Time filter

Source Type

Charlottesville, VA, United States

Voutchkova A.M.,Yale University | Osimitz T.G.,Science Strategies LLC | Anastas P.T.,Yale University
Chemical Reviews | Year: 2010

A study was conducted to demonstrate a comprehensive molecular design framework for reduced hazard. The study aimed at providing a relatively detailed understanding to chemists untrained in toxicology the current state of knowledge of the relationships between physical-chemical properties and toxicological hazard of chemicals. It informed about the available tools hat needed to be used by these chemists to define such relationships that guided the design of safer chemicals. Another significant objective of the investigations was to reduce the hazard or intrinsic toxicity of chemicals to humans and the environment. Mechanistic toxicology was demonstrated as another field of research that aimed at understanding and identifying the molecular events that led from initial exposure to the chemical to the ultimate manifestation of toxic injury to the organism.

Osimitz T.G.,Science Strategies LLC | Eldridge M.L.,University of Tennessee at Knoxville | Sloter E.,WIL Research Laboratories LLC | Welsh W.,UMDNJ Robert Wood Johnson Medical School | And 5 more authors.
Food and Chemical Toxicology | Year: 2012

Eastman Tritan™ copolyester, a novel plastic from Eastman is manufactured utilizing three monomers, di-methylterephthalate (DMT), 1,4-cyclohexanedimethanol (CHDM), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) in various ratios. As with most any polymer, the monomers along with the high molecular weight oligomers, whose toxicity is most commonly represented by the monomers, make up the predominate amount of free chemicals available for leaching into the environment and/or foods. In light of the high level of public concern about the presence of endocrine (primarily estrogenic) activity ascribed to certain plastics and chemicals in the environment, Tritan's™ monomers were evaluated using QSAR for binding to the androgen receptor and estrogen receptors (alpha and beta) as well as a battery of in vitro and in vivo techniques to determine their potential androgenicity or estrogenicity. The findings were universally negative. When these data are coupled with other in vivo data developed to assess systemic toxicity and developmental and reproductive toxicity, the data clearly indicate that these monomers do not pose an androgenic or estrogenic risk to humans. Additional data presented also support such a conclusion for terephthalic acid (TPA). TPA is also a common polyester monomer and is the main mammalian metabolite formed from DMT. © 2012 Elsevier Ltd.

Osimitz T.G.,Science Strategies LLC | Welsh W.J.,UMDNJ Robert Wood Johnson Medical School | Ai N.,UMDNJ Robert Wood Johnson Medical School | Ai N.,Zhejiang University | And 2 more authors.
Food and Chemical Toxicology | Year: 2015

The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells. None of the QSAR models predicted that any of the monomers possessed appreciable binding affinity for either AR or ER. Binding assays showed no evidence of interaction with either the AR or the alpha or beta ER receptors. Similarly, the AR and ER transactivation assays were negative. Moreover, six of the seven monomers have been subjected to 13-week and developmental toxicity studies in rats with no androgen- or estrogen-related effects being noted. Given the negative results of the in vitro screening assays (except PMG which demonstrated cytotoxicity) as well as available repeated dose and developmental and reproductive studies, the data suggest that none of the monomers tested exhibit androgenic or estrogenic hazards. © 2014 Elsevier Ltd.

Driver J.,Infoscientific.com Inc. | Ross J.,Risksciences.net LLC | Pandian M.,Infoscientific.com Inc. | Assaf N.,Valent BioSciences Corporation | And 2 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2013

Postapplication exposure assessment related to indoor residential application of pesticide products requires consideration of product use information, application methods, chemical-specific deposition, time-dependent availability and transferability of surface residues, reentry time, and temporal location and macro-and microactivity/behavior patterns (Baker et al., 2000). Children's mouthing behavior results in potential postapplication exposure to available pesticides in treated microenvironments through the nondietary ingestion route, in addition to the dermal or inhalation routes. Children's activities and associated behaviors may result in multiple or repeat contact of dermal areas (clothed and unclothed body areas and hands) with treated surfaces, or surfaces that may have indirect sources of residues. Further, some surfaces contacted may have transferable pesticide residues and others may not. Transfer of residues from the indoor residential environment to the dermal surface (e.g., hands) of an individual has been assumed to be linear as a function of time and number of contacts. However, studies suggest that this transfer process to the hands and other body areas may be rapidly saturable. In the most recent U.S. Environmental Protection Agency (EPA), Office of Pesticide Programs (OPP) "Residential Exposure Assessment Standard Operating Procedures" (U.S. EPA, 2012), the input variable for the number of dermal contacts (with treated surfaces) is an exponent, making the relationship nonlinear. Further, removal processes such as hand washing and transfer to untreated surfaces are important to consider. Predictive algorithms for estimating children's hand-to-mouth-related incidental ingestion exposures post pesticide application have been developed by the EPA/OPP and incorporated into probabilistic models. A review of literature addressing variables used to estimate potential incidental ingestion exposure is presented. Data relevant to input variables for predictive algorithms are discussed, including the results of a multiyear, pesticide transferable residue measurement program conducted by the Non-Dietary Exposure Task Force (NDETF) and the associated distributional characterization for this key variable. Sources of conservative bias in current hand-to-mouth, incidental ingestion exposure estimation and the role of biomonitoring to evaluate predicted exposures are discussed. © 2013 Taylor and Francis Group, LLC.

Lake B.G.,University of Surrey | Price R.J.,University of Surrey | Osimitz T.G.,Science Strategies LLC
Pest Management Science | Year: 2015

A number of non-genotoxic chemicals, including some pesticides, have been shown to increase the incidence of liver tumours in rats and/or mice. Frameworks for analysing the modes of action (MOAs) by which chemicals produce liver tumours in rodents and the relevance of such tumour data for human risk assessment have now been established. One common MOA for rodent liver tumour formation by non-genotoxic chemicals involves activation of the constitutive androstane receptor (CAR). Key and associative events for a CAR-activation MOA include receptor activation, liver hypertrophy, induction of cytochrome P450 enzyme activities, increased replicative DNA synthesis, altered hepatic foci and liver tumours. While some effects of rodent CAR activators can be observed in human liver, a major species difference is that, unlike rodents, CAR activators do not increase replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent liver tumour formation is thus not plausible for humans, and hence such compounds do not pose a hepatocarcinogenic hazard for humans. © 2014 Society of Chemical Industry.

Discover hidden collaborations