ScienceDirect Publication: Regulatory Toxicology and Pharmacology
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Correction to: Bailey, LA; Goodman, JE; Beck, BD. 2009. ?Proposal for a revis...
27 Jul 2010 at 1:40pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 27 July 2010
Barbara D., Beck
Safety evaluation of proanthocyanidin polymer-rich fraction obtained from ste...
24 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 23 July 2010
Marco Antonio, Costa , Kelly, Ishida , Vanessa, Kaplum , Éryca Danielle Alves, Koslyk , João Carlos Palazzo, de Mello , ...
The widespread use of medicinal plants among the Brazilian population warrants an assessment of the potential risks associated with their intake. Stryphnodendron adstringens (barbatimão) is one of the most frequently used medicinal plants in Brazil, and the risks associated with its use have yet to be investigated. This study evaluated the genotoxic safety of the use of the proanthocyanidin polymer-rich fraction (F2) of stem bark of S. adstringens. The micronucleus test with 750, 1,500, and 2,250 mg.kg-1 of F2 administered in Mus musculus (Swiss) outbred mice, showed respectively, 5.0±0.8 (Mean±S.D.), 9.1±1.7, and 10.6±1.9 micronucleated polychromatic erythrocytes (MNPCE). A positive control...
Logarithmic dose transformation in epidemiologic dose-response analysis: Use ...
24 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 23 July 2010
Michael E., Ginevan , Deborah K., Watkins
Dose-response models based on the logarithm of dose or exposure are utilized in the analysis of both toxicologic and epidemiologic data. While the applications are similar, fundamental differences in the studies conducted by each discipline affects the interpretation of the use of the logarithmic dose transformation. Using numerical illustrations and examples from the literature, this paper explores the implications of using logarithmic dose transformation in epidemiologic studies and provides some caveats for consideration in interpreting epidemiologic studies based upon logarithmic dose transformation.
Interpreting REACH Guidance in the Determination of the Derived No Effect Lev...
23 Jul 2010 at 1:42pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 22 July 2010
Marisa L., Kreider , E. Spencer, Williams
Under the new European chemicals regulation, REACH, a new safety value, the Derived No Effect Level (DNEL) must be established for all chemicals manufactured, imported or used in the EU in quantities greater than 10 metric tonnes per year. The DNEL is to be calculated for all relevant exposure pathways, exposure populations, and endpoints of toxicity. The EU has published guidance on how to derive the DNEL, but this guidance has yet to be put into practice and is in some places not prescriptive. Using the Agency for Toxic Substances and Disease Registry (ATSDR) dataset, we have determined inhalation DNELs...
Human Chemosensory Perception of Methyl Isothiocyanate: Chemesthesis and Odor
13 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 13 July 2010
William S., Cain , Michael L., Dourson , Melissa J., Kohrman-Vincent , Bruce C., Allen
An unpublished laboratory study by M. Russell and T. Rush (1996) showed that human subjects sense the presence of methyl isothiocyanate (MITC) via the eyes at concentrations as low as hundreds of ppb in air, with dependence upon duration of exposure. The longer the stimulation, the lower the concentrations sensed. Application of benchmark concentration (BMC10) modeling indicated a best estimate of 330 ppb by the end of 4 hours. With a confidence limit (BMCL) applied, the level dropped to 220 ppb, when employing a probit model. Receptors known as TRPA1 ion channels present in trigeminal and associated peripheral afferent nerves...
Evolution of seed allergen quantification - from antibodies to mass spectrometry
11 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 11 July 2010
Severin E., Stevenson , Norma L., Houston , Jay J., Thelen
Development of accurate, high-throughput approaches for protein allergen quantification is important for the seed industry as a means to monitor natural variability in expression and ensure introduced transgenes do not collaterally alter the expression of any known allergen. Analytical approaches for protein quantification have undergone a renaissance in recent years with the emergence of soft-ionization approaches and advanced mass spectrometers capable of achieving low attomolar sensitivity. These advances coupled with bioinformatic tools to mine mass spectral data are collectively referred to as proteomics, and allow for the large-scale study of proteins with high precision and quantitative accuracy. In this review,...
A Framework for Assessing Causality and Adverse Effects in Humans with a Case...
11 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 11 July 2010
Julie E., Goodman , David D., Dodge , Lisa A., Bailey
Following exposure to a substance, several biological events can occur that may eventually, depending on the exposure dose and duration, lead to adverse effects. We developed a framework to evaluate whether an exposure is causally related to an effect and whether that effect is adverse. An exposure is not likely to be causal if an effect is: not statistically significantly different in exposed and non-exposed study subjects; isolated or independent; secondary; observed because of study limitations; or unrelated to the apical effect and not associated with functional impairment. Adaptive effects are not adverse and, although effects that overwhelm homeostasis often...
The value of acute toxicity studies to support the clinical management of ove...
11 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 11 July 2010
Kathryn, Chapman , Stuart, Creton , Hugo, Kupferschmidt , G. Randall, Bond , Martin F., Wilks , ...
Acute toxicity studies are no longer required to support first clinical trials of pharmaceuticals in man. However, it is unclear in the wording of the revised ICH M3 whether acute toxicity studies are required later in drug development (e.g. phase 3) in order to support the management of overdose. The NC3Rs held a workshop in January 2010 with representatives from international poison centres, the pharmaceutical and chemical industries, and regulatory and government bodies to explore further whether acute toxicity studies are used to support the clinical management of overdose of pharmaceuticals and whether this work can be translated to other...
Metabolome variability in crop plant species ? when, where, how much and so w...
11 Jul 2010 at 1:45pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 11 July 2010
Howard V., Davies , Louise V.T., Shepherd , Derek, Stewart , Thomas, Frank , Richard M., Röhlig , ...
?Omics? technologies provide coverage of gene, protein and metabolite analysis that is unsurpassed compared with traditional targeted approaches. There are a growing number of examples indicating that profiling approaches can be used to expose significant sources of variation in the composition of crop and model plants caused by genetic background, breeding method, growing environment (site, season), genotype X environment interactions and crop cultural practices to name but a few. Whilst breeders have long been aware of such variation from tried and tested targeted analytical approaches, the broad-scale, so called ?unbiased? analysis of the metabolome now possible, offers a major upside...
Assessment of undesirable events in cosmetic market surveillance Background, ...
8 Jul 2010 at 1:47pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 7 July 2010
B., Bons , F., Audebert , C., Bitaudeau , N., Cachin , L., Colson , ...
Numerous methods for assessing undesirable events associated with drugs have been published, reflecting the need for experts to work with recognized methodologies. In the same way, the need for the development of a method adapted to cosmetic products has proved to be essential.In this perspective, in 2005 a causality assessment method was developed by Colipa and has been applied since then by most of its cosmetics member companies in Europe. This method is based on three main criteria: likelihood of symptoms, chronology of event versus the product use and results of medical investigations or re-exposure to the suspected product. The...
Evaluating Biological Variation in Non-Transgenic Crops: Executive Summary fr...
6 Jul 2010 at 1:41pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 6 July 2010
Nancy, Doerrer , Gregory, Ladics , Scott, McClain , Corinne, Herouet-Guicheney , Lars, Poulsen , ...
The International Life Sciences Institute Health and Environmental Sciences Institute Protein Allergenicity Technical Committee hosted an international workshop November 16-17, 2009, in Paris, France, with over 60 participants from academia, government, and industry to review and discuss the potential utility of ?-omics? technologies for assessing the variability in plant gene, protein, and metabolite expression. The goal of the workshop was to illustrate how a plant?s constituent makeup and phenotypic processes can be surveyed analytically. Presentations on the ?-omics? techniques (i.e., genomics, proteomics, and metabolomics) highlighted the workshop, and summaries of these presentations are published separately in this supplemental issue. This...
Comparative testing for the identification of skin sensitizing potentials of ...
3 Jul 2010 at 2:47pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 3 July 2010
Christine, Garcia , Nicholas, Ball , Stuart, Cagen , Juan-Carlos, Carrillo , Hans, Certa , ...
The Local Lymph Node Assay (LLNA) is the preferred test for the identification of skin-sensitizing potentials of chemicals in Europe and is also the first choice method within REACH. In the formal validation, only a very few surfactant chemicals were evaluated and SDS was identified as a false positive. In this study, ten nonionic sugar lipid surfactants were tested in an LLNA, guinea pig maximization test (GPMT) and human repeated insult patch test. Of the 10 surfactants tested in the LLNA, 5 showed stimulation indices above 3.0. Three of five positive reactions were concomitant with signs of skin irritation indicated...
Background incidence of serum creatinine threshold rises in a predominantely ...
1 Jul 2010 at 1:42pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 30 June 2010
Yanfang, Liu , Christine, Hunt , Chanchal, Bains , John G, Weil
 Objective: Serum creatinine (Cr) is used to monitor renal function during pre-marketing clinical trials . Standard thresholds for a serum creatinine (Cr) increase predictive of renal injury remain to be established in this setting. Study Design and Setting: Aggregated clinical trial data were utilized to evaluate the background frequency of Cr increases of ?0.3mg/dl and ?0.5mg/dl from baseline. Results: 10,018 subjects who participated in 15 clinical trials were included: 311 (4 %) male, 7521 (96%) female, mean age of 48.1 years. Mean follow-up time was 6 months. The incidence of Cr increase ? 0.3mg/dl from baseline was 7.5 per 1000 person-months (95%CI 6.81-8.24) and 1.2...
Gene expression profiling for food safety assessment: examples in potato and ...
30 Jun 2010 at 1:40pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 30 June 2010
Jeroen P., van Dijk , Carlo, Leifert , Eugenia, Barros , Esther J., Kok
Since the mid 1990s, microarray analysis has become one of the few tools that can analyse the entire contents of a cell regarding a specific information type. Especially since the development of whole genome microarrays the technique can be considered truly holistic. Most DNA based microarrays are used for the analysis of the total of messenger RNAs (transcriptome) and provide a snap-shot of what?s going on in a cell population at the time of sampling. Within the last few years also full genome plant microarrays have become available for several crop species. With these it has been shown that several...
An Evaluation of Chemical Photoreactivity and the Relationship To Phototoxicity
30 Jun 2010 at 1:40pm
Publication year: 2010
Source: Regulatory Toxicology and Pharmacology, In Press, Accepted Manuscript, Available online 30 June 2010
Mark H., Kleinman , Mark D., Smith , Edit, Kurali , Sarah, Reeser , Kaina, Jiang , ...
The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290 - 700 nm, and that are either applied locally/topically, or ?reach? (EMEA)/?significantly partition? (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component...

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