Anna Callan

Maternal exposure to metals—Concentrations and predictors of exposure

A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations of metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01-0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01-0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation.

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Fetal growth is determined by a complex interplay of genetic, nutritional, environmental, and hormonal factors. Greater than expected fetal growth has been positively associated with the risk of the development of some cancers in childhood, particularly acute lymphoblastic leukemia, and the biological mechanisms underlying such associations are thought to involve insulin-like growth factors (IGFs). Circulating IGF levels are highly correlated with fetal growth, and IGFs are believed to play an important role in carcinogenesis; however, these two bodies of evidence have not been well integrated and, as a result, the potential underlying biological mechanisms linking the IGF system with the development of specific childhood cancers have not been elucidated. This review aims to draw together and summarize the literature linking the IGF system, rapidity of fetal growth, and risk of some specific childhood cancers; suggest explanations for some of the inconsistencies observed in previous studies of these associations; and propose an integrated framework for the putative involvement of the IGF system in the development of at least some childhood cancers. If the challenges involved in studying the complex IGF system can be overcome, this field presents an exciting opportunity to elucidate etiological pathways to childhood malignancies.

Cadmium, lead and mercury exposure in non smoking pregnant women

Recent literature suggests that exposure to low concentrations of heavy metals may affect both maternal and child health. This study aimed to determine the biological heavy metals concentrations of pregnant women as well as environmental and dietary factors that may influence exposure concentrations. One hundred and seventy three pregnant women were recruited from Western Australia, each providing a sample of blood, first morning void urine, residential soil, dust and drinking water samples. Participants also completed a questionnaire which included a food frequency component. All biological and environmental samples were analysed for heavy metals using ICP-MS. Biological and environmental concentrations of lead and mercury were generally low (Median Pb Drinking Water (DW) 0.04 µg/L; Pb soil <3.0 µg/g; Pb dust 16.5 µg/g; Pb blood 3.67 µg/L; Pb urine 0.55; µg/L Hg DW <0.03; Hg soil <1.0 µg/g; Hg dust <1.0 µg/g; Hg blood 0.46 µg/L; Hg urine <0.40 µg/L). Cadmium concentrations were low in environmental samples (Median CdDW 0.02 µg/L; Cdsoil <0.30 ug/g; Cddust <0.30) but elevated in urine samples (Median 0.55 µg/L, creatinine corrected 0.70 µg/g (range <0.2-7.06 µg/g creatinine) compared with other studies of pregnant women. Predictors of increased biological metals concentrations in regression models for blood cadmium were residing in the Great Southern region of Western Australia and not using iron/folic acid supplements and for urinary cadmium was having lower household annual income. However, these factors explained little of the variation in respective biological metals concentrations. The importance of establishing factors that influence low human exposure concentrations is becoming critical in efforts to reduce exposures and hence the potential for adverse health effects.

Concentrations of polybrominated diphenyl ethers (PBDEs) in residential dust samples from Western Australia

Polybrominated diphenyl ethers (PBDEs) are one of the most common types of brominated flame retardants applied to foams, plastics and textiles to prevent fires. These flame retardants are now regulated and are either banned or being voluntarily phased. However, as these chemicals are persistent humans continue to be exposed. Dust has been identified as an important source of exposure and hence residential concentrations are of interest. The aim of this paper was to determine the concentrations of PBDEs in samples of residential dust from the homes of pregnant women in Western Australia. Thirty residential dust samples were analysed for concentrations of 32 PBDE congeners. Samples were collected from urban and rural areas. PBDEs were detected in all residential dust samples with the sum of the most common PBDEs (Σ(7) of BDEs 47, 99, 100, 153, 154, 183 and 209) ranging from 60.4 to 82400 ng g(-1) (median 571 ng g(-1)). DecaBDE makes up the highest proportion of PBDEs in residential dust, on average 66% of Σ(32)PBDEs. We did not find a relationship between housing characteristics nor the presence of appliances and PBDE concentrations. Dust from urban areas had significantly higher concentrations of BDE-209 and Σ(32)PBDEs than dust from rural areas of Western Australia (p values 0.01 and 0.03 respectively). PBDEs were present in residential dust in Western Australia at concentrations higher than reported previously in Australia. Further investigation of sources with a larger sample size is required to determine associations between PBDE concentrations and potential exposure sources and geographical regions.

Polybrominated diphenyl ether (PBDE) concentrations in plasma of pregnant women from Western Australia.

PBDEs are a class of brominated flame retardants applied to consumer goods to reduce their flammability. These compounds are lipophilic, persistent and bioaccumulate through the food web. PBDEs have been detected in human blood, adipose tissue and breast milk. There are a small number of studies reporting concentrations of PBDEs in Australian populations. These indicate that concentrations are higher than in studies reporting concentrations from Europe but lower than those from Northern America. The aim of this paper was to determine the concentrations of PBDEs in the plasma of pregnant women participating in the Australian Maternal Exposure to Toxic Substances (AMETS) study in Western Australia. The samples comprised 164 pregnant women, aged 18 years and over, who were non-smokers and not occupationally exposed to persistent substances. Participants provided blood samples at 38 weeks gestation and these were analysed for five PBDE congeners. Maternal health and birth outcomes data were also obtained. The median for sum PBDE concentrations in plasma was 53.9 pg g(-1) (range 13.2 to 1390 pg g(-1)ww). Concentrations were adjusted for the estimated plasma lipid content. The concentrations of Σ5PBDE ranged from 2.44 to 258 ng g(-1) lipid with a median of 9.97 ng g(-1) lipid. BDE-47 was the dominant congener (median 21.4 pg g(-1), range <4.95 to 1030 pg g(-1)) followed by BDE-153 (median 12.2 pg g(-1), range <2.94 to 353 pg g(-1)). There were no significant associations between maternal, housing or dietary factors and concentrations of PBDEs in this study. Maternal PBDE concentrations were not associated with infant birth weight. This study builds upon previous Australian research and shows that concentrations in this sample of Western Australian women were higher than in parts of Europe.

Urinary bisphenol A concentrations in pregnant women

Bisphenol A is a chemical that is present in a number of products and types of food packaging. Prenatal exposure to bisphenol A may cause behavioural changes in young children. The aim of this study was to investigate exposure to bisphenol A in pregnant Australian women as a surrogate of neonatal exposure. First morning void urine samples were collected from 26 pregnant women at around week 38 of gestation. Bisphenol A was detectable in 85% of the samples analysed. The median concentration in this group of women was 2.41μg/L with a range of <LOD - 5.66μg/L. Women experiencing their first pregnancy had slightly higher urinary bisphenol A concentrations, as did women with a pre-pregnancy BMI of <25, however these relationships did not reach significance. This study provides the first information on bisphenol A exposure in Australia and reveals that pregnant women have measured biological concentrations of urinary bisphenol A similar to those reported for pregnant women in other developed countries. Given the potential impacts of prenatal bisphenol A exposure, further research in this area is warranted.

Estimating maternal and prenatal exposure to glyphosate in the community setting

Glyphosate is a herbicide in common use, in both agricultural and residential settings. Controlled residue studies show that glyphosate persists in food crops, allowing for the potential of a large number of people to be exposed. Glyphosate is generally considered safe however there are a number of studies suggesting formulations or additives that may have adverse health effects. To assess the degree of exposure of pregnant women, this study measured glyphosate in composite food samples and estimated exposure based on food frequency questionnaire. 43 pregnant women were recruited and completed a self administered questionnaire with a food frequency component and provided a composite food sample. Twenty food samples were analysed with very low glyphosate concentrations (mean 0.08 mg/kg, range 0.002-0.5 mg/kg) with residues detected in more than 75% of the samples. Maternal dietary exposure was very low (0.001 mg/kg bw/day) and was considerably lower than the predicted National Estimated Daily Intake of glyphosate (0.02 mg/kg bw/day). The estimated exposure based on measured glyphosate in composite food samples corresponded to 0.4% of the acceptable daily intake for glyphosate, and the predicted concentration from dietary information was 4% which is comparable to the National Estimated Daily Intake of 5.5% of the Acceptable Daily Intake of glyphosate. Prenatal exposures were estimated to be significantly lower. While residues of glyphosate are present in food, this study demonstrates that exposure concentrations are low and confirms the current models used to estimate glyphosate exposure.

Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 μg/g creatinine (range <0.065-1.03 μg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

Environmental and toenail metals concentrations in copper mining and non mining communities in Zambia

Copper mining contributes to increased concentrations of metals in the environment, thereby increasing the risk of metals exposure to populations living in and around mining areas. This study investigated environmental and toenail metals concentrations of non-occupational human exposure to metals in 39 copper-mining town residents and 47 non-mining town residents in Zambia. Elevated environmental concentrations were found in samples collected from the mining town residents. Toenail concentrations of cobalt (GM 1.39 mg/kg), copper (GM 132 mg/kg), lead (21.41 mg/kg) selenium (GM 0.38 mg/kg) and zinc (GM 113 mg/kg) were significantly higher in the mining area and these metals have previously been associated with copper mining. Residence in the mining area, drinking water, dust and soil metals concentrations were the most important contributors to toenail metals concentrations. Further work is required to establish the specific pathways of exposure and the health risks of elevated metals concentrations in the copper mining area.

Metals in commonly eaten groceries in Western Australia: a market basket survey and dietary assessment

Children’s dietary exposure to metals has received limited attention in Australia. This study undertook a market basket survey and analysed 253 food and beverages for metals. These data were used in conjunction with recent average diet data for children in Western Australia to model dietary metals exposure, with mean metals intakes calculated for boys and girls aged 8, 12, 13 and 16 years. Results show that for some metals, including cadmium, nickel and manganese, dietary intake guidelines have been exceeded in younger children. The mean modelled cadmium intake in children aged 8 years was almost 60% of the World Health Organisation (WHO) guideline and exceeded the European Food Safety Authority (EFSA) guideline. Nickel and manganese intake was higher in younger children than reported in international studies. Modelling based on the 95% percentile of dietary consumption exceeded the respective guidelines or upper level of intake for several of the metals studied. The findings from this study support the need for further investigation into the exposure of children to metals from diet and the health implications of exposure.