Neurobehavioral screen

An early assumption in developing this screen was that a starting point should be a methodology familiar to laboratory animal veterinarians. If as many as possible of the actual evaluations incorporated into the screen were adapted from familiar canine neurologic examination procedures, this should confer a significant benefit. This approach governs the methodology employed for evaluation. 

General Observations The following assessments are to be made with the dog walking about freely in the procedure room. All end points (other than body temperature, heart rate, and where otherwise noted) are scored on a scale of 1 (least response) to 5 (greatest response), with a score of 3 denoting a normal response. 

Palpatation The head, trunk, and limbs are palpated to assess the 

1 Musculoskeletal Head, neck, limbs, and trunk are palpated, noting any evidence of muscular atrophy (local or generalized), twitching, or other involuntary muscular actions. 

Cranial Nerves Routine assessment of the cranial nerves is performed as follows  

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To simplify this presentation, datasets drawn only from neuromuscular screening activity were used. However, the evaluation and approaches should be valid for all similar screening datasets, regardless of source. The methods are not sensitive to the biases introduced by the degree of interdependence found in many screening batteries that use multiple measures (such as the neurobehavioral screen). 

Moser, V.C., Becking, G.C., MacPhail, R.C., and Kulig, B.M., The IPCS collaborative study on neurobehavioral screening methods, Fundam. Appl. Toxicol., 35,143-151,1997. 

Moser, V. C., G. C. Becking, V. Cuomo, et al. The IPCS collaborative study on neurobehavioral screening methods IV. Control data. Neurotoxicol. 18 947-967, 1997. 

Moser, V.C. (1995). Comparisons of the acute effects of cholinesterase inhibitors using a neurobehavioral screening battery in rats. Neurotoxicol. Teratol. 17 617-25. 

The protocols in this unit are divided into (1) observational assessments, and (2) manipulative tests. Each protocol is further subdivided into specific tests or endpoints (Table 5.4). These various end points may be combined into a battery of tests for neurobehavioral screening. Most or all of these protocols or end points should be used in the context of a broad neurobehavioral test battery, whereas judicious selection of specific end points may be appropriate for more focused neurological testing. Originally developed by Gad [4], Moser [7], and Moscardo [8], the functional observational battery provides excellent detailed descriptions of the method using rats, the most common species used. 

Zhu, Y., et al.. Analysis of neurobehavioral screening date dose-time-response modeling of continuous outcomes. Regulatory Toxicology and Pharmacology 2005,41 240-255. 

MacPhail RC, Tilson HA, Moser VC, Becking GC, Cuomo V, Frantik E, Kulig BM, Winneke G (1997) The IPCS collaborative study on neurobehavioral screening. Background and genesis. Neurotoxicology 18 925-928... 

Mattsson JL, Spencer PJ, Albee RR (1996) A performance standard for clinical and functional observational batter y examinations in rats. J Am Coll Toxicol 15 239-254 McDaniel KL, Moser VC (1993) Utility of neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypeimethrin. Neurotoxicol Teratol 15 71-83 Meng Y, Dukat M, Bridgen DT, Martin BR, Lichtman AH (1999) Pharmacological effects of methamphetamine and other stimulants via inhalation exposure. Drug Alcohol Depend 53 111-120... 

Moser VC, Cheek BM, MacPhail RC. 1995. A multidisciplinary approach to Toxicological screening III. Neurobehavioral toxicity. J Toxicol Environ Health 45 173-210. 

Moser, V.C., Cheek, B.M. MacPhail, R.C. (1995) A multidisciplinary approach to toxicological screening 111. Neurobehavioral toxicity. J. Toxicol environ. Health, 45, 173-210 Miiller-Tegethoff, K., Kasper, P. Muller, L. (1995) Evaluation studies on the in vitro rat hepatocyte micronucleus assay. Mutat. Res., 335, 293-307 Murray, H.E., Ray, L.E Giam, C.S. (1981) Phthalic acid esters, total DDTs and polychlorinated biphenyls in marine samples from Galveston Bay, Texas. Bull, environ. Contam. Toxicol, 26, 769-774... 

The Neurobehavioral Evaluation System 2 (NES2) is a neurobehavioral evaluation system designed to facilitate screening of populations at risk of nervous system damage due to environmental agents. This evaluation system is administered on a microcomputer. Epidemiologic research influenced the sets of tests that were included in this battery. An expert committee convened by the World Health Organization (WHO) and the National Institute for Occupational Safety and Health (NIOSH) proposed a set of core tests for this battery. Many of the core tests that were... 

A minimal risk level (MRL) is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration and route of exposure. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and others to identify contaminants and potential health effects thai may be of concern at hazardous waste sites. The chronic-duration oral MRL of 1 picogram/kilogram/day or pg/kg/day for TCDD, or total TEQs, (ATSDR 1999) was based on neurobehavioral effects in monkeys. Based on this value, an EMEG of 50 ppt (0.05 ppb) TCDD, which is equivalent to 50 ppt (0.05 ppb) TEQs, was derived for exposure from contaminated soil. Uncertainty factors of 90 (total) were used in the calculations of the MRL (for further details, see ATSDR 1999). Based on a review of more recent literature, ATSDR scientists conclude that the MRL of 1 pg/kg/day is approximately two orders of magnitude below the noncancer health effect levels observed in recent studies. This is also true for cancer effect levels. 

Assessments of motor function are often included in the neuropsychological test batteries utilized in occupational exposure studies. Typically, these tend to be relatively simple measures of motor capabilities, probably for two reasons. The first is that the inclusion of vigilance tasks such as those described previously depends on motor coordination in addition to sensory capabilities therefore, toxicant-induced changes in such performances may already be indicative of motor impairment. This can then be pursued by inclusion of some additional and more direct assessments of motor function in the battery. The second reason relates to logistical reasons and practicalities. Test batteries such as the WHO Neurobehavioral Core Test Battery and the NFS are typically taken to the site where measurements of subjects are to be made. Thus, portability is a major consideration, and more complex assessments of motor function would incur greater equipment needs. Since the purpose of these batteries is generally to screen for adverse effects, studies providing more precise delineations of affected functions can be pursued at a later time. 

The examples of tests presented in each section are certainly not exhaustive but were chosen because they are often used or because they promise to contribute substantially to the understanding of behavioral toxicity. The first step in a tier approach is a neurobehavioral observational screen, the tool of choice for initial identification of potentially neurotoxic chemicals. The use of such screens, other behavioral tests methods, or what are generally called clinical observations does, however, warrant one major caution or consideration. That is, short-term (within 24 h of dosing or exposure) observations are insufficient on their own to differentiate between pharmacological (reversible in the short term) and lexicological (irreversible) effects. To so differentiate, it is necessary to either use additional means of evaluation or have the period during which observations are made extended through at least 3 or 4 days. 

Bushnell. P. J., Moser, V. C.. and Samsam. T. E. (2(X)1). Comparing cognitive and. screening tests fur neurotoxicity Effects of acute chlotpytifos on visual signal detection and a neurobehavioral test battery in rats. Neun toxicol Teratol 23, 33-44. 

Maternal depressive symptoms are associated with neurodevelopmental patterns of reduced arousal and increased stress. Among 13 808 screened subjects from Honolulu, 1632 were eligible and 176 mothers were enrolled prenatal metamfetamine exposure combined with maternal depression was not associated with any additional neurodevelopmental differences [35 ]. When adjusted for co-variates, metamfetamine exposure was associated with lower arousal and higher lethargy scores. Only 136 biological mothers with child custody (50 of whom had used metamfetamine) had the Addiction Severity Index (ASI) administered at 1 month. The NICU Network Neurobehavioral Scale (NNNS) was administered to the neonate within the first 5 days of fife by an examiner blinded to metamfetamine exposure. There were several limitations to this study. The severity of depression in the mothers was assessed not at the neonatal visit but after 1 month. Since only the biological mothers were included in the study, the sample size was limited, because several infants who had been exposed to metamfetamine were placed in foster care or the care of relatives, so that data from their biological mothers was not assessed. 

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