Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

CiteULike is a free service for managing and discovering scholarly references - click here to get started.

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Ross, J.F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ross, J.F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ECOs, FOBs, and UFOs: Making Sense of Observational Data

J.F. Ross

The Procter & Gamble Co, Miami Valley Laboratories, Cincinnati, Ohio 45253

Systematic observations of rat behavior are required for both standard subchronic safety studies and for neurotoxicity studies. The requirements specify subjective out-of-cage observations (eg, posture, gait, and reactivity to various stimuli such as, auditory, tactile, and noxious) using defined scales. Measurement of forelimb/hind limb grip strength, landing foot splay, and locomotor activity are also required. The observational endpoints are organized into a battery, eg, the Environmental Protection Agency functional observational battery (FOB) or expanded clinical observations (ECO). Functional and neuropathologic data are most easily integrated when the functional endpoints are organized as a neurologic exam (ie, each endpoint has a known anatomical basis and there are sufficient endpoints to cover the nervous system). Current batteries do not constitute a neurologic exam. Although ECOs and FOBs contain some components of a neurologic exam (ie, observations of gait, response to pinch), the anatomic basis for other components (eg, hind limb splay) is poorly defined. And although some functions (eg, somatomotor) are well characterized by current batteries, others (eg, vision, somatosensation) are evaluated less effectively. The measurement of locomotor activity in a novel environment is one of the most problematic parts of current functional testing batteries, although contemporary technology may provide opportunities for improving this test. The influence of inherent limitations of functional test methods is magnified by factors associated with testing for neurotoxicant-related effects during safety studies. First, most personnel at contract laboratories have little or no formal training in conducting and interpreting a neurologic examination. Second, most neurotoxicant-related lesions are bilateral, which paradoxically may produce more subtle effects than unilateral lesions. Third, most chemicals will be tested only once, and sponsors are reluctant to evaluate results in "real time" and amend protocols to add endpoints (eg, neurophysiological tests) to clarify functional effects. Pathologists should have realistic expectations about the opportunities for integrating functional and neuropathologic findings.

Key Words: Neurotoxicity • Functional Observational Battery (FOB) • clinical observations • safety testing • hazard identification • risk assessment

References

  • Balaban, CD (1985). Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity. Brain Res 356: 21-42.[Medline] [Order article via Infotrieve]
  • Crofton KM, Zhao X., Sayre LM, Genter MB (1996). Characterization of the effects of N-hydroxy-IDPN on the auditory, vestibular, and olfactory systems in rats. Neurotoxicol Teratol 18: 297-303.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Edwards PM, Parker VH (1977). A simple, sensitive, and objective method for early assessment of acrylamide neuropathy in rats. Toxicol Appl Pharmacol 40: 589-591.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • File SE (1985). What can be learned from the effects of benzodiazepines on exploratory behavior? Neurosci Biobehav Rev 9: 45-54.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Fix AS, Ross JF, Stitzel SR, Switzer RC (1996). Integrated evaluation of central nervous system lesions: Stains for neurons, astrocytes, and microglia reveal the spatial and temporal features of MK-801-induced neuronal necrosis in the rat cerebral cortex. Toxicol Pathol 24: 291-304.[Abstract/Free Full Text]
  • Krebs-Thomson K., Lehmann-Masten V., Naiem S., Paulus MP, Geyer MA (1998). Modulation of phencyclidine-induced changes in locomotor activity and patterns in rats by serotonin. Eur J Pharmacol 343: 135-143.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Laouris Y., Kalli-Laouri J., Schwartze P. (1990). The postnatal development of the air righting reaction in albino rats. Quantitative analysis of normal development and the effect of preventing nectorso and torso-pelvis rotation. Behav Brain Res 37: 37-44.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Meyer OA, Tilson HA, Byrd WC, Riley MT (1979). A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav Toxicol 1: 233-236.[CrossRef]
  • Milani H., Steiner H., Huston JP (1989). Analysis of recovery from behavioral asymmetries induced by unilateral removal of vibrissae in the rat. Behav Neurosci 103: 1067-1074.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Moser VC, Ross JF (eds) (1996). Training Video and Reference Manual for a Functional Observational Battery. American Industrial Health Council, Washington, D.C.
  • Mueller K., Hollingsworth EM, Cross DR (1989). Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy. Psychopharmacology 97: 74-79.[CrossRef][Medline] [Order article via Infotrieve]
  • Oliver JE, Lorenz MD (1983). Handbook of Veterinary Neurologic Diagnosis. W. B. Saunders, Philadelphia.
  • Peele DB, Allison SD, Bolon B., Prah JD, Jensen KF, Morgan KT (1991). Functional deficits produced by 3-methylindole-induced olfactory mucosal damage revealed by a simple olfactory learning task. Toxicol Appl Pharmacol 107: 191-202.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pellis SM, Pellis VC, Chen YC, Barzci S., Teitelbaum P. (1989). Recovery from axial apraxia in the lateral hypothalamic labyrinthectomized rat reveals three elements of contract righting: Ceppalocaudal dominance, axial rotation and distal limb action. Behav Brain Res 35: 241-251.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pryor GT (1991). A toluene-induced motor syndrome in rats resembling that seen in some human solvent abusers. Neurotoxicol Teratol 13: 387-400.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ross JF (1988). Characterization of a murine model for human bismuth encephalopathy. Neurotoxicology 9: 581-586.[Web of Science][Medline] [Order article via Infotrieve]
  • Ross JF (1996). Distribution of bismuth in the brain after intraperitoneal dosing of bismuth subnitrate in mice: Implications for routes of entry of xenobiotic metals into the brain. Brain Res 725: 137-154.[Web of Science][Medline] [Order article via Infotrieve]
  • Ross JF, Handley DE, Fix AS, Lawhorn GT, Carr GJ ( 1997). Quantification of the hindlimb extensor thrust response in rats. Neurotoxicol Teratol 19: 405-411.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ross JF, Lawhorn GT (1990). ZPT-related distal axonopathy: Behavioral and electrophysiologic correlates in rats. Neurotoxicol Teratol 12: 153-159.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ross JF, Mattsson JL, Fix AS ( 1998). Expanded clinical observations in toxicity studies: Historical perspectives and contemporary issues. Regul Toxicol Pharmacol 28: 17-26.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Simon P., Dupuis R., Costentin J. (1994). Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 61: 69-64.
  • Steiner H., Bonatz AE, Huston JP, Schwarting R. (1988). Lateralized wall-facing versus turning as measures of behavioral asymmetries and recovery of function after injection of 6-hydroxydopamine into the substantia nigra. Exp Neurol 99: 556-566.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Symons LA, Tees RC ( 1990). An examination of the intramodal and intermodal behavioral consequences of long-term vibrissae removal in rats. Dev Psychobiol 23: 849-867.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Thinus-Blanc C., Save E., Poucet B., and Buhot MC (1991). The effects of reversible inactivations of the hippocampus on exploratory activity and spatial memory. Hippocampus 1: 365-371.[CrossRef][Medline] [Order article via Infotrieve]
  • Thinus-Blanc C., Scardigli P., and Buhot MC (1991). The effects of superior colliculus lesions in hamsters: Feature detection versus spatial localization. Physiol Behav 49: 1-6.[CrossRef][Medline] [Order article via Infotrieve]
  • Treit D., Fundytus M. (1988). Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol Biochem Behav 31: 959-962.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • US Environmental Protection Agency (1996). Health Effects Test Guidelines. OPPTS 870.6200. Neurotoxicity Screening Battery. Environmental Protection Agency Publication No 712-C-96-23B. Washington, D.C.
  • US Environmental Protection Agency (1997). Zeta-Cypermethrin. Pesticide tolerance. OPP-300577; FRL-5754-8. Fed Reg 62: 63235-63244.
  • US Environmental Protection Agency (1998). Fipronil. Pesticide tolerance. OPP-300612; FRL-5768-3. Fed Reg 63: 38483-38495.
  • US Environmental Protection Agency (1998). Guidelines for neurotoxicity risk assessment. Fed Reg 63: 26925-26954.
  • Whishaw IQ, Gorny B. (1999). Path integration absent in scent-tracking fimbria-fornix rats: Evidence for hippocampal involvement in "sense of direction" and "sense of distance" using self-movement cues. J Neurosci 19: 4662-4673.[Abstract/Free Full Text]
  • Whishaw IQ, Maaswinkel H. (1998). Rats with fimbria-fornix lesions are impaired in path integration: A role for the hippocampus in "sense of direction." J Neurosci 18: 3050-3058.[Abstract/Free Full Text]
  • Wineski LE (1982). Movements of the cranial vibrissae in the golden hamster (Mesocricetus auratus). J Zool Lond 200: 261-280.[Web of Science]

Toxicologic Pathology, Vol. 28, No. 1, 132-136 (2000)
DOI: 10.1177/019262330002800116
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Ross, J.F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ross, J.F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?