Severity scoring of manganese health effects for categorical regression

Abstract

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data.

Dietary Manganese Exposure in the Adult Population in Germany—What Does it Mean in Relation to Health Risks?

“…reported a mean exposure to manganese from the basal diet of 4.5 mg kg −1 bw per day and 11 mg kg −1 bw per day for rats and mice, respectively . Therefore, the non‐considering—and in part non‐reporting—of the manganese intake from the basal diet is a common limitation in rodent studies, in particular in studies in which effects have been observed at additional dose levels of only a few milligrams per kilogram body weight or lower . Consequently, the relevance of effects observed at additional doses that were far below the basal intake from the chow remains unclear.…”

Dose-Related Severity Sequence, and Risk-Based Integration, of Chemically Induced Health Effects

“…The latter issue has been addressed in more detail ( Dourson et al , 1997 ; Teuschler et al 1999 ), and analysis stratified over groups (eg, sex, species) has also been discussed ( Guth et al , 1997 ). Recently, a severity scoring system for manganese toxicity was developed by an international panel ( Mattison et al , 2017 ), which was used for characterizing the U-shaped dose-response ( Milton et al , 2017 ). The level of toxicity (associated with excess) was described by a 9-graded severity scale.…”

Estimation and Correlation Analysis of Heavy Metals of Some Well Water in Zakho City, Iraq

“…As shown in Table 3, these metals in all well water samples were observed to be below the maximum permissible limit set by WHO. Although these metals are considered as an essential nutrient, but at high doses they have been reported to cause damage to the kidneys and can become fatal, as well as, they may cause a decrease in fetal growth (Cassat & Skaar;Mattison et al;Olmedo et al, 2013;Salgueiro et al, 2000;Schaible & Kaufmann, 2004). Lead is considered as the most significant toxin of the heavy metals, and the inorganic forms are absorbed through ingestion by food and water, and inhalation (Jaishankar, Tseten, Anbalagan, Mathew, & Beeregowda, 2014).…”