Fd Cos,net. Toxicol. Vol. 7, pp. 383--403. Pergamon Press 1969. Printed in Great Britain

TOXICOLOGY: ABSTRACTS AND COMMENTS

C O L O U R I N G MATTERS

1761. Clearing out the azo dyes! Despopoulos, A. (1968). Renal and hepatic transport of food dyes. J. Pharmac. exp. Ther. 163, 222.

The hepatic and renal excretion of four food colourings, Amaranth (16185)*, Sunset Yellow FCF (15985), Tartrazine (19140) and Brilliant Blue FCF (42090), was investigated in vitro using isolated perfused rat livers and surviving slices of rabbit-kidney cortex. As sulphonic-acid derivatives, all might be expected to be actively transported by the liver and kidney. It was found that with all four the pattern of biliary excretion resembled that of the hippurates and sulphonamides, but only the first three colourings were actively concen- trated by slices of rabbit-kidney cortex. Brilliant Blue FCF was not concentrated to any appreciable extent in the renal slices and did not appear to undergo renal metabolism. In the liver it was apparently metabolized and it seemed that the metabolite was the predom- inant substrate for transport. Metabolic alteration of the azo dyes in vitro appeared to be negligible.

These results obtained with isolated organs demonstrate what the liver and kidney are capable of achieving when appropriate quantities of these colourings are made available. Following oral administration of the compounds, however, there is negligible intestinal absorption and only very small quantities are in practice presented to the liver and kidney for elimination.

1762. Trypan blue and the testis Kormano, M. (1968). Penetration of intravenous trypan blue into the rat testis and epi- didymis. Acta histochem. 30, 133.

The red fluorescence of trypan blue under ultraviolet light has been used to demonstrate the distribution of the dye in the testis and epididymis of normal, cryptorchid and cadmium- injected rats. Trypan blue was administered intravenously in a dose of 15 ml/kg as a 1% solution in 0.9 % saline. The rats were killed 5 or 15 min after the injection and the testes were quickly frozen in liquid air and later 10-/z sections were prepared with a cryostat microtome. Cadmium-treated rats had received a subcutaneous dose of 0-03 mmoles cadmium chloride/kg l, 2, 3 or 6 hr or 1.5 yr prior to the trypan blue treatment.

In normal rats, the dye accumulates within a few days in the interstitial tissues of the testis and is transported across the seminiferous epithelium. From there it is carried with the products of the testis to the epididymis where it appears to be preferentially absorbed by the cells of the excurrent ducts. In cadmium-treated animals the extravasation of the dye into the interstitial tissues of the testis is greatly enhanced as early as 1 hr after cadmium

* c.I. (1956) nos are given in brackets. 383

384 FLAVOURINGS, SOLVENTS AND SWEETENERS

administration, but extravasation of the dye in the regenerated capillaries seems to be less marked, a finding for which no explanation is offered. No significant difference in the degree of penetration of trypan blue was seen in a third group of rats in which artificial cryptor- chidism had been induced by some unspecified method for 1-2 months prior to treatment, and the distribution of dye was similar to that in normal animals.

This work suggests that under normal conditions the testicular capillaries have a low permeability to trypan blue, but after pretreatment with cadmium chloride the permeability is greatly increased.

[The use of fluorescence microscopy for examining the distribution of trypan blue is of potential value in the investigation of its teratogenic effects in both mammalian and avian species. Various studies (Cited in F.C.T. 1964, 2, 85; ibm 1968, 6, 663) have suggested that trypan blue is a potent teratogen which acts extra-embryonically.]

FLAVOURINGS, SOLVENTS AND SWEETENERS

1763. Glutamate gluttons Schaumburg, H. H., Byck, R., Gerstl, R. & Mashman, J. H. (1969). Monosodium L- glutamate: Its pharmacology and role in the Chinese restaurant syndrome. Science, N.Y. 163, 826.

Kramer, S. Z., Sherman, P. A. & Seifter, J. (1967). Effects of gamma-aminobutyric acid (GABA) and sodium L-glutamate (glutamate) on the visual system and EEG of chicks. Int. J. Neuro-pharmacol. 6, 463.

Thompson, D. J. & Nelson, T. S. (1968). Effect of monosodium glutamate on blood ketones in sheep. J. Nutr. 96, 415.

Diners in Chinese restaurants can hardly blame the chef for any uncomfortable sensations they may encounter--instead they can but look dejectedly at the remains of delicacies richly endowed with monosodium glutamate (MSG), the villain of the piece (Cited in F.C.T. 1968, 6, 781).

In two of the original victims of this malaise, similar attacks were provoked not only by monosodium L-glutamate but also by monopotassium L-glutamate, DL-glutamic acid and L-glutamic acid but, no doubt to the relief of the volunteers, monosodium D-glutamate, monosodium L-aspartate, sodium chloride and glycine were each without effect (first paper, cited above). A dose-response relationship was established in a group of 56 other volunteers, 1"5-12 g being the range of minimum doses required to produce the symptoms, which were characterized first by a burning sensation (15-25 min after dosage) then by chest pain and finally by facial pressure. Intravenously, 25-125 mg MSG sufficed to produce these symp- toms in 17-20 sec after administration. An empty stomach accentuated the effects of oral doses of MSG, so a generous ration of an appetizer free from MSG may prove prophylatic in sensitive individuals. But the mechanism of the production of these sensory phenomena still remains a mystery.

Two experimental studies in animals throw no further light on the mechanisms involved. One study was concerned with the changes induced by MSG in the brain and in the retinal electrical activity of chicks (second paFer , cited above), while the other demonstrated that MSG had a greater ability than propylene glycol to lower blood-ketone levels in sheep after the levels had been raised experimentally by butyric-acid treatment.