Neurotoxicity screening methods are sensitive to experimental history.
Toxicity studies commonly include unavoidable environmental differences (experimental history) among test groups, such as chemical taste, odor and irritation. The influence of environmental variables on USEPA guideline neurotoxicity tests was evaluated using an environmental enrichment model. 6-week-old male Fischer 344 rats were housed for 13 weeks in pairs with access to an exercise wheel, trained to run on a rotating rod and handled frequently. Control animals were housed singly, lacked the exercise wheel and rotating rod training, and had only routine interaction with caretakers. At the end of 13 weeks, flash evoked potentials (FEPs), somatosensory evoked potentials (SEPs), auditory brainstem responses (ABRs), grip performance, motor activity (MA), elements of the functional observational battery (activity and reactivity to handling/restraint) and brain histopathology with glial fibrillary acidic protein immunohistochemistry (GFAP IHC) were evaluated. Animals from the enriched group demonstrated changes (P < 0.05) in FEPs, SEPs and grip performance. Enriched animals were more active and reactive to their surroundings, and were highly reactive to physical restraint. Control (unenriched) animals showed little to no exploratory behavior and were more tolerant of restraint. Differences in experimental history can be detected using elements of standard guideline tests and may confound interpretation of such data if not taken into consideration.
Spencer
P J
PJ
Toxicology Research Laboratory, Dow Chemical Company, Midland, MI 48674.
Mattsson
J L
JL
Johnson
K A
KA
Albee
R R
RR
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry; D005071:Evoked Potentials / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006799:Housing, Animal; D008297:Male; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D014116:Toxicology / Q000379:methods*
D005904:Glial Fibrillary Acidic Protein