David W. Chrislip

Chronic Neurologic Sequelae to Cholinesterase Inhibition among Agricultural Pesticide Applicators

To test the hypothesis that chronic neurologic sequelae are associated with cholinesterase depression short of frank organophosphate poisoning, we compared 45 male subjects who had a history of moderate cholinesterase inhibition with 90 male subjects who had neither past cholinesterase inhibition nor current pesticide exposure. Cholinesterase-inhibited subjects were defined as having had a history of (a) red blood cell cholinesterase at 70% or less of baseline or (b) plasma cholinesterase at 60% or less of baseline absent symptoms of frank poisoning. In the subject comparison evaluation, only 1 of 27 neurologic tests (i.e., serial digit performance) was significant statistically, but it was opposite of the direction hypothesized. In a companion study for which the same battery of neurologic tests and the same subjects were used, neurologic sequelae were related to high exposures among subjects who sought treatment for organophosphate poisoning. The data in the current study, in which the subjects experienced lower exposures short of frank poisoning, provide some evidence that preventing acute organophosphate poisoning also prevents neurologic sequelae.

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 nights 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.

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.

Examining associations between job characteristics and health: linking data from the Occupational Information Network (O*NET) to two U.S. national health surveys.

Objective:To determine whether the Occupational Information Network (O*NET) database can be used to identify job dimensions to serve as proxy measures for psychosocial factors and select environmental factors, and to determine whether these factors could be linked to national health surveys to examine associations with health risk behaviors and outcomes. Methods:Job characteristics were obtained from O*NET 98. Health outcomes were obtained from two national surveys. Data were linked using Bureau of Census codes. Multiple logistic regression was used to examine associations between O*NET factors and cardiovascular disease, depression, and health risk factors. Results:Seven of nine work organization or psychosocial factors were significantly associated with health risk behaviors in both the National Health and Nutrition Examination Survey III and National Health Interview Survey. Conclusions:This study demonstrates a method for linking independently obtained health and job characteristic data based on occupational code.

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.

The Relationship Between Blood Lead Levels and Neurobehavioral Test Performance in NHANES III and Related Occupational Studies

Objectives. The goals of this study were two-fold: (1) to assess the relationship between blood lead levels and neurobehavioral test performance in a nationally representative sample of adults from the third National Health and Nutrition Evaluation Survey and (2) to analyze the results from previously published studies of occupational lead exposure that used the same neurobehavioral tests as those included in the survey. Methods. Regression models were used to test and estimate the relationships between measurements of blood lead and performance on a simple reaction time, a symbol-digit substitution, and a serial digit learning test in adults aged 20–59 years who participated the survey. Mixed models were used to analyze the data from the occupational studies. Results. The blood lead levels of those participating in the survey ranged from 0.7 to 41.8 μg/dl. The estimated geometric mean was 2.51 μg/dl, and the estimated arithmetic mean was 3.30 μg/dl. In the survey, no statistically significant relationships were found between blood lead concentration and performance on the three neurobehavioral tests when adjusted for covariates. In the occupational studies, the groups exposed to lead consistently performed worse than control groups on the simple reaction time and digit-symbol substitution tests. Conclusions. The results from the survey and the occupational studies do not provide evidence for impairment of neurobehavioral test performance at levels below 25 μg/dl, the concentration that the Centers for Disease Control and Prevention define as elevated in adults. The average blood lead level of the exposed groups in the occupational studies was 41.07 μg/dl, less than 50 μg/dl, the minimum concentration that the Occupational Safety and Health Administration requires for medical removal from the workplace. Given the evidence of impaired neurobehavioral performance in these groups, the 50 μg/dl limit should be reevaluated.

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.

Comparison of Performance from Three Continents on the WHO-Recommended Neurobehavioral Core Test Battery1

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.