A5010715348- Carcinogens and Genotoxicity Assessment
- Effects and risks of endocrine disrupting chemicals
- Pesticide and Herbicide Environmental Studies
- Pesticide Exposure and Toxicity
- Toxic Organic Pollutants Impact
- Animal testing and alternatives
- Chemical Safety and Risk Management
- Pesticide Residue Analysis and Safety
- Risk and Safety Analysis
- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Immunotoxicology and immune responses
- Environmental Toxicology and Ecotoxicology
- Renal Transplantation Outcomes and Treatments
- Retinoids in leukemia and cellular processes
- Alcohol Consumption and Health Effects
- Advanced Causal Inference Techniques
- Antibiotics Pharmacokinetics and Efficacy
- Ovarian function and disorders
- Environmental and Social Impact Assessments
- Smoking Behavior and Cessation
- Health, Environment, Cognitive Aging
- Potato Plant Research
- Mycotoxins in Agriculture and Food
- Fungal Plant Pathogen Control
Triangle
2021
AT Sciences (United States)
2017
Syngenta (United States)
2002-2016
Syngenta (Switzerland)
2005-2015
Syngenta (China)
2004-2014
St. Francis College
1999
DuPont (United States)
1987
University of Michigan
1977
Based on existing data and previous work, a series of studies is proposed as basis toward pragmatic early step in transforming toxicity testing. These were assembled into data-driven framework that invokes successive tiers testing with margin exposure (MOE) the primary metric. The first tier integrates from high-throughput vitro assays, vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, modeling. assays are used to separate chemicals based their relative selectivity interacting...
Hazard identification and risk assessment paradigms depend on the presumption of similarity rodents to humans, yet species specific responses, extrapolation high-dose effects low-dose exposures can affect estimation human from rodent data. As a consequence, relevance framework concept was developed by International Programme Chemical Safety (IPCS) Life Sciences Institute (ILSI) Risk Science (RSI) with central tenet being mode action (MOA). To perform MOA analysis, key biochemical, cellular,...
Defining the mode(s) of action by which chemicals induce tumors in laboratory animals has become a key to judgments about relevance such tumor data for human risk assessment. Frameworks analyzing mode information appear recent U.S. EPA and IPCS publications relating cancer This FORUM paper emphasizes that analytical frameworks depend on both qualitative quantitative evaluations relevant information: (1) presenting events animal action, (2) developing “concordance” table side-by-side...
Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have human diseases been tested animals firmly establish causative link. Bacterial pathogens are perhaps oldest examples, and tobacco smoke lung cancer asbestos mesothelioma provide two more recent examples. With advent toxicity testing guidelines protocols, took was intended anticipate or predict potential adverse effects humans,...
Classification schemes for carcinogenicity based solely on hazard-identification such as the IARC monograph process and UN system adopted in EU have become outmoded. They are a concept developed 1970s that chemicals could be divided into two classes: carcinogens non-carcinogens. Categorization this way places same category agents with widely differing potencies modes of action. This is how eating processed meat can fall sulfur mustard gas. Approaches hazard risk characterization present an...
Cyproconazole, a triazole fungicide, causes hepatocellular adenomas and carcinomas in CD-1 mice at dose levels of 100 200 ppm. The constitutive androstane receptor (CAR) has been shown to play significant role the overall mode action for several nongenotoxic rodent carcinogens such as phenobarbital. liver effects dietary cyproconazole or phenobarbital were investigated after 2, 7, 14 days male CD-1, C57BL/6J, C3H/HeNClrBR mice. Cyproconazole produced similar, dose-responsive all three...
The causal relationship between atrazine exposure and the occurrence of breast cancer in women was evaluated using framework developed by Adami et al. (2011) wherein biological plausibility epidemiological evidence were combined to conclude that a is "unlikely". Carcinogenicity studies female Sprague-Dawley (SD) but not Fischer-344 rats indicate high doses caused decreased latency an increased incidence adenocarcinoma fibroadenoma mammary tumors. There no effects on any other tumor type male...
The previously-published physiologically based pharmacokinetic model for atrazine (ATZ), deisopropylatrazine (DIA), deethylatrazine (DEA), and diaminochlorotriazine (DACT), which collectively comprise the total chlorotriazines (TCT) as represented in this study, was modified to allow scaling humans. Changes included replacing fixed dose-dependent oral uptake rates with a method that delayed absorption observed rats administered ATZ bolus dose suspended methylcellulose vehicle. Rate constants...
Thiamethoxam (CGA293343; 3-(2-chloro-thiazol-5-ylmethyl)-5-methyl- [1,3,5]oxadiazinan-4-ylidene-N-nitroamine) was shown to increase the incidence of mouse liver tumors in an 18-month study; however, thiamethoxam not hepatocarcinogenic rats.Thiamethoxam is genotoxic, and, given late life generation tumors, suggests a time-related progression key hepatic events that leads tumors.These were identified series studies up 50 weeks showed time-dependent evolution relatively mild dysfunction within...
Concern over substances that may cause cancer has led to various classification schemes recognize carcinogenic threats and provide a basis manage those threats. The least useful have binary choice declares substance or not. This overly simplistic approach ignores the complexity of causation by considering neither how causes cancer, nor potency mode action. Consequently, are classified simply as "carcinogenic", compromising opportunity properly these kinds substances. It will likely be very...