Spontaneous incidence of convulsions, tremors, salivation and ataxia in control animals: A multi-site retrospective analysis comparing non-human primates, dogs, minipigs, rabbits, rats and mice

The background incidence of common neurological clinical signs was evaluated in commonly used laboratory animal species. Salivation, tremors and ataxia can be considered as premonitory clinical signs to seizures but can also be observed in normal healthy animals in the absence of seizures. We characterized and compared the incidence of spontaneous convulsions, tremors, salivation and uncoordination/ataxia in control non-human primates, dogs, minipigs, rabbits, rats and mice from drug safety testing studies. A retrospective analysis was conducted with data from GLP facilities in North America and Europe including non-human primates (n = 8805), dogs (n = 24,553), minipigs (n = 2359), rabbits (n = 21,476), rats (n = 312,261) and mice (n = 131,272). Data from telemetered and jacketed animals were included. For rats and mice, the incidence of spontaneous convulsions was lowest at less than 6 weeks of age, was stable from 6 to 26 weeks of age and then increased progressively for older animals reaching 0.66 % in rats and 0.60 % in mice above 38 weeks. When comparing species, the incidence of spontaneous convulsion was lowest in minipigs (0 %) followed by mice (0.03 %), rats (0.06 %), rabbits (0.07 %), dogs (0.11 %) and non-human primates (0.17 %). Uncoordination/ataxia was observed in all species with increasing incidence in mice (0.04 %), minipigs (0.21 %), rats (0.23 %), rabbits (0.32), non-human primates (0.79 %) and dogs (1.00 %). As expected, dogs presented the highest incidence of salivation followed by non-human primates and minipigs. Spontaneous salivation was minimal in mice, rats and rabbits. Spontaneous tremors were observed in 1.6 % of dogs and non-human primates and reached 1 % in minipigs. The incidence of tremors in mice, rats and rabbits was negligible. The data summarized provides a robust characterization of spontaneous neurological clinical signs across multiple research facilities which can help during interpretation of safety pharmacology studies involving neurological assessments.