J. Soc. Cosmet. Chem. 26 3-15 (1975) ¸ 1975 Society of Cosmetic Chemists of Great Brita#t The action and fate of sodium pyridinethione when applied topically to the rabbit H. C. S. HOWLETT* and N.J. VAN ABBI•? Presented on 28th August 1974 in London at the IFSCC VIIIth International Congress on 'Cosmetics--Quality and Safety' organized by the Society of Cosmetic Chemists of Great Britain. Synopsis--TOXICOLOGICAL studies of SODIUM PYRIDINETHIONE have warranted a study of absorption, distribution and excretion following topical therapy to RABBITS. The extent of percutaneous absorption of sulphur-35 labelled sodium pyridinethione has been related to the skin's structural integrity by RADIOMETRIC assay for sulphur-35 analysis. The distribution of the drug and METABOLITES for the mjaor tissues and body fluids has been established, and the metabolic fate of the drug has been determined using a RADIO- CHROMATOGRAPHIC technique. The safety evaluation of sodium pyridinethione needs to include the study of absorption, distribution and excretion following topical therapy. Using a radiometric assay for asS, the extent of percutaneous ab- sorption of asS-labelled sodium pyridinethione has been examined in rela- tion to the skin's structural integrity. Distribution of the drug and meta- bolites in the major tissues and body fluids has been established, and the metabolic fate of the drug determined using a radiochromatographic technique. * Pharmacology Department, School of Pharmacy, City of Leicester Polytechnic, Leicester. ? Beecham Products Ltd, Beecham House, Great West Road, Brentford, Middlesex.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The heavy metal salts of 2-pyridinethiol-l-oxide first synthesized by Shaw et al. (1) were first demonstrated to have antibacterial properties by Cox (2). Safety of the zinc salt was extensively studied by Brauer, Opdyke and Burnett (3) and by Opdyke et al. (4) and this compound is currently incorporated into several formulations for application to the scalp. Unlike the zinc salt, the sodium salt is readily water soluble, a property which, according to Davson and Danielli (5) can influence percutaneous absorption. The study reported here was intended: (1) to establish the threshold dose levels for signs indicative of sodium pyridinethione toxicity in acute studies (2) to determine the extent of percutaneous absorption and ensuing toxicity of sodium pyridinethione applied to abraded and intact skin (3) to record the distribution and metabolic fate of sodium pyridinethione following dermal application. MATERIALS AND METHODS Materials Sodium pyridinethione and pyridine-N-oxide-2-sulphonic acid were pro- vided by Olin Research Centre, New Haven, Conn. Sodium pyridinethione labelled with •5S was synthesized at Beecham Research Laboratories, Betchworth, Surrey, as a white powder, shown by tlc and ir examination to be 90•o pure. All other chemicals and solvents were of analytical reagent grade and were used without further purification. Throughout the experi- mental work polyethylene apparatus was used to reduce drug losses from adsorption during recovery operations. Preparation of animals Acute toxicity studies Two groups of five New Zealand white rabbits (1-1.5 kg) received an anaesthetic dose of sodium pentobarbitone 35 mg kg -•, before i.v. infusion of sodium pyridinethione as a 4• w/v aqueous solution, at a constant rate of 20 mg (0.5 ml) per min into the cannulated jugular vein. The carotid artery was cannulated for blood pressure studies and the heart rate calcu- lated from the electrocardiograph. One group of anaesthetized rabbits