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A bstr a ct

Pr e v

io u s s

t u

d

ie s ha v e h y pot

h

e siz e

d

that

C

a r

b

o n D

i

s u

l f i d

e

(

C Sj

)

to x ic

i

t y

i

s

b

a s e

d

o n t

h

e c

h

e

l

at

i

o n

o

f

c op pe r an

d

z

i

nc

io n s

b

y t

h

e

d i

t

h io c a r

b

a

m

ate

d

e r

i

v at

i

v e s a r

is

in

g

f

r o

m

t

h

e r e a ct

i

on o

f C S

j

w i

t

h

a

m

i

n e s. T

h

e pr

i

m

a ry o

b

j

e ct

i

v e o

f

t

h i

s stu

d

y

w

a s to

i

nv e st

i

gate t

h

e pote nt

i

a

l i

n v o

l

v e

m

e nt o

f

tr a c e

m

eta

l

s

in

t

h

e

m

eta

b

o

l i

s

m

o

f C S

j

in

e x

p

o s e

d

r ats.

C S

j

w

a s a

d

m

in

i

ste r e

d i

n a

ir a

t

0

,

5 0

,

15 0

, o r

5 0 0

p p

m

to s e

p

a r ate gr o ups o

f 60 y

o ung a

d

u

lt

m

a

l

e

Sp

r a

g

ue-

D

a

w l

e

y

r ats

f

o r

6 h

r

/ d

a

y

,

5 d

ays

/w k

,

f

o r

6

.

5 m

on t

h

s. T

h

e

d ie

t c o n s

i

ste

d

o

f N I H 0 7

pe

l l

ets

(

Z

ie

g

l

e r Br ot

h

e r s,

G

a r

d

n e r, P

A

)

an

d

tap

w

ate r

fr

o

m b

ot t

l

e s.

A f

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h

a

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to

C

Sj

f

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6

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m

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s

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w

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in u e

d

.

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n e r ats

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o

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e a c

h

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p

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g

r o u

p i

n c

lu

d i

n g c onfr o

l

s

w

e r e c

h

o s e n r a n

d

o

m l

y.

C

u

m

u

l

at

i

v e v o

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e

d

u r

i

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w

a s c o

l l

e cte

d d

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in

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0

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8

,

8

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16

,

16

-

2 4

, an

d 2 4

-

4 8 h

o u r s

f

o

l l

o

w i

n

g

t

he

la s

t

C S

j e x

p

o s u r e.

T

h i

rty

-s e v en

m

eta

l

s

w

e r e

m

e a s u r e

d in

t

h

e u r

i

n e

b

y

in

d

u ct

iv e

l

y c o u

p l

e

d

p

l

a s

m

a ato

m

ic

e

m

i

s s

i

on

s

p

e ctr o s c op y

(

I C P

-

A E S

)

.

L i

n e a r r e

g

r e s s

i

o n ana

l

ys

is u s

i

n

g

c r e at

i

n

i

ne n o r

m

a

l i

z e

d

c o n c e ntr at

i

o n s

f

o r e a c

h

e x

p

o s u r e

g

r o u

p

o v e r t

i

m

e r e v e a

l

e

d

stat

is

t

i

c a

l l

y s

i

gn

i fi

c an t

(p

<

0

.

0 5

)

c o r r e

l

at

i

o n

c o e

f fi

c

ie n

ts

f

o r B,

C

a, I,

M

g, P,

P

t, a n

d Sr

i

n t

h

e c o ntr o

l

gr o up ;

Ca

, I,

M

g,

M

n, a n

d

P

in

the

5 0

p p

m

gr o up ;

S

e an

d Si i

n t

h

e

1 50

p p

m

gr o up ; a n

d

B, Ca,

M

g,

M

n , an

d

P

in

t

h

e 5 0 0 p p

m

gr o up.

W

i

t

h

t

h

e e x c ept

i

o n o

f P

t,

S

e, a n

d Si

, t

h

e

m

eta

l

c o n c e ntr at

i

o n s

w

e r e

d

e c r e a s

i

ng o v e r t

i

m

e. L

in e a r

r egr e s s

io n

an a

l

ys

i

s u s

i

ng tota

l m

eta

l

(n g

)

pe r t

i m

e pe r

i

o

d i

n ste a

d

o

f

c r e at

in

i

n e n o r

m

a

l i

z e

d

(|

jg

/ m

g

)

c o n c entr at

io

n s, y

ie

l d

e

d

s

i m i l

a r r e s u

l

ts.

S i

n c e t

h

e

m

a

j

o r

i

t y o

f m

eta

l

s

w i

t

h

a s

i

gn

i f

i c ant c o r r e

la

t

io n

c o e

f fi

c

i

e nt

in

b

ot

h

ana

l

ys

i

s

w

e r e

i

n t

h

e n o n-e x

po s e

d

gr o u

p

,

i

t

i

s un

l i k

e

l

y t

h

at t

h

e v a r

i

at

i

ons

w

e r e a

r e su

lt

o

f C S

2 e xpo s u r e.

F

utu r e stu

d i

e s s

h

o u

l d

c o n c e ntr ate o n

d

ete r

m i

n

in

g t

h

e n atu r a

l fl

u ctu at

i

o n s

(2)

A C K N

O

WL E D

G

M

E

N

T

I

w i

s

h

to e x

p

r e s s

m

y s

i

nc e r e ap pr e c

i

at

i

o n an

d

gr at

i

tu

d

e to s e v e r a

l i

n

d i

v

i d

ua

l

s

f

o r t

h

e

i

r

s up

p

o rt an

d

enc o u r a

g

e

m

ent.

F i

r st, I a

m

t

h

an

k f

u

l f

o r

D

r.

C l i

nt

C

o x a n

d

Dr.

Sh

a n e

Q

u e

H

e e

w h

o

p

r o v

i d

e

d

t

h

e

d

ata t

h

at

w

a s t

h

e

b

a s

i

s

f

o r t

h i

s te c

h

n

i

c a

l

r epo rt. I e spe c

i

a

l l

y

w

a nt

to t

h

a nk Dr. Co x fo r the u n s el fi sh

m

e nto ring a n

d

s up po rt yo u ha v e g

i

v e n

m

e o v e r t

h

e

l

a st

s e ver a

l

ye a r s.

Y

ou

k

ne

w w h

e n to pu s

h m

e an

d w h

e n

I

n e e

d

e

d

e n c o u r a

g

e

m

e nt.

I w i l l

a

l w

ays

b

e gr ate

f i

a

l f

o r your gene r o s

i

t

y

o

f

t

i

m

e an

d

your

b

e

l i

e

f i

n

m

e.

T h

a n

k

s

f

o r s e r v

i

ng

o n

m

y c o

m

m

it te e!

To

D

r .

M

i k

e

S

y

m

o n s, I

w

ant to s ay a s

p

e c

i

a

l

t

h

an

k

s

f

o r agr e e

i

ng to

b

e a

m

e

m b

e r o

f m

y

c o

m m

i

tte e e v e n t

h

o ug

h I w

a s n e v e r a stu

d

en t o

f

yo u r s. T

h

an

k

s

f

o r yo u r gr a c

i

o u s at t

i

tu

d

e

a n

d i

nput

d

u r

i

ng t

h i

s pr o

j

e ct.

T o

D

r .

B

a

l l

,

m

y c o

m

m

i

tte e c

h

a

i

r an

d

a

d

v

i

s o r , I a

m d

e ep

l

y

i

n

d

e

b

te

d

to yo u

f

o r

y

o u r

e n c o u r a

g

e

m

e nt an

d i

n c r e

d i b l

e

p

at

i

e n c e.

N

ot o n c e

d i d I h

e a r a n e

g

at

i

v e o r

d i

s c o u r a

g i

n

g

w

o r

d fr

o

m

you e v e n t

h

ou g

h I

m

o st a s s u r e

d l

y

d

e s e r v e

d i

t. Y o u r s up po rt an

d

s e n s e o

f

h

u

m

o r

k

ep t

m

e

m

ot

i

v ate

d

.

T h

an

k

s

f

o r

h

e

l

p

i

ng

m

e

k

e ep

l i f

e

i

n pe r spe ct

i

v e.

To

C

.L. La s s

i

te r, I

w

a nt to say t

h

a n

k

s

f

o r a

l w

ays

b

e

i

ng

w i l l i

n

g

to

h

e

l

p

m

e

w i

t

h

r eg

i

str at

i

o n

s e

m

e ste r a

ft

e r s e

m

e ste r. Yo u

w

e r e a

l w

ays a

p l

e a s u r e to

d

e a

l w i

t

h

. T

h

an

k

yo u

f

o r a

l l

yo u r

h

e

l p

.

To

m

y pa r e nts,

I w

an t to s a

y

t

h

a n

k

s

f

o r te a c

h i

ng

m

e to "

N

e v e r

Q

u

i

t" . T

h

a n

k

s

f

o r a

l l

yo u r s up

p

o rt an

d

e n c o u r a

g

e

m

e nt. I c o u

l d

n ot

h

a v e

b

et te r

p

a r e nts.

F i

n a

l l y

, to

m

y

w i f

e

K i m

a n

d m

y s o n Lo

g

an. T

h

a n

k

s

f

o r

y

o u r

l

o v e an

d

u n

d

e r stan

d i

ng

(3)

T a

b l

e o

f C

on te nts

P

age

L

i

st o

f

Ta

b l

e s v

i

L

i

st o

f

F

i

gu r e s v

i i

1.

0

Ba c

k

gr o un

d

1

1. 1 So u r c e an

d U

s e s of C S 2

1

1.

2 C h

e

m i

c a

l

a n

d

P

h

ys

i

ca

l

Pr o

p

e rt

i

e s

2

1

.

3

M

eta

b

o

l i

s

m

2

1.

4 T

o x

ic

E f f

e cts

7

1

.

5 U

r

i

n a r

y

M

a r

k

e r s

1 1

1.

5

.

1

Io

d i

n e

A

z

i d

e

1 1

1.5.

2

T

h i

o et

h

e r s

12

1.

5

.

3

T

T C A

12

2.

0

M

ate r

i

a

l

s an

d

M

et

h

o

d

s

13

3.

0 R

e su

lt

s

18

4

.

0

D

is c u s s

i

o n an

d C

onc

lu s

io

n s

2 8

5

.

0 S

ug ge st

io n s

f

o r Fu rthe r

St

u

d

y

3 3

6

.

0

Re

f

e ren c e s

3 5

7.0 A

p

pe n

d i

c e s

4 8

7. 1

A

p

p

e n

d i

x

A

L

a

b

o r ato ry

D

ata

A

- 1

7.

2 A

p

p

e n

d i

x B Cr e at

i

n

in e

A d

j

u ste

d

Data

B

- 1

7.

3 A

p

p

e n

d i

x

C

L

in e a r r e

gr e s s

i

o n P

l

ots o

f

M

eta

l

s

(j

xg

/

m

g

)

v s T

im

e

C

-

1

7

.

4 A

p

p

en

d i

x

D

L

in e a r

Regr e s s

i

on

P l

ots o

f

M

eta

ls

(|

i g

/

m

g

)

v s

E

xpo sur e

D

- 1

7.

5 A

p

p

e n

d i

x E L

i

n e a r Regr e s s

i

on

P l

ots o

f

M

eta

l

s

((

ag

)

v s T

im

e

E

- 1

7.

6 A

p

p

en

d i

x F L

in e a r

Regr e s s

i

o n

P l

ots o

f

M

eta

l

s

(|

.i

(4)

L I ST O

F

T A B

L E

S

Page

T

a

b l

e

1

-

1

T h

e

C h

e

m i

c a

l

l

d

ent

i

t y o

f C

a r

b

o n D

i

s u

l f i d

e

3

Ta

b l

e 1-2 P

h

ys

i

c a

l

an

d C h

e

m

i

c a

l

Pr opert

ie s o

f C

a r

b

o n D

i

s u

l fi d

e

4

Ta

b l

e

3

- 1

M

eta

l

s

w i

t

h

S

i

gn

i f

i c an t

C

o r r e

l

at

i

on

w i

t

h T i m

e

(

c r e at

i

n

in e a

d

j

u ste

d

)

1

8

Ta

b l

e

3

-

2

0 p

p

m

L

i

n e a r Regr e s s

i

o n

A

na

l

ys

i

s Re s u

lt

s

(

c r e at

in

i

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d

j

u ste

d

)

1 9

Ta

b

le

3

-3

5 0

p p

m L i

n e a r Regr e s s

i

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n a

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lt

s

(

c r e at

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)

2 0

T

a

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p p

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)

2 0

T

a

b l

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3

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50 0 p p

m

L

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n e a r

R

egr e s s

i

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l

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s Re s u

lt

s

(

c r e at

in

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ne a

d

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)

2 1

Ta

b l

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3

-

6

2 4-

4 8 h

r

L i

n e a r Regr e s s

i

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i

s Re s u

lt

s

(

c r e atin

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u ste

d

)

2 2

Ta

b l

e

3

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M

eta

l

s

w i

th Si

gn

i fi

c a nt

C

o r r e

l

at

i

o n

w i

t

h T i m

e

(

tota

l

m

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l

|ig

)

2 4

T a

b l

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3

-

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Op

p

m

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in e a r

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i

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s

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e s u

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tota

l m

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)

2 5

Ta

b l

e

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9

50 p p m L i

n e a r R e

g

r e s s

i

o n

A

na

l

ys

i

s

R

e s u

l

ts

(

tota

l

m

eta

l

\i

g)

2 5

Ta

b l

e

3

-

10

1 50 p p

m

L

i

n e a r

R

e

g

r e s s

i

on

A

na

l

ys

i

s Re s u

l

ts

(

tota

l

m

eta

l

^ g

)

2 6

T

a

b l

e

3

-

1 1

5 0 0

p p

m

L

i

n e a r Regr e s s

io n

A

na

l

ys

i

s Re s u

l

ts

(

tota

l m

eta

l

|ag

)

2 6

Ta

b

le

3

- 12 1

6

-

2 4 h

r L

i

n e a r R

egr e s s

i

o n

A

na

l

ys

i

s Re s u

lt

s

(

tota

l

m

eta

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|ig

)

2 7

Ta

b l

e

4

-

1

Co

m

pa r

i

s o n o

f

L

in

e a r Re

g

r e s s

i

o n Re s u

l

ts

f

o r Ca

(

c r e at

in

i

n e a

d

j )

2 9

(5)

L I

ST

O

F F I

G U R E S

Page

F

i g

u r e

1

- 1 Pr o

(6)

M

etals a s Potent ial B io

m

a r ke r s of Ex po s u r e to C a rbo n

D

isul fi de.

b

y

A l

a n

G

. Pa r

h

a

m

1.

0 B

a ck gr ou n

d

1

.

1 So u r c e s a n

d U

s e s o

f C S

j

C S

j

i

s r e

le a s e

d fr

o

m b

ot

h

n atu r a

l

an

d

m

a n

m

a

d

e s o u r c e s.

C S

j

i

s r e

le a s e

d i

n s

m

a

l l

a

m

o u nts

fr

o

m

s e v e r a

l

n atu r a

l

s o u r c e s

in c

lu

d i

ng v o

lc a n o e s

, s o

i l m i

c r o

b

e s, a n

d

o c e a n

s e

d im

e nts

(

A

T

SD

R

,

19 9 6

)

.

C

o

m

b

u st

i

o n o

f

c a r

b

o n a c e o u s

m

ate r

i

a

ls c o n

ta

i

n

in

g

s u

l fi

i r

a

l

s o r e

l

e a s e s

C S

j.

U

nt

i l

a

b

o ut

19 5 0

,

C S

j

w

a s

p

r o

du c e

d

c o

m

m

e rc

i

a

l l

y

b

y

h

e at

i

n

g

c

h

a r c o a

l

to

7 5 0

-

9 0 0

°

C in

the

pr e sen c e o

f

v apo r

i

z e

d l

o

w

a s

h

s ul

fi

j r

(

A

T

SD R

, 1

9 9 6

)

.

S i

n c e t

h

e e a r

l

y n

in

ete enth c e ntu ry,

C S

2

h

a s

b

e e n u s e

d i

n t

h

e

m

a n u

fa c

tu r e o

f

s u

l fi

i r

m

atc

h

e s, e x tr a ct

io n

o

f f

ats, c o

l d

v u

lc a n

iz a

tio n o

f

r u

b b

e r, synthe s

is o

f

ot

h

e r c

h

e

m i

c a

l

s

(

e.

g

.

, c a r

b

o n tetr a c

h l

o r

i d

e

)

, a s a r e a cta nt

i

n t

h

e

m

a n u

f

a ctu r e o

f

ce

l l

op

h

ane, a n

d i

n t

h

e

c o n v e r s

i

o n o

f

c e

l l

u

lo s e

in

to r ayo n

f

i

b

e r s

(

A T S D R

,1

9 9 6

,

G

r a

h

a

m

, et a

l

.

19 9 5

,

K l

a a s s e n,

19 9 6

)

.

M

a ny o

f

t

h

e s e u s e s

h

a v e

b

e e n

p h

a s e

d

o ut o v e r t

h

e ye a r s

b

y r ep

la c

in

g

C S

2 w

i

t

h

othe r s o

l

v e nts.

W

h i

le t

h

e

C h

e

m i

c a

l m

an u

f

a ctu r

in

g

in

d

u stry st

i l

l u s e s C Sj to synt

h

e s

iz e

othe r c

h

e

m

ic a

l

s, t

h

e

l

a rge st u s e r o

f C S

j

i

s st

i l l

t

h

e v

is c o s e

-r ayo n

i

n

d

u stry.

S i

n c e

C S

j

s e r v e s a s a r e age nt r at

h

e r t

h

a n a s o

lv e

nt

i

n t

h

e c o n v e r s

io n

o

f

c e

l l

u

l

o s e to

l i

qu

i d

v

i

s c o s e,

le s s

to x

i

c c o

m

po i

m d

s a r e n ot c u r r e nt

l

y a v a

i l

a

b l

e

(

Dr e x le r, et a

l

.

19 9 3

)

.

A

c c o r

d i

n g to

the

la

te st

d

ata a v a

i l

a

b l

e

fr

o

m

t

h

e

T

o x

i

c

R

e

l

e a s e

I

n v e nto ry

(

T R

I

,

19 9 8

)

, o v e r

4

3

,

4 4 6

,

4 15

p

o un

d

s o

f C S

2

w

e r e r e

l

e a s e

d

to t

h

e a

i

r

d

u r

i

ng t

h

at ye a r;

h

o

w

e v e r , t

h

e

m

o st

s

i g

n

i f

i c a nt e xpo s u r e s o c c u r

in

o c c upat

io n a

l

s et t

in

gs. T

h

e

m

a

i

n r o ute o

f

e x

p

o s u r e

i

s

thr o ug

h i

n

h

a

l

at

i

o n a

l

tho u

g h

s

i

gn

i fi

c a nt a

b

s o r p t

i

o n t

hr o u

gh

t

h

e s

k in

c an a

l

s o o c c u r. In

o c c upatio n a

l

s et tin gs, a c o

m b in a

t

io n

o

f

t

h

e s e t

w

o r o ute s

i

s

l i k

e

l y

.

(7)

1.2 C he

m

ic al an

d

P h ysic al Pr oper tie s

C S

2

i

s v e ry v o

la

t

i l

e, a n

d

a ny r e

l

e a s e s to t

h

e env

ir o n

m

e nt r e s u

l

ts

i

n

q

u

i

c

k

v o

l

at

i l i

z at

i

o n

to t

h

e at

m

o sp

h

e r e

(

A

T

S

D R, 1

9 9 6

;

K l

a a s s e n , 1

9 9 6

)

. H o

w

e v e r ,

C S

j

h

a s a lo

w

a

f fi

n

i

ty

f

o r s o

i l

; t

h

e r e

f

o r e,

i f la r

ge a

m

o unts a r e sp

i l l

e

d

, s o

m

e

m

ay

b

e tr anspo rte

d i

nto

gr o u n

dw

ate r. T

h

e c

h

e

m

i

c a

l

i

d

e nt

i

ty a n

d

t

h

e p h ysic al a n

d

che

m i

c a

l

pr ope rt

ie s o

f

C

S

j

c a n

b

e

f

o i

m d i

n

T

a

b le s

1

-

1

a n

d 1

-

2

, r e s

p

e ct

i

v e

l

y.

1.

3

M

eta

b

o

l is

m

W

h

et

h

e r t

h

e e x

p

o s u r e to

C S

2 o ccu r s t

h

r o ug

h i

n

h

a

l

at

i

o n, o r a

l

, o r

d

e r

m

a

l

r o ute, t

h

e

a

b

s o rpt

i

o n

is s u

b

stan t

ia

l

an

d

r ap

i d

. T

h

e

C S

j

is

ta

k

e n u

p i

n t

h

e

b l

o o

d

an

d d i

str

i b

ute

d

t

h

r o ug

h

o ut t

h

e

b

o

d

y

(

A T SD R

,

19 9 6

)

.

D

u e to t

h

e

l i p

o

p h i l i

c n atu r e o

f C S

2,

i

t

i

s

m

a

in

l y

d

epo s

i

te

d i

n

l i

p

i d

-r

i

c

h

o r

ga n s s u c

h

a s t

h

e

b

r a

i

n a n

d l i

v e r

w h

e r e

i

t

i

s

m

eta

b

o

l iz e

d

to

t

h i

o c a r

b

a

m

ate s.

(

A

T

S

D R

, 1

9 9 6

;

C

o x et a

l

.

, 1

9 9 2

)

. Te

i

s

i

nge r an

d S

o u c e

k

(

1

9

4

9

)

r epo rte

d

t

h

at r ap

i d

a

b

s o r

p

t

i

o n o ccu r r e

d i

n

h

u

m

a n s u

b

j

e cts.

Su

b

j

e cts

w

e r e e xpo s e

d b

y

in

h

a

l

at

i

o n to 1 7

-5 1

p

p

m

f

o r 1

-4

h

o u r s. T

h

e a

m

o i

m

t o

f C

S

j a

b

s o r

b

e

d w

a s

m

e a sur e

d b

y

d

ete r

m i

n

i

ng

l

e v e

l

s

i

n

i

n s

p i

r e

d

a

i

r, e x

p i

r e

d

a

i

r,

b l

o o

d

a n

d

u r

i

ne u nt

i l i

t

h

a

d d i

s a

p p

ea r e

d

f

r o

m

t

h

e

b lo o

d

an

d

u r

i

n e. T e

i

s

i

n

g

e r a n

d So u c e

k

(

19 4 9

)

f

o u n

d

t

h

at

8 0

%

o

f

t

h

e

i

n

h

a

le

d

C S

j

w

a s r eta

i

n e

d d

u r

i

ng t

h

e

fi

r st

fi ft

e e n

m

in u

te s o

f

e x po s u r e an

d

t

h

en

d

e c r e a s e

d

to

a

b

o ut 4

0

%

a

ft

e r 4 5

m

in

u te s. Ve ry

l i

tt

le

(

0

.

0 6

%

)

o

f

t

h

e

C S

j

w

a s e

l i

m

in a

te

d i

n t

h

e u r

in e

.

(8)

T

a

b l

e

1

-

1

.

C h

e

m

i

c a

l I d

e n

t

i

t

y

o

f C

a r

b

o n

D i

s u

l fi d

e

*

C hara cteri stic Information Refe r e n c e

C hem ic alname

S ynonym

(

s

)

Reg iste r ed t

ra

de n ame

(

s

)

C hemic al fo rmu la

Chemic al s tr uctur e

Ca rbo n dis ul fi de H SD B 1 9 9 5

Ca rbo n b isul p hi de;c a rbon H S D B 19 9 5 dis ulp h i de;c a rbo n s ul fi de;

carbon s ul p h i de; d ith io carbonic

a nh y dri de; s ulpho c a rbo nic anh yd ri de

W

eevi lt ox® H S D B 1 9 9 5

Casw el l No. 1 6 2® H S D B 19 95

CS,

S=C=S

I de nti fi c atio n n um be r s :

CA Sreg istry N IO SH R T EC S

E PA ha z a rdo u s wa ste

OH

M

/TAD S

D OT/UN /N A /I

M

CO sh i p p ing

H SDB NCI

7 5-15-0

F F 6 6 50 0 00

P 0 2 2

(

pu r e

)

F-00 5

(

a s a mix tu r e c ompone nt

)

7 2 16 6 3 3

UN 1 131 ; I

M

C O 6 1

52 C 04 5 9 1

H SD B 1995 H S D B 199 5

H S D B 19 9 5

H S D B 19 95 H SD B 1995

H S D B 19 9 5

H S D B 19 9 5

C A S = C hemical A bstra cts Se r vic e s; DOT / UN/ N A / I

M

CO = De

partme nt of Tr anspo rtatio n/U nited Natio n s/ No rth Ameri c a/ In te

m

atio n al

M

ari time D ange r o u sGo ods Code; E P A = En vir o nme ntal Pr ote ctio n

A ge n cy ; H S DB = Ha z a rdo u s Substanc e s Data Ba nk ;NC I = N atio n al Ca n cer In stitute

; N I OSH = Natio n al In stitut e fo r Occ upa tion al Safety a nd He alth ; O H

M

/ TAD S = O il a nd Haz a rd

o u s

M

ateri als/ Te chnic al

As sist an c e Data S ystem; R T E C S = Registryo fTo xic Eff e cts of Chemic al Substanc e s

*

S

(9)

T

a

b l

e

1

-

2

*

P

h

y

s

ic a

l

a n

d C h

e

m i

c a

l

P

r o

p

e rt

i

e s o

f C

a r

b

o n

D

i

s u

l

f

i

d

e

Propert y Informa ticm Refe re n c e

M

ole c ula r w eig

h

t Colc M

-P h ysicalstate

M

el ti ng point

Boi l ingpoint De n sit

y at l S

X

a t 20°C a t3 0°C O do r

Odo r thr e shold:

W

ater Air

So lub il ity:

W

a t e r

a t2 0°C at2 2°

C Orga n ic s o lvents

76. 14

C le a r, c olo rle s s, o r fain tly yel low Colo rle s s

H igh ly r efr a c tive, mob ile l iqui d

-1 10 .8

°

C

-1 11 .5

°

C 46.5

"'

C

(

at 7 6 0 to r r

)

1.2 7 0 55 g / mL 1.263 2 g /

m

L 1.2 4 81 g / m L

Pu r e s td isti llates have

swe et, ple a sing, a nd e the r e al odor; c om me r cial and re age n t grades a re fo ul s

m

ell ing

0.00 2 6 m g / L

(

faint odo r

)

0.31-0.6 5 m g / m

^

(

0.1- 0.2 ppm

)

low = 0.0243 mg/ m

^

(

0.008 p pm

)

hig h = 2 3.1 m g / m

^

(

7.39 p pm ) 0.3 1 m g/m

^

(

0. 1 pp m ) (r e spo nse in 5 0

%

of s ub

j

e c t s)

0.6 5 m g/m ^

( 0.2 pp m ) (r espo n s e in 100% of s ub

j

e c t s

)

0.0 5 mg/ m ^

(0

.0 2 p pm

)

(

pe r c ep tio n in huma n s) 0.04 m g / m

^

(0

.01p p m )

(

n onpe rc eption w ith adve r s e r ef le x respons e in huma n s

)

29 40 m g/ L 2 300 m g/ L

M

is cJble w ithanh ydrous metha n ol, cthan ol, ethe r, be nze n e, ch loro

¬ form, c arbo n tetr a ch lo ri de,

W

ind holz 19 8 3 Sa x a nd Lew is 19 87

W

in tto olz 19 8 3

W

ind holz 19 83

W

e a st 19 89 H S D B 19 9 5

W

ind holz 198 3

W

ind holz 1983

W

in tUiolz 198 3

W

ind holz 19 8 3 F lick 1985;

W

ind ho lz 19 8 3

Ve rs chu e re n 19 8 3 AC G I H 19 86 Ruth 1986 Ruth 198 6

M

CA 196 8

M

CA 1968

Ve rschu eren 19 8 3

Ve r s chu e r e n 19 8 3

W

ind holz 19 8 3 Vers chue ren 19 8 3

(10)

T

a

b

l

e

1

-

2

*

P

h y

s

i

c a

l

a n

d

C h

e

m i

c a

l P

r o

p

ert

i

e s o

f C

a r

b

o n

D i

s u

l f

i

d

e

(

c o nt inu e

d

)

Prope rt y Informatio n Refe re nce

Pa rtitio n co ef ficie n t s :

Log K«

Vapo r pres sure at lO'

C

at I

C

C at 2 0°

C

atl O' C at 2 5'

C at 30°

C

He n ry's law c o n sta nt Autoi gnition t em peramr e

Fla sh point

Fla o u n abil it y li

m

its in air

Co n v e r sion factors Exp lo siv e l im it s

1.8 4- 2

.16

(

calculated

)

1.8 0

127.0 n u nHg 2 0 0 m

m

H g

26 0m m Hg 29 7.5m

m

H g 352.6 m m H g 43 0 m

m

H g 1.2 2x 10-^

atm m

V

mo l 10 0°

C

12 5- 135 ' C

-3 0°C

(

closed c up

)

1- 5 0

% (

v/v

)

*

(

e xp losiv e ra nge

)

1.3- 50

%

0.3 2 p p m = 1

m g / m^ lowe r = 1%

up per = 50

%

Ve r schuere n 1978 H S DB 1995

Fl ick 19 8 5 Ver schu ere n 1983 Vers chuere n 19 83 T i m mcrman 19 78

W

orthing 198 7 V e r s chu e r e n 19 8 3 E P A 19 8 1

W

ind holz 19 8 3; Sa x a nd Lewis 19 87

W

ort h ing 1987 N F PA 19 86; Sax a nd

Lew is 19 87 ;

W

ind holz 1983 F l ick 198 5;

W

ind holz 19 8 3 NF P A 1986 ;

W

eiss 19 80

Be a u champ etal. 19 8 3 O H

M

T A D S 1995

"

v/v = pe r c e n t "v olume in volu

m

e,

"

wh ich ex pre s se s t he n um be r of m i l li l iters of pu re analy te vapo r in 10 0 m i l iili tere o f air mixture

(

AC G I H 199 5

)

S

(11)

the retain ed C Sj

w

a s e xhaled a nd le s s tha n 1

%

w

a s e x c r eted in the uri n e. T h is ind icate

d

t

h

at

7 0

-

9 0

%

o

f

the c a r

b

o n

d i

s u

l fi d

e

w

a s

m

eta

b

o

l i

z e

d

.

P h

ys

i

c a

l

e x e rt

io n

in c r e a s e s

t

h

e

i

n

h

a

la

tio n an

d

a s a r e s u

l

t in c r e a s e s the inte r n a

l d

o s e o

f

C Sj

(

Dr e x

l

e r, et a

l

., 1

9 9

3 ; Co x,

19 9 2

)

.

St

u

d i

e s o

f

r ats a

l

s o

i

n

d i

cate

C S

j

i

s

q

u

i

c

k l

y a

b

s o r

b

e

d

a

ft

e r

in

h

a

l

at

i

o n e x po su r e

(

A T SD R

,

19 9 6

)

.

M

c

K

e nna a n

d D i St

e

f

ano

(

19 7 7

a

)

e xpo s e

d m

a

l

e

S

pr agu e

-D

a

w l

ey r ats to

6 4 0

p p

m

C S

j. T

h

ey r e

p

o rte

d

an e x

p

o n e nt

i

a

l in c r e a s e

in

C S

2

in

b l

o o

d w h i

c

h

r e a c

h

e

d

ste a

d

y state

a

ft

e r

9 0 m i

n ute s.

A ft

e r e x

p

o s u r e stop pe

d

, the e

l i

m

i

n at

i

on o

f b l

o o

d C S

j

w

a s

b i

p

h

a s

i

c

w i

th

h

a

l f

-

l iv e s o

f 6

a n

d 8

5

m

i

n ute s.

C S

j c o n c en tr atio n s r e a c

h

e

d

ste a

d

y state a r o un

d

4-

5

h

o u r s. Lo s s o

f fi

"

e e

C S

j

w

a s r ap

i d in

a

l l

t

i

s s u e s e x c ept the

l i

v e r an

d k i d

n eys

(M

c

K

e r

m

a

a n

d

D

i St

e

f

a n o, 1

9 7 7

a

)

.

Be a u c

h

a

m p

et a

l

(

19 8 3

)

pu

b l i

s

h

e

d

a c r

it

i

c a

l

r e v

i

e

w

o

f l i

te r atu r e on

C S

j to x

ic

it

y

in

19 83

.

F

i g

u r e 1-

1 d

ep

ic

ts t

h

e

m

eta

b

o

l ic

pat

h w

ay s pr opo s e

d b

y Be a u c

h

a

m

p et a

l

.

R

e a ct

io n

(

i

)

h

a s

b

e e n

d

e

m

o n str ate

d i

n v

iv

o a n

i

m

a

l

stu

d i

e s, r e a ct

i

o n s

(

i i

-v

)

i

n v

i

tr o stu

d i

e s, a n

d

r e a ct

i

o n s

(

v

i

-

i

x

)

a r e pr o

p

o s e

d m

eta

b

o

l i

c pat

h w

ays

in

a n

i

m

a

l

s an

d h

i

m

i a n s.

A

c c o r

d i

n g to

Be a u c

h

a

m

p et a

l

.,

C S

j

i

s

fi

r st

m

eta

b

o

l i

z e

d b

y cyto c

hr o

m

e P -4 5 0

to an u n sta

b l

e o x y ge n

i

nte r

m

e

d ia

te

(

r e a ct

i

o n

i

)

. T

h

e o xy ge n

in

te r

m

e

d ia

te e

it

h

e r

d

egr a

d

e s to ato

m i

c s u

l f

u r an

d

c a r

b

o ny

l

s u

l fi d

e

(

r e a ct

i

o n

i i

)

o r

h

y

d

r o

l

yz e s to

f

o r

m

ato

m

i

c s u

l fi

i r an

d

m

o n ot

h i

o c a r

b

o n ate

(

r e a ct

i

on

i i i

)

. T

h

e

A

to

m ic s u

l f i

a r e

i

t

h

e r c o v a

l

en t

l

y

b i

n

d

s to

m

a c r o

m

o

le c u

le s

(

r e a ct

i

on

iv

)

o r

i

s o x

i d i

z e

d

to

p

r o

d

u cts s u c

h

a s s u

l f

ate

(

r e a ct

i

o n v

)

.

U

n

l i k

e an

i

m

a

l

s

(12)

ON

F ig

u r e

1

-

1

.

P

r o

p

o s e

d

M

e

t

a

b

o

l i

c

P

a

t

h w

a

y

s

f

o r

C

a r

b

o n

D i

s u

l fi d

e *

G S H

A

m

i

n o a c

i d

s

^

H S

-

C

-

N H

-

R

H S

-

C

-

SG

* ^

C H

, -

C

H

-

C O O H

S

N H

C y

s

t

e

i

n e

-H S

-

C

-

S

-

R

(

i

)

(

t

h i

az o

l id i

n e>

2

-th i

o n e-

4

-c a r

b

o x

y l i

c a c

i d

)

?

C H

-

C H

-

C O O H

S

N H

\

/

C

li

o

G S H

(

2

-o x -o

th

i

a z o

l i d i

n e-

4

-c a r

b

o x

y l i

c a c

i d

)

S

=

C

=

0

U

r e a

I

\

_

c

y

c

l

e

I

O

j ,

N A D P

M

F O

S

=

C

=

S

^

.

0

(

»

)

/

C

o v a

l

e n

t

b i

n

d i

n

g

m

a c r o

m

o

l

e c u

l

e s

(

V

C

a r

b

o n

i

c a n

h

y d

i

I I

(

D i

t

hi

o c a r

b

a r

m

a

t

e s

)

i

A

o

=

c

c

=

s

C H

j

-

N

H

(

2

-

th

i

o -

5

-

thi

a 2 o

l i di

n o n e

)

"

S

=

C

-

0

-

:

H S

-

C

=

0

S

t

T h i

o u r e a

H

2

N

-

d

N H

2

(

i

x

)

H

(13)

s ul fu r to s ul fate in hu

m

ans do e s n ot c o ntri

b

ute si gn

i

fi c an t

l

y to the

m

eta

b

o

l i

s

m

o

f

C Sj.

T h

e c a r

b

o ny

l

s u

l f

i

d

e

f

o r

m

e

d i

n rea ct

i

o n

(

i i

)

m

ay

b

e c o n v e rte

d

to

m

o n ot

h i

o c a r

b

o n ate

b

y

c a r

b

on

i

c a n

h

y

d

r a s e

(

r e a ct

i

on v

i i i

)

.

M

on ot

h i

o c a r

b

o n ate

m

ay

d

egr a

d

e

i

n r e a ction

(

i

x

)

,

r e

g

e n e r at

i

ng c a r

b

o n

y l

s u

l fi d

e o r

f

o r

m

i

n

g

c a r

b

o n

d i

o x

i d

e a n

d

s u

l fi d

e

b i

s u

l fi d

e

i

o n

(

H S

"

)

(

r e a ct

i

o n v

i i

)

. T

h

e

H S

"

c a n t

h

e n

b

e o x

i d i

z e

d

to s u

l f

ate o r ot

h

e r n onv o

l

at i

l

e

m

eta

b

o

l i

te s

(

r e a ct

i

on v

i

)

.

1.

4 T

o x

i

c

E f f

e cts

C S

2

h

a s

b

e e n a

h

e a

l

t

h

c o n c e r n

i

n t

h

e v

i

s c o s e r ayo n

fi b

e r pr o

d

u ct

i

o n

b

e c a u s e o

f i

ts

m

any

e

f f

e cts s u c

h

a s c e ntr a

l

a n

d p

e r

i p h

e r a

l

n e u r oto x

i

c

i

t y,

i

n c r e a s e

d

c a r

d i

o v a s c u

l

a r

m

o rta

l i

t y,

i

n

j

u ry to t

h

e s ens o ry o rga n s, an

d d i

stu r

b

a n c e s

i

n

h

o r

m

o n a

l

a n

d

r epr o

d

u ct

i

v e

f i m

ct

i

on s

(

B

e a u c

h

a

m

p et a

l

.,

19 8 3

;

R i i h i m

a

k i

, 1

9 9 2

)

.

S

e v e r a

l

e

p i d

e

m i

o

l

og

i

c a

l

stu

d i

e s

h

a v e

r epo rte

d

an

i

n c r e a s e

i

n

m

o rta

l i

ty a

m

ong v

i

s c o s e r ayo n

w

o r

k

e r s e x po s e

d

to c a r

b

o n

d i

s u

l fi d

e.

(

H

e

m

b

e rg , et a

l

.

,

19 7 0

,

19 7 3

;

T

o

l

o n e n et a

l

.

19 7 5

,

19

7

9

)

. T

h

e s e

w

o r

k

e r s

w

e r e po s s

i b l y

e x po s e

d

t

h

r o u g

h

m

u

l

t

i

p

l

e r o ute s to

C S

j a n

d

to ot

h

e r c

h

e

m

i

c a

l

s; t

h

e r e

f

o r e,

n o

d

e

f

i n

i

t

i

v e c o n c

l

u s

i

on s c a n

b

e

m

a

d

e r ega r

d i

ng

i

n

h

a

l

at

i

on e xpo s u r e a n

d d

e at

h

.

H

o

w

e v e r , s o

m

e o

f

t

h

e stu

d i

e s a r e

d i

s c u s s e

d f

u rt

h

e r

b

e

l

o

w

.

A

n

i

n

h

a

l

at

i

o n stu

dy

c o n

d

u cte

d w i

t

h p

r e

g

n a nt r ats e x

p

o s e

d

to

64 2

p p

m C S

j

p

r o

d

uc e

d

3 3

% m

o rta

l i

t y a

m

o ng

d

a

m

s. Pr egn an t r ats e x

p

o s e

d

to

2 2 5

p

p

m

C S

2

p

r o

d

u c e

d 3 5

%

m

o rta

l i

t y a

m

ong

p

ups

(

Le

h

otz

k

y et a

l

.

19 8 5

;

A T S

D

R

(14)

S

p y

k

e r et a

l

r eporte

d

t

h

at 2

7

pe o

p l

e

w

e r e e x

p

o s e

d

to

C

S2 a

ft

e r a r ai lr o a

d

a c c

i d

e nt.

R

e sp

i

r ato ry c

h

a nge s

i

nc

l

u

d

e

d

r e

d

u c e

d

v

i

ta

l

c a

p

a c

i

ty a n

d d

e c r e a s e

d

pa rt

i

a

l

pr e s s u r e o

f

a rte r

i

a

l

o xy ge n.

(

Sp

y

k

e r,

19 82

)

.

N

o

i

n

f

o r

m

at

i

o n o n e xpo s u r e c o n c e ntr at

i

o n s

w

a s

a v a

i l

a

b l

e.

S

e ver a

l

e

p i d

e

m i

o

l

o

g i

c a

l

stu

d i

e s

h

a v e r e

p

o rte

d i

n c r e a s e

d m

o rta

l i

t y

f

r o

m

c a r

d i

o v a s c u

l

a r

d i

s e a s e a

m

o n g

C S

j e xpo s e

d w

o r

k

e r s

(

He

m

b

e rg, 1

9

7

0

;

T i l l

er,

19 6 8

;

B

a

l

c a r o v a,

1 9 9 1

)

.

T

i l l

e r et a

l

.

(

19 6 8

)

, c on

d

u cte

d

a r etr o s

p

e ct

i

v e stu

d

y o

f 2 2 3

v

i

s c o s e r ayo n

w

o r

k

e r s an

d

r e

p

orte

d

a stat

i

s t

i

c a

l l

y s

i g

n

i fi

c a nt

i

n c r e a s e

(

2

.

5

-

f

o

l d

)

i

n

d

e at

h

s

d

u e to co r o n a r

y

h

ea rt

d i

s e a s e

fr

o

m

19 3 3

to

19 62 b

et

w

e e n

C S

j-e x

p

o s e

d

a n

d

n o n e x

p

o s e

d w

o r

k

e r s

i

n t

h

e s a

m

e

p

l

ant.

T h

e

w

o r

k

e r s

w

e r e e xpo s e

d f

o r

m

o r e t

h

an 1

0

ye a r s to

C S

j

l

e v e

l

s a

b

o v e 2

0

p p

m

(

T

i l l

e r,

19 6 8

;

C

o x ,

19 9

2

)

.

T

o

l

o n e n et a

l

(

19 7 9

)

, c o n

d

u cte

d

a pr o spe ct

i

v e

m

o rta

l i

t y stu

d

y

(

1

9 6 7

-

1 9 7 7

)

i

n

w h i

c

h 3

4 3 v

i

s c o s e r ayo n

w

o r

k

e r s

w

e r e

i

n

d i

v

i d

u a

l l

y

m

atc

h

e

d w i

t

h

w

o r

k

e r s

fr

o

m

a

l

o c a

l p

ape r

m i l l

.

T h i

s stu

d

y r epo rte

d

n o s

i g

n

i f

i c a nt

d i ff

e r e n c e s

i

n

l i f

e st y

l

e s o

f

t

h

e t

w

o gr o ups. T

hi

s stu

d

y a

l

s o r epo rte

d

a

2

.

5

-

f

o

l d i

n c r e a s e

i

n

d

e at

h d

u e to

c o ron a ry

h

e a rt

d i

s e a s e a

m

o ng v

i

s c o s e r ayo n

w

o r

k

e r s.

N

ur

m i

n e n a n

d H

e

m

b

e r

g

(

1

9 8 5

)

d i d

a

f

o

l l

o

w

-up stu

d

y o

f

t

h

e s a

m

e

w

o r

k

e r s to

d

ete r

m i

n e t

h

e

i

n c

i d

e n c e o

f

c a r

d i

o v a s c u

l

a r

m

o rta

l i

t y

fr

o

m

19 6 7

to

19 8

2. T

h

e e xpo sur e s r a nge

d fr

o

m

2 2

- 1

O

p p

m

w i

t

h

a

d

e c r e a s e

i

n e x

p

o s u r e a

ft

e r

19 7 2

. Fo r t

h i

s r e a s o n

d i ff

e r e nt ye a r s

w

e r e gr o upe

d f

o r a n a

l

ys

i

s.

F

r o

m

1

9

6 7- 1

9 7

4 t

h

e r e

w

a s a 4

.7

-

f

o

l d

in c r e a s e

i

n

m

o rta

l i

t

y c o

m

pa r e

d

to t

h

e pape r

m

i l l

w

o r

k

e r s.

D

u r

i

ng t

h

e pe r

i

o

d 19 7 2

-

19 7 4

, t

h

e r

i

s

k

r at

i

o

d

r op

p

e

d

to

3

.2.

W

o r

k

e r s

w i

t

h

h i

g

h

c o r o n a ry r

i

s

k f

a cto r s

w

e r e r e

m

o v e

d fr

o

m

e x

p

o s v i r e,

w h i

c

h

r e s u

l

te

d i

n a r

i

s

k

r at

i

o o

f

(15)

1.0

d

uri n g the ye a r s 1 9 7 4 - 1 9 8 2

. Balc a r o v a et al.

(

1 9 9 1

)

, als o r epo rted s

i

gni fi c a ntl y

h i

g

h

e r

m

o rta

l i

t y

fr

o

m

c a r

d i

o v a s cu

l

a r

d i

s e a s e a

m

ong e xpo s e

d

v e r s e s un e xpo s e

d

w

o r

k

e r s. T

h

e

y

a

l

s o r epo r te

d

t

h

at a

m

o ng t

h

o s e e xpo s e

d

, t

h

e

w

o r

k

e r s

w i

t

h

"

h i

g

h

"

e x po s u r e s

h

a

d

a

h i

g

h

e r

m

o rta

l i

ty r ate t

h

an t ho s e

w i

t h

l

o

w

e x po s u r e s to

C

S

j.

S

e v e r a

l

st u

d i

e s

h

a v e

d

e

m

o n str ate

d

t

h

at

C S

j a

f f

e cts

l i

v e r e n zy

m

e s.

S

e r u

m

c

h

o

l

e ste r o

l

s o

m

et

i m

e s

i

n c r e a s e s a

ft

e r e x po s u r e to

C S

j

p

e r

h

a

p

s a s a r e s u

l

t o

f i

n c r e a s e

d h

e

p

at

i

c c

h

o

l

e ste r o

l

syn t

h

e s

i

s

(

A T S D R

,

19 9 6

)

.

T

h

e

m

o st c o

m

m

o n an

d w

e

l l d

o c u

m

e nte

d

ta r

g

et o

f C S

j s e e

m

s to

b

e t

h

e n e r v o u s syste

m

.

A l

m

o st e v e ry pa rt o

f

t

h

e pe

ri

p

h

e r a

l

a n

d

c e ntr a

l

n e r v o u s syste

m h

a s

b

e e n s

h

o

w

n to

b

e

a

f f

e cte

d b

y c

h

r o n

i

c

C S

j e x po s u r e

(

A

T

S D R

, 1

9 9 6

)

.

P h y

s

i

o

l

o

g i

c a

l

, a s

w

e

l l

a s

b

e

h

a v

i

o r a

l

,

c

h

an

g

e s

h

a v e

b

e e n r e

p

o rte

d i

n

p

e r s o n s e x

p

o s e

d

to

C S

2. Repo rte

d b

e

h

a v

i

o r a

l

c

h

a n

g

e s

i

n c

l

u

d

e c o n

f

u s

i

o n,

i

r

ri

ta

b i l i

ty,

i

n s o

m

n

i

a, o v e rt

p

syc

h

o s

i

s, s u

i

c

i d

a

l

ten

d

e n c

i

e s,

m

e

m

o ry

d

e

f

ects, a n

d

r ap

i d

c

h

a nge s

i

n

m

o o

d

(

Ba

k

e r,

19 8 3

)

.

G

r a

h

a

m

et a

l

.

(

19 9 5

)

r epo rte

d

t

h

at

t

h

e

m

o st c o

m m

o n c

h

r o n

i

c p

h

ys

i

o

l

o g

i

c a

l

e

f f

e ct

i

s a

d i

sta

l

s e n s o

ri m

oto r ne u r opat

h

y.

T h i

s

h

a s

b

e e n c o n

f i

r

m

e

d i

n a n

im

a

l

stu

d i

e s a s n e u r o

fi l

a

m

e nto u s a x o n o

p

at

h

y

p ri m

a

ri l

y

a

f f

e ct

i

n

g l

o n

g

a x o n s.

(

G

r a

h

a

m

, 1

9 9 5

)

.

E

n c e

p h

a

l

opat

h

y

h

a s a

l

s o

b

e e n r e

p

o rte

d

a

ft

e r

c

h

r o n

i

c

l

o

w

-

l

e v e

l

e x

p

o s u r e s;

h

o

w

e v e r,

i

t

i

s st

i l l

u n c

l

e a r

i f

t

h i

s

i

s a

d i

r e ct to x

i

c o

l

o

g i

c a

l

e

f f

e ct o

f C S

j e x

p

o s u r e o r a r e s u

l

t o

f

t

h

e

i

n c r e a s e

i

n c

h

o

l

e ste r o

l

a n

d h i gh

e r

b l

o o

d

pr es su r e r e

l

ate

d

to

C S

(16)

O

n e o

f

t

h

e

m

a

i

n

h

e a

lt

h

e

f f

e cts r e s u

l

tin

g fr

o

m C S

2

i

n

h

a

la

t

io n

e x

p

o s u r e

i

s n e u r oto x

i

c

e

f f

e cts

(

A

T

SD

R

,

19 9 6

)

.

A l

m

o st e v e ry pa rt o

f

t

h

e c e ntr a

l

a n

d

pe r

i

p

h

e r a

l

ne r v o u s

s

y

ste

m

s

is a

ff

e cte

d b

y c

h

r o n

ic

C S

j e x po s u r e

(

B

a

k

e r,

19 8 3

)

.

T h

e r e

h

a v e

b

e e n a n u

m

b

e r

o

f

stu

d ie s

,

b

ot

h

c

l i

n

ic a

l

a n

d

e xpe r

i m

e nta

l

, t

h

at c ons

i d

e r e

d

t

h

e

m

e c

h

a n

i

s

m

w h

e r e

b

y

C S

j

pr o

d

u c e s n e u r oto x

ic

le s

i

o n s

(

M

c

K

e nn a an

d D i St

e

f

a n o, 197 7 ;

B

u s, 1 9

8

5 ;

M

a

g

o s, 1 9 7 2

)

.

S

o

m

e o

f

t

h

e

h

y pot

h

e s e s

f

o r

C S

j n e u r o

p

at

h y i

nc

l

u

d

e

d ir e c

t e n zy

m

at

i

c

i

n

h i b i

t

io n

, to x

i

c

e

ff

e ct o

f C S

2

m

eta

b

o

l i

te s, a n

d

c

h

e

l

at

i

o n o

f

o

l i g

o e

l

e

m

e nts

(M

a r o n

i

et a

l

.

, 1

9

7

9

)

.

A

s

e a r

l

y a s

19 5 6

,

S

o u c e

k

a n

d

M

a

d l

o r epo rte

d

t

h

at

C S

j

in

the

b

o

d

y r e a cts

w it

h

a

m

i

n o a n

d

t

h i

o

l

gr o ups r esu

lt

i

ng

i

n t

h

e

f

o r

m

at

i

on o

f d i

t

h i

o a n

d

tr

i

th io c a r

b

a

m

ates

(M

ago s,

19 7 2

)

.

T h

e s e

m

eta

b

o

l it

e s a r e

k

no

w

n to

f

o r

m

n o n-

i

o n

i

z e

d

c o

m

p

l

e x e s

w i

th po

l

yv a

l

e nt

m

eta

l i

o n s

(

D

j

u r

i

c,

19 6 7

)

.

C

o

h

e n et a

l

(

19 5 6

)

a n

d S

c

h

e e

l

(

19 6 5

)

su spe cte

d

t

h

at c

h

e

l

at

i

n

g

str u ctur e s o

f

the s e c o

m p

o un

d

s r epr e s en te

d

a

b

a s

i

c

m

e c

h

an

i

s

m

o

f C S

j to x

i

c

i

ty .

C

o

h

e n

et a

l

a n

d S

c

h

e e

l

c o n

fi

r

m

e

d b i

o

lo

g i

c a

l

c

h

a n

g

e s

i

n v o

lv

i

n

g m

eta

l

-s

h i f ts

i

n a n

i

m

a

l

s e x

p

o s e

d

to

C S

2

(M

ago s, 1

9

7

2

)

t

hr o u

g h

a n e x

p

e r

im

e nt

w h

e r e r a

b b i

ts

w

e r e c

h

r o n

ic a

l l

y e x po s e

d

to

7

5

0

p p

m

C S

2

(

B

r

i

e

g

e r, 19 6 7

)

.

T h

e pr e s e n c e o

f d i

t

h io c a r

b

a

m

ate s a n

d

t

h ia z o

l i d

o n e

w

a s

c on

fi

r

m

e

d b

y u

l

tr a v

i

o

le

t spe ctr op

h

oto

m

etry

(

Br

i

ege r, 19 67

)

.

T h

e

d i

str

i b

ut

i

o n o

f

c o

p p

e r

a n

d

z

i

nc

i

n t

h

e t

i

s s u e s o

f

e x po s e

d

r a

b b i

ts

d i f f

e r e

d

gr e atly t

h

a n t

h

e c o ntr o

l

s. Ra

b b i

ts that

w

e r e

g i

v en

d i

etar

y

s u

p p l

e

m

e nt s c onta

in

in

g

c o

p p

e r, z

in c

, c o

b

a

l

t,

m

an

g

a n e s e,

i

r o n, a n

d

c a

l

c

i

u

m

s

h

o

w

e

d l

e s s

w

e

i

g

h

t

l

o s s an

d

n o to x

i

c

i

n

j

u ry

(

B

r

ie

ge r, 1

9 6

7

)

.

M

c

K

e nna a n

d

D

i

ste

f

ano

(

19 7 7

)

r epo rte

d

a

d

e c r e a s e

i

n t

h

e a ctiv

i

ty o

f

c op pe r

-r equ

i

r

in

g e n zy

m

e,

d

opa

m

in e

-P

-h y

d

r o xy la s e, in r e spo n s e to in c r e a s e

d

C Sj inhalatio n e x po s u r e

(

A T S D R,

19 9 6

)

. Lu

k

a s et a

l

.

(

1

9 7 4

)

m

e a s u r e

d

z

i

n c a n

d

c o

p p

e r c on c e ntr at

i

o n s

in

the ner v e

(17)

tis s u e s of C S2 expo sed r ats.

W

h i le he d i d n ot f ind a si gn i f ic an t d i f fe r enc e in the a

m

o u nt

o

f

z

i

n c

i

n e x po s e

d

v e r s e s the c o ntr o

l

r ats, t

h

er e

w

a s a s

i g

n

i f i

can t

d i ff

e r enc e

in t

h

e

le v e

l

o

f

c o

p p

e r

f

o u n

d i

n t

h

e n e r v e t

i

s s u e

(

L

u

k

a s et a

l

., 1 9

7

4

)

.

L

u

k

a s

(

1

9

7

0

)

a

l

s o c o n

fi

r

m

e

d i

n

a n e a r

l i

e r stu

d

y t

h

at r ats s up

p l

e

m

e nte

d w i

th

m

eta

l

s a

l

ts

w

e r e le s s

l i

kel y to

d

e v elop

pe r

i

p

h

e r a

l

n e u r o

p

at

h

y. Lu

k

a s et a

l

(

1

9

7

4

)

r e

po rte

d

t

h

at c

h

an ge s

in

m

eta

l m

eta

b

o

l i

s

m

o

f

pe r

i p h

e r a

l

n e r v e t

i

s s u e

m i

g

h

t

b

e a pat

h

o

l

og

ic

a

l l i

n

k in

t

h

e

d

e v e

lo

p

m

ent o

f C S

j

into x

ic a

t

i

o n. Br

i

ege r

(

1 9 4

9

)

n ote

d

t

h

at

d

ep

l

et

i

o n o

f b i

o

lo

g

i

c a

l l

y a ct

iv e

tr a c e

m

eta

l

s

c o u

l d i

nte r

f

e r e

w i

t

h

e n zy

m

at

i

c

f

u nct

i

o n

(

Br

i

e

g

e r, 1

9 4 9

)

. Z

i

n c,

fo r

e x a

m

p

l

e,

i

s a n

e s s e nt

i

a

l

c o -

f

a cto r o

f

c

yto c

hr o

m

e o x

i d

a s e, tyr o s

in a s e

,

m

o n o a

m

in e

, p

h

e n o

l

, a n

d

ot

h

e r

t

i

s s u e o x

i d

a s e s

w h i le c o

p pe r

i

s

im

p

o rta nt

fo r

l

a ctate

de

h y

d

r o ge n a s e, c a r

b

o n

i

c a n

h

y

d

r a s e,

g l

uta

m

ate

d

e

h

y

d

r oge n a s e, a

l

c o

h

o

l d

e

h

y

d

r o

g

ena s e, an

d

ot

h

e r e n zy

m

e s.

1

.

5

U

r

i

n a ry

M

a r

k

e r s

1.5.1 Io

d i

ne

A

z

i d

e

Be auc

h

a

m p

et a

l

.

(

19 8

3

)

r e

p

o rte

d

that 1

0

-

3

0

%

o

f

t

h

e a

b

s o r

b

e

d C S

2

w

a s e x c r ete

d b

y the

l

u ng an

d k i d

n ey

i

n e x

p

o s e

d h

u

m

a n s .

T h

e r e

m

a

in

d

e r

w

a s e x c r ete

d

a s v a r

i

o u s

m

eta

b

o

l it

e s

b

y the

k i d

ney.

D

j

ur

i

c et a

l

.

(

1

9 6 7

)

e sta

b l i

s

h

e

d

a c o r r e

l

at

i

on

b

etwe en

C S

j

e x po s u r e a n

d

u r

in a r

y e x c r et

io n

o

f

m

eta

b

o

l i

te

(

s

)

t

h

at c ata

l

yz e

d

t

h

e r e a ctio n o

f i

o

d in e

w i

t

h

s o

d iu

m

a z

i d

e

in

h

i

m

i a n s.

C

o x

(

19 9 5

)

c o n

f

i r

m

e

d

t

h i

s c o r r e

la

t

io n

in

C S

j -e x

po s e

d

r ats.

W

h i l

e t

h

e

i

o

d i

n e

-a z

i d

e te st c an r e

l i

a

b l

y

d

ete ct e xpo s u r e s to

C S

j a

b

o v e

l 6

p p

m

i

n

(18)

1

.

5

.2

T h i

oet

h

e r s

Total c o n c e ntr at

i

o n

m

e a s u r e

m

e nts o

f i hi

o c o

m

po u n

d

s

(

g

l

utat

h i

o n e c on

j

u

g

ate s,

m

e r c aptu r

i

c a c

i d

s, an

d

ot

h

e r s u

l f

ur

-c o nta

i

ning

C

Sj

m

eta

b

o

l i

te s

)

c a n a

l

s o s e r v e a s a

m

a r

k

e r o

f

e xpo su r e. Tota

l

c o n c e ntr at

i

o n s o

f

t

h i

o c o

m

po un

d

s c o r r e

l

ate

w

e

l l w i

t

h C S

2

e x

p

o s u r e

d

o

w

n to a

b

o ut

6

p p

m C S

j

i

n a

i

r

in

C S

j

-e x

p

o s e

d h

u

m

ans

(

Be a u c

h

a

m

p

et a

l

.,

1

9 8 3

;

V

a n

D

o o

m

et a

l

.,

19 8 1

;

C

o x et a

l

.,

19 9 5

)

.

W

h i l

e tota

l

t

h i

o c o

m

po u n

d

s c o r r e

l

ate

w

e

l l w it

h C S

2 e x

p

o s u r e, t

h

e c o

m p

o u n

d

s a r e n ot a

b

s o

l

ute

l

y s

p

e c

i f i

c

f

o r

C S

, e x

p

o s u r e

(

A T SD R

,

19 9 6

)

.

1.

5

.

3

T T

C A

In

19 8

1, v an D o o

m

et a

l

.,

(

19 8 1

)

i d

e nt

i f i

e

d 2

-t

h i

ot

h i

a z o

l i d i

n e-4

-c a r

b

o xy

l i

c a c

i d

(

T T C A

)

a s a c o n

j

u

g

at

i

o n

p

r o

d

u ct o

f C S

2 an

d g l

utat

h i

o n e

in t

h

e u r

i

n e o

f w

o r

k

e r s e x

p

o s e

d

to

C S

2.

F

u rt

h

e r stu

d i

e s

h

a v e

d

ete r

m

i

n e

d

t

h

at e x c r et

i

o n r ate s o

f T T C A i

n t

h

e i i r

i

n e o

f

e xpo s e

d

i

n

d i

v

i d

u a

l

s c o r r e

l

ate s

w

e

l l w it

h

a

i

r

l

e v e

l

s o

f C S

j e s

p

e c

i

a

l l y

o n c e t

h

e

l

e v e

l

s a r e n o r

m

a

l i

z e

d

to u r

in

a r

y

c r e at

i

n

in

e c on te nt

(

A

T

SD R

,

19 9 6

;

T

o

l

o s an

d C

o x, 198 9

)

.

C S

j

l

e v e

l

s o

f 2

.5

p

p

m

an

d

a

b

o v e c an

b

e

d

ete cte

d w i

t

h

t

h i

s

m

etho

d

(

A

T

SD

R

, 1 9

9 6

)

. T

h i

s

m

a

k

e s the

T

T C A

te st

m

o r e s en s

it

i

v e a n

d

s

p

e c

i f i

c t

h

a n t

h

e

i

o

d i

n e-a z

i d

e te st

(

C

o x ,

19 9 5

)

.

References

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