Half-life of polybrominated biphenyl in human sera.

Polybrominated biphenyl (PBB), a flame-retardant material, was introduced into the food chain in Michigan in 1973 due to a manufacturing and distribution mistake. Following public concern about the long-term health effects of PBB in humans, a cohort of PBB-exposed Michigan residents was assembled in 1975. We initiated this study to determine the half-life of PBB in human sera and to understand how continued body burden relates to the possible adverse health consequences of PBB exposure. To determine the half-life, eligible persons were selected from the cohort if they had at least two PBB measurements 1 year apart and had an initial level > or = 20 pbb. There were 163 persons who met the criteria with a median PBB level of 45.5 ppb. The estimated half-life is 10.8 years (95% CI, 9.2-14.7 years). The body burden of PBB in exposed persons will decrease only gradually over time. For persons with an initial level of 45.5 ppb of PBB, it will take more than 60 years for their PBB levels to fall below the current level of detection of 1 ppb.

PCB congener profile in the serum of humans consuming Great Lakes fish.

The State of Michigan has a long history of research into human exposure to environmental contaminants through consumption of recreationally caught fish. A large cohort of Lake Michigan residents who eat fish (fish-eaters) and those who do not eat fish (nonfish-eaters) established in 1980 served as the basis for the congener-specific polychlorinated biphenyl (PCB) exposure evaluation reported here. In this paper we present the serum PCB congener profile for a subset of this cohort who were over 50 years of age. Serum samples were collected in 1993-1995 and were evaluated by a dual column capillary column gas chromatography procedure capable of detecting over 90 PCB congeners. This evaluation demonstrated significant PCB exposure in the fish-eaters (mean serum PCB of 14.26 ppb; n = 101). This elevated exposure allowed the establishment of a detailed profile of the PCB congeners found in humans exposed by this route. Twenty-two congeners of varying concentrations were the most prevalent and constituted over 95% of the total PCB present in most subjects. Four congeners, 138/163 (2,2',3,4,4',5-PCB/2,3,3',4', 5,6-PCB), 180 (2,2',3,4,4',5,5'-PCB), and 153 (2,2',4,4',5,5'-PCB), accounted for 55-64% of the total PCB load. Other congeners, some of toxicologic significance, were also detected by this analytical protocol. Nonfish-eaters had lower total serum PCB levels (mean = 4. 56; n = 78), but the same general pattern of PCB congeners was present. It was demonstrated that careful selection of a subset of prevalent PCB congeners could provide a cost-effective assessment of exposure without losing critical scientific information.

Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.

The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study.

A field biochemical epidemiology study was conducted using the Michigan cohort consisting of 51 rural residents exposed to polybrominated biphenyls (PBB). The study had three major objectives: a) to determine the serum half-life of the major PBB congener, hexabromobiphenyl (HBB), in the human, b) to determine if the PBB-exposed subjects had elevated cytochrome P-450I function as determined by the caffeine breath test (CBT) and the caffeine urinary metabolite ratio (CMR), and c) to determine the applicability of the CBT and CMR in field studies. PBB serum levels were detected in 36 of the 51 PBB-exposed subjects. The serum half-life of HBB was determined by comparing the current serum HBB values to the subject's previous serum values obtained 5 to 8 years earlier. The median HBB half-life was 12 years (range 4-97 years). The CBT and CMR were elevated in the subjects exposed to PBBs as compared to the values obtained from urban nonsmokers and were similar to those found in adults who smoke. A gender effect was seen in the PBB-exposed subjects, the median CBT and CMR values of the females being lower than the values of males. There was a correlation between the CBT and the HBB serum values (r2 = 0.2, p = 0.01) but not between CMR and HBB serum values. The CBT and CMR were easily conducted in the field and appear to be useful metabolic probes of cytochrome P-450I activity in human environmental toxicology.

Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings.

Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted.

An improved technique to facilitate transcervical thymectomy for myasthenia gravis.

We have used the transcervical method of thymectomy in patients with myasthenia gravis and believe that complete thymectomy is accomplished with minimum morbidity. For the past eight years we have used an improved technique for the transcervical approach, employing a specially designed sternal retractor that permits improved visualization of the anterior mediastinum. We have reviewed 65 patients operated on between 1977 and 1986. Patients were assessed using a modified Osserman classification (0 = asymptomatic; 1 = ocular signs and symptoms; 2 = mild generalized weakness; 3 = moderate generalized weakness; 4 = severe generalized weakness, respiratory dysfunction, or both). The mean grade for all patients at the time of thymectomy was 2.7. At most recent follow-up, the mean clinical grade was 0.5. In addition, 85% of patients were free of generalized weakness, 95% had improved by at least one grade, and 86% had improved by two or more grades. Comparing these results with those reported following thymectomy through a sternotomy reveals that the transcervical approach gives equivalent results.

Effects of exposure to PCBs and related compounds on growth and activity in children.

Two hundred thirty-six children from two established cohorts at risk for exposure to polychlorinated biphenyls (PCBs) and related contaminants were evaluated at age 4 years. Prenatal exposure (assessed by cord serum PCB level) was associated with lower weight, an effect consistent with reports of growth retardation in laboratory rats and in children exposed at high levels in Taiwan and at general population levels in Japan. The highest exposed children weighed 1.8 kg less on the average than the least exposed. Contemporary body burden (assessed by 4-year serum PCB level) was associated with reduced activity based on composite ratings provided by the child's mother and two independent examiners. This effect, attributable to lactation exposure, was strongest among the offspring of women with above average milk PCB levels who breast fed for at least 1 year. While the weight deficit is consistent with previous data linking developmental effects of low-dose human PCB exposures specifically to the prenatal period, activity is the first domain found to be affected by lactation at contemporary levels of exposure.

Environmental exposure and lifestyle predictors of lead, cadmium, PCB, and DDT levels in Great Lakes fish eaters.

A previously characterized cohort of 115 Great Lakes fish eaters and 95 non-fish-eating regional controls was reexamined in 1989. Levels of blood lead and cadmium and serum PCB and DDT were measured. Lifestyle characteristics, including recent and historic fish consumption, were evaluated as predictors of contaminant levels using multivariate regression analysis. Significantly elevated serum PCB and DDT levels were observed in fish eaters, compared with controls. Historic fish consumption, rather than recent consumption, was identified as the primary predictor of current serum levels. Mean blood lead and cadmium were also significantly higher in fish eaters than in controls. However, the primary predictors of lead and cadmium were behavioral exposures--specifically smoking and self-reported occupational and recreational exposure-rather than fish consumption. These findings illustrate the importance of evaluating a variety of possible sources when investigating human exposure to environmental contaminants.

Serial PBB levels, PCB levels, and clinical chemistries in Michigan's PBB cohort.

Half of a cohort of 3683 Michigan residents exposed to polybrominated biphenyls (PBBs) in 1973 and 1974 had 2 serum PBB determinations at a 1- or 2-yr interval. The median decrease in serum PBB levels during both 1- and 2-yr intervals was 1 microgram/L. The geometric mean serum polychlorinated biphenyl (PCB) level (6.3 microgram/L) exceeded that of PBB (4.1 micrograms/L), although the range of PCB levels (smaller than 1-57 microgram/L) was narrower than that of PBB levels (smaller than 1-3150 micrograms/L). Mean PCB and PBB levels were higher for males, and mean PCB levels increased with age. In a subgroup with higher-than-average PBB levels, serial clinical chemistry tests during 4 different years showed no consistent significant correlation with serum PBB levels. Tests with greater sensitivity and specificity for hepatic microsomal enzyme induction and thyroid status are needed in future evaluations of the most highly exposed subgroup of the cohort.

Partitioning of polybrominated biphenyls (PBBs) in serum, adipose tissue, breast milk, placenta, cord blood, biliary fluid, and feces.

Polybrominated biphenyl (PBB) concentrations in specimens from adult males and females were used to determine the distribution of PBBs in body tissues and the partitioning ratio between types of tissues. Specimens of serum, adipose tissue, biliary fluid, and feces were tested by gas chromatography. In addition, parturient women provided breast milk, placenta, and cord blood for testing. There was a significant correlation between serum and adipose PBB levels. Pregnant and nonpregnant women and male chemical workers had similar serum to adipose tissue concentration ratios, which ranged from 1:140 to 1:260. Males from farms had a significantly different ratio of 1:325-329. Potential exposure to the fetus and newborn was demonstrated. Cord blood contained one-tenth of the concentration found in maternal serum which indicated partial placental passage. Human milk contained PBBs at 107 to 119 times the quantity found in maternal serum. Polybrominated biphenyls were detectable in bile and feces demonstrating transfer into the intestinal tract. The concentration of PBBs in feces represented a minor proportion of the total body burden indicating a slow rate of excretion.

Determinants of polychlorinated biphenyls (PCBs) in the sera of mothers and children from Michigan farms with PCB-contaminated silos.

Blood samples were collected from 28 mothers and from 38 school-aged children from Michigan farms on which there were polychlorinated biphenyl (PCB)-contaminated silos. The samples were analyzed for PCBs and other contaminants, including polybrominated biphenyls (PBBs) and dichlorodiphenyl trichloroethane (p,p'-DDT + p,p'-DDE) via packed column gas chromatography. The PCBs were quantified, using the Webb-McCall method, with Aroclors 1016 and 1260 used as reference standards. Approximately 42% of the children had serum PCB levels above the detection limit of 3.0 ng/ml. The values ranged from 3.1 to 23.3 ng/ml, with a mean of 6.8 ng/ml. In contrast, PCBs were detected in 86% of the mothers. The mean serum concentration was somewhat higher for the mothers (9.6 ng/ml), but the range was similar to that found for the children. PBBs were not detected in any of the children, but were present in trace amounts in 25% of the mothers. Conversely, DDT was present in 66% of the children and 93% of the mothers. As with PCBs, DDT concentrations were somewhat higher in the mothers. DDE accounted for 89% of the total DDT in serum. Various potential sources of exposure were evaluated as possible determinants of serum PCB levels, using hierarchical multiple regression. Years of residence on a silo farm and consumption of PCB-contaminated Great Lakes fish both accounted for significant portions of the variance in maternal serum PCB levels. Exposure via breast-feeding explained a large and highly significant proportion of the variance in the children's serum PCB concentrations, suggesting that breast milk was the primary source of PCB exposure for these children.(ABSTRACT TRUNCATED AT 250 WORDS)

Michigan's fisheater cohorts: a prospective history of exposure.

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinal comparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.

Historical changes in serum PCB and DDT levels in an environmentally-exposed cohort.

A previously characterized cohort of 115 Great Lakes fisheaters and 95 non-fisheating controls was re-examined in 1989 to evaluate changes that had occurred in serum PCB and DDT levels since the 1982 study. Substantial and significant decreases in mean serum DDT levels had occurred in both fisheaters (25.8 ppb vs 15.6 ppb) and controls (9.6 ppb vs 6.8 ppb) over this time period. In contrast, only a slight decrease in serum PCB levels was observed, and in fisheaters only. No association between individual changes in serum PCB or DDT levels and self-reported changes in Great Lakes fish consumption was observed. The findings from this longitudinal examination of serum PCB and DDT levels confirm earlier cross-sectional surveys of western populations, and demonstrate that the prohibition of DDT has been successful in reducing the level of DDT contamination in human populations.

Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children.

Because prenatal exposure to polychlorinated biphenyls (PCBs) and related contaminants has been associated with reduced birth weight, neonatal behavioral anomalies, and poorer recognition memory in infants born to women who have consumed Lake Michigan sports fish, 236 children, previously evaluated for PCB-related deficits in infancy, were assessed at 4 years of age. Prenatal exposure (indicated by umbilical cord serum PCB level) predicted poorer short-term memory function on both verbal and quantitative tests in a dose-dependent fashion. These effects cannot be attributed to a broad range of potential confounding variables, the impact of which was evaluated statistically. Although much larger quantities of PCBs are transferred postnatally via lactation than prenatally across the placenta, exposure from nursing was unrelated to cognitive performance. The data demonstrate the continuation of a toxic impact received in utero and observed initially during infancy on a dimension of cognitive functioning fundamental to learning.

Time trends in sport-caught Great Lakes fish consumption and serum polychlorinated biphenyl levels among Michigan Anglers, 1973-1993.

Polychlorinated biphenyls (PCBs) remain public health concerns because of their persistence in the environment and their potential health impact. We linked data from three mixed cross-sectional/longitudinal surveys of Michigan anglers conducted by the Michigan Department of Public Health in 1973-1974, 1979-1982, and 1989-1993 to examine the association between sport-caught fish consumption and serum PCBs. The reported weight of fish consumed declined over the three surveys (median 40, 38, and 31 lb/yr). Serum Aroclor 1260 levels were 2-3 times higher in fish-eaters than in nonfish-eaters in all three surveys in both men and women. In nonfish-eaters, serum PCB levels rose between 1973-1974 and 1979-1982 [adjusted change = 0.30 log(ppb), p = 0.01] and then declined between 1979-1982 and 1989-1993 [adjusted change = -0.16 log(ppb), p = 0.002]. Among fish-eaters, serum PCB levels also rose between 1973-1974 and 1979-1982 [adjusted change = 0.45 log(ppb), p < 0.001] but were unchanged between 1979-1982 and 1989-1993 [adjusted change = -0.09 log(ppb), p = 0.14]. Predictors of serum PCB levels included annual fish consumption, gender, and age. We conclude that background human serum levels of Aroclor 1260 had declined by 1989-1993 from earlier peak levels. Among consumers of sport-caught Great Lake fish, serum PCB levels did not significantly decrease, probably due to continued exposure and the long half-life of PCB.

Determinants of polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyl trichloroethane (DDT) levels in the sera of young children.

Serum samples from 285 4-year-old Michigan children were evaluated for levels of 11 environmental contaminants. Polychlorinated biphenyls (PCBs) were found in half the samples tested; polybrominated biphenyls (PBBs) in 13-21 percent; dichlorodiphenyl trichloroethane (DDT), in more than 70 percent. Nursing (Mothers' milk) was the principal source of these exposures. Congener-specific analysis documented the presence of at least one highly toxic PCB congener, 2,3',4,4',5-pentachlorobiphenyl. The data demonstrate the multigenerational impact of female exposure to persistent organic environmental contaminants.

Toronto General Hospital controlled trial data plasma exchange therapy in Guillain-Barré' syndrome.

The mechanism by which plasma exchange (PE) may benefit patients with acute Guillain-Barre' syndrome (AGBS) is unclear. It is possible, therefore, that the response of patients with AGBS is influenced by the choice of replacement solution (whole plasma vs. albumin or similar protein-containing solution). This report compares the outcome in 57 patients with AGBS treated at the Toronto General Hospital (TGH) using conventional therapy (27), PE with plasma replacement (15) and PE with albumin replacement (15). Fifteen patients (5 treated conventionally, 8 by PE with plasma replacement, 2 by PE with albumin replacement) were treated before the Baltimore coordinated multicenter trial. Forty-two patients (22 treated conventionally, 7 by PE with plasma replacement and 13 by PE with albumin replacement) were then entered at the TGH into the multicenter trial. The best outcome was observed in those patients (9) in whom PE was started within 14 days of the first neuropathic symptoms and plasma was used as replacement. The mean improvements in clinical grade in this subgroup of patients of 1.11 at four weeks after starting treatment and 1.71 at six weeks were significantly better than the corresponding improvements in the conventionally treated group of 0.35 (p less than 0.01) and 0.94 (p less than 0.05). The response of patients (9) exchanged within 14 days of onset, but replaced with albumin (grade change of 0.67 at four weeks and 0.86 at six weeks), was not significantly different from that of the conventionally treated patients. These data support the need for a randomized trial to compare PE using plasma replacement and PE using albumin replacement in patients with AGBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer among a Michigan cohort exposed to polybrominated biphenyls in 1973.

The long-term health effects of human exposure to polybrominated biphenyls are not known. In this nested case-control study, we evaluated the association between site-specific cancer risk and serum polybrominated biphenyl levels among a Michigan cohort accidentally exposed to polybrominated biphenyls in 1973. The Michigan Department of Public Health has followed 3,899 people through 1993, among whom 195 primary cancers were identified in 187 persons. Controls were 696 randomly selected cancer-free individuals who were frequency matched to cases by sex and age (in 5-year strata). Baseline serum polybrominated biphenyl levels were measured using standard methods. We found an increasing dose-response relation for digestive system cancer risk with higher serum polybrominated biphenyl category [4-20 parts per billion (ppb), 21-50 ppb, and > 50 ppb] after adjustment for age, family cancer history, cigarette smoking, alcohol drinking, and baseline serum polychlorinated biphenyl level. Adjusted odds ratios (ORs) for each category were 8.23 [95% confidence interval (CI) = 1.27-53.3], 12.3 (95% CI = 0.80-191), and 22.9 (95% CI = 1.34-392), respectively. Univariate analysis for polybrominated biphenyl level and lymphoma risk also showed a dose-response relation, with corresponding ORs of 3.24 (95% CI = 0.24-95.9), 20.5 (95% CI = 1.51-608), and 32.6 (95% CI = 3.33-861).

Changes in serum PBB and PCB levels over time among women of varying ages at exposure.

The identification of host factors that are predictors of changes in serum polyhalogenated biphenyl contaminants over time has been a difficult challenge in epidemiologic studies of exposed individuals. Of particular concern are age at exposure, reproductive and lactational histories, and changes in body mass index. Using both cross-sectional and longitudinal approaches, this study examined factors related to high initial serum PBB and PCB levels and changes in these levels over time among women of varying ages at exposure (n=1772; age range<1 to 45 years). In 1973, PBB exposure occurred through consumption of farm products contaminated with PBB added to cattle feed. Exposures to PCBs began in 1941 through PCB-contaminated silo sealant deteriorating into animal feed. The Michigan Department of Public Health began enrolling participants in 1977 and has continued to follow them through annual updates. At enrollment, questionnaires were administered to obtain demographic, lifestyle, and anthropometric measurements, medical/reproductive and occupational histories, and contaminated food consumption patterns. Blood samples were collected for PBB and PCB analysis at enrollment for all participants; additional serum tests were done on a subset of the population during follow-up. Median serum levels at enrollment were 2.0 ppb PBB and 5.0 ppb PCB. A decline in serum PBB level over an interval that ranged from 1 to 146 months (median=31) was observed for 44.6% of the women (median=1.0 ppb), while 12.2% showed an increase (median=1.0 ppb). PCB levels declined in 50.3% of the women (median=3.0 ppb) while 12.2% increased (median=2.0 ppb). Relative to women whose contaminant levels were stable, higher initial serum level was a predictor of decline for both PBB and PCB (OR=1.66, 95% CI 1.52-1.82; OR=3.26, 95% CI 2.58-4.12, respectively); a yearly increase in interval between tests was related to declining PCBs (OR=1.65, 95% CI 1.46-1.87). In addition, age< or =10 years at exposure (OR=1.72, 95% CI 1.03-2.86) and residence on a quarantined farm (OR=1.40, 95- CI 1.03-1.90) were predictors of a decrease in PBBs. Factors related to an increase in PBB levels were age< or =10 years at exposure (OR=0.30, 95% CI 0.10-0.96) and initial PBB level (OR=1.24, 95% CI 1.15-1.33); and for PCBs, high initial level (OR=1.34, 95% CI 1.17-1.53) and body mass index (OR=1.07, 95% CI 1.01-1.13). One or more live births during the interval between tests were not related to changing levels of either contaminant; breastfeeding data were not available for examination. Early age at exposure appears to be an important predictor of changes in serum PBB levels over time.

Motor function in aging Great Lakes fisheaters.

Exposure to contaminants in Great Lakes fish has been linked to impaired neuropsychological functioning in children, but neurological function of exposed adults has not been evaluated. This report describes a cross-sectional analysis of the effects of PCB/DDE exposure from contaminated fish on fine motor function in older adults. The subjects were 50-90-year-old Michigan residents who were members of a previously established study cohort. Fisheaters ate 24 lbs or more of sport-caught Lake Michigan fish/year at the time they were originally recruited in 1980-1982. Age- and sex-matched non-fisheaters ate 6 or fewer lbs/year. Outcome measures were scores on the Static Motor Steadiness Test (SMST) and Grooved Pegboard Test (GPT). PCB/DDE exposure was determined through serum analyses performed at the time of recruitment into the present study in 1993-1995. Because of the high correlation between serum PCB and DDE levels in this sample (Spearman r=0.64, P<0.0001), the effects of the two contaminants were assessed jointly using a single derived exposure variable=Low=both PCB and DDE at or below the medians of their respective distributions, intermediate=PCB and/or DDE in the third quartile, and high=PCB and/or DDE in the upper quartile. In unadjusted analyses, high exposure to PCBs/DDE was associated with significantly poorer performance on the GPT (P=0.03). However, in the multiple regression model, age and gender emerged as the most significant factors affecting GPT scores, and exposure to PCB/DDE was not significant. Performance on the SMST was not related to PCB/DDE exposure in initial unadjusted analyses, but performance with the dominant hand was marginally (P=0.052) associated with exposure in the final model. Scores on the SMST improved slightly as PCB/DDE exposure increased. A similar trend was not observed for the nondominant hand (P=0.46). These findings suggest that PCB/DDE exposure from Great Lakes fish has not significantly impaired hand steadiness or visual-motor coordination in this sample of older adults.