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.

Prevalence and differentials of low birth weight in Niamey, Niger.

This study provides population representative data on live births occurring in Niamey, Niger during the period 1980 to 1985. A total of 5097 live births were systematically sampled from maternity registers over the study period. Due to legislation and incentives to register all live births, between 90 and 95 per cent of all live births are represented in this study. The data here suggest that low birth weight (LBW) prevalence may be lower in this urban area than it is in the region as a whole; and that the demographic risk factors are similar to those found in other developing countries. Finally, in many developing countries, maternity coverage of attended births may be quite high, suggesting that record or prospective studies examining trends in LBW and risk factors for perinatal outcomes might be convenient and implemented at very low cost.

Development of information-based planning in Niger.

The authors present their experiences in assisting the government of Niger to develop automated information systems for health care management. They discuss the structure of the health system, the role of donor assistance, the process of initiating automated systems, and the technical requirements and costs of the system. Finally, they draw general conclusions that may be useful for those attempting similar efforts.

Neurobehavioral effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone.

Subjects were tested for neurobehavioral performance in an environmental chamber to detect the presence of subclinical central nervous system effects from 4-hr exposures to methyl isobutyl ketone (MIBK) at 100 ppm, methyl ethyl ketone (MEK) at 200 ppm, MIBK at 50 ppm with MEK at 100 ppm, or a placebo (i.e., a 5-min presentation of 25 ppm MEK-MIBK at each exposure period outset). Subjects were 68 males and 75 females recruited from local universities; ages ranged from 18 to 32 years. Ethanol by ingestion (95%-0.84 ml/kg) was used as a positive control. Five psychomotor tests (choice reaction time [CRT], simple reaction time [SRT], visual vigilance, dual task [auditory tone discrimination and tracking], memory scanning), one sensorimotor test (postural sway), and a test of mood (profile of mood states) were used to measure neurobehavioral effects. Additionally, chemical measurements (blood and breath) and reports of sensory and irritant effects were measured. The chemical exposures produced statistically significant performance effects on only 4 of 32 measures (% correct responses-visual vigilance, movement time-CRT, SRT, % incorrect responses-dual task). These effects, however, were not substantial and could not be attributed directly to the chemical exposures. Alcohol ingestion, however, produced significant decrements on every performance test except memory scanning and mood. An interaction occurred between gender and alcohol ingestion, such that more statistically significant performance decrements were found for females than for males. Significant odor sensations and irritant effects were reported by the subjects during the chemical exposures. The MEK results agree with earlier MEK experiments at comparable exposure conditions, and the MIBK results are consistent with a recent Swedish study that used MIBK exposures and showed no significant behavioral performance decrements from single MIBK exposures at 50 ppm with 50 W exercise. Additionally, the MIBK-MEK combination exposure showed no evidence of any interaction effects on either the behavioral or chemical measurements. The principal effects resulting from exposures to MEK and MIBK at the durations and concentrations used in the study are limited to sensory and irritant effects.

Comprehensive school-based services for pregnant and parenting adolescents in West Dallas, Texas.

A cohort of 339 Black (n = 210), Hispanic (n = 118), and other (n = 11) adolescent mothers in Dallas, Texas, were followed from the start of their pregnancy through the school year of the delivery to assess differences in numbers of prenatal care visits, postpartum care, repeat deliveries, and school continuation rates. Approximately one-half the teens received reproductive services at a comprehensive, school-based clinic and one-half at a categorical (Title XX) family planning and prenatal care clinic. Adolescents attending the school-based clinic were more likely to be in school at conception and averaged more prenatal visits than those served by the categorical provider. However, during the pregnancy and following the delivery, school dropout rates for the two sets of teens converged. School continuation rates were higher among a subset of adolescents attending the Dallas Independent School District school for pregnant teens than among other teens. Hispanic teens were two times more likely than their Black counterparts to drop out of school. No differences were found in repeat birth rates, by ethnicity, clinic site, or school attended.

Pediatric AIDS: adolescence, delinquency, drug abuse, and AIDS.

Sexual promiscuity often is part of the lifestyle of teenagers who are delinquent and abuse drugs, and that behavior puts them at increased risk of contracting HIV infection/AIDS. Many of these juveniles are runaways or live in disorganized homes, and as a result they are hard to reach and it is extremely difficult to provide health and other services to them. Indeed, these youths at risk most frequently may be identified and helped when they run afoul of the law and enter the judicial system. With that in mind, concerned professionals in San Antonio have developed an innovative program to provide primary care, drug abuse treatment and rehabilitation, and AIDS prevention education to the youthful offenders admitted to the Juvenile Detention Center of Bexar County. They hope it will give some of these youngsters the help and the opportunity they need to grow up, become productive citizens, and stay alive.

Pediatric AIDS: psychosocial impact.

There is no question that the domain of the American family has been invaded by the HIV infection/AIDS epidemic. The disease, and particularly its form affecting children (pediatric AIDS), has had marked psychosocial impact on patients and families (intellectual/cognitive, emotional/behavioral, spiritual, and financial) and on our society in general (adverse or favorable). These impacts of pediatric AIDS are discussed in the present communication.

Pediatric AIDS: systematic approach to patient management.

In order to provide comprehensive care to infants, children, and adolescents with HIV infection/AIDS, a systematic approach to clinical management had to be developed. This approach involves "case management" by experienced health professionals, including initial evaluation and needs assessment, planning of services, brokerage of services, continuity of intervention until an outcome is reached. The care is delivered in hospitals, clinics, homes, residential facilities, respite care centers, and hospices. The care team needs to be multidisciplinary and well integrated.

Pediatric AIDS: impact on health systems.

For 9 years we have recognized HIV infection/AIDS as an unstoppable epidemic affecting infants, children, and adolescents as well as adults. Now we see the tremendous impact of this disease on the health systems of this country. During these past 9 years, we have witnessed the transformation of the epidemic from one primarily affecting male homosexuals to one invading the average US family through heterosexual and vertical transmissions and through needle-sharing practices of intravenous drug abuse. It has been estimated that 2% to 3% of the HIV infection/AIDS cases involve the pediatric age group. If 1.5 million Americans have HIV infection by 1991, as predicted, we should anticipate 30,000 to 45,000 infected pediatric patients by the end of that year. What has been the impact of this epidemic on the health systems involved in care, prevention, and research of pediatric HIV infection/AIDS? This article investigates that question.

Blood coagulation factors in the elderly.

To investigate causes of the age-dependent increase of thromboembolic events, plasma coagulation parameters were determined in healthy elderly blood donors in comparison with young, and elderly diseased blood donors. Partial thromboplastin and thrombin clotting times were slightly shortened, whereas prothrombin and reptilase clotting times were unaltered. Plasma concentration of clotting factors like F I, VII, VIII: C, X, HMW-kininogen and prekallikrein were increased, whereas the coagulation inhibitor antithrombin III was decreased. Concerning fibrinolysis, plasminogen and alpha-2-antiplasmin were not affected by age, but plasminogen activators in the euglobulin fraction were lower. This shift in the pattern of coagulation factors favors enhanced fibrin formation and delayed fibrinolysis in the elderly. Higher intermediary products demonstrate that activation of coagulation and fibrinolysis happen more often in elderly healthy people. Together with blood stasis and vessel wall damage, this shift of the hemostatic balance contributes to a higher incidence of thromboembolic disorders in the aged.

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.

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.

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.

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.

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.

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.

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.

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.

Prenatal interactions between ethanol and the industrial solvent 2-ethoxyethanol in rats: maternal and behavioral teratogenic effects.

Behavioral and neurochemical deviations in the offspring of rats exposed to 100 ppm ethoxyethanol during gestation have been reported previously. Since this compound is likely metabolized in the same manner as ethanol, the present study investigated the interactive effects of ethanol and ethoxyethanol on prenatal development. Groups of 15-20 pregnant Sprague-Dawley rats were given 10% ethanol in the drinking water with or without concomitant inhalation exposure to 100 ppm ethoxyethanol during gestation days 7-13 or 14-20. Another group was exposed to 200 ppm ethoxyethanol on gestation days 7-13, and sham-exposed controls were included for both gestation periods. Ethanol alone on days 14-20 and 200 ppm ethoxyethanol reduced overall weight gain during pregnancy. As in the previous research, pregnancy duration was extended in the groups given ethoxyethanol, but not in groups given ethanol alone. Neuromotor ability, as assessed by an ascent test and by a rotorod, was reduced by 200 ppm ethoxyethanol and by ethanol alone on gestation days 7-13. The group given ethanol plus ethoxyethanol on days 14-20 spent significantly longer in the start area of an open field, and this group as well as that given 200 ppm ethoxyethanol were less active than controls in the open field and in the shuttle box. When compared with previous research, it appears that ethanol early in gestation may reduce the effects, but later in gestation may enhance the effects of prenatal ethoxyethanol.