Chlorpyrifos and neurodevelopmental effects: a literature review and expert elicitation on research and policy.

BACKGROUND: Organophosphate pesticides are widely used on food crops grown in the EU. While they have been banned from indoor use in the US for a decade due to adverse health effects, they are still the most prevalent pesticides in the EU, with Chlorpyrifos (CPF) being the most commonly applied. It has been suggested CPF affects neurodevelopment even at levels below toxicity guidelines. Younger individuals may be more susceptible than adults due to biological factors and exposure settings. METHODS: A literature review was undertaken to assess the evidence for CPF contributing to neurodevelopmental disorders in infants and children. Other literature was consulted in order to formulate a causal chain diagram showing the origins, uptake, and neurological effects of animal and human exposure to CPF.The causal chain diagram and a questionnaire were distributed online to scientific experts who had published in relevant areas of research. They were asked to assess their confidence levels on whether CPF does in fact contribute to adverse neurodevelopment outcomes and rate their confidence in the scientific evidence. A second questionnaire queried experts as to which kind of policy action they consider justifiable based on current knowledge. In a special workshop session at the EuroTox congress in Dresden in 2009 the results of both questionnaires were further discussed with invited experts, as a basis for a policy brief with main messages for policy makers and stakeholders. RESULTS: Most experts who responded to the first questionnaire felt that there was already enough evidence to support a ban on indoor uses of CPF in the EU. However, most felt additional research is still required in several areas. The responses from the first questionnaire were used to formulate the second questionnaire addressing the feasibility of government action. In turn, these expert participants were invited to attend a special session at the EuroTox congress in Dresden in 2009. CONCLUSIONS: Some of the evidence that CPF contributes to neurodevelopmental disorders is still disputed among experts, and the overall sense is that further research and public awareness are warranted. There have been campaigns in North America making the potential exposure concerns known, but such information is not widely known in the EU. The ability of government action to produce change is strongly felt in some quarters while others believe better knowledge of consumer use trends would have a greater impact.

Policy relevant results from an expert elicitation on the health risks of phthalates.

BACKGROUND: The EU 6th Framework Program (FP)-funded Health and Environment Network (HENVINET) aimed to support informed policy making by facilitating the availability of relevant knowledge on different environmental health issues. An approach was developed by which scientific agreement, disagreement, and knowledge gaps could be efficiently identified, and expert advice prepared in a way that is usable for policy makers. There were two aims of the project: 1) to apply the tool to a relevant issue; the potential health impacts of the widely used plasticizers, phthalates, and 2) to evaluate the method and the tool by asking both scientific experts and the target audience, namely policy makers and stakeholders, for their opinions. METHODS: The tool consisted of an expert consultation in several steps on the issue of phthalates in environmental health. A diagram depicting the cause-effect chain, from the production and use of phthalates to potential health impacts, was prepared based on existing reviews. This was used as a basis for an online questionnaire, through which experts in the field were consulted. The results of this first round of consultation laid the foundation for a new questionnaire answered by an expert panel that, subsequently, also discussed approaches and results in a workshop. One major task of the expert panel was to pinpoint priorities from the cause-effect chain according to their impact on the extent of potential health risks and their relevance for reducing uncertainty. The results were condensed into a policy brief that was sent to policy makers and stakeholders for their evaluation. RESULTS: The experts agreed about the substantial knowledge gaps within the field of phthalates. The top three priorities for further research and policy action were: 1) intrauterine exposure, 2) reproductive toxicology, and 3) exposure from medical devices. Although not all relevant information from the cause-effect chain is known for phthalates, most experts thought that there are enough indications to justify a precautionary approach and to restrict their general use. Although some of the experts expressed some scepticism about such a tool, most felt that important issues were highlighted. CONCLUSIONS: The approach used was an efficient way at summarising priority knowledge gaps as a starting point for health risk assessment of compounds, based on their relevance for the risk assessment outcome. We conclude that this approach is useful for supporting policy makers with state-of-the-art scientific knowledge weighed by experts. The method can assist future evidence-based policy making.

Sex-specific incidence and temporal trends in solid tumours in young people from Northern England, 1968-2005.

BACKGROUND: This study examined sex-specific patterns and temporal trends in the incidence of solid tumours in the Northern Region of England from 1968 to 2005. This updates earlier analyses from the region where sex was not considered in depth. Sex-specific analyses were carried out to determine whether sex differences might provide clues to aetiology. METHODS: Details of 3576 cases, aged 0-24 years, were obtained from a specialist population-based cancer registry. There were 1843 males (886 aged 0-14 years and 957 aged 15-24 years) and 1733 females (791 aged 0-14 years and 942 aged 15-24 years). Age-standardized incidence rates (per million population) were calculated. Linear regression was used to analyze temporal trends in incidence and annual percentage changes were estimated. Analyses were stratified by sex and by age-group. RESULTS: There were marked differences in incidence patterns and trends between males and females and also between age-groups. For males central nervous system (CNS) tumours formed the largest proportion of under-15 cases and germ cell tumours was the largest group in the 15-24's, whilst for females CNS tumours dominated in the under-15's and carcinomas in the older group. For 0-14 year olds there were male-specific increases in the incidence of rhabdomyosarcoma (2.4% per annum; 95% CI: 0.2%-4.5%) and non-melanotic skin cancer (9.6%; 95% CI: 0.0%-19.2%) and female-specific increases for sympathetic nervous system tumours (2.2%; 95% CI: 0.4%-3.9%), gonadal germ cell tumours (8.6%; 95% CI: 4.3%-12.9%) and non-gonadal germ cell tumours (5.4%; 95% CI: 2.8%-7.9%). For 15-24 year olds, there were male-specific increases in gonadal germ cell tumours (1.9%; 95% CI: 0.3%-3.4%), non-gonadal germ cell tumours (4.4%; 95% CI: 1.1%-7.7%) and non-melanotic skin cancer (4.7%; 95% CI: 0.5%-8.9%) and female-specific increases for osteosarcoma (3.5%; 95% CI: 0.5%-6.5%), thyroid cancer (2.8%; 95% CI: 0.1%-5.6%) and melanoma (4.6%; 95% CI: 2.2%-7.1%). CONCLUSION: This study has highlighted notable differences between the sexes in incidence patterns and trends for solid tumours. Some of these sex-specific differences could have been obscured if males and females had been analysed together. Furthermore, they suggest aetiological differences or differential susceptibility to environmental factors between males and females.

Geographical analysis of thyroid cancer in young people from northern England: evidence for a sustained excess in females in Cumbria.

A previous study found a thyroid cancer excess in Cumbria following the Chernobyl explosion, but did not analyse sex-specific effects. This study examines sex differences in the incidence of thyroid cancer. Ninety-five primary thyroid carcinomas (69 females, 26 males) diagnosed in those aged 0-24 during 1968-2005 were identified from the Northern Region Young Persons' Malignant Disease Registry. Age-standardised incidence rates (ASRs), rate ratios (RRs) and 95% confidence intervals (CIs) were calculated. For males, the ASR was 0.6 per million person-years during the pre-Chernobyl period (1968-1986), and was 1.8 per million person-years during the post-Chernobyl period (1987-2005). For females, the ASR was 2.4 pre-Chernobyl and was 3.9 post-Chernobyl. The previously noted excess in Cumbria was entirely confined to females (Cumbrian females: RR for post-Chernobyl compared with pre-Chernobyl=10.8; 95% CI: 1.4-85.3). These findings may be consistent with sex-specific differences in susceptibility to an environmental exposure, such as fallout from the Chernobyl nuclear accident.