Phthalate Diesters and Their Metabolites in Human Breast Milk, Blood or Serum, and Urine as Biomarkers of Exposure in Vulnerable Populations

BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants

Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

Background: The ‘exposome’ represents the accumulation of all environmental exposures across a lifetime. Topdown strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual’s metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods: High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Results: Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4- deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. Conclusions: This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research. Keywords: metabonomics, cadmium, environmental health, exposome, metabolomics, molecular epidemiolog

Impact of soil properties on critical concentrations of cadmium, lead, copper, zinc and mercury in soil and soil solution in view of ecotoxicological effects

Concern about the input of metals to terrestrial ecosystems is related to (i) the ecotoxicological impact on soil organisms and plants (Bringmark et al. 1998; Palmborg et al. 1998) and also on aquatic organisms resulting from runoff to surface water and (ii) the uptake via food chains into animal tissues and products, which may result in health effects on animals and humans (Clark 1989). Effects on soil organisms, including microorganisms/macrofungi and soil fauna, such as nematodes and earthworms, are reduced species diversity, abundance, and biomass and changes in microbe-mediated processes (Bengtsson and Tranvik 1989; Giller et al. 1998; Vig et al. 2003). Effects on vascular plants include reduced development and growth of roots and shoots, elevated concentrations of starch and total sugar, decreased nutrient contents in foliar tissues, and decreased enzymatic activity (Prasad 1995; Das et al. 1997). A review of these phytotoxic effects is given by Balsberg-Påhlsson (1989). Effects on aquatic organisms, including algae, Crustacea, and fish, include effects on gill function (Sola et al. 1995), nervous systems (Baatrup 1991), and growth and reproduction rates (Mance 1987). Environmental quality standards or critical limits, often also denoted as Predicted No Effect Concentrations, or PNECs, for metals in soils and surface waters related to those effects serve as a guide in the environmental risk assessment process for those substances