Susan A. Korrick

Evidence on the Human Health Effects of Low Level Methylmercury Exposure

Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.

Which fish should I eat? Perspectives influencing fish consumption choices.

Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.

Lead, Diabetes, Hypertension, and Renal Function: The Normative Aging Study

In this prospective study, we examined changes in renal function during 6 years of follow-up in relation to baseline lead levels, diabetes, and hypertension among 448 middle-age and elderly men, a subsample of the Normative Aging Study. Lead levels were generally low at baseline, with mean blood lead, patella lead, and tibia lead values of 6.5 μg/dL, 32.4 μg/g, and 21.5 μg/g, respectively. Six percent and 26% of subjects had diabetes and hypertension at baseline, respectively. In multivariate-adjusted regression analyses, longitudinal increases in serum creatinine (SCr) were associated with higher baseline lead levels but these associations were not statistically significant. However, we observed significant interactions of blood lead and tibia lead with diabetes in predicting annual change in SCr. For example, increasing the tibia lead level from the midpoints of the lowest to the highest quartiles (9–34 μg/g) was associated with an increase in the rate of rise in SCr that was 17.6-fold greater in diabetics than in nondiabetics (1.08 mg/dL/10 years vs. 0.062 mg/dL/10 years; p < 0.01). We also observed significant interactions of blood lead and tibia lead with diabetes in relation to baseline SCr levels (tibia lead only) and follow-up SCr levels. A significant interaction of tibia lead with hypertensive status in predicting annual change in SCr was also observed. We conclude that longitudinal decline of renal function among middle-age and elderly individuals appears to depend on both long-term lead stores and circulating lead, with an effect that is most pronounced among diabetics and hypertensives, subjects who likely represent particularly susceptible groups.

Prenatal Exposure to Mercury and Fish Consumption During Pregnancy and Attention-Deficit/Hyperactivity Disorder-Related Behavior in Children

OBJECTIVE To investigate the association of prenatal mercury exposure and fish intake with attention-deficit/hyperactivity disorder (ADHD)-related behavior. METHODS For a population-based prospective birth cohort recruited in New Bedford, Massachusetts (1993-1998), we analyzed data for children examined at age 8 years with peripartum maternal hair mercury measures (n = 421) or maternal report of fish consumption during pregnancy (n = 515). Inattentive and impulsive/hyperactive behaviors were assessed using a teacher rating scale and neuropsychological testing. RESULTS The median maternal hair mercury level was 0.45 μg/g (range, 0.03-5.14 μg/g), and 52% of mothers consumed more than 2 fish servings weekly. In multivariable regression models, mercury exposure was associated with inattention and impulsivity/hyperactivity; some outcomes had an apparent threshold with associations at 1 μg/g or greater of mercury. For example, at 1 μg/g or greater, the adjusted risk ratios for mild/markedly atypical inattentive and impulsive/hyperactive behaviors were 1.4 (95% CI, 1.0-1.8) and 1.7 (95% CI, 1.2-2.4), respectively, for an interquartile range (0.5 μg/g) mercury increase; there was no confounding by fish consumption. For neuropsychological assessments, mercury and behavior associations were detected primarily for boys. There was a protective association for fish consumption (>2 servings per week) with ADHD-related behaviors, particularly impulsive/hyperactive behaviors (relative risk = 0.4; 95% CI, 0.2-0.6). CONCLUSIONS Low-level prenatal mercury exposure is associated with a greater risk of ADHD-related behaviors, and fish consumption during pregnancy is protective of these behaviors. These findings underscore the difficulties of balancing the benefits of fish intake with the detriments of low-level mercury exposure in developing dietary recommendations in pregnancy.

Organochlorine exposures during pregnancy and infant size at birth.

Background: Organochlorines, including polychlorinated biphenyls (PCBs) and pesticides, are environmentally persistent contaminants that concentrate in the food chain as well in human adipose tissue and readily cross the placenta. Methods: To follow up on studies suggesting an association of organochlorine exposure with reduced birth size, we investigated the association of PCBs and organochlorine pesticides (including p,p′-dichlorodiphenyl dichloroethene [p,p′-DDE], the major degradation product of p,p′-dichlorodiphenyl trichloroethane [p,p′-DDT], and hexachlorobenzene [HCB]), with birth weight, crown-heel length, and head circumference. We evaluated a cohort of 722 infants born between 1993 and 1998 to mothers residing near a PCB-contaminated harbor and Superfund site in New Bedford, Massachusetts. Results: Small negative associations were observed for PCBs and birth weight; associations were weaker for birth length and head circumference. There was evidence for effect modification by smoking during pregnancy on the association between PCBs and birth weight. No associations were found with p,p′-DDE or HCB for any measures of birth size. Conclusions: This study supports the growing literature that demonstrates at most a weak association between very low-level organochlorine exposure and birth size.

Prenatal Organochlorine Exposure and Measures of Behavior in Infancy Using the Neonatal Behavioral Assessment Scale (NBAS)

Background Previous literature suggests an association between organochlorines and behavioral measures in childhood, including inattention. Objective This study was designed to assess whether prenatal organochlorine exposure is associated with measures of attention in early infancy. Methods We investigated an association between cord serum polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyl dichloroethene (DDE) levels and measures of attention from the Neonatal Behavioral Assessment Scale (NBAS) in a cohort of 788 infants born 1993–1998 to mothers residing near a PCB-contaminated harbor and Superfund site in New Bedford, Massachusetts. Results Medians (ranges) for the sum of four prevalent PCB congeners and DDE levels were 0.19 (0.01–4.41) and 0.30 (0–10.29) ng/g serum, respectively. For the 542 subjects with an NBAS exam at 2 weeks, we observed consistent inverse associations between cord serum PCB and DDE levels and NBAS measures of alertness, quality of alert responsiveness, cost of attention, and other potential attention-associated measures including self-quieting and motor maturity. For example, the decrement in quality of alert responsiveness score was −0.51 (95% confidence interval, −0.99 to −0.03) for the highest quartile of exposure to the sum of four prevalent PCB congeners compared with the lowest quartile. We found little evidence for an association with infant orientation, habituation, and regulation of state, assessed as summary cluster measures. Conclusions Our findings provide evidence for an association between low-level prenatal PCB and DDE exposures and poor attention in early infancy. Further analyses will focus on whether organochlorine-associated decrements in attention and attention-related skills in infancy persist in later childhood.

Polychlorinated biphenyls, organochlorine pesticides and neurodevelopment.

Purpose of review Although environmental levels of polychlorinated biphenyls and certain organochlorine pesticides – hexachlorobenzene, dichlorodiphenyl trichloroethane and its primary metabolite, dichlorodiphenyl dichloroethene – are generally on the decline, early-life exposures to these prevalent contaminants continue. The review will describe current understanding of the potential neurodevelopmental consequences of low-level exposures to these contaminants. Recent findings Animal models suggest that early-life exposures to polychlorinated biphenyls, dichlorodiphenyl trichloroethane/dichlorodiphenyl dichloroethene or hexachlorobenzene are associated with decreased cognitive or behavioral function in later development. Despite almost 30 years of research, however, results of human studies are inconsistent regarding the nature of the observed effects and their persistence over time. Overall, epidemiologic studies support modest associations of primarily prenatal polychlorinated biphenyl exposures with differences in neuromotor development, decrements in cognition and behavioral deficits, particularly regarding attention and impulse control. There are limited published human data regarding potential neurodevelopmental toxicities of early-life exposures to dichlorodiphenyl trichloroethane/dichlorodiphenyl dichloroethene and hexachlorobenzene. Summary Exposures to polychlorinated biphenyls, dichlorodiphenyl trichloroethane/dichlorodiphenyl dichloroethene and hexachlorobenzene are likely detrimental to neurodevelopment. Effective control of exposure is complicated by variable exposure sources and variable contaminant levels in food, particularly fish, for which it is important to balance the risk of contaminants with nutritional benefits.

Neuropsychological measures of attention and impulse control among 8-year-old children exposed prenatally to organochlorines.

Background: We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher’s rating scale for a birth cohort in New Bedford, Massachusetts (USA). Objectives: Our goal was to corroborate these findings using neuropsychological measures of inattentive and impulsive behaviors. Methods: We investigated the association between cord serum polychlorinated biphenyls (PCBs) and p,p´-dichlorodiphenyl dichloroethylene (p,p´-DDE) and attention and impulse control using a Continuous Performance Test (CPT) and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III). Participants came from a prospective cohort of children born during 1993–1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138, 153, and 180 (ΣPCB4)] and p,p´-DDE were 0.19 (0.01–2.59) and 0.31 (0–14.93) ng/g serum, respectively. Results: We detected associations between PCBs and neuropsychological deficits for 578 and 584 children with CPT and WISC-III measures, respectively, but only among boys. For example, boys with higher exposure to ΣPCB4 had a higher rate of CPT errors of omission [rate ratio for the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI): 0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = –2.0; 95% CI: –3.5, –0.4). Weaker associations were found for p,p´-DDE. For girls, associations were in the opposite direction for the CPT and null for the WISC-III. Conclusions: These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sex-specific effects should be considered in studies of organochlorines and neurodevelopment.

Cumulative Exposure to Lead in Relation to Cognitive Function in Older Women

Background Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. Objective We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. Methods Patella and tibia bone lead—measures of cumulative exposure over many years—and blood lead, a measure of recent exposure, were assessed in 587 women 47–74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. Results Mean ± SD lead levels in tibia, patella, and blood were 10.5 ± 9.7 μg/g bone, 12.6 ± 11.6 μg/g bone, and 2.9 ± 1.9 μg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: −0.099 to −0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. Conclusions These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age.

Association of blood lead levels with onset of puberty in Russian boys

Background Epidemiologic studies suggest a temporal trend of earlier onset and longer duration of puberty, raising concerns regarding the potential impact of environmental factors on pubertal development. Lead exposure has been associated with delayed pubertal onset in girls; however, epidemiologic data in boys are limited. Methods We used multivariable logistic regression models to explore the cross-sectional association of blood lead levels with growth and pubertal onset based on physician-assessed testicular volume (TV) and pubertal staging in 489 boys 8–9 years of age from Chapaevsk, Russia. We used multivariable linear regression models to assess associations of blood lead levels with somatic growth at the study entry visit. Results The median (25th–75th percentile) blood lead level was 3 μg/dL (2–5 μg/dL). Height, weight, body mass index, birth weight, and gestational age were predictive of the onset of puberty as assessed either by TV (> 3 mL), genitalia stage (G2), or both. Blood lead level was inversely associated with height (p < 0.001) and weight (p = 0.06) after adjustment for birth weight, gestational age, and age at examination. In multivariable adjusted analyses, boys with blood lead levels ≥ 5 μg/dL had 43% reduced odds of having entered G2 compared with those with lower levels (odds ratio = 0.57; 95% confidence interval, 0.34–0.95, p = 0.03). Conclusions Relatively low environmental blood lead levels were associated with decreased growth and differences in pubertal onset in periadolescent Russian boys. Future analyses of this prospective cohort will address pubertal onset and progression in relation to lead and other environmental chemicals.