Neurotoxicity testing during long-term studies.
Several tests and methods for the investigation of neurotoxicity were performed with female Wistar rats for up to 187 days. The methods were validated by testing 10 rats treated with beta,beta'-iminodipropionitrile (IDPN) and 10 control rats. Cage side observation of the animals revealed signs of altered behavior and motor dysfunction of the IDPN-treated rats. Results of a neuromuscular screen indicated changes in gait, righting reflex, grip strength and performance of the negative geotropism test. Investigation of the animals in activity monitors and on the accelerating rotarod showed changes of several parameters. The motor nerve conduction velocity, measured 6 months after the first treatment, was reduced by 6.7 meters per second in the IDPN group compared to controls. From the results of the tests it can be concluded that the methods chosen can be used during long-term studies but may be most useful for animals not older than 12 months.
Ivens
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I
Institut für Toxikologie Industriechemikalien, Wuppertal, FRG.
D000818:Animals; D005121:Extremities / Q000294:innervation; D005260:Female; D005684:Gait / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009132:Muscles / Q000294:innervation; D009431:Neural Conduction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012018:Reflex / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile