21 U.S.C. 371, 379e, 379e note.
The Commissioner of Food and Drugs finds that the following lists of color additives are provisionally listed under section 203(b) of the Color Additive Amendments of 1960 (sec. 203(b), 74 Stat. 405 (21 U.S.C. 379e note)). Except for color additives for which petitions have been filed, progress reports are required by January 1, 1968, and at 6-month intervals thereafter. Specifications for color additives listed in paragraphs (a), (b), and (c) of this section appear in the respective 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 Commissioner has been notified of studies underway to establish the safety of the color additive for such use. The color additives listed in paragraphs (a), (b), and (c) of this section may not be used in products which are intended to be used in the area of the eye. The color additives listed in paragraphs (a), (b), and (c) of this section are provisionally listed until the closing dates set forth therein.
(a)
(b)
(c)
For
(a)
(b) [Reserved]
(c)
(1) Groups of 50 rats are being fed diets containing FD&C Red No. 1 at levels of 5 percent, 2 percent, 1 percent, 0.5 percent, and 0 percent. At this stage of the tests, which have now been in progress for from 15 months to 18 months, 116 animals from the 250 being fed FD&C Red No. 1 at various levels and 27 of the 100 controls have died. Of these, 11 being fed at the 5 percent level, 16 being fed at the 2 percent level, 11 being fed at the 1 percent level, and 2 being fed at the 0.5 percent level, have shown liver damage. None of the controls that have died have shown liver damage.
(2) Groups of 100 mice are being fed diets containing 2 percent, 1 percent, 0.5 percent, and 0.1 percent FD&C Red No. 1, with 400 mice as controls. All mice on dosage levels of 2 percent and 1 percent died before the seventieth week. Gross liver damage has been observed in all groups fed at the 0.5 percent diet and above.
(3) Groups of 4 dogs are being fed diets containing 2 percent, 1 percent, 0.25 percent, and 0 percent FD&C Red No. 1. Three of the dogs on the 2 percent dosage level died before 32 weeks; the other is living. Three of the dogs on the 1 percent dosage level died or were sacrificed within 13 months. All deceased or sacrificed dogs have shown liver damage grossly and/or microscopically. Deceased dogs on the 1 percent and 2 percent dosage level showed poor physical condition.
(d)
(1) Rats of the Osborne-Mendel and Sprague-Dawley strains were fed FD&C Red No. 4 for 2 years at levels of 5 percent, 2 percent, 1 percent, and 0.5 percent of the diet. No effect was found.
(2) Mice of the C3Hf and C57BL strains were fed FD&C Red No. 4 for 2 years at levels of 2 percent and 1 percent of the diet. No effect was found.
(3) Dogs were fed FD&C Red No. 4 at levels of 2 percent and 1 percent of the diet. Adverse effects were found at both levels in the urinary bladder and in the adrenals. Three dogs of five fed on the 2-percent level died after 6 months, 9 months, and 5
(e)
(f)
(g)
(h)
(i)
(j)
(k)
(l) [Reserved]
(m)
(n)
(o)
(p) [Reserved]
(q)(1)
(2)
(r) [Reserved]
(s)
(t)
(u)
For
(a) Certificates issued heretofore for colors being removed from the provisional list (§ 81.10(a)) are cancelled and of no effect after December 1, 1960, and use of such color additives in drugs or cosmetics after that date will result in adulteration.
(b)(1) Certificates issued heretofore for the color additive designated FD&C Red No. 1 are cancelled as of the date of the publication of this Order, and use of this color additive in the manufacture of foods, drugs, or cosmetics after that date will result in adulteration.
(2) The Commissioner finds that no action needs to be taken to remove foods, drugs, and cosmetics containing this color additive from the market on the basis of the scientific evidence before him, taking into account that the additive is not an acute toxic substance and that it is only used in small amounts in foods, drugs, and cosmetics.
(c) Certificates issued for FD&C Red No. 4 and all mixtures containing this color additive are cancelled and have no effect after September 23, 1976 insofar as food, ingested drugs, and ingested cosmetics 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 externally applied
(d) Certificates issued for the following color additives and all mixtures containing these color additives are canceled and have no effect after October 4, 1966, and use of such color additives in the manufacture of foods, drugs, or cosmetics after that date will result in adulteration:
(e) Certificates issued for the following color additives and all mixtures containing these color additives are canceled and have no effect after July 1, 1968, and use of such color additives in the manufacture of drugs or cosmetics after that date will result in adulteration:
(f) Certificates issued for D&C Yellow No. 11 and all mixtures containing this color additive are canceled and have no effect after April 30, 1968, insofar as ingested use is concerned. Use of this color additive in the manufacture of ingested drugs or cosmetics subject to ingestion after that date will result in adulteration.
(g) Certificates issued for D&C Red No. 17, D&C Red No. 31, D&C Red No. 34, D&C Orange No. 4, and D&C Violet No. 2, and all mixtures containing these color additives, are canceled and have no effect after December 31, 1968, insofar as ingested use is concerned. Use of these color additives in the manufacture of ingested drugs or cosmetics subject to ingestion after that date will result in adulteration.
(h)(1) Certificates issued for FD&C Violet No. 1 and all mixtures containing this color additive are canceled and have no effect after April 10, 1973, and use of such color additive in the manufacture of foods, drugs, or cosmetics after that date will result in adulteration.
(2) The Commissioner finds that no action needs to be taken to remove foods, drugs, and cosmetics containing this color additive from the market on the basis of the scientific evidence before him.
(i) Certificates issued prior to July 1, 1968, for D&C Brown No. 1 and Ext. D&C Violet No. 2 and all mixtures containing these colors are canceled and have no effect. This cancellation does not apply to certificates issued after March 15, 1973, for D&C Brown No. 1 and Ext. D&C Violet No. 2, which are provisionally listed in § 81.1(b) and (c) respectively for coloring externally applied cosmetics.
(j)(1) Certificates issued for FD&C Red No. 2 and all mixtures containing this color additive are canceled and have no effect after January 28, 1976, and use of this color additive in the manufacture of food, drugs, or cosmetics after this date will result in adulteration.
(2) 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, drugs, and cosmetics containing the color additive.
(k)(1) Certificates issued for D&C Red No. 10, D&C Red No. 11, D&C Red No. 12, and D&C Red No. 13, their lakes and
(2) The Commissioner finds, on the basis of the scientific evidence before him, that no action has to be taken to remove from the market, drug and cosmetic products containing the color additives.
(l)(1) Certificates issued for Ext. D&C Yellow No. 1 and all mixtures containing this color additive are cancelled and have no effect after December 13, 1977, and use of this color additive in the manufacture of drugs or cosmetics after this date will result in adulteration.
(2) The Commissioner finds, on the basis of the scientific evidence before him, that no action has to be taken to remove from the market drugs and cosmetics containing the color additive.
(m)(1) Certificates issued for Ext. D&C Green No. 1 and all mixtures containing this color additive are cancelled and have no effect after November 29, 1977, and use of the color additive in the manufacture of drugs or cosmetics after this date will result in adulteration.
(2) The Commissioner finds, on the basis of the scientific evidence before him, that no action has to be taken to remove from the market drugs and cosmetics containing the color additive.
(n)(1) Certificates issued for D&C Orange No. 10, D&C Orange No. 11, their lakes, and all mixtures containing these color additives are cancelled and have no effect as pertains to their use in ingested drugs and cosmetics after April 28, 1981 and use of these color additives in the manufacture of ingested drugs or cosmetics after this date will result in adulteration.
(2) The agency finds, on the basis of the scientific evidence before it, that no action has to be taken to remove from the market drugs and cosmetics to which the color additives were added on or before April 28, 1981.
(o)(1) Certificates issued for D&C Blue No. 6 and all mixtures containing this color additive are cancelled insofar as its use in drugs and cosmetics is concerned and have no effect after December 13, 1977, and use of the color additive in the manufacture of drugs or cosmetics after this date will result in adulteration. The color will continue to be certified for use in the coloring of surgical sutures.
(2) The Commissioner finds, on the basis of the scientific evidence before him, that no action has to be taken to remove from the market drugs and cosmetics containing the color additive.
(p)(1) Certificates issued for D&C Green No. 6, its lakes and all mixtures containing this color additive are cancelled and have no effect as pertains to their use in ingested drugs and cosmetics after May 4, 1982 and use of the color additive in the manufacture of ingested drugs or cosmetics after this date will result in adulteration.
(2) The agency finds, on the basis of the scientific evidence before it, that no action has to be taken to remove from the market ingested drugs and cosmetics containing the color additive.
(q) [Reserved]
(r)(1) Certificates issued for D&C Red No. 19 and D&C Red No. 37, their lakes, and all mixtures containing these color additives are cancelled and have no effect as pertains to their use in ingested drugs and cosmetics after February 4, 1983, and use of these color additives in the manufacture of ingested drugs or cosmetics after this date will result in adulteration.
(2) The agency finds, on the scientific evidence before it, that no action has to be taken to remove from the market ingested drugs and cosmetics to which D&C Red No. 19 and D&C Red No. 37 were added on or before February 4, 1983, or externally applied drugs and cosmetics to which D&C Red No. 37 was added on or before June 6, 1986.
(3) Certificates issued for D&C Red No. 37, its lakes, and all mixtures containing this color additive are cancelled and have no effect as pertains to its use in externally applied drugs and cosmetics after June 6, 1986, and use of this color additive in the manufacture of externally applied drugs or cosmetics after this date will result in adulteration.
(4) Certificates issued for D&C Red No. 19, its lakes, and all mixtures containing this color additive are cancelled and have no effect as pertains to its use in externally applied drugs and cosmetics after July 15, 1988, and use of this color in the manufacture of externally applied drugs or cosmetics after this date will result in adulteration.
(5) The agency finds, on the scientific evidence before it, that no action has to be taken to remove from the market externally applied drugs and cosmetics to which D&C Red No. 19 was added on or before July 15, 1988.
(s)(1) Certificates issued for D&C Red No. 8 and D&C Red No. 9, their lakes, and all mixtures containing these color additives are canceled and have no effect as pertains to their use in mouthwash, dentifrices, and ingested drugs, except ingested drug lip products, after January 6, 1987, and use of these color additives in the manufacture of mouthwash, dentifrices, and ingested drugs, except ingested drug lip products, after this date will result in adulteration.
(2) The agency finds, on the basis of the scientific evidence before it, that no action has to be taken to remove from the market mouthwash, dentifrices, and ingested drugs to which the color additives were added on or before January 6, 1987. Ingested drug lip products, however, are regulated for use in §§ 74.1308 and 74.1309.
(3) Certificates issued for D&C Red No. 8, and D&C Red No. 9, their lakes, and all mixtures containing these color additives are cancelled and have no effect as pertains to their use in ingested drug and cosmetic lip products and in externally applied drugs and cosmetics after July 15, 1988, and use of these color additives in the manufacture of ingested drugs and cosmetic lip products and in externally applied drugs and cosmetics after this date will result in adulteration.
(4) The agency finds, on the basis of the scientific evidence before it, that no action has to be taken to remove from the market ingested drug and cosmetic lip products and externally applied drugs and cosmetics to which the color additives were added on or before July 15, 1988.
(t)(1) Certificates issued for D&C Orange No. 17, its lakes, and all mixtures containing this color additive are cancelled and have no effect as pertains to its use in ingested drugs and ingested cosmetics after March 31, 1983 and use of this color additive in the manufacture of ingested drugs or ingested cosmetics after this date will result in adulteration.
(2) The agency finds, on the scientific evidence before it, that no action has to be taken to remove from the market drugs and cosmetics to which the color additive was added on or before March 31, 1983.
(3) Certificates issued for D&C Orange No. 17, its lakes and all mixtures containing this color additive are cancelled and have no effect as pertains to its use in externally applied drugs and cosmetics after July 15, 1988, and use of this color in the manufacture of externally applied drugs or cosmetics after this date will result in adulteration.
(4) The agency finds, on the scientific evidence before it, that no action has to be taken to remove from the market externally applied drugs and cosmetics to which D&C Orange No. 17 was added on or before July 15, 1988.
(u)(1) Certificates issued for FD&C Red No. 3 and all mixtures containing this color additive are cancelled and have no effect as pertains to their use in cosmetics and externally applied drugs after January 29, 1990. Certificates issued for FD&C Red No. 3 lakes and all mixtures containing these lakes are cancelled and have no effect as pertains to their use in food, drugs, and cosmetics after January 29, 1990. Certificates issued for D&C Red No. 3 lakes and all mixtures containing those lakes are cancelled and have no effect as pertains to their use in drugs and cosmetics after January 29, 1990. Use of this color additve in the manufacture of cosmetics and of externally applied drugs and any use of the lakes of FD&C Red No. 3 (including the lakes of D&C Red No. 3) after this date will result in adulteration.
(2) The agency finds, on the scientific evidence before it, that no action must be taken to remove from the market food, drugs, and cosmetics to which the provisionally listed color additive or its lakes were added on or before January 29, 1990.
For
Certificates issued for the color additives listed in § 81.25 and for all mixtures containing these color additives are limited to the conditions stated in § 81.25. The use of these color additives in drugs and cosmetics in any other manner will result in adulteration. Each of these color additives shall bear a label statement of the tolerance and use limitations applicable to it.