4,4'-bis[4-[bis(2-hydroxyethyl)amino]-6-anilino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid

Endpoint summary

Additional information

Results on intestinal absorption and skin penetration of CAS 16090 -02 -1 were reported by Black et al. (1977). Two groups of 6 rats each were treated by oral gavage with 0.5 ml of a solution containing 0.007% tritiated substance in 1% (w/v) detergent (alkyl benzene sulfonate and sodium tripolyphosphate) or in an aqueous solution. All animals were placed in separate metabolic cages and urine and feces samples were collected every 24 hours for up to 4 days. At scheduled necropsies after 24, 48 and 96 hours blood samples were taken by heart puncture and selected organs were sampled for radioanalysis. The bulk of radioactivity from both treatment groups was excreted in the feces, mostly during the first 24 hours. Small amounts were present in the urine. Recovery of radioactivity was essentially complete after 48 hours (total recovery > 92% with 48 hours). No significant amount of radioactivity was found in urine, blood and feces samples from 16 rats treated topically with 0.2 ml of a solution containing 0.007% tritiated substance in 1% aqueous detergent. In two rats, treated topically with 0.5 ml of a solution containing 0.43 mg/ml tritiated test material in ethanol, however, small amounts of radioactivity were detected in feces, large and small intestines and their contents as well as in the content of the stomach. Only minor amounts of radioactivity were found in the liver, bladder, kidneys, and heart of one of the treated animals. Approximately 0.1% of the applied dose (i.e. approximately 0.01 μg/cm²) had been absorbed through the skin during two days.

Forbes (1976) found after application in methanol, 14C-activity was lost from the skin of hairless mice at a constant rapid rate for the first 2 hours; thereafter loss continued at a lesser rate.

These findings are confirmed by absorption, distribution and excretion experiments in rats published by Mücke et al. (1975) (CIBA-Geigy, 1972b). Following an oral dose of 14C-labeled of CAS 16090 -02 -1 in water at 5.9 mg/kg bw to rats of both sexes, rapid and complete excretion of radioactive material was observed, with an excretion half life ranging from 7-13 hours. Feces were practically the only route of excretion (more than 95% of the administered radioactive material was excreted within 48 hours), indicating, in combination with the short half life times, that no significant amounts were absorbed from the gastro-intestinal tract. No radioactivity was found in blood, liver kidney, brain, muscle, or fat 96 hours after dosing (limit of quantification 0.005 - 0.01 ppm equivalents). The total recovery of radioactivity was 97.5% and 95.2% of the orally applied dose for males and females, respectively.

Only very limited information is available on the biotransformation (metabolism) of CAS 16090 -02 -1 in experimental animals. Little or no cis-isomer was produced by Beagle dogs fed with 2000 mg/kg bw of the trans isomer (Burg et al., 1977).

Another study done with CAS 13863 -31 -5 (CIBA-GEIGY Limited, Basel, Switzerland 1973) similar to OECD Guideline 417 followed the fate of ¹⁴C-labeled test substance, another fluorescent whitening agent, in the rat. After an oral dose of approximately 5 mg/kg bw nearly all the administered radioactivity was rapidly excreted with the feces. The average residue in all tissues examined was less than 0.005 ppm test substance equivalents. Most of the radioactivity in the feces was not extractable with either methanol or water because probably the compound is tightly bound to cellulose in the feces.

A further study done with CAS 13863 -31 -5 (CIBA-GEIGY Limited, Basel, Switzerland 1975a) was similar to OECD Guideline 427 which examines the skin absorption.¹⁴C-labeled test substance was topically applied to the depilated back of male rabbits at a dose of 20 µg/cm².Within three days approximately 2% of the applied radioactivity was excreted with urine and feces; by far the major portion was still on the skin. The subcutaneous tissue underneath the application area contained 0.2% and the total skeletal muscle certainly less than 1% of the applied radioactivity assuming the radioactivity found in muscle underneath the subcutaneous tissue of the application area to be representative for the total muscle radioactivity. The radioactivity in the blood, monitored during 72 hours, contained only minute amounts of radioactivity. Even at the peak, reached within two hours, the amount present in the total blood was still below 0.1%. After six hours the blood radioactivity was below the limit of quantitation or even below the limit of detection being 0.016% and 0.006% or 2.7 ppb and 0.9 ppb, respectively. From these data it is assumed, that the test substance is not absorbed by rabbits after topical application. The small amount of radioactivity excreted with urine and feces is probably due to impurities present in the¹⁴C-labeled test substance used in this study and to degradation products which may be formed in trace amounts on the skin during prolonged contact with the compound.

Conclusion: Since all stilbene fluorescent whitening agents of this category show similar physico-chemical parameters it can be stated that after oral exposure, rats excrete stilbene fluorescent whitening agents almost completely in the feces within 48 hours. There was no measurable skin penetration of stilbene fluorescent whitening agents when topically applied in a detergent solution to rats. When applied at 0.43 mg/ml in ethanol, approximately 0.01 μg/cm² penetrated rat skin within 2 days. This shows that all category members are almost completely excreted after oral exposure and that a dermal absorption is poor.