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Currently Skimming:

The Scope and Promise of Behavioral Toxicology
Pages 395-414

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From page 395...
... Systemic toxicants, in contrast, are presumed to exhibit thresholds, perhaps at the point at which they overwhelm compensatory mechanisms.
From page 396...
... refers to the lowest exposure level producing statistically significant increases in the frequency or severity of adverse responses. Other effect levels are defined by similar standards.
From page 397...
... BEHAVIORAL PHARMACOLOGY With the introduction of the minor tranquilizing and antipsychotic drugs in the 1950s, and the demonstration that chemotherapy could be a legitimate option in the treatment of behavior disorders, an intense search began for new agents ~ It was accompanied by a swelling interest in the behavioral mechanisms underlying the clinical actions of these drugs. These two developments combined to establish a technology and a discipline hospitable to their goals.
From page 398...
... drugs are administered therapeutically at doses great enough to influence behavior, so that behavioral pharmacologists study high doses either to try to detect active agents or to differentiate their behavioral effects. A BT study might entail these aims as well, but must always consider the importance of its findings for risk estimates, which implies action at low doses.
From page 399...
... What we find currently in most assessments of animal behavior is an arbitrary selection of experimental parameters combined with relatively high exposure levels. We seem to have appropriated a technology without an appreciation of what that transfer of technology requires to make it work.
From page 400...
... The device itself, and the psychophysical procedures governing testing, are wholly inadequate for such a purpose, as so cogently discussed by Maurissen (1988~. Another example is the various reaction time measures included in many batteries.
From page 401...
... This is achieved, in higher animals, chiefly through the agency of the nervous system and by means of reflexes." Although Western scientists tend to view Soviet data with some skepticism, in part because the standards of scientific publication seem to be looser in the USSR, the Soviet approach still managed to generate enough curiosity in the West to stimulate tests of its validity. One aspect of Soviet doctrine that still separates it from Western toxicology, however, is the principle that any deviation from baseline functional parameters due to toxic exposure must be interpreted as an adverse effect (Glass, 1975~.
From page 402...
... · LEVER PRESSES ~ OBERNARD WEISS 12060 N = 4 120 RAT 1 ~~ 60 I\ 1 20 it.
From page 403...
... was preparing to respond to what later became the Toxic Substances Control Act, legislators in the United States were already drafting requirements that behavioral disturbances be included among the criteria of adverse effects. At present, several legislative initiatives and federal agencies define and regulate chemical exposures and include behavior among the aspects of toxicity to be considered in determining safety.
From page 404...
... The upper curve depicts the distribution of intelligence test scores for instruments such as the Stanford-B~net and Wechsler Intelligence Scale for Children. Its mean is 100 and its standard deviation is 15.
From page 405...
... Toxic Torts Litigation is exerting a significant impact on the acceptance of behavioral criteria of toxicity. Courts in the United States are now evaluating suits by workers claiming injury from exposure to organic solvents, metals, pesticides, and other neurotoxic substances.
From page 406...
... Here, the validation theme takes the form of chemically induced lesions and behavioral endpoints that are assumed to be analogues of human function such as short-term memory. The second theme, which I can amplification, addresses risk estimation directly and its ultimate goal of coupling exposure levels with risk incidence or severity.
From page 407...
... Delayed irreversible effects are associated, for example, with MPTP exposure in adults and methylmercury exposure in the fetus. Clinical and Behavioral Criteria For all these categories, our past evaluations of adverse effects were based largely on clinical endpoints, still the main basis for estimates of the hazards of systemic toxicants acting on organs other than the central nervous system.
From page 408...
... These are clinical criteria based on examinations conducted in rural Iraq, not on the kind of careful neuropsychological evaluation possible in major medical centers. It is provocative to consider what kind of results might have emerged from the application of what are considered to be more sensitive and specific tests currently found in neuropsychological testing centers, such the Bayley Scales of Infant Development used by Bellinger et al.
From page 409...
... Most of the six participating laboratories would have selected that dose, a total of 24 mg/kg, as the LOAEL, on the basis of indices such as maternal and offspring weight gain together with a variety of behavioral indices. Unfortunately, the protocols included neither sensitive morphological indices nor measurements of methylmercury tissue levels, so that a direct comparison with neurotoxic health risk estimates based on human data is not feasible, but crude parallels can be constructed from knowledge of levels prevailing in fish.
From page 410...
... Although no one disputes that such differences exist, that recognition exercises little influence on experimental design and analysis. Even in the laboratory within a group of rats of the same age and strain, we see remarkable differences in the behavioral response to toxicants such as lead and have had to develop special statistical techniques to quantify these differences.
From page 411...
... / _ . _—-In ~ ~ ~ 1 o 4.0 8.0 12.0 16.0 20.0 SCORE FIGURE 3 Hypothetical distributions showing interpretive difficulties arising from studies of populations comprised of both responders and nonresponders.
From page 412...
... REFERENCES American Conference of Governmental Industrial Hygienists.
From page 413...
... 1981. Modification of rat operant behavior by ozone exposure.


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