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Absorption of polymeric food colourings
TOXICOLOGY:
BIBRA
ABSTRACTS
COLOURING Absorption
of polymeric
it was equal to about 0.9% of the total equivalents administered. After oral administration of i4Clabelled PSAE itself, a negligible proportion of the’ 14C was excreted in the urine in 72 hr, whereas after oral administration of i4C-labelled SCAP, 8.9’4 of the radioactivity appeared in the urine, of which 45% was unchanged SCAP and 52% was SA. This indicated that the urinary SA in rats given PSAE-TA was derived from further metabolism of SCAP, rather than directly from cleavage of the azo and sulphonamide bonds. From calorimetric determination of total (labelled and unlabelled) urinary SA, which was equivalent to over 20% of the dose following administration of tartrazine itself, it was calculated that use of the polymeric form of the dye reduced absorption by about 95%. No unchanged tartrazine was found in the urine after dosing with either tartrazine or PSAE-TA. When the 14C-labelled polymer derivative of sunset yellow (PSAE-SY) was administered orally, the urine contained 6.9% of the administered radioactivity, which in the absence of detectable unchanged sunset yellow or SA was assumed to be ANSA. In rats given 14C-labelled sunset yellow, total urinary activity represented 8.5% of the dose. Intact dye accounted for l-2%, and the remainder was again assumed to be ANSA. Urinary excretion of SA was equivalent to 37-40% of the dose after administration of either labelled or unlabelled sunset yellow. About 1.5% of the unchanged dye was also excreted in the bile, but excretion of PSAE-SY in the bile was not examined. The study indicated that azo-bond cleavage occurred as readily in the polymer derivatives PSAE-TA and PSAE-SY as in the dyes themselves but the resulting SA moiety remained, in both cases, attached to the polymer backbone. The authors suggest that the decrease in absorption of unchanged dye and of the SA produced by azo reduction resulting from the use of polymeric derivatives may be significant in developing non-sensitizing substitutes for tartrazine and sunset yellow. [This is an interesting development, which is still at a relatively early stage of investigation. The resistance of the polymers to absorption from the gut and the apparent absence of any significant retention of the dyes or their metabolites in the body will need further confirmation. Further work will also be needed to establish conclusively the chemical structures responsible for the cases of human hypersensitivity associated with these colourings.]
Honohan, T., Enderlin, F. E., Ryerson, B. A. & Parkinson, T. M. (1977). Intestinal absorption of polymeric derivatives of the food dyes sunset yellow and tartrazine in rats. Xenobiotica 7, 765. Water-soluble azo dyes such as tartrazine and sunset yellow are cleaved at the azo bond by gut bacteria (Cited in F.C.T. 1969, 7, 87). The products of tartrazine fission are sulphanilic acid (SA) and 1-(4-sulphophenyl)-3-carboxy-4-amino-5-pyrazolone (SCAP), which may be further metabolized to SA, whereas sunset yellow produces SA and I-amino-2naphthol-6-sulphonic acid (ANSA) (ibid 1963, 1, 101; Roxon et al. Fd Comet. Toxicol. 1967, 5, 447). Ingestion of tartrazine may provoke allergic reactions such as asthma and urticaria (ibid 1973, 11, 685), and the FDA has proposed that it should be declared by name on food products (Food Chemical News 1976, 18(47), 29). Sunset yellow has also been implicated in occasional cases of hypersensitivity (Baer & Leider, J. inoest. Dem. 1949, 13, 223; Michaelsson & Juhlin, Br. J. Derm. 1973, 88, 525). In the latter study, SA failed to produce urticaria or other objective signs of allergy in eight subjects sensitive to sunset yellow and tartrazine. Polymeric antioxidants which are absorbed to only a very limited extent from the gut have recently been developed (Cited in F.C.7: 1977, 15, 357; ibid 1978, 16, 321) and parallel work is in hand on colourings (ibid 1978, 16, 321). The metabolic fate of polymeric derivatives of tartrazine and sunset yellow is compared with that of the free colourings in the paper by Honohan et al. cited aboye. In both cases the polymer was a polysulphanilamidoethylene (PSAE), a polyaminoethylene backbone being linked through a sulphonamide group to the azo dye. When rats were given, by gavage, the polymeric derivative of tartrazine (PSAE-TA), uniformly labelled with ‘%Z in the 1-p-sulphophenyl ring, 4.6% of the i4C appeared in the urine. Over half of this was identified as SCAP and about 40% as SA. After administration of similarly labelled tartrazine, urinary radioactivity accounted for almost the same proportion (4.0%) of the dose, 44% being SCAP in this case. SA represented a further 43% of the excreted radioactivity. Thus the amount of SA derived from the aminopyrazolone moiety was approximately the same for both forms of tartrazine; in the case of PSAE-TA,
Mutations
COMMENTS
MATTERS
food colourings
FLAVOURINGS,
AND
SOLVENTS
AND
SWEETENERS
Whether saccharin is or is not a bladder carcinogen is a subject of continuing controversy. Mutagenicity studies have also presented problems of interpretation and a review of 17 such studies concluded that they had produced only conflicting or equivocal results
from saccharin
Batzinger, R. P., Ou, S.-Y. L. 8~ Bueding, E. (1977). Saccharin and other sweetners: Mutagenic properties. Science, N.Y. 198, 944. 91
BIBRA
ABSTRACTS
COLOURING Absorption
of polymeric
it was equal to about 0.9% of the total equivalents administered. After oral administration of i4Clabelled PSAE itself, a negligible proportion of the’ 14C was excreted in the urine in 72 hr, whereas after oral administration of i4C-labelled SCAP, 8.9’4 of the radioactivity appeared in the urine, of which 45% was unchanged SCAP and 52% was SA. This indicated that the urinary SA in rats given PSAE-TA was derived from further metabolism of SCAP, rather than directly from cleavage of the azo and sulphonamide bonds. From calorimetric determination of total (labelled and unlabelled) urinary SA, which was equivalent to over 20% of the dose following administration of tartrazine itself, it was calculated that use of the polymeric form of the dye reduced absorption by about 95%. No unchanged tartrazine was found in the urine after dosing with either tartrazine or PSAE-TA. When the 14C-labelled polymer derivative of sunset yellow (PSAE-SY) was administered orally, the urine contained 6.9% of the administered radioactivity, which in the absence of detectable unchanged sunset yellow or SA was assumed to be ANSA. In rats given 14C-labelled sunset yellow, total urinary activity represented 8.5% of the dose. Intact dye accounted for l-2%, and the remainder was again assumed to be ANSA. Urinary excretion of SA was equivalent to 37-40% of the dose after administration of either labelled or unlabelled sunset yellow. About 1.5% of the unchanged dye was also excreted in the bile, but excretion of PSAE-SY in the bile was not examined. The study indicated that azo-bond cleavage occurred as readily in the polymer derivatives PSAE-TA and PSAE-SY as in the dyes themselves but the resulting SA moiety remained, in both cases, attached to the polymer backbone. The authors suggest that the decrease in absorption of unchanged dye and of the SA produced by azo reduction resulting from the use of polymeric derivatives may be significant in developing non-sensitizing substitutes for tartrazine and sunset yellow. [This is an interesting development, which is still at a relatively early stage of investigation. The resistance of the polymers to absorption from the gut and the apparent absence of any significant retention of the dyes or their metabolites in the body will need further confirmation. Further work will also be needed to establish conclusively the chemical structures responsible for the cases of human hypersensitivity associated with these colourings.]
Honohan, T., Enderlin, F. E., Ryerson, B. A. & Parkinson, T. M. (1977). Intestinal absorption of polymeric derivatives of the food dyes sunset yellow and tartrazine in rats. Xenobiotica 7, 765. Water-soluble azo dyes such as tartrazine and sunset yellow are cleaved at the azo bond by gut bacteria (Cited in F.C.T. 1969, 7, 87). The products of tartrazine fission are sulphanilic acid (SA) and 1-(4-sulphophenyl)-3-carboxy-4-amino-5-pyrazolone (SCAP), which may be further metabolized to SA, whereas sunset yellow produces SA and I-amino-2naphthol-6-sulphonic acid (ANSA) (ibid 1963, 1, 101; Roxon et al. Fd Comet. Toxicol. 1967, 5, 447). Ingestion of tartrazine may provoke allergic reactions such as asthma and urticaria (ibid 1973, 11, 685), and the FDA has proposed that it should be declared by name on food products (Food Chemical News 1976, 18(47), 29). Sunset yellow has also been implicated in occasional cases of hypersensitivity (Baer & Leider, J. inoest. Dem. 1949, 13, 223; Michaelsson & Juhlin, Br. J. Derm. 1973, 88, 525). In the latter study, SA failed to produce urticaria or other objective signs of allergy in eight subjects sensitive to sunset yellow and tartrazine. Polymeric antioxidants which are absorbed to only a very limited extent from the gut have recently been developed (Cited in F.C.7: 1977, 15, 357; ibid 1978, 16, 321) and parallel work is in hand on colourings (ibid 1978, 16, 321). The metabolic fate of polymeric derivatives of tartrazine and sunset yellow is compared with that of the free colourings in the paper by Honohan et al. cited aboye. In both cases the polymer was a polysulphanilamidoethylene (PSAE), a polyaminoethylene backbone being linked through a sulphonamide group to the azo dye. When rats were given, by gavage, the polymeric derivative of tartrazine (PSAE-TA), uniformly labelled with ‘%Z in the 1-p-sulphophenyl ring, 4.6% of the i4C appeared in the urine. Over half of this was identified as SCAP and about 40% as SA. After administration of similarly labelled tartrazine, urinary radioactivity accounted for almost the same proportion (4.0%) of the dose, 44% being SCAP in this case. SA represented a further 43% of the excreted radioactivity. Thus the amount of SA derived from the aminopyrazolone moiety was approximately the same for both forms of tartrazine; in the case of PSAE-TA,
Mutations
COMMENTS
MATTERS
food colourings
FLAVOURINGS,
AND
SOLVENTS
AND
SWEETENERS
Whether saccharin is or is not a bladder carcinogen is a subject of continuing controversy. Mutagenicity studies have also presented problems of interpretation and a review of 17 such studies concluded that they had produced only conflicting or equivocal results
from saccharin
Batzinger, R. P., Ou, S.-Y. L. 8~ Bueding, E. (1977). Saccharin and other sweetners: Mutagenic properties. Science, N.Y. 198, 944. 91