oversight

Present Federal Programs Addressed to Environmental Carcinogens

Published by the Government Accountability Office on 1977-02-12.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

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                                     REYARKS BY ELMER 3. STAATS
                              COMPTROLLER GENERAL OF THE U N I T E D STATES
                                   AT T H E ~ O N F E R E N C EON THE FEDERAL
                               REGULATION OF ENVIRONMENTAL CARCINOGENS)-
                                   CENTER FOR C O N T I N U I N G EDUCATION
                                            (WASHINGTON, D .C                 >
                                              APRIL 1 2 , 1977




            FPRESENT         FEDERAL PROGRAMS ADDRESSED TO ENVIRONMENTAL CARCINOGENS
            i                                                                                                                  p-‘

                                                           &)o            mool
                       I n r e c e n t y e a r s , t h e General Accounting O f f i c e h a s p l a c e d
             i n c r e a s e * e m p h a s i s o n e v a l u a t i n g t h e e f f e c t i v e n e s s of F e d e r a l
             p r o g r a m s and s u g g e s t i n g ways i n which t h e s e p r o g r a m s c a n b e n a d e

             more c o s t - e f f e c t i v e .    T h i s d o e s n o t mean t h a t we h a v e l o s t o u r
                                   I



             i n t e r e s t i n t h e f i n a n c i a l a s p e c t s o f t h e s e programs nor i n t h e
             economy and e f f i c i e n c y w i t h w h i c h t h e s e p r o g r a m s a r e managed.
             I t s i n p l y means t h a t w e a r e a t t e m p t i n g t o c a r r y o u t t h e i n t e n t

             of t h e C o n g r e s s i n l e g i s l a t i o n e n a c t e d i n 1 9 7 0 a n d e x p a n d e d upon
             i n 1 9 7 4 t h a t we a n a l y z e t h e c o s t s and b e n e f i t s of F e d e r a l
             programs.

                       I n o r d e r € o r GAO t o b e t t e r p e r f o r m a n a l y s e s of F e d e r a l
             p r o g r a m s w i t h t e c h n i c a l c o n t e n t , w e h a v e had a p o l i c y for

             s e v e r a l y e a r s of a d d i n g t o o Q r s t a f f p e r s o n s w i t h s p e c i a l i z e d
             training i n various technical disciplines.                                  Disciplines
             r e p r e s e n t e d i n c l u d e e n g i n e e r i n g , economics, medicine, bio-
             c h e m i s t r y , c h e m i s t r y , p s y c h o l o g y and a u t o m a t i c d a t a p r o c e s s i n g .

             T h e s e s t a f f members h e l p u s a n a l y z e comglex t e c h n i c a l issues
             s u c h a s t h o s e I w i l l be d i s c u s s i n g with you t o d a y .
            W e i n GAO a l s o h a v e a u n i q u e o p p o r t u n i t y - - b e c a u s e      of o u r
-   c e n t r a l l o c a t i o n i n t h e l e g i s l a t i v e branch--to         examine Grograms
    €or w h i c h r e s p o n s i b i l i t y i s v e s t e d i n s e v e r a l F e d e r a l a g e n c i e s .
    F e d e r a l h e a l t h c a r e and h e a l t h r e s e a r c h p r o g r a m s a r e e x c e l l e n t

    examples.          Our d i s c u s s i o n t o d a y c e n t e r s upon a GAO r e p o r t of
    June 1 6 , 1976, e n t i t l e d "Federal E,fforts t o P r o t e c t t h e P u b l i c
    from C a n c e r C a u s i n g C h e m i c a l s Are Not Very E f f e c t i v e . "
            The basic reason f o r t h e conclusion stated i n t h i s r e p o r t

    was t h a t some chemicals w h i c h a r e known t o p r o d u c e c a n c e r a r e
    n o t r e q u l a t e d a t a l l and t h a t t h e F e d e r a l Government, t n r o u g h
    t h e s e v e n a g e n c i e s c h a r g e d w i t h some p h a s e o f r e g u l a t i o n , d o e s

    n o t have uniform p o l i c i e s .
              Chemicals f o u n d i n our e n v i r o n m e n t - - t h e          a i r and w a t e r ,
    o u r f o o d , o u r w o r k p l a c e s , c i g a r e t t e s , and o t h e r t o b a c c o prod-
    ucts--are        evidently responsible for a considerable portion
    o f t h e c a n c e r cases r e p o r t e d i n t h i s c o u n t r y .          There have

    b e e n estimates t h a t u p t o 90 p e r c e n t of c a n c e r i s caused by
    environmental factors.
            We, a s i n d i v i d u a l s , c a n e x e r t v e r y l i t t l e c o n t r o l o v e r o u r
    exposure t o environmental contaminants.                              We h a v e l i t t l e c h o i c e
    b u t t o b r e a t h e our c i t y ' s a i r o r d r i n k t h e water p i p e d i n t o
    o u r homes.         Some e x p o s u r e s s u c h a s d r i n k i n g a l c o h o l i c b e v e r a g e s
    and smoking a r e largely v o l u n t a r y a t t h e i r o u t s e t , a l t h o u g h

    I should note t h a t t h e voluntary i n i t i a l exgosure is o f t e n

    c o n d i t i o n e d by s o c i a l p r e s s u r e s .   When and i f a d d i c t i o n o c c u r s ,
    i t would be d i f f i c u l t t o c a l l f u r t h e r e x p o s u r e " v o l u n t a r y . "

                                                           - 2 -
        Most e x p o s u r e s seem t o be a m i x t u r e o f v o l u n t a r y and
involuntary, although t h e involuntary aspects of t h e exposure
seem t o c l e a r l y p r e d o m i n a t e .     For i n s t a n c e , there has been
d i s c u s s i o n r e c e n t l y o f p o s s i b l e l i n k s b e t w e e n c a n c e r and
d i e t , particularly high-fat diet.                      C e r t a i n l y you c a n e x e r c i s e
c o n t r o l o v e r y o u r d i e t , e v e n t o t h e e x t e n t , a s some h a v e ,
o f becoming a v e g e t a r i a n .          B u t i n a s o c i e t y seemingly dedicated

t o consuming l a r g e q u a n t i t i e s o f red meat, c o n t r o l i s d i f f i c u l t .
        Since w e can e x e r t only l i m i t e d c o n t r o l over t h e environ-
mental contaminants i n our d a i l y l i v e s , it is important t h a t
t h e F e d e r a l a g e n c i e s empowered t o p r o t e c t u s f r o m e x p o s u r e t o

h a r m f u l chemicals h a v e r a t i o n a l and e f f i c i e n t programs f o r

r e s e a r c h and r e g u l a t i o n .   T h e t o p i c of my t a l k t h i s morning

i s b a s i c a l l y t h e - s u b s t a n c e of. t h e t h e r e c e n t GAO r e p o r t w h i c h
d e a l t broadly w i t h t h i s problem.

         I n o u r r e p o r t , w e c o n c e n t r a t e d on i n v o l u n t z r y e x p o s u r e o f
humans t o e n v i r o n m e n t a l f a c t o r s , makinq o n l y p a s s i n g r e f e r e n c e
t o t h e r o l e of s o c i a l and i n d i v i d u a l h a b i t s i n cancer c a u s a t i o n .
T h i s morning, I w i l l d i s c u s s F e d e r a l c a n c e r research and

r e g u l a t o r y p o l i c y , h i g h l i g h t i n g t h e f i n d i n g s from o u r r e p o r t
on these s u b j e c t s .

        The p r i n c i p a l a u t h o r i t y f o r i d e n t i f y i n g and/or r e g u l a t i n g

c a n c e r - c a u s i n g chemicals o r t h e p r o d u c t s i n which t h e y a p p e a r
is c e n t e r e d i n seven Federal a g e n c i e s .



                                                      - 3 -
Government's. research on cancer's cause and prevention; the
                                      4rC%
National Institute of Environmental HeaYth"S
National Institute for Occupational Safety and Health, and
some regulatory agencies also co d ct or sponsor such research.
                        /3   e cO O G q p
       The Environmental Protection Agency is responsible f o r regu-
lating air and water pollutants (many of these pollutants are
                                            for regulating pesticides.
The Occupational Safety and Health Administration sets and
   ,
enforces standards to protect workers from safety and health
hazards, including hazardous chemicals, in workplaces.           The
           coocqd
Food &6bDrug    Administration is responsible for the safety
of foods? food and color additives, drugs, medical devices,
                          A 6 c 0067 3-
and cosmetics. The Consumer Product Safety Commission has
jurisdiction over every consumer product not covered by any
other agency, except those products specifically excluded
by the Consumer Product Safety Act.

       Several sources indicate that almost 2 million chemical
compounds exist today and that about 250,000 new compounds
are created annually.    About 300 to 500 new compounds, some
of which may be carcinogenic, get into the environment and
into commercial use each year, and € o r most of them there
is no Federal authority requiring that they be proven safe
before significant human exposure occurs through use or
marketing.
                                            .
.   I




               For t h e Government, e a s e o f r e g u l a t i o n o f c h e m i c a l c a r c i n -
    o g e n s d e p e n d s on where t h e b u r d e n o f p r o o f a s t o t h e s a f e t y of
    chemicals l i e s .            T h a t i s , m u s t t h e manufacturer p r o v e t h a t a
    c h e m i c a l i s s a f e b e f o r e t h e c h e m i c a l can b e u s e d o r m a r k e t e d , o r
    m u s t t h e Government p r o v e l a c k o f s a f e t y a f t e r t h e chernical i s
    a l r e a d y i n use?
               The r e c e n t l y e n a c t e d T o x i c S u b s t a n c e s C o n t r o l A c t g i v e s
    t h e E n v i r o n m e n t a l P r o t e c t i o n Agency t h e a u t h o r i t y t o r e q u i r e

    t h a t c h e m i c a l m a n u f a c t u r e r s t e s t p r o d u c t s t h a t may p o s e a n

    u n r e a s o n a b l e r i s k t o human h e a l t h o r t h e e n v i r o n m e n t .        Com-
    p a n i e s p l a n n i n g t o p r o d u c e a new c h e m i c a l o r t o market a n
    e x i s t i n g s u b s t a n c e f o r a new p u r p o s e now h a v e t o n o t i f y
    EPA 90 d a y s i n a d v a n c e , g i v i n g t h e a g e n c y a c h a n c e t o h o l d

    u p m a r k e t i n g w h i l e more t e s t i n g i s b e i n g d o n e o r e v e n t o ban
    a chemical i n a n e x t r e m e case.
               The a c t d o e s n o t a p p l y t o f o o d a d d i t i v e s , i n c l u d i n g f o o d

    c o l o r s , d r u g s , o r p e s t i c i d e s , a l l of which a r e a l r e a d y covered
    by s t a t u t e s which r e q u i r e p r e m a r k e t c l e a r a n c e by t h e Government.
               I n o u r J u n e 1 6 r e p o r t w e recommended a c o o r d i n a t e d a n d
    uniform Federal p o l i c y t o d e a l w i t h t h e unresolved s c i e n t i f i c
        issues, w h i c h , i n o u r o p i n i o n , h a v e hampered more e f f e c t i v e
    r e g u l a t i o n and r e s e a r c h e f f o r t s .     Among t h e s e u n r e s o l v e d
        issues a r e t h e f o l l o w i n g :
               --Which      c h e m i c a l s s h o u l d be t e s t e d ?
               --How     s h o u l d t e s t s be c o n d u c t e d ?
       --How s h o u l d t e s t r e s u l t s be e v a l u a t e d ?
        --What     d o a n i m a l t e s t s mean € o r humans?
        A l t h o u g h t h e F e d e r a l a g e n c i e s , i n t h e i r coninents on

o u r r e p o r t , a g r e e d t h a t a uniform F e d e r a l p o l i c y was n e e d e d ,
t h e y d i d n o t a g r e e on w h i c h agency s h o u l d develoD i t ,                We
recommended t h a t t h e D i r e c t o r of t h e Cancer I n s t i t u t e b e g i v e n
t h a t r e s p o n s i b i l i t y b e c a u s e of t h e a u t h o r i t y v e s t e d i n h i m by

t h e N a t i o n a l Cancer A c t of 1 9 7 1 .         S e c t i o n 4 0 7 of t h e a c t r e q u i r e s
t h a t t h e Cancer I n s t i t u t e D i r e c t o r d e v e l o g a c a n c e r r e s e a r c h

program t h a t would be c o o r d i n a t e d w i t h r e l a t e d programs of
o t h e r r e s e a r c h i n s t i t u t e s and o t h e r F e d e r a l and non-Federal
programs.
        We d i d n o t i n t e n d t h a t N C I u n i l a t e r a l l y s e t r e g u l a t o r y
p o l i c i e s or p o l i c i e s f o r other research agencies.                    Xowever,
w e d i d i n t e n d t h a t N C I be t h e f o c a l p o i n t f o r s e e i n g t h a t a
u n i f o r m p o l i c y is e s t a b l i s h e d and t h a t NCI more a c t i v e l y
coordinate a l l Federal p o l i c i e s dealing with carcinogens
s o t h a t these p o l i c i e s r e f l e c t t h e l a t e s t s c i e n t i f i c advances
and a f f o r d maximum p r o t e c t i o n t o t h e p u b l i c .
        We b e l i e v e t h a t t h e m a t t e r s I w i l l t o u c h o n t h i s mcrning--
t h e q u e s t i o n of what i s t e s t e d , how t h e t e s t s a r e p e r f o r m e d ,

and how t h e r e s u l t s a r e e v a l u a t e d - - n u s t    be a d d r e s s e d and

a g r e e d upon by a l l a g e n c i e s .       R e g u l a t i o n of carcinogens would
p r o c e e d more smoothly and r a t i o n a l l y i f F e d e r a l a g e n c i e s
had u n i f o r m t e s t g u i d e l i n e s and p r o c e d u r e s f o r d e t e r m i k i n g

                                                    - 6 -
whether a t e s t e d chemical i s a c a r c i n o g e n .                   W e believe t h a t

t h e s e i s s u e s a r 2 among t h e m o s t i m p o r t a n t t h a t m u s t b e r e s o l v e d
by a c o o r d i n a t e d F e d e r a l p o l i c y on c h e m i c a l c a r c i n o g e n s .
                                 -
SELECTION OF CHEMICALS FOR TESTING

        B e c a u s e t h e Government h a s t h e b u r d e n of p r o v i n g w h e t h e r
o r n o t many of t h e c h e m i c a l s i n o u r e n v i r o n m e n t a r e c a r c i n o g e n i c ,
i t m u s t u s e i t s l i m i t e d t e s t i n g r e s o u r c e s wisely.          T h i s means

t h a t s t r i c t c r i t e r i a m u s t b e u s e d i n s e l e c t i n g chemicals f o r
testina.         The C a n c e r I n s t i t u t e i s now c o n s i d e r i n g p r o d u c t i o n
and p u b l i c e x p o s u r e d a t a , i n a d d i t i o n t o chemical s t r u c t u r e ,
when s e l e c t i n g c h e m i c a l s f o r i t s t e s t i n g program.
        The C a n c e r I n s t i t u t e i s t h e o n l y F e d e r a l a g e n c y t h a t
r o u t i n e l y t e s t s l a r g e n u m b e r s of c h e m i c a l s f o r t h e i r c a n c e r -
causing potential.                T h e s e t e s t s h a v e s h o r t - t e r m i m p a c t on

r e g u l a t o r y d e c i s i o n m a k i n g by s u c h a g e n c i e s a s FDA and E P A .
However, t h e p r i n c i p a l f u n c t i o n of t h e C a n c e r I n s t i t u t e i s c o
d e t e r m i n e why c e r t a i n chemicals cause c a n c e r , and how w e c a n
i n t e r v e n e i n t h e p r o c e s s of c a r c i n o g e n e s i s .
        I t t h u s becomes n e c e s s a r y t o s e g r e g a t e f o r p o l i c y p u r p o s e s

and f o r o u r d i s c u s s i o n t o d a y t h e t e s t i n g of c h e n i c a l s f o r regu-
l a t o r y p u r p o s e s f r o m t h e s t u d y o f chemicals a s p a r t of a b a s i c
r e s e a r c h p r o g r a n on t h e mechanisms of c h e m i c a l c a r c i n o g e n e s i s .
ANIMAL
--          TESTING

        Because t e s t i n g s u s p e c t e d chemicals on humans i s n e i t h e r
ethical nor practical, s c i e n t i s t s u s e animals;                         Animal t e s t i n g


                                                  - 7 -
t a k e s f r o m 3 t o 4 y e a r s f r o m s t a r t t o f i n i s h and n o w , c o s t s

from $150,000 t o $205,000 f o r each chemical.                                Experience
indicates t h a t chemicals t h a t are carcinogenic i n animals

c a n b e e x p e c t e d t o b e c a r c i n o g e n i c i n p e o p l e , and v i c e

versa.       The way a t e s t i s d e s i g n e d - - t h e         number of a n i m a l s

u s e d , d o s e l e v e l s , t h e l e n g t h of t h e t e s t , a n d o t h e r
l a b o r a t o r y conditions--can           d i r e c t l y a f f e c t t h e v a l i d i t y of

t h e r e s u l t s and t h e i r v a l u e t o r e g u l a t o r y a g e n c i e s .
        The C a n c e r I n s t i t u t e h a s d e v e l o p e d s t a n d a r d t e s t i n g g u i d e -

l i n e s w h i c h c o m m e r c i a l l a b s u n d e r i t s c o n t r a c t f o l l o w when
c o n d u c t i n g animal tests.           I n s t i t u t e o f f i c i a l s hope t h a t t h e s e
g u i d e l i n e s , i s s u e d i n J a n u a r y 1 9 7 5 , w i l l (1) make r e s e a r c h
r e s u l t s more e a s i l y c o m p a r a b l e and more a p g l i c a b l e t o humans,
( 2 ) increase the tests'                s e n s i t i v i t y , and ( 3 ) p r o v i d e b e t t e r d a t a
f o r r e g u l a t o r y agency decisionmaking.                   U n f o r t u n a t e l y , however,

the r e g u l a t o r y a g e n c i e s h a v e n o t a g r e e d o n a s e t of s t a n d a r d s ,
o r minimum g u i d e l i n e s , f o r t e s t i n g s u s p e c t e d c a r c i n o g e n i c
chemicals.          C a n c e r I n s t i t u t e o f f i c i a l s b e l i e v e t h a t t e s t s con-

ducted according t o t h e i r g u i d e l i n e s w i l l provide an adequate
s c i e n t i f i c base f o r r e g u l a t o r y a c t i o n s , b u t a p p a r e n t l y r e g u l a t o r y
a g e n c i e s are not a s c o n f i d e n t a s t h e C a n c e r I n s t i t u t e .

DATA EVALUATION
        The C a n c e r I n s t i t u t e g u i d e l i n e s c o v e r t h e c o n d u c t of t e s t s ,
b u t t h e y d o n o t c o v e r a n a l y s i s of t h e d a t a t h e t e s t s p r o d u c e .
E v a l u a t i o n of t e s t r e s u l t s p r e s e n t s s e r i o u s p r o b l e m s f o r r e g u l a t o r y


                                                     - 8 -
 .   .

agencies.         These problems i n c l u d e determining whether a t e s t
a n i m a l h a s c a n c e r o r some o t h e r t u m o r o u s g r o w t h , d e c i d i n g
w h e t h e r o r n o t a chemical s h o u l d be c l a s s i f i e d a s a c a r c i n o g e n ,

a n d e x t r a p o l a t i n g d a t a f r o m a n i m a l s t o man.

         P a t h o l o g y i s t h e s c i e n c e i n v o l v e d i n s t u d y of g r o s s o r
m i c r o s c o p i c s a m p l e s of a n i m a l t i s s u e s i n o r d e r t o d e t e r m i n e

w h e t h e r c e l l s , t i s s u e s o r o r g a n s a r e a f f e c t e d by a d i s e a s e .

Hclman tumor p a t h o l o g y i s , I u n d e r s t a n d , f a i r l y w e l l d e f i n e d
a t t h i s point, although patholcgists w i l l . s t i l 1 disagree a t
t i m e s o n t h e e v a l u a t i o n of b i o p s y m a t e r i a l .     Animal tumor
p a t h o l o g y i s e v i d e n t l y n o t a s w e l l d e v e l o p d a s human tumor
p a t h o l o g y a t t h i s time.        Rodent p a t h o l o g y is e s p e c i a l l y
i m p o r t a n t , s i n c e many of t h e b i o a s s a y s a r e c o n d u c t e d u s i n g
rodent populations.                 We would e x p e c t t h e c o n t i n u e d d e v e l o p m e n t
of a n i m a l p a t h o l o g y t o resolve t h e p r o b l e m s m e n t i o n e d above.

         T h e r e a r e d i s a g r e e m e n t s as t o w h e t h e r a c h e m i c a l w h i c h
causes n o n m a l i g n a n t ( b e n i c j n ) ' t u m o r s s h o u l d b e c l a s s i f i e d a s   2

carcinogen.           T h e s e d i s a g r e e m e n t s h a v e r e s u l t e d i n s e v e r a l law
s u i t s and much d e b a t e i n t h e s c i e n t i f i c community.
         C l a s s i f y i n g c h e n i c a l s a s c a r c i n o g e n s h a s o c c u p i e d much time
and e n e r g y i n regulatory a g e n c i e s a n d t h e s c i e n t i f i c community
i n t h e y s t decade.             I am n o t g o i n g t o g o i n t o t h e d e t a i l s of

t h i s p r o b l e m a t t h i s time, b u t I d o w i s h t o s t r e s s t h a t GAO
r e c o g n i z e s t h e i m p o r t a n c e of t h i s groblern a n d i t s i m p l i c a t i o n s
for b o t h r e s e a r c h and r e g u l a t o r y a g e n c i e s .



                                                     - 9 -
--
EXTRAPOLATING          RESULTS

       One o f t h e m o s t c r i t i c a l p r o b l e m s i n r e g u l a t i n g c a r c i n o g e n s
i s t r y i n g t o p r e d i c t t h e human r i s k o f r e l a t i v e l y l o w e x p o s u r e s
t o chemicals s o l e l y on t h e b a s i s of t h e r e s u l t s of a n i m a l t e s t s .
        H i s t o r i c a l l y , t o x i c o l o g i s t s have a p p l i e d " s a f e t y f a c t o r s "
t o a n i m a l t e s t r e s u l t s and h a v e assumed t h a t a n a n i m a l ' s r e a c t i o n
would n o t d i f f e r from a p e r s o n ' s r e a c t i o n by more t h a n t h a t
factor.        A p p l i c a t i o n of s a f e t y f a c t o r s has b e e n p r e d i c a t e d o n a
disease meeting t h e f o l l o w i n g . t h r e e c o n d i t i o n s :
        --The      d i s e a s e p r o c e s s is r e v e r s i b l e ;
        --A     s a f e t y t h r e s h o l d e x i s t s ; and
        --The      chemical i s a c u t e l y t o x i c .

U n f o r t u n a t e l y , these c o n d i t i o n s d o n o t h o l d f o r c a n c e r .        The
c a n c e r p r o c e s s seems t o be i r r e v e r s i b l e , n o s a f e t y t h r e s h o l d
f o r a c a r c i n o g e n c a n be m e a s u r e d , and carxer i s a d i s e a s e w h i c h
c a n c - d u r a f t e r e x p o s u r e t o low l e v e l s o f a c h e m i c a l , w i t h
d i s e a s e becoming a p p a r e n t many y e a r s a f t e r e x p o s u r e t o t h e
chenicaf o c c u r r e d .
        T h e a p p l i c a t i o n of " s a f e t y f a c t o r s ' ' t o c a r c i n o g e n s i s , t h e r e -

f o r e , n o t c o n s i s t e n t w i t h t h e s c i e n t i f i c u n d e r s t a n d i n g of t h e
carcinogenic process.
        Most s c i e n t i s t s a g r e e t h a t a chemical t h a t c a u s e s c a n c e r
 i n a n i m a l s i s a p o t e n t i a l c a n c e r h a z a r d f o r humans.             Most
 s c i e n t i s t s also a g r e e w i t h t h e f o r m e r D i r e c t o r o f t h e N a t i o n a l
C a n c e r I n s t i t u t e t h a t " t h e r e i s no p r a c t i c a l s c i e n t i f i c method


                                                       -   10   -
.     .   .


     t o prove e x p e r i m e n t a l l y t h e s a f e t y o f any l e v e l of exposure
     t o a carcinogen."             T h u s , a n y c h e n i c a l t h a t c a u s e s cancer i n

     a n i m a l s i s presumed t o b e a p o t e n t i a l cause of c a n c e r i n humans,
     r e g a r d l e s s of t h e l e v e l o f human e x p o s u r e .
     -
     FACTORS                             ----
                  OTHER THAN P U B L I C HEALTH

              I n some cases, laws r e q u i r e t h a t r e g u l a t o r y a g e n c i e s t a k e
     i n t o a c c o u n t f a c t o r s o t h e r t h a n t h e c a r c i n o g e n i c r i s k s of a
     chemical when d e c i d i n g w h e t h e r o r how t o r e g u l a t e t h e chemical.
              I f regulatory agencies took only s c i e n t i f i c f a c t o r s i n t o

     a c c o u n t when d e c i d i n g how o r w h e t h e r t o c o n t r o l human e x p o s u r e
     t o c a r c i n o g e n s ? g i v e n c u r r e n t s c i e n t i f i c knowledge, d e m o n s t r a t i o n
     t h a t a chemical c a u s e s c a n c e r i n a n i m a l s would be s u f f i c i e n t

     f o r t h e agencies t o s e t a z e r o exposure l e v e l t o t h e chemical
     f o r humans; t h i s would e f f e c t i v e l y b a n many w i d e l y - u s e d
    . c h e m i c a l s and would a l s o p o s e p r o b l e m s f o r m a r k e t i n g o f food-
     s t u f f s w h i c h h a v e become i n a d v e r t a n t l y c o n t a m i n a t e d w i t h p e r -
     s i s t e n t p e s t i c i d e s such as Dieldrin o r natural carcinogenic
     substances such as aflatoxins.
              There a r e r a r e pieces of l e g i s l a t i o n , s u c h a s t h e Delaney

     C l a u s e of t h e Food, D r u g , and Cosrnetic A c t , w h i c h r e q u i r e t h a t
     a chemical w h i c h c a n be detected i n f o o d be banned € o r human
     use o n c e t h e c h e m i c a l h a s b e e n shown, by " a p p r o p r i a t e " t e s t s ,
     t o cause c a n c e r i n a n i m a l s .       More commonly, h o w e v e r , laws
     r e q u i r e r e g u l a t o r y a g e n c i e s t o weigh h e a l t h r i s k s a g a i n s t
     t h e s o c i a l , economic, and o t h e r p o s s i b l e b e n e f i t s of a chemical



                                                         -   I1   -
--       for which regulation is being considered.    Therefore, decision-
         making by regulatory agencies on carcinogens usually involves
         both scientific and non-scientific data.
              For instance, the Federal Environmental Pesticide Control
         Act of 1972 defines a pesticide's "unreasonable adverse effects
         on the environnent" as "any unreasonable risk to man or the
         environment, taking into account the economic, social, and
         environmental costs and benefits of the use of any pesticide."
         This legislative language calls for balancing the risk of
         cancer against such factors as crop yield and quality, and the
         cost of producing a crop without resorting to the pesticide
         in question.
              In early 1975, the Office of Management and Budget required
         executive branch agencies--including FDA and OSHA--to prepare
         inflationary impact statements f o r any proposed regulatory action.
              When Federal agencies take i n t o account factors other

         than scientific data when regulating carcinogens, such non-
         scientific factors should be clearly identified in the public
         records of the regulation, and should not be confused with
         scientific data.   Further, it is necessary to avoid attributing
         a regulatory decision to scientific data when the decision
         is really based on non-scientific data.     It is important that

         risk-benefit balancing show the impact on public health of
         regulating--or n o t regulating--a chemical, as well a s the
         impact of the regulation on the balance sheets of an industry
         or the pay envelopes of a group of workers o r costs to the
     .   consumer.
                                        -   12   -
REPORT
---        CONCLUSIONS

        Our r e p o r t c o n c l u d e d , h a t t h e p u b l i c h a s b e e n e x p o s e d
t o c a r c i n o g e n i c chemicals s u c h a s a s b e s t o s and b e n z i d i n e .
I n a d d i t i o n , new chemicals which may be c a r c i n o q e n i c a r e
e n t e r i n g t h e e n v i r o n m e n t because i n some cases p r e m a r k e t
testing is insufficient o r lacking.                          For example, i n d i r e c t
f o o d a d d i t i v e s , s u c h a s p a c k a g i n g m a t e r i a l s , which m i g r a t e
t o t h e food i n amounts of l e s s t h a n o n e o r two p a r t s p e r
m i l l i o n , are n o t always s u b j e c t e d t o t h e long-term t e s t i n g
which c a n c e r experts .agree a r e n e c e s s a r y t o d e t e r m i n e a

chemical's carcinogenicity.
        Even i f a l l c h e m i c a l s a r e s u b j e c t e d t o l o n g - t e r m t e s t i n g ,
Federal a g e n c i e s have problems a c c e p t i n g t h e r e s u l t s of t h o s e

t e s t s and a p p l y i n g t h e n t o p e o p l e b e c a u s e t h e a g e n c i e s d o n o t
h a v e minimum t e s t g u i d e l i n e s f o r d e t e r m i n i n g a c h e m i c a l ' s
carcinogenicity or scientific principles t o help the agencies
a p p l y a n i m a l t e s t r e s u l t s t o humans.
        A s a r e s u l t o f t h e s e p r o b l e m s , some c a r c i n o g e n i c c h e m i c a l s

are n o t r e g u l a t e d a t a l l , w h i l e o t h e r s r e c e i v e i n c o n s i s t e n t
regulation.          A u n i f o r m F e d e r a l p o l i c y on how t o i d e n t i f y and

r e g u l a t e chemical c a r c i n o g e n s i s needed.             Some o f t h e issues
which w e b e l i e v e s h o u l d be i n c l u d e d i n s u c h a p o l i c y a r e
the
        --chemicals         t h a t s h o u l d be t e s t e d ,
        --test      g u i d e l i n e s t h a t s h o u l d be f o l l o w e d ,

                                                 -   13   -
        - - p r o c e d u r e s t h a t s h o u l d be u s e d f o r e v a l u a t i n g
             t e s t r e s u l t s , and
        - - € a c t o r s o t h e r t h a n p u b l i c h e a l t h which s h o u l d
            be c o n s i d e r e d .

CRITICISM OF' THE DELANEY CLAUSE
---
        Most of t h e c r i t i c i s m of t h e D e l a n e y C l a u s e r e l a t e s t o
t h e r i g i d s t a n d a r d i t i m p o s e s on FDA, r e q u i r i n g t h e a g e n c y
t o p r o h i b i t o r b a n a n y f o o d a d d i t i v e w h i c h , when - p r o p e r l y
t e s t e d , causes c a n c e r i n animals o r humans.                     These c r i t i c s
u s u a l l y c a l l € o r r e p e a l of t h e l e g i s l a t i o n t o a l l o w FDA
t o exercise g r e a t 2 r s c i e n t i f i c d i s c r e t i o n .

        I n o u r work, w e h a v e a c c e p t e d t h e p u b l i c p o l i c y j u d g m e n t
embodied i n t h e D e l a n e y C l a u s e .           L e t m e b r i e f l y r e v i e w two

of t h e c o n s i d e r a t i o n s t h a t l e d u s t o t h a t p o s i t i o n .
        F i r s t , t h e congressional intent.                   Xhen t h e f o o d a d d i t i v e
amendments were added t o FDA's l e g i s l a t i v e a u t h o r i t y i n 1 9 5 8 ,
t h e D e l a n e y Clause was i n c l u d e d t o draw s p e c i a l a t t e n t i o n t o            .


t h e p r o b l e m s of c a n c e r .    The C o n g r e s s was a w a r e t h a t t h e
amendrnents would read and mean t h e same w i t h o r w i t h o u t
t h e D e l a n e y Clause.        N e v e r t h e l e s s , i t i n c l u d e d t h e Clause
t o e m p h a s i z e i t s i n t e n t t h a t no s u b s t a n c e t h a t m i g h t cause
c a n c e r i n humans b e s a n c t i o n e d € o r u s e i n f o o d .
        S e c o n d , t h e u n i q u e n e s s of t h e c a n c e r r i s k t o human
health.        As I s t a t e d e a r l i e r , cancer d i f f e r s f r o m o t h e r
d i s e a s e s c a u s e d by e n v i r o n m e n t a l c o n t a m i n a n t s i n t h a t t h e



                                                -   14   -
.   .

    cancer process seems to be irreversible, no safety threshold
        for a carcincgen can be measured, and clinical symptoms of
        the disease usually become apparent only after long latent
    periods.         Also, scientific c o ~ s e n s u sseems to be t h 2 t any
        exposure to a carcinogen involves some risk, and that the
        risk cannot be quantified.
            Now that the Delaney Clause is to be invoked against
        an additive that very many people, for whatever reason, con-                       -   L




        sider essential to their food supply, the Congress is being
        called upon to reevaluate the need for such a strict require-
    ment.      Consider for a moment what could happen if the Congress
        were to repeal the Delaney Clause.                   FDA would be left with its
        basic responsibility to insure the safety of food additives.
        It would be allowed to consider such factors 2s the probable
        consumption of the additive, cumulative effects o € the additive
        in the human diet, and appropriate safety factors--if such
        "appropriate" factors exist--€or interpretincj animal test
        results.
             So    we would have FDA making the same risk-benefit decisions
        on food additives which currently plague s o inany of the Federal
        regulatory agencies.            We at   GAO      are concerned with such general
        questions as
             --How valuable are risk-benef it compariscns in
                  d ec isionmak ing ?                                              ..

             --How accurate can risk-benefit analyses become?


                                                -   15   -
                                    c
.   -

        I   .




                        --What      a r e l e g i t i m a t e c o s t s and b e n e f i t s o f
                             r e g u l a t o r y o p t i o n and how c a n t h e y b e
                             quantified?
                W e are c o n t r i b u t i n g t o t h e p u b l i c d i s c u s s i o n of r e a u l a t o r y

                options.         For e x a m p l e , we reported t o S e n a t o r Tunney on
                Decenber 4, 1 9 7 5 , a b o u t t h e expected c o s t s t o i n d u s t r y
                from t h e Toxic Substances C o n t r o l A c t .                   Our e f f o r t s , I
                would l i k e t o t h i n k , b a l a n c e d t h e estimat.es w h i c h t h e
                i n d u s t r y and t h e EPA had g i v e n t o t h e Committee.

                --
                RELATED      GAO RETORTS

                        By t h i s time, some of you may b e a s k i n g y o u r s e l v e s w h a t

                t h e G e n e r a l Accounting Office is doing i n s u c h a t e c h n i c a l

                area.       L e t m e r e s p o n d t o t h i s u n a s k e d q u e s t i o n i n two ways:

                by f i r s t d i s c u s s i n g o u r l e g i s l a t e d r e s p o n s i b i l i t y a n d t h e n
                some of o u r r e l a t e d work i n t h e a r e a .
                        O u r r e s p o n s i b i l i t y , i n s h o r t , i s t o e v a l u a t e and recom-
                mend improvements i n F e d e r a l p r o g r a m s w h e r e v e r w e c a n .                 We
                t r y t o show w h a t i s a n d i s n o t b e i n g a c c o m p l i s h e d and compare
                t h a t t o t h e i n t e n t of t h e C o n g r e s s , a s b e s t w e c a n i n t e r p r e t

                i t ; and some o f you who h a v e t r i e d t o i n t e r p r e t t h e laws
                know t h i s i s n o t always a n e a s y t h i n g .
                        Our e x p e r i e n c e i n t h e g e n e r a l a r e a o f e n v i r o n m e n t a l
                h e a l t h and s a f e t y h a s p r o d u c e d a number of r e p o r t s o v e r t h e
                p a s t few y e a r s d e a l i n g w i t h s p e c i f i c p r o d u c t s s u c h a s maleic
                h y d r a z i d e and s a c c h a r i n , and s p e c i f i c g r o b l e m s s u c h a s d e l a y s
                 i n d e v e l o p i n g o c c u p a t i o n a l h e a l t h s t a n d a r d s f u r t o x i c chemicals.

                                                              -   16   -
I would l i k e t o comment on some of t h e s e e f f o r t s , b e g i n n i n g

w i t h t h r e e - r e c e n t r e p o r t s t o S e n a t o r Gaylord N e l s o n on F D A ' s
p e r f o r m a n c e i n d e t e r m i n i n g t h e s a f e t y o f t h r e e a d d i t i v ,as--

FD&C Red No. 2 , s a c c h a r i n , and a s p a r t a m e .

        --
        RED NO.       2   -   On O c t o b e r 2 0 , 1 9 7 5 , GAO r e p o r t e d t h a t FDA

had a l l o w e d t h e u s e o f t h e food c o l o r a d t i t i v e f o r 1 5 y e a r s
w i t h o u t making a f i n a l d e t e r m i n a t i o n of i t s s a f e t y .          During

t h a t time s c i e n t i f i c s t u d i e s q u e s t i o n e d i t s s a f e t y , i n c l u d i n g
its a b i l i t y t o cause cancer.                One o f t h e problems F D A f a c e d
i n e v a l u a t i n g t h o s e s t u d i e s was t h e t e s t p r o t o c o l s .      Even-
t u a l l y , FDA banned Red No- 2 b e c a u s e new e v i d e n c e showed
t h a t i t caused a s t a t i s t i c a l l y s i g n i f i c a n t i n c r e a s e i n t h e

number of ?align2112 tumors i n t e s t a n i m a l s .                      I am s u r e t h e

issues i n F D A ' s r e g u l a t i o n o f Red No. 2 w i l l b e f u l l y e x p l o r e d
by t h i s m o r n i n g ' s p a n e l .

                -
        SACCHARIN         -   Although t h i s a r t i f i c i a l sweetener had
been " g e n e r a l l y r e c o g n i z e d a s s a f e " f o r y e a r s , by F e b r u a r y
1 9 7 2 q u e s t i o n s a b o u t i t s p o t e n t i a l t o c a u s e c a n c e r became

p r e v a l e n t enough f o r FDA t o r e c o n s i d e r i t s s a f e t y .            FDA

i s s u e d an i n t e r i m r e g u l a t i o n t o a l l o w t h e continued u s e
of s a c c h a r i n i n f o o d f o r a l i m i t e d time w h i l e t h e c a n c e r
q u e s t i o n s were r e s o l v e d .     T h a t l i m i t e d time had been e x p e c t e d
t o e x t e n d t o mid-1978.              GAO reviewed t h e c h r o n o l o g y o f t h e

s a c c h a r i n i s s u e and i n a n August 1 6 , 1 9 7 6 , r e p o r t c o n c l u d e d
t h a t t h e e x t e n d e d u s e of any food a d d i t i v e whose s a f e t y h a s

n o t been e s t a b l i s h e d and f o r which q u e s t i o n s of c a r c i n o g e n i c i t y

h a v e been r a i s e d could e x p o s e t h e p u b l i c t o u n n e c e s s a r y r i s k ,
                                               -   17   -
The key i s s u e which caused t h e s c i ' e n t i f i c d e b a t e was

a g a i n t h e t e s t p r o t o c o l s ; i n t h i s case t h e r o u t e of
a d m i n i s t r a t i o n , t h e dose l e v e l s , t h e t i s s u e p r o c e s s i n g ,
and t h e number of a n i m a l s t h a t s u r v i v e d t h e t e s t p e r i o d .
        On March 9 , 1 9 7 7 , FDA announced i t s i n t e n t i o n to b a n
t h e use of s a c c h a r i n i n foods and b e v e r a g e s .                The d e c i s i o n
was b a s e d on t h e r e s u l t s of a C a n a d i a n s t u d y which showed
t h a t some r a t s f e d s a c c h a r i n developed c z n c 2 r and was
                  I



e s s e n t i a l l y r e q u i r e d by t h e D e l a n e y C l a u s e .
        ASPARTAME        -   T h i s i s a n o t h e r a r t i f i c i a l s w e e t e n e r which
w d s developed i n 1965 b u t h a s n o t y e t been marketed.                             Our

April          1976 , r e p o r t on FDA,'s r e g u l a t i o n of aspar tame p o i n t e d
out a problem i n e v a l u a t i n g a n i m a l t e s t s .                A by-product        of
a s p a r t a m e was f e d t o r a t s for 115 w e e k s and r e s u l t e d i n a
s i g n i f i c a n t i n c i d e n c e of u t e r i n e p o l y p s i n two t e s t g r o u p s .
A l t h o u g h three g r o u p s of p a t h o l o g i s t s , i n c l u d i n g o n e g r o u p
from FDA, r e v i e w e d t h e d a t a and c o n c l u d e d t h a t t h e p o l y p s
were not " c a n c e r o u s , p r e c a n c e r o u s , or p o t e n t i a l l y c a n c e r o u s . "
FDA a g r e e d t o c o n s i d e r t h e c a r c i n o g e n i c p o t e n t i a l of t h e

polyps a t a p l a n n e d p u b l i c h e a r i n g on a s g a r t a m e ' s safety.
I u n d e r s t a n d that t h e s e s c i e n t i f i c i s s u e s h a v e y e t t o b e

resolved      .
        I m i g h t add t h a t GAO is now l o o k i n g a t F D A ' s e n t i r e

program f o r r e g u l a t i n g food and c o l o r a d d i t i v e s , i n c l u d i n g
i t s c r i t e r i a f o r r e v i e w i n g s a f e t y and i t s a b i l i t y t o pro-
t e c t t h e p u b l i c from u n s a f e a d d i t i v e s .

                                           -   18   -
        Pesticides         - GAO      r e p o r t e d t o Congresswoman J u l i a Hansen
i n October 1974 t h a t q u e s t i o n s regarding t h e s a f e t y of a
p a r t i c u l a r p e s t i c i d e u s e d on p o t a t o e s and o t h e r c r o p s had
n o t b e e n answered.           We p o i n t e d o u t t h a t r e s e a r c h e r s had
r a i s e d t h e p o s s i b i l i t y t h a t t h e p e s t i c i d e , maleic h y d r a z i d e ,
may csuse c a n c e r o r m u t a t i o n s o r nay a f f e c t r e p r o d u c t i o n .
EPA commented t h a t t h e d a t a i t r e l i e d on t o a p p r o v e t h e use
of t h e p e s t i c i d e were v a l i d and t h a t t h e s t u d i e s GAO c i t e d

had v a r i o u s s c i e n t i f i c w e a k n e s s e s , s u c h a s i n g r o p e r r o u t e s
of administration.                W e r e c o g n i z e d t h a t t h e e v i d e n c e was n o t
c o m p e l l i n g a n d recommended t h a t t h e EPA f u r t h e r e v a l u a t e
i t s r i s k t o human h e a l t h and t h e e n v i r o n m e n t .
        I n December 1 9 7 5 w e r e p o r t e d t o t h e C o n g r e s s t h a t EPA's
p e s t i c i d e r e g i s t r a t i o n program was n o t a d e q u a t e l y p r o t e c t i n g
t h e G u b l i c and t h s e n v i r o n m e n t from p e s t i c i d e h a z a r d s .       Some
of t h e c o f l c i i t i o n s we found that l e d t o t h a t c o n c l u s i o n were:
        . - - s a f e t y d a t a , i n c l u d i n g i n f o r m a t i o n on c a n c e r ,
              g e n e t i c c h a n g e s , b i r t h d e f e c t s , and repro-
              d u c t i o n , had n o t b e e n s u b m i t t e d t o s u p p o r t
              m a r k e t i n g many p e s t i c i d e s ;
        - - s a f e t y and e f f i c a c y d a t a were n o t r e q u i r e d
             f o r t h e p e s t i c i d e s as m a r k e t e d , o n l y f o r
             t h e i n d i v i d u a l . a c t i v e i n g r e d i e n t s ; and
        - - i n e r t i n g r e d i e n t s (such as v i n y l c h l o r i d e )
             were n o t s u b j e c t e d t o t h e f u l l r a n g e of
             safety testing.
EPA i s c u r r e n t l y engaged i n a m a s s i v e r e r e g i s t r a t i o n program

t o e v a l u a t e e x i s t i n g s a f e t y d a t a on all a p p r o v e d p e s t i c i d e s .
A l t h o u g h originally           scheduled t o be comgleted i n October 1 9 7 6 ,

                                                   -   19   -
EPA now e s t i m a t e s t h a t i t s r e v i e w w i l l n o t b e c o m p l e t e d f o r

another 5 t o 7 years.
        O c c u p a t i o n a l H e a l-
                                       th   -    I n May 1 9 7 3 , OSHA i s s u e d a n emer-
g e n c y t e m p o r a r y s t a n d a r d t o r e g u l a t e employee e x p o s u r e t o 14
chemicals c o n s i d e r e d t o be c a r c i n o g e n i c .          I h September o f
t h a t y e a r , e i g h t members of t h e House of R e p r e s e n t a t i v e s

asked GAO t o r e v i e w OSHA's b a s i s f o r t h a t s t a n d a r d .

        W e r e p o r t e d t h a t OSHA's d e c i s i o n was based on t h e s c i e n -
t i f i c e v i d e n c e a v a i l a b l e a t t h e time, t h e c r i t e r i a e s t a b l i s h e d
by a c o m m i t t e e of t h e S u r g e o n G e n e r a l , a p e t i t i o n from a
p u b l i c i n t e r e s t g r o u p and a u n i o n , and p u b l i c comments o n
t h a t petition.          We c o n c l u d e d t h a t OSHA's d e c i s i o n t o i s s u e

t h e s t a n d a r d was r e a s o n a b l e .

        This p a s t O c t o b e r , GAO c r i t i c i z e d t h e E P A f o r n c t moni-
t o r i n g t h e h e a l t h of i t s l a b o r a t o r y p e r s o n n e l e v e n t h o u g h
many of them were b e i n g e x p o s e d on a c o n t i n u i n g d a i l y b a s i s
t o h i g h l y t o x i c chemicals, i n c l u d i n g c a r c i n o g e n s .
        Drugs     -   I n a 1 9 7 3 r e p o r t t o t h e c h a i r m a n of a s u b c o m m i t t e e
of t h e S e n a t e Government O p e r a t i o n s C o m m i t t e e , GAO d i s c u s s e d
F D A ' s s u p e r v i s i o n o v e r t h e i n v e s t i g a t i o n a l u s e of s e l e c t e d

drugs.       One t o p i c of t h a t r e p o r t was t h e human t e s t i n g or'
d r u g s w i t h major s a f e t y q u e s t i o n s .       W e examined s i t u a t i o n s

where d a t a from a n i m a l t e s t s i n d i c a t e d p o s s i b i l i t i e s of
m a j o r d r u g - r e l a t e d a d v e r s e e f f e c t s i n humans and FDA p e r -
mitted c l i n i c a l testing.                 Because some o f t h e animal t e s t                  '




                                                 -   20   -
J




    'i




     results raised the possibility of the drug being a carcinogen,
     we recommended that FDA at least document the benefit/risk
     determinations that were being made before allowing human
     testing.
             The Chairman of the House Commerce Committee' s Oversight
     Subcommittee was interested in the use of cancer-causing drugs        .

     in food-producing animals.      We reported to him in February
     1975 that nitrofurans--one class of animal drugs--had been
     considered suspected carcinogens since at least 1967 but
     that at the time of our report FDA had not taken effective
     action to remedy the public health hazard.
             I am not trying to be a Monday morning quarterback and
     say that we should have known then what we         know now.   I
     know that improvements and refinements in test methods
     that take-place almost every day,          What I am trying to sug-
     gest, however, is that a uniform policy, at least in the
     Federal Government, might prevent public exposure to cancer-
     causing chemicals by selecting proper chemicals for testing,
     applying some minimum standards t o those tests, evaluating
     the test results against soms agreed-upon criteria, and
     balancing the results against the socio-economic factors
     which have been deemed proper by the Congress.
             In conclusion, I leave with you the question as to what
     should be the proper role of the Federal Government in this
         important area.   This has been a subject of debate for many


                                       -   21   -
years and it is a far from settled matter at this point.
In my opinion, the issue can be best described as a
scientific-socio-political-economic choice which should
be resolved by the Congress as a matter of high priority.
The form of this decision and the timing of actions which
flow-from it will be based primarily on the best scientific
evidence that our research scientists and 2hysicians can
bring to bear upon it.   Despite this, it is possible that
the incontrovertible evidence needed to make such a decision
may not be obtainable--at least in the minds of those who
would place greater emphasis upon the political and economic
issues involved.   But the stakes are high and scientists
should not hesitate to develop to the best of their ability
the data on the precise relationship between chemical use
and disease--for without this scientific effort our political
leaders are faced with a much more difficult d2cision as to
what should be a rational national policy.




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