Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)

Endpoint summary

Additional information

A valid metabolism study is done by CIBA in 1972. The test substance was given male and female rats in a single oral dose of 5 mg/kg 14 -C-test substance. More than 90 per cent of the administered radioactivity was excreted within 48 hours of dosing. The faeces being the main, and practically only, route of elimination. Little or no radioactivity was found in the urine (0.03% of the dose) and expired air (< detection limit). Blood, muscle, fat, brain, kidney and liver were examined for residual radioactivity. Residues in all tissues were less than 0.01 ppm. Practically all the radioactivity in the faeces was extractable with methanol; (94 % for males and 98 % for females). Thin layer chromatography of the extract showed that the extracted radioactivity from both sexes co-chromatographed exactly with the UV-treated parent compound. The TLC results suggest that the test substance is converted from the trans-trans isomer to the cis-trans or cis-cis during its passage through the gut or during handling for analytics. If in solutions the test substance is known to undergo photo-isomerization withing minutes. The above results indicate that test substance is neither absorbed nor metabolised in the rat. The rate of excretion is probably only dependent on the rate at which it passes through the gastro-intestinal tract.

In vitro skin penetration of the substance was assessed in porcine (Wollny 1995). Porcine ears were obtained from a local slaughter-house on the day of slaughter and before the pigs were steam-cleaned. The outer ear region was washed and cleaned with cold water. After carefully shaving, the skin was removed by dissection. The skin sample was then stored in a freezer until use (within a week). The thickness of the skin varied between 2 and 3 mm. The surface area of the skin which was in contact with the test substance during the penetration-assay was 1.13 cm2.

For the determination of the absorption of the test article the skin was mounted in glass diffusion chambers with a diameter of 1.13 cm2 (area of skin) and a volume of 7 ml. These chambers are subdivided in an upper part (donor chamber) and in a lower part (receptor chamber). A recorded volume of physiological saline (0.9% NaCl-solution) was placed in the receptor chamber of each diffusion cell, followed by the application to the donor chambers of 200 μl of the test article dissolved in bi-distilled water.

Three concentrations of the test article (100, 10, and 1μg/ml chamber volume) where tested using 4 chambers at each concentration. The top of the donor chamber was covered with Parafilm. The diffusion chambers were placed in an incubator at 37 °C. Samples (0.5 ml) were taken from the receptor chambers after 0, 0.5, 1, 4, 8, and 24 hours and analysed by liquid scintillation counting. The volume of the fluid in the receptor chamber was kept constant by the addition of 0.5 ml of fresh receptor fluid to the receptor chamber immediately after removal of each sample. By plotting the time dependent increase in concentration of the test article in the receptor chamber, the permeation rate was determined.

The positive control was 14C-mannitol since it is known to permeate porcine skin. The control chambers showed a time dependent permeation of 14C-mannitol with a permeation constant of 1.3x10-4 cm/h. Due to a leaking chamber only 3 chambers could be evaluated of the four in the test group with 100μg/ml.

For test substance exposed porcine skin, penetration to receptor fluid was not detected at any concentration tested in the time range up to 24 hours.

Results from this study are considered reliable as indication of skin penetration by the test substance. The study design is acceptable. Porcine skin is considered a suitable representative of human skin as indicated by the Opinion (23 June 1999) of the EU Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP).

From the study results it appears that the substance will not penetrate full thickness skin. However, current interpretation of in vitro percutaneous penetration study results (SCCNFP 1999, above) indicate a substance is considered to be absorbed not only if detected in the receptor chamber (penetration), but also if found in skin layers below the stratum corneum where it may be taken up by the cutaneous circulation. Accordingly, it is conservative to assume some portion of dermally occurring substance will be available for absorption by the circulation.

The test substance molecule was designed to have substantivity to fabric and it is not unreasonable to assume percutaneous penetration to be restricted by substantivity to skin.

In an older dermal resorption study (Ciba 1976) the test substance was examined by bathing hairless female mice in a detergent solution containing 0.2% of 14C-labelled material of 95% purity.

Mice were bathed for 15 minutes. After washing for 2 minutes in tap water and dripping down for 3 minutes, one group of animals was sacrificed and investigated for uptake of radioactivity, whereas other groups were kept in metabolism cages for another 4, 24 or 72 hours. Immediately after exposure and washing, 0.3% of the initial dose was found in the body. No distinction could be made whether this represents the test substance or a radioactive impurity. Most of the absorbed dose was detected in the skin where its content decreased by half during the 72h observation period.

The available data indicates that the substance is poorly absored and has no potential for bioaccumulation.