We address here the importance of epidemiological evidence in risk assessment and decision-making in Europe. To illustrate this, titanium dioxide (TiO 2 ) was used as a model compound. TiO 2 is widely used as an odorless white pigment and opacifying agent. A recent systematic review assessing the weight of evidence on the relationship between exposure to TiO 2 (all forms) and cancer in humans questions the assumptions that TiO 2 is an inert material of low toxicity. Based on this new data, France submitted a proposal to classify TiO 2 as a possible human carcinogen under the European regulation. The European Chemicals Agency Risk assessment committee concluded that TiO 2 (all forms) warrants a classification as a suspected human carcinogen via inhalation (Category-2) under the CLP regulation (for Classification, Labeling and Packaging of chemicals). No considerations was given to TiO 2 particle size, which may affect human health effects. Consequently, further epidemiological studies are needed to assess possible associations between different physical-chemical characteristics of TiO 2 exposures and their impact on human health. This would allow strengthening the evidence on which to build the most appropriate regulation and to guaranty safe use given any exposure route of any TiO 2 particle shape or size.
ObjectivesAnimal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers.MethodsWe reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years.ResultsThe HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3.ConclusionThis analysis shows that HWSE can hide an exposure–response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure–effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.
Diseases of fruit and foliage caused by fungi and oomycetes are generally controlled by the application of fungicides. The use of decision support systems (DSSs) may assist to optimize fungicide programs to enhance application on the basis of risk associated with disease outbreak. Case-by-case evaluations demonstrated the performance of DSSs for disease control, but an overall assessment of the efficacy of DSSs is lacking. A literature review was conducted to synthesize the results of 67 experiments assessing DSSs. Disease incidence data were obtained from published peer-reviewed field trials comparing untreated controls, calendar-based and DSS-based fungicide programs. Two meta-analysis generic models, a "fixed-effects" vs. a "random-effects" model within the framework of generalized linear models were evaluated to assess the efficacy of DSSs in reducing incidence. All models were fit using both frequentist and Bayesian estimation procedures and the results compared. Model including random effects showed better performance in terms of AIC or DIC and goodness of fit. In general, the frequentist and Bayesian approaches produced similar results. Odds ratio and incidence ratio values showed that calendar-based and DSS-based fungicide programs considerably reduced disease incidence compared to the untreated control. Moreover, calendar-based and DSS-based programs provided similar reductions in disease incidence, further supporting the efficacy of DSSs.
This probabilistic approach yields quantitative insight into both the possible range and the relative likelihood of values for model outputs. It thereby provides a better support in decision-making and improves transparency. Int J Occup Med Environ Health 2018;31(4):475-489.
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