Henry G. Abadin

Breast-Feeding Exposure of Infants To Cadmium, Lead, and Mercury: a Public Health Viewpoint

The purpose of this report is to provide an overview of the public health implications of exposure via breast milk to cadmium, lead, and mercury for nursing infants and to provide health-based guidance. Daily intakes were calculated and compared with guidance values used for public health assessments at hazardous waste sites. Cadmium, lead, and mercury under normal conditions are found in breast milk at concentration ranges of < 1 μg/L, 2-5 μg/L, and 1.4-1.7 μg/L, respectively. Women exposed environmentally or occupationally can have higher levels in their breast milk. Concentrations of about 5 μg/L (cadmium), 20 μg/L (lead), and 3.5 μg/L (mercury) appear to be adequate screening levels. Many factors affect both the distribution of cadmium, lead, and mercury in breast milk and the health consequences to an infant. It is not clear what additional impact low-level exposure via breast milk may have on an infant born with a body burden to one of these metals. There is sufficient evidence to make the case that contaminated breast milk is a source of potential risk to infants in certain populations. Prevention strategies that include behavior modification and proper nutrition should be communicated to women at risk. Identification and elimination of exposure pathways and a critical analysis of the benefits of breast feeding versus heavy metal exposure are needed on a site-specific or individual basis. Research is required to better understand the impact of low-level exposure to heavy metals via breast milk. Breastfeeding should be encouraged under most circumstances.

Lead and δ-Aminolevulinic Acid Dehydratase Polymorphism: Where Does It Lead? A Meta-Analysis

Background Lead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. Objective Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. Data source We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid–chelatable lead, or blood pressure. Data extraction Sample sizes, means, and standard deviations were extracted for the genotype groups. Data synthesis There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 μg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 μg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. Conclusion Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes.

Association of low-level blood lead and blood pressure in NHANES 1999-2006

This study investigated whether low blood-lead levels (≤10 μg/dL) were associated with blood pressure (BP) outcomes. The authors analyzed data from National Health and Nutrition Examination Survey 1999-2006 and participants aged 20 years or older. Outcome variables were systolic and diastolic BP measurements, pulse pressure, and hypertension status. Multivariable linear and logistic regressions stratified by race/ethnicity and gender were performed. Blood lead levels (BLL) were significantly correlated with higher systolic BP among black men and women, but not white or Mexican-American participants. BLLs were significantly associated with higher diastolic BPs among white men and women and black men, whereas, a negative association was observed in Mexican-American men that had, also, a wider pulse pressure. Black men in the 90th percentile of blood lead distribution (BLL≥3.50 μg/dL) compared to black men in the 10th percentile of blood lead distribution (BLL≤0.7 μg/dL) had a significant increase of risk of having hypertension (adjusted POR=2.69; 95% CI: 1.08-6.72). In addition, blood cadmium was significantly associated with hypertension and systolic and diastolic blood. This study found that, despite the continuous decline in blood lead in the U.S. population, lead exposure disparities among race and gender still exist.

10:Metal Ions Affecting the Neurological System

Several individual metals including aluminum, arsenic, cadmium, lead, manganese, and mercury were demonstrated to affect the neurological system. Metals are ubiquitous in the environment. Environmental and occupational exposure to one metal is likely to be accompanied by exposure to other metals, as well. It is, therefore, expected that interactions or “joint toxic actions” may occur in populations exposed to mixtures of metals or to mixtures of metals with other chemicals. Some metals seem to have a protective role against neurotoxicity of other metals, yet other interactions may result in increased neurotoxicity. For example, zinc and copper provided a protective role in cases of lead-induced neurotoxicity. In contrast, arsenic and lead co-exposure resulted in synergistic effects. Similarly, information is available in the current literature on interactions of metals with some organic chemicals such as ethanol, polychlorinated biphenyls, and pesticides. In depth understanding of the toxicity and the mechanism of action (including toxicokinetics and toxicodynamics) of individual chemicals is important for predicting the outcomes of interactions in mixtures. Therefore, plausible mechanisms of action are also described.

DDT/DDE and breast cancer: a meta-analysis.

The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. We searched PubMed and Web of Science for studies published through June 2012 assessing DDT/DDE exposure and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE (1.05; 95% CI: 0.93-1.18) and DDT (1.02; 95% CI: 0.92-1.13). Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls (11.30 ng/g lipid; p=0.01). No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans.

Metal ions affecting the hematological system.

Many metals are essential elements and necessary for proper biological function at low intake levels. However, exposure to high intake levels of these metals may result in adverse effects. In addition, exposures to mixtures of metals may produce interactions that result in synergistic or antagonistic effects. This chapter focuses on metals that affect the hematological system and how exposures to mixtures of metals may contribute to their hematotoxicity. Exposure to arsenic, cadmium, copper, lead, mercury, tin or zinc has been shown to produce some effect on the hematological system. Binary interactions resulting from exposure to combinations of metals may increase or decrease the hematotoxicity induced by individual metals. For example, copper, iron, and zinc have been shown to have a protective effect on the hematotoxicity of lead. In contrast, co-exposure to manganese may increase the hematotoxicity of lead.

13. Historical View on Lead: Guidelines and Regulations

Lead has been used in many commodities for centuries. As a result, human exposure has occurred through the production and use of these lead-containing products. For example, leaded gasoline, lead-based paint, and lead solder/pipes in water distribution systems have been important in terms of exposure potential to the general population. Worker exposures occur in various industrial activities such as lead smelting and refining, battery manufacturing, steel welding or cutting operations, printing, and construction. Some industrial locations have also been a source of exposure to the surrounding communities. While the toxicity of relatively high lead exposures has been recognized for centuries, modern scientific studies have shown adverse health effects at very low doses, particularly in the developing nervous system of fetuses and children. This chapter reflects on historical and current views on lead toxicity. It also addresses the development and evolution of exposure prevention policies. As discussed here, these lead policies target a variety of potential exposure routes and sources. The changes reflect our better understanding of lead toxicity. The chapter provides lead-related guidelines and regulations currently valid in the U. S. and in many countries around the world. The reader will learn about the significant progress that has been made through regulations and guidelines to reduce exposure and prevent lead toxicity.

Windows of sensitivity to toxic chemicals in the development of reproductive effects: an analysis of ATSDR’s toxicological profile database

ABSTRACT Development of the fetus is a complex process influenced by many factors including genetics, maternal health, and environmental exposures to toxic chemicals. Adverse developmental effects on the reproductive system have the potential to harm generations beyond those directly exposed. Here, we review the available literature in Agency for Toxic Substances and Disease Registry toxicological profiles related to reproductive-developmental effects in animals following in utero exposure to chemicals. We attempt to identify windows of sensitivity. In the discussion, we correlate the findings with human development. The endpoints noted are fertility, estrus, anogenital distance, sex ratio, spermatogenesis, and mammary gland development. We identified some windows of sensitivity; however, the results were hampered by chronic-exposure studies designed to detect effects occurring throughout developmental, including multi-generational studies. This paper demonstrates the need for more acute studies in animals aimed at understanding time periods of development that are more susceptible to chemically induced adverse effects.