Deconjugation of soy isoflavone glucuronides needed for estrogenic activity.

Soy isoflavones (SIF) are present in the systemic circulation as conjugated forms of which the estrogenic potency is not yet clear. The present study provides evidence that the major SIF glucuronide metabolites in blood, genistein-7-O-glucuronide (GG) and daidzein-7-O-glucuronide (DG), only become estrogenic after deconjugation. The estrogenic potencies of genistein (Ge), daidzein (Da), GG and DG were determined using stably transfected U2OS-ERα, U2OS-ERß reporter gene cells and proliferation was tested in T47D-ERß cells mimicking the ERα/ERß ratio of healthy breast cells and inT47D breast cancer cells. In all assays applied, the estrogenic potency of the aglycones was significantly higher than that of their corresponding glucuronides. UPLC analysis revealed that in U2OS and T47D cells, 0.2-1.6% of the glucuronides were deconjugated to their corresponding aglycones. The resulting aglycone concentrations can account for the estrogenicity observed upon glucuronide exposure. Interestingly, under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating these glucuronides than human breast tissue S9 fraction. Our study confirms that SIF glucuronides are not estrogenic as such, and that the small % of deconjugation in the cell is enough to explain the slight bioactivity observed for the SIF-glucuronides. Species differences in deconjugation capacity should be taken into account when basing risk-benefit assessment of these SIF for the human population on animal data.

State of the art in benefit-risk analysis: food and nutrition.

Benefit-risk assessment in food and nutrition is relatively new. It weighs the beneficial and adverse effects that a food (component) may have, in order to facilitate more informed management decisions regarding public health issues. It is rooted in the recognition that good food and nutrition can improve health and that some risk may be acceptable if benefit is expected to outweigh it. This paper presents an overview of current concepts and practices in benefit-risk analysis for food and nutrition. It aims to facilitate scientists and policy makers in performing, interpreting and evaluating benefit-risk assessments. Historically, the assessments of risks and benefits have been separate processes. Risk assessment is mainly addressed by toxicology, as demanded by regulation. It traditionally assumes that a maximum safe dose can be determined from experimental studies (usually in animals) and that applying appropriate uncertainty factors then defines the 'safe' intake for human populations. There is a minor role for other research traditions in risk assessment, such as epidemiology, which quantifies associations between determinants and health effects in humans. These effects can be both adverse and beneficial. Benefit assessment is newly developing in regulatory terms, but has been the subject of research for a long time within nutrition and epidemiology. The exact scope is yet to be defined. Reductions in risk can be termed benefits, but also states rising above 'the average health' are explored as benefits. In nutrition, current interest is in 'optimal' intake; from a population perspective, but also from a more individualised perspective. In current approaches to combine benefit and risk assessment, benefit assessment mirrors the traditional risk assessment paradigm of hazard identification, hazard characterization, exposure assessment and risk characterization. Benefit-risk comparison can be qualitative and quantitative. In a quantitative comparison, benefits and risks are expressed in a common currency, for which the input may be deterministic or (increasingly more) probabilistic. A tiered approach is advocated, as this allows for transparency, an early stop in the analysis and interim interaction with the decision-maker. A general problem in the disciplines underlying benefit-risk assessment is that good dose-response data, i.e. at relevant intake levels and suitable for the target population, are scarce. It is concluded that, provided it is clearly explained, benefit-risk assessment is a valuable approach to systematically show current knowledge and its gaps and to transparently provide the best possible science-based answer to complicated questions with a large potential impact on public health.

Residues of persistent organic pollutants (POPs) in human milk in Hong Kong.

Data on pesticide body load in the south China region are scarce. Here, we report the concentrations of 24 persistent organic pollutants (POPs), in 10 pools of human milk samples, collected at 2-6weeks postpartum from 238 primiparous women living in Hong Kong and south China, who participated in the 2002-2003 WHO exposure study. Residues were determined by gas chromatography with electron capture detector and confirmed by gas chromatography with mass spectrometry. The mean levels of alpha-HCH (mean 0.6ngg(-1) fat), beta-HCH (940ngg(-1) fat), gamma-HCH (1.8ngg(-1) fat), dieldrin (1.0ngg(-1) fat) and HCB (21.8ngg(-1) fat) were much lower than the 1985 estimates. Mean levels of alpha-HCH, gamma-HCH, dieldrin, cis-heptachlor-epoxide (0.7ngg(-1) fat), sum-chlordane (6.1ngg(-1) fat), trans-nonachlor (12.0ngg(-1) fat), BDE 47 (1.9ngg(-1) fat) and sum PBDE (3.4ngg(-1) fat) were comparable to the international median levels of the 15 other countries participating in the 2002-03 WHO exposure study. Hong Kong had the highest level of beta-HCH, possibly a residual effect of previous high exposures in the 1970s. Body loads of beta-HCH and chlordane were lower among mothers with younger age while mothers born in mainland China had lower levels of beta-HCH, cis-heptachlor-epoxide, oxy-chlordane and trans-nonachlor. Levels of toxaphene, endrin, endosulfan, bromcyclene and nitrofen were not detected in all or almost all of the milk pools. Continuous monitoring of POPs in human milk, especially beta-HCH, is needed for surveillance and interpretation of time trends, and for linkage to strict enforcement of agricultural regulations.

DDT levels in human milk in Hong Kong, 2001-02.

High levels of p,p'-DDT were detected in Hong Kong breast milk sampled in 1976 and 1985. Monitoring DDT levels in human breast milk in this region is important to identify trends in exposure. As part of the 2002-03 WHO/EURO coordinated exposure study, the concentrations of DDT and its metabolites were determined in 10 pooled milk samples classified by geographic origin and dietary history, comprising milk samples from 238 primiparous mothers giving birth in Hong Kong. Analysis was performed by Gas Chromatography (GC) with electron capture detector and confirmed by GC/Mass Spectrometry. The sum-DDT concentration (range: 0.92-2.05 mg/kg fat) was age-dependent and indicated a decreasing trend since the 1970s. Mothers who recently came from mainland China had higher p,p'-DDT to p,p'-DDE ratios, suggesting a more recent exposure compared to women mainly residing in Hong Kong. The average Hong Kong sum-DDT level (1.50 mg/kg fat) was among the highest of the contemporary levels (range: 0.12-1.97 mg/kg fat; median: 0.40 mg/kg fat) in the 16 countries/regions participating in the 2002-03 WHO/EURO exposure study. This is probably due to the previous extensive DDT exposure and continuing use of DDT in agriculture in mainland China. Despite the apparent decrease of DDT body load over 30 years, the environmental health hazard from DDT contamination in the Pearl River Delta region remains a concern. Measures to eradicate illegal use of DDT in mainland China and regular food monitoring programs are needed in the region. Despite the presence of DDT and other persistent organic pollutants in human breast milk, breastfeeding should continue to be strongly supported for its life-long benefits to infants.