BY Saran Z . Taylor Sclence 3311zy 3esoarcF. S ; v ~ s ; o n Congress;or,ai Eesearzh Servzce NORTHERN KENTUCKY UNlVERSlTY LIBRARY CRS- 1 ISSUZ DEPINITICN for Arclflcral sweeteners have been a source of controversy ~n the U.S. o v e r 73 y e a r s . The safety of three l o w ca1cr:e s7~eeceners -cyclamate, saccharin, a n d a s p a r t a m e -- c o n t ~ n u e s t o b e d e S a t e d . D r ~ v ~ n t gnese zssues !-.as Seer. a n 1 n t e r 7 l a y o f a l a r g e co!-.sl~?,erd e n a z s f o r l o w c a l c r ~ e s w e e t e n e r s & n S c c n z r o v e r s y ccccern;ng c e r t a ~ n s a f e z y s t a n 5 a r C s s e t fsrt?, L E e "od, ,rug a n 5 C o s m e t ~ c A c t (FCC:). 7 As the a r t i f i c i a l sweetener d e S a z e c o n t i n u e s , p o l i c y m a k e r s may wlsh to c 3 n s i d e r c h e a ~ p r o p r i a t e n e s so f t 2 e f o o d a d d l t i v e s a f e t y standards of che FDCA, iccluding the Delaney clause, and the impact of these standards on the cnder the FSCA; n a t u r e of s u b s t a n c e s t 5 a E a r e a p p r o v e d a n d d e n l e d a p p r o v a i ~ 3 ae p p r o p r i a t e n e s s o f ccncinued e x t e n s l ~ n s of the Sacchzric Stucy and L a S e l i ~ g.Act i n l i g h t o f zP.e a p p r o v a l cf a s p a r t 2 c e ; ar.6 h e a p p r o ? r i a z e n e s s z t ? ! ~s v a : i ~ a z i ~ r , ~ a d s ,j y .-,,- - ;:r?.\-=h sveg:a&l:y Ls = a c > e 52:. 25 cycLar:a=e r h : . zhs approval of aspartaxe. 1 s lasue Srief crovi5es %azkgrcun5 ::fcr~.azi~n a n t 5 . e F 2 C A p r o v i s i s ~ s z o s t psrzlnon: artific:al s~eeter.ers, ?,iqhlighr:ng che 3elaney zlazse ccnzroversy; , analyzes s c ~ e n t i f ~ cz p * policy issues concerning cyclamate, saccharin, and aspartame. - .l A. BACKGROUND AND POLICY ANALYSIS 3eg;laz;on o f f s o d a d d i z ; v e s , :rcl-CL~-.g a r t ~ f l c l a l swee:erers, :s carr:eS (FGA) s c c o r 5 ~ n g to tne a3~zhor;ty o u t c y c P e F o o d a n d C r ~ gAdrn;nlstrat~a?. conferred S y tne FDCA. F o o d r e g c l a t l o n o r l g l n a t e d w:~h the Pure Food an5 15 :t contained "ary D r u g Ac: o f 1905 w h l c h d e e m e d f o o d t o b e a d u l t e r a t e d p o l s o n o u s o r d e l e t e r ~ o u s ~ n g r e d i e n t sw h l c h m a y r e n d e r s u c n a r t l c l e 1 n ~ u r - o u 5 to health." L a t e r , the Federal Food, Drug a n d Cosmetlc Acc of 1938 (F3CA) expanded the deflnitlon of adalterated food co lnclude foods contalrlng any poisonous or deleterious substance which may render it injurious to health; but in case the substance i s not a n a d d e d s u b s t a n c e , s u c h f o o d s h a l l n o t be c o n s i d e r e d adulterated under this clause if the quantity of such substance in such food does not ordinarily render i t [ F D C A s e c t i o n 402 (a) (1) 1 . injurious to health. CRS- 2 IB85119 UPDATE-07/12/85 In 1 9 5 8 , t h e F D C A w a s a m e n d e d t o a d d r e s s specifically t h e s a f e t y of food additives through the Food Additives Amendment. Many different substances are considered food additives in a colloquial sense, but a s u k t a n t i a l number provided o f t h e s e a r e e x c l u d e d f r o m t h e s c r i c t d e f i n i ~ i o n of " f o o d a d d i t i v e " ~n the F3CA as a r e s u l t of t h ~ s amendmen:. A c c o r d ~ n g to the legal lncended use of d e f l n l t l o n , " f o o d a d d l t l v e " r e f e r s t o " a n y substance t h e w h ~ c h r e s u l ~ s sr r e ~ s 3 ~ a S bl e~ e x p e c z e 5 t 2 r e s z l t , d ~ r e c t l y o r indirectly, in i ~ sbecoming a c o m p o n e n z or o z h e r w i s e affeczing the characteristics of any fooe . . . . " ?e law n o 3-ly defines 5 3 3 3 adrJi:i7qe, u kut eescri3es s?ecific =c e x c e p t i o n s t o t h e d e f i p - l t i o n of f o o d a d d i t i v e . The exceptions accorcinq z h e F9C.q a r e : 1 ) g e s c i c i d e c h e m ~ c a l s x s e C i z :he product:sn, szoraqe, v t r a n s p s r t o f r a w a g r i c u l t u r a l c o m m o d i r ~ e s ;2 ) s u 5 s t a n c e s c h a t a c c ~ C e p . z a l l y o r crior u n a v o i d a b l y g e t i n t o f o o d ; 3 ) c o l o r additives; 4 ) n e w a c i n a l d r u g s ; 5 ) s a n c ~ i o n e d s c b s t a x c e s , i.e., added su9stances t ap?roval zrior e n a c t m e n t o f t h e 1 9 5 6 F o o d Additives Amendmen:; and (5j " G X A S ~ ~s ~ b s c a n c e s , [FDCA sectioz 2011. i.e., a d d e d s u b s t a n c e s g e n e r a l l y recognizee as safe . . S,z;:z?.ces = " z = z e l ~ r:z ~ 2 ~ z 2 f :+JS a?sTb7e ::s=rfi c a z e q 3 r ~ 2 s 2 7 2 -. .---a A L < = - . m t o 'he 3DZA 3 r 3 * ~ i s i 3 z s s p e ~ i f ~ ct o ,^1 a ,ulclves. m-" -..e a r t i f -2La: .. - ,- .,, - = , s;?ee:lners s a z a n a r i n 225 a s ? a r = a ~ . e? r e c,srs:zers< f ~ s z ai;- - - - -= -a-. .. , y c l z ~ , z = ei,..-zs2 S ~ . : * S s;?s:s::,=e ~r j- i- -7, -? ):r.en ?;A ~r.:=:&-efi yecyst=-= ,-- - - - ' - -a -L =--- -- L - :?.= -- , -s '. -52. 19 L a - iLn u - , , - - - - - '- ' I C n - - cr-- L 3- 7 i l i U,..." r. " - A 7 > T h e F o o d A d d i t i v e s Amendneric s e t 3p a p r e r ~ a r k e t a p p r o v a l s y s ~ e x f o r f o o d a d d i t i v e s [ F D C A s e c t i o n 4 0 9 (b)(l)]. The system placed the Burden of proof seeking additive concerning additive safety on the industry or petitioner approval. The petitioner must establish food addizive safety znder the p r o p o s e d cond::ions studies ~ o "A. The of 2se 9 y subnitcing appropriaze ? D C A d o e s n o t s p e c i f i c a l l y d e f l n e :he :erm " S a f e , " b u t d o e s l i m i c a p p l i c a t i o n [ F D C A section o f t h e t e r m E O r e f e r s o l e l y t o t h e " h e a l t h of m a n o r a n i m a l s " 1 . E e f o r e t h e a m e n S 3 e n t , P 3 A h e l d =?.e B u r 5 e n f z r ~ r a v i n q a n a l r e a d y u-safe. ATAn-'r,nF --r. . ,- - - . n F 4 ,- >.T ,-dvisisn +,-n:*n73i z I f 2 - + : - V . . C IL- u - ,-.. ~ . ~ rT:, ' I~ e2' -,-, ,-.iu ,orc;czge.-,:c 5 ~ 3 5adC:zives, 22ce AS5itives e . i s --i... a& -i. . zl?':se. -..-; e l a c s e az--:ss 27.1~ h ~ , , -s1,TtL-ay > ? A ---,,, - .. - L G r , ~ e rc ~ a u s e sa ~ p e a r i? :ce F D C A s e c c i o n s t h a t p e r t a ~ n t o c o l o r a d d i t i v e s a n d a n i n a l d r u g s [ s e c t i o n s 706 (b) ( 5 ) ( 5 ) a n d 5 1 2 (d) ( 1 ) (H) , r e s p e c t i v e l y j . F D A i s p r o h i b i t e d f r o m a p p r o v i n g [FDCA section 409 (c) (3) ( & ) 1 . The the use of carcinogenic food additives following anti-cancer language pertains to food additives. r.r.n - + --- 35 the " 3 e l z n e y " A L ? r s v i d e d , . t h a c n o a d d ~ c l v e s n a l l c e deernee c o b e s a f e lf :c :s f o u n d t o ~ n e u c ec a - c e r w 9 e n ~ n g e s t e c S y m a n 3 r a n ~ m a l ,o r ~ f 1 t 1 s f o u n d , a f t e r t e s t s w h l c h a r e a p p r o p r ~ a c e f o r :he e v a l u t l o n o f t h e s a f e c y o f f o o d a d d l t ~ v e s ,t o l n c i i ! c ~ c a n c e r ~ n m a n o r animal, [ F D C A s e c t l o n 409 (c) ( 3 ) ( A ) 1 . Several different views exist concerning the value and appropriateness of the Delaney clause. Historically, this controversy has been a n undercurrent in many food safety issues, including the artificial sweetener issues. In 1977, FDA proposed the ban of saccharin under the Delaney clause. Cyclanate was banned in 1970 under the general food safety provisions of the F D C A , but t h e e x i s t e n c e of t h e D e l a n e y c l a u s e p l a y e d a key role in the cyclamate decision. In a d d i t i o n , t h e D e l a n e y c l a u s e c o u l d a p p l y to other artificial CRS- 3 s w e e t e n e r s i n t h e f u t u r e if e v i d e n c e d e m o n s t r a t e s them to be Therefore, a brief analysis of the Delaney debate i s in order. carcinogens. P o s i t i o n s concerning t h e D e l a n e y c l a u s e c a c b e b r o a d l y g r o c p e d i n t o three categories: opposition to the clause, support for the clause, and the belief the clause is of little consequence. In general, Delaney critics believe the c l a u s e h a s b e c o n e antiq:;ated as modern tecP,nical c a p a 2 F l i t y ? a s r~a5e detection of increasingiy s m a l l a n o u n r s of food carcinogens 2oss;Sle. C r i t i c s o S j e c t t ~ t h e f a c t t h a t z k e 3 e l a r e y c l a u s e i s a ~ .aSso1u:e prohibition o f c a r c i n o g e n i c f o o d additives a n d S o e s no: c a k e I z z o accszr,; :?.e p c z e n c y sr 5 o s e o f t h e c a r c i ? , o g e n , o r 2 i s t i n g " i s ? betwee?. ar.Lnal a n 2 h x x a c carcinogens. The 3elaney clause is said to S e a risk" standard. Because nany a e l a n e y c r i t i c s j e l i e v e - h a t n o t a l l c a r c i n o g e n s p o s e e q u a l r i s k s z o P.umans, insceac of t9e they advocate the use of "quantitative risk assessment" -,-ves. D e l a n e y c l a u s e t o r e g u l a t e c a r c i n o g e n i c f o o d add;'; -. - - I n g e n e r a l , a d Y v 7 o c a t e sof = h e 2 e l a n e y c l a ~ s e 3el;eve 2P.e c:a'~se orrers Setter protection to public health than risk assessment woule. The zlaxse is said to encourage caution in food additive regulation. While only two food 2-choroanaline), additives have been banned under the clause, (Flectol H and advocates argue the clause has been important in preventing approval of potenzially hazardous food adcitives. xany Dslaney advocates also dis~rast Secause risk assessment for evaluation of c a r c i n o g e n i c foot a d d i t i v e s differen: m a t h e m a t i c a l m o d e l s c a n p r o d u c e d i f f e r e n t r l s k estimates for =he lit-lp is :<no>j?-! same suSstance. in a d d i t i z n , m a n y a r e c e n c e r n e d z k z t -" aSoz: c a z c e r , a n 2 p a s s z 5 l e c2aulat:ve c r sy:.erqisric e5fec;s of =ayz:ro~e?.s r o b e z c z c ~ ~ r efd3 r L n a r ~ 5 ka s s e s s ~ . o n ~ . + ?_r-r\LPe' '..." - .. - ~ e r s p e z ~ i vcoccern;?.; e -he az - > r c p r l a t e ? e s s 3 f :ye 3e:arec-zL3e safezy p r o a ~ s ~ c c sc f :r,e 1 s =?-at t h e c l a ~ s e1 s r e d u r ~ d a n t v ~ r nt h e gem.eral FDCR. T h e S e n a t e r e p o r t z h a t a c c o m p a n ~ e d t h e 1 9 5 8 F o o d Addit;ves b l l l s t a t e d t h a t t h e l n t e n t o f t 9 e legislation w a s t o p r e v e n t t h e a d d l c i o n t o f o o d o f a n y substance causing, not only cancer, S u t any dlsease or dlsablllty. The report further stated thac the Food Addltlves blll read and meanz the same with or w l t h o u t t h e D e l a n e y c l a u s e ( S . R e p o r t no. 2 4 2 2 , 85th C o n g r e s s , 2d soF,e sesslc?., 1 9 5 s ) . K o r e r e c e n l l y , tP.;s perspecc;ve h a s b e e n reiterated Q y f 3 o d l a w e x p e r t s . m- h e f a c ~:cat o ? l y t d o f o s 5 add:t~~,-es h a v e e ~annsd u ~ ~ d etrh e D e i a n e y c l a u s e s - n c e 1 9 5 8 i s s o m e t i ~ e sc l t e d a s e v l d e n c e zhac zne Dela'ney c l a u s e 1 s l e s s c o n s e q ~ ~ e n t l a tl h a n t h e p u b l i c d e b a t e m i g h t s u g g e s t . The term l'cyclarnate" r e f e r s to several chemical derivatives of sweeter than table cyclohexylsufarnic a c i d w h i c h a r e a p p r o x i m a t e l y 3 0 t i m e s sugar. Unlike table sugar, cyclamate is considered a "non-nutritive'' sweetener Secause the body cannot extract energy from it. Cyclamate was introduced in 1937 and was approved a s a n over-the-counter drug for the dietary management of obesity and diabetes in 1951. Cyclamate was s u b s e q u e n t l y p r o d u c e d by A b b o t t L a b o r a t o r i e s a n d m a r k e t e d as a table-top sweetener under the trade-name "Sucaryl." CRS- 4 IB85119 UPDATE-07/12/85 The more potent artlficlal sweetener, saccharin, had already been on the market for many y e a r s but c o n s u m p t ~ o n was ilmlted because l t had a n unpleasant aftertaste. Following = h e a p p r o v a l o f e y c i a m a t e , i t was learned that a 1 0 to l mlxture of cyclamate and saccharln reddced tne bltter aftertaste o f saccharin a n d o f f e r e d m a n y f o o d processing advantages. Thls discovery i e d t o t h e d e v e l o p n e n t o f m a n y s y c l a n a t e - c c z z a i ? - i n g f o o 5 s . -r s c 5 A d C i t i v e a a ~ , e r C n e r t 3 f 1 9 5 5 , A f t e r ;he F 3 Z A w a s a n e n S e 2 S y :he c y c l a m a t e w a s r e c l a s s i f i e d a s a G 2 A S s u S s t a n c e ( g e n e r a l l y r e c o g n ~ z e da s s a f e ) ' w s r e dofi:eZ f c r xs? ir, f a o 5 ? r o d s c z s . iz';3~ever, a n 2 c o s p e c i f ~ c ilrriita~ians cyclamate-containing products were required c o Sear iajels i n d i c a ~ z n g zhe foocls s h o u l e 5 e u s e C S y t h c s e w h s s h o s l 5 r e s z r i c z z 2 e i r i?.cake s f c a l c r i e s . ' - -- - -5 2 , - -- -- -z;.-s 7 2 5 5 ,?-IS , ; ,. - -..- - -- - .. ; ..;- -- -.- .-. --.2- ..- --- - . . 3c:ence ( N A 3 ) nrlCercso:< a s eval,a=~ar. 3 5 z 5 e sza:::s cf eyzlamaze. - 3 irs f i n a l r e p o r = , t h e F N S q u e s t i o n e d = h e effect:veress of a r t i f a; - sTdee:eners i n a i d i n g w e i g h t r e d u c t i o n a n d t h e s a f e t y of t h e s w e e t e n e r s u n d e r conditions o f w i d e s p r e a d use. The FNB report did not appear to dampen publlc enthusiasm f o r a r t i f i c i a l s w e e t e n e r s but i t did m o t i v a t e furzher sweetener r e s e a r c h . --, .? 4 - C = * -..i Yhile M a n y a r t i f i c i a l s w e e t e n e r s t u d i e s w e r e c ~ n d u c z e dd u r i n g c h e 1 9 5 C s . n o t a l l o f t h e s e s t u d i e s i n d l c a z e d d e l e t e r i o u s e f f e c t s f r o m c y c l a m a ~ e ,e ? o u g h o f tr.em 2 i d t o r a i s e q u e s t l e n s 250.2: r:'e ap?rzpr:azer,ess z f z3.e G3;S scacss - szed issaed a ? : e ~ c r z n C u x :taz 1.. 3 f cyclainace. 3 n D e c . 5 , 1 9 5 8 , ?ZA - - --d,,ox;ng c z c c e r r s a j c a z z n e s a i ? t y c f cyclar,a:s: li a , .2 - 2=?ST. ro~or:ed :c a i c e r i n z e s t i ~ , ~ :func:ion a c 2 c a i a s s z o c l s o f z e n l c ~ ; 2 ; - 2 Ll?i??.2:? 5) P a d 3eer. reported ~2 d a m a g e z C e liver s f g u i n e a ~ i q s ,s;cf, a c 5 :?,cr!<:s%; -,, a l t e r z c y c l a r ~ a z e x a s r s p o r z e s z o ?,a-~ez - e ~ccenz:al se;azcl:ar, ;f c e r t a i n t h e r a p e u t i c d r u g s a n d c h e a S s o r p t i o c of virarnin K ; a n e 4 ) s o m e a n i m a l species were reported to convert a portion of the cyclamate consumee to cyclohexyiamine (CHA) , a toxic by-product. - - - - 7 - n FDA decided to remove cyclamate from the l i s t of GRAS substances in 0czo:er 1969 a f t e r scientific evidezce sxqgested c y c l a ~ , a z e r , a y be a t h l s dec:si?? :$as s a c n s o r e d s y Ascoz: carcirogen. T h e p i v z t a l s c u e y :r, L a S o r a t o r i e s a n d w a s c o r d ~ c t e d by t h e F c o d a n d 3rug 3esearc" La9ora:ories to saccharin ( F D R L ) . :n t h e F D R L s t u d y , r a t s w e r e f e d a 1 0 t o 1 c y c l a m a t e Of t h e 82 r a t s t e s t e d , 12 mixture, and some of the rats were also fed C H A . developed bladder tumors. This study die nor conclusively establisr. cyclamaze as the caxse of the Sladder rumors Secause s a c c h a r i ~ was also Yet, aeca~dsecyclanaze was ixplicazed a s a present in t h e t r e a t a e n t mixcure. possible carcinogen, i t was removed from the G2AS list. Department of Health, Education and Welfare (DHEW) Secretary Finch announced on Oct. 1 8 , 1 9 6 9 that cyclamate would be removed from the l i s t of GRAS substances. H e noted that while cyclamate had not been shown to cause c a n c e r i n h u m a n s , h e w a s r e q u i r e d by l a w t o t a k e a p r u d e n t c o u r s e . CRS- 5 IB85119 UPDATE-07/12/85 ... T h u s , my decision t o remove cyclamates from the l i s t o f a p p r o v e d s u b s t a n c e s in no s e n s e should b e interpreted as a "lifesaving" or emergency ~ ~ e a s u r e . I h a v e a c t e d u n d e r t h e p r o v i s i o n s o f ~ h el a w b e c a u s e it i s imperative to follow a prudent course in all m a t t e r s o f public health. S p e c i f ~ c a l l y ,z n e s o - c a l l e d Delar.ey a m e n d m e n t e n a c t e e 1 1 y e a r s a g o s t a t e s t n a z a n y f o o d a d d l ~ ~ v~eu s cb e r e m o v e d fror, t 2 e n a r k e z 1 5 i 2 h a s =?en sn37;n Z 3 c a c s e caccer when ieZ to kcmans or aninals. under the gereral faoC WPL1le c y c l a c a t e as r e m o v e C fror, t n e SR-AS l i s t s a f e z y provisions o f c h e F D C A , a n d n o c u n d e r t n e 3 e l a n e y c l a u s e , z n e clause a p z e a r e d c o influence :he dee;sicn n a d e ~ y S e c r e t a r y FincP.. " over-rne-zaur.zer C r u g s z a t 3 ~ sof zyclaxaze ;aszed fzr less 5 o ; v ' e v e ~ ,-,.,e mh ,,.e 3SP. ,nan o n e y e a r , a n d c y e l a c a t e w a s 3 a n n e d o u t r i g h c o n A G ~ . 2 7 , ;97C. occurred when FDA concluded cyclamate did not meet the standard for "effectiveness" required for drugs according to the FGCA [ 3 5 FR 135441. The The Advisory S a n c o m p l i e d w i t h t h e a d v i c e o f a n XEW M e d i c a l A d v i s o r y G r o u c . Group belleved thaz c o scbstanzial evidence exiszsd indicating cyclana~e compounds were effeczive a t any level in the treatment of oSesity or diabetes. In addizion, the Advisory Group endorsed an outright ban of . c y c l a m a z e b e c a u s e ef c o n c e r r ~ s t 3 . a ~ i c n l g 9 t n s r be s a f e , e v e n h.hez u s e C wlzn medzcal s u p e r - ~ L s i c ~ . i. , HZW acted w l t h o ~ ~ tsac' i c i e ~ . ~ Cr1t;cs of the cyclamate ban belleve sclentlflc evldence. Abbott Labs has soughc approval of cyclamate a s a food ban. In November 1973, ASbotc L a ~ s a d d l t l v e o n t w o occasions s l n c e t h e submitted a f o o d a d d l t l v e p e t l t l o n t o F D A , c l t l n g n e w c y c l a m a t e s t u d i e s [ ~ o o d Addltlve Petltlon 4A 29751. FDA announced ~ t sflnal declslon denylng a p p r o v a l of z y c l a ~ a i e ;n S e p z e m n e r l 9 E O ~ e c a u s e 4 b S o z z 222s ha5 :a:-ed ro e s z a b l ~ s h t.?e s a f e r y of c y c l a n a z e . "A Z e r ~ i e d t n e 9ez:ti~n o n b :;: grodr.ds: 1) c y c l a m a t e h a C n o t n e e 3 s n o w n n o - t o c a u s e c a n c e r ; a n d 2) c y c l a m a t e ?.ad n c z cacse h e r l t a ~ l e damage. The final d e c i s ~ o n followed b e e n s h o w n not t o l e n g t h y l l t l g a t ~ o n S e f o r e a n adm1nlstrat:ve l a x judge. A S ~ o t tL a S s a n d t h e C a l o r l e Control Councll ICCC), an l ~ d u s t r l ~t r a d e grouc, su~rnltceda second food addltlve pecltlon rcncernlr.g c y c l a n a ~ e :n A declslon on thls petltlon 1 s p e ~ d l n g . FDA commissioned the Novern~er 1982. N A S t o r e a s s e s s a l l r e l e v a n t s c l e n t ~ f l cd a t a concerning the carcinogen~clzy of cyclamate ~n November 1983. T h e f l n d l n g s of t h l s r e v l e w w e r e p u b l ~ s h e d ~ n J u n e 1985. The NAS report stated that the sclentlflc evldence dld cot ~ n d l c a c e cyclamate das by ltself carclnogenlc, but that some studles The NAS revlew followed a 1984 s u g g e s t e d ~ t h a s cancer-promoting a c t l v l t y . F9A evaluation, conducted Sy the Center for Food Safety and Applied Nutrltlon, Cancer Assessment Committee, whlcn reported there were CRS- 6 IB85119 UPDATE-07/12/85 insufficient credible data to implicate cyclamate a s a carcinogen. FDA is currently reviewing the NAS report and has stated that a final decision on cyclamate may be possible in 1985. Some groups have cautioned FDA against reapproving cyclaaate withouz considering health risks other than the risk of cancer. Concern has been expressed about adverse eff eczs such as reproductive abnormalicies, acrophy of che testicles, and birth defects. S a C ~ h a r l P 2 s a n ar5:f:c~al s w e e t e x e r Xcowr, c h e n l c a l l y as " 2, 3 elhydro-3 335 z ~ m e s as o x o ~ e n z ~ s u i f o n a z o l e .B~y w e l g n t , saccharin 1 s a p p r o x l m a t e i y s w e e t a s c a S l f s c g a r . T 3 e 2 u a a n b o d y c a n n o t a s e saccPar:n for erergy s o 1.5 1 s consleered a "non-rutrlclve" sweetener. O n Mar. 9 , 1 9 7 7 , t h e FDA proposed a saccharin ban a g a i n because researc9 indicated it was a n animal carcinogen. T h e p i v o t a l s t u d y i n "A's decision was a " t w o g e n e r a t i o n a l " rat study conducted by scientists xith the Healzh ? r o c e c c i o ~ ?3rap.ck o f . t 5 e C a n a d ~ a n g o v e r n m e n z . In t 3 i s s t ~ d y ,t w o s~ccessive generations of rats were fed high doses of saccharin. The second generaricr. male rats developed cancerous and noncancerous Siadder tumors. i -n e s t u Z y w a s c c c s - d e r e d s i g n i f i c a n t S e c a n s e i t d e m o n s t r a t e e ~ r . 2s ~a c c h z r ~ n z a s s e 2 j l a d i e r - ., .,, - o T s . I n p r e v l ~ u s s z x C i e s i: .?.az- b e e r c z ~ l e a r wPiet?.er ~acc?~ar:n c r a s a c 2 : m ~ a - ~ I.y,z ip-.t. .;,.aE r2;Fozs>>;s fcr -c.-. .- ,- u- -- 2 . -%'22"32 =?A% 3312;2-: :. -lc,se cf z 9 e ?DCA p r ~ 9 . i " ~ z~n e x t i r k e z ~ ~ q o f f o c 5 aC8:t:ves zkaz zaxse i n ?,an o r an:r,&l, c:P,e Ia?.a?lan s z c 6 y c = r , a s l l s 5 ' 2 ; . t~ z r s ~ z s s = c s 2 2 : za:eer sacchar:?. . - 1 -L - L - A. ,"-"u-i . - . > - m -- ? n: ,+ In 1 9 7 7 , saccharin was the only artificial sweetener approved for use in the United States. Eecause of the popularity of artificially sweetened f o o d s , p a r t i c u l a r l y d i e t s o f t d r i n k s , a n d t h e l a c k of a s a c c h a r i n s u b s t i t u t e , news of the proposed ban spawned a public outcry. The public response in t u r n aoz5vazed C o n q r e s s to prevenz 3 3 A f r o n ba?.ning ~ a c c ? ~ a r i n ,a = l e z s z c~xporarl;y. C o n g r e s s intervened by pass:ng t h e S a c c n a r ~ nS t u d y a n d L a b e l l n g A c t (P.L. on Nov. 23, 1g77. T h l s l a w 1 s sometimes r e f e r r e d t o a s t Q e " s a c c h a r l n m o r a z o r l u m . " T h e A c t : 1) p r o n l S i k e d F D A f r o m l a p l e m e n t l n g t h e p r o p o s e d S a n o f s a c c h a r l ~f o r 1 8 w o n t Q s ; 2) reqd;red t h a t w:tn;n 93 days of enactment, all packages of sacchar:: a?d f o o d c o n t a l n l n g s a c c h a r ~ nw o u l d c a r r y l a b e l s w a r n l n g that che proddct may c a u s e c a n c e r ; a n d 3) p r o v l d e d f o r a s t u d y o f t h e t o x l c l t y a n d c a r c l n o g e n l c l t y of saccharln and ~ t l s m p u r l t l e s , a n y h e a l t h b e n e f l t s a s s o c ~ a z e dw l t h t h e u s e o f n o n - n u t r l t l v e s w e e t e n e r s , a n d t h e evaluation o f F e d e r a l r e g u l a t o r y p o l i c y . 9 5 - 2 0 3 ) , w h i c h w a s s l g n e d l n t o l a w by P r e s i d e n c C a r t e r requested in An expert panel with the NAS carried out the study Congress the P.L. 9 5 - 2 0 3 . In November 1978, the panel issued a report that assessed The panel stated that saccharin risks associated with saccharin consumption. CRS- 7 IB85119 UPDATE-07/12/85 w a s a c a r c i n o g e n o f r e l a t ~ v e l yl o w p o t e n c y b u t n i g h t be of moderate rlsk no further studles were b e c a u s e o f t h e l a r g e population e x p o s e d ; a n d t h a t ;n March 1979, the n e e d e d t o establish t h e c a r c l n o g e n l c l t y o f s a c c h a r ~ n . p a n e l r e l e a s e d a s e c o n d r e p o r t , v ~ h r c h z s s e s s e d U.S. f o o d s a f e t y p o l l c y . T P. e second report called on Congress EO modlfy the pollcy ln order t o g l v e Pi34 m o r e d l s c r e t l o n l n r e g u l a ~ i n g c a r c ~ n o g e n l ca n d o t n e r c o x l c s u b s t a n c e s ~ n ehe food scpply. O v e r 170 s a c c h a r i n s t n 5 i e s h a v e S e e n p u S l l s h e 5 s i n c e 1977. Rece?.: srudies t h a z ?.ave r e e e l v e d a a r t l c ~ l a r a:zo?,tioc were corL2ccze5 S y e I~ternati2nal = n ,Nacie2al Center Research and 3eve1opment Corporatisn (IRDC), t T o x i c o l o g i c a l R e s e a r c h (NCTF?), a n d t h e N a c i o n a l C a n c e r Institute ( N C I ) . A THE NATIONAL C E N T E R FOR T O X I C O L O G I C A L R E S E A R C H A 1 9 8 3 s t u d y c o n d u c t e d by the NCTR, an FDA U & (NCTR) STUDIES laboratory, examlned the deslgned tc tie rate a = vh;ch c x ~ o r sw e r e s r o c u - e d by a y o t h e r ~ n g d n carclr.ogen, 1-letryi~.:tres,rea ( M N U ) . A l o h d o s e o f MNU ~ 7 a s applied d l r e c ~ l y z o tP.e b l a d d e r s of tPe experimental r a t s . The rats were then fed saccnarln doses ranglcg from one to flve percent of d l e t , Sy welgh~. A dose repocse a s reportee thst lndlcated that the greater the saccharln dose, the more q u l c ~ l y tumors were ?reduced. A l i r ~ l t a t l o n o f :he N C X sstudy 1 s s a l d t o 59 t h a t t b e 2 o s e r e s p o n s e d a s c o t consistent arncng r a z s r e c e l v l n g t h e n l g h e s t s a c c h a r ~ n dose (5% of Zlet). The lnvestlgators suggested thls ;nconslscency probaSly occurred Decause che maxlmum tolerated saccharln dose for the rats was exceeded. tumor-promoting e f f e c t s of s a c c h a r r n l n r a t s . The study was d e t e r ~ ~ n1e5 s a c c - a r l ? b7ould ~ n s r e a s e t h e ? u - S e r of z d r ~ c r s ,o r T h e response of mice to saccharin appears to differ from that of rats. In a NCTR study which examined the effect of saccharin o n the promotion o f liver tumors, saccharin was reported to inhibit tumor development. Whether human cells respond to saccharin more like rat or mouse cells is unclear. NCTR is CRS- 8 IB85119 currently studying the response of human cells i n culture. these studies a r e expected within two years. UPDATE-07/12/85 The findings of Many saechari? s z ~ 2 ~ e P,ave s Seep. c s n d u c t e d in a po~xla:i=rs t3 d e t e r n i n e i f a r t i f i c i a l sxeetep.er ccnscmptio' i n c r e a s e s h c m a ~r i s k a f S l a d d e r carcer. 3 e ir,pace o f s a c c h a r i n co?su!~pc:oc alone is i - -'- F -F 7 ~ ~ l =t o e v a l u a z e -. bscaxse caneor 9ens;a;ly has a I c n q :=-en: peris2 an<, sz:Zy -.,c a ~ p r o p r i a t e t i n e i n r e r v a l , C a z a n s s s 2 e z s ? s i 2 e r e d f r ~ r ,y e a r s w h e n saczP.arir n a n d c y c l a m a t e w e r e b o t h marketed. i h e s:ud:es Sased on tuman poplula:lons (epidernioloqical studies) n a v e no: e s t a 5 l i s h e d a E i z c r e a s e d r l s k of klaCder c a n c e r f o r :he g e n e r a l p c p n l a t ~ o n u s i n g a r ~ i f i c i a l s w e e c e n e r s . - A -- ,-. i' ? . ^ ' . . _:zi:zatl-cs c f =c.e s:,~d.:. Z S Z ~ I ~ ; ~7 ~s.; . ~~ < l res2l:s w e r s 2 a s e e o z :nzerv:eb:s c f p a r t i c l p a x z s , t;i.ers :s sc-e ~r.:ery2i:~:.: - . - '2^n..'2=31~ sr!:ee=e;.er ~ c ~ s ~ ~ , ,z. - - ~ ;_,..- ~- ~ a r ! t : f ~ l p . q325: ar;;r:clal . . d~L s~5 . z h a s a r t i f l c ~ a l s;deere?e:- z s n s : ~ z p : ~ c n 5 1 2 r.c: S e c s x e idieesprea2 2r.t;: z,osz participants were well into adulthood. Therefore, the study wzs usable t~ assess the long-term impact of artificial sweetener consumption drring pregnancy and childhood. I n a d d i t i o n , NCI could ?ot clearly distinguish between the effects of cyclamate and saccharin in this study because ?he Sweeteners were marketed together in the same food products during the 1960s. tccne :he s t T .o m - .+ h o f zP.e F i n a l l y , s o s e c r i t i c s ~f t h e 3 C I s t u e y h a v e ~ c f ' p a + c e r c a ~ n?op;lac;sn su2qrcu9s exper:ence L L ~ t i e a levidence csnTJii?cinq -,.,,I?. a preliminary reporz a Pigher than average bladder cancer risk. c o n c e r n i n g tP.e s t u e y , N C I n o t e d t h a t t h e p o s s i b i l i t y c o u l d not Se excluded t h a t t h e higPier r i s k a s s c c i a z i o n s i d e n t i f i e d f o r c e r t a i n s u S q r o i ~ p s rey?resenz chance variations. --j-Lsre . re s i i e = c 22 ----a- A , \ - + T h e Saccharin Study and Labeling Act has been amended three times to extend the moratorium on the proposed San of saccharin. While the moratorium on May 2 5 , 1985, e l a p s e d o n A p r . 2 2 , 1 9 8 5 , P.L. 99-46 w a s s i g n e d i n t o l a w which extended the moratorium a g a i n , untii May 1 , 1987. A n i m p o r t a n t a r g u m e n t u s e d t o s u p p o r t e x t e n s i o n s of t h e m o r a t o r i u m i n past was the lack of another approved artificial sweetener. Aspartame the was CRS- 9 .approved f o r u s e l n a n u m b e r o f d r y f o o d p r o d u c t s ~n 1981. In July 1983 aspartame was also approved for use ~n carbonated beverages. Many manufacturers of a r t ~ f l c i a l l y sweetened food products d o not consider a s p a r t a m e a c o n p i e t e s u S s t l t * ~ t ef o r saccharin b e c a u s e s a c c h a r ~ n n a s cerzain ~n f o o d processing a d v a n t a g e s ( e . g . , s a c c h a r i n 1 s m o r e s t a S l e t h a n a s p a r z a m e l i q u l d s a n d w h e n heated). Xowever, the approval of aspartame may erode t ~ e f ~ z ~ r ~ef t n e s u p p o r t f o r e x z e n s ~ o n so f z c e s a c c h a r 1 2 n ~ r a t c r l ~ ?:I-. a p p r o v a l o f a s p a r t a n e :s f n r z h e r e x p a n e e d . O n c e c o c s c m e d , a s p a r t a m e L S S r o k e n d o w - t o f o r r ~ t h e t w o c o n s t ~ t 2 e n t sa s z n o acld and methanol, substances that occur naturally l n foods. Aspartaae may also breaK down to form dlketoplperazlne (DKP) w h e n a d d e d to llquzdc or e x p o s e d to a c l d o r p r o l o n g e d h e a t . a scie-tlsr w S.Z. A s p a r t a ~ ex a s a c c i 5 e n z a l l y d i s c o v e r e d i n 1 9 6 5 b y S e a r l e a n d Cov,pa?.y. 3ea:izinq ~ 9 . e potential u s e s f s r zh? sweerer:er, S e a r l e ... = . ex:er.,i-~e :es::y.z ~szab;Fs:p, :?e s z f 2 ; : ~ Sf as;)ay---,- .. 2 zonsany s z S r i = z e d i t s researc:r. f - - d i n g s z c t k ? 'Ch a n 5 se2qLt a p c r c ~ a l of ascarz2r.e ;r ;.;arch 1 3 7 3 . .ne sc;;dies in5:zaseS aspar:zr,e x a s s a f e f c r t?.e gep.erzl r - -u- .r. '- -- a c- - ~ n ,S u c S e a r l e reconr,erS?d i z S e a v o i G e d > y I~.div:=ca_s xit5 phenylketonuria (PKU), a rare genetic disease. People afflicted with TKU must restrict consumption of the amino acid phenylalanine in order LO ?revent Searle's food additive rnentzl r e t a r d a t i o n . I n J u l y 1974, F D A a p p r o v e d petition for aspartame. However, several formal objections were raised about t h e a p p r o v a l b e c a u s e o f c o n c e r n s t h a t a s p a r t a m e u s e by c h i l d r e n m i g h t cause In D e c e m b e r 1 3 7 5 , 3 3 s s a y s d c h e a p p r o v a l of a s p a r t a a e !;:ti1 a brain damage. c o m p r e h e n s i v e revieid of p e r z l n e ~ t researzh coliid be complezed. F2A reexamined the Searle research and concluded i c was valid. In a d d ~ t i o n , FDA established a Public 3oard of Inquiry to clarify the evidence concerning aspartame consumption and Srain damage., T h e Board cpncluded that aspartame consumption would not pose a n increased risk of brain damage, Dut raised questions about its potential to cause Srain tumors [48 P R 392851. A s u b s e q u e n t study s a t i s f i e d F 3 A t h a t a s p a r t a m e consunction a l s o uould nct increase the risk of developing brain tumors. - i Jul a1 ion lY tS ark ' P T - On appro condi actua produ When - - 1981, artam e f prova1 , on th e q u i r,ed t s a ta b l A ommissio uS in a arl was req a r k t. Als sta e ?hen top sweetene lf er umbe ired , t 1ket r th rth r HC 1 1 dry fo to o n i t o r th e abel of n u r cs: cont pr duct labe 0 ayes, J d produ amount aspartam i n s ?he was a 1 ordered s. As a a sp a r t a m e containing l a 1a n i n e . required I to bear instructions indicating that aspartame should not be used in because of its tendency to break down when exposed to prolonged heat 273201. cooking [ 3 9 FR Inltlally, aspartame was not approved for use ln llquid produczs because rt could break down more easily ln llqdids, loslng sweetness a n d forming D K P , an undes;reaSlo b y - ~ r o d u s t . E c w e v e r , en :u:y 8 , 1953, 2 . a ~ e z 4 e C t?e a s p a r z a n e r e q u l a c l 3 n s c c a p p r o v e u s e LP. c a r b o n a z e d b e v e r a g e s and carsonazed a f - 9 ~ Searle s y r ~ pS a s e s . T n e e x p a n d e e a p p r o v a l of as?ar=ane =c^','red 1) z 2 e st2z;l:ty zi as;arta.%e :L a;saizze5 ev;SenC? t k a c s a z i s f l e d ?'2A t c a c : .-.. . ,-l,-ds w a s s u f f i c z e n t f c r :?.e n c r m a l s n e l f - l ~ f e o f car5sna:ee =evera:es, a?.? would no2) r h e l n c r e a s e ~ n a s p a r t a m e c o n s u c p r l o ~ .resulting f r o m a p p r o v a l nave zoxrc effects. S e a r l e c,rren-ly m a r ~ e t s as?ar:ame ~ n e e r:-e trade name "Equalw as a :able-top swee:er.er, and a s "N'2craSweecn wne?. u s e d as a ''-sweetener addee + ^ foods + ,,-,rq c n e rnac12fac:~rlng ? r c z e s s . - u - L - iV Some c r l t l c s a r e n o t c o n v i n c e d t h e s a f e t y o f a s p a r t a m e h a s b e e n a d e q u a z e l y under the current condlticns of use. The following list c a p s u l l z e s s o n e o f t h e ~ e yc o n c e r n s e x p r e s s e e S y c r i t ~ c s : established 1) ,'2) 3) T h e y s u g g e s t t h a t t h e p i v o t a l s z u d l e s o n w h i c h F'CA ;ts ip.lt$al a ~ ? r o v a l c f a s p a r t a m e w e r e c o n d u z t e d p c e r l y 2 n d m s s c <::ere n e v f r r e 2 l i c a t f 2 . base5 T h e y s1;qgest t?.at s o z e s z f e z y c3ncsry1s ;):?re :z: adequzze:y rsss:vfg, :p.cl"e:r.c :::F,f=p.er assar;s?,-,e riiay lr.crsase c C e r i s k 3 f :rain t:zars, z a y ~ ~ ~ z e r a cw i :ch d i e t a r y c a r b o h y d r a t e a n d a f f e c t b e h a v i o r , m a y l n t e r a c t w:th monosodium glutamate (MSG, a seasoning) and increase t h e r i s k o f S r a i n d a m a g e , w h e t h e r c h e b r e a k d o w n products o f a s p a r t a m e ( p h e n y l a l a n i n e , a s p a r t i c a c i d , m e t h a n o l , DK?) may be harmful, and whether aspartame is safe a t the levels . . - . no^ b e i n g c o n s u m e C , a n d w k e n m a r k e t ? - ;n ~iqz12s. T h e y s u g q e s t t3.e r e g s l a c o r y p r o c e s s ??A f o l l c w e d ~ e f o r ea p p r o v i n g a s p a r t a m e a p p e a r e d t o l g n o r e s y s t e m a t z c a l l y some of the safety concerns expressed S y some FDA s c i e ~ t l s t s a n d m e n b e r s o f t h e Public B o a r d of I n q u l r y . In addiclon, they s u g g e s t sor,e s c l e n t l s t s w h o f a v o r e d :he a p p r o v a l o f a s p a r t a m e z n i 9 & i C l d s o S e l l e v l n q i: w o u l d n o ~ e m a r k e = e d l n liquids S e c a u s e o f t h e t e n d e n c y o f a s p a r t a m e t o b r e a k d o w n ~ n l~qulds. Such concerns as those listed above prompted Senator Metzenbaun request a n investigation of the approval of aspartame Sy the A c c o u n t i n g O f f i c e , i n M a y 1985. (OH) t o General THE CENTERS FOR DISEASE CONTROL (CDC) AND F D A S T U D Y Since aspartame was approved, FDA has received numerous health complaints the consumption of aspartame. In which consumers believe are linked LO February 1384, CDC and FDA initiated an investigation of these complaints. T h e i n v e s t i g a t i o n w a s designed to d e t e r m i n e ~r a pattern couid be d e f i n e d f o r deiai:eB szudy. t h e r e p o r t e d s y n p z o m s x?,;ck w o c l i i z S i c a = e a ~ . e e df o r n o r e It was recognizee a t e outset ihai there were l ~ m ~ t a z i z r ~i sn an i n v e s t i g a t i o n of a l r e a d y r e z ~ r t e e s y ~ p t o m s . T h e s z c 2 y x o u l d 5 e x r l i ~ e l y z o e s t a S l i s h a ca3Gse a n d s f f e c z relazior,sL;p Letween syiripzo?,s a n 2 a s ? a r L a n e consurnpiion. A l s o , t h e ir.ves:iqa;io?. as p r c 5 a S l y n o r e l i k e l y = o 5 e z e e t r a r e 2 n d s e r i o u s c c n d i t i o n s o c c u r r i n g s h o r t l y a f c e r asparzarne c s e , t n a n symptoms co?,no~.i n t h e p o p u l a t i o n a n Z c h o s e o s c u r r i n q a l o n g t F r e a f c e r u s e . , ? vt & , FDA has ~ o c t3angeC its position concerning the safety of aspartame since i: w a s a p p r o v e d i n 1 9 8 1 a n d 1 9 8 3 . T h e a g e ~ c yh a s m a i n t a i n e d that aspartano i s safe and i s the mosx tested food additive in history. The F9k position is that all che health questions that have been raised so far have been 23equarely a55ressee. . There are no ?laps to chan9e the regclatior. sf asparzarne c n l e s s n e w r e s e a r c h i n 5 i c a t o s a r e e v 2 l a a t i c n i s n e e C a 2 . A t t h e Apr. 2 , 1 9 8 5 h e a r l n g o n t h e 5 a c c h a r 1 n ' m o r a t o r 1 u m , b e f o r e t h e S e n a t e Committee o n L a b o r a n d H u m a n R e s o u r c e s , FDA Commlssloner Young scated he f a v o r e d h a v l n g m o r e t h a n o n e a p p r o v e d a r t ~ f l c l a ls w e e t e n e r o n t n e m a r k e c . He suggested multlple sweeteners offered publlc health advanrages. Speclflcally, because there would not be heavy rellance on only one cf e a c h . s w e e t = r n r i:ol:ld Se r e , tkere5y soleotener, tP.e cor.sum?tlon ~lt:g:.tlng a n y p o r e n t l a i l y n a z a r d o s s ~ e a l z ? .e f f e c ~ s . lndustry may also ~ e n e f l t from havlng multlple T h e f o o d processing approved sweeteners. Artlflclal sweereners nave dlff eren* chenlrlal p r o p e r t l e s n a ~ l n gs o m e m o r e s t a b i e , b e t t e r t a s z l n q , o r m o r e economical t o c s e I n addiclon, some artlflclai sweete~er l n d ~ f f e r e nf~o o d s o r b e v e r a g e s . inlxtures h a v e s y n e r g l s t l c sweete?.:ng propertles so that a smaller amoccz of two or more sweeteners can be used than ~f only one sweetener were used ~n a wlder varlety of artlflclally food. Industry may be able to develop a selection of sweetened food products lf t h e r e w e r e a m o r e versatile s w e e t e n e r s a n d s w e e t e n e r c o m b ~ n a t l o n savailable. The actual impact multiple sweeteners would have on public health is unknown. Whether or not consumers would in fact reduce their reliance on one sweetener is also unknown. Consumers a r e currently increasing their reliance o n a s p a r t a m e d e s p l t e t h e f a c t t h a ~D o t h a s p a r t a m e a n d s a c c h a r ~ n a r e o n the market. I n a d d l t l o n , ~ f t h e p u b l l c continues t o b e welght-conscious, a n d lf a wlder varlety of a r t l f l c ~ a l l y sweezened food products become avaliable, t o t a l a r t l f l c i a i s w e e t e n e r c o n s d m p t ~ oc~o u l d ~ n c r e a s e . T!-I~ puollc health impact of ~ n c r e a s e d exposures t o many artlficlal sweeteners, or the n u t r l t l o n a l ~ m p a c to f h l g h a r t l f l c l a l s w e e t e n e r c o n s ' ~ m p t l o n l n l l e b o f other d l e t a r y c a r S o h y C r a z e s , 2 s ,nclear. P O I N T S FOE? F U R T H E R C O N S I D E R A T I O N A c t t o e x t e n d to F a y i , 1 9 f 7 , t c e A m e n d s t h e Sacccarl?. S t x C y a n d 5aSe;;ng p e r ~ o d S ~ r i n gd h l c h z t e S e c r e z a r y o f X e a l t h a n d E d m a n S e r v ~ c e sn a y E o take c e r t a l n a c t l o n s t o r e s t r l c c t h e c o c t l n u e d u s e o f saccharin o r of any food, d r u g , or cosmeclc conta-nlng s a c c h a r ~ n . Introduced Feb. 2, 1985; referred to Committee on LaSor and Human Resources; hearlng heid Apr. 2 , 1985. The require aspartame measure was reported to the Senate wlth an amendment to c o n t e n t l a b e l l n g o n s o f t d r l n ~ s ,A p r . 2 2 , 1 9 8 5 . The Senate passed the blil lleu a n d r e j e c t e d t h e a m e n d m e n t o n M a y 5 , 1 9 8 5 . T h e H o u s e p a s s e d S . 484 ~ n o f H.R. 7 9 1 o n M a y 1 4 , 1 9 8 5 . President R e a g a n s ~ g n e dt h e b ~ l l r n c o l a w o n May 2 5 , 1985. H.R. 7 9 1 (Foley) the period during A m e n d s t n e Saccharin S t u d y a n d L a b e i l n g k c c t o e X h n d whlch the Secretary of Health and Huzan Servlces may not taKe certaln actlons L O r e s t r l c t t h e continued u s e of s a c c h a r l n o r o f a n y f o o d , d r u g , o r cosmeclc referre2 to Coam:z:ee cr c ~ n t a i n i n g sacchar;?, I ~ . t r o 5 c c e dJ a n . 3 0 , 1 9 2 5 ; E n e r g y a n d C o m m e r c e , c n e S u ~ c o n n l c c e e or. H e a l t n a n 2 t n e Z n v l r o n ~ e n t . Congress. Senace. C o m m i c c e e on L a S o r a c 3 Ea?,an X e s o u r c e s . S. 4 8 4 , a b i l l c o excend z n e m o r a t o r i u n o n the ban of s a c c h a r l n for zhree years. Eearing, 99zh Congress, Ist s e s s i ~ n . April (not yet prinzed) . 2 , 1585. L.S. U.S. Congress. Senate. C0mm;ttee o n L a b o r a n d H x m a n R e s o u r c e s . SubcommlEtee on Eealzh and Sclentlflc Research. Tne saccharln Dafi a n d f o o d s a i e c y ?ol:cy, 1S79. H e a r l n g , 9 6 t n C o n g r e s s , ;st sesslon. M a y 9 , 1979. F a s h l n g t o n , U.S. G o v c . P r l n t . O f f . , 1 9 7 9 . 323 p . U.S. Congress. House. Commlztee on Interstate and Forelgn Subcommittee o n H e a l t h a n d t h e E n v i r o n m e n t . Commerce. Moratorium o n t h e s a c c h a r l n b a n . H e a r l n g o n H.R. 7 7 5 3 , A ,crlr.q t h e I n s c ~ t u ~of e ?!ed~c;r.e o f t k e h'atlonal A c a d e r ~ y 2 5 S c ~ e r c e s :.o c o n 5 d c E a o > e - y e a r r e v l e w o n zPLe Hearing, t o x l c ~ t ya n d carc:nogen:lclty of f o o e aCdlt:ves. 9 5 t h C o n g r e s s , 1 s s~e s s l o n . June 27, 1977. Washington, U.S. G o v t . P r l n t . O f f . , 1 9 7 7 . 143 p . 7-0 U.S. Congress. Senate. Committee on Euman Resources. m Subcommittee on Healch and Scientific Research. Ihe banning of saccharin, 1977. Hearing, 95th Congress, 1st session. June 7 , 1977. W a s h i n g t o n , U.S. G o v t . P r i n t . Off., 1 9 7 7 . 173 p. U.S. Congress. House. Committee on Interstate and Foreign Commerce. Subcommittee on Health and the Environment. P r o p o s e d s a c c h a r i n ban - - Oversight. Hearing, 95th Congress, 1st session. March 21 a n d 2 2 , 1977. W a s h i n g t o n , U.S. . Govt. Print. Off., 1977. 592 p . U.S. Congress. Senace. S e l e c t Committee o n S m a l l B u s ~ n e s s . F o o d A d d ~ t ~ v e s :C o m p e t ~ t ~ v er,e g u l a c ~ r ya n d s a f e z y p r o b l e m s , parts a n d ;I. Hearings, 9 5 ~ hC o n g r e s s , 1 s c sess:on. January 13 and 14, 1 9 7 7 . W a s h l n g c o n , U.S. G o v t . P r i n t . O f f . , 1 9 7 7 . 3 7 9 p. U.S. Congress. Ecuse. Comin:t:ee on tne Judlclary. Su~conm:ctee Nc. 2 . .C y z l a ~ a t e s . z- e a r l n g s C E 8.2. 4 2 5 4 , 3 . R . $180, z.9. 4255, E.3. 4970, -- . 5 -E X . 2 2 2 . 2 , . 5 , 2.2. 5 zear::,~, 9 2 6 C o n q r e s s , Is: sess:on. Sss:e?,>er 29 a?.d 3 3 ; C c +,"ver ^ 5 , 197;. W a s h l n g c o n , U.S. G o v t . P r : r . z . Off., i971. 384 p . U.S. Congress. Bcuse. C o m m l z t e e o n Governmen: O p e r a z ~ o n s . Cyclamate sweeteners. 3sar:ngs, 91st Zsnqress, 2 6 sess~or.. Z s n e 1 0 , 1570. h'asklngco?., 2.9. 3 s v z . ?rr?,t. 3 i f . , 1 5 7 C . 1 0 3 p. U.S. Congress. House. C o m m i t t e e o n Appr0pr:atlons. Study of the D e l a n e y c l a u s e a n d o t h e r anticancer c l a ~ s e s . H e a r l n q s , 9 3 r d Congress, 2 C session. Y a y 5 , 1 9 7 4 , p a r c 8. Wash:ngton, C.S. G o v t . P r l n t . O f f . , 1 8 0 p. U.S. Congress. House. Committee on che Judlclary. C o m p e n s a t ~ o nf o r l o s s e s r e s u l t i n g f r o m t h e b a n o n c y c l a m a t e s (H.R. 1 3 3 6 6 ) . Washlngton, 1971. 1 9 p. ( 9 2 d C o n q r e s s , 2d s e s s l o n . House. R e p o r t no. 92-10-5) . U.S. Congress. Senate. Committee on Aqriculture, K-trition and Forestry. Food safety: where are we? Washington, 1979. comm. print) 578 p. (96th Congress, 1st session. U.S. Congress. Senate. C ~ m m l t t e eo n C o m m e r c e , S c i e n c e , a n d T r a n s p o r r a t ~ o n . Saccharin S c u S y , a n d L a S e l l n g a n d A d v e r t - s l n q Washlngton, 1977. 7 p. (95th C o n g r e s s , 1 s t Act ( S . 1750). s e s s ~ o n , S e n a t e , R e p o r t no. 95-369). U.S. Congress. Senate. Commtee on Human Resources. Amending the P u b l i c H e a l t h S e r v i c e A c t (S. 1 7 5 0 ) . Washington, 1977. 2 2 p. Report no. 95-353). Senate. (95th Congress, 1st session. CHRONOLOGY OF EVZNTS 05/25/85 - - P r e s ~ d e n tR e a g a n s i g n e d S. 484 (P.L. 9 9 - 4 6 ) e x ~ e s d ~ ntgh e s a - c h a r ~ n n s r a z 3 r : u r , 35/14/85 -- 05/97/85 - - ? h e S e n a t e p a s s e d S . 454. T h e H o u s e p a s s e 6 S. 484 i n :leu - ~ x c i lX a y i , 198'. o f E.8. 791. . 2 4 / ~ 2 / 3 5 - - T h e S e c a t e 2snr.itzse ori , a ~ o r a n d E::nan 3ssosrces hel5 h e a r i n g o n S. 4 6 4 , a b i i l c o e x t e n d t h e s a c c h a r i n moratoriur?,; a n d z o r e v i e w t h e s t a t u s o f c y c l a m a t e a n d -5?aTza:e. 07/00/84 -- The Nacional Academy of Sciences, at the request of 2 FDA, initiated a review of the scientific evidence concerning t h e c a r c i n o g e n i c i z y of c y c l a n a y e . 33/30/8t - - -,?.e '3A 2nd initiated a ?er:er; f o r "sease Cencrsl (C23) study of consumer complarnts concerzlng aspartame. 07/08/83 -- F D A approved the use of aspartame in carbonated beverages and carbonated syrup bases. 34/22/% -- K.L. 11/12/82 - - A b b o t t L a b o r a t o r i e s a n e :he 07/24/81 -- FDA approved aspartame for use in certain dry food 9 8 - 2 2 (S. S 9 ) w a s sicr.?C i 3 - L ~l a w , e:z:zer.l:ng s a c c h a r i n mcratori3rc u n z i l A p r i l 2 2 , 1 9 P 5 . =:ye C a l o r ~ eC o n ~ r o lC o ~ n c i l f ~ l e d :he s e c o n d p e t l t i o n f o r c y c l a m a t e u s e a s a f o o d a d 3 l t i v e since t h e b a n of c y c l a m a t e i n 1969. products. 10/00/80 -- F D A P u b l i c B o a r d of I n q u i r y i s s u e d a r e p o r t c o n c e r n i n g aspartame safety. 09/16/80 -- F D A announced the final decision which denied the food a d d i t i v e p e t i t i o n f o r c y c l a m a t e s u b m i t t e d by A b b o t t Laboratories. 05/17/80 - - P.L. 02/04/80 -- 9 5 - 2 7 3 w a s s ~ g n e c i ~ n t ol a w w h i c h e x t e n d e d t h e s a c c h a r i n m o r a t c r ~ u m u c t i l Z ~ n e3 C , 198;. An FDA Administracive L a w Gudge issued che second Initial Decision on zhe cyclamate f9od addizive petition w h i c h s a i d t h e p e ~ i t i o n e r ,h b b o z t L a b o r a t o r i e s , h a d This f a i l e d t o e s t a b l i s h t h e s a f e c y of c y c l a m a t e . d e c i s i o n folloT:iee a review of furz5er 5earing evi5ence w3ich had b e ~ n r e q u e s t e d by c h e C o m m i s s i o n e r o f F 3 B . 12/20/75; - - T h e p r e l i m i n a r y f i n d i n g s o f t h e N a t l o n a l C a n c e r I n s ~ i t u t es t u d y o c h x m a n S l a c d e r c a n c e r w e r e a n n o u n c e d 5:y P E A . - h e f i n S i n g s i n d i c a t e 5 a r t ~ f i c i a ls x e e c e x e r consur,ption did n o z i n c r e a s e t3e risk c f S l a d d e r cancer in the general population, but may increase t h e r i s k i n c e r t a i z z=~,:ati:n s : ;,b- Lc L~ y-=, ~2-s~ " K c : ? , a s 5 C percent. r;l 05/09/70 - - T h e S e n a t e Comrnictee o n L a b o r a n d H u m a n R e s o u r c e s , S u b c o m m i t t e e o n H e a l c h a n d S c i e n t i f ~ cR e s e a r c h h e l d a h e a r i n g o n t h e p r o p o s e d D a n of s a c c k a r l n a n 5 f o o d safety policy. 04/11/79 - - T h e H o u s e C o m m ~ t z e eo n I n t e r s ~ a t e a n d P o r e l g n C o n m e r c e , S u S c o m r r ~ c t e e o n H e a l t n a n d Z n e 2nv:ronment neld an svers=qhz hearlng concerrlng tne prozcsed za?. cf s a c c - a r - c 2?.2 z.?e f:nd:n;s zf z n e T?.S c o n c e r n ~ z g = h e carc;zogenlclty af sacc?.zr:n. 23/32/32 - - ,as 12/00/76 -- 08/04/78 -- An FDA Admlnlstrazlve Law Judge lssued an iniclal ? / P A S r a l e a s e c :rie f ~ ~ d ~ nofg zsh o f o o l safe; 4' p o l ~ c y s t u d y , w h ~ c hw a s m a n d a c e d n n d e r t h e S a c c n a r z n Study a n d Labeilng Act l n 1977. In the report, NAS called for major changes ln existlng food safety laws. TI' confirmed the validity cf the asparcane s c , ~ d i o s cor.ducted by S e a r l e . F'DA D e c i s i o n o n t h e f o o d a d d l t i v e p e t i c l o n concerning cyclamate, and concluded che petztioner, Abbott L a D o r a c o r ~ e s ,had not e s t a S i ~ s h e d tne safety of cyclamate. 01/25/78 -- 11/23/77 - - P.L. 9 5 - 2 0 3 , T h e S a c c h a r i n S t u d y a n d L a S e l i n g A c t The FDA and National Cancer Institute announced a m a j o r s t u d y designed t o d e t e r m i n e if a r t i f i c i a l sweetener consumption increases the risk of bladder cancer in humans. was signed into law. The law required a moratorium on the proposed ban of saccharin, product labeling, and a NRS review of saccharin research studies and food safety policy. 06/27/77 -- 95/97/77 - - T h e S e n a t e Conni=:ee T h e H o u s e C o m m ~ t c e eo n E n e r g y a n d C o m m e r c e , S u S c o m m i c t e e o n H e a l t h a n d c h e Environment h e l d a h e a r i n g o n a b l l l c o n c e r n z n g a s a c c 3 a r ~ n% o r a t o r l c x , a:d on receKt sazcharzr studles. o c H c x a n 3 e s o c r c e s , Scbc33tr.i~;ee 2 : Health and Scienrific 4esoarch held a hearing t o evalsare he s c i e n t i f i c S a s i s f o r t h e b a n o f s a c c h a r i n p r o p o s e d by FDA. 0 5 / 1 8 / 7 7 a n c 05/19/77 - - " ,he F B A h e l d p d k l l z h e a r ~ n g s on :he 5an of s a c c h a r ~ r . proposed 03/24/77 -- 03/21/77 a n d 03/22/77 -- T h e E o u s e C o m m i ~ t e e o n I n t e r s t a c e a n d F o r e i g n C o m m e r c e , S u b c o r n ~ ~ i z ~oene S e a l r n a n d ~ h e E n v i r o n m e r c .n e- ~- c a P.earin.2 o n :he p r s p o s e 5 S a n cf s a c c h a r i n . T h e S e n a t e Cornmitree o n H u m a n R e s o u r c e s , S u b c o m m i t t e e on Health and Scienrific Research held a hearing to c o n s i d e r t h e prop.osed b a n o f s a c c h a r i c . 01/13/77 and 01/14/77 - - T h e S e n a t e S e l e c t C o m m i t t e e o n S m a l l Business held a hearing concerning the Competitive, regulatory and safety problems associated with food additives. 1 0 / 3 4 / 7 6 - - R b b o t t L a b s . a n d tP.3 C a l o r i e C o n t r o l C c 2 n c i L f i l e d a f o r z a l o j j e c t ~ o n L C F 3 . k ~ d e n ~ a lo f he c y c l a c a t e f o o d a25i:;ve p e t i t i o n a n d r e q u e s t e d a f o r x a l e v i d e n ~ i a r yh e a r i n g . 12/00/75 -- 12/00/74 - - The N A S recommended t3at more research S e Zone 10/04/76 -- The denial of the food additive petition concerning F D A s t a y e d r e g u l a t i o n s w h l c h w o u l d h a v e permitted marketing of aspartame. O R the carcinogenicity of saccharin, Dased on the findings of a review of saccharzn studies which was conducted a t the request of FDA. c y c l a m a t e , s u b m i t t e d by A b b o t t L a b s . w a s p u b l i s h e d i n the Federal Register. 02/00/76 -- 07/00/74: -- FDA 1;/15/73 - - A 2 S o t c L a S s . f ~ ; e Z a :sod 03/02/73 -- The T e m p o r a r y C o m m i t t e e for the Review of Data o n the C a r c i n o g e n i c i t y of C y c l a m a t e o f t h e N a t i o n a l I n s t i t u t e s Of H e a l t h i s s u e d t h e i r f i n a l r e p o r t . The report stated that the evidence did not establish the carcinogenicity of cyclamate or its principle metabolite, cyclohexylamine, in experimental animals. approvee aspartane for use a s a food a d d i r ~ v e . ad5:z:ve p e t ~ t ~ srze q x e s z ~ ~ q I C A a p p r o v a l o f c y c l a n a t e a s a s v e e z e c l n g a g e r t ~n f o o e . S e a r l e f ~ l e da f o o d a d 5 r t r v e petltro:. r e q u e s t l n q ap?rrcva; of a s p a r t a m e a s a s w e e t e n l n g a g e n t r n f o o d . - - . 3. ~- ~ / 3 5 / - ;- - " ~ ~Eo>:se e 's~n:tzee o n t?.e ? s / 2 ~ / 7 :2 7 2 C?/32/'1 s ; ~ d ~ c : a r y , s u ~ c o ~ n ~ t tNeo .e 2 h e 1 5 a h e a r ~ n q 2: s e v e r a G -- -LA".-A Y L - yC12?tZLS. cl;ls r e y- - 06/10/70 -- The House Committee on Government Operations held a hearing on cyclamate sweeteners. 10/18/65 -- F D A a n n o u n c e 8 c y c l a m a t e w o u l d b e r e m o v e d f r o m t h e l r s r sf G R A S s u b s z a n c e s b e c a u s e of r e s e a r c h w h l c h s u g g e s t e d c y c l a m a t e may c a u s e ladder c a n c e r l n t e s t a n l m a l s . Saccharin - - of r l s k a n d d e m o c r a c y . C o o p e r , R l c h a r d M. C o s m e t r c L a w J o u r n a l , v. 4 0 , , 1 9 6 5 . p. 34-65. Food Drug I r c r e a s e d t u z s r ~ r e r z l e n c es?.own :n F o 5 E C t e ~ l c a lN e w s . ;rom~:ion siu?y. S c t o ~ e r j:, 1 3 i j - p . 5:-53. NCTR szccmar;? S a c c h a r r n c a r c l n o g e n ~ c r t y confirmed by C a l o r r e Food Chemical News. Control Councrl study. May 1 5 , 1983. p. 3 - 8 . H o w s a f e r s y o u r d:et s o f t ir:nn7 Graves, Florence. Magazine, J u l y / A u g u s t 1 9 8 4 . p. 2 5 - 4 3 . H e n t e l o f f , T h o m a s 0. T h e D e l a n e y F y t n s . Journal, August 1978. p. 3 9 6 - 4 0 4 . Common Cause The Food, Drug, Cosmetrc Law Artificial H o o v e r , R o b e r t N. a n d P a t r i c i a H a r t g e s t r a s s e r . Sweeteners and Human Bladder Cancer - - Preliminary Results. The Lancet, Apr..19, 1980: 837-840. National Academy of Sciences/National Research Council. A s s e m b l y o f L i f e S c i e n c e s / I n s t i t u t e of M e d i c i n e . Committee for a Study on Saccharin and Food Safety technical P o l i c y . 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APPENDIX 1 REGULATORY S T A T U S O F S A C C H A R I N , C Y C L A M A T E , AND A S P A R T A M E IN E U R O P E AS O F A P R I L 2 4 , 1 9 8 3 BELGIUM ( s a c c h .- T F B ; cycl.-T; aspart.-T) NZTHERLANDS DENMARK ( s a c c h .- T F B ; cyc1.-T; aspart.-TFB) N3RWhY FINLAND ( s a c c h .- T F B ; Cycl. -TB) PORTUGAL FRANCE ( s a c c h .- T ; c y c 1 . - T ; aspart.-") SPAIN (sa~ch.-TFS: cycl. -TB) ( s a c c h .- T F B ; cyc1.-TFB; aspart.-T) ( s a c c h . - T ; c y c l . -T) ( s a c c h .- T F B ; c y c l . - T F B ) ( s a c c h . -TFB) GREAT B R I T A I N GREECE ( s a c c h . -T) SWEDEN ( s a c c h . -TB; a s p a r t . -TFB) SWITZERLAND WEST c y c l . -?; (sacch.-TF3; a s p a r t . -TFB) GERXAXY isacc2.-TFS; cyci.-TF3; cycl.-TP3; aspart.-T) SYMBOLS : ;zgredlent "T" 13 It F = Approved as cable top sweetener " 8 " = A p p r o v e d a s 1 ~ g r e d 1 e n t 13 b e v e r a g e s = Approved foor2s I1 as CRS-21 APPENDIX 2 PER CAPITA CONSUMPTION OF ARTIFICIAL SWEETENERS, 1963-83 [ K E Y : pounds of sweetener consumed compared co the pourds of sugar n e e d e d t o a c h l e v e the same s w e e t n e s s * (in p a r e n t h e s ~ s ) . */ **/ T h e sweecr:ess i a c z o r s u s e d z o c a l c s l a t e t h e p o u z e s a: s u g a r 2 r e a s s u m e d t o be: C y c l a ~ a = e ,3 C cines :he sb;eetness a f s u g a r ; S a c c h a r i n , 3 3 3 t i x e s = h e s w e e t n e s s o f s c g a r ; an5 R s ~ a r t a s e , 2 C s times the sweetness of sugar. C y c l a m a t e w a s removed f r o m the G R A S l i s t in October 1 9 6 9 , a n d was banned in August 1970. Source: Adapted from USDA Economic Research Service consumption data.