title: 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.
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada; R. Samuel McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, 118-850 Peter Morand Drive, Canada. Electronic address: dmattison@risksciences.com.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Mattison
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada.
authors.forename: Brittany
authors.initials: B
authors.lastname: Milton
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada; R. Samuel McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, 118-850 Peter Morand Drive, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krewski
authors.affiliation: Institute of Environment and Health, Cranfield University, College Road, Cranfield MK43 0AL, Bedfordshire, United Kingdom.
authors.forename: Len
authors.initials: L
authors.lastname: Levy
authors.affiliation: College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
authors.affiliation: School of Medicine and Health, Lancaster University, Bailrigg, Lancaster, LA1 4YW, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Aggett
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université catholique de Louvain, Avenue Mounier 53.02, 1200 Brussels, Belgium.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Roels
authors.affiliation: ScitoVation, 6 Davis Drive, PO Box 110566, Research Triangle Park, NC, 27709-2137, USA.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada; R. Samuel McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, 118-850 Peter Morand Drive, Canada.
authors.forename: Nataliya A
authors.initials: NA
authors.lastname: Karyakina
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada; R. Samuel McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, 118-850 Peter Morand Drive, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Shilnikova
authors.affiliation: Risk Sciences International, 55 Metcalfe Street, Suite 700, K1P 6L5, Ottawa, Canada.
authors.forename: Siva
authors.initials: S
authors.lastname: Ramoju
authors.affiliation: International Manganese Institute, 17 rue Duphot, 75001 Paris, France. Electronic address: doreen.mcgough@manganese.org.
authors.forename: Doreen
authors.initials: D
authors.lastname: McGough
mesh_terms: D000818:Animals; D003300:Copper / Q000633:toxicity; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008345:Manganese / Q000633:toxicity*; D020149:Manganese Poisoning / Q000209:etiology*; D012044:Regression Analysis
chemical_list: D008345:Manganese; D003300:Copper
keywords: Categorical regression; Database; Exposure-response assessment; Manganese toxicity