ASSESSMENT OF CHEMICALS USING A BATTERY OF NEURO-BEHAVIORAL TESTS - A COMPARATIVE-STUDY

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 5  (1) , 91-117
Abstract
Single-dose LD10 [10% of the lethal dose] and LD50 were determined in male, Fischer-344 rats for acrylamide monomer, arsenic trioxide, chlordecone, lead acetate, methylmercury hydroxide, monosodium salicylate, tetraethyl tin and triethyl lead chloride. Proportions of the single-dose LD10 were used in a subacute study to estimate the 28 day old LD20 [20% of the lethal dose] for each chemical. Proportions of the 28 day LD20 were used in a subchronic (105 days of dosing) study to determine the effectiveness of a battery of neurobehavioral tests for detecting and characterizing the neurotoxic effects of each chemical. The battery consisted of undifferentiated motor activity, forelimb and hindlimb grip strengths, rotation orientation, thermal sensitivity, startle responsiveness to acoustic and air-puff stimuli, and performance of a multisensory conditioned pole-climb avoidance response task [CAR]; body weight and rectal temperature were also monitored. The battery of tests was administered on 8 occasions, before, at 3 wk intervals during dosing (oral or i.p. 5 days/wk for 15 wk) and at 3 and 6 wk after dosing. Normative data (controls from each experiment) indicated fair overall stability of the measures over the 8 test sessions, but experiment-to-experiment variability in this regard was clearly evident. The inherent statistical sensitivity of the tests varied greatly as estimated by their coefficients of variation, which ranged from 1% (rectal temperature) to > 100% (rotation orientation). Intercorrelations among the various measures were low to moderate indicating relatively little redundancy. The various measures were differentially affected by the 8 chemicals: body weight by all 8, rectal temperature by 1, undifferentiated motor activity by 3, forlimb grip strength by 2, hindlimb grip strength by four, rotation orientation by 1, thermal sensitivity by 1; startle responsiveness by 3, and CAR performance by 5. A profile analysis using the slopes of the dose-response functions after 15 wk of dosing indicated clearly different patterns of effect among the 8 chemicals. A composite score derived from a multidimensional analysis of the data suggested that the 8 chemicals could be ranked from most to least neurotoxic as defined by these tests as acrylamide > methylmercury > chlordecone > tetraethyl tin > triethyl lead > lead acetate > arsenic > monosodium salicylate. This ranking and the results in general were in good agreement with what was known about these chemicals from other experiments with animals and from human experience. This battery of tests, or subsets thereof, may have utility in the assessment of the potential neurobehavioral toxicity of various chemicals.