Document OERBkg0bmEp0Yve5kjKnK6Mjj

f: "*TP> i ! /.'. `ju JiiJpc* i" - j - ; . . '. - : *v r " /.; a: * v .**/. if ..Acr*#3^*v^V.t... -: A- 1 v3-|___ i%VW^wT* .^gfeMns'-**?***** -- ;s^t. .x*-r*\sf?gr/rto. r..***3*f**.*~vtfs..s ' ^fy&Asax+.&tz.jfCi ' r-f: jt; -.; 4. ?* . ./" \W .*, ' w ._.*- ' . * ,s <s: I . '\S` -rfv;A t.-StV" "' .>.vrr*|'4o.r. *'-: H l. -. Vo'^-T.- - .V.- - - - *'* K<v,.Ar<iar^ . %.rHTl\n nr.. *-' < - .*. J-siu . * 5Tv'. U* . ,. ~rn`-:____ * .. -v> * ..`C.'fO'.'JA?- .: <5. ' ` ;'-r--: -r- :\-V- - * ' tj <?. -'r;- ;u--U'i - '. a :* ..: v:.*N. "-L* *>'>' . .. i-f :t ** ' *I.ziV-'-.;i . * U -i -- '-< ' .' -: < . *. . c-f; .-' ' : `v? f*\ : . -i ''X . .* .i.^gKycjx* -ir . ;s. fi, .:- i j x : *. ,`.4i Cj. j ,vw;. THURSDAY,SEPTEMBER'23,i976 i,. *'*.*. .< 44- * -. ; *. . c. ' V;.*l V. : " ^T.-'V. ". 1 -. `V*A*v*5` PART II: 7.V- 3>iv" .. . . iV. IV ,s*, (* *"?***" ' . -i ; .* ;. * * * ; . ^departmentof %* *' t .9r**. * V, .... HEALTH, EDUCATION, AND * . s ,'> ',K\ ' ... :*' , 'n : V.v: *; ` * r V: r>:-y WELFARE Food and Drug Administration ' . ;r^* 4 COLOR ADDITIVES .*/ see 1-0021 ' 1352 , RULES AND REGULATIONS ,v;, * J Title 21--Food and Drugs . , cherries, short-term Ingested drugs, and lowed. For the purpose of this order, a ; CHAPTER I--FOOD AND DRUG ADM1NISTRATION, DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE L :!V " SUBCHARER ^t-GENERAL- externally applied drugs and cosmetics. recommendation or suggestion for use Concern about the safety of FD&c Red longer than 6 weeks shall be considered No. 4 when used In food and Ingested a recommendation for continuous ad drugs was first raised In 1964. The basis . ministration." for. concern about possible harm from The Commissioner's conclusions in KW'.'- (DocketNo.7eN-038ej ingesting FD&C Red No. 4 was a 7-year 1965 that FD&C Red No. 4 could safely PART B--COLOR ADDITIVES feeding study In which dogs were fed the be* used in maraschino cherries and color additive at levels of 2 percent and short-term ingested drugs were based on Termination of Piovbional Listing and Car- 1 percent In the diet. Adverse effects con the following: [ ' tification of FD&C Red No. 4 for Use in sisting of hemorrhagic papillomas In the - , Maraschino Cherries and Ingested Drugs urinary bladder detected both grossly 1. The OlvUloQ of Pharmacology of FDA had completed phase one ot. an FD&C Red The Pood and Drug 'Administration and microscopically, and atrophy of the No.' 4 feeding study which had begun In ..s (FDA),Is all certificates and zona glomerulosa in the adrenals .seen October !&.' The results of that study terminating the provisional 11sLug and microscopically, were found at both feed- - showed no sdverse effects, either grossly or - .certification, and hcnco the approval, of - the color additive FD&C Red No. 4 for use.' .-In maraschino cherries and Ingested drugs, effective September 23,1976. Pub lished elsewhere in this issue of the tag levels. Three of the five dogs fed at the 2 percent level died during the study after 6 months, 9 months, and 5& years. Two of the dogs fed at the 2 per cent level and all five of the dogs fed . microscopically. In eight young dogs fed 400 milligram i (mg) per day of FD&c Red No. 4 for a mon ha. * 3; In another study no significant advene effects were detected In guinea pigs fed FD&C .Red No. 4 for-fi months at the l percent level Federal Register are regulations listing at the 1 percent. level survived to the la the diet.* . FD&C Red No. 4 lor use In externally ap- completion of the 7-year study. 3^ No adverse effects were found Jn rats ^ piled drugs and cosmetics and denying On the basis of the results of this study, and mice fed FD&O Red No. 4 la | 2-year the petition for listing with respect to use the provisional listing of FD&C Red No. 4 study. - in- maraschino cherries and ingested for use in food, ingested drugs, and In 'drugs. - .. Section 8.501 (21 CFR 8101) of the * color additive regulations designates those'color additives that are provision.ally listed under section 203(b) of the ' transitional provisions of the Color Addl- - / tive Amendments of i960 (Title XI. Pub. 'I* 85-818, 74-Stat. 404-407 (21 US.C. 376 note)), on an interim basis pending completion of scientific Investigations needed for determinations about "per gested cosmetics was terminated by reg ulation published In the Federal Regis ter of December 11, 1964 (29 FR 16983). Because no questions about the safety of FD&C Red No. 4 for external uses were raised by the feeding study, the Decem ber 21,.* 1964 regulation provisionally listed the color additive under the name Ext D&C Red No. 24 for use In exter nally applied drugs and cosmetics. . In 1965, the National Cherry Growers manent listing" in accordance with sec-, and Industries Foundation ard the Mar tion 706 of the Federal Food. Drug, and aschino Cherry and Glace Fruit Associa Cosmetic Act (sec. 706. 74 St&t. 399-403 tion requested that FD&C Red No. 4 (21 U-S.C, 376)). ' - The color additive FD&C Red No; 4 has been in use in food for many years, having been originally approved for food ' use under Its common name ."Ponceau SX" through Issuance on April'2.1929 of Service and Regulatory Announcement . Food and Drug (SRAFD) No. 3. Supple ment No. 1, by the Food. Drug, and In secticide Administration, Department of Agriculture. SRAFD No. 3 supplement No.. 1. adu-sl FD&C Red No. 4 to the again be provisionally listed for limited food use In maraschino cherries. The Commissioner of Food and Drugs, In a regulation published in the Federal Reg ister of August 19. 1965 (30 FR 10269), concluded that this limited use of FD&C Red No. 4 in food would present no po tential for harm to the public and there fore restored the color additive to the provisional list, restricting use of the color to maraschino cherries at a level of 150 parts per million (ppm). The regu latlon also simultaneously revoked the 4. A teutatlTe no-effeet level could be ex trapolated from the 7-year feeding ' udT / ; from the advene reactions In the dogs fed' : FD&C Red No. 4 at the 1 percent dietary level aa cocnnared to the reactions In those dogs fed at the 2 percent dietary leveL B. Oont imptlon of FD&C Red No. 4 from maraschino cherries (apnroxlznately I mg of the color additive per cherry) and short- terra Invested" drugs (5 mg per day uad-r permitted conditions of use) would be A dolor additive petition (CAP 61) reeking the "permanent" listing of FD&C Red No. 4 for use In maraschino cherries, short-term ingested drugs, and exter nally applied drugs and cosmetics was submitted to FDA on March 27.19GB by FMA. The Toilet Goods Association, now the Cosmetic. Toiletry and Fragrance Association (CTFA). and the Certi fied Color Manufacturers Association (CCMA) joined the PMA as copetitioners to list FD&C Red No. 4. A notice of Ji'ing of the petition was published In the Fed eral Recxster of November 20, 10G8 (33 FR 17205). Submission of this petition to li<t ' FD&C Red No. 4 was deferred until 1968 ' list of color additives accepted for volun tary certification. FD&C Red No. 4 was approved for drug and cosmetic use as a permitted "coal-tar" color after enact ment of the Federal Food. Drug, and Cos metic Act in 1938 by order published in the Federal Register of May 9, 1939 (4 FR 1922,1936). Under section 706 of the. act. os re. vised by the Color Additive Amendments of 1960. a color additive may be approved . only if data establish that it is safe under its permitted conditions of use. However, the transitional provisions of those amendments provide for provisional list provisional listing for Ext. D&C Red No. 24 and provisionally listed FD&C Red No. 4 for ue in externally applied drugs and cosmetics. In 1965, the Pharmaceutical -Manufac turers Association (PMA) requested that FD&C Red No. 4 be restored to the pro visional list for use in ingested drugs. The Commissioner concluded that con sumption of the color additive from In gested drug use would be minimal and. by regulation published in the Federal of"Register' October 14, 1965 (30 FR 13056). amended the provisional listing for FD&C Red No. 4 to permit Its use to permit completion of a 2-year feeding study wKh dogs that had been initiated by Hazleton Laboratories, Inc., on March 18. 1965. This study was intended to establish unequivocally a no-effcct level for the urinary and adrenal carets seen jn the 7-year feeding study dis cussed above. The 58 dogs in the Ha/lcton study were fed FD&C Red No. 4 at level? of 0. 20,50. and 250 mllllgraras'kiloj-ram of body weight per day. The dogs In the Hazleton study showed lesions in the urinary bladder ir. all' groups fed FD&C Red No. 4. No do*s in the control group, however, showed le ing of color additives in use in 1960 for a in short-term. ingested drugs with spe sions in the urinaiy bladder. Y.Tiilc llar- period of time necessary to complete the cific limitations. The regulation, under leton concluded in a report rtvriv,--i by scientific Investigations needed to estab 5 8.503(C) <2) (21 CFR 8.S03rc) (2) >. Per FDA on October 7. 1569. that the It.or.-; lish their safety. Under this procedure. mitted FD&C Red No. 4 to be used in found were "related directly lo ib* FD&C Red No. 4 was provisionally listed ingested drugs provided that "the label techniques of repeated cathrtcrix..l:on for use in food, drugs, and cosmetics on ing does not recommend nor su"2ct con which was required to study the level of July 12. 1960. and appeared officially on tinuous administration to patients, end urinary potassium" and not to the Irces- the provisional list published in the Fed ..the amount of FD&C Red No. 4 used is tion of FD&C Red No. 4. FDA paihoh gist; eral Register of October 12, 1960 (25 FR such that notmoTe than 5 mtlHgrams'ot who reviewed the study results eonri 9759). FD&C Red No. 4 is currently provi the color additive is consumed per day if Otherwise. In an August 23. 1972 :..osionally listed for use In .maraschino the recommended drug dosage is fol mndum.to Dr. Charles KoktX'-l. A. si it* FEDERAL REGISTER, VOL. 41, NO. 186--THURSDAY, SEPTEMBER 23, 1 97S 5CC 1-0022 tV ' RULES AND REGULATIONS 41^1 J ) V? M' * -> C \ Vn . t' ant Director for Petitions Review, Divi ties and the need for an additional study ject to regulatory action. This prohii.i- sion of Toxicology. FDA. Dr. Stuart have been-known to the Industry spon tion applies to the use of straight colon. Levin, one of the FDA reviewing pathol sors for several years, is an Insufficient lakes, mixtures of FD&C Red No. 4 or ogists, concluded: basis to warrant continued provisional its lakes with other colors, and mixture- -though Haslton Labs has submitted a statement by several pathologists and a con curring article' (Journal of the American ttrdlral Association, 103:100, 1005) proposing listing of the color additive. Under the transitional provisions of the Color Addi tive Amendments of 1960, continued pro visional listing of a color additive Is ap of straight colors and lakes with ingredi ents functioning only as diluents. Th<- Commissioner concludes that the pro tection of the public health docs not re that emorrhaglc polyp* In two low dose ani propriate only when studies in progress quire the recall from the market of mar mals might have been caused by catheteriza or under evaluation are capable of dem aschino cherries and ingested dn:cf tion, the facta remain that the lealone were onstrating the safety of the color addi containing the color additive, or iho similar in type to those seen In uneatheter- tive Involved. There Is currently no study destruction of foods or drugs in prepara ized PDA dogs (in the earlier FDA study), and such lesions were not seen in eontrol dogs.* 1 believe these should be considered compound-related lesions. available or underway to resolve the un certainties about FD&C Red No. 4 and therefore it would not be proper to ex tion to which the color additive lias al ready been added. Man*ifacturers of new drugs and iu-v. tend the provisional listing for FD&C Red animal drugs (including certifiable mm* ' Review by FDA of microslides of the No. 4 for at least 3 years--the time re blotics for animal use) that are lugcstiM kidneys, urinary bladder and adrenals of quired to conduct and evaluate a 2-year and contain FD&C Red No. 4 may either all dogs in the Hazleton study . also feeding study and to report the findings delete the color additive or substitute a 'showed atrophy of the zona glomerulosa to FDA for evaluation. The Commis different color In accordance with the of the adrenal cortex at all feeding levels sioner concludes, therefore, that con provisions of S 314.6(d) (3) and <c> or after 2 years. This response. It was con tinued provisional listing of FD&C Red' 1514.8(d) (3) and <e),asoppropiiatc 2i cluded, was induced by ingestion of FD&C No. 4 lor use In maraschino cherries and CFR 314.8(d) (3) and (c). and 5l4.8'd> Red No. 4. Food and Drug Administration short-term ingested drugs is no longer (3) and (e) ).The applicant shall submit scientists ultimately concluded that an appropriate. data providing the new composition end unequivocal no-effect level for FD&C Red The current "closing date" for con , showing that the change in composition No. 4 could not be determined from the tinued use of FD&C Red No. 4 was post- ' does not interfere with any assay or Hazleton study and that an additional poned to September 30, 1976 by a regu other control procedures used in manu study-involving dogs, was necessary be lation published In the Federal Register facturing the drug, or that the assay and fore a final determination could be made of January 5, 1976 <41 FR 754). That control procedures have been revised iv concerning the safety of FD&C Red No. postponement was based on the assump make them adcouate. Also, the appli 4. Because of the limited use of the color tion that a study was cither underway in_ cant shall submit data available to i -- additive, however, the Commissioner response'to FDA's June 25, 1975 letter to tnbllsh the stability of the rcrL><-<: concluded that FD&C Red No. 4 should Dr. Kirschman.or would be undertaken formulation or. if the data are too limited continue to be provisionally listed pend soon thereafter to resolve the uncertain to support a conclusion that the drug win ing further scientific investigations. The * Commissioner's conclusion that ties about the safety of FD&C Red No. 4 when Ingested. Because there are no retain its declared potency for a reason able marketing period, a couimitmcn; t>. existing data appeared to be inadequate studies In progress or under evaluation test the stability of marketed baluhev <: to establish a no-effect level in the dog that can resolve these uncertainties, the reasonable intervals, to submit the for FD&C Red No. 4 was conveyed to the Commissioner finds that the basis for the as they become available, ami to rcmi: petitioners as early as November 25.1969. postponement no longer exists and here from the market any batch found to fall The Commissioner's conclusion that an by terminates the postponement of the outside the approved specifications f--r additional study was required to resolve the questions' concerning the urinary closing date for the provisional listing of FD&C Red No. 4 for use in maraschino the drug. The Commissioner is swore that sup bladder lesions before the color additive could be demonstrated to be safe as re cherries and short-term ingested drugs in accordance with section 203(a) (2) of plies of alternative color additives n;..> be difficult to obtain immediately. C :i- quired by section 706 of the act was the transitional provisions of the Color sequently. food and drug labeling Mat lormally communicated to CTFA, one of Additive Amendments of i960. Also, un ing that the product contains "artiiir:;.! the petitioners, and to Hazleton Labora- der section 203(d) (1) (E> of the amend color" because of the prior inclusion , torles, by letters on October 8,1974. The ments. the Commissioner concludes that FD&C Red No. 4 may continue to ;> need lor an additional 2-year feeding the provisional listing of FD&C Red No. used with the uncolored producl dur.;> study was also made known by FDA to the Inter-Industry Color Task Force, 4 for these uses should be terminated because'such action is necessary to pro the time necessary to obtain supplli: : alternative color ingredients or consisting of representatives of the food, tect the public health, in that questions the current supplies of labeling arc v,.. drug, and cosmetic industries represent have been raised about the -safety of the whichever occurs first. . ing the petitioners, and at several meet color additive when ingested and the The Commissioner has cnrc/ully ings between FDA personnel and the available data do not permit a determi sldered the environmental effects of't i; l- CTFA-Color Additive Petition Commit nation that this use is safe. Published actlon and bc'*nure.thc action will i : tee. By letter of June 25,1975, to Dr. John elsewhere In this issue of the Federal significantly affect the quality of i.u- Klrschm&n. chairman 'of the Inter Register is a notice denying the portion human environment, has concluded ih..; industry Color Task Force, FDA advised of the petition proposing to list FD&C an environmental impact, statement the sponsoring industries In detail of the Red No. 4 for use in maraschino cherries not required. A copy of the FDA en reasons why a new.study was needed. 'and Ingested drugs. The safety of FD&C vironmental assessment, together v : ! Most recently, separate letters to CTFA. Red No. 4 in externally applied drugs and copies of the other riocumi-nts i.- - CCMA and PMA in January and Febru cosmetics has been demonstrated and a tioned above, arc on file with tin? Ji* ary of 1976-officially reiterated the need regulation listing the color additive for ing Clerk. Food and Drug Admbii.- for an additional study. those uses is published elsewhere in this tion, Rm. 4--65. 5600 Fish.crs Lane. R-. - In recent months, the commercial issue of the Federal Register. vUic. MD 20852. Because this a-t`o:. . sponsors and some industrial users of All certificates heretofore issued for final (not proposed), an inflation ... FD&C Red No. 4 have expressed a wUllng- batches of FD&C Red No. 4 for use in pact eva'uation is not required by -ness to begin the 2-year feeding study maraschino cherries and ingested drugs Uve Order 1)821 (3A CFR. 1975 O. - necessary to resolve the questions re are hereby cancelled, effective Septem pllallon. p. 203). garding the safety of the color additive ber 23. 1976. After September 23, 3976, Therefore, under the transitional j. when ingested. The Commissioner con adding FD&C Red No. 4 to any food or visions of the Color Additive Aim-, cludes. however, that this belated will ingness to undertake a study to resolve the uncertainties about the safety of _-FD&C Red No. 4. when those uncertain- Ingested drug will cause such product to be adulterated within the meaning of the Federal Food. Drug, and cosmetic Act (21 U.8.C. 301 et seq.) and sub- inents of I960 (Title 'll. Pub'. L. C6-' : 74 Stilt. 404-407 (21 U.S C. 37G r.O'and under authority delegated to ' Commissioner (21 CFR 6.1> (recni'i FEOEBAL BECI5IEB, VOL 41,. NO. 1 4--THUftSOAY, SEPTEMSEB 23, 1976 see 1"0023 .41854 . RULES AND REGULATIONS tlon' published In the Federal Rccistee fleeting In the `'Closing date** column the ditions set forth below for use in coloring Of June 15. 19T6 (41 FR 24262)). Part 8 Commissioner's extension - published externally applied drugs and eownctica of Chapter'! of Title 21 of the Code of under Docket No. 76N-0365 -elsewhere and that certification is necessary for Uto Federal Regulations Is amended as fol in this issue) to read as follows: protection of the public health. This lows: * r. *............ .. 1. In 1 8501, the entry for FD&C Red No. '4-In the stable In paragraph (a) Is 2.501* .Provisional lists of color addU Uycsu v':** - * order "permanently" lists FD&C Red No. .4 for use in externally applied drugs and cosmetics under ntfw M 8.4103 end 8.71GH <21 CFR 8.4103 and 8.7163). The provi . revised In the ^Restrictions" column (re- (a) sional listing of FD&C Red No. 4 for use in externally applied drugs and cosmetics ClosfiicdaU -- * Under J 8501(a) (21 CFR 8501<a>>. Drug uid ncnrnWIo us* RlSUJcUOAS ' N^. ' ` 9 , ' JJ>\ 4 C; fed ..chapter).-., VS *w'ifV.- No. t (mo. i &4IU of tbli__ ; ------------- ....... - Doe. 3t, 1970,or unlit - ti ensotwabelislohaetdflc.1 d'*_fo F. oaepcpolileodrificdruuOgarnotlnljdr ' ooanwlicj. - which is extended to December 31. 1976 by regulation published elsewhere in this * Issue of. the Federal Register under Docket No. 76N-4365, will be deleted when this order becomes effective on October 27. 1976, unless this order is 'iLokMOnly.* '.` '* - y V *" . . ? * % ;* 1 ^ * i*iy t - Effective date: These regulations shall 2!*In 5 8.502, the flush paragraph ap be effective September 23.1976. pearing. after' paragraph <d) (3). con cerning FD&C Red No. -4, is revised to (Title H. Pub. U &S-S18, 74 SUt. 404-407 (21 TT.S.C. 376 note).) read as follows: . Dated: September 17, 1976. 8.302 Termination of provUiooal lUl-: - < Inga of color additive*. , . _ .V f^ ^ *, Sherwik Gardner. Acting Commissioner y'('(3d>);-*** *;5 * of Food and Drugs. |PR DOC.76-278L7 Filed 9-33-7e;S:46 ami stayed by the timely filing of objections, in which case the provisional listing will continue until December 31. 1976 unless terminated or extended bv regulation. This order does not list FD&C Red No. 4 for use In lakes as requested In the peti tion. The Commissioner notes that pro posed regulations related to* the use of color additives in lakes were published in the Federal Register of May 11.1965 i?0 FR 6490). The Commissioner advises that new p-oposed regulations governing the use of color additives In lakes will; The Commissioner of Food and Drugs has concluded that available data do not per mit the establishment of a safe level of use of this color additive In food, ingested drugs and ingested cosmetics. In order to protect the public health, the Com missioner hereby terminates the provi sional listing of FD&C Red No. 4 for use In food and Ingested drugs. The Com missioner has previously terminated the provisional listing of FD&C Red No. 4 for use In ingested cosmetics. Section 9.63 of this chapter is retained In Part 9 to permit the use of lakes of FD&C Red No. 4 in externally applied drugs and cosmetics. be published in the Federal Register In * " (DocketNo.7SN-03C7J ' the near future and concludes that the listing of colors for use in lakes can best PART S--COLOR ADDITIVES be implemented by general regulations. PART 9---COLOR CERTIFICATION Listing of FD&C Red No. 4 for Use in Externally Applied Drugs and Cosmetics FD&C Red No. 4 will, therefore, continue to be approved for use in lakes for color ing externally applied drugs and cosmet ics under the general provisional listing The Food and Drug Administration for "Lakes (FD&C)" under S850la (FDA) is "permanently** listing FD&C (21 CFR 8.501(a)). Red No. 4 for use in externally applied This order establishes specifications drugs and cosmetics, effective October for the certification of batches of FD&C 27,1976. Objections to this order may be . RcdV'No. 4 which`are more restrictive filed by adversely affected persons by than those currently prescribed under October 26, 1976. Elsewhere in this issue i 9.63 (21 CFR 9.63). Additionally, the of the Federal Register the Commis identity Of the color has been revised to sioner of Food and Drugs Is isuing regu be consistent with current chemical no lations terminating the provisional list menclature. The identity nomenclature 8^03 [Amended] ing of FD&C Red No. 4 for use In mara and the specifications currently pre schino cherries and ingested drugs and scribed in $ 9.63 become obsolete upon ' 3. In 5 8.503, paragraph *(c> is revoked. denying that portion of the petition seek the effective date of new {8.4103 and *' 4. In f 8.510, paragraph <c> is revised ing "permanent'' listing of the color ad 18.7163. However, It is necessary to ii P. to read as follows. 8510 'Cancellation of certificate*. ditive for those two uses. A notice published in the Federal Reg ister of November 20.1968 (33 FR17205) maintain $ S.C3 to provide for Die u.-.c of the color additive in lakes. Accordingly, { 9.63 Is revised to reference the Identity ' * " % (c)` Certificates Issued for FD&C Red stated that a petition (CAP 61) for the' nom.e.n.c.lature and specifications "permanent'' listing of FD&C Red No. 4. scribed by J 8.4103. pre- `i --No. 4 and all mixtures containing this as a color additive for use in maraschino Therefore, under provisions of thc color additive are cancelled and have no cherries, ingested drugs, and externally .Federal Food. Drug, and Cosmetic Act effect'after September 23. 1976 insofar applied drugs and cosmetics had been (sec. 706 (b), (c). and (d). 74 Stal. 3C9- as food. Ingested drugs, and ingested cos filed by the Toilet Goods Association, Inc. 403 (21 U-S.C. 376 (b). (c>. <d>)); under metics are concerned, and use of this color additive in the manufacture of food, ingested drugs, and ingested cosmetics after this date will result in adulteration. The certificates shall continue in effect for the use of FD&C Red. No. 4 In exter nally applied drugs and cosmetics. The Commissioner finds, on the basis of the scientific evidence before him that no * action has to be taken to remove from the market food, ingested drugs and ingested `cosmetics containing the color additive. ma , * * (now the Cosmetic, Toiletry and Fra grance Association, 1133 15th St., NW,, Washington. D.C. 20005): the Pharma ceutical Manufacturers Association (1155 15th St.. NW.. Washington. D.C. 20005); and the Certified Color Industry Com mittee (now the Certified Color Manu facturers Association. 900 17th SL, NW., Washington, D.C.-20006), c/o Hazleton Laboratories. Inc.. FO Box 30. Falls Church, VA 22046. The petition v.as filed pursuant to section 706 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. the transitional provisions of the Color Additive Amendments of I960 (Pub. L. 86-618. Title II,' 74 StaL 404-407 *21 U.S.C. 376 note)); and under authority delegated lo the Commissioner 2i *?fl 5.1) (rccodification published in the 1 :aF.r.AL Recistuk of June 15. 1976 ill i-'I*. 24262'), Parts 8 and 9 of Chapter 1 ! Title 21 of iho Code of Federal ltc. .Utions arc amended as rollons: 1. Part 8 is amended: | C.501 U a,led] 'Notice and public procedure are not 376). - a. In paragraph la) of 18.501 Provi .necessary prerequisites to the promulga- The Commissioner has evaluated the sional lists of color additives (as anwudcd -.tlon of thtg order because section 203 data in the petition and' concludes that elsewhere in this Issue of the rvrv-Ai. (d> (2) of Pub. L. 86-518 so provides. FD&C Red No. 4 is safe under the con- Register under Docket No. 7CN-C. >. FEDERAL REGISTER, VOL 41. NO. 186-----THURSDAY, SERTEMSER 23. 1V76 see -*-0024 ROLES AND REGULATIONS 41855 :the entry for PD&C Red No. 4 for use (d> EabeKntr. The- label of the color (See. 7M (b). (). (d). 74 3tat. 3R9-403 (37 in externally applied drugs and cosmetics additive 'and any - mixtures prepared OJ.C. 378 (b), (c). tod- (d>); Tltte XT. Pub. la deleted: b. In | 8.502, the flush paragraph ap therefrom-Intended solely or In part for coloring purposes shall conform to: the L. S6-61S,. 74 SUL 404-407 (31 UA& 376 note).), pearing' alter paragraph (d)(3), con requirements of 18.32. Datedr September 17^ 1976. cerning FD&C Red No. 4, Is revised to - ' Ce> Certification. AH batches of FD&C read as follows: Red No. 4 shall be certified in accordance with regulations In-. Subpart A of this { &503 Termination of provisional lut part, * ings of color additives. d. By adding to Subpart G new I 8.7163 Sarswiw Gardner. Acting Commissioner - ' of Food and Drags, IPS Doc.73-37819 Plied ft-43-?;B:43 am) to read as follows: (d) (3). The Commissioner of Food and Drugs _ has concluded that available data do not permit the establishment of a safe level 8.7143- FD&C Red No. 4. - (a) Identity and specifications. The color additive FDTcC Red No. 4 shall con form In identity and specifications to the )Docket No. 76N-0365] FART &--^COLORf ADDITIVES Terr ilnation cl Provisional Listing for Color Additives * of use of this color additive In food, in gested drugs and Ingested cosmetics, hi -order to protect.the public health, the rv\mTr^<r.nr hereby terminates the * provisional Mating of FDIcC Red No. 4 *, for use In food and Ingested drugs. The * Commissioner has previously terminated the provisional listing of FDfcC Red No. *4 for use In Ingested cosmetics. FD&C *, Bed No. 4 Is listed for use In externally applied drugs and cosmetics by If 8.4103 x and' 8.7163, respectively. Section 0.63 of this chapter Is retained in Part 9 to per- requirements-of t 8.4103(a)(1) and (b), (b) Uses and restrictions. JFD&C Red No. 4 may be safely used for coloring externally applied'cosmetics in amounts consistent ` with good ' manufacturing .practice. (c) Zabelina. The label of the color additive shall conform to the require ments of f 8.33. - - (d) Certi/Ication. All-batches of FD&C Red No. 4 shall be. certified in acoord- ance with regulations- in Subpart A of this part, The Food and Drug Administration (PDA) is terminating the provisional list ing. and hence the approval, of alumi num stearate, bentonite, calcium silicate, calcium stearate, gold. lithium stearat . magnesium aluminum silicate, magnesium stearate, and zinc stearate for use as color additives, in cosmetics, effective October 26. 1976. Section 8.501 (21 CFR 8.501) of the eolor additive regulations designates those & dor additives that are provision ally listed, pursuant to section 203(b) of mil the use of. lakes of FDfcC Red No. 4 2. Part 9 is amended^by revising 19.63 the transitional provisions of the Color in externally '.applied .'drugs and cos to read as follows: Additive Amendments of'1960 (Title IT. metics. 5 9.63 FD&C Red No. 4. ' Pub. B. 86-6)8, 74 Stab 404-407 (21 ' *'". ' UJS.C. 376 note)), on an interim basis c. Byadding to Subpart E new I 8.4103 to read as follows: The color additive* FD&C Red No. 4 shall conform in Identity and specifica tions to the requirements of I 8.4*03 (a) pending completion of scientific Investi gations needed for determinations as to "permanent" listing In accordance with &4103 FDC Red No. 4. (2) and (b) of this chapter. FD&C Red (a) Identity. (1) The color additive FD&C'Red No. 4 Is-principally the disodltuxL salt of 3-C (2,4-dImethyl-5-sulfophcnyD azo3-4-hydroxy-1-naphthalenesulfonic acld- No. 4 Is restricted to use In externally applied drugs and cosmetics. Any person who will be adversely af fected by the foregoing order may at any time on or before October 26. 1976 file with the Hearing Clerk, Pood and Drug - .i - CS) Color additive mixtures for use in externally applied drugs made with FD&C Red No. 4 may contain only those diluents that are suitable and -that are listed In Subpart 7 of this part for use In color additive mixtures for coloring externally applied drugs. (b) Specifications. FD&C Red No. 4 shall conform to the following specifica tions' and shall be free from impurities other- than those named to the extent that such' Impurities may be avoided by good'manufacturing practice: Administration, Rm. 4-85, 5600 Fishers Bane, Rockville, MD 20852, written ob jections thereto. Objection/ shall show wherein the person lUingwill be adversely affected by the order, specify with par ticularity the provisions of' the order deemed objectionable, and state the grounds for the objections. Objections shall be filed in accordance with the re quirements of ! 8.19 (21 CFR 8.19). If a hearing is requested, the objections shall state the issues for the hearing, shall be supported by grounds factually and legal _. Sum of volatile matter (at* 135* C.) ly sufficient to Justify the relief sought, . chioridtv and raUtta (calculated as so*j ' dlua salts), not more tban 13 percent. Water-lMolubie matter, not more than on J percent:-. 6-Aralno-3,4-dlmetliyl - I - bensenesulfonle and shall Include a detailed description and analvsis of the-factual information Intended to be presented in support of the objections in the event that a hearing is section 706 of the Federal Food, Drug, and Cosmetic A*** <sec. 706, 74 8tat. 399403 <21 TBS.C. 376) >. A notice published In the Federal Reg ister Of August 6. 1973 (38 FR 21200). stated' that petitions- (CAP 8C0071. 8C0078. and 9C0094) for the "perma nent" listing of aluminum stearate, ben tonite, calcium silicate, mldum stearate, kaolin, lithium stearate, magnesium alu minum silicate, magnesium stearate, and zinc stearate had been filed by the Cos metic. Toiletry and Fragrance Associa tion. Inc. (CFTA). 1133 15th St.. NW., Washington, DC 20005, c/o Hazleton Laboratories, Inc.. P.O. Box 30, Falls Church. VA 22046. The petition was filed pursuant to section 706. of the act. Pro visional listing for these nine substances has been continued pending completion of the evaluation of available data to de termine whether the substances should be "permanently" listed. On August 9.1976. CTFA wrote to FDA requesting that the color additive peti -.'add, salt; pot more than 0.3 per- held. Five copies of all documents shall be tions for these nine substances be with *'? 'cent. 4-Kxdroxyl-l-naphthalenesulfonlc add, todlura salt, not more than 0.2 percent. filed and should be-identified with the Hearing Clerk docket number found in drawn without prejudice to future fl ing. Published elsewhere in this issue of the Subsidiary colors, not more than 3 percent. Laid (as 7b), not more than 10 parts per J millIon. brackets in the heading of this order. Re ceived objections may be seen in the Feoeral Register is a notice arnrnwr ii't: the withdrawal of the petitions. The Commissioner is terminating the *'.ro- .arsenic (aa as), not more than 3 pasts per above office during working hours, Mon vlsional listing of these nine substances ; .* millIon. day through Friday. for use as color additives in cosmetics, ` Mercury (as Hg), not more than 1 part per .).' million. Total color, not leas than 87 percent. This order shall become effective Octo ber 27. 1976,' except as to any provisions Ky (c). Uses and restrictions. FD&C Red that may be stayed by the filing of proper v- - No. 4 may be safely used in externally objections. Notice of the filing of objec i: . applied drugs in amounts consistenLwith tions or lack thereof will be announced effective October 26, 1976. beeau- e there are no pending color additive petitions or progress reports for them as required by S 8.501. In Us letter requestin'! withdrawal of the petitions. CTFA stated that a sui vey good manufacturing practice. by publication in the Federal Register. disclosed that none of Its member firms FEDERAL -REGISTER, VOL 41,' NO. THURSOAV, SEPTEMBER 23, 1976 see i-0025 41856 -RU1.ES and regulations were usInf any of the nine substances _ -Federal Food. Drug, and Cosmetic Act Effective date: These regulations shall .covered by Its three petitions for coloring ` and subject to. regulatory action. The become effective October 26, 1976. cosmetics, although certain of the sub stances are used In cosmetics for non coloring purposes. However, CTFA ad vised that'its survey was limited to its Commissioner concludes that the protec tion of the public'llealth does not require the recall from the market of cosmetics, if any, containing- any of the 10 sub (Title It. Pub. L, 86-618,' 74 Stat. 404-107 (21 OS.0.376 note).) .V.' Dated: September 17,1976. - members' practices and did not cover those of the entire cosmetic Industry. The Commissioner Is not aware of any person ' who Is currently coloring cosmetics with stances lor use as color additives, or the destruction of products In preparation to which any of the 10 substances have already been added. 1 Sherwxh Gardner. Acting Commissioner oi Food and Drugs. any of the nine substances covered by the Nothing In thu action precludes the [PR DOC.76-27S32 Filed 9-22-76;B:45 ami CTFA petitions. However, because of the Commissioner from determining that any possibility- that some cosmetic manufac 'of the 10 substances that are the subject turers are using one or more of the nine of this regulation is in use to color cos [Docket NO. 76N-C365] 'substances, to color their products and metics, and is* therefore, a color additive PART 8--COLOR ADDITIVES because there are no Questions of safety - regarding their use, the Commissioner is ' making * the termination of the pro under section 706 of the act. The Com missioner expressly reserves the right in such an Instance to require the prompt. ... Subpart-- Provisional Regulations Postponement of Closing Dates visional list for the nine substances effec- submission of a color additive petition for ` The Commissioner of Food and Drugs, -tlve October 26,1976. This 30-day period the substance, or to require that its use on his own initiative, Is postponing the will-permit both an orderly change in 'be terminated, or to take any other reg closing date for the use of 72 provisionally any. cosmetic formulations that contain ulatory action, including court enforce listed color additives until December 31. . any of the nine substances as color addi ment action, deemed appropriate. 1976. The Commissioner is also post tives and time for any interested person .! In its August 9.1976 letter withdrawing poning the closing'date for the provi to submit & color additive petition for any its three color additive petitions for the sional listing of FDkC Red No. 4 for ex of the nine substances.-.* nine substances, CTFA requested that the ternal'drug and cosmetic use until De Gold, the 10th substance that Is the use of cosmetic labeling listing any of the cember 31, 1976, or until the regulation subject of .this regulation, was provision- -substances as colorsadditives In ac listing tlie color additive'for these uses, ally listed for use as a color additive In cordance with S 701.3 (21 CFR.70U) be published else* rhere in this issue of the cosmetlcs,-and appeared on the so-called 'Harvey list" of color additives, published in the Federal Register of October 8. 1974 <39 FR 36126). Thpt notice stated that provisional listing would continue for those "Harvey list" color additives for which color additive petitions or progress reports were submitted by December 31, 1974. A progress report on gold was sub mitted and'the closing date for the pro visional listing of gold, as well as those for other provisionally listed color addi- tiyes.was postponed until.December 31, 1975, by regulation published In the Fed eral Rzcssix*. of April 4, 1975 (40 Fit 15087). No color additive-petition for gold or progress report under S 6.501 was sub mitted by/'-the* postponed closing date. December*!, 1975. However, through in advertence, the closing date for the pro visional listing of .gold was postponed along with those of the other provision' ally listed color additives by regulation permitted for 1 year so that existing, Federal Register, becomes effective, stocks of labeling may be depleted. The whichever, comes first. This order be Commissioner concludes that this re comes effective September 23, 1976. quest is reasonable. 'Consequently, cos metic labeling listing any of the 10 sub stances that are the subject of this regr uiatlqn as color additives, may continue to* be used until current supplies are ex hausted, or until September 23, 1976, whichever occurs first. TJnderTltlc II of the Color Additive Amendments of 1960 (sec. 293(a)(2), Pub. L. 86-618, 74 Stat. 404 (21 US.C. 376 note)) and under authority dele gated to him (21 CFR 5.1), the Com missioner is authorized to postpone the closing date of a provisional listing oi a The Commissioner has reviewed this color additive on his own initiative or regulation pursuant to Part 6 (21 CFR upon the application of an interested Fart 6) and concludes that it will not person. Section 203(d) (1) of Title II re 'significantly affect the quality of the hu quires promulgation, insofar as practi man environment. Because this action Is cal, of a current listing of color additives final--not proposed--an Inflation Impact and the particular uses thereof deemed 'evaluation is not required by Executive Order 11821 (3ACFR. 1975 Compilation, p. 203). Copies of the documents men tioned above are. on file with the Hearing Clerk. Food and Drug Administration, Rm. 4-65, 5600 Fishers Lane. Rockville, MD 20852. provisionally listed. The current closing date. September 30. 1976, established by a regulation pub lished in the Federal Register of Janu ary 5. 1976 (41 FR 754), was based upon the Commissioner's conclusion that post ponement until September 30. 1976. was published In the Federal Register of . Therefore, under the transitional pro consistent with the objective of carrying January 5. 1976 <41 FR 754), The Com visions accompanying the Color Additive to completion, in good faith and as soon missioner is terminating the provisional Amendments of 1960-to the Federal Food, listing for gold for use as a color additive Drug, and Cosmetic Act (Title XX, Pub. L. in cosmetics in this regulation because 88-618, 74 Stat. 404-407 (21 U5.C. 376 no color additive petition or progress re- note)) and under authority delegated to port has been submitted as required by ' the Commissioner <21 CFR 5.1) (recodli 8.501. Furthermore, the Commissioner cation published in the Federal Reg - is not aware of any person who is cur ister of June 15, 1976 (41 FR 24262)), rently coloring cosmetics with gold. The Part 8 of Chapter I of Title 21 of the termination is, however, being made Code of Federal Regulations is amended effective October 26. 1976, to permit both as follows: as reasonably practicable, the scientific investigations necessary for making a de termination as to listing these color ad ditives under section 706 of the Federal Food. Drug, and Cosmetic Act (21 TJ.S.C. 376). The Commissioner also advised that a final determination on the listing under section 706 of many of the provisionally listed color additives was expected to be completed before September 30. 1976. an orderly change in any cosmetic for mulations that contain gold as a color 8.501 CAmended] and that, if appropriate, further post ponements of the (dosing date would be additive and time for any interested per In paragraph (g) of S 8.501 Provisional made for provisionally listed colors for son to submit a color additive petition for lists of color additives, the entries for which final determinations were not i>os- gold. aluminum stearate, bentonite, calcium sible. After October 26. 1976. adding alu minum stearate, bentonite, calcium sili cate, calcium &tearate. gold, kaolin, lith ium stearate, magnesium aluminum silicate, magnesium stearate, and zinc stearate to any cosmetic for use as a color silicate, calcium stearate, gold, kaolin, lithium stearate, magnesium aluminum silicate, magnesium stearate, and zinc stearate are deleted. Notice and public procedure are not necessary prerequisites to the promulga Published elsewhere in this is.ue of the Federal Register are documents: 1. Terminating the provisional listim* for FDkC Red No. 4 for use in marasJumcherries and ingested drugs: additive will cause such product to be tion of this order because section 203(d) 2. Listing in FDiiC Red No. 4 for use i-i adulterated within the meaning of the (2) of Pub. L. 86-618 so provides. externally applied drugs and cosmetics: FEDA.l REGISTER, VOL 41, NO. 1S6--THURSOAf, SerttMSe*. 23. 197A see l~002b ' RULES AND REGULATIONS 4185 3. Deiying the portion of the petition Effective,date: Thisordershall become Carbon black is defined In the **n -to list FDfcC Red No. 4 for me to mara- . effective September23;1976..- cyclopedia of Industrial Chemical Analy 1 schlno cherries and Ingested drugs; <se. aoa{*>{3>, <d)(i). Pub. ?.of-iclaTrebormn ibnlaatcinkgfothreusperoIvnisfiooonda.l,ldisrutignsg, atlt *-40*7(211 ~tSo'oC'3v7r9a^rtaiV'' and cosmetics; . Datedi. September 17,1976, 74 -sis**' aw "the generic term for a ' aridvariety oT finely divided earbonaceou pigments produced by the pyrolysis o -hydrocarbon gases or oils**' (Schubert S. Denying; the petition to list carbon * black for Use In. food, drugs, and cos- ..metlcs; '. ' 6. Terminating the provisional- listing . -`of 10 substances for use as color additives . ta'Cosmeties. * r 7. Also published in'this issue of the ` * Federal gccisim is a proposal to post* ; ; ponefurther the closing date for the use . : Of certain of these 72 provisionally listed color`additives. The preamble to that .proposal sets forth the Commissioner's tentative? conclusions with respect- to ` "listing or provisional listing for each of ` SKBrwnr Gardner, . ~ v' Acting Commissioner, f'oodutidOrup*! (EE.Doc.7$-27823 Filed -23-76;8:45 am) (DocketNO. 76N-0376] PART S--COLOR ADOfTIVES > Termination of Provisional Listing of Carbon Black The Fbod and Drug Administration (FDA) is 'terminating the provisional listing and hence the- approval, of car bon black (all-gas cjha--nne--l black) fortuwse. Ford, and Lyon. "Analysis of Carboi Slack.** in "Encyclopedia of Industrie' Chemical Analysis" 8:174-243 (1989)). There are five basic types-0/ carbon black that are classified according to the source of raw materials or-znethod of manufac ture: Impfagement or channel carbons, lam) black.. thermal 'blacks, acetylene blacU*. and furnace carbons (ibid.). Of these five types, only the impingement or channel carbon, and* more specifically, that type produced by`using all natural gas, bu been provisionally listed for use in food,-drugs,'and cosmetics. The other four types of carbon blacks, including PubltolHd ctoh*r ,,chnnd procewmin*natural/as that "0ta.7escrZef7, _x . Nothingin this action affectethe Com- missioner's authority under the trmurf- tional provisions of the Color Additive . Amendments of 1980 to terminate a clos ing date', terminate a listing, or impose *restrictions with respect to a specific ..color^iuv.on. tothiaissueof theProMAJLlteoisixate a notice denying the ^^to*ynnBcennwtlyr" lirt LcAatrubwoMn bi^1 <.--aU. _-_g_^channel black), for use in food, drugs, and cosSmecettiicosn. 8301 (31 CFR 830l> of the 'color additive regulations designates 3thos-e gcolo-r *adSditFive2s t5hat Sare 5pr"ovTisiSon5- ja ofl-enrlehed, have never been and are not now provisionally listed. abcmt the safety of carbon black (all-gas channel black) In food, drugs, and cosmetics stems from the possibility that extractable polynuclear - The postponement of the cloossiinng dcatie auy prwronviasiioonr"s of ttth>ea rC?on,lortr Ad- are also referred to as opolvyecvycllic Jatrmomatiec until December 31. 1976. accomplished by this regulation, is necessary to provide *ddljtt*liv*e**- Ay*mrv?e,n,d,%mne^nsttsa*t.^404I9-46007 (Title H. (21UAC. hydrocarbons, comprise a large family of chemicals where two to seven benzene a brief period within wUdi toj^ interim basis pending rings have fused in an angular arrange- orders for thosercolors identified in the 376 no . rr<f--Mfiy. investigations ment to form the FNA molecule. The par- proposaT as suitable for listing and to determinations about "per- ticular FNA*s that have raised the great- afford the public an opportunity to com- neeo* aeeordance with sec- est concern are those containing three to her 30, 1970, closing date, the Commis- . black) was used eomraer- strated to be carcinogens. Analysis of .sioner concludes that notice and public dT_.__ cosmetics prior furnace blacks has disclosed the presence -procedure on .this regulation are im- cl^lW m . Color Additive of 3,4-benzpyrene and 13-benzanthru- practicable and contrary to the public to e^c f ,--0 Accordingly, under cene. Surest and that good cause exists for Asemcetinodnm2e0n3ts(bo)f(2) of the transitional As explained more fully below in this thi* postponement as a final provisions of the amendments, carbon preamble, carbon black produced by the 'order. The regulation, to be effective Sep- black (all-gas channel black) was channel process using all naturai gas . tember 23,1976. will permit the uninter- deemed provisionally listed for use in appears least likely of the carbon blacks rupteduse.of the affected color additives., food, drugs, and cosmetics on July 12, to contain extractable PNA's. and toxicTherefore,-in accordance with 5 VJS.C. 1960. Carbon black, (all-gas channel ity studies on this compound have not `.653(b) (B), and-(d) (D.and (3), this black) appeared on the provisional list disclosed any adverse effects. The Com' .postponement is issued as a final regula for use In food and cosmetics when that missioner cannot reasonably conclude tion and is.being made effective on Sep-' list was initially publ_is_h__e_d in the Fed- however, that use of carbon black (all- tember 23, 1976. A 60-day comment .n^t.u^.ERCeg^isTteorf'oofSOccttoobeerr 12, I960 (<2255, .g__a_s__c_h_a_n__n_e_l__b_la__c_k_)__i_s--sa.fe______ t_h_e_r_e_ period is being provided on the proposed *"**:_. * carbon black (all- are adequate data available to establish ' -regulation related to the 72 provisionally *** in drugs was provl- that the color additive contains no listed color additives published elsewhere fr^alivlisted- when the list was first extractable PNA*s. In addition, the com- in this issue of the Federal Register. Amended by notice published in the Fed- missioner cannot "permanently" list car- Therefore, under the transitional pro- zTT- ofwxcister August 16,1961 <26 FR bon black (all-gas channel black) in the visions accompanying the Color Additive absence of data, that permit cstabl^l:- Amendments of 1960 to the Federal Pood, -^.tinn 706 of the act, as revised meat of specifications, Le.. precise physi- Drug. and Cosmetic Act (sec. 203(a) (2). Amendments of cal and chemical properties of the color (d) (1). Title H. Pub. L. 86-618; 74 StaL \LqI Sir additive may be approved ^diUve. to differentiate all-gas channel * 404-405 (21 T7-S.C. 376 note) > and under .authority delegated to the Commis- itiv i?dSa establish that it is safe under oJn^ly^iftdta^tace^statioonsnn wsao\fll:u"ses. HHoowffcevveerr,f black from furnace carbons, lampolack, thermal blacks, acetylene blacks, end sllsiohneedri.n.<th2e1FCEFDRER5.A1L) R(EreCcBoTdEifiRcoaftiJounnpuebl5- / 1976 (41 FR 24262)). Part 8 Is amended 4V;as follows: | 8.501 ' CAtnendcdl 1*. In S 8-501 Prot>titona2 2i$(s 0/ color adt'r dittoes,-the closing dates tor the color ; additives'listed In paragraphs (a), (b), athmeendtnm_m_e_sn_itU_s_opnraolvidTPevwrfowov^ridpsnirnooenvis"ioofnatl*h*l--oisste ing of color additives'in use in 1960 for a period of time, necessary to complete the scientific investigations needed to es tablish their safety. In accordance with this procedure, carbon, black (all-gas channel black) has been provisionally listed since 1960 and is currently provi channel blacks manufactured with oilenriched natural gas. The petitioners have previously been advised by FDA that such data would be required for "permanent** listing. Hie petitioners were also advised tlict the color additive would, even If "perma nently" listed, be subject to batch cer tification by FDA. Because samples of the \`.. (c), (f), and fgT are changed to read sionally listed, for use in food, drugs, and carbon black (all-gas channel black) }/?,. "December 31, 2976/* cosmetics. used in the various toxicological tests to FEDERAL REGISTER, VOL 4Tt NO. 18*--^THURSDAY, SEPTEMBER 23, 1974 see 1-0027 -41858 . " RULES AND REGULATIONS Allah the safety of the color were not PNA's is needed have been known since channel black) for use in food, drugs, and .available for current analysis, the spe- shortly alter the first color additive peti- - cosmetics Is no longer appropriate. reifications for..certification were to ln- tion for carbon black was submitted on The current closing date for continued 7clude~'physical and chemical properties November 8,3963. The firstpetition (CAP use of carbon black (all-gas channel , ol commercially -available carbon black 9), submitted to FDA by Carl A. Nau, black) was postponed to September 30. `.(all-gas channel black) that would dif MJ3,, Medical Center, University of 1976 by a regulation published in the Fed ferentiate it from the other types of car- Oklahoma, Oklahoma City. Oklahoma, eral Register of January S', 1976 (41 PR ` bon blocks and thus assure that the color was rejected for filing because It lacked. 754). That postponement was based on 'certified was identical to the color tested, Inter alia, (1) chemistry data adequate the assumption that scientific investiga 'as well as a requirement that no ex- to establish specifications for the color tions in progress would soon provide the ' tractable PNA's .be measurable using an additive and (2) adequate Information data necessary to establish specifications "analytical method of suitable sensitivity, . aboUt the nature of the volatiles present. for the color additive and that an analyt In general, FNA*s appear to be present Dr. Nau withdrew his petition In a letter ical method to 'detect extractable'^PNA's In carbon blacks as a byproduct of the da>d July 11,1966. * sensitive to 2 ppb would be developed. Be manufacturing'Process and are probably- Subsequent to the withdrawal of Dr. cause it has now become clear that the' formed during'combustion (H. I*. Falk -ftau's petition, FDA received letters from necessary data are not available and will `and P. E. Steiner, "The Identification of H. ynHTitatiTn ft Co. and from the Toilet not soon be forthcoming, the Commis Aromatic Polycyclic Hydrocarbons In Goods Association stating their intention sioner finds that the basis for the post Carbon Blacks," Cancer Research, 12:40- ' to conduct the studies necessary to sup ponement no longer exists and hereby :43,1952). Studies on carbon blacks have port "permanent" listing for carbon terminates the 'postponement of the Indicated that PNA's are not formed black (all-gas channel black) for use in closing date for the provisional fisting of during the manufacture of the color ad food, drugs, and cosmetics. Thereafter, carbon black (all-gas channel black) for ditive unless the temperature of pyroly the types of data required on carbon use in food, drags, and cosmetics In ac sis, Le, the subjection of organic com- black were discussed at meetings between cordance with section 203(a) (2) of the 'pciinds to very high temperatures in at FDA and the-Toilet Goods Association. transitional.provisions of the Color Addi mospheres deficient In oxygen, reaches On April 25. 1969, a color additive peti tive Amendments of 1960. Also,' under .. 1100* C. -In a review of the available data tion (CAP 9C0092) was submitted by the section 203(d)(1)(E) of the amend `on carbon blacks submitted with the col- Toilet Goods Association (now the Cos ments. the Commissioner concludes that ,or additive petition, for the listing of car- metic. Toiletry and Fragrance Asso the provisional listing of carbon black ' bon black (all-gas channel black) (CAP ciation. mcn 1133 15th St. NW.. Wash (all-gas channel black) should be 'ter 9C0092), Jack L. Radomsld, MJP-. Profes- ington. D.C. 20005), the Pharmaceutical minated because such action Is necessary sor of Pharmacology, University of `Manufacturers Association (1155 15th St. to protect the public health, in that ques- - 'Miami, School of Medicine, Coral Gables, NW-, Washington. D.C. 20005) and the tlons have been raised about the safety of * ` Florida, noted that carbon black, (all-gas National Confectioners Association of .the color additive and the available data channel black) appears to be free of the UA. Inc, (1225 19th St. NW. Wash do not permit a determination of safety. PNA's and speculated that this might be ington, D.C. 20036). c/o Hazleton Labora Published elsewhere in this Issue of the attributable -to the fact that pyrolysis tories. Inc. PiO. Box 30, Palls Church, Federal Register is a notice denying the mperatures do not routinely exceed Va. 22046. seeking the "permanent" list petitlon proposing to list "permanently" iOO* C during the production of the ing certification of carbon black carbon black (all-gas channel black) for color additive.' (all-gas channel black) for use In food, use in food, drugs, and cosmetics. ' The sensitivity of the analytical meth drugs, and cosmetics. ods used -in the studies upon which Dr. ' The Commissioner's conclusion that Radomsld relied is not known; there- the Toilet Goods Association petition was - fore, it cannot 'be determined whether Inadequate because It did not contain de the methods employed were sufficiently tails concerning the manufacturing proc precise to conclude with reasonable cer- ess and methods of analysis for the color talnty that extractable PNA's are not in additive was conveyed to the petitioners fact present in the commercially avail as early as May 7, 1969. The petitioners able color additive. Based upon their re * were also* asked during a conference with view of the data submitted with the peti FDA on February 10, 1970. to submit in tion and other pertinent data, FDA sci enlists have concluded that the analyt formation to the agency concerning the specifications for carbon black (oil-gas ical methods employed in the available channel black). Again, FDA advised the . studies probably were not capable of de petitioners of the need for additional tecting extractable PNA's much below 'data by letter of December 7, 1973. The 100 parts per million (ppm). The Com- Commissioner has repeatedly sought The provisional listing of carbon black (all-gas i.channel black) is hereby ter minated.* effective September 23, 1976. After September 23. 1976, adding car bon black (all-gas channel black) to any food, drug, or cosmetic will cause such product to be adulterated within the meaning of the Federal Food, Drug, and Cosmetic Act (21 UJS.C. 301 et seq.) and subject to regulatory action. This pro hibition applies to the use of carbon black, mixtures of carbon black with other colors or their lakes, and such mix tures with ingredients functioning only as diluents. The Commissioner concludes that the protection of the public health - missioner has previously concluded, in a regulation published In the Federal Reg ister of September 23. 1974 (39 FR from the petitioners data adequate to es tablish specifications for carbon black (all-gas channel black) that would per does not require the recall from the market of food, drugs, and cosmetics containing the color additive, or the de 34188) establishing safe conditions of use for the food additive citric acid obtained from Cojtdida lipolytica under 1121.1259 ^ (21 CFR 121.1259), that an analytical method must be sufficiently sensitive to detect extractable PNA's to a level of 2 parts per billion (ppb). The Commission er Is not aware of a reliable method for detecting extractable PNA's in carbon black (ali-gas channel black) that is sen sitive to a level of 2 ppb and. as described below, persistent efforts to obtain this required method from the petitioners have been unavailing. mit him to conclude with reasonable cer struction of products in preparation, to tainty that the commercially available 'which the color additive has already been carbon black (all-gas channel black) had added. been manufactured from all-natural This action applies to externally ap gas using the impingement or channel plied products as well as to those in process, data demonstrating the absence tended for ingestion, and to pet food and of PNA's in benzene extraction of carbon animal feed as well as to human food. black (all-gas channel black) using an Manufacturers of new drugs and new analytical method sensitive to 2 ppb, and animal drugs, including certifiable anti specifications for permissible levels of biotics for animal use, containing carbon lead and arsenic. black (all-gas channel black) may either As noted, data adequate to resolve the .delete the color additive or substitute a Commissioner's concerns about the safety different color In accordance with the of carbon black (all-gas channel black) provisions of 5 314.8(d) (3) ` and (e) or The agency's conclusions that existing data are inadequate to establish specifi have not been provided to FDA, and it does appear likely that they will soon be $ 514.8(d) (3) and (e), as appropriate (21 CFR 314.8(d)(3) and <e>, 514.8(d) (3` cations fori carbon black (all-gas chan forthcoming. The Commissioner con and (e)). The applicant shall submit nel blackV'and that ai^ appropriately cludes therefore that continued provi .data providing the new composition and sensitive anlytlcal method to detect sional listing for carbon black (all-gas showing that the change in composi- J i i I , i t j ) i 4 i FEDERAL REGISTER, VOL 41, NO.-U4--THURSDAY, SEPTEMSER 23, 1974 see 1-0028 f RULES AND REGULATIONS 41: tlon does not Interfere with any essay .of carbon black as part of this action Commissioner <21 CFR 5.1) (recodii. or other control _ procedures - used In .but'rather Intends to Include them as tlon published in the Febcsal Rxcxs manufacturing the*drug, or that the as-. part of a planned review of the available Of June 15. 1976 (41 FR 24262)). Pai say' and other control procedures have data for the regulated food additives. of Chapter I of Title 21 of the Code been revised'to make them adequate. The' Federation' of American Societies Federal Regulations Is amended as 1 Also, ` the applicant shall submit data for Experimental Biology (FASEB) wQl lows: available to establish the stability of the revised formulation, or if the data are soon be reviewing the available literature' concerning the use of carbon In the proc 8.501 I Amended] too limited to support a conclusion that essing of food as part of the ongoing re- 1. In i 8.501 ProxHsional lists oj co. . the drug.till retain its de-.'ared potency [vlew of substances that are generally additives; .for a reasonable marketing period, a recognised as safe (GRAS). Included In a. Paragraph- te) is' revoked and i commitment to test' the stability of this review will be substances such as . served.- marketed batches at reasonable Inter charcoal or activated charcoal whose use b. In paragraphs (f) and (g). the enl vals. to.submlt the data from such tests .in food has been considered GRAS. The .foi . carbon black (prepared by the "lu 'as they become available, and to recall GRAS review of carbon may also Involve plLgement" or ."channel** process) fromthe market any batch found to fall certain applications of carbon black (all deleted. - 'outside the approved specifications for gas channel black). The Commissioner 2. In S 6.502, new paragraph (g> the drag. has not considered the use of carbon for added to read as follows: - The Commissioner Is aware that sup plies of alternative color additives may be difficult to obtain Immediately. Con sequently, food and drug labeling stat uses other than coloring as part of this action, instead, he concludes that action on the various uses of carbon that are to be reviewed by FASEB as part of the 8.502 "Termination of provisional lng of color additives. i .* li ing that the product contains "artificial GRAS review should await the receipt <g) Carbon black {prepared bp th. color** because of the prior Inclusion of -.of the final reports of their evaluation. "impingement* or 'channel** process) carbon black (all-gas channel bltck) may The Commissioner has carefully don- The Commissioner of Food and Drugs, ii continue to be used with the oncolored ,'sldered the environmental effects of this . order to protect the public health, hercb;. ..product during the time necessary to ob action and, because the action will not terminates the provisional listing of car tain supplies of alternative color In significantly affect the quality of the bon black (prepared by the "impinge gredients or until the current supplies of human environment, has concluded that ment'* or "channel** process) for use lr. labeling are used, whichever occurs first. .an environmental Impact' statement is food, drugs, and cosmetics. Carbon black (all-gas channel black) not required. A copy of the FDA environ- Notice and public procedure sow not Is the subject of food additive regula- 'mental assessment, together with copies necessary prerequisites to the promul ;tiocs`ln Subpart F of Part 121 <21 CFR of the other documents mentioned above, gation of this order because section 203 'Part 121) for Its use In food-contact are on file with the Hearing Clerk, Food (d) (2) of. Pub. L. 86 618 so provides. articles as acoloront (e.g.. in paragraph. "(b) (3) (xxvi) of i 121.2514 Resinous and polymeric coatings) and as a filler (e.g., "In -paragraph (c) (4) (v) of 1121.25(12 Rubber' articlea*-Intended for repeated and Drug Administration, Rm. 4-65| 5600 Fishers Lane, Rockville. Md. 20852. Be-caure this action Is final (not proposed), an Inflation Impact evaluation Is not re quired by Executive Order 11821 <3A Effective date. These regulations be effective September 23. 1976. (Title n. Pub. &. 86-618. 74 Stat. 404-407 (31 UA.C.376 note).) ^use)These*' uses generally were sup , CFR. 1975 Compilation, p. 203). Dated: September 17.1976. ported by_data showing an absence of migration of. the carbon black from the Therefore.' under the transitional pro visions of the Color Additive Amend '* ments of 1963 (Title n,- Pub. L. 86-618, -food-contact surface to food. The Com-. 14 Stat. 404-401 (21 UjS.C. 316 note)) Shexwih Gasdnek, Acting Commissioner Food end Drugs. mlssioner has not considered these uses .and under authority delegated to the {PR Doc.76 37824 Piled 9-32-78; 8:45 am / \.V **. Jt. 'X .1t 'f FEDERAL REGISTER, VOL 41. NO. 1*4--THVRSOAY. SEPTEMBER 23. 1974 see 1-0029 .. 141860 :l !0-4>roP05ED'sRULES ; "'DEPARTMENT OF HEALTH, -nations 'for -many of the provisionally regulation-published elsewhere-la this Is - ""'EDUCATION, AND -WELFARE -`llsted'-color --additives `before Septem- sue of the Federal-Register, effective -ber 30, *1976,-the FDABureau-of Foods October 26,-1976.- Also published else- . ' ' TPoocf and Onsg Administration .- has reviewedeach of-the-petitions to list -where in this issue of the-Federal Recis- V*1. -1'[ 21CFR Part 8 ] 'the 84 provisionally'listed color additives ter is a notice announcing the withdraw V" ~'* / {Docket Ho. 76N-03W1 ' and other pertinent data. This review in al of the color additive-petitions seeking volved -evaluation -of 64 color additive to list "permanently'' *all of these sub PROVISIONALLY USTED COLOR -petitions Becking*"permanent" listing for stances .except gold. No color additive V ADDITtVCS *83 provisionally listed -color additives. petition or progress report had been sub i. Proposed Postponement of Closing Dates 'The 64 color additive petitions were re- mitted on gold, the 64th provisionally . The Commissioner of Food and Drugs. viewed !in accordance, -with the criteria 'for "pe__r_m__a_n_e__n_t_"_l_is__ti_n_g__set _fo__r_t_h__in___s_ec- 'listed color additive, as required by 3 S-501 of the color additive regulations (21 CFR, von dta '.own initiative, is proposing to -^lon 706 (b) <5) LA) of the act In particu- `8.501). ^postpone the closing date for the use of ^iar, the Bureau of Foods reviewed avafl- :-tcertahrprovistonally listed color additives toxicity chemJstry-and usage data _ beyond December 31,1976. The postpone- reexamined previous evaluations of sment would be conditioned on the under- ithese data to determine If safe conditions . taking of appropriate scientific invest!- -.of me for ^ coior -additives could be gallons and the submission of data to the ^established for purposes of "permanent" The remaining .'72 color additives on the provisional list have been grouped into thi following S categories based on .the review of the Individual .petitions seeking their "permanent" listing; 'Food and Drug Administration (FDA) on ;Hating under section 706 of the act. The A. .Color additives for-which sale condi a prescribed schedule, tolerated pemons ^yje^ also involved examination of cor- tions of use can be establisheC nd for which have until November 22, 1976,-to submit Vrepondenee and memoranda of aieet- > "permanent** listing is appropriate: xorntnenta. .. under Title ifr *the ` Color Additive lngsfto -assure'that. In each instance In .whl^ axrior additive petition has pre- . B.'Color, additives that require additional iahart-tt tea eye area studies; ^lAmcodmeat* of.WJO '(see 203(a)(2), been found to contain inadequate C. Color additives that require addition*! , iPuh.:L.i86-618, .74 Stat. 40i (21 \3,C* \m insufficient-data or in which addi- .short-term toxicity studies; D. Color additives that require, additional J75j`^2ran?w4^?er- "utforityl dele' jtlonal data or studies-were required to -chemistry`data to'establish safe conditions gatedsift him, the CommIsaloner is au- s^x-esnoilvv#e iumnic-pert*a!innttilees-nabouiit the usafefettvy of of use; . rthoriredto-postpone-thexlcasing date of `the color, the petitioners had been ap - 2. Coloradditives that require newxhronle ' a provisional-listing of a color additive prised of the deficiencies or uncertain- "toxicity studies. ^on hisrown initiative or upon the appU-cation-jof.-an 'Interested person. Section .`203(d) (!) Of Title U requires promulga- tton, insofar as practicable, of a current Jlstlng of-color additives and the partic*lilar uses.thereof deemed.provisionally listed.- - ` )' The closing date, September 30, 1976, was established by a regulation pub lished in the Federal Register of Janu ary^. 1976 (41 FR 754) for 84 provl sionally listed color additives based upon ' the`Commissioner's conclusion that the postponement was consistent with the objective of carrying -to completion. In . good faith and as soon as reasonably -ties.-Copies`of the correspondence and manedmtohreanpdeati`t^`'ioonf emrse_ae_ntindg_tsheb_iretrweperee_n_s_eF_n_Dt_aA'tiv^^vktag them ofthe need'for addi- itlonal data or studies, are -on file with -the Hearing Clerk,Food and Drug Administration, Rm. 4-65. '6600 Fishers -Lane. Rockville. MD 20862.; ' i The available data on 20 of these 72 .provisionally listed color additives are adequate to support final determinations of safety and regulations "permanently" listing the color additives are being pre pared. The Commissioner anticipates that these regulations will be issued be fore December 31,1976. The remaining 52 Final determinations have been made on 12 of the 84 provisionally listed color -additives on the baste of the Bureau of provisionally listed color additives can not be "permanently" listed at this time because the available data are Inadequate Foods' review of the petitions seeking "permanent" listing for them. The 12 colors and the action taken-with respect *to each are as follows: to make final determinations. The Comnilssioner concludes, however, that there arc no significant questions of safety re garding any of these 52 color additives, practicable, the scientific investigations 1. FDdeC Red No, 4. The provisional and that continued provisional listing for necessary for making a determination as listing for FDScC Red No. 4 for use in them presents no risk to the public , to noting these color additives under sec maraschino cherries and ingested drugs health. tion 706 of the Federal Food. Drug, and Cosmetic Act (21 U.S.C. 376). In the pro posal to postpone the closing dates, pub is terminated by . regulation published elsewhere in this issue of the Federal Register, effective September 23, li76. Most (49) of these 52 color additives are provisionally Itsted for use only jn drugs and/or cosmetics. Three--FD&C lished in the Federal Register of No Also published elsewhere In this Issue of Yellow No. C, FDitC Green No. 3 and vember 14, 1975 (40 FR 53039). the Com- the Federal Register are a notice deny FDfcC Blue No. 2--are provisionally listed : mlssioner also advised that a final deter ing the portion of the petition seeking for use in food as well. Additionally. 7 of mination on the "permanent" listing un` der section 706 of the act of many of the provisionally listed color additives "permanent" listing of FD&C Red No. 4 for use In maraschino cherries arid In gested drugs and a regulation "perma thcs.t 52 eolors--FDfcC Yellow No. 5. FD&C Red No. 3. FD&C Slue No. 1. an- natto. caramel, carmine and carotene-- was expected to be completed before Sep nently" listing the color additive for use arc "permanently" listed for use in food tember 30. 1976. The Commissioner also In externally applied drugs and cosmetics. and ingested drugs. stated that. If appropriate, further post- 2. Carbon block (all-pos channel Under the transitional provisions of - ponements would be made for individual black). The provisional listing for carbon the Color Additive Amendments o( i960, color additives for which final determi black (all-gas channel black) for use In however, continued provisional listing of nations were not possible. food, drugs, and cosmetics' is terminated a color additive is appropriate only when The Commissioner has postponed the by regulation published elsewhere In this studies in progress or under evaluation closing date for the provisional listing of issue of the Federal Register, effective arc capable of demonstrating Die safety 72 color additives until December 31. September 23.1976. Also published in this of the color additives involved. The Com 1976. by regulation published elsewhere issue of the Federal Register is a notice missioner proposes, therefore, to cerdi- In this issue of the Federal Recister. denying the petition to list "penni- tlcn ' further postponement of th.' effective September 23. 1976. The brief nently" carbon black (all-gas channel closing dates for. the use of these GJ postponement is necessary to allow time black) for use In food, drugs, and provisionally listed color additives on ' for public comment on this proposal, to cosmetics. compliance with specific requirements to prepare notices "permanently" listing 20 3. Aluminum stearate, bentonite, cal be contained in a new $ 8.505 of the color of the provisionally listed color addi cium silicate, calcium stearate, gold, additive regulations. Section 8.605 would tives and Jo provide for the uninter- kaolin, lithium stearate, magnesium explicitly set forth the' type of additional . runted use of the remaining color aluminum silicate, magnesium stearate, studies that must be conducted and date, tadditives. * and zinc stearate. The provisional listing tha*. must be submitted to FDA to dem In accordance with the Commissioner's fort hese 10 substances for use as color onstrate the safety of the color additives stated intention to make final determl- additives in cosmetics Is terminated by involved. The type and extent cf the ttOEftAl RECJSTEft, VOL 4), NO. 186--THURSDAY, SEPTEMBER 23. 1976 sec 1-0030 PROPOSED RUtES 41 studies and data required are based on The 20 color additives to be "perma Of the 14 color additives listed ab< the recent Bureau of Poods' review, of nently" ' listed and their * uses are as 7 appeared on-the so-called "Har the 64 individual color additive petitions. follows: list" published in the Federal Regis' The majority -of- the 52 provisionally ~ i ntr Green No." S* (externally applied * ^ October 6, 1974 (39 PR 3612' list.ed color a_ d dJiitti*ves involved_i requiire dru*gs and e**o*u^aette*)*. ' Fr -- aalliulmmiMiniutmm powder,aamnmn<ia06ttmo, bismuth o; only a single type of data. e.g,, short a. D&C Yellow Mo. 7' (externally applied chloride, caramel, carotene, eopi term eye area studies, or short-term drugs aad coemetlca). powder, and zinc oxide. Petitions for 1 toxicity studies, or additional chemistry data or chronic toxicity studies. In sev 3. D&C Yellow No.* 8 . (externally applied itnip , 7 "Harvey list" colors and the remain] 7 color additives and other pertin< eral instances described below, however, 4. DiO Yellow No. 11 (externally applied data have been reviewed and are ac more than one. type of data or study are required. drug* and cosmetics). . 5. DAO Bed Mo. 17 (externally applied drug* and cosmetic*). qu&te to establish the safety of 8 of t 10 provisionally listed colors for whl Proposed ' } 8.505 would require that - g. D&C Bed No.'' SI (externally applied ' "permanent" listing for external and i each of the petitioners agree in writing drugs and cwawtki). , seated cosmetic use Is sought and for t . within SO days of the effective date of 7. DAO Bed No. 64 (externally appUed 4 : irovlsionally listed color additives S the regulation to undertake the scien'tifle investigations necessary to permit ' FDA to make final determinations on the color additives/and that the petitioners drugs and cosmetics)*. ' 6. OW Violet Mo.. 3 (externally appUed drugs and coametlca) 9. DAO Brown No. 1 .(externally appUed cosmetics). which permanent, listing for exterrt cosmetic use only is sought. The da are inadequate, however,-to "perma. ently" list any of the 14 colors for eo or other interested persons undertake " io; Ext. d*c Yellow No. 7 (externally ap- metic use in the area of the ere becau those scientific investigations, file prog- pued drugs and coametlca). - each of the color additive petitions f- ress reports with FDA. and submit the .final results within fixed time periods prescribed In the regulation. Addltion- * afiy. the petitioners would be required to notify FDA immediately of any findings that indicate a potential for a color addl- . tlve to cause adverse effects. Failure of * the petitioners for any additive to com ply with the requirements contained in . { 8.505 would result in Immediate termi nation of the provisional listing of the color additive. New S 8.505 would also * establish closing dates for each of the . categories of color additives listed above by which the provisional listing would be * terminated, except In extraordinary `.,cir_cumstances. , ,, _ . U. Ext. DAC Violet No. 3 (externally ap- , thi se 14 color additives lacks results fro. 12. ]>aO Blue No. 4 (externally appUed a short-term eye area study with rabbi drugs and coemeUea).' tn which the color additive Is repeated' 13. Axuleae (externally applied eoemetlcs). instilled into the eye for 4 weeks. 17 , 14. Iron oxide* (all oosmeUc* Including studies' involving repeated use in areae of the eye) 16. Mangmaeee violet (all coametlca includ ing use la area of the eye). " is. Ultramarine blye- (externally applied coaxnetiee Ineluding use In area of the eye). Into the eye will provide an added mea: ure of assurance that each of the colt additives may be used safely in cosmetic for use in the area of the eye. 17. Ultramarine green (externally applied The petitioners for these 14 color o< ooametlee Including use In area of the eye). dltlves were advised by FDA on July 31 18. Ultramarine pink (externally applied *1969 that short-term eye area studic cosmetics including.uae In area of the eye). involving repeated Instillation of the 19. Ultramarine' red (externally applied coametlca Including use In area of the eye). 20. Ultramarine violet (externally applied cosmetics Including uae In area of the eye). color Into the eves of test animals wouli *be required before final determination could be made on "permanent" llstlnt Considerable discussion thereafter en Notices "permanently" listing these 20 -s-u--e--d---b--e--t-w--e--e--n---F--D---A- ---a-n--d- --the__p_e_t_it_io__n_e_r The proposed provision for postpone- - color additives are currently'being pre- concerning the format and conduct of tli. - meat in extraordinary circumstances of .pared; the Commissioner expects that., eye area studies. The petitioners subsc- the closing dates beyond those in 5 8.505 wm be published In the Federal :* quently prepared a protocol, conducted is included in anticipation of the pos- RECISTrx before, the December 31, 1976 pilot toxicological studies, and submitted sibillty, although unlikely, that unfore- Tht provisional listing for the results to FDA. The results of thi seeable and unavoidable occurrences or these color additives will be terminated 'situations may make compliance with ' I 8.505 * extremely impracticable, If not -.'virtually' impossible, and which-would therefore require in fairness that the. provisional listing be further postponed. A request for further postponement on `the grounds of "extraordinary circum stances" would'have to be submitted In writing and state in detail the basis .for * the request. The Commissioner does not anticipate that "extraordinary circum stances" will occur and therefore fully expects that no color additive will be provisionally listed after December 3X. . when the "permanent" listing becomes effective, unless any regulation is stayed - by the filing of valid objections, in which case the provisional listing for that color would continue. B. Color additives that require addi tional short-term eye area studies: Color additive petitions for 14 of the 72 pro visionally listed color additives- seek "permanent" listing for use In cosmetics, including cosmetics intended for use in the area of the eye. "Permanent" listing -for all types of cosmetic use, l.e.. In gested, external, and area of the eye, is 1980, the proposed closing date for those' sought for the following 10 provisionally f!Sr.d<tLv.es i0T vw?,ch ne7 <?ronif^listed color additives: toxicity studies are belog required.----- The requirements of proposed < 8.505 are set forth In detail in the following dls. cusslon of the five categories of provision-. . ally listed color additives. 1. Anastto. . 2. Bismuth oxychloride. 3. Bronze powder. 4. Caramel. 5. Carmine. pilot studies were evaluated by FDA anc the petitioners were advised to initiate the eye area studies on each of the 14 color additives. Eye area studies on these 14 color additives arc either underway or have been contracted for and will begin very shortly. The Commissioner proposes to post pone the closing dates for the provisional listing of these 14 color additives until July 1, 1977, to provide sufficient time for the petitioners to complete the eye area studies, conduct the pathology work in the rabbits, analyze and write up the' results, and submit them to FDA for review. This brief period would also in clude time for FDA to evaluate the re sults and to prepare regulations either "permanently" listing the colors or termi nating the provisional listing for use in the area of the eye, based on the results of studies.* A. Color additives for which safe con 6. Carotene. ' ~ Proposed I 8.505(al would require that ditions of use can be established and for which "permanent" listing is appropri ate: The Commissioner concludes, based on the Bureau of Foods' review, that the 7. Copper, -metallic powder. 8. XIIc* . 9, Guanine (pearl eeaeace). 20. Zlne oxide. each of the petitioners advise FDA St; writing of the status of the eye area studies within 30 days after the effective date of the final regulation, and that safety of 20 of the 72 provisionally listed "Permanent" listing for externa] and they complete the studies and submit color additives has been demonstrated. area of the eye use only Is sought for the the results to FDA within 45 days after There are no adverse effects associated following four provisionally listed color the effective date of the final regulation. with the.use of any of these 20 color addi- additives: The Commissioner is of the opinion that -tlves under the conditions of use in the - petition; the chemistry and usage data '* are adequate for "permanent" listing. 1. Aluminum powder. X' Chromium hydroxide green. 3. Chromium oxide greens. 4. Ferric ferrocyanldo. - these short periods of time to comply with proposed } 8A05(a) are reasonable because the petitioners have advised ttOERAl REGISTER, VOL.'41, NO. 184--THURSDAY, SEPTEMBER 23, 1*76 SCC 1-0031 ^-<1S62 ^ ' -PROPDSDrR.m.ES ' ,,JFDA that the eye area studies are under- _ their use in externally applied cosmetics. - if SUt. DSC Yellow No. 1 (externally applied s, war or will aooo-bcgln. New i 6.605 would r.These studies Involve appUcatlouof the * drugs and cosmetics) '`.also require that the petitioners notify color to the Intact and abraded skin of 8. FDitC Yellow"JNo. o (food, drugs and cos ,'^FDA^Immediately of any findings that rabbits for 00 days. Color additive petl- metics) `^indicate a-potential for any color addl-fa tlons for these two colors -were submitted *' 7.D&C Yellow No.' 10 (drugs and cosmetics) S..D&C Bed No. 0 (drugs and cosmetics) 'rttve!to'cause adverse effects. Failure to ..In response to the October 6. 1974 notice 9. DAO Bed No.-7-(drugs and cosmetics) submit the status letter within 30 days'and the colors were'provisionally'listed . 10. 'D*OBedNo.27 (drugs and cocunetlcs) Z3or*to submit tho final results within 48' thereafter while the petitions and other - 11. DitC Bed No. 38 (drugs and coemetio) * .days or to provide Immediate notification data were evaluated. Review of the petl- . 12. D&C Bed No. 30 (drugs, cosmetics, said ,;of indicating a potential for a* lions and other data' on bismuth exy- . surgical suture*) ~'t'color'iaddltive' to. cause adverse effects chloride and caramel disclosed the need 13. D&C Blue No. a (drugs, cosmetics, and Vwrmld.iesult.lnrlnunedlate termination - lor additional skin studies because data surgical sutures) ,of the provjtional`.illstinf ;for: the color were lacking to establish that the colors ,addltive .for'useria'.the area .of the cyi. * were safe for use la* externally applied ^.Tho'CommIsstaner.would.'ln any event, cosmetics. As noted above,-.blsmuth oxy- 14. Logwood (sutures) 15; Oraphlto (externally applied cosmetics - Vv" - Including use In area of the eye) > ^.terminatethe'-provisional'listing and chloride and caramel require shbrt-term The chemistry dita lacking on these 15 .'^permanently* list'the colors or deny the eye area studies. As explained below in . colors consist of. s iftlclently.precise ana .^.petitions for these'14'colors for eye area this preamble, caramel also requires a" lytical raethods and other information ~*Ca.' anH 'ftennanently*!,jllst them for ' chronic study to determine If It causes to enable FDA to Identify and define the '.other' uses,`.supported by`available data chronic adverse effects. Including .car- color additives more accurately than cur ba. y_ _,.JYuly.'*s" *h4 L.1ft9g7fl7*,-,unless e xt*-r--a-.o^rJdl_in---a---r---y-- dnogeulcity, upon external application. ' rently available data permit. Detailed ^circumstances wereshown.. ! Proposed i 8bD5.(b)` would postpone specifications and precise analytical -As' dlyussed.'below In this preamble, the closing date for bismuth citrate, bis methods are required to certify batches V-caramel!also requires-a chronic study muth oxychloride, caramel and lead of each color* adultlve as equivalent to . - to if it.c&uses chronic adverse . acetate until September 30, 1977. These the batches of each color additive used *. effects. Including carcinogenicity when p' os*tponemen*ts wou'ldJ be conditioned on In conducting animal studies to establish ".externally, applied, and-a short-term the written agreement by each of the the safety of tho color. . 7'toxicity study. The closing date for earn- petitioners within 30 days after this reg The closing date for the provisional ."mel would be postponed under proposed ulation becomes .effective, to. undertake listing for use of these 15 colors would be ; 18^0S(d)` until December 31, 1980, only the required studies needed to provide'as- ! postponed until. September 30. 1977. If the petitioner complies'with | 8.505(a) suranee that use of the color additives is .under proposed $ 8-505(c>, which would "and (b). ' <V -w sale for purposes of "permanent"' list condition the postponement on the writ The Commissioner concludes that the ing. New {8.505(b) would also require ten agreement fay each petitioner, within * 'continued provisional listing of these 14 . that the results of the absorption studies . 30 days after this regulation becomes ef ; color additives under their intended con- and the results of subchronic studies be fective, to undertake to develop and sub dltlons of use until July 2, 1977. does not .submitted to FDA within 180 daw after mit to FDA'the necessary chemistry data '.present a hazard to the public health. this regulation becomes effective, end .and analytical methods required to es ' C. Color additives that require addi- that the petitioners notify FDA immedl- tablish specifications for each color addi ` tional short-term toxicity studies: Of the ately of any findings - that indicate a tive and to certify batches of each color ' 73' provisionally ` listed color additives, potential for any of the color additives to additive where certification is necessary. * bismuth citrate, bismuth oxychloride, * cause adverse effects. Failure to comply Proposed 18.505(c) would also require 7 caramel and lead acetate cannot-be-**per- with any of the requirements contained that the chemistry data and analytical . manently* listed at this time because short-term toxicity studies are needed to : provide additional assurance that their -. use -is safe.. Bismuth citrate-and lead in S 8.505(b) would result lh'Immediate ' termination of the provisional listing for . 'the color additive. . Alter'submission of the stud-y resu, lts, methods be'fsubmltled to FDA within 210 days alter' the regulation becomes ef fective and that FDA be notified Immedi ately of findings that Indicate a poten -acetate, which are petitioned for use to ' color hair, require short-term absorption studies because earlier studies suggest a .potential for percutaneous absorption. The required short-term absorption studies Involve administration- of the will promptly review them and. If they are adequate to establish safe con-. dltlons of use, the color additives would be permanently listed. If the data are inadequate, the provisional listings would be terminated. The Commissioner would. tial for any of the color additives to cause adverse effects. Failure to comply with the requirements contained in S 8.505(c) would result In immediate termination of the provisional listing for the color ad ditive Involved. . ` product containing the color additive to . in any event, make final determinations the hairfor 90 days under renditions of . on each of the colors and terminate their ' we. During and at the completion of the provisional listing by September 30,1977, .'.period of administration of the product, unless extraordinary circumstances were Personnel of the FDA Bureau of Foods will be available to clarify the type of data and analytical methods required .and to consult with the petitioners. If .urine and blood tests would be conducted '.to determine of the color additive has shown.. The closing date for caramel would be December 31, 1980, if the con necessary. The chemistry data and ana lytical methods for each color will be been absorbed, through .the'skin 'into the ,body systems, t,.* V ditions of S 8.S05 (a) and (b) are met. The Commissioner concludes that con . promptly reviewed by FDA after their, submission and. if the data and analyti ' An'absorption 6tudy on bismuth citrate tinued provisional listing of these lour cal methods are adequate to establish at a level of-0.25 percent of the product colors until September 30, 1977, does not specifications.. the Commissioner would ' has been completed and suggests that ' there may be absorption. Accordingly, an present a hazard to the public health. D. Color additives that require addi publish a notice in the Federal Register `"permanently" listing the color additives `additional absorption study is necessary tional chemistry data to establish safe that do not require chronic toxicity stud at the 0.5 percent use concentration "be conditions of use: Of the 72 provisionally ies. If the data and* methods are Inade cause the petition seeks a "permanent" listed color additives. 15 cannot be "per quate for any color, the provisional list listing for use at that higher concentra manently" listed at this time because ing would be terminated.- The Commis tion. In addition, a 90-day study with complete chemistry data are lacking to sioner would, in any event, terminate the rabbits, as described below, is required establish specifications for them. The 15 provisional listing and "permanently" .lor bismuth citrate because of the possi colors and their provisionally listed uses list, or deny the petition, for each of bility of absorption and the absence of these 15 colors by September 30, 1977,. 'data * concerning' the distribution of except as noted below, unless extraordi absorbed bismuth In the body. 1. Die Orong*'No.'4 (externally applied nary circumstances were shown. Bismuth oxychloride and caramel, 2 of the 21 color additives that appeared on -.the so-called "Harvey list" In the October C8/1974 Fme&ai/Regestm,'require short- - llerm-skin studies with Tabbits to support - drugs and cosmetics) 2. D&c Orange No. 6 (drugs and cosmetics) 3. DAC Orange No. 11 (externally applied drugs and oosmeUes) 4. Ext. DiC Green No. l (externally applied drugs and coecnetlcs) Nine of the fifteen color additives also require new chronic toxicity studies: DAC Orange No. 5, FDftC Yellow No. 6. D&C Yellow No. 10. DfcC Red No. 6. DAC Red No. 7. D&C Red No. 27. D&C Red FEDERAL REGISTER,; VOL 41, NO. 186--THURSOAY, SEPTEMBER 23. 1976 sec 1-0032 PROPOSED^RUfES 41SG3 .No.. 38. DAC Red No. 30. and DlC Blue ministration. Rm. 4:-85,'*5600' Pishera stance than those studies conducted over 1N0..6. The closing date-Ior each of these iane. Rockville. Md. 20852. a decade-ago. The Commissioner con- colors would be postponed under pro - 'The available studies do not show .any -chides that new chronic toxicity studies posed S 8J>05<d) until December 31.1980. .advene effects associated with use of any on these 31 provisionally listed color ad- .. .to permit completion ot the chronic tox- -of the 31 color-additives under: their In- diUves -must be conducted to provide' . ilclty- studies.- but only-if the chemistry :tended' conditions of use. However.-the data that are essential for current deter . .data and analytical methods are supplied deficiencies In the studies make It Impos minations about their safety,.N .In accordance with 18.505(e). sible for the-Commissioner currently to Three of the thirty-one color additives "jt The Commissioner concludes that con- conclude that the color additives are safe for which new chronic studies are re- tlnued provisional listing of these -15 for purposes of '"permanent* listing un ' qulred--FDAC Red No. 3. DAC -Red No. * color.additives under their Intended con- der section 706 of the-act. Additional 33, and DAC Orange No. 10--may also re of'use until September 30. 1977. chronic toxicity feeding studies and. in quire.new reproduction studies. Repro* does not;present aihazard.to the public -the case of caramel.* 2-yearmouse skin - duetion studies on these three colors have z*: .health. -.painting study are required *to provide recently been evaluated by FDA and, al : E. Color additives that require new data to permit final determinations to be though oo adverse effects were seen, ' chronic toxicity studies: Of the 72 pro- -made on listing these color additives. question*' have been raised because the * -visional]? listed color additives; 31 can- .Final determinations cannot be made In -procedures prescribed In the protocol for .-* mot be "permanently'-' listed because the .the absence of such new data because to randomly selecting the animals were not .available toxicity data--though eugges- do so would require that the Commis followed precisely. The Bureau`of Foods P~\ thre of no advene effects--are derived sioner Ignore the substantial advances has met on several occasions with the . from studies that, do not.meet' contem :made in testing color and-food additives petitioners In recent months to deter porary. standards generally accepted elnce the presently available studies were mine whether the deviation from the within the scientific community as mlnl- -conducted.. The - Commissioner advises .protocol affected the'validity of the re ' mum requirements for the design and that because-of such Improvements in sults of the studies. The petitioners will * -conduct of toxicological studies to estab -test methodology. FDA Is also reviewing soon submit data to support their view lish safety. . the data that supported the approval of that the studies are valid ones. The Com- ` These color additives and their pro many food additives and "permanently*. tnlssloner concludes that the petitioners visionallylisted Uses are as follows: ; * 1. 7DSO YiUov Ho'. 8 (eoametlca and #xr .'ternary applied drug*) .. - 2.FDAO Tallow Ho. C (food, drugs and eoa- .listed color additives and Is contemplat ing a "cyclic* review of those substances and may, in the future, requirenew stud ies to be conducted on them. should b i provided this brief period to' submit data In support of their view be cause the study results were negative. The Commissioner anticipates that FDA ` zoatlca) Although not all of the studies on the will soon resolve the questions regard 3. DAO Tallow Ho. 10 (drags an0 cosmetics) . 4. FD&C had Hq. S (cosmetics and extem- ally applied drag*) 8. DAC Red No. 6 (drugs and cosmetics) -Es . s 6. DAG Red No. V (drugs and coemetics) 31 color additives are deficient In each of the respects listed In the following paragraphs, the deficiencies In the stud ies for color additive are signlfl- ing the reproduction studies on these three colors. When the questions are re solved. a notice will be published In the Federal Register announcing the resolu 7. DAO Bad Ho. 8 (drugs and cosmetics) * cant enough to make a final determina tion. Section 8.505 will be amended If S. *DAO Red No. 9 (drags and coamatlcs) tion impossible at this time and to war new reproduction studies on these three ; 9. DAC Red No. 10 (drugs and cosmetics) rant new chronic studies. The available colors are required. /V* / .10, DAO RadHo. n (drdga and coametlcs) Wl'-' 11. DAC Rad No. 13 (drugs and eoametlca) 'jk- .. 13.. DAC Rad No. 13 (drugs and eoametlca) * 13. DAO Rad No. 19 (drags and eoametlca) } id. DAO Red No. 31 (drags and eoametlca) Jjv'.. *18. DAO Rad No, 33 (drags and cosmetics) . studies on these 31 color additives are de ficient in the following respects: 1. Many of tb studies were conducted using group* of sniffle!*. Le~ control .end those fed tbe color additive, that are too Caramel, one of the color additives that appeared' on .the so-called "Harvey list,'"' requires a chronic skin painting study to evaluate its potential for caus ing chronic adverse effects and carcino-, -IS. DAO Rad No. 37 (drugs and cosmetics) ,*2y" -17. DAO Red Ho. 28 '(drug* and eosmetlca) .-*& .\j18. DAO Bad No. 30 (drugs,-eoemettes. and smaU to permit conclusion* (o be' drawn today on tbe chronic toxioity or carcinogenic potential or tbe color. Tbe smell number of V..' surgical vutum). 19. DAC Red Ho. 33 (drugJ and cosmetics) *30. DAO Red Ho. 36 (drugs and cosmetics) 1 animals used doe* not. In and of Itself, cause this result, but when considered together with tbe other deflclenele* In this 31. DAO Fad No. 37 (drugs and cosmetics) listing, doe* do so. By and large, tbe studies 32. FD&O Orean No. 3 (food, drugs and cos- 35 animals In each group; today FDA recom- .. metlca) - mends using at least 50 animals per group. genlcity when used In productsIntended for external application. A single color additive petition for caramel and six other "Harvey list" color additives was submitted in December 1975, In January 1976. FDA rejected the pctitfon by letter and Indicated that separate petitions for the seven color additives were necessary. 23. DAO Orean No. 6 (drags and cosmetics) 3. In a number of the studies, the num A color additive petition for caramel was . 34. DAC Green No. 6 (drugs and cosmetics) ` 38. FDAC Blue No. 1 (cosmetic* and exter- nallyappUed drugs) JT*' 33. FDAO Blue No.- 3 (food and Ingested .. M?-' drugs) .. DAC Blue No. 6 (drugs, cosmetics, and ber of animals surviving to a meaningful ago .was Inadequate to permit conclusions to.be drawn today on th* chronic toxicity or carcinogenic potential of tbe color additives tested. 3. In a number of the studies,' an insuffi submitted on February 27, 1976. The 2- * year mouse skin painting study to be re quired for caramel will provide assurance that the color additive Is safe for external use. ` surgical sutures) cient number of animals was reviewed his The Commissioner proposes to post ,i?V 38. DAC Orange No. 6 (drugs and cosmetics) T* *-.'.39. DAC Orange No. 10 (drug* and cosmetics) )?.." 30. DAC Orange Ho. 17 (drugs and cosmetics) ; > ,V 31. Caramel (cosmetics) The chronic toxicity studies to estabrj;, Ush the safety of these color additives were conducted during the 1950's and tologically. Hat number of tbe studies, an Insuffici ent number of tissues was examined In those animals selected for pathology. 5. In a number of the studies, leslana or tumors detected under grass examination were not examined microscopically. pone the closing date for the 31 provi sionally listed color additives that require new chronic toxicity studies until De cember 31. 1980. This 4-ycar period is necessary to plan, conduct and evaluate the chronic toxicity studies that would be required by proposed 8.505(d). Tite --..1080's by laboratories under-contract" The Inadequacies of the available provisional listing would he continu.rd Y* / with the various petitioners and. in some--studies are attributable to the dynamic for the 4 years based on the Commis \*V. Instances, by FDA itself. Review of these " and ever-improving scientific techniques sioner's conclusion that continued vse of .-.`/.studies by the Bureau of Foods disclosed" for testing various types of substances. -the 31 color additives under their in _Vi*" that, when Judged by -contemporary They are not, at least In most Instances, tended conditions of use presents no haz >r-standards for toxicological studies, the. the result of Inherent defects in the ard to the public health. New 5 8.505 \: ? studies conducted to support the petitions -studies or failure to conduct them com- (d) would condition the postponement ,>* ff. to "permanently'' list the 31 color add!-' petenUy. Studies conducted In accord- Oh the written agreement by each of tho , ' -'3' lives were deficient in the basic respects ance with current standards will provide petitioners, within 30 days after the reg discussed below. Memoranda surnmar- results that are more useful and reliable ulation becomes effective, to conduct the . lzlng these evaluations are on 'file with in evaluating chronic toxicity and the required studies. New | 8.505(d) would ' "r. the Hearing Clerk, Food and Drug Ad- carcinogenic potential of the test sub- also require that protocols for the con- A ;J fEOERAL REGISTER, VOL,- 41, NO. .186--THURSDAY, SEPTEMBER 23. 19/6 see 1-0033 41864-5'' *' x PROPOSED RULES tiuct of the studies be submitted to PDA 72 provisionally listed color additives. been found. Copies of the FDA environ for review and acceptance or rejection Should the Commissioner conclude that mental and inflation impact assessments within SO days after f 8.505 becomes ef those data need updating, the Commis -are on file with the Hearing Clerk, Food fective. Personnel from the Bureau of sioner will take appropriate action. One and Drug Administration. Foods will be available to consult with of' the alternatives the Commissioner - Accordingly, the Commissioner Is pro the various petitioners concerning the' would seriously consider is publishing posing to add a new sentence to the in Resign of protocols and will promptly regulations proposing a cyclic review of - troductory text and change the closing review the protocols and advise the peti ."permanently" listed color additives. dates listed in paragraphs (a), (b), <c), tioners in writing wuether they are ac Three of the color additives that re (f) and <g) of { 8.S01, and to establish ceptable or, if not. what modifications quire new chronic studies--FD&C Blue a new S 8.505; are necessary. All protocols will be No. 1. FD&C Red No. 3. and FD&C Yellow Therefore, under the transitional pro placed on file with the Hearing Clerk.' No. 5--were * "permanently" listed for visions' of the Color Additive Amend Pood and Drug Administration. Ro. 4-. food and Ingested drug use by. regula ments Of 1960 (Title II. Pub. L. 86-618.74 .65, 5600. pishers . Lane,'- Rockville, Md. tions published in the Federal Register 6tat. 404-407 (21 U.S.C. 376 note)) and 20852.., j: ' .Of May 8. 1969 <34 FR 7445. 7446, 7447). under authority delegated to him' (21 New 18.505(d) would also require that The three colors were not, however, "per- - CFR 5.1) ' ('Modification published in' the petitioners submit to IDA semian m&nently" listed for ingested cosmetic * -the Federal Register of June 15, 1976 nual progress reports on the studies and use. The Commissioner recognizes that (41 FR 24262)) the Commissioner pro notify PDA Immediately of any findings use of these three colors in food and ln- poses,that Part 8 of Subchapter A of Title that indicate a potential for any of the . Bested drugs is more substantial than 21 of the Code of Federal Regulations be color additives to cause, adverse effects. their - use in Ingested cosmetics. The amended as follows: Reports of' the results of the studies Commissioner is of the opinion, none 1. By amending { 8.501 by revising the 'would be required to submitted to FDA theless, that it- Is appropriate to condi ' introductory text and the tables In within, 42 months after this regulation tion the continued provisional listing for paragraphs \a). (b), (c), (I) and (g> to .becomes effective. After promptly re the three colors on' the undertaking of read as follows: - viewing the results, FDA would, by December:-31. 1980. publish regulations either'"permanently" listing Individual color additives or terminating the provi sional listing if "permanent" listing Is in appropriate. Failure to submit the writ ten agreement within 20 days, or the pro new chronic studies. It is likely that new chronic studies on the three colors would be required as part of the contemplated cyclic review of the permanently*' listed color additives. New chronic studies will, therefore, not only support continued provisional listing of.these three colors 8.501 Provisional li*U of color liver. . The Commissioner of Food and Drugs finds that the following lists of color ad ditives are provisionally listed under sec tion 203 (b) of the Color Additive Amend tocol within 60 days, or the semiannual reports, or to notify FDA immediately of potential' adverse effects, or to submit the final report of the results within 42 months would result in Immediate ter mination of the provisional listing for the color' additive Involved. "The Commis sioner-would, in any event, terminate the provisional listing for these 31 color ad ditives by December 31, I960, unless ex traordinary circumstances were shown Justifying further postponement. The Commissioner concludes that con tinued provisional listing of these 31 color additives under their Intended con ditions of use until December 31, 1980, for use in ingested cosmetics, but also generate data appropriate for use In a review of other uses. It will thus be in the Interest of all-persons who use the three colors to have-new chronic studies conducted at this time. Nothing in this proposed action affects the Commissioner's authority under the transitional provisions of the Color Addi tive Amendments of 1960 to terminate a closing date, terminate a listing, or im pose restrictions with respect to any color additive on the provisional list. The Commissioner has carefully con sidered the environmental effects of the proposed regulation . and, - because the ments of 1960 (sec. 203(b), 74 Stat. 405 (2i UJS.C. 376 note)). Except for color additives for which petitions have been filed, progress reports are required by January l, 1968. and at 6-month Intervals thereafter. Specifications for color addi tives listed In paragraphs (a), (b), and (c) of this section appear in the respec tive designated sections. The listing of color additives In this section is not to be construed as a listing for surgical suture use unless color additive petitions have been submitted for such use or the Com missioner has been notified of studies un derway to establish the safety of the color additive for such use. The color does not present a hazard to the public proposed action will not significantly additives listed in paragraphs (a), <b>. health. The* closing date for color addi-' th-es subject to paragraphs (b'< and (c) affect the quality of the human environ ment. has concluded that an environ ' and (c) of this section may not be used in products which ore intended to be used as well as (d> of 9 8,505 would be post poned until December 31, 1980. only if the requirements of paragraphs (b) and mental impact statement Is not required. in the area of the eye. The color additives The Commissioner has , also carefully listed in paragraphs (a), (b), (c), (f), considered the inflation impact of the' and (g) of this section are provisionally (c) are met. proposed regulation as required, by Ex listed until the closing dates set forth The Commissioner advises that FDA . Is currently evaluating the data that formed the- basis for the "permanent" listing of color - additives in previous years. It is anticipated that many of the ecutive Order 11821, OMB Circular A107, and the Guidelines issued by the De partment of Health. Education, and Wel fare, and no major inflation impact has therein, conditioned on compliance with the applicable requirements of para graphs (a), (b), (c), and (d) of 9 8.505. (a) * . past decisions to list "permanently*; color additives were based on data derived from studies that suffer from the same deficiencies as those described above. In Ckoine dal# Food um Pin* nd cestuctic me 2U<ctr4#U>-<t that event, the Commissioner will eon. elder-what action is appropriate to up date those data, including conditioning continued "permanent" listing on the undertaking, over a period of time, of studies of the sort that the Commis- T.fi. A C. *rn No. S (ire, R23 o( tMi chapter)........................ Dee. Jl.l'JiO Df. 31.1360 F.l). A c. yellow No. 4 (see. 4J74 I this ehatft*r)__......................do.'....................rto_------ F.P.4 C. yUo* No. 6 (see. 0.41 f(hischapter).............do............. do..- F.D. A C. red No. 3 (sec. 4.242 l this chapter)................... ..do.'....................lo._........ F-D. A C. blue No. 1 (see. 8.204 f this duiiitrr) ___________..do.1*..........do---------F-U. A C. blue No. 3 (see. 4.4022 of this clmptor).._____________ _do........ Fod#rudgasi>.*i it,y >L U Lakes (F.D. A C.) (sec. 9.100< Ud chapter)............................................................... aloner proposes to require for 31 of the ''Ukniy. FEOEKAl BECISTEB, VOL 4!, NO. 184---- THURSDAY, SEPTEMBER 23, 1976 see i-0034 PROPOSED RULES 4ISG3 Cb> k' . .of- this section'shall agree In writing by .(30 .days After-.effective date of Anal Giotloc data , .RoorrteUoo* regulation) to undertake the -eye area ** studies.. (2) A lull written report of the results - ft 4. Y- D.4C. 4 (ore. 8.4070 <) and (fa) of thk eiapier).-- -D.C.ndN.t to. .UI Tthb chapter).. , D. A Ct-rad Ho. 7 to. 9.142 (Ihb efroiXrrL . D. A C. rad He. ** (mc I.1U ** JW ehiUtfL - D. A C. rad No. B to. 9.LM ortbUcitofHd)- J. A C. red Ne. 10 (eee. ilU of |hb chfcptor) J>. A C. rad No. It (ere. at* ul IM rfwpttr) D. A C. red No. 22-to. 0.1S7 of this chapter) .S.A.C.red N.Uto..meflhtichapter) D.A C.red No. W to. this chapter) -D. A C, rad No. 21 to. 0,l ol this chapter) . J). A C. ted No. 32 (ve. hWl of this chapter). . D.AC, red No. 27 (sea. 0.172 e( this chapter) - D. A'C. red No. 2> (see. 9.173 ( this chapter). .D.A C. rad No. 30 &e. 0.173 of this chapter)___ D. A C. rad No. to. 0.171 el thb chapter). D, A C. rad No. TO (eee. 0.1*1 ol this chapter). * D. A C. red No. 37 bee. 0.102 elthlachapter)___ D. A C. orence No. 4 (sec. *.201 oI thb chapter).. D.A C.naitlKJIrt.UBtltkbdM|M<rU D. A C. orance No. to (see. 0J07 oI thb chapter). D.A C. orence No. II (sec. 0JO* Ol this chapter). ]). A C. ereon No. 17 (err. !L21t of thb ehaiacr). D. A C. blue No. 0 (sec. 0.242 of thb chapter). __________ lakes (D.A CJ to. 0230 ol thb chapter)__________________ _______. .dol .do. _db. ,, See. t-SB. ___ D)>oo.. ,, Do. . Do. . _ .Do. -- Do. ___.do...._._ ^ . dept. 30,1077 Kstcmsl ora or If. ..-Doe. 311900 8ec 1.301. __...do..,,,,_' .'Srpt. M.10T7 ." . Dee. Ji.itoO . Do.. . .do--__ " of the studies shall he submitted to the Division, of Food and Color Additives. Food and Drug Administration, 200 C St SW, Washington. DC 20204. by (45 days after effective date of final regula tion). (3) The petitioners shall Immediately notify the Division of Food and Color Additives .of any findings that'indicate 'a potential for 'the color .additive to cause i dverse effects. (b) The closing date for bismuth citrate, bismuth oxychloride, caramel, and 'lead acetate is postponed until Septem*ber 30.1977,'while short-term studies are conducted and evaluated, and subject to -compliance with the requirements of this paragn ph. (1) The petitioners for the four color Ir- (c) * additives listed in paragraph <b) of this section shaM agree in writing by (30 days after effective date of final regulation) ClMinf dot* lUMrtetiorti to undertake' the short-term studies on lv. the colO.'additives. * & Kxt.- D. A C. yellow N. 1 (M. MOl ol Uib chapter).___-.1---------_____ sepcsaim tv . (2) A full written report on the ab sorption- studies for bismuth citrate and lead acetate and a full written report on the subehronlc studies for bismuth cit V * rate, bismuth oxvchlorjde. an-l caramel 1.' <f) * * ' Kanrkllou) shall be submitted to the Division of Food and Color Additives,-Food and Drug Administration, 200 C St. SW., Washing ton, DC 20204. by (180 days after ef Surgical fatun un fective date of final regulation). only. (3) The petitioners shall Immediately notify the Division of Food and Color , (g) * " Additives of any findings that Indicate & pbtenti~l for the color additive to cause ' Color oddlUr* Clodof dal* fiwtrictioiu adverse effects. (c) The closing date for the following Aluminum prdtr.._..... Aniutto_______________________ IHsmutb eitrato______....______ July 1,1977 Non*. ___--do. . Do. Sept. 30,1077 For use as a color com* Bismuth Myehlarid<kTM.,,,... OraiM powder................... ponrot In half dya. .........do............... Now. July 1.1977 Do. Caramel......................................... Cormlne_'_.. ....... Carateno--................... Chromium hydroxide (nen,,,, Chromium srldt pseni............. Dec. 31,1960 July 1.1977 Hr* __..do ____do.,,____ ' Do. Do. Do. Do. Do. Comm-, tnetalllc powder............ ..do .... Do. Tcrne lertocyanloe (Iron blue). Da. Graphite........'...___ Guanine (pearl essence) lead x-etete.,....______ Scpu 30.1077 y 1.1077 NowP.*. Sept. 30,1077 For use as a color corn* .. VUca...... * poncut la tiolr dr*. -------------------------------------------------------------------------------------- July 1.1077 Do. * Zinc oxide_.________________________________________ ________................._______do..^,,. Do. 15 color additives is postponed until September 30,1977. while chemistry data and analytical methods to establish specifications for them ore dc\ eloped and evaluated ar.d subject to com pliance with the requirements of tills paragraph: FDttC Yellow No. C, D&C Yellow No. 10. D&C Red No. 6, DJ.C Red No. 7. D&C Red No. 27. DJ.C Red No. 28. D&C Red No. 30. D&C Oranue No. 4, D&C Orange No. S. D&C Orange No. 11. D&C Blue No. 6. Ext. D&C Yellow No. 1, Ext. D&C Green No. 1, graphite, and logwood. (1) Each of the petitioners for the 15 2. By adding, new 5 8.505 to read as - follows: r* 8.505 Condilloiu of provisional litting. '** The dosing dates for the use of the color additives provisionally listed In graphs (a), (b>, (c). and <d) of this section are not complied with, the pro visional listing for the color additlve(s) involved will be terminated immediately. (a) The closing date for the following 14 color additives is postponed until color additives listed in paragraph (c) -of this section shall agree in writing by (30 days after effective date of final regulation) to undertake to develop the necessary chemistry data and analyti cal methods for the color additives. } 8.501 are postponed until the dates es tablished In that section conditioned on .- compliance- with the requirements of paragraphs (a). (b). (c>. and <d> of this ... section, where applicable. The closing '.dates will not be postponed beyond the .".dates in i 8.501 unless extraordinary cirifeumstanees are shown. Requests lor fur- .$-.ther postponement based on extraordii-'nary circumstances shall be submitted in .writing and state In detail the basis for July 1.1977. while 4-week eye area studies <2) The required chemistry data arid in the rabbit are conducted and evalu analytical methods shall be submitted tc* ated. and subject to compliance with the the Division of Food and Color Additives. requirements of this raragra-h: Food and Drug Administration. 200 C num powder, annatto. bismuth oxychlo St. SW.. Washington. DC 20204. by <1R0 ride. bronze powder, caramel, carmine, .days after effective date of final rcgul.i- carotene, - chromium hydroxide* green, tion). chromium oxide greens, copper (metallic (3) The petitioners shill immediately powder), ferric ferrocyanlde. guanine notify the Division of Food and Color (pearl essence), mica, and zinc oxide. Additives of any findings that indicate a (1) Each of the petitioners for the 14 potential for tbe color additive to causo /the request. If the requirements of para color additives listed in paragraph (a) adverse effects. see V* ,?ED&Al *fttSTE*,..VOL 41, -NO. } SEPTEMfttt. 23, . t97& 1-0035 41866 PROPOSED RULES ' _ ' r<d) 'The closing date for the following (1) Each of the petitioners for the 31 Additives of any findings that indicate 31 color additives Is postponed until De color additives listed In paragraph <d) * potential for the color additive to cause cember 31,1980, while chronic toxicity of this section shall agree in writing by adverse effects. feeding studies and in the case of cara <30 days after effective date of final regu- Interested persons may, on or before mel, a 2-year mouse skin painting study, . latlon) to undertake the required studies November 22. 2976. submit to the Hear are conducted and evalated, and subject on the color additives. ing Clerk, Food and Drug Administra to compliance with* the requirements of (2) Each of the petitioners shall sub- tion, Rxn. 4-65,5600 Fishers Lane. Rock this paragraph:'- FD&C Yellow NO. 5, mlt a protocol for the conduct of the ville, M~n 208S2, written comments (pref FD&C Yellow No. 6. D&C Yellow No. 10. studies to the Division of Food and Color. erably in quintupllcate and Identified FD&CRed No. 3, D&C Red No. 6, D&C Additives, Food and Drug Adminlstra- with the Hearing Clerk docket number Red No. 7. D&C Red No. 8. D&C Red No. tion. 200 C St/'SWn Washington, DC found In brackets in the heading of this 9, D&C Red No. 20, D&C Red No. 21, D&C - 20204, for review, and acceptance or re- document) regarding this proposal. Re Red No.'12, D&C Red No. 13.' D&C Red jection. by (60 days after effective date ceived comments may be seen in the No. 19,`D&C Red No. 21, D&GRed No. 22, of final regulation) . above ofDee during working hours, Mon D&C Red No. 27. D&C.Red No. 28, D&C Red No. 30,.D&C Red`No. 33. D&C Red No. 38. D&C Red No. 37. FD&C Green No. 3, D&C Green No. 6, D&C Green No. 8, FD&C Blue Nol l; FD&C Blue No. 2, D&C Blue NO. .8, D&C Orange No. 8, D&C Orange No,. 10, D&C.Oxange-No,' 1, and <31 A full report of the. studies con- 1 day through-Friday.' ducted on the color'additives shall, be submitted to the Division of Food and Dated; September 17,' 1976. - Color Additives by <42 months after ef fective date of final regulation). <4> The petitioners shall immediately Shxrwik Gasdhw, Acting Commissioner ; of Food and Drugs. notify the Division .of Food and Color [PH DOC.76-27825 Pila 9-23-76:6:45 Am) *V.!` v fCOEKAL REGISTER, VOL. 41, .NO. 166--THURSDAY, SEPTEMSER 23. 1176 see 1-0036 { NOTICES 41S67 V". DEPARTMENT OF HEALTH, r * "' EDUCATION, AND WELFARE , .Food and Drug Administration . permit a' determination about'the safety of the use* of FD&C Red No. 4 when In gested. ' The Commissioner has fully considered A notice published' in the Federal Register of July 24,1973 (36 FR 19851). stated that a petition (CAP 9C0092) liad been filed for the "permanent" listing o( ' r/'/s-.'v '- [Doctot No.760-03693 : .... the data submitted in support of the pe carbon black (all-gas channel black) as a . - C0L0R AOOITIVES tition and other pertinent data related color additive for use in food,'dmgs. and to the use of FD&C Red No. 4 in mara cosmetics, including cosmetics for ap , -d-;. Denial of PctHion'for Listing of FD&C Red schino cherries and ingested drugs and plication in the area of the eye, by the No, 4 for Use In Maraschino Cherries and . concludes that the data before him do Cosmetic. Toiletry and Fragrance Asso Ingested Drugs not establish that Ingested use of FD&C ciation, Inc. (CTFA>, the National Con / ^ - . . The Pood and Drug Administration Red No. 4 will be safe. The portion of the fectioners Association (NCA). and the _ . - (PDAJ> Is denying the portion of a peti- ' petition seeking listing for use in mara Pharmaceutical Manufacturers Associa .>WNation to list "permanently'' FD&C Red No. schino cherries and Ingested drugs is tion (PMA). c/o Hazleton Laboratories. -* *"' ~:.lr,4 as'a color additive that seeks listing therefore denied. Inc., P 5 Box 30. Falls Church, VA 2224G. ;fofuse In maraschino cherries and In .".Any person-who will be adversely The p< fitlon was filed pursuant to section vested' drugs because evidence Is lack* ' tag that the color Is safe for those uses. ... Objections to this order may be filed by *.. adversely affected persons by October 26, affected by the foregoing order may at any time on or before October 26. 1976, file with the Hearing Clerk, Food and Drug Administration, Rm. 4-65, 5600 706 of the Federal Food, Drug, and Cos metic Act (21 UJS.C. 376). Of the five basic types of carbon black, only carbon black produced with natural 1976. Published elsewhere In this issue Fishers Lane. Rockville. MD 20652, writ gas using the impingement or channel of the FroUAL Rxcxster are regulations . ten objections thereto. Objections shall process has been provisionally listed un terminating the provisional'listing of . show wherein the person filing will be der i 8-501 (21 CFR 8.501). The petition FD&C Red No. 4 for use in maraschino adversely affected by the order, specify to use carbon black for use with food cherries and ingested drugs and "per with particularity the provisions of the. drugs, and cosmetics seeks listing only for manently" listing FD&C Red No. 4 for order deemed objectionable.' and state * "all-gas channel black." Carbon black ' use in externally applieddrugs .and cos- the grounds for the objections. Objec (all-gas channel black) cannot be "per * metics. - tions shall be filed In accordance with the manently" listed without data adequate A notice published in the Federal requirements of l 8.19 (21 CFR 8.19). If to establish specifications for the color. Racism of November 20. 1966 (33 FR a hearing is requested, the objections These specifications are necessary to en 17205) stated that a petition (CAP 61) shall state the issues for the hearing,'1 able FDA to certify batches of carbon , for. the' "permanent" listing of FD&C shall be supported by grounds- factually black as being the type produced with Red No.'4 as a color additive for use In and legally sufficient to justify the relief natural gas using the Impingement or maraschino cherries. Ingested drugs, and sought, and shall include a detailed de- channel process. Without adequate data externally applied drugs and cosmetics scription and analysis of the factual in to establish specifications and to certif* had been filed by The Toilet Goods As formation intended to be presented in batches of carbon black as "all-gas chan sociation.. Inc. (now the Cosmetic, support of the objections in the event nel black," there 1s no assurance that llv Tollery. and Fragrance Association. 1133 that a hearing is held. Five copies of all carbon black being used is the type rev . 35th St., NW,, Washington. DC 20005): documents shall be filed and should be ered by the petition and for which texir- the Pharmaceutical Manufacturers As- Identified with the Hearing Clerk docket ity data have been submitted to and 'sociatlon <1155 15th St.. NW,, Washing number found in brackets in the heading reviewed by FDA. The Commissioner ton, DC 20005); and the Certified Color of this order. Received objections may be concludes that safe conditions of u-.* 'Industry Committee (now the Certified seen in the above office during working cannot be established without adequate Color Manufacturers Association, 900 hours, Monday through Friday. specifications for carbon black (uii-ga: ' 17th St.. NW,, Washington. DC 20006) This notice is issued under provisions channel black). ,'. c/o Hazleton Laboratories. Inc., PO Box of the Federal Food, Drug, and Cosmetic Furthermore, carbon black, includlm? ' 30, Falls Church, VA 22046. The petition * Act (secs. 701, 706. 52 Stat. 1055-1056, all-gas channel black, may contain )o'\ i was filed pursuant to section 706 of the 74 Stat. 399--403 (21 D.S.C. 371, 376)) levels of polynuclear aromatics (PNAV. Federal Food. Drug, and Cosmetic Act and under authority delegated to the some of which are known careinop*n.v .(21 U.S.C.376). Commissioner (21 CFR 5.1) (recodifica All-gas channel black is the least hl'd.v Results from chronic dog feeding tion published In the Federal Register of the carbon blacks to contain PN'l's. studies with FD&C Red No. 4 have raised June 15. 1976 (41 FR 24262)). but there is no analytical method cur i/.. questions about the safety of the color additive when ingested. These studies Dated; September 17, 1976. rently available that is sufficiently sensi tive to detect extractable PNA's at low and other avallable'data bearing on the Sherwik Gardner. levels. The Commissioner conclude- th.<! safety of FD&C Red No. 4 are discussed Acting Commissioner safe conditions of use for carbon bl.icl. , >; in detail In the preamble to the regula-. of Food and Drugs. (all-gas channel black) cannot be estab `' tloa published elsewhere in this issue of 1 - U. the Federal Recister terminating the .g provisional listing of the color for use in (FR Doc.76-27818 Filed 0-22-76:8:45 un| lished without an approprLitely sensitive analytical method for detecting extract able PNA's. maraschino cherries and ingested drugs. (Docket No. 76C-0376] The questions regarding the specifica V- The available data do not permit estab.-.jVlishment of a no-effect level for FDitC Red No. 4 in the dog. and a safe level for human ingestion cannot, therefore, be COLOR ADDITIVES Denial of Petition for Permanent Listing of Carbon Black tions for carbon black (all-gas clunm' black) and the Commissioners ::i.suc cessful efforts to obtain the nccc.-sarv additional data to resolve the que -ion . established. Furthermore, chronic feed- The Food and .Drug Administration from the petitioners are discussed r:. I;; ing studies on FD&C Red No. 4 in rats and (FDA) is denying a petition to list car-, tail In the preamble to the tj* mice conducted by FDA in the early bon black (all-gas channel black) as a published elsewhere in this issue.--: tii - 1960`s to determine whether the color color additive for use in food, drugs, and Federal Register tormina l ine tin.* pro ] ' additive is a carcinogen have recently cosmetics because the available data are visional listing for carbon black. Jr. been reevaluated and found to be inade- insufficient to establish safe conditions of The Commissioner has fully cons.ii lorr i. ? v quate by contemporary standards for use for the color additive. Objections to the data submitted in support c. tl \ts: such studies. The Commissioner con- this order may be filed by adversely af petition and other pertinent data n-'.i-.e-- . .^eludes that without chronic feeding fected persons by October 26. 1976. Pub to the use of carbon black fall-wa* * r- * 'studies that meet contemporary stand- lished elsewhere in this issue of the Fed nei black) and concludes that- the ' *t ''Jj-ards, for purposes of "permanent" list-* eral Register Is a regulation terminating before him are insufficient to cm.-1 ing under section 706 of the act (21 the provisional listing of carbon black sale conditions of use for the color ; ifV V.IILS.C. 376) there are insufficient data to for use In food, drugs, and cosmetics. live. The petition to list carbon \-;.c. FpAt.REGJSTet;-.ypU;,41;-NO; 186-^-TPUSSOAY;. SEPrEMSE* 23'. 19.76' see *-0037 41868 NOTICES (all-gas - channel. black) -Is therefore under authority delegated to the Com manent"' listing of aluminum stearate, denied. missioner <21 CFR 5.1) (recodlficatlon bentonite, calcium silicate, calcium Any person, who will be adversely af published in the Federal Register, of stearate, caolln, lithium stearate, mag fected by the foregoing order may at any June 15. 1976 (41 FR 24262)). nesium aluminum silicate, magnesium time on or before October 29. 1976, file with the Hearing Clerk, Pood and Drag Dated: September 17, 1976. stearate, and zinc stearate-had been filed by the Cosmetic, Toiletry and Administration, Em. 4-65, 5600 Fishers lane, Rockville, MD 20852, written ob jections thereto. Objections, shall show She*win Gardner. Acting Commissioner .. 0/ Food end Drugs. Fragrance Association. Inc. (CTFA' ` 1133 15th St.. NW,, Washington. DC 20005, c/o Hazleton Laboratories. Inc.. wherein the person filing will be ad versely affected by the order, specify (FR Doc.76-27830 Filed 8-22-7e;8;4S am] P.O. Box 30. Falls Church. VA 22040. The petitions were filed pursuant to .with particularity the provisions of the section 706 of the Federal Food. Drug, order deemed objectionable, and state [Docket No. 76C-0S631 and Cosmetic Act (21 DjS.C. 376). On the grounds for the objections- Objectlons shall befiled In accordance with the requirements- of $ 8J.9 (21' CFR ft.19). If a hearing is requested, the objections COSMETIC, TOILETRY AND FRAGRANCE ASSOCIATION - Withdrawal,of Color Additive Petitions August 9, 1976, CTFA wrote to FDA re questing that the color additive petitions for the. nine i uhstances be withdrawn without* prejudice to future filing. - shall'state. the i^ia for the hearing, The Food and Drug Administration Therefore, In accordance with 5 8.8(c) be supported by grounds factually (FDA) Is announcing the withdrawal of the color additive regulations (21 CFR and legally sufficient to justify the relief without prejudice of three petitions to 8.8(c)); under the Federal Pood. Drug, sought, and shall include a detailed de "permanently" list aluminum stearate, and Cosmetic Act (sec. 706(d), 74 Stat. scription and analysis of the factual In bentonite, calcium silicate, calcium stea .402 (21 U.S.C. 376(d))) ; and under au formation Intended to be presented In rate, kaolin, lithium stearate, magnesium thority delegated to the Commissioner support of the objections in the event aluminum silicate, magnesium stearate, <21 CFR 5.1) (recodlficatlon published that a hearing is held. Five copies of all and zinc stearate for use as color addi In the Federal Register of June 15,1976 documents shall be filed and should be tives'In cosmetics. Published elsewhere (41 FR 24262)). notice is given that identified with-the Hearing Clerk docket in this issue of the Federal Register color additive petitions 8C0071, 8C0078. number found in brackets in the hearing Is a regulation terminating the provi and 9C0094 have been withdrawn wILh- of thi order. Received objections may be sional listing of those nine substances ' out prejudice +o future filing. seen In the above office during working - and a tenth, gold, for use'.as color ad hours, Monday through Friday. ditives In cosmetics. Dated: September 17, 1976. * Uhls notice Is issued under provisions A notice published In the Federal of the Federal Food, Drug, and Cosmetic Register of August 6. 1973 (38 FR Act (secs. 701, 706, 52 Stat. 1055-1056, 74 . 21200), stated that petitions (CAP SC- ~~Sherwin Gardner. Acting Commissioner of Food and Drugs. Stat. 399-403 (21' U.S.C. 371, 376)) and 0071, 8C0078, and 9C0094) for the "per [FR DOC.7S-27821 Filed S^2Z-T;8:45 am] i t iKDUAL K&SlUt VOC 43, KQ, DQJEiDAX, *E?1EMK* 23, 1974 see 1-0038