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Biomedical subjects

J V Setzer

Publications and source records attributed to J V Setzer.

At least 19 recordsLinked to original sources
PubMed1989

Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone.

A total of 137 volunteers were recruited and tested for neurobehavioural performance before, during, and after a short duration (4 h) exposure to acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a placebo. Ethanol (95%-0.84 ml/kg) was used as a positive control. Performance testing was computer controlled and took place in an environmental chamber with four test stations. The total test regimen before, during, and after exposure covered 10 hours and 32 measures were collected. The measurements were extracted from two biochemical (venous blood and alveolar breath) tests, four psychomotor (choice reaction time, visual vigilance, dual task (auditory tone discrimination and tracking), memory scanning) tests, one sensorimotor (postural sway) test, and one psychological (profile of mood states (POMS] test. The exposure to 250 ppm acetone produced small but statistically significant changes in performance from controls in two measures of the auditory tone discrimination task and on the anger hostility scale (men only) of the POMS test. Neither MEK nor the combined acetone/MEK exposures produced statistically significant interpretable results. The combination exposure provides some indication that there was no potentiation of the acetone effects with the coexposure to MEK or vice versa. More pronounced performance decrements occurred with ethanol at 0.07-0.08% BAC. Significant (less than 0.05) differences were evident on both the auditory tone and tracking tests in the dual task and there was partial significance on the visual vigilance test (0.05-0.06) and some postural sway measures (less than 0.09). These findings agree with an earlier Japanese study in showing some mild decrements on behavioural performance tests with exposures to acetone at 250 ppm.

Acetone↗
PubMed1988

Effects of short duration exposures to acetone and methyl ethyl ketone.

Workers are commonly exposed to mixtures or combinations of chemical agents, and these mixtures often consist of solvents. One group of solvents that has been extensively studied for its neurotoxic properties has been the ketones. However, previous research has focused on neuropathies produced by extended exposures and not on the simple pharmacokinetics or the reversible central nervous system (CNS) effects from short-duration exposures. In this research, 137 volunteers were recruited and tested for neurobehavioral performance changes and biochemical indicators during and after a short-duration (4-h) exposure to either acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a chemical-placebo. Ethanol (95%, 0.84 ml/kg) was used as a positive control. Testing took place in an environmental chamber with four test stations. The computer-controlled test regimen took 10 h, and several measures were collected: (1) biochemical measurements of venous blood and alveolar breath; (2) psychomotor tests of choice reaction time, visual vigilance, dual task (auditory tone discrimination and tracking), and memory scanning; (3) one sensorimotor (postural sway) test; and (4) one psychological (Profile of Mood States [POMS]) test. Blood and breath concentrations during and after exposure did not demonstrate any interaction between the two solvents, nor were statistically significant sex differences present during uptake or elimination. The 250-ppm acetone exposure produced small but statistically significant differences from controls in two measures of the auditory tone discrimination task, and on the anger-hostility scale (males only) of the POMS test. The other chemical exposure conditions, MEK at 200 ppm and combination MEK with acetone, produced no consistent statistically significant results, which suggests there was no potentiation of the acetone effects with the co-exposure to MEK or vice versa under these test conditions. Ethanol at 0.07-0.08% blood alcohol concentration (BAC) caused significant decrements on both the auditory tone and tracking tests in the dual task.

Acetone↗
PubMed1987

Body burden profiles of single and mixed solvent exposures.

The dynamics of inhaled solvents have not been studied extensively for exposure conditions involving combinations of chemical agents. An ongoing laboratory study examining psychomotor performance effects on human volunteers exposed to spray paint agents offered an opportunity to gather data on the body burden profiles produced by the inhalation of two solvents alone and in combination. Breath and blood samples were collected from 70 male and female subjects who were randomly assigned to four treatment conditions: chemical placebo, 250 ppm acetone, 200 ppm methyl ethyl ketone, or 125 ppm acetone/100 ppm methyl ethyl ketone. The exposures lasted for four hours. No interaction between the two solvents affecting uptake or elimination was noted. There were no significant differences between the uptake and elimination in males and females. The results are discussed in relation to physiological simulation modeling of the exposure.

Acetone↗
PubMed1986

Neurobehavioral evaluation of soil and structural fumigators using methyl bromide and sulfuryl fluoride.

Neurobehavioral functions affected by methyl bromide exposure were evaluated in California structural and soil fumigators using methyl bromide and sulfuryl fluoride. Sampling data revealed that structural fumigators are exposed for up to 1.5 hrs/day to 0-2.2 ppm methyl bromide and/or 10-200 ppm sulfuryl fluoride, and soil fumigators can be exposed to 2.3 ppm methyl bromide over an 8-hr day. Subjects were grouped for statistical analysis on the basis of exposure history: Those exposed primarily (80% or more of the work period with exposure potential) to methyl bromide (N = 32), primarily to sulfuryl fluoride (24), or to a combination of methyl bromide and sulfuryl fluoride (40-60% of each) for a minimum of one year (18), and those not exposed to high concentrations of any chemicals (29 Referents). Fumigators using methyl bromide reported a significantly higher prevalence of 18 symptoms consistent with methyl bromide toxicity than did Referents. Methyl bromide fumigators did not perform as well as Referents on 23 of 27 behavioral tests (chosen to reflect methyl bromide effects), and were significantly lower on one test of finger sensitivity and one of cognitive performance. These consistent differences suggest that even the low levels of methyl bromide found in fumigation today may produce slight neurotoxic effects. found in fumigation today may produce slight neurotoxic effects. The greater number of symptoms and reduced performance on all cognitive tests in sulfuryl fluoride fumigators compared to the Reference Group plus the absence of published research on this compound suggest that the data base for sulfuryl fluoride is inadequate.

Adult↗
PubMed1984

Effects of acute exposure of toluene and methyl ethyl ketone on psychomotor performance.

Organic solvents are used frequently in industry and workers are often exposed to various combinations of these chemicals. Several are CNS depressants, and the purpose of this experiment was to assess the behavioral effects of 4-hour inhalation exposures to two solvents, toluene and methyl ethyl ketone (MEK) alone and combined. Ethanol at 0.08% blood levels was used as a positive control. A total of 144 paid volunteers were randomly assigned to one of eight treatment combinations in a series of four two-group between subjects studies. Testing was carried out in an exposure chamber, and participants were tested before, during, and after the treatment or control condition on three performance tasks. The tasks measured alertness and psychomotor function and produced a total of 28 measures on each individual over the approximate 8 h of testing. Results indicated that toluene at 100 ppm produced a small but significant impairment on one measure of a visual-vigilance task by lowering the percentage of correct hits. MEK at 200 ppm produced no interpretable significant effects on any of these measures. Additivity was not evident when individuals were exposed to MEK (100 ppm) and toluene (50 ppm) in combination, as no significant performance differences were noted. Ethanol, at 0.08%, affected both the visual-vigilance and a choice-reaction time task at statistically significant levels on two measures, confirming the sensitivity of these two tasks to CNS depressants.

Adolescent↗
PubMed1984

Neurobehavioral assessment of chronic low-level methyl bromide exposure in the rabbit.

The research reported here was intended to identify the concentration at which methyl bromide begins to produce neurotoxic effects in the rabbit, a species known to be sensitive to this compound. Rabbits were exposed via inhalation to 27 ppm methyl bromide over a period of 8 mo for a total exposure duration of 900 h. Biweekly neurobehavioral tests, consisting of the latency rates of the ulnar and sciatic nerves and the amplitude of the eyeblink reflex of the orbicularis oculi muscle, failed to uncover any untoward consequences of the exposures. The rabbits gained weight and otherwise appeared to be healthy. In contrast to reports available in the literature, these findings suggest that long-term exposures to methyl bromide, in the present concentration range, are tolerated by this species. Also detailed in this report is the course of recovery of a separate group of rabbits previously given subchronic exposures to 65 ppm methyl bromide. These animals developed severe neuromuscular losses and had impaired blink reflexes and body weights. The symptoms partially subsided within 6-8 wk after removal from the exposures, suggesting that recovery from a nonfatal but seriously debilitating exposure is possible.

Animals↗
PubMed1984

Reproductive toxicity of the industrial solvent 2-ethoxyethanol in rats and interactive effects of ethanol.

The solvent, 2-ethoxyethanol, induced complete embryomortality in pregnant rats exposed to three times the current Federal permissible exposure limit (PEL). Following exposure to ethoxyethanol at a concentration only one-half the current PEL, the offspring evidenced behavioral and neurochemical deviations from controls. Subsequent studies found that ingestion of ethanol with concomitant inhalation of ethoxyethanol vapors early in pregnancy appeared to reduce the number of both behavioral and neurochemical deviations found for ethoxyethanol. In contrast, the concomitant exposure to ethanol and ethoxyethanol later in gestation potentiated the behavioral and neurochemical effects of ethoxyethanol. This research indicates that the industrial solvent 2-ethoxyethanol presents an occupational reproductive hazard and raises the issue of the importance of an interaction of social habits with occupational exposure to such hazards. The results would suggest that occupational physicians should advise pregnant workers in the chemical industry of the adverse effects of ethanol during pregnancy and of the possible interactions with other chemicals and should encourage them to be especially cautious with ethanol consumption since they may be at greater risk.

Air Pollutants, Occupational↗
PubMed1984

Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats.

Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.

Abnormalities, Drug-Induced↗
PubMed1981

Methyl chloride and diazepam effects on performance.

Human behavioral effects resulting from the ingestion of an average dose of diazepam and from 3 h of inhaling either 100 ppm or 200 ppm of methyl chloride (MeCl) were studied in the laboratory. Each of 56 volunteers was randomly assigned to one of six groups comprising the combinations of diazepam and placebo and one of the two levels of MeCl plus control. Each individual was tested in an environmental room on three tasks involving components of eye-hand coordination, mental alertness, and time discrimination. Both pretreatment and treatment data were obtained. Diazepam produced a significant 10% impairment in task performance, whereas the effect of 200 ppm of MeCl was marginally significant (average performance impairment of 4.5%). When the two agents were combined, total impairment was equal to the sum of the individually induced losses. Large interindividual differences in breath and blood levels were found for MeCl.

Adolescent↗
PubMed1981

Ethoxyethanol behavioral teratology in rats.

2-ethoxyethanol, a solvent developed for nitrocellulose and also used in lacquers, dyes, varnish removers, and in numerous industrial processes, was evaluated for possible functional effects in offspring of rats exposed during gestation. A dose finding study revealed that no offspring survived inhalation exposure (7 hours/day) from gestation days 7-13 or 14-20 at 900 ppm, and there were approximately 34 percent neonatal deaths even after prenatal exposure to 200 ppm-the current Federal occupational standard. Consequently, pregnant Sprague-Dawley rats were exposed to 100 ppm ethoxyethanol for 7 hours/day on gestation days 7-13 or 14-20. The only effect observed in the mothers was slightly prolonged gestation in he mothers exposed on days 14-20 of gestation (p less than .001). Behavioral testing of offspring from dams exposed to ethoxyethanol on gestation days 7-13 revealed: (a) impaired performance on a rotorod test of neuromuscular ability (p = .002); (b) prolonged latency of leaving the start area of an open field (p = .009); and (c) marginal superiority in avoidance conditioning begun on day 34 of age (p = 061). Offspring from dams exposed to ethoxyethanol on gestation days 14-20: (a) were less active than controls in a running wheel (p = 0.32), and (b) received an increased number and duration of shocks in avoidance conditioning begun on day 60 of age (p = .004). Neurochemical evaluation of whole-brain samples from newborn pups revealed significantly decreased levels of norepinephrine in offspring from both exposure periods (p less than .01). In regional analyses of brains from 21-day-old offspring of dams exposed to 100 ppm ethoxyethanol on gestation days 7-13, the cerebrum had significant elevations in acetylcholine (p less than .01), norepinephrine ( p less than .01), and dopamine (p less than .05), the cerebellum had nearly a 3-fold increase in acetylcholine (p less than .01); the brainstem had an increase in norepinephrine (p less than 0.01); and the midbrain had excesses of acetylcholine (p less than .01), norepinephrine (p less than .05) and protein (p less than .05). In brains from 21-day-old offspring of dams exposed to ethoxyethanol on gestation days 14-20, the cerebrum had significant elevations in acetylcholine, dopamine, and 5-hydroxytryptamine (p less than .05). Overall, the results indicate that there are behavioral and neurochemical alterations in offspring of rats following prenatal exposure to 100 ppm ethoxyethanol.

Animals↗
PubMed1981

Neurobehavioral effects of methyl bromide inhalation exposures.

Methyl bromide, a neurotoxic agent with a permissible US exposure limit of 20 ppm, is used primarily as a fumigant by an estimated 75,000 workers in the United States. This project was developed to evaluate the neurobehavioral effects of chronic and subchronic exposure to methyl bromide. One group of rats and rabbits was exposed to 65 ppm of methyl bromide for a total exposure of four 25-h weeks, or 100 h, and rats were exposed to 55 ppm of methyl bromide for a total exposure of 36 30-h weeks, or 1,080 h. Comparable control groups were given similar treatment, but no exposure. Behavioral tests of open field activity and limb coordination were conducted weekly during both phases of the experiment with rats, and eyeblink reflexes were measured weekly in rabbits. Nerve conduction velocity measurements were taken weekly from both rats and rabbits during the 65-ppm four-week exposures and monthly from rats during the 55-ppm 40-week exposures. Exposure to 65 ppm for four weeks significantly reduced eyeblink responses and nerve conduction velocity in rabbits but had no effect on rats. Exposure to 55 ppm of methyl bromide for 36 weeks had no effect on nerve conduction velocity, open-field activity, or coordination in rats.

Animals↗
PubMed1979

Effects of oral and intramuscular carbaryl administrations on repeated chain acquisition in monkeys.

A type of learning task was utilized to determine the effective dose of carbaryl on Macaca fascicularis for both oral and in routes of administration. Monkeys were required to press four buttons in a set order; the order was changed daily. A baseline reversal design was utilized to test all animals several times at each concentration. The im carbaryl injections resulted in consistent, statistically reliable decrements in total session time and increases in errors at 5 and 10 mg/kg for the 4 animals in this section of the experiment, but produced no change in performance at 1 mg/kg. Errors increased in 3 of 4 monkeys after 3 mg/kg injections. Oral doses as high as 50 mg/kg were not consistently effective in changing performance on the task in any of 5 animals included in this section of the experiment. Some support was given to the suggestion that monkeys are more tolerant of carbaryl than are rats. These are the first reported effects (other than the LD50) of carbaryl in monkeys.

Administration, Oral↗
PubMed1978

An electrodiagnostic study of the neurotoxicity of methyl n-amyl ketone.

The neurotoxicity of methyl n-amyl ketone was investigated in a chronic inhalation study lasting 9 months. Rats and monkeys were exposed 6 hrs/day, 5 days/week, to mean MAK levels of 0, 131, and 1025 ppm. Electrodiagnostic measures of nervous system function revealed no neurotoxic impairment at either MAK exposure. Body weights were similarly unaffected. Gross and histopathology also indicated no adverse effects of MAK. It was concluded that MAK does not possess neurotoxic properties similar to those possessed by methyl n-butyl ketone.

Action Potentials↗
PubMed1977

Effects of methyl n-butyl ketone behavior and the nervous system.

The effects of methyl n-butyl ketone (MBK) on nervous system function and operant behavior were investigated in monkeys and rats. Mean MBK exposure levels approximated 100 and 1000 ppm and lasted up to 10 months. Both exposures were 6 hours/day 5 days/week. Results showed that the 1000 ppm exposure effected 1) reduced motor conduction velocities in ulnar and sciatic-tibial nerves, 2) decreased the amplitude of evoked muscle action potentials, 3) lengthened implicit time of visual evoked potentials, 4) impaired operant behavioral performance, and 5) reduced body weight. Reductions in nerve conduction velocities and evoked muscle action potentials were found at 100 ppm. Recovery, as measured by sciatic-tibial nerve conduction velocity, was found to occur 6 months and 2 months after termination of the 1000 ppm and 100 ppm MBK exposures, respectively.

Action Potentials↗
PubMedDate not supplied

Neurophysiological and neuropathological evaluation of primates exposed to ethylene oxide and propylene oxide.

Over 500,000 workers in the United States are exposed to ethylene oxide and propylene oxide. These two solvents are used as chemical intermediates, as well as components in the manufacture of fumigants and food preparation. The neurophysiologic and neuropathologic effects of these two organic oxides were investigated in five groups of 12 primates after exposure to 50 or 100 ppm ethylene oxide, 100 or 300 ppm propylene oxide, or no chemical (sham-exposed). Animals were exposed for 7 h/day, 5 days/wk for 24 months. Body weights, electroencephalograms, and motor nerve conduction velocities of the sciatic and ulnar nerves were assessed six times throughout the exposure period. Although the monkeys exposed to 100 ppm ethylene oxide had significantly lower mean weights, nerve conduction velocities did not differ significantly among the groups. Following termination of exposures, ten animals (two from each exposure group) were sacrificed for neuropathological examinations. Multiple axonal bodies were found in the nucleus gracilis in seven of eight oxide-exposed animals, and demyelination was found in two monkeys exposed to ethylene oxide. In contrast, a single axonal body was found in one of the two sham-control monkeys. However, the lack of a dose-response relationship suggests that this effect may not be related to oxide exposure. In a follow-up study, nerve conduction velocity and neuropathology were assessed in the remaining monkeys seven years after exposure terminated, but again, treatment-related effects could not be detected.

Action Potentials↗
PubMedDate not supplied

Neurobehavioral effects of methyl N-butyl ketone and methyl N-amyl ketone in rats and monkeys: a summary of NIOSH investigations.

The results from four NIOSH investigations concerning the neurobehavioral effects of methyl n-butyl ketone (MBK) and methyl n-amyl ketone (MAK) on experimental animals are summarized. The investigations were initiated following clinical reports of neurologic sequelae in humans exposed to these ketone solvents. In order to explore both acute and chronic effects of MBK and MAK, two general types of studies were conducted: 1) neurophysiologic evaluation of monkeys and rats following chronic inhalation, and 2) behavioral effects in rats following oral or intraperitoneal administration. Results from chronic inhalation studies after 4 months of 1000 ppm MBK exposure (all exposures: 6 hrs/day, 5 days/week) showed the following: decreased motor nerve conduction velocities (NCV) in the ulnar and sciatic-tibial nerves, reduced amplitude of evoked muscle action potentials (MAP), lengthened latency of components of the visual evoked brain potential, decreased body weight, and hindlimb drag. Decrements in sciatic-tibial NCV and MAP amplitude were found after 9 months exposure to 100 ppm MBK. In contrast, exposure to approximately 1000 ppm MAK for 9 months had no adverse affects on neurophysiologic indicators of nervous system integrity. Dose-response investigations of the effects of MBK (oral) and MAK (ip) showed for both solvents a reduction in the response rate of rats trained on a multiple schedule of reinforcement.

Action Potentials↗