Neurobehavioral test performance in the third National Health and Nutrition Examination Survey.

The third National Health and Nutrition Examination Survey (NHANES III) contained three computerized neurobehavioral tests from the Neurobehavioral Evaluation System (NES): simple reaction time, symbol-digit substitution and serial digit learning. The neurobehavioral data that were collected came from a nationally representative sample of adults 20-59 years old. Performance on the tests was related to sex, age, education level, family income and race-ethnicity. Performance decreased as age increased, and increased as education level and family income increased. Differences in performance between sexes, levels of education and racial-ethnic groups tended to decrease as family income increased. The relationship between age and performance on the symbol-digit substitution test varied by education level and by racial-ethnic group. The relationship between age and performance on the serial digit learning test varied by racial-ethnic group. Questionnaire variables that were related to performance on one or more of the tests included the reported amount of last night's sleep, energy level, computer or video game familiarity, alcoholic beverages within the last 3 h and effort. Persons who took the tests in English or Spanish performed differently on the symbol-digit substitution and serial digit learning tests. Performance on all the tests decreased as test room temperature increased.

Neurologic function among termiticide applicators exposed to chlorpyrifos.

Chlorpyrifos is a moderately toxic organophosphate pesticide. Houses and lawns in the United States receive a total of approximately 20 million annual chlorpyrifos treatments, and 82% of U.S. adults have detectable levels of a chlorpyrifos metabolite (3,5, 6-trichloro-2-pyridinol; TCP) in the urine. The U.S. Environmental Protection Agency has estimated that there are 5,000 yearly reported cases of accidental chlorpyrifos poisoning, and approximately one-fourth of these cases exhibit symptoms. Organophosphates affect the nervous system, but there are few epidemiologic data on chlorpyrifos neurotoxicity. We studied neurologic function in 191 current and former termiticide applicators who had an average of 2.4 years applying chlorpyrifos and 2.5 years applying other pesticides, and we compared them to 189 nonexposed controls. The average urinary TCP level for 65 recently exposed applicators was 629.5 microg/L, as compared to 4.5 microg/L for the general U.S. population. The exposed group did not differ significantly from the nonexposed group for any test in the clinical examination. Few significant differences were found in nerve conduction velocity, arm/hand tremor, vibrotactile sensitivity, vision, smell, visual/motor skills, or neurobehavioral skills. The exposed group did not perform as well as the nonexposed group in pegboard turning tests and some postural sway tests. The exposed subjects also reported significantly more symptoms, including memory problems, emotional states, fatigue, and loss of muscle strength; our more quantitative tests may not have been adequate to detect these symptoms. Eight men who reported past chlorpyrifos poisoning had a pattern of low performance on a number of tests, which is consistent with prior reports of chronic effects of organophosphate poisoning. Overall, the lack of exposure effects on the clinical examination was reassuring. The findings for self-reported symptoms raise some concern, as does the finding of low performance for those reporting prior poisoning. Although this was a relatively large study based on a well-defined target population, the workers we studied may not be representative of all exposed workers, and caution should be exercised in generalizing our results.

Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers.

OBJECTIVES: This study assessed the health effects associated with occupational exposure to methyl bromide and sulfuryl fluoride among structural fumigation workers. METHODS: A cross-sectional study of 123 structural fumigation workers and 120 referents in south Florida was conducted. Nerve conduction, vibration, neurobehavioral, visual, olfactory, and renal function testing was included. RESULTS: The median lifetime duration of methyl bromide and sulfuryl fluoride exposure among workers was 1.20 years and 2.85 years, respectively. Sulfuryl fluoride exposure over the year preceding examination was associated with significantly reduced performance on the Pattern Memory Test and on olfactory testing. In addition, fumigation workers had significantly reduced performance on the Santa Ana Dexterity Test of the dominant hand and a nonsignificantly higher prevalence of carpal tunnel syndrome than did the referents. CONCLUSIONS: Occupational sulfuryl fluoride exposures may be associated with subclinical effects on the central nervous system, including effects on olfactory and some cognitive functions. However, no widespread pattern of cognitive deficits was observed. The peripheral nerve effects were likely caused by ergonomic stresses experienced by the fumigation workers.

A mathematical model of performance on a simple reaction time test.

A nonlinear function with components for learning and fatigue was used to model individual performance on a simple reaction time test. The relationships between the parameters of the model and the mean and variance of the reaction times are discussed. The function is used to analyze data from a field study of agricultural workers exposed to organophosphate pesticides. Exposure had a significant effect on the relationships between education level and initial performance, age and fatigue rate, and age and performance variability. Parameter estimates from the model were able to distinguish between effects that the mean and standard deviation of the reaction times were unable to distinguish.

Neurobehavioral test methods for environmental health studies of adults.

The Agency for Toxic Substances and Disease Registry convened a workshop in Atlanta, GA, that evaluated approaches and methods to ascertain whether there are neurobehavioral sequelae to children and adults exposed to hazardous substances in the environment. This article, developed from that Workshop, recommends testing methods [to identify neurotoxic insult] for immediate use in environmental health field studies of adults. A list of broad functional domains or modalities affected by chemicals was identified from the occupational and related literature (learning and memory, coding, sustained attention, higher intellectual function, strength, coordination, speed, vision, somatosensory, and affect). A core set of tests was selected that should assess those functions with the greatest demonstrated sensitivity to established neurotoxic chemicals, and a secondary set was selected to assess a broader group of functions. The core tests should be used in all investigations where neurotoxic effects would be targeted for identification; secondary tests would be used where suggested by questionnaire or symptom data or by knowledge of the effects of chemicals at the hazardous waste site.

Comparison of performance from three continents on the WHO-Recommended Neurobehavioral Core Test Battery.

To address the need for standardized test batteries, an expert group convened by the World Health Organization (WHO) and the U.S. National Institute for Occupational Safety and Health during 1983 proposed the Neurobehavioral Core Test Battery (NCTB) to identify nervous system effects of chemical exposures in human populations worldwide. To determine the feasibility of using the NCTB in varied cultures, a cross-cultural assessment was conducted under WHO auspices. Data were collected in 10 countries of Europe, North and Central America, and Asia from over 2300 males and females who were not exposed to chemicals at work, within five age ranges between 16 and 65. Results suggest that performance on two NCTB tests (Simple Reaction Time, Benton Visual Retention) is very similar in a broad range of countries and that performance on four other NCTB tests (Santa Ana, Digit Symbol, Digit Span, Aiming) is relatively more variable from country to country, in both males and females. However, data collected from very poorly educated males in one country revealed very low performance levels suggesting that the NCTB may not provide an adequate reference group for identifying (behavioral) neurotoxic effects in such populations. More research is thus needed on evaluating neurotoxicity in poorly educated subjects.

Reproductive and developmental toxicity of N,N-diethyl-m-toluamide in rats.

N,N-Diethyl-m-toluamide (mDET, DEET) is widely used as a topical insect repellent. It is the active ingredient in many consumer formulations, which usually contain 10-25% mDET in an alcohol base. More concentrated consumer products are also available, including some that are pure technical grade mDET. Persons living or employed in mosquito-infested areas may have very high seasonal exposures to mDET. Because contradictory reports had been published on the reproductive and developmental toxicity of mDET, a series of studies was conducted in male and female Sprague-Dawley rats. All treatments were administered by daily subcutaneous injections of undiluted mDET. A dose finding study was done using 12 time-mated females per group treated on Gestational Days (GD) 6-15 with 0.50, 0.62, 0.78, 0.92, or 1.2 ml mDET/kg/day. No females survived 10 days of mDET dosing with 1.2 ml/kg/day. Deaths occurred in all other groups except the low dose (0.50 ml/kg/day). Pregnant females treated on GD 6-15 with 0 or 0.30 ml/kg/day were used for the teratology study. Half of each group was euthanized on GD 20: the second half was singly housed in nesting boxes and allowed to deliver litters. Live pups were counted and weighed soon after birth on Postnatal Day (PD) 0 and again on PD 3, 9, and 14. Proven fertile males were treated 5 days/week for 9 weeks with 0, 0.30, 0.73, 1.15, or 1.80 ml mDET/kg/day for a male dose-finding study. Each group consisted of 20 males. No males survived the 1.80 ml/kg/day. Deaths occurred in all remaining dose groups except the 0.30 ml/kg/day and control group. Immediately following the final treatment of the male dose study, 11 males were randomly selected from the 0.30 and 0.73 ml/kg/day groups. They were cohabited for 7 days with 4 females per male during post-treatment Weeks 1 and 2. Half of the females were euthanized 12-14 days after the last day of cohabitation for a dominant lethal study; the remaining females were singly housed in nesting boxes and allowed to deliver litters. Live pups were counted and weighted on PD 0 and 3. There was no evidence of reproductive or developmental toxicity in any of these assays, but there were signs of neurotoxicity in treated adult male and female rats, which may relate to reports of neurotoxicity in humans heavily exposed to mDET-containing insect repellents.

Effects of acute oral administration of lithium compounds on multiple schedule performance in rats.

Adult male Sprague-Dawley rats were given acute oral administrations of lithium carbonate or lithium chloride at concentrations of 100, 200, and 300 mg/kg. Barpressing performance on a multiple fixed ratio 20/fixed interval 5 minute schedule was measured daily. The 200 and 300 mg/kg administrations of lithium chloride produced significant decreases in barpressing performance and all levels of lithium carbonate produced significant changes in performance. A 24 hour delay in the maximal behavioral effect of the 300 mg/kg dose of lithium carbonate paralleled previous findings showing delays in peak brain lithium levels after oral administration of lithium carbonate.

A behavioral examination of workers exposed to carbon disulfide.

The present study was conducted with a group of 298 textile workers. Of the workers studied 131 had worked at least one year in a rayon plant where there were CS2 exposures of varying degree, but generally below 20 ppm, which is the U.S. occupational exposure limit. The remaining 167, who worked in plants that manufactured other textiles where any CS2 exposure was considered inconsequential, comprised a comparison group. The 298 workers completed a checklist of symptoms characteristic of various neurobehavioral syndromes. Mood and excitability were measured by the Profile of Mood States, and by a mania scale from the Minnesota Multiphasic Personality Inventory, respectively. Cognitive and psychomotor performance was studied by application of four standard tasks: the Neisser letter search, the memory span test, the eye-hand coordination test, and a combined simple and complex reaction time test. The results indicated an absence of behavioral changes of any major significance, suggesting that effects here may only be marginal. The major finding related to the significant cluster of reported symptoms of neurobehavioral ailments.