g pe r

i

o

d

, a n

d

t

h

at t

h

e

d i

str

i b

ut

i

o n a n

d

r ete nt

i

o n o

f

D

M

A i

n t

h

e

l

u ngs w a s

d

o se

d

e

p

e n

d

e nt. D

M

A i

s a tu

m

o r

p

r o

m

ote r

i

n the

l

u n

g

, a n

d

t

h

e

d

o se

d

e

p

e n

d

e nt

d i

str

i b

ut

i

o n a n

d

l

o n

g

e r r ete nt

i

o n o

f

D

M

A i

n the o r

g

a n

m

a

y h

a v e a r o

l

e

i

n t

h i

s e

f f

e ct

(

Y a

m

a n a

k

a et a

l

.

, 1

9 9 6

)

.

T h is e xpe ri

m

e nt

i

s

i m

po rta nt

i

n t

h

at it r e v e als the r e a r e

d

i f fe r e n c e s in the r e spo n s e of the

b

o

d

y's

d i

str

i b

ut

i

o n , up ta

k

e, a n

d

a

b

s o rpt

i

o n o

f

a r s e n

i

c w he n the c

h

e

m i

c a

l

s a r e a

d m i

n

i

ste r e

d

at

a

h i

g

h l

e v e

l

o

f

c o n c e ntr at

i

o n

(

1

1 1

m

g

/ k

g v e r s e s 1 1 1

m

g

/k

g

)

, a n

d

t

h

at a

b

s o rpt

i

o n at t

h

e

h i

g

h

e r

l

e v e

l m

ay

b

e

m

o r e

h

a r

m f

u

l

to

p

a rts o

f

t

h

e

b

o

d

y.

In 19 9 9,

M

. F. Hu

g h

e s, E.

M

.

K

e nyo n, et a

l

.

(

H

u

gh

e s et a

l

, 1

9 9 9

)

p

e r

f

o r

m

e

d

a stu

dy

w

i

t

h

thr e e str a

i

n s o

f

c r o s s-

i

n

b

r e

d m i

ce

, B

6 C 3F l

/ C

r

l B R

,

C 57

B L / 6 N C

r

l

Br, a n

d

C 3 H / H

e

N C

r

l B R

to e x a

m i

n e t

h

e

d i f f

e r e n c e

i

n a

b

s o rp t

i

o n a n

d

e

l i m i

n at

i

o n o

f

a r s e n

i

c.

T h

e

r a

d i

o

l

a

b

e

l

e

d

a r s e n ate o r a r s e n

i

te wa s a

d m i

n

i

ste r e

d

o r a

l l

y at t

w

o

d i f f

e r e n t

d

o s e

l

e v e

l

s.

D i f f

e r e n c e s

w

e r e n ote

d i

n t

h

e w

h

o

l

e

b

o

d

y r ete nt

i

o n o

f

r a

d i

o a ct

i

v

i

t y

b

y t

h

e thr e e str a

i

n s o

f

m i

c e a

ft

e r a

d m i

n

i

str at

i

o n o

f

a r s e nate. T

h i

s stu

d

y r e v e a

l

e

d

that a

p p

r o x

i m

ate

l y 5 0

%

o

f

the

h i g h do s e o f a r s e n ate wa s e x c r eted

i

n 5 ho u r s

b

y the B

6C 3 F 1

a n

d

C 3 H

m i

c e, c o

m

pa r e

d

to

8

(14)

a r s e n ate r e s ulte

d i

n a n

i

n c r e a s e

i

n t

h

e a

m

o u nt o

f

a r s e n

i

c a

b

s o r

b

e

d i

n t

h

e

b

o

d

y t

i

s s u e

N

o

str ain

d i f f

e r e n c e s w e r e o

b

s e r v e

d

w

i

t

h

a r s e n

i

te,

b

ut w

i

t

h i

n c r e a s e

d d

o s e, t he c

l

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f

a r s e n

i

c wa s s

l

o

w

e r a n

d

t

h

e t

i

s s u e r ete nt

i

o n o

f

a r s e n

i

c wa s

h i

g

h

e r. Ho

w

e v e r, t

h

e stu

d

y

c o n c lu

d

e

d

t

h

e r e

w

a s n o s

i

gn

i fi

c a nt

d

i f fe r e n c e

i

n t

h

e

d

is

p

o s

i

t

i

o n o

f

a r s e n

i

c

b

et

w

e e n t

h

e t

h

r e e

str a

i

n s o

f m i

c e e x c ept

f

o r the e x c r et

i

o n ti

m

e o

f

5

h

o u r s v e r s u s

8 h

o u r s. T

h

e r e s u lts fr o

m

t

h i

s

stu

d

y a r e

i m

po rta nt to t

h

e e xpe r

i m

e nt a n

d m

o

d

e

l d

is c u s s e

d i

n t

h i

s pape r a s they s

h

ow a

(15)

T h

e

L

a

b

o r a

t

o r

y E

x

p

e r

i

m

e n

t

A ni

m

al a n d A r s e nic Sele ct io n

T h

e e x pe r

i m

e nt

b

e

g

a n w

i

t

h

t

h

e s e

l

e c t

i

o n o

f

te n

f

e

m

a

l

e

m i

c e o

f

t

h

e str a

i

n

B 6 C

3 F 1

f

ro

m

t

h

e

C h

a r

l

e s

R i

v e r La

b

o r ato r

i

e s

i

n Rale

i

g

h

,

N

.

C

. T

h

e s e

m

ic e

w

e r e

i d

e nt

i fi

e

d

a s

A

n

i m

a

l

s 1 t

h

r o ug

h

1

0

(

A

n

l

- A n 1

0

)

f

o r t

h

e e xpe r

i m

e nt a n

d h

a

d

a n a v e r a

g

e

b

o

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y we

i

g

h

t o

f

2 4

.7

g

r a

m

s. Du r

i

n

g

t

h

is e xpe ri

m

e n t, t

h

e

m i

c e

w

e r e

m

a

i

ntain e

d i

n

i

n

d i

v

i d

u al

m

eta

b

o

l i

s

m

c a

g

e s w

i

t

h f

oo

d

a n

d

ta

p w

ate r

p

rov

i d

e

d

a

d l i b i

tu

m

a cco r

d i

n

g

to

g

u

i d

e

l i

nes

(

N

I

H

,

19 9 6

)

e sta

b

l is

h

e

d b

y the

N

atio n al In stitute s of He a

lt

h. T

h

e c age

d

a n

i m

als

w

e r e

k

ept

i

n a r o o

m

w

h

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h

e

h

u

m i d i

ty wa s

5 0

+

10

pe r c e nt, t

h

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m

pe r atu r e

w

a s

2

2 + 1

d

egr e e

C

, a n

d

t

h

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ts

cyc

l

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o n

(

l i

g

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t

)

a n

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f f

(

d

a r

k

n e s s

)

e v e ry 12

h

o u r s.

A

s a

p

a rt o

f

t

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e

p

r e

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p

r epa r at

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f

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i

n

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tial

b

o

d

y

w

e

i

g h t o

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h

a n

i m

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d

a n

d

r e c o r

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.

T h

e

[

A

s

]

a r s e n

ic

a c

i d

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ta

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n e

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r o

m

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a

m

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at

i

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l L

a

b

o r ato ry,

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o s

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a

m

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.

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. a n

d

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i

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.

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e ''^

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s

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as

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t

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a s o

l

ut

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d i

u

m

a r s e n ate-

h

e

p ta

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y

d

r ate

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s

h

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e

m i

c a

l

,

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a

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r

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aw n,

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.

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.

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h

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R

ad io a ct ivity

M

e a s u r e

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s a pa rt o

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p

r e

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e

fi

n e

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r at

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p

s

w

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(16)

wo u l d be a c c u r ate A ' ^ ^Ce sta nda rd

w

a s u s ed fo r a qu al ity c o ntr ol che ck of t

h

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ete cte

d i

n e a ch

m

o u s e c o ul d

b

e

c o r r e cte

d f

or

d

e c ay. For t

h

e ga

m m

a c o u nte r sta n

d

a r

d

, t

w

o uC i of ''^

A

s

w

a s e v e nl y d ivi

d

e

d

in

to

fi

ve v

i

a

l

s T

h

e s e v

i

a

l

s

w

e r e

m

e a s u r e

d

e a c

h d

a

y i

n t

h

e

g

a

m

m

a c o u nte r

b

e

f

o r e t

h

e

d

a

i l y

s a

m p l

e s o

f

u r

i

n e a n

d f

ec es

w

e r e

m

e a s u r e

d

s o a ct

i

v

i

t

y i

n t

h

e sa

m p l

es c o u

l d b

e c o r r e cte

d f

or

d

e c ay.

E

xpe ri

m

e n tal Pr o c edu r e

T

h

e e xpe r

i m

e nta

l d

o s

in

g a n

d d

ata r e c o r

d i

n g

b

ega n o n Ju n e 2 2, 1

9 9 9

, a n

d w

a s

p

e r

f

o r

m

e

d

s e r

i

a

l l

y

f

o r e ac

h

o

f

t

h

e te n

m i

c e.

F i

r st, e a c

h m

o u s e w a s r e

m

o v e

d fr o

m i

ts c a

g

e.

T

h

e

l

e v e

l

o

f

a r s e n

i

c r a

d i

o a ct

i

v

i

t y

w

a s

d

ete r

m i

n e

d b y

w

h

o

le

-

b

o

d

y ga

m m

a c o u nt

i

n

g i

n a

C

a n

b

e r r a

,

M

e r

i d

e n ,

C T

,

m

o

d

e

l

2

2 9 0

-

S

s

m

a

l l

a n

i m

a

l

c o u nte r to

i d

e nt

i f y

a n

d

r e

co r

d

t

h

e pr e

-d

o s e

m

e a s u r e o

f

a r s e nic

f

o r t

h

e a n

i m

a

l

. T h is wa s a c c o

m

p

l i

s

h

e

d b

y p la c

i

ng t

h

e

m

o u s e

i

n a

tu

b

e t

h

at

i m m

o

b i l i

z e

d i

t, a n

d

t

h

e n p

l

a c

i

n g t

h

e tu

b

e

i

nto t

h

e

w h

o

l

e

b

o

d y

c o u nte r

f

o r

m

e a s u r e

m

e nt,

w h i

c

h

r e

q

u

ir e

d

t

w

o

m in u

te s Be

f

o r e t

h

e

m

o u s e w a s p

l

a c e

d i

n t

h

e tu

b

e, t

h

e

cle a n, e

m p

t

y

tu

b

e

w

a s p

la c e

d

i

nto t

h

e c o u nte r a nd

m

e a s u r e

d

fo r o n e

m

in u te

f

or a

b

a c

k

gr o u n

d

m

e a s u r e

m

e nt.

N

e xt

, a

d

os e o

f 0

.

5 m g A

s

/k g

(

a

p p

r o x

i m

ate

l y

2 u

C i

)

w

a s a

d m i

n

i

ste re

d

to t

h

e

m

o u s e

b

y o r a

l

ga v age

(

1

0 m

l

/

k g

)

, a n

d

again t

h

e

m

o u s e

w

a s p la c e

d i

nto t

h

e w

h

ole

b

o

d

y

c o u nte r

f

o r t

w

o

m

in u te s to

d

ete r

m in e

a n

d

r e c o r

d

t

h

e

p

o st-

d

o s e

m

e a s u r e

(17)

On the

fi

r st

d

ay of the e xpe ri

m

e nt, data v alu e s fo r the pr e

-do s e

m

e a s u r e, fe c e s a n

d

u r

i

n e

w

e r e r e c o r

d

e

d

a s z e ro s

i

n c e n o a rs en

i

c wa s

p

r e s e nt

f

r o

m

the

p

r e v

i

ou s

d

ay .

N

e x t, t

h

e

i

n

it

i

a

l d

o s e o

f

a rse n

i

c w a s a

d m i

n

i

ste r e

d

, a n

d

t

h

e

l

e v e

l

o

f

r a

d i

o a ct

i

v

i

t y

i

n the

m

o u s e

w

a s

m

e a s u r e

d

a n

d

r e c o r

d

e

d

a s the po st-

d

o s e

m

e a s u r e.

A f

te r o

b

ta

i

n

i

n

g

the

p

o st

-

d

o s e

m

ea s u r e, t

h

e

m

o u s e w a s p la c e

d i

n a cle a n

m

eta

b

ol is

m

c age s o u r

i

n e a n

d f

e c e s c o u l

d b

e c o

l l

e cte

d d

u rin

g

t

h

e next

2 4 h

o u r pe r

i

o

d

. In a

d d it

i

o n, u r

i

n e an

d f

e ce s

f

r o

m

t

h

e c a

g

e

f

o r t

h

e pr e v

i

o u s

d

a y w a s

c o

l l

e cte

d

, e x c ep t

f

o r t

h

e

fi

r st

d

ay, a n a

l

yz e

d

that

d

ay a n

d

the a

m

o u nt o

f

r a

d i

o a ct

i

v e a r s e n

i

c

wa s r e c o r

d

e

d

to

p

r o v

i d

e

d

ata

f

o r e a c

h

a n

i m

al.

S

e e Ta

b l

e 1

f

o r a n e x a

m

p

l

e o

f

the

d

ata s et

o

b

ta

i

n e

d f

o r

A

n

i m

a

l 6

. Fo r a r e v

i

ew o

f

t

h

e s e

d

ata

f

o r a

l l

te n a n

i m

a

l

s r efe r to

A

p pe n

d

ix 1

.

T

h

e

m

eta

b

o

l i

s

m

c age s

h

a

d

a w

i

r e

b

ot to

m

s o the e x c r eta c o u

l d f

a

l l

thr o u

g h

.

U

n

d

e r n e at

h

t

h

e

w ir e

b

ot to

m

, t

h

e r e wa s a

f

u n n el to s epa r ate the u r in e a n

d

t

h

e

f

e c e s into c ups w

h i

c

h

we r e

T a

b

le 1 D ai

l y

Data Re a

d i

ngs fo r An

i m

al 6

f

r o

m

the Expe r

i m

e nt

Or a

l l

y A

d m i

niste r e

d

Ar s e n

i

c

Date Po st-D o s e

M

e a s u r e

m

e nt

(

ug

A

s

)

P

r e

-Do s e

M

e a s u r e

m

e nt

(

ug

A

s

)

U

r

i

n e

M

e a s u r e

m

e n t

(

ug

A

s

)

Fe c es

M

e a s u r e

m

e nt

(

u g

A

s

)

6 /2 2 / 9 9

1

1

.

3 6

0

.

0

0

.

0

0 0

6 /2 3 / 9 9

1 1

.

3 7

0

.

32 9 8

1 1

.2

8

1

.

0 0 1

6/

2

4 / 9 9

1 1.

0 5

0

.5

185

10 4 7

1

.

9 3 5

6 /

2 5

/ 9 9

1

1.7

6

0

.

54 6 3

9 9 5 7

3

.

4

7

6

6/ 2 6 /

9 9 1 2.2

9

0

.5 5 2 5 1 0.5 1 1

6 70

6/ 2 7 / 9 9

1 2. 1 1

0 6 84 7

9

.

4 17

2

.

5 18

6 /

2

8/ 9 9

1 1.

9 6

0

7 4 2

6

10.50 1.4 9 2

6/

2

9 / 9

9

6

/

3

0 / 9

9

7

/

1

/ 9 9

1 2. 18

1

1.

7 4

0

.

0

0

8

6 8 8

0

.

9

13 0

0

.

9 34 7

1 0.2 0

10.

7

5

10

.

7 5

1.5 7 0

2. 121

2

.

12 1

(18)

c o

l l

e cte

d

e v e ry

2

4

h

o u r s.

A d d i

t

i

o n al l y

, t

h

e u r

i

n e

w

a s

k

ept c ol

d b y

p

l

a c

in

g d

ry

i

c e a r o u n

d

the

u rin e c o ntain e r

in

the

m

eta

b

ol is

m

c age On c e the u rin e w a s c o

l l

e cte

d

, it

w

a s

k

ept o n

f

r o zen

ge

l

pa c

k

s o r p

l

a c e

d i

n the r e

f

r

i g

e r ato r u nt

i l i

t c o u

l d b

e a n a

l

yz e

d i

n a Pa c

k

a r

d

In str u

m

e nts

(

M

e r

i d

e n, C T

)

M

o

d

e

l 5 5

3

0

ga

m m

a c o u nte r.

A ft

e r a n a

l

ys

i

s, t

h

e u r

i

n e a n

d f

e c e s we r e p

l

a ce

d

in

a -7 0°

C fr e e z e r fo r sto r age. T h is pr o c e

d

u r e

w

a s r epe ated dai l y fo r e a ch of the te n

m

ic e

f

r o

m Ju n e

2

2, 1

9 9 9

to

J

u

l

y 1, 1

9 9 9

.

A f

te r the

l

a st pr e-

d

o s e

m

e a s u r e o n

Ju

l

y 1

' ^'

,

fi

v e o

f

t

h

e

m i

c e, a n

i m

a

l

s

6

thr o ug

h

1

0

,

we r e s a c r

i fi

c e

d b

y c a r

d

ia c pu n ctu r e u n

d

e r

C

0 2

-in

d

u c e

d

a n e sthe s

i

a. Fol lo

w

in

g s a c ri

fi

c e o

f

the a n

i m

a

l

s, t

h

e

ir

s

k i

n

(

w i

t

h h

a

i

r

)

, a t

h i gh m

u s c

le

,

l i

v e r,

lu n

g

s a n

d k i d

n eys we r e r e

m

o v e

d

a n

d

te sted

f

o r r a

d io a c

tiv

i

ty

i

n the ga

m m

a c o u nte r. T

h

e r e

m

ain

i

ng c a r c a s s

w

a s

m

e a s u r e

d

fo r

r a

d io a c

t

i

vity a n

d

s a v e

d f

o r

fu r

the r te stin

g

. T he r e

m

ainin

g

fi v e

m i

c e

, a n i

m

als 1t

h

r o u

g

h 5,

we r e

m

o n

it

o r e

d

unt

i l Ju

l y 9

"^ to r e c o r

d

the e

q

u

i

va

le n

t o

f

the

i

r r a

d i

o a ct

iv e

p

r e-

d

o

s e

m

e a s u re,

b

ut they

d i d

n ot r e c e

i

v e a n

y

a

d d it

i

o n a

l d

os

i

n

g

.

O

n

J

u

l

y

9

*

, a n

i

m

a

l

s

1

t

h

rou

g h 5 w

e r e

sa c r

i fi

ce

d

, a n

d

t

h

e s a

m

e o r

g

a n s we r e

h

a r v e ste

d

a n

d m

e a s u r e

d f

o r r a

d i

o a ct

i

v

it

y. Data

f

r o

m

the e xpe r

i m

e n t a r e pr o v

i d

e

d i

n

A

p pe n

d i

x 1, a n

d A

p pe n

d i

x 2 c o nta

i

n s a s u

m m

a ry o

f

t

h

e

d

ata

(19)

A

n a

ly

s

i

s a n

d S

u

m m

a r

y

o

f E

x

p

e r

i

m

e n

t

a

l D

a

t

a

Ex

p

e ri

m

e n tal Data

R

e v ie

w

T

h

e r a

d i

o a ct

iv e a r s e n

ic c o n c e n

tr at

i

o n

d

ata c ol le cte

d d

u r

i

n

g

t

h

e e x pe r

i m

e nt a n

d

d is

p

la

ye

d i

n A p pe n

d i

x 1

w

e r e s u

m m

a r

iz e

d

a n

d

pr o c e s s e

d

r e

l

at

i

v e to t

h

e

d

o s e

m

e a s u r e

m

e nt to

o

b

ta

i

n t

h

e

p

er c e nt o

f

a r s e n

ic

pr e s e nt

i

n t

h

e u r

in e

,

f

e c e s, a n

d

v a r

i

o u s

b

o

d

y pa rts ta

k

e n

f

r o

m

t

h

e

m i

ce at s a c r

i f

i c e, a n

d

t

h

e s e pe r c e nta

g

es we r e n o r

m

a

l i

z e

d

so t

h

e s u

m

o

f

t

h

e

f

ra ct

i

o n s o

f

a r s e n

i

c pr e s e nt

i

n a

l l

o r

g

a n s, t

i

ssu e s, a n

d

e x c r eta e

q

u a

l

1 0

0 p

e r c e nt.

T h is s e c

t

io n

d

e s c r

i b

e s

h

o

w

t

h

e

d

ata

f

r o

m A

p

p

e n

d i

x 1

w

e r e s u

m m

a r

i

z e

d

a n

d

a n a

l

yz e

d

to u n

d

e r sta n

d

the upta

k

e a n

d

d is

p

o s

i

t

i

o n o

f

a r s e n

ic

b

y v a r

io u s

b

o

d

y c o

m

po n e nts, a s we

l l

a s t

h

e a

m

o u nt e x c r ete

d fr

o

m

t

h

e

b

o

d

y .

A l

t

h

o u

g

h

t

h

e

l

a

b

o r ato ry

d

ata

i d

e nt

i f

i e

d

t

h

e a

m

o u nt o

f

r a

d io a c

t

iv e a r s e n

i

c pr e s e nt

in

t

h

e

h

a r v e ste

d b

o

d

y

p

a rts, t

h

e

p

er c e nt o

f

a r s e n

i

c pres e nt

in

ea c

h

o

f

t

h

e

b

o

d

y pa rts r e

la

t

iv

e to

t

h

e a

m

o u nt a

d m i

n

i

ster e

d

(

i

.e. t

h

e n o r

m

a

l i

z e

d

pe r centa

g

e

)

i

s u s e

f

u

l f

or c o

m

pa r

is o n

w i

t

h

m

o

d

e

l

e st

i m

ate s a n

d

ot

h

e r e x pe r

i m

e nta

l d

ata.

D o s e

M

e a s u r e

m

e n t

C

alc u lat

i

o n

T

h

e

d

ata s u

m m

a ry

p

r o c e

du r e

b

e

g

a n

b

y c a

l

c u

l

at

i

n

g

t

h

e D o s e

M

e a s u r e fo r e a c

h

a n

i m

a

l

w

h i

c

h

c o n s

i

ste

d

o

f

ta

k i

n

g

t

h

e

d i f f

eren c e

b

et wee n po st-

d

o se a n

d p

r e-

d

o s e r e c o r

d i

n

g

s a n

d

s u

m m i

ng th

i

s

d

i f fe r e n c e fo r t

h

e

du r a

t

i

o n o

f

t

h

e e xpe r

i m

e nt a s s

h

own

i

n Ta

b l

e 2

f

o r A n

i m

a

l 6

.

T

h i

s s u

m

o

f

t

h

e

d i

f

f

e r e n c e o

f d

ai ly po st-

d

o s e a n

d

pr e-

d

o s e

m

e a s u r e

m

e nts

fo r e a c

h a ni

m

al

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