Objective: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus.Study design: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted.Results: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. Conclusion:The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.

Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.

Objective: To determine genotoxicity, cytotoxicity and methemoglobinemia of a mixture of lidocaine (LD) and prilocaine (PL) (EMLA ® ) in an experimental model.Study design: Newborn hairless rats were studied in a prospective random and masked design. Groups I-III received topically LD-PL mixtures at 5, 10 or 20% respectively; group IV: petrolatum (negative control); group V: 5-fluorouracil 5% (genotoxicity and cytotoxicity positive control); and group VI: aniline (methemoglobinemia positive control). Blood samples were collected every 24 h from 0-144 hours. Genotoxicity and cytotoxicity were assessed by the micronucleus assay. Changes in micronucleated erythrocytes and micronucleated polychromatic erythrocytes evaluated genotoxicity, and polychromatic erythrocytes in 1,000 total erythrocytes were used to determine cytotoxicity. Methemoglobin values were quantified by spectrophotometry.Results: The micronucleated erythrocytes number increased proportionally to the LD-PL mixture dose (p = 0.04), from 60% in group II until 90% in group III in relation to their basal value; however, no cytotoxicity effect was observed. Methemoglobin values increased in groups II, III, V and VI from the second day (p < 0.05). M.L. Lemus-Varela et al. / Lidocaine and prilocaine cream in an experimental modelConclusion: Topical administration of LD-PL mixture (10% and 20%) to neonatal rats show genotoxic effects and produces methemoglobinemia. Clinical implications of these findings require urgent further investigation before continuing to use LD-PL mixture routinely.