International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

Comparison of transcriptional responses in liver tissue and primary hepatocyte cell cultures after exposure to hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine

BACKGROUND: Cell culture systems are useful in studying toxicological effects of chemicals such as Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), however little is known as to how accurately isolated cells reflect responses of intact organs. In this work, we compare transcriptional responses in livers of Sprague-Dawley rats and primary hepatocyte cells after exposure to RDX to determine how faithfully the in vitro model system reflects in vivo responses. RESULTS: Expression patterns were found to be markedly different between liver tissue and primary cell cultures before exposure to RDX. Liver gene expression was enriched in processes important in toxicology such as metabolism of amino acids, lipids, aromatic compounds, and drugs when compared to cells. Transcriptional responses in cells exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours were different from those of livers isolated from rats 24 hours after exposure to 12, 24, or 48 mg/Kg RDX. Most of the differentially expressed genes identified across conditions and treatments could be attributed to differences between cells and tissue. Some similarity was observed in RDX effects on gene expression between tissue and cells, but also significant differences that appear to reflect the state of the cell or tissue examined. CONCLUSION: Liver tissue and primary cells express different suites of genes that suggest they have fundamental differences in their cell physiology. Expression effects related to RDX exposure in cells reflected a fraction of liver responses indicating that care must be taken in extrapolating from primary cells to whole animal organ toxicity effects

Follow-up study on lead exposure in children living in a smelter community in northern Mexico

<p>Abstract</p> <p>Background</p> <p>To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations.</p> <p>Methods</p> <p>This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents.</p> <p>Results</p> <p>Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations.</p> <p>Conclusions</p> <p>B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.</p

Dental amalgam and mercury in dentistry

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Mercury in dentistry has re-emerged as a contentious issue in public health, predominantly because so many people are inadvertently exposed to mercury in order to obtain the benefits of dental amalgam fillings, and the risks remain difficult to interpret. This commentary aims to examine the issues involved in public policy assessment of the continued use of dental amalgam in dentistry.AJ Spence

Refinement of arsenic attributable health risks in rural Pakistan using population specific dietary intake values

Background: Previous risk assessment studies have often utilised generic consumption or intake values when evaluating ingestion exposure pathways. If these values do not accurately reflect the country or scenario in question, the resulting risk assessment will not provide a meaningful representation of cancer risks in that particular country/scenario. Objectives: This study sought to determine water and food intake parameters for one region in South Asia, rural Pakistan, and assess the role population specific intake parameters play in cancer risk assessment. Methods: A questionnaire was developed to collect data on sociodemographic features and 24-hour water and food consumption patterns from a rural community. The impact of dietary differences on cancer susceptibility linked to arsenic exposure was evaluated by calculating cancer risks using the data collected in the current study against standard water and food intake levels for the USA, Europe and Asia. A probabilistic cancer risk was performed for each set of intake values of this study. Results: Average daily total water intake based on drinking direct plain water and indirect water from food and beverages was found to be 3.5 L day-1 (95% CI: 3.38, 3.57) exceeding the US Environmental Protection Agency’s default (2.5 L day-1) and World Health Organization’s recommended intake value (2 L day-1). Average daily rice intake (469 g day-1) was found to be lower than in India and Bangladesh whereas wheat intake (402 g day−1) was higher than intake reported for USA, Europe and Asian sub-regions. Consequently, arsenic-associated cumulative cancer risks determined for daily water intake was found to be 17 in children of 3-6 years (95% CI: 0.0014, 0.0017), 14 in children of age 6-16 years (95% CI: 0.001, 0.0011) and 6 in adults of 16-67 years (95% CI: 0.0006, 0.0006) in a population size of 10000. This is higher than the risks estimated using the US Environmental Protection Agency and World Health Organization’s default recommended water intake levels. Rice intake data showed early life cumulative cancer risks of 15 in 10000 for children of 3-6 years (95% CI: 0.0012, 0.0015), 14 in children of 6-16 years (95% CI: 0.0011, 0.0014) and later life risk of 8 in adults (95% CI: 0.0008, 0.0008) in a population of 10000. This is lower than cancer risks in countries with higher rice intake and elevated arsenic levels (Bangladesh and India). Cumulative cancer risk from arsenic exposure showed the relative risk contribution from total water to be51%, from rice to be44% and wheat intake 5%. Conclusions: The study demonstrates the need to use population specific dietary information for risk assessment and risk management studies. Probabilistic risk assessment concluded the importance of dietary intake in estimating cancer risk, along with arsenic concentrations in water or food and age of exposed rural population