David A. Otto

Blood Lead, Hearing Thresholds, and Neurobehavioral Development in Children and Youth

NHANES II audiometry data were used to confirm a previously observed link between blood lead (PbB) level and hearing threshold. Other indicators of neurological development, such as age at which a child first sat up, walked, and spoke, and the presence of speech difficulties and hyperactivity were also examined to determine if they were significantly related to lead exposure. The probability of elevated hearing thresholds at 500, 1000, 2000 and 4000 Hz increased significantly (p less than .0001) with increasing PbB for both ears. PbB levels were also significantly related to delays in the age at which children first sat up, walked, and spoke and to the probability that a child was hyperactive. Lead was not related to the probability of a child having a previously diagnosed speech impairment.

The comparative developmental neurotoxicity of lead in humans and animals

The effects of lead on neurobehavioral development have been extensively investigated in humans as well as animals. This valuable lode of research findings offers a basis for comparing the developmental neurobehavioral toxicity of lead across species and for assessing the validity of animal models of developmental neurotoxicity. Comparisons of human and animal findings suggest that the greatest qualitative similarities involve relatively complex behavioral processes such as cognition and learning. Quantitative comparisons based on dose-response relationships for these endpoints are difficult to make because the relationships are sometimes nonmonotonic (U-shaped) and because blood lead levels may not be directly comparable between species. However, the lowest levels of exposure at which developmental neurobehavioral effects have been observed are similar: 10-15 micrograms/dl in children, less than 15 micrograms/dl in primates, and less than 20 micrograms/dl in rodents. Although the convergence between animal and human findings for other neurobehavioral endpoints is not as striking, sensory-evoked potentials and communicative processes offer two promising areas for continued investigation and cross-species comparison.

Exposure of Humans to a Volatile Organic Mixture. II. Sensory

Time-course functions for symptoms of the sick building syndrome were derived from 66 healthy males who, during separate sessions, were exposed to clean air and to a volatile organic compound (VOC) mixture. The mixture contained 22 VOCs (25 mg/m3 total concentration) commonly found airborne in new or recently renovated buildings. Subjects rated the intensity of perceived irritation, odor, and other variables before, and twice during, 2.75-h exposure periods. Eye and throat irritation, headache, and drowsiness increased or showed no evidence of adaptation during exposure, whereas odor intensity decreased by 30%. These results indicate that irritation intensity and other symptoms are not related in any simple way to odor intensity, which suggests that the symptoms may not be a psychosomatic response to the detection of an aversive odor. Instead, subthreshold levels of VOCs may interact additively or hyperadditively and stimulate trigeminal nerve receptors. Also, air quality ratings improved by 18% during exposure, which suggests that both odor and irritation intensity may influence assessments of air quality.

Effects of age and body lead burden on CNS function in young children. I. slow cortical potentials.

The effects of body Pb burden on slow cortical potentials were studied in 63 children aged 13-75 months. Slow wave (SW) voltage during sensory conditioning varied as a linear function of blood lead (PbB) level. The slope of this function, moreover, changed systematically with age. For children under 5 years of age, SW voltage tended to be positive at low PbBs and to be negative above 30 micrograms/dl. For children over 5 years of age, SW voltage tended to be negative at low PbBs and to be less negative (or positive) above 30 micrograms/dl. These results provide evidence of altered CNS function at the lowest Pb effect level ever reported.

Neurobehavioral and sensory irritant effects of controlled exposure to a complex mixture of volatile organic compounds

Subjective reactions of discomfort, impaired air quality, irritation of mucosal membranes, and impaired memory have been reported in chemically sensitive subjects during exposure to volatile organic compounds (VOCs) found in new buildings. Sixty-six normal healthy male subjects aged 18-39 were exposed for 2.75 hr to a complex VOC mixture at 0 and 25 mg/m3. Each subject completed control and exposure sessions at one-week intervals in counterbalanced order. Measurements included comfort ratings of eye, nose and throat irritation, symptom questionnaire and computerized behavioral tests. Subjects found the odor of VOCs unpleasantly strong and reported that VOC exposure degraded air quality, increased headache and produced general discomfort. VOC exposure did not affect performance on any behavioral tests.

Feasibility and validity of three computer-assisted neurobehavioral tests in 7-year-old children☆

Three tests from the computerized Neurobehavioral Examination System (NES) were administered to a group of 917 Faroese children at approximately 7 years of age. The NES Continuous Performance Test (CPT) was modified to use animal silhouettes as stimuli instead of letters. Almost all children completed Finger Tapping (FT), the modified CPT, and Hand-Eye Coordination (HE). However, 18% of the children missed at least 25% of the stimuli on the CPT (full test period), and 37% of the children did not improve their HE performance by at least 10%, as compared to the first trial. Boys obtained better results than girls, and older children performed better than younger ones. However, both factors were confounded by acquaintance with computer games. Children who used glasses, who had strabismus, or who had decreased contrast sensitivity obtained less satisfactory scores, especially on CPT and HE. The NES performance was significantly associated with functional neurological performance, including catching a ball, diadochokinesia, and finger agnosia. Slight, though statistically significant, decrements were seen with increased levels of prenatal exposure to neurotoxicants, as indicated by the mercury concentrations in cord blood obtained at the time of birth. In conclusion, the tests were feasible in this age group after slight modifications, and the test results showed meaningful associations with major predictors, thus supporting the validity of the data.

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.

Effects of age and body lead burden on CNS function in young children. II. EEG spectra

This study explored the effects of age and PbB upon EEG power spectra and various measures of hemispheric laterality in children, aged 13-75 months, watching a display (cartoon). The following are the principle conclusions: (1) The delta- and theta-band amplitude decreased with age. (2) When only bilaterally synchronized EEG between P3 and P4 was considered, the amplitude of P3 was estimated as greater than P4 in all frequency bands and for all ages. Previous reports have not shown lateral EEG dominance in children below 75 months. (3) When lateral dominance measures consider only the relationship between synchronized EEG at P3 and P4, bilateral communality in the delta band increased with age. (4) Increased PbB generally produced an increase in the relative amplitude of synchronized EEG between P3 and P4 in all frequency bands. This was true for PbB levels well below 15 micrograms/dl, among the lowest level PbB effects previously reported. No clinical or behavioral effects of PbB values have been reported below 15 micrograms/dl. It appears to be theoretically and practically important to understand the functional significance of bilaterally synchronized activity. The signal processing of the CNS can be explored using these methods. Greater understanding of these data would help define the extent and etiology of PbB effects on the CNS

Impact of contrast sensitivity performance on visually presented neurobehavioral tests in mercury-exposed children.

Presentation of neuropsychological tests on a computer screen may involve a visual challenge to the examinee. The possible need for adjustment for visual contrast sensitivity on test performance was therefore determined from data on 917 mercury-exposed children who were examined at age 7 years. Contrast sensitivity was found to be associated with performance on the computer-assisted Continuous Performance Test. However, it showed similar associations with performance on traditional pencil-and-paper tests, especially Bender Visual Motor Gestalt Test and Wechsler Intelligence Scale for Children-Revised (WISC-R) Block Designs. Contrast sensitivity was not associated with prenatal mercury exposure, and adjustment for visual function had only a negligible effect on the regression coefficients for mercury as predictor of neuropsychological deficits. The mercury-associated neurobehavioral deficits are therefore unlikely to be due to mercury-induced visual system dysfunction causing secondary deficits in cognitive domain testing. Visuospatial processing appears to be a determinant in contrast sensitivity performance, and careful consideration of whether to control for contrast sensitivity in future studies of neurotoxicant effects is therefore recommended.

Neurobehavioral evaluation system (NES): Comparative performance of 2nd-, 4th-, and 8th-grade Czech children

The Neurobehavioral Evaluation System was designed for field studies of workers, but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests, such as simple reaction time, can be performed by preschool children. However, little comparative data from children of different ages or grade levels are available. Studies of school children in the Czech Republic indicate that 2nd-grade children could perform the following NES tests satisfactorily: Finger Tapping, Visual Digit Span. Continuous Performance, Symbol-Digit Substitution, Pattern Comparison, and simpler conditions of Switching Attention. Comparative scores of boys and girls from the 2nd, 4th, and 8th grades and power analyses to estimate appropriate sample size were presented. Performance varied systematically with grade level and gender. Larger samples were needed with younger children to achieve comparable levels of statistical power. Gender comparisons indicated that boys responded faster, but made more errors than girls.