Doerrer NG

References (2)

Title : The use of mode of action information in risk assessment: Quantitative key events\/dose-response framework for modeling the dose-response for key events - Simon_2014_Crit.Rev.Toxicol_44 Suppl 3_17
Author(s) : Simon TW , Simons SS, Jr. , Preston RJ , Boobis AR , Cohen SM , Doerrer NG , Fenner-Crisp PA , McMullin TS , McQueen CA , Rowlands JC
Ref : Crit Rev Toxicol , 44 Suppl 3 :17 , 2014
Abstract : Abstract The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
ESTHER : Simon_2014_Crit.Rev.Toxicol_44 Suppl 3_17
PubMedSearch : Simon_2014_Crit.Rev.Toxicol_44 Suppl 3_17
PubMedID: 25070415

Title : A tiered approach to systemic toxicity testing for agricultural chemical safety assessment - Doe_2006_Crit.Rev.Toxicol_36_37
Author(s) : Doe JE , Boobis AR , Blacker A , Dellarco V , Doerrer NG , Franklin C , Goodman JI , Kronenberg JM , Lewis R , McConnell EE , Mercier T , Moretto A , Nolan C , Padilla S , Phang W , Solecki R , Tilbury L , van Ravenzwaay B , Wolf DC
Ref : Crit Rev Toxicol , 36 :37 , 2006
Abstract : A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Systemic Toxicity Task Force proposes an approach to systemic toxicity testing as one part of the overall assessment of a compound's potential to cause adverse effects on health. The approach is designed to provide more relevant data for deriving reference doses for shorter time periods of human exposure, and includes fewer studies for deriving longer term reference doses-that is, neither a 12-month dog study nor a mouse carcinogenicity study is recommended. All available data, including toxicokinetics and metabolism data and life stages information, are taken into account. The proposed tiered testing approach has the potential to provide new risk assessment information for shorter human exposure durations while reducing the number of animals used and without compromising the sensitivity of the determination of longer term reference doses.
ESTHER : Doe_2006_Crit.Rev.Toxicol_36_37
PubMedSearch : Doe_2006_Crit.Rev.Toxicol_36_37
PubMedID: 16708694