The use of categorical regression in the assessment of the risks of nutrient deficiency and excess.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies – thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner.

Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans.

Since the inception of the in the early 1970s, this has developed 119 Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as (Group 1). Volume 100 of the , compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009.

Key characteristics of 86 agents known to cause cancer in humans.

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the , 120 agents met the criteria for classification as (Group 1). Volume 100 of the provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations.

The application of PBPK models in estimating human brain tissue manganese concentrations.

Mn is an essential element that causes neurotoxicity in humans when inhaled at high concentrations. This metal has well-recognized route-dependent differences in absorption, with greater proportionate uptake for inhalation versus dietary exposure. Physiologically-based pharmacokinetic (PBPK) models for Mn have included these route specific differences in uptake and their effect on delivery of Mn to target tissues via systemic circulation.

Modeling U-shaped dose-response curves for manganese using categorical regression.

Introduction: Manganese is an essential nutrient which can cause adverse effects if ingested to excess or in insufficient amounts, leading to a U-shaped exposure-response relationship. Methods have recently been developed to describe such relationships by simultaneously modeling the exposure-response curves for excess and deficiency. These methods incorporate information from studies with diverse adverse health outcomes within the same analysis by assigning severity scores to achieve a common response metric for exposure-response modeling.

Severity scoring of manganese health effects for categorical regression.

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.

Modeling U-Shaped Exposure-Response Relationships for Agents that Demonstrate Toxicity Due to Both Excess and Deficiency.

Essential elements such as copper and manganese may demonstrate U-shaped exposure-response relationships due to toxic responses occurring as a result of both excess and deficiency. Previous work on a copper toxicity database employed CatReg, a software program for categorical regression developed by the U.S.