Toxicity assay in repeated doses of Dermatophagoides siboney allergen extract in mice.

Allergen extracts are used for hyposensitivity and immunotherapy treatments, reducing significantly clinical symptoms of allergic diseases. Because of its wide use in immunoallergen therapy, we evaluated the Dermatophagoides siboney allergen extract to establish the potential toxicity following repeated subcutaneous dosing in Cenp:NMRI mice. Animals were randomly distributed into two groups, control (vehicle) and treated (166.6 UB/animal), and they were observed daily for clinical signs of toxicity following treatment. Body weight was weekly measured. At the end of the study, blood samples were collected for hematology and serum chemistry analysis and animals were euthanized for gross necropsy and histological examination of tissues. There were not significant differences in body weight or hematology parameters between control and treated animals. Differences were noted in uric acid, blood urea nitrogen and glucose; however, these alterations were not considered to be of biologic relevance. Pathology evaluations demonstrated hemorrhagic and inflammatory lesions at the administration site in both experimental groups. We conclude that repeated dosing of 166.6 UB did not cause significant toxic effects in the mouse model.

Hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in African green monkeys (Cercopithecus aethiops sabaeus). Its use in non-clinical toxicological studies.

BACKGROUND: The purpose of this study is to better characterize the hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in young adult Cercopithecus aethiops sabaeus of both sexes. The rhesus and cynomolgus monkeys are widely used as experimental primate models. However, only few articles have been published testing toxicological effects of pharmaceuticals on African green monkey. METHODS: The present study was carried out with the recompilation of all parameters recorded before the first drug administration in five sub-chronic or chronic toxicological studies performed on 66 Cercopithecus aethiops sabaeus, born in Cuba. RESULTS: This study provides hematological, biochemical, respiratory, cardiovascular and electroneurophysiological data for both choosing animals to be included into experiments and monitoring these parameters during the study. CONCLUSIONS: We conclude that this study provides valuable integrated data for determining the health status, including electroneurophysiological parameters, data not previously reported for this species, of the African green monkey.

Local and systemic toxicity of h-R3, an anti-epidermal growth factor receptor monoclonal antibody, labeled with 188osmiun after the intracerebral administration in rats.

h-R3 is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb). This receptor is over-expressed in the majority of tumors of epithelial origin, including glioblastomas. 188Rhenium (188Re) constitutes an ideal radionuclide for imagining and radioimmunotherapy, and its toxicity is known, nevertheless, it is unknown if 188Os, as 188Re's daughter, has any local or systemic toxicity effect when it is administered intracerebrally for treating intracranial tumors. For this reason we decided to assess the toxicity of stable 188Os once the complete decay of 188Re has occurred, by administering intracerebrally to rats the h-R3 labeled with 188Os. Forty rats (20 each sex) were distributed randomly into four experimental groups (ten per group): control group received 5microL of glucoheptonate solution vehicle; two other groups were treated with unlabeled or labeled h-R3 with 188Os. The remaining group served as a non-treated control group. A single 5 microL dose (2.5 microL into each lateral ventricle) of neutral solution containing 50 microg of h-R3 labeled initially with 13.25 microCi of 188Re was stereotactically administered into lateral ventricles 8 days after the conjugation with the radionuclide was done. Each animal was observed daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out at the end of the study. All animals gained weight by day 14. There were no changes in hematological and clinical chemistry, but minimal histopathological changes were observed at the application sites. This study shows that single doses of 188Os-h-R3 is tolerable and causes minimal local and no systemic toxicity effects in rats.