Document N2XvQjvKv4xkKZ7Qvg9p9n1m8

^T SOCIETY OF TOXICOLOGY Poster ABSTRACT FORM See format for heading (other aide), leave double apace between heading end ebstract. Abstract must be single spaced. There will be a charge ,of S5 for any abstract which needs to be retyped. Leave no margins -- type must be within rectangle. Single space, elite type, except fpr double space between body of text end title and authors. Deadline for receipt in Executive Secretary's office is October 1, 1SS4. Follow instructions accompanying this form. Submit original and two copies. Original must be on this form. Proof carefully. au d it o r y an d v is u al ev o k ed po t en t ial s in c h il d r e n WITH UNDUE LEAD ABSORPTION, D.A. Otto, S.B. Baumann, G.S. Robinson, S.R. Schroeder, D.G. Kleinbaum, C.N. Barton and P, Mushak. U.S. Environmental Protection Agency, Research Tri angle Park, NC. Sponsor: R.S. Dyer Name and address of author to contact: David A. Otto (HD-5S) U.S. Environmental Protection Aoency Research TriangLe Park/ NC 27711 Visual impairments have been demonstrated- behaviorally and electrophsiologically in rats and monkeys neonatally exposed to. lead (Pb). Little evidence exists on auditory and visual effects of Pb exposure in humans, although we observed in creased latencies of brainstem auditory evoked potentials (BAER) in children with histories of undue Pb absorption (Otto et al. Environ. Res., in press). BAEPs and pattern-reversal visual evoked potentials (PREP) were recorded in 80 children aged 3 to 7 with blood lead (PbB) levels ranging from 6 to 47 u g/dl* Elevated hearing thresholds were observed in children with higher PbB levels* The latencies of BAEP waves I and III varied inversely with PbB contrary to pre diction, a possible result of adjusting stimula tion level for hearing threshold. PI latency, the most clinically relevant PREP measure, did not vary significant-ly with blood lead (.PbB) level. An exploratory analysis of P1N2 amplitude, however, varied inversely with PbB consistent with other data suggestive of Pb--related visual impairment* Since the: PREP reflects conemediated photopic visual function, other mea sures of scotopic visual function may provide more sensitive indices of lead exposure effects in humans Telephone 5A1-iU6 Indicate whether you prefer a platform or poster session. Platform - -- -- Poster Either ^ Select one topic category from EACH of three lists below which you think best describes your work Type of Study Envi ronmenta l r Type of Toxicant Metal TypnfTaqpt Central Nervous System Other Please check box if you would be willing to servt as session chairman & Signature of Sponsor TYPE OF STUDY Analytical Aquatic Clinical Developmental /Reproduction Environmental General Toxicology Evaluation Hypersensitivity Inhalation In Vitro Mechanism Metaboiism/Disposirion Mutagenesis Oncogenesis Reactive intermediates Regulatory Rev. 6/84 TYPE OF TOXICANT Air Pollutants/Gases Drug/Cosmetic Food Additives Haiogenated Hydrocarbon Metal Natural Produets Pesticides Solvems/Vapors Other TYPE OF TARGET Cardiovascular Cellular Centra! Nervous System Derma! Hematological Hepatic or Gastrointestinal Immune Moleculsr/Genetic Ocular Peripheral Nervous System Pulmonary Rena! Reproductive TEH 0350263 N36712 DU P050298900 OBJECTIVE To replicate and extend results of previous work (Otto et al, 1985) on the relationship of blood lead (PbB) levels and sensory evoked potentials in young children. HYPOTHESES (1) Auditory nerve conduction velocity as indexed by the latencies of waves III and V of the brainstem auditory evoked potential (BAEP) will increase directly with PbB levels. (2) N1P1 amplitude of the pattern-reversal visual evoked potential (PREP) will vary inversely with PbB. METHODS Subjects. Eighty children (50 girls) aged three to seven from low-income Black farrri lies considered to be at risk for Pb poisoning and referred by county health departments were evaluated. Pb-based paint from deteriorated housing was the primary source of exposure. BAEP. Children were screened for middle ear infection by otoscopic examination or tympanometry. Hearing thresholds were determined audiometrically using a 2KHz pure tone or electrophysiologically using descending BAEP in tensities. Two averages of 2000 alternating polarity binaural clicks (11.1/ sec) presented at 60 dBSL were recorded from children lying down in a darkened mobile laboratory. BAEPs were recorded between the vertex (Cz) and linked mastoids using a 0.1-3 KHz bandpass. PREP. Visual acuity was checked using a children's eye chart. Children were seated 5 ft. from a Grass Visual Pattern Generator (VPG-1) for full-field presentation of a black and white checkerboard pattern reversing twice per sec. 24* squares at 90% contrast were used. Two averages of 200 reversals were recorded binocularly from an Oz-Cz derivation using a 1-300 Hz bandpass. PbB Measurement. Venipuncture samples were drawn on test day. PbB levels were determined by the Ediger and Coleman (1972) modification of the Delves cup micro atomic absorption spectrometric procedure (Delves, 1970). Previous PbB levels of children were also obtained from county health depart ments when available. TEH 0350264 N36712.01 DU P050298901 RESULTS Table I. Descriptive statistics for control, PbB and electrophysiological variables. Table II. Summary of statistical analyses of BAEP/PREP measures Fig. 1. Hearing thresholds increased linearly with maximal PbB Fig. 2. Representative BAEPs from five boys with varying maximal PbB histories (click intensity 80+5 dBSPL) Fig. 3. Linear (wave I) and curvilinear (waves III, V, IPLs I-V, X--III) relationships of BAEP measures and maximal PbB. Wave I latency decreased linearly as PbB increased, while latencies of waves III, V, I-V and I-III decreased below 25 mg/dl, but increased above this level. Fig. 4. Representative PREPs from five children with varying maximal PbB histories. Only P1N2 amplitude varied significantly (decreased) with PbB level. PI latency increased (nonsignificantly) with increasing PbB. Fig. 5. Relationship of P1N2 amplitude and maximal PbB. CONCLUSIONS (1) Curvilinear relationships of BAEP waves III, V and interpeak latencies I-III and I-V suggest possible biphasic effect of Pb on nerve conduction in auditory pathway. Only the ascending portions of curves above 25 mg/dl are consistent with predictions. (2) Observations of elevated hearing thresholds and decreased wave I latencies in children with elevated PbB are incompat4He. hysfol-&giea4- daa__su.' involved in s>'chflphys i caI-4u4gment- thresholds Wt, uA fk a neon w w&i v<afaift'wj hexuiwcj 1055, (3) Visual evoked potential findings did not confirm hypothesis 2, although P1N2 amplitude varied in predicted direction. Inconsistencies of present and earlier (Otto et al, 1985) findings may be due to the photopic nature of PREPs. Animal studies suggest that Pb selectively alters scotopic (rod) function. Further study of Pb effects on scotopic vision in mar is needed to resolve this question. TEH 03s 0265 DUP050298902 TABLE I. SAMPLE MEANS FOR DEMOGRAPHIC AND ELECTROPHYSIOLOGICAL VARIABLES VARIABLE____________________ N___________ MEAN AGE (Months) SES CHILD IQ MATERNAL 10 HOME 75 58*4 75 70.8 75 86.1 75 63.4 75 59.8 CURRENT PbB (ng/dl) MAXIMUM PbB 75 20.6 75 26.7 BRAINSTEM AUDITORY EVOKED POTENTIAL LATENCY I (MSEC) LATENCY III LATENCY V IPL I-III IPL III-V IPL I-V 64 1.72 65 3.85 65 5.72 64 2.13 65 1.86 64 3.99 PATTERN-REVERSAL VISUAL EVOKED POTENTIAL N1 LATENCY (MSEC) PI LATENCY N2 LATENCY N1P1 AMPLITUDE (yV) P1N2 AMPLITUDE 70 68.6 70 100.3 70 145.2 70 15.5 70 10.9 SD 11.7 6.2 11.7 11.3 15.1 9.7 14.1 MIN 33 55 60 40 20 6.2 6.2 0.14 0.19 0.24 0.15 0.13 0.22 1.47 3.51 5.26 1.89 1.57 3.63 3.6 5.9 15.2 7.2 5.5 60.5 90.0 123.5 2.95 2.17 MAX 94 84 119 94 87 47.4 56.0 2.14 4.50 6.46 2.55 2.17 4.45 81.0 129.5 197.5 40.6 26.7 f tew 0350166 " DUP050298903 TABLE II. EXPLORATORY ANALYSIS OF LINEAR, QUADRATIC AND CUBIC TRENDS IN THE RELATIONSHIP OF MAXIMUM PbB LEVELS AND ELECTROPHYSIOLOGICAL MEASURES: p-VALUES Dependent Variable Polynomial* Linear BRAINSTEM AUDITORY EVOKED POTENTIAL LATENCY I LATENCY III LATENCY V IPL I-III IPL I-V IPL III-V .035 .020 .06 .016 .037 .63 .008 .44 .98 .12 .08 .26 PATTERN-REVERSAL VISUAL EVOKED POTENTIAL N1 LATENCY PI LATENCY N2 LATENCY N1P1 AMPLITUDE P1N2 AMPLITUDE .048 .14 .77 .35 .013 .12 .08 .58 .17 .001 Quadratic .28 .003 .007 .005 .020 .51 .06 .38 .55 .26 .64 Cubic .60 .98 .98 .60 .76 .92 .16 .19 .50 .72 .68 Polynomial-test of the set of three trends 03s0267 DUP050298904 RELATIONSHIP OF HEARING THRESHOLD VS. PbB HEARING THRESHOLD dbSPL 0 3 6 12 18 21 24 27 30 33 96 36 42 45 48 51 PbB, ug/dl Fij.a BRAINSTEM AUDITORY EVOKED POTENTIALS IN BOVS. WITH VARYING Pb EXPOSURE HISTORIES TEH 0350268 DUPO 502 98905 BRAINSTEM AUDITORY EVOKED POTENTIAL LATENCY AS A FUNCTION OF MAXIMAL PbB LATENCY. MSEC WAVE I MAXIMUM PbB, ug/dl LATENCY, MSEC Fn ta $ TEH 0350269 DUP050298906 Vn .DS X I DUP050298907 PATTERN-REVERSAL VISUAL EVOKED POTENTIALS) IN CHILDREN WITH VARYING Pb EXPOSURES) REPLICATION STUDY: PATTERN REVERSAL VISU