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

Facing the Challenge of Data Transfer from Animal Models to Humans: the Case of Persistent Organohalogens

A well-documented fact for a group of persistent, bioaccumulating organohalogens contaminants, namely polychlorinated biphenyls (PCBs), is that appropriate regulation was delayed, on average, up to 50 years. Some of the delay may be attributed to the fact that the science of toxicology was in its infancy when PCBs were introduced in 1920's. Nevertheless, even following the development of modern toxicology this story repeats itself 45 years later with polybrominated diphenyl ethers (PBDEs) another compound of concern for public health. The question is why? One possible explanation may be the low coherence between experimental studies of toxic effects in animal models and human studies. To explore this further, we reviewed a total of 807 PubMed abstracts and full texts reporting studies of toxic effects of PCB and PBDE in animal models. Our analysis documents that human epidemiological studies of PBDE stand to gain little from animal studies due to the following: 1) the significant delay between the commercialisation of a substance and studies with animal models; 2) experimental exposure levels in animals are several orders of magnitude higher than exposures in the general human population; 3) the limited set of evidence-based endocrine endpoints; 4) the traditional testing sequence (adult animals – neonates – foetuses) postpones investigation of the critical developmental stages; 5) limited number of animal species with human-like toxicokinetics, physiology of development and pregnancy; 6) lack of suitable experimental outcomes for the purpose of epidemiological studies. Our comparison of published PCB and PBDE studies underscore an important shortcoming: history has, unfortunately, repeated itself. Broadening the crosstalk between the various branches of toxicology should therefore accelerate accumulation of data to enable timely and appropriate regulatory action