Toxicity and antidotal treatment by synthesized and optimized ferric(III) hexacyanoferrate(II) for thallium

Abstract

Abstract Background The active pharmaceutical ingredient (API) of USFDA-approved Radiogardase®-Cs capsule is ferric(III) hexacyanoferrate(II) which is commonly known as Prussian blue insoluble (PB). It enhances the elimination of radioactive or non-radioactive caesium/thallium (Cs(I)/Tl(I)) from the body. The API of Radiogardase®-Cs capsules is not available commercially; therefore, in-house API was synthesized and evaluated. The present study includes toxicity evaluation and in vivo Tl(I) removal efficacy of in-house synthesized and optimized PB prepared by direct (PB-1) and indirect (PB-2) synthesis methods. PB-1 and PB-2 were evaluated for acute and sub-acute oral toxicity in accordance with OECD guidelines in rats. Results No significant changes were observed in treatment groups as compared to the control group of acute and sub-acute oral toxicity studies. The food intake, water consumption, body weight, clinical signs, organ weight and histopathological, biochemical and haematological parameters were monitored. The study found no evidence of mortality. The results indicated that the synthesized PB-1 and PB-2 were safe. As a result, the study further examined PB-1 and PB-2 for removal of Tl(I) in rats. A significant increase in Tl(I) removal was observed when PB-1 and PB-2 were administered orally to rats in comparison to no treatment group. The Tl(I) removal efficacy of PB-1 and PB-2 was comparable to Radiogardase®-Cs treated group. Results showed reduction in the body burden of Tl(I) as well as a higher level of elimination of Tl(I) in faeces and urine. Conclusions The study provides substantial support regarding Tl(I) removal efficacy and safety of in-house synthesized PB-1 and PB-2 which can be used for formulation development.