Behavioral Measures of Neurotoxicity (1990) / Chapter Skim
Currently Skimming:
Methods and Issues in Evaluating the Neurotoxic Effects of Organic Solvents
Methods and Issues in Evaluating the Neurotoxic Effects of Organic Solvents
Pages 159-183
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 159... ...
As a result, recommended occupational exposure limits for many of these compounds have been proposed (American Conference of Governmental Industrial Hygienists, 1986; NIOSH, 1987~. Despite the emphasis on the occupational setting, however, solvent exposure is not limited to the workplace.
|
From page 160... ...
By applying animal neurobehavioral methods to the study of solvents, the possibility of addressing many of the questions regarding solvent neurotoxicity is becoming increasingly feasible. The present chapter considers some of the interpretative issues that have developed regarding the risks to human health associated with solvent exposure and examines the possible use of animal behavioral methods in this area.
|
From page 161... ...
This may explain, in part, the modest effects seen in human exposure studies and the limited doseresponse data obtained. Application of Animal Behavioral Methods Acute Effects of Single Exposures Animal studies using operant techniques are being employed increasingly to examine the effects of inhaled organic solvent vapors on behavioral performance, and guidelines for the use of schedulecontrolled operant techniques for neurotoxicity evaluation have recently been proposed by the U.S.
|
From page 162... ...
Results from acute exposure studies conducted in our laboratory using positive reinforcement also indicate measurable effects of solvents at occupationally relevant levels. In a recent study, for example, the effects of low aromatic white spirits were examined in rats working on a two-choice visual discrimination task for water reward.
|
From page 163... ...
Thus, although the number of studies aimed at examining the acute behavioral effects of low-level solvent exposure is limited, the data available suggest that the rat may prove to be a more useful model for estimating human observable effect levels than might be expected on the basis of the results obtained in high-level, short-duration exposure studies.
|
From page 164... ...
As a result, acute solvent effects are usually mentioned only in passing in discussions of solvent neurotoxicity (Baker and Fine, 1986; Grasso et al., 1984; Spencer, 1985~. Different lines of evidence from the human literature, however, indicate that a need exists for more careful consideration of acute solvent effects particularly in the context of chronic exposure.
|
From page 165... ...
In studies investigating the effects of styrene on learned discrimination performance, we have also found a rapidly developing tolerance to the effects of styrene on speed and accuracy measures of discrimination performance during the first week of exposure. As Figure 2 shows, rats exposed to 100, 350, and 1,225 ppm of styrene for 18 hours a day and tested on a visual discrimination task (described above)
|
From page 166... ...
Given the indications from the human literature that similar phenomena also occur in exposed workers, and the problems associated with the interpretation of the nature of the deficits seen in occupational behavioral studies, it appears that animal studies examining
|
From page 167... ...
In addition to the social, psychological, and economic consequences of any addiction, the long-term abuse of solvent-containing products has been associated with a number of neurotoxic effects, including psychosis, hallucinations, sensory and motor disturbances, and convulsions. Although the acute encephalopathy produced by solvent inhalant abuse appears reversible in most cases, reports indicate that in some patients severe CNS effects may persist indefinitely (Boor and Hurtig, 1977; Grabsky, 1961; King, 1982; Knox and Nelson, 1966; Satran and Dodson, 1963; Weisenberger, 1977~.
|
From page 168... ...
CHRONIC SOLVENT EFFECTS ON THE PERIPHERAL NERVOUS SYSTEM The Role of Animal Studies The effects of organic solvents on the peripheral nervous system provide some of the strongest evidence for the potential of these compounds to produce irreversible nervous system damage, and animal studies have played an important role in both helping to identify the causative agent in outbreaks of human disease (Allen, 1980) and elucidating the underlying mechanisms of action.
|
From page 169... ...
Following the outbreak of human disease at a manufacturing plant in Texas, animal studies were undertaken which showed that dermal exposure to BHMH produced functional signs of peripheral neuropathy within three weeks of exposure (Spencer et al., 1985~. In addition, neuropathological studies indicated that BHMH exposure produced axonal degeneration of the optic tracts, ascending and descending spinal tracts, and peripheral nerve (Spencer et al., 1985~.
|
From page 170... ...
, for example, have demonstrated the utility of such an approach to study differences in the neurotoxic profiles of various compounds and to evaluate their relative neurotoxic potential. In our own laboratory, a battery of tests was developed to examine different types of disturbances in sensory-motor function, including changes in spontaneous activity, grip strength, coordinated hindlimb movement, and peripheral nerve conduction velocity (Kulig, 1989~.
|
From page 171... ...
the inte~ritv of nerinh~rA1 nerve function O ~ ~ ~ ~ ~ ~ ~ ~ is assessed by measuring the peak latency and amplitude of the compound nerve action potential measured noninvasively from the caudal nerve with techniques similar to those described by Rebert and his colleagues (Rebert et al., 1983~. In order to evaluate whether these tests were sufficiently sensitive and reliable for use in extended exposure studies, the effects of carbon disulfide (CS2)
|
From page 172... ...
0 6 12 18 24 30 36 42 WEEK OF EXPERIMENT FIGURE 5 Effects of carbon disulfide on hindlimb grip strength during and following 36 weeks of exposure. 90 80 70 60 50 40 30 10 o T C~ T ~ ~ ~ 1 1 ~ 0~018 ~ CS2 75 · ~ CS2 225 ~ ~ CS2 700 ppm 20 _ Exposure I 1 1 1 1 1 1 0 6 12 18 24 30 36 42 WEEK OF EXPERIMENT FIGURE 6 Effects of carbon disulfide on coordinated movement during and following 36 weeks of exposure.
|
From page 173... ...
Results indicated swollen axons and nerve fiber degeneration in the 700-ppm group in the sciatic, tibial, and caudal nerves as well as in the spinocerebellar tracts and the superior colliculus. Taken together, these data demonstrate the ability of currently available neurobehavioral methods to quantify the progressive development of chemically induced changes in peripheral nerve function and to study the relationship between neurofunctional changes and the morphological changes.
|
From page 174... ...
There is, however, a need in the further development of neurobehavioral methods to evaluate the long-term operating characteristics of any given test in order to better understand its strengths and limitations in the chronic exposure situation. CHRONIC TOXIC ENCEPHALOPATHY In addition to their effects on peripheral nerve, organic solvents have also been shown to produce irreversible effects on brain func
|
From page 175... ...
In addition, compared to nonexposed control subjects, exposed workers with no subjective symptoms or clinical signs of overexposure also showed changes in psychological test performance. The finding of psychological changes in the absence of overt signs and symptoms together with epidemiological studies indicating that occupational exposure to carbon disulfide in the viscose rayon industry was associated with higher rates of suicide (Mancuso and Locke, 1972)
|
From page 176... ...
Given the fact that the test instruments sensitive to the effects of acute solvent exposures in the experimental exposure situation are often the same as those that are sensitive in detecting changes in psychological functioning in cross-sectional occupational studies (Gamberale, 1985) , a differentiation of acute neurotoxicant effects from mild toxic encephalopathy based on the selection of the test instrument does not seem feasible.
|
From page 177... ...
As a result, the authors were forced to revise their earlier diagnoses of solvent-induced dementia and to conclude that the poor test performance of these patients was related not to solvent exposure, but to the lower level of intelligence and education in their subject sample. It is apparent from the discussion above that if appropriate controls are used, well-designed neurobehavioral studies can be used to evaluate acute neurotoxicant effects, to monitor the safety of workers exposed to known neurotoxic agents, and to identify possible occupational hazards.
|
From page 178... ...
Animal Models of Cognitive Effects Although the study of learning and memory has occupied the interest of psychologists for many years, some of the paradigms developed to study memory function, such as one-trial passive avoidance learning, are obviously unsuitable for repeated evaluation of cognitive changes in chronic exposure studies. There are, however, techniques described in the literature which, with further study, may provide useful approaches to examining those behavioral processes that would seem to be most likely affected by exposure to centrally acting neurotoxic agents.
|
From page 179... ...
Apparently, even the setting of occupational exposure limits to avoid acute, intoxicating effects on the nervous system has eluded an experimental basis. Moreover, psychologists working at the human level have been virtually left on their own to identify neurotoxic agents in the workplace and to sort out, as best they can, the complex issues surrounding chronic human exposures.
|
From page 180... ...
1979. Chronic painters syndrome: Chronic toxic encephalopathy.
|
From page 181... ...
1971. Psychological picture of manifest and latent carbon disulfide poisoning.
|
From page 182... ...
1979. A method for the routine assessment of fore- and hindlimb grip strength of rats and mice.
|
From page 183... ...
1981. Neurobehavioral toxicity of carbon disulfide.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.