ABSTRACT
1R&D, Safety Pharmacology and Toxicology - Angelini Santa Palomba Research Center - Acraf Piazzale della Stazione, 00040 S. Palomba - (RM), Italy c.landolfi@angelini.it - www.angelinipharma.com
2Expert in Toxicologic Pathology, Timrat, 23840, Israel
This study was conducted to verify the tolerability of the vehicle 0.5% methylcellulose aqueous solution (MTC) given intraperitoneally (IP) in repeated toxicology studies in the mouse. 0.5 % Methylcellulose aqueous solution is a clear viscous vehicle commonly used in the acute, sub-chronic and chronic oral toxicity studies in the rodents. After oral administration MTC 0.5 % solution, like cellulose, it is proven to be not digestible, not toxic, and not allergenic.
In order to assess the effects of intraperitoneal administration of 0.5% MTC solution (10 ml/kg body weight) male CD-1 mice were ip treated for 4 weeks. Control animals received water under the same experimental conditions. At the end of the treatment period, animals were sacrificed and a gross pathology evaluation was performed. In addition, an histopathological analysis on liver, spleen and kidneys was performed. Animals were checked during the treatment period for clinical signs, body weight changes and mortality.
No evident clinical signs and body weight changes were observed as compared with control animals. At necropsy all 0.5% MTC treated mice showed altered liver (congested/dark and thickened capsule) and spleen (abnormal size and capsular inflammation). In addition increased liver and spleen relative weight were observed in all 0.5% MTC receiving mice relative to control group. Histopathology indicated severe inflammatory reaction, consisting predominantly of histiocytic infiltration in all examined organs in 0.5% MTC treated mice.
In conclusion our study indicated that the IP administration of 0.5% MTC solution is not tolerated under this route.