Excretion of radioactivity from rats and rabbits following cutaneous application of two 14C-labeled azo dyes.

A benzidine-derived azo dye, C.I. direct black 38 (DB38), and a p-phenylenediamine-derived dye, C.I. direct black 19 (DB19), labeled with carbon-14 in their aromatic amine moieties, were applied to the shaved dorsal skin of male Fischer-344 rats and New Zealand rabbits. Application sites were protected with nylon gauze and elastic bandage assemblies. Following application of measured amounts of radiolabeled dye in 0.1 M pH 10.2 carbonate buffer, serial urine and fecal samples were obtained from individual animals in metabolism cages at 24, 48, 72, 96, 120, and 144 h. Aliquots of urine and fecal homogenates were assayed for radioactivity by scintillation counting. Cumulative excretion of radioactivity from rats receiving DB38 was 0.05% of total dermal dose at 144 h in urine, and 0.16% of total dermal dose in feces. Cumulative excretion of radioactivity from DB38-treated rabbits at 144 h was 3.12% of total dermal dose in urine, and 5.12% in feces. From rats and rabbits receiving topical DB19, cumulative excretion of radioactivity at 144 h was less than that from DB38-treated animals. In rat urine, 0.04% of total dermal dose appeared; in rat feces, no radioactivity was recovered. In rabbit urine, 0.04% of dermal dose was found; 0.01% appeared in rabbit feces.

Chromatographic assays for traces of potentially carcinogenic metabolites of two azo dyes, Direct Red 2 and Direct Blue 15, in rat, hamster and human urine.

Specific, precise and sensitive methods are described for determining traces of potentially carcinogenic metabolites of Direct Red 2 and Direct Blue 15 in rat and hamster urine and to monitor the urine from workers who may be occupationally exposed to these dyes. This methodology is generally applicable to metabolites of azo dyes based on benzidine or three of its congeners. The benzidine-congener free amines, their mono and diacetylated analogs and alkaline hydrolyzable conjugates were determined after appropriate extraction and hydrolysis by HPLC or EC/GC. Residues of metabolites in rat, hamster, and human urine were determined at levels as low as 1 ppb. Supplementary information is also presented concerning hydrolysis of diacetylated metabolites and the stability of Direct Red 2 and Direct Blue 15 in rat, hamster and human urine.

Absorption and distribution of C.I. Solvent Red 24 in rats; intra-tracheal administration of 14C labeled dye.

1-((2-methyl-4-[(2-methyl phenyl)azo] phenyl)azo)-2-naphthalenol (C.I. Solvent Red 24) was prepared having a 14C label on the methyl group of the central ring and was administered in suspension intra-tracheally to a male and a female rat. After 96 hours in metabolism cages, the animals were sacrificed and 14C counted in various organs and in urine/feces samples taken periodically up to 96 hours. Absorbed colorant was defined as that percentage of the total dose of radioactivity not present in the lung parenchyma after 96 hours relative to the total amount recovered and amounted to about 60%. Of this, about 98% was excreted in the urine and feces, the latter being the major excretory pathway. No free colorant was found in either feces or urine. Fractional percentages of the absorbed radioactivity were found in various tissues including the liver, and 4-amino-2',3(14C) dimethylazobenzene was identified in the urine after acid hydrolysis.

Experimental papillary necrosis of the kidney. 3. Effects of reserpine and other pharmacologic agents on the lesion.

Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete.

Renal tubular flow dynamics during angiotensin diuresis in the rat.

1. Tubular size and lissamine green transit times were measured in rat kidneys undergoing a diuretic response to angiotensin II (0.5 mug/kg per min), and compared with the changes observed during diuresis induced by osmotic diuretics, noradrenaline and chlorothiazide.2. Angiotensin always caused a marked prolongation in proximal and distal tubular transit times; individual distal convolutions were coloured for prolonged periods, and lissamine green appeared in high concentration in distal tubules.3. Marked changes were observed in superficial tubular calibre during a stable diuretic response to angiotensin. Where distal tubular diameter was normal for the rate of urine flow, proximal tubular volume was generally reduced. In a number of experiments, however, distal tubules were markedly dilated, and in these cases proximal tubular volume was also often increased. Angiotensin may therefore be capable of causing a degree of internal hydronephrosis in the rat kidney.4. Prolongation of dye transit times, and the appearance of a concentrated lissamine green bolus in distal tubules, was suggestive of a decreased superficial nephron flow rate, indicating that the diuretic effect of angiotensin may take place only through deeper nephrons.