Magnetic resonance imaging T1 indices of the brain as biomarkers of inhaled manganese exposure.

Excessive exposure to manganese (Mn) is linked to its accumulation in the brain and adverse neurological effects. Paramagnetic properties of Mn allow the use of magnetic resonance imaging (MRI) techniques to identify it in biological tissues. A critical review was conducted to evaluate whether MRI techniques could be used as a diagnostic tool to detect brain Mn accumulation as a quantitative biomarker of inhaled exposure. A comprehensive search was conducted in MEDLINE, EMBASE, and PubMed to identify potentially relevant studies published prior to 9 May 2022. Two reviewers independently screened identified references using a two-stage process. Of the 6452 unique references identified, 36 articles were retained for data abstraction. Eligible studies used T1-weighted MRI techniques and reported direct or indirect T1 measures to characterize Mn accumulation in the brain. Findings demonstrate that, in subjects exposed to high levels of Mn, deposition in the brain is widespread, accumulating both within and outside the basal ganglia. Available evidence indicates that T1 MRI techniques can be used to distinguish Mn-exposed individuals from unexposed. Additionally, T1 MRI may be useful for semi-quantitative evaluation of inhaled Mn exposure, particularly when interpreted along with other exposure indices. T1 MRI measures appear to have a nonlinear relationship to Mn exposure duration, with R1 signal only increasing after critical thresholds. The strength of the association varied depending on the regions of interest imaged and the method of exposure measurement. Overall, available evidence suggests potential for future clinical and risk assessment applications of MRI as a diagnostic tool.

Derivation of whole blood biomonitoring equivalents for titanium for the interpretation of biomonitoring data.

Biomonitoring equivalents (BEs) have been increasingly applied for biomonitoring purposes by regulatory bodies worldwide. The present report describes the development of a BE for titanium based on a 4-step process: (i) identification of a critical study/point of departure (PoD) supporting an established oral exposure guidance value (OEGV);, (ii) review the available oral PK data and application of a pharmacokinetic model for titanium; (iii) selection of the most appropriate biomarker of exposure in a specific tissue and calculation of steady-state tissue levels corresponding to the PoD in the critical study; and (iv) derivation of BE value adjusting for the uncertainties considered in the original OEGV assessment. Using the above 4-step approach, a blood BE value of 32.5 µg titanium/L was derived. Key components of the analysis included a pharmacokinetic model developed by investigators at the Netherlands National Institute of Public Health (RIVM) and a two-year rodent bioassay of titanium conducted by the US National Cancer Institute. The most sensitive pharmacokinetic parameter involved in the current BE derivation is the oral absorption factor of 0.02%. The provisional BE proposed in this article may be updated as new information on the pharmacokinetics of titanium becomes available.

Derivation of whole blood biomonitoring equivalents for lithium for the interpretation of biomonitoring data.

INTRODUCTION: Lithium salts have numerous industrial uses and are also used in the treatment of bipolar disorders. The main source of lithium exposure to the general population is drinking water and foods. Lithium is nephrotoxic at higher doses. Thus, oral exposure guidelines for lithium have been derived, including ICH's permitted daily exposure (PDE = 0.008 mg lithium/kg-bw/day) adopted by Health Canada and the United States Environmental Protection Agency's (U.S. EPA) provisional peer reviewed toxicity value (PPRTV = 0.002 mg lithium/kg-bw/day), both based on human data. OBJECTIVE: To derive whole blood biomonitoring equivalents (BEs) associated with PDE and PPRTV to interpret population-level biomonitoring data in health risk context. METHOD: A simple kinetic relationship based on plasma clearance value (0.5 L/kg-bw/day) and the oral absorption fraction (100%) was used to derive blood BEs for PDE and PPRTV. RESULTS: This analysis resulted in BE values in plasma and whole blood of 16 and 10 µg/L, respectively, based on the PDE values developed by the Health Canada and of 4.2 and 2.7 µg/L, respectively, based on the PPRTV developed by U.S. EPA. CONCLUSION: The derived BE values can be used to interpret population-level biomonitoring data.

International case studies of psychosocial ripple effects of bovine spongiform encephalopathy (BSE) in European countries.

The public is increasingly concerned about risks associated with food. Food-borne diseases can easily mobilize public concerns and create strong emotional, behavioral, and political reactions with significant negative economic and psychosocial outcomes. This was observed in various countries globally experiencing the presence of prion disease bovine spongiform encephalopathy (BSE). This study highlights case-study material from various countries for key psychosocial impacts such as the public's worry and fear vis-a-vis beef consumption and the loss of confidence and trust in authorities stemming from the occurrence and management of the BSE crisis. These psychosocial impacts and resultant public behavioral responses are presented at a number of levels including individual, family, community, and societal for several European countries, with special emphasis on the UK case study. Given failures to identify the scope of individual concern about prion diseases, and to address these concerns in decision-making processes and risk communication strategies, there remains a need for further systematic research and psychosocial monitoring of the ripple effects of BSE.