U.S. GOVERNMENT REGULATION

II. U.S. GOVERNMENT REGULATION

Accum’s book initiated a flurry of investigations and reports on food adulteration in the United States; Hutt and Hutt (1984) list a number of treatises published in the mid- to late-1800s which served to prompt state governments increasingly into legislating the safety of the food supply. Consideration of this issue reached a national climax with the National Board of Trade’s 1879 competition to award $1000 to the person submitting the best draft of a food adulteration act; the competition winner, announced in 1880, was one G. W. Wigner of England (Hutt and Hutt, 1984). Wigner [cited in Hutt and Hutt (1984)] outlined seven specific elements which defined food adulteration, the first and sixth being

If any substance, or any substances, has, or have been mixed with it, so as to reduce, or lower, or injuriously affect its quality, strength, purity, or true value.

If it be colored, or coated, or polished, or powdered, whereby damage is concealed, or it is made to appear better than it really is, or of greater value.

This increased awareness was however insufficient to compel Congress into legislating adulteration at the national level; although bills were introduced as early as 1879 Congress chose instead (not atypically) to further investigate the issue (Hutt and Hutt, 1984). The This increased awareness was however insufficient to compel Congress into legislating adulteration at the national level; although bills were introduced as early as 1879 Congress chose instead (not atypically) to further investigate the issue (Hutt and Hutt, 1984). The

a Food Inspection Decision in 1906, the first such pertaining to the use of colorants: the coal tar derivative Martius Yellow was declared unsafe for foods (Marmion, 1979). Concurrent with the food preservatives research conducted by Dr. Harvey W. Wi- ley’s Poison Squad in the Bureau of Chemistry, Dr. Bernhard C. Hesse was investigating the suitability of the available coal tar dyes (some 700) as food colorants (NAS/NRC, 1971). Hesse’s literature search and subsequent physiological studies, along with Wiley’s work, led to the passage of the Pure Food and Drug Act of 1906, the first comprehensive federal legislation regulating additives (IFT, 1986). Hesse’s findings were specifically in- corporated into the Act through the Food Inspection Decision of 1907, which recognized seven dyes as meeting the requisite suitability standards. These are listed in Table 1.

Hesse’s criteria for assessing the suitability of dyes for food use were incorporated into the 1906 legislation; these included the requirements that all dyes be manufactured under strict control, and tested via human and animal physiological studies before being certified as suitable for food use (NAS/NRC, 1971). The certification process was, how- ever, a voluntary process overseen by the Secretary of Agriculture (NAS/NRC, 1971); nevertheless, the dye industry quickly saw the advantages to marketing certified colorants, and by 1908 the first voluntary certified dye was available (Marmion, 1979). Under this process ten additional dyes were certified for food use in the years prior to 1938 (see Table 2 ), although two of these (Sudan I and Butter Yellow) were almost immediately delisted for causing contact dermatitis in dye workers (NAS/NRC, 1971).

While the groundwork had been laid with the Act of 1906, the question of enforce- ment remained problematic. In 1907 the Secretary of Agriculture created the Board of Food and Drug Inspection, charged with conducting hearings on alleged violations, and in 1908 President Roosevelt commissioned the Referee Board of Consulting Scientific Experts to rule on specific issues pertaining to food adulteration (Hutt and Hutt, 1984). The USDA Bureau of Chemistry, however, remained the enforcing agency of record. (Wiley had chaired the Board of Food and Drug Inspection.) In 1927 the Bureau evolved into the Food, Drug, and Insecticide Administration, which within three years became the Food and Drug Administration. Hutt (1996) notes that the 1906 Act required the Bureau to

Table 1 Colorants Permitted for Use in Foods Following FID No. 76, July 1907

Year Common name

Color index

delisted Ponceau 3R

1938 FDA nomenclature

number

1961 Amaranth

FD&C Red No. 1

1976 Erythrosine

FD&C Red No. 2

— Indigotine

FD&C Red No. 3

— Light Green SF

FD&C Blue No. 2

1966 Napthol Yellow S

FD&C Green No. 2

1959 Orange 1

FD&C Yellow No. 1

FD&C Orange No. 1

Table 2 Additional Colorants Permitted for Use in Foods, 1907–1938

Year Common name

CI Year

delisted Tartrazine

1938 FDA nomenclature

number

listed

— Sudan I

FD&C Yellow No. 5

1918 Butter Yellow

1918 Yellow AB

1959 Yellow OB

FD&C Yellow No. 3

1959 Guinea Green B

FD&C Yellow No. 4

1966 Fast Green FCF

FD&C Green No. 1

— Brilliant Blue FCF

FD&C Green No. 3

— Ponceau SX

FD&C Blue No. 1

1976 Sunset Yellow FCF

FD&C Red No. 4

— Source : NAS/NRC (1971); Marmion (1979).

FD&C Yellow No. 6

enforce the legislation solely in response to malfeasance; the Act mandated no premarket approval process other than the voluntary certification schema.

As early as 1917 the Bureau of Chemistry had noted the shortcomings of the Act of 1906, specifically with regards to various economic repercussions of food adulteration (Hutt and Hutt, 1984). A bill was eventually put before the Senate in 1933 which became upon its passage the Federal Food, Drug and Cosmetic Act of 1938. From the standpoint of food colorants the 1938 Act was notable for making certification mandatory and for creating three specific certified categories: colors suitable for foods, drugs, and cosmetics (FD&C); colors suitable for drugs and cosmetics (D&C); and colors suitable for externally applied drugs and cosmetics (Ext. D&C). The fifteen food colorants then listed (the origi- nal seven of Hesse in addition to the eight which had been successfully listed in the intervening years) were again subjected to toxicological testing; in 1940 those colorants were again deemed suitable for use, although subject to the 1938 Act’s provisions regard- ing specifications, uses and restrictions, labeling, and certification (refer to 21 C.F.R. §74, 1996).

Following passage of the Food, Drug and Cosmetic Act, and prior to the amending legislation of 1958, four additional dyes obtained certification as food colorants (see Table 3). However, in the early 1950s three incidences involving excessively applied colorants in popcorn and candies prompted the FDA to begin a more rigorous toxicological testing program (NAS/NRC, 1971; Noonan, 1972). As a consequence FDA delisted FD&C Red

Table 3 Additional Colorants Permitted for Use in Foods, 1939–1956

Year Common name

CI Year

delisted Napthol Yellow S a FD&C Yellow No. 2

FDA nomenclature

number

listed

1959 Oil Red XO

1956 Orange SS

FD&C Red No. 32

1956 Benzyl Violet 4B

FD&C Orange No. 2

1973 a Potassium salt.

FD&C Violet No. 1

No. 32, and FD&C Orange Nos. 1 and 2 in 1956. Although manufacturers petitioned the FDA to consider the safety of the colorants in the context of proper usage, FDA instead chose to interpret the ‘‘harmless and suitable’’ standard of the 1938 Act as ‘‘harmless per se ,’’ meaning absolutely harmless at all levels. Lower court challenges to this interpre- tation culminated in the 1958 Supreme Court case Flemming v. Florida Citrus Exchange, in which the Supreme Court ruled that the FDA did not have the authority to set quantity limitations; that is, a zero toxicity criterion was established (Noonan, 1972; Taylor, 1984). This led to the subsequent delisting of the four FD&C Yellow dyes, Nos. 1, 2, 3, and 4 in 1959.

It was clear that the ‘‘zero toxicity’’ criterion of the Flemming case would eventually disallow the use of any synthetic colorant; the FDA was being forced to delist colorants regardless of their true capacity to endanger public health (Noonan, 1972). In response the color manufacturing industry, through the Certified Color Industry Committee, and the FDA helped to initiate legislation which became the Color Additives Amendments of 1960. The Amendments established an alternative safety standard to the 1938 Act; how- ever, in order to ensure public health the Amendments called for premarket approval of all colorants, now referred to as ‘‘color additives.’’ Color additives encompassed a wider set of colorants than the synthetic coal tar derivatives regulated by the 1938 Act; a color additive was defined as ‘‘a dye, pigment or other substance made . . . or . . . derived from

a vegetable, animal, mineral or other source and that, when added or applied to a food, drug, or cosmetic or to the human body or any part thereof, is capable . . . of imparting

a color thereto’’ [21 C.F.R. §70.3(f), 1996]. Both synthetic and natural colorants were subject to premarket safety evaluation, but certification (as a guarantee of purity) was only required for synthetic colorants (Newsome, 1990).

Additionally, the Color Additives Amendments prescribe how the FDA determines the safety of color additives. With regards to the safety standard, the Color Additives Amendments replaced the ‘‘harmless per se’’ standard with a general safety clause based upon a premarket evaluation of the color additive’s safety; ‘‘safety’’ was not explicitly defined in the statute, but was interpreted as ‘‘convincing evidence that establishes with reasonable certainty that no harm will result from the intended use of the color additive’’ [21 C.F.R. §70.3(i), 1996]. As Taylor (1984) notes, the burden of proof of an additive’s safety was now incumbent upon the manufacturer, and that proof had to be evidentiary in nature. The factors which have to be considered by FDA in the safety determination include exposure, cumulative effects, pertinent safety factors, and availability of practica- ble analytical detection methodology (Bachrach, 1984); the approved process for de- termining safety is detailed in the FDA publication Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food (the so-called Redbook).

If the color additive is known or suspected of causing cancer, however, the Color Additives Amendments invoke a Delaney clause similar to that of the Food Additives Amendment of 1958. The Delaney clause explicitly states that a color additive ‘‘shall be deemed unsafe, and shall not be listed for any use . . . if the additive is found . . . to induce cancer’’ [21 U.S.C. §376(b)(5)(B), 1976]. Though this is frequently misinterpreted as yet again meaning ‘‘harmless per se,’’ the Delaney clause was not intended represent an absolute ban; in 1984 the Supreme Court upheld this reasoning in the case of Scott v. Food and Drug Administration , regarding the presence of a carcinogenic impurity in D&C Green No. 5 (Bachrach, 1984). It was argued that the presence of para-toluidine, If the color additive is known or suspected of causing cancer, however, the Color Additives Amendments invoke a Delaney clause similar to that of the Food Additives Amendment of 1958. The Delaney clause explicitly states that a color additive ‘‘shall be deemed unsafe, and shall not be listed for any use . . . if the additive is found . . . to induce cancer’’ [21 U.S.C. §376(b)(5)(B), 1976]. Though this is frequently misinterpreted as yet again meaning ‘‘harmless per se,’’ the Delaney clause was not intended represent an absolute ban; in 1984 the Supreme Court upheld this reasoning in the case of Scott v. Food and Drug Administration , regarding the presence of a carcinogenic impurity in D&C Green No. 5 (Bachrach, 1984). It was argued that the presence of para-toluidine,

[If data suggest that] the color additive, including its components or impurities, induces cancer in man or animal, the Commissioner shall determine whether . . . cancer has been induced and whether the color additive, including its components or impurities, was the causative substance. If it is his judgment that the data do not establish these facts, the cancer clause is not applicable; and if the data considered as a whole establish that the color additive will

be safe under the conditions that can be specified in the applicable regulation, it may be listed for such use . (21 C.F.R. §70.50, 1996; emphasis added)

This interpretation, the basis for the so-called constituents policy, was upheld by the court. The primary difficulty associated with the Color Additive Amendments was not the inclusion of the Delaney clause, but rather the failure of the Amendments to allow previ- ously listed colorants as having generally recognized as safe (GRAS) status. As Hutt (1996) notes, this meant that all color additives, regardless of previous status or type, were subjected to the regulatory requirements of the Amendments; this is the basis of Title II in the Color Additive Amendments, which allowed provisional listing status for then- current colorants until their safety and suitability could be ascertained. Unfortunately, as Hutt (1996) also notes, Congress did not establish a statutory deadline for this provisional

status; the courts have instead extended the transitional period from the original 2 1 / 2 years until the present day. Much of the delay was due to increased testing requirements imposed by the FDA, especially with respect to carcinogenicity. Only two new certified colors have been permanently listed in the years following the passage of the Color Additive Amendments: FD&C Red No. 40 and its alumina lake. The ten certified color additives currently permanently listed for use in foods in the United States are presented in Table 4; the lakes of FD&C Blue No. 1, Blue No. 2, Green No. 3, Yellow No. 5, and Yellow No. 6 continue to have provisional status.

The Color Additive Amendments also saw the creation of the class of uncertified colors (colors exempt from certification): the natural-source and nature-identical (synthetic

Table 4 Certified Color Additives Permanently Listed for Use in Foods CI EEC

Year Common name

number (re)listed Brilliant Blue FCF

FDA nomenclature

number

E133 1969 Indigotine

FD&C Blue No. 1

E132 1983 Fast Green FCF

FD&C Blue No. 2

1982 Erythrosine

FD&C Green No. 3

E123 1969 Allura Red AC

FD&C Red No. 3

E129 1971 Allura Red AC Lake

FD&C Red No. 40

1994 Tartrazine

FD&C Red No. 40 Lake

E102 1969 Sunset Yellow FCF

FD&C Yellow No. 5

FD&C Yellow No. 6

E110 1986

Citrus Red No. 2 a —

1966 a Restricted to the coloring of orange skins, not to exceed 2 ppm by weight.

Orange B b —

b Restricted to the coloring of casings or surfaces of frankfurters and sausages, not to exceed 150 ppm by weight.

Source : 21 C.F.R. 74 (1996); Marmion (1979); Jukes (1996); von Elbe and Schwartz (1996).

Table 5 Color Additives Exempt from Certification Permanently Listed for Use in Foods CI EEC

Color additive

number

number Restrictions a

Annatto extract

E160b β-Apo-8′-carotenal

E160e nte 15 mg b Beets, dehydrated (beet powder)

E162 Canthaxanthin

E161g nte 30 mg b Caramel

E150 β-Carotene

E160a Carrot oil Cochineal extract; carmine

E120 Cottonseed flour, toasted, partially defatted Ferrous gluconate

E579 Ripe olives Fruit juice Grape color extract

E163 Nonbeverages Grape skin extract (enocianina)

E163 Beverages Iron oxide, synthetic

E172 Sausage casings Paprika

E160c Paprika oleoresin Riboflavin

E101 Saffron

Titanium dioxide

E171 nte 1% c Turmeric

E100 Vegetable juice

Turmeric oleoresin

a nte—not to exceed. b Per pound or pint. c By weight.

Source : 21 C.F.R. §73 (1996); Marmion (1979); Rayner (1991); Jukes (1996), von Elbe and Schwartz (1996).

dyes which are identical to natural pigments) colors. The FDA does not recognize any category of colorant as being ‘‘natural,’’ as the addition of any colorant to food results in an artificially colored product (Newsome, 1990). As noted previously, these colorants are subject to the same safety standard as certified colors, but do not require chemical purity certification. The color additives exempt from certification are listed in Tables 5

(for direct consumables) and 6 (for animal feeds).