Pyrrolidine dithiocarbamate (PDTC) was examined for its potential in the intranasal treatment of human rhinovirus infections. Prior to clinical testing, a comprehensive non-clinical programme was performed to evaluate the general toxicity of PDTC. The animal experiments included investigations in rodents with study durations ranging from single dose to repeated dosing over a period of 28 days. The routes of administration were intranasal, inhalative, oral and intravenous for single-dose toxicity and pharmacokinetic studies, and intranasal for repeated dose studies. Blood and tissue samples were obtained from PDTC-treated rats to analyse pharmacokinetics and tissue distribution. Accumulation of selected metals due to PDTC treatment was examined in liver, brain, nerves and fat tissues.Pyrrolidine dithiocarbamate (PDTC) applied intranasally (up to 121 mg ⁄ kg) or via single inhalation (1.64% PDTC applied for 4 hr) or repeated intranasal dosing up to 28 days (up to 102 mg ⁄ kg ⁄ day) did not result in major systemic toxicities or local intolerance. Pharmacokinetic evaluations indicate a very rapid absorption of PDTC after intranasal application. A high single intravenous or oral dose of PDTC induced neurotoxicity. The neurotoxic effects are in accordance with the toxicity profile described for dithiocarbamates (DTCs) with effects on the autonomous and nervous system. The intravenous LD 50 was defined at 282 mg ⁄ kg in mice and at 306 mg ⁄ kg in rats. The oral LD 50 was calculated at above 1500 mg ⁄ kg for mice and rats. The results from in vitro and in vivo genotoxicity studies do not elucidate a genotoxic potential for PDTC.Concluding from the toxicology data set, PDTC qualifies as a valuable drug candidate for intranasal or inhalative administration.Pyrrolidine dithiocarbamate, a very effective NF-jB inhibitor [1], known to inhibit inflammatory processes [2], is suggested as a key factor in the treatment of human rhinovirus (HRV) infections. Unpublished in vitro data strongly support this hypothesis. Thus, the aim of this project was to describe the toxicity profile of PDTC allowing for clinical use of the potential HRV drug candidate. Pyrrolidine dithiocarbamate is a compound of the class of DTCs. Dithiocarbamates and their disulphides have been used in medicine, industry and agriculture for more than 20 years. The compounds class reported biological effects include ability to influence oxidative stress, apoptosis, enzyme inhibition or modulation of transcription as well as inhibition of inflammatory processes via NF-jB inhibition [1,[3][4][5][6][7][8].Two DTCs, diethyldithiocarbamate and its disulphide disulphiram (Antabuse) are marketed drugs: Diethyldithiocarbamate is used in the treatment of nickel intoxication, Antabuse is marketed for alcohol aversion therapy. The potential clinical use of closely related compounds is currently being explored for various indications including the treatment of ocular inflammations [9,10], infection caused by rhinovirus [11] and coxsackievirus [12], methicillin-resi...