A Proposed Working Definition for the Novel Concept of Neurobehavioral Hormesis

It is proposed that a novel concept, neurobehavioral hormesis, be considered for integration into the field of toxicology. Hormesis results in a non-linear dose response where low dose exposures to toxicants cause beneficial effects, and detrimental effects at higher doses. Hormesis has not been systematically incorporated into traditional risk assessment methodologies, yet there is recent evidence that this pattern of results is relatively prevalent. In this paper, hormesis is applied to neurobehavioral toxicology, and an operational definition is proposed for application to putative examples of neurobehavioral hormesis. The two primary criteria used for the operational definition are: (1) performance is enhanced with low dose exposure and denigrated at higher doses, and (2) the change in behavior persists following a recovery period. In recent research from our laboratory it was reported that rats exposed to JP-8 jet fuel vapor demonstrated such a pattern of neurobehavioral performance on tests of learning and memory. Specifically, animals with long-term exposure to low concentrations of jet fuel demonstrated enhanced performance on specific operant tasks as compared both to controls and to animals exposed to higher concentrations. The effect was most apparent during complex versus simple operant tests, and was observed months following the last exposure to jet fuel. The effects meet both criteria for the proposed working definition of neurobehavioral hormesis, and thus provide evidence of the validity for considering neurobehavioral hormesis in published and future research, and suggests a more systematic investigation of existing literature may be warranted. Also, it provides additional support for the overall proposal to include hormetic effects in formal risk assessment paradigms.

[1]  Yoko Hirata,et al.  Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in rat striatal tissue slices , 2001, Neuroscience Letters.

[2]  Incorporating hormesis in the routine testing of hazards , 1998, Human & experimental toxicology.

[3]  Y. Dragan,et al.  Implications of hormesis on the bioassay and hazard assessment of chemical carcinogens , 1998, Human & experimental toxicology.

[4]  E. Calabrese,et al.  Reevaluation of the Fundamental Dose–Response Relationship , 1999 .

[5]  E. Calabrese,et al.  Hormesis as a default parameter in RfD derivation , 1998, Human & experimental toxicology.

[6]  G. Wenger.  The effect of phencyclidine and ketamine on schedule-controlled behavior in the pigeon. , 1976, The Journal of pharmacology and experimental therapeutics.

[7]  Balster Rl,et al.  The effects of acute and repeated toluene exposure on operant behavior in mice. , 1981 .

[8]  S. Wolff,et al.  Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. , 1984, Science.

[9]  H. Wada.  Toluene and temporal discrimination in rats: effects on accuracy, discriminability, and time estimation. , 1999, Neurotoxicology and teratology.

[10]  I. Kennedy,et al.  Effect of lithium and lanthanum on herbicide induced hormesis in hydroponically‐grown cotton and corn , 1997 .

[11]  A. Appleby,et al.  PLANT GROWTH STIMULATION BY SUBLETHAL CONCENTRATIONS OF HERBICIDES , 1972 .

[12]  I. Geller,et al.  Effects of acetone and toluene vapors on multiple schedule performance of rats , 1979, Pharmacology Biochemistry and Behavior.

[13]  E. Calabrese.  Expanding the reference dose concept to incorporate and optimize beneficial effects while preventing toxic responses from nonessential toxicants. , 1996, Regulatory toxicology and pharmacology : RTP.

[14]  R. Yerkes,et al.  The relation of strength of stimulus to rapidity of habit‐formation , 1908 .

[15]  R. Balster,et al.  A direct comparison of inhalant effects on locomotor activity and schedule-controlled behavior in mice. , 1998, Experimental and clinical psychopharmacology.

[16]  C. Dallas,et al.  Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations. , 1998, Neurotoxicology and teratology.

[17]  E J Calabrese,et al.  Hormesis: A Highly Generalizable and Reproducible Phenomenon With Important Implications for Risk Assessment , 1999, Risk analysis : an official publication of the Society for Risk Analysis.

[18]  R. Viale,et al.  Membrane-associated thiamin triphosphatase. II. Activation by divalent cations. , 1976, The Journal of biological chemistry.

[19]  Donald J. Himnan.  Tolerance and reverse tolerance to toluene inhalation: Effects on open-field behavior , 1984, Pharmacology Biochemistry and Behavior.

[20]  E J Calabrese,et al.  Chemical hormesis: its historical foundations as a biological hypothesis , 2000, Human & experimental toxicology.

[21]  E. Calabrese,et al.  The Dose Determines the Stimulation (and Poison): Development of A Chemical Hormesis Database , 1997 .

[22]  A. Stebbing,et al.  Hormesis--the stimulation of growth by low levels of inhibitors. , 1982, The Science of the total environment.

[23]  W. Allender.  Effect of trifluoperazine and verapamil on herbicide stimulated growth of cotton , 1997 .

[24]  E. J. Calabreseci.  Evidence that hormesis represents an "overcompensation" response to a disruption in homeostasis. , 1999, Ecotoxicology and environmental safety.