Benchmark dose analysis of multiple thyroid toxicity endpoints in ovariectomized rats exposed to propylthiouracil
Publication date: Available online 19 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hao Chen, Xiaopeng Zhang, Xudong Jia, Zhaoping Liu Benchmark dose (BMD) analysis is generally recognized superior to generate a point of departure (PoD) to conduct risk assessment on environmental toxicants, comparing with the traditionally employed no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL) methods. However, only a few studies compared the two on producing PoD of thyroid toxicity caused by environmental chemicals. Here, we presented BMD analyses on several thyroid toxicity...
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Investigation and comparison of the transfer of TSNA from tobacco to cigarette mainstream smoke and to the aerosol of a heated tobacco product, THS2.2
Publication date: Available online 19 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Guy Jaccard, Athanasios Kondylis, Irfan Gunduz, Johannes Pijnenburg, Maxim Belushkin Tobacco-specific nitrosamines (TSNA) levels in tobacco cut filler and cigarette smoke were measured in more than 1000 commercially available cigarettes sampled between 2008 and 2014. Relative contributions to their transfer from tobacco to the mainstream smoke in terms of direct transfer by distillation, pyrorelease, and pyrosynthesis were evaluated on the basis of the comparison with the transfer of nicotine from tobacco to smoke. N&p...
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Assessment of structurally modified plant virus as a novel adjuvant in toxicity studies
Publication date: Available online 19 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): N.A. Nikitin, V.A. Zenin, E.A. Trifonova, E.M. Ryabchevskaya, O.A. Kondakova, A.N. Fedorov, J.G. Atabekov, O.V. Karpova Spherical particles (SPs) generated by thermally denatured tobacco mosaic virus (TMV) coat protein can act as an adjuvant, as they are able to enhance the magnitude and longevity of immune responses to different antigens. Here, the toxicity of TMV SPs was assessed prior to it being offered as a universal safe adjuvant for the development of vaccine candidates. The evaluation included nonclinical studi...
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Drug adulteration of food supplements: A threat to public health in the European Union?
Publication date: Available online 19 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Edyta Czepielewska, Magdalena Makarewicz-Wujec, Filip Różewski, Elżbieta Wojtasik, Małgorzata Kozłowska-Wojciechowska Food supplements have been playing an increasingly important role in the consumers' awareness nowadays. They are widespread and – according to popular belief – healthier and safer than synthetic drugs. In the European Union (EU) food supplements are classified as foodstuffs and thus not subjected to any specific safety assessments prior to commercialisation. With the growing popul...
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Study on the developmental toxicity of β-ionone in the rat
In conclusion, except for a higher embryolethality at a maternally toxic dose, BIO caused no embryotoxic effect over the dose range tested and the study NOAEL for maternal and developmental toxicity was 500 mg of BIO/ kg of body weight/day. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Prioritization before risk assessment: The viability of uncertain data on food contact materials
Publication date: Available online 19 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Eelco N. Pieke, Kit Granby, Bruno Teste, Jørn Smedsgaard, Gilles Rivière The shortage of data on non-intentionally added substances (NIAS) present in food contact material (FCM) limits the ability to ensure food safety. Recent strategies in analytical method development allow investigating NIAS by using chemical exploration; but this has not been sufficiently investigated in risk assessment context. Here, exploration is applied on two paperboard FCM samples followed by risk prioritization for chemicals th...
Source: Regulatory Toxicology and Pharmacology - June 20, 2018 Category: Toxicology Source Type: research

Characterization and safety evaluation of HPPD W336, a modified 4-hydroxyphenylpyruvate dioxygenase protein, and the impact of its expression on plant metabolism in herbicide-tolerant MST-FG Ø72-2 soybean
In conclusion, HPPD W336 was demonstrated to be as safe as other food proteins. No adverse metabolic effects were identified related to HPPD W336 expression in MST-FGØ72-2 soybean. Graphical abstract (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 15, 2018 Category: Toxicology Source Type: research

Feasibility of using urinary TDGA as a biomarker for VCM exposures
The objective of this article is to evaluate the feasibility of using urinary TDGA as a biomarker of VCM exposure in a community health risk assessment setting where the concentration of VCM in air is typically very low (likely below 1 ppm). To achieve this objective, we examine the fraction of urinary TDGA associated with different levels of VCM exposures of three studies from different countries, using estimations of the TDGA metabolite predicted by a PBPK model. It is demonstrated that differences in background TDGA have considerable effect on the adequacy of TDGA as a biomarker of VCM. We conclude that, in a communit...
Source: Regulatory Toxicology and Pharmacology - June 14, 2018 Category: Toxicology Source Type: research

A monitoring survey and dietary risk assessment for pesticide residues on peaches in China
Publication date: Available online 14 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Zhixia Li, Jiyun Nie, Zhen Yan, Yang Cheng, Feng Lan, Yunan Huang, Qiusheng Chen, Xubo Zhao, An Li The presence of pesticide residues in fruit has been of extensive concern worldwide. In this paper, pesticide residues in peach samples in China and their dietary exposure risks for the Chinese general population and children were evaluated. Thirty-nine different pesticides were detected, and 92.3% of samples contained one or more pesticide residues. The most frequently detected pesticide was carbendazim with a detection ...
Source: Regulatory Toxicology and Pharmacology - June 14, 2018 Category: Toxicology Source Type: research

Prediction of tissue concentrations of monoclonal antibodies in mice from plasma concentrations
The objectives of this study were to develop and evaluate allometric methods for predicting tissue-to-plasma partition coefficients (Kp) in mice from experimentally determined in-vivo volume of distribution at steady state (Vss) for monoclonal antibodies (mAbs). The Vss was allometrically predicted (using a fixed exponent 1.0 or 0.9) in a given tissue of the mice. The Kp was predicted using Vss and tissue specific physiological parameters. In total, Kp values were predicted for 20 mAbs, 121 tissues, and 665 tissue concentrations. The predicted Kp values and tissue concentrations were compared with the experimental results ...
Source: Regulatory Toxicology and Pharmacology - June 14, 2018 Category: Toxicology Source Type: research

Safety evaluation of xylanase 50316 enzyme preparation (also known as VR007), expressed in Pseudomonas fluorescens, intended for use in animal feed
Publication date: August 2018 Source:Regulatory Toxicology and Pharmacology, Volume 97 Author(s): Roxanna Van Dorn, Diane Shanahan, Vince Ciofalo Xylanase 50316 enzyme (also known as VR007) can be added to the diets of monogastric animals to hydrolyze the glycosidic linkages of xylans that are found in these animal feeds. This enzyme was produced from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested in acute, subchronic, and genotoxicity studies. Dosages of the test article preparation ranged from 5000 μg/plate for in vitro toxicity studies to 2000 mg/kg/day for in vivo toxicity studies. Th...
Source: Regulatory Toxicology and Pharmacology - June 13, 2018 Category: Toxicology Source Type: research

A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats
Publication date: August 2018 Source:Regulatory Toxicology and Pharmacology, Volume 97 Author(s): Hiroto Bushita, Yuichi Ito, Tetsuji Saito, Yuko Nukada, Naohiro Ikeda, Hideaki Nakagiri, Kazutoshi Saito, Osamu Morita Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil—which mainly consists of oleic and linolenic, linoleic acids—have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential...
Source: Regulatory Toxicology and Pharmacology - June 12, 2018 Category: Toxicology Source Type: research

Modeling the impact of changes in tobacco use on individual disease risks
Publication date: Available online 9 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): S. Djurdjevic, Z. Sponsiello-Wang, P.N. Lee, J.S. Fry, R. Weitkunat, F. Lüdicke, G. Baker Reduced Risk Products (RRPs) do not burn tobacco and produce lower levels of toxicants than in cigarette smoke. The long-term effects of using RRPs on health are difficult to assess in a pre-market setting and a modeling approach is required to quantify harm reduction. The Population Health Impact Model (Weitkunat et al., 2015) follows a hypothetical population of individuals over time, creating their tobacco use histories and...
Source: Regulatory Toxicology and Pharmacology - June 10, 2018 Category: Toxicology Source Type: research

Fate of inhaled Nano-CeO2 revisited: Predicting the unpredictable
Publication date: Available online 6 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Juergen Pauluhn This paper compares the pulmonary kinetics of inhaled nano-CeO2 from two published repeated inhalation studies of 13-week duration in rats. This database was used to predict the outcome of a 2-year chronic inhalation study with a focus on the no observed adverse effect level (NOAEL) and range of conditions causing kinetic lung overload up to and beyond the maximum tolerated dose (MTD). Modeling identified nano-CeO2 to be typical poorly soluble, low-toxicity particles (PSLTs), although even partial dissol...
Source: Regulatory Toxicology and Pharmacology - June 7, 2018 Category: Toxicology Source Type: research

A comparison of in vitro cytotoxicity assays in medical device regulatory studies
Publication date: Available online 6 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Xuemei Liu, Denise P. Rodeheaver, Jeffrey C. White, Ann M. Wright, Lisa M. Walker, Fan Zhang, Stephen Shannon Medical device biocompatibility testing is used to evaluate the risk of adverse effects on tissues from exposure to leachates/extracts. A battery of tests is typically recommended in accordance with regulatory standards to determine if the device is biocompatible. In vitro cytotoxicity, a key element of the standards, is a required endpoint for all types of medical devices. Each validated cytotoxicity method has...
Source: Regulatory Toxicology and Pharmacology - June 7, 2018 Category: Toxicology Source Type: research

Biomonitoring Equivalents for cyanide
Publication date: Available online 7 June 2018 Source:Regulatory Toxicology and Pharmacology Author(s): C.R. Kirman, A.M. Belknap, A.F. Webster, S.M. Hays Exposure to cyanide is widespread in human populations due to a variety of natural and anthropogenic sources. The potential health risks of excess cyanide exposure are dose-dependent and include effects on the thyroid, the male reproductive system, developmental effects, neuropathies and death. Many organizations have derived exposure guideline values for cyanide, which represent maximum recommended exposure levels for inhalation and oral routes of exposure. Biomonitori...
Source: Regulatory Toxicology and Pharmacology - June 7, 2018 Category: Toxicology Source Type: research

In vitro and in vivo DFO-chelatable labile iron release profiles among commercially available intravenous iron nanoparticle formulations
Publication date: August 2018 Source:Regulatory Toxicology and Pharmacology, Volume 97 Author(s): Amy Barton Pai, Manjunath P. Pai, Dan E. Meyer, Brian C. Bales, Victoria E. Cotero, Nan Zheng, Wenlei Jiang Intravenous (IV) iron formulations are complex colloidal suspensions of iron oxide nanoparticles. Small changes in formulation can allow more labile iron to be released after injection causing toxicity. Thus, bioequivalence (BE) evaluation of generic IV iron formulations remains challenging. We evaluated labile iron release in vitro and in vivo using a high performance liquid chromatography chelatable iron assay to deve...
Source: Regulatory Toxicology and Pharmacology - June 6, 2018 Category: Toxicology Source Type: research

High dose targeted delivery on cancer sites and the importance of short-chain fatty acids for metformin's action: Two crucial aspects of the wonder drug
Publication date: August 2018 Source:Regulatory Toxicology and Pharmacology, Volume 97 Author(s): Kunal Maniar, Vandana Singh, Amitava Chakrabarti, Rajasri Bhattacharyya, Dibyajyoti Banerjee Metformin is a popular anti-diabetic drug currently being explored for its role in cancer and gut microbiome amongst other areas. Recently, Adak T et al. explicatively reviewed metformin's effects as an anti-cancer drug and a gut microbiome modulator. We feel that the authors have not adequately addressed some of the key concerns around metformin in their report and in this correspondence, we seek to add some of the issues that need t...
Source: Regulatory Toxicology and Pharmacology - June 1, 2018 Category: Toxicology Source Type: research

Energy drink exposures reported to Texas poison centers: Analysis of adverse incidents in relation to total sales, 2010 –2014
Publication date: August 2018 Source:Regulatory Toxicology and Pharmacology, Volume 97 Author(s): Stephen W. Borron, Susan H. Watts, Jessica Herrera, Joshua Larson, Salvador Baeza, Richard L. Kingston The ill-defined term “energy drink” includes a disparate group of products (beverages, shots, concentrates, and workout powders) having large differences in caffeine content and concentration and intended use. Hence, inaccurate conclusions may be drawn when describing adverse events associated with “energy drinks”. The FDA is considering new regulation of these products but product specificity is need...
Source: Regulatory Toxicology and Pharmacology - May 31, 2018 Category: Toxicology Source Type: research

PM2.5 and ozone, indicators of air quality, and acute deaths in California, 2004 –2007
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Cheng You, Dennis K.J. Lin, S. Stanley Young Since the London Great Smog of 1952 was estimated to have killed over 4000 people, scientists have studied the relationship between air quality and acute mortality. Currently, the association between air quality and acute deaths is usually taken as evidence for causality. As air quality has markedly improved since 1952, do contemporary datasets support this view? We use a large dataset, eight air basins in California for the years 2004–2007, to examine the possible association ...
Source: Regulatory Toxicology and Pharmacology - May 27, 2018 Category: Toxicology Source Type: research

Lack of value of juvenile animal toxicity studies for supporting the safety of pediatric oncology phase I trials
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Thomas Visalli, Nancy Bower, Tushar Kokate, Paul A. Andrews Toxicity studies in juvenile animals (JAS) are sometimes performed to support clinical trials in pediatric oncology patients, and there are differing conclusions on the value of JAS for pediatric drug development. This manuscript provides a review of the pediatric clinical data for 25 molecularly-targeted and 4 biologic anticancer therapeutics. Other publications that evaluated the value of JAS in pediatric drug development focus on differences in toxicity between juve...
Source: Regulatory Toxicology and Pharmacology - May 26, 2018 Category: Toxicology Source Type: research

Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Melvin E. Andersen, George Cruzan, Michael B. Black, Salil N. Pendse, Darol E. Dodd, James S. Bus, Satinder S. Sarang, Marcy I. Banton, Robbie Waites, Debra B. Layko, Patrick D. McMullen Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(−/−) knockout (C5...
Source: Regulatory Toxicology and Pharmacology - May 23, 2018 Category: Toxicology Source Type: research

A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Matthew Clark, Thomas Steger-Hartmann Although lack of efficacy is an important cause of late stage attrition in drug development the shortcomings in the translation of toxicities observed during the preclinical development to observations in clinical trials or post-approval is an ongoing topic of research. The concordance between preclinical and clinical safety observations has been analyzed only on relatively small data sets, mostly over short time periods of drug approvals. We therefore explored the feasibility of a big-data...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Pesticide exposure and risk of Parkinson's disease: Dose-response meta-analysis of observational studies
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Dandan Yan, Yunjian Zhang, Liegang Liu, Nian Shi, Hong Yan The cause of late onset Parkinson's disease (PD) remains unknown. Evidence suggested that lifelong exposure to pesticides might contribute to the development of neurodegenerative diseases, but the results were controversial. Relevant studies were identified by searching PubMed and Web of Science through September 2017. We included cohort and case-control studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) of three or more cate...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Safety evaluation of genetically modified DAS-40278-9 maize in a subchronic rodent feeding study
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Shiying Zou, Tianqi Lang, Xu Liu, Kunlun Huang, Xiaoyun He Genetically modified (GM) maize, DAS-40278-9, expresses the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The aad-1 gene, which expresses the AAD-1 protein, was derived from Gram-negative soil bacterium, Sphingobium herbicidovorans. A 90-day sub-chronic toxicity study was conducted on rats as a component of the safety evaluation of DAS-40278-9 maize. Rats ...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Cantharides poisoning: A retrospective analysis from 1996 to 2016 in China
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Youyou Zhang, Xiaowei Zhou, Jie Zhang, Chuhuai Guan, Liang Liu Cantharides poisoning may cause serious adverse reactions or even death.We attempt to retrieval articles automatically and manually with the key words of "cantharides" and " poisoning " or " side effects ", then summarized and analyzed the cases of cantharides poisoning from 1996 to 2016 in China, to provide some reference for clinical drug use and forensic identification. Finally, 91 cases were conformance to require; general data, cli...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Canadian, European and United States new drug approval times now relatively similar
The objectives of this analysis were to assess whether consistency in Health Canada's (HC's) approval times identified in 2011 has been sustained and to compare HC's approval times with those of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Between 2002 and 2016, 460 new drugs were approved by at least one of the agencies: 351 (76.3%), 319 (69.3%) and 392 (85.2%) by HC, the EMA and the FDA, respectively – all three approved 252 (54.8%). Overall medians and inter-quartile ranges of approval times for HC, the EMA and the FDA were 364 days (343–651), 371 days (322–434) an...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Subchronic toxicity study in rats evaluating genetically modified DAS-81419-2 soybean
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Zhi-Yong Qian, Shu-Jing Zhang, Li Zhang, Jing Zhang, Ying-Hua Liu, Qing-Hong Zhou, Shu-Qing Jiang, Shu-Fei Li A 90-day feeding study in rats was conducted to evaluate the subchronic oral toxicity of genetically modified (GM) DAS-81419-2 soybean. Wistar rats were fed with diets containing toasted soybean meal produced from DAS-81419-2 soybean grain that expresses the Cry1F, Cry1Ac, and Pat proteins or containing conventional soybean at doses of 30.0%, 15.0%, 7.5%, or 0% (control group) for 90 consecutive days. The general behavi...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Recent updates and challenges on the regulation of precision medicine: The United States in perspective
Publication date: July 2018 Source:Regulatory Toxicology and Pharmacology, Volume 96 Author(s): Lin-Chau Chang, Thomas E. Colonna The rapid progress in “omics”, such as genomics, metabolomics, microbiomics, has paved the path for precision medicine and revolutionized the development of drugs and devices promising to meet unmet medical needs. The aim of the present study was to investigate the current regulatory framework established by the United States Food and Drug Administration (USFDA) and to identify challenges and concerns through study of related literatures in the PubMed database. We found that efforts...
Source: Regulatory Toxicology and Pharmacology - May 17, 2018 Category: Toxicology Source Type: research

Assessment of the mode of action underlying development of forestomach tumors in rodents following oral exposure to ethyl acrylate and relevance to humans
Publication date: Available online 5 May 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Chad M. Thompson, Mina Suh, Grace Chappell, Susan Borghoff, Robert Ellis-Hutchings, Karin Wiench, Lavorgie Finch, Deborah M. Proctor Chronic repeated gavage dosing of high concentrations of ethyl acrylate (EA) causes forestomach tumors in rats and mice. For two decades, there has been general consensus that these tumors are unique to rodents because of: i) lack of carcinogenicity in other organs, ii) specificity to the forestomach (an organ unique to rodents which humans do not possess), iii) lack of carcinogenicity by o...
Source: Regulatory Toxicology and Pharmacology - May 9, 2018 Category: Toxicology Source Type: research

Assessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence
The objectives of this clinical study were to demonstrate a reduction in exposure to selected harmful and potentially harmful constituents (HPHCs), and to assess product use behavior, in Japanese healthy adult smokers who switched to a novel tobacco vapor product (NTV). 60 smokers were randomly assigned for 5 days to either (a) a group who switched to an NTV (n = 20), (b) a group who continued to smoke their own brand of conventional cigarettes (CC, n = 20) or (c) a smoking abstinence group (SA, n = 20). Fifteen biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day 3 and 5. Product...
Source: Regulatory Toxicology and Pharmacology - May 6, 2018 Category: Toxicology Source Type: research

Application of a direct aerosol exposure system for the assessment of biological effects of cigarette smoke and novel tobacco product vapor on human bronchial epithelial cultures
Publication date: Available online 3 May 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Shinkichi Ishikawa, Kazushi Matsumura, Nobumasa Kitamura, Kanae Ishimori, Yuichiro Takanami, Shigeaki Ito Recent advancements in in vitro exposure systems and cell culture technology enable direct exposure to cigarette smoke (CS) of human organotypic bronchial epithelial cultures. MucilAir organotypic bronchial epithelial cultures were exposed, using a Vitrocell exposure system, to mainstream aerosols from the 3R4F cigarette or from a recently developed novel tobacco vapor product (NTV). The exposure aerosol dose was con...
Source: Regulatory Toxicology and Pharmacology - May 4, 2018 Category: Toxicology Source Type: research

Evaluation of airborne asbestos exposure from routine handling of asbestos-containing wire gauze pads in the research laboratory
Publication date: Available online 30 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Ediberto Garcia, Daniel Newfang, Jayme P. Coyle, Charles L. Blake, John W. Spencer, Leonard G. Burrelli, Giffe T. Johnson, Raymond D. Harbison Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire...
Source: Regulatory Toxicology and Pharmacology - May 1, 2018 Category: Toxicology Source Type: research

The safety of green tea and green tea extract consumption in adults – Results of a systematic review
Publication date: June 2018 Source:Regulatory Toxicology and Pharmacology, Volume 95 Author(s): Jiang Hu, Donna Webster, Joyce Cao, Andrew Shao A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallo...
Source: Regulatory Toxicology and Pharmacology - May 1, 2018 Category: Toxicology Source Type: research

Initial hazard assessment of 4-benzylphenol, a structural analog of bisphenol F: Genotoxicity tests in vitro and a 28-day repeated-dose toxicity study in rats
Publication date: Available online 27 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Toshime Igarashi, Hideki Serizawa, Katsumi Kobayashi, Hiroshi Suzuki, Mariko Matsumoto, Takako Iso, Tomoko Kawamura, Kaoru Inoue, Atsushi Ono, Takashi Yamada, Akihiko Hirose 4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis. Since its safety is largely unknown, we conducted toxicity tests as part of screening risk assessment in an existing chemical safety s...
Source: Regulatory Toxicology and Pharmacology - April 27, 2018 Category: Toxicology Source Type: research

An Adverse Outcome Pathway (AOP) for forestomach tumors induced by non-genotoxic initiating events
Publication date: Available online 21 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Deborah M. Proctor, Mina Suh, Grace Chappell, Susan J. Borghoff, Chad M. Thompson, Karin Wiench, Lavorgie Finch, Robert Ellis-Hutchings The utility of rodent forestomach tumor data for hazard and risk assessment has been examined for decades because humans do not have a forestomach, and these tumors occur by varying modes of action (MOAs). We have used the MOA for ethyl acrylate (EA) to develop an Adverse Outcome Pathway (AOP) for forestomach tumors caused by non-genotoxic initiating events. These tumors occur seconda...
Source: Regulatory Toxicology and Pharmacology - April 22, 2018 Category: Toxicology Source Type: research

Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective
Publication date: Available online 19 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): John L. Vahle, Ulf Anderson, Eric A.G. Blomme, Jean-Christophe Hoflack, Daniel P. Stiehl Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug disco...
Source: Regulatory Toxicology and Pharmacology - April 19, 2018 Category: Toxicology Source Type: research

Minimum datasets to establish a CAR-mediated mode of action for rodent liver tumors
Publication date: Available online 16 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Richard Peffer, Matthew LeBaron, Michael Battalora, Werner Bomann, Christoph Werner, Manoj Aggarwal, Rocky Rowe, Helen Tinwell Methods for investigating the Mode of Action (MoA) for rodent liver tumors via constitutive androstane receptor (CAR) activation are outlined here, based on current scientific knowledge about CAR and feedback from regulatory agencies globally. The key events (i.e., CAR activation, altered gene expression, cell proliferation, altered foci and increased adenomas/carcinomas) can be demonstrated b...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

Safety assessment of ethanolic extract of Olea europaea L. leaves after acute and subacute administration to Wistar rats
Publication date: Available online 17 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Camille Gaube Guex, Fernanda Ziegler Reginato, Kássia Caroline Figueredo, Andreia Regina Haas da Silva, Fernanda Brum Pires, Roberta da Silva Jesus, Cibele Lima Lhamas, Gilberti Helena Hübscher Lopes, Liliane de Freitas Bauermann Olea europaea L., popularly known as olive, is a plant widely used worldwide. Its leaves, fruit and oil are extensively consumed and present important pharmacological properties. However, studies regarding the toxicity of olive leaves are still limited in the literature. Therefore...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

In silico toxicology protocols
Publication date: Available online 17 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Glenn J. Myatt, Ernst Ahlberg, Yumi Akahori, David Allen, Alexander Amberg, Lennart T. Anger, Aynur Aptula, Scott Auerbach, Lisa Beilke, Phillip Bellion, Romualdo Benigni, Joel Bercu, Ewan D. Booth, Dave Bower, Alessandro Brigo, Natalie Burden, Zoryana Cammerer, Mark T.D. Cronin, Kevin P. Cross, Laura Custer, Magdalena Dettwiler, Krista Dobo, Kevin A. Ford, Marie C. Fortin, Samantha E. Gad-McDonald, Nichola Gellatly, Véronique Gervais, Kyle P. Glover, Susanne Glowienke, Jacky Van Gompel, Steve Gutsell, Barry Ha...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

Exposure to beta-cypermethrin impairs the reproductive function of female mice
This study aimed to investigate the effects of beta-cypermethrin (β-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the β-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the β-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the β-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicle...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

Targeted inhibition of tumor survival, metastasis and angiogenesis by Acacia ferruginea mediated regulation of VEGF, inflammatory mediators, cytokine profile and inhibition of transcription factor activation
Publication date: Available online 18 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Kunnathur Murugesan Sakthivel, Chandrasekaran Guruvayoorappan Acacia ferruginea extract (AFE) was studied for anti-metastasis/-angiogenesis activity against B16F-10 melanoma cells in C57BL/6 mice. In vitro cytotoxicity of AFE was first screened using MTT assay and it was shown to inhibit B16F-10 cells with IC50 value of 52.94 μg/ml. Anti-metastatic activity of AFE in vivo revealed administration of AFE (10 mg/kg.b.wt) in three different regimens has shown reduced metastatic colony formation in lungs and prolo...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

Quantitative risk assessment of tobacco products: A potentially useful component of substantial equivalence evaluations
Publication date: June 2018 Source:Regulatory Toxicology and Pharmacology, Volume 95 Author(s): Kristin M. Marano, Charlene Liu, William Fuller, P. Robinan Gentry Quantitative risk assessment (QRA), a scientific, evidence-based analytical process that combines chemical and biological data to quantify the probability and potential impact of some defined risk, is used by regulatory agencies for decision-making. Thus, in tobacco product regulation, specifically in substantial equivalence (SE) evaluations, QRA can provide a useful, practical, and efficient approach to address questions that might arise regarding human health ...
Source: Regulatory Toxicology and Pharmacology - April 18, 2018 Category: Toxicology Source Type: research

Acute and subchronic toxicities in dogs and genotoxicity of honokiol microemulsion
This article aims to conduct toxicity test research on honokiol microemulsion(HM) to provide reference frame for the safe dose design as well as the toxic and adverse reaction monitoring in clinic. High performance liquid chromatography (HPLC) method was adopted to determine the concentration, stability and uniformity of HM and the results indicated that the test sample was conformed to the toxicity test requirements. In the acute toxicity test, six intravenous drip dosages, namely, 100.0, 66.7, 44.4, 19.8, 8.8, and 3.9 mg/kg were set, with one beagle dog in each dosage, respectively. In addition, the results also demons...
Source: Regulatory Toxicology and Pharmacology - April 13, 2018 Category: Toxicology Source Type: research

A human relevance investigation of PPAR α-mediated key events in the hepatocarcinogenic mode of action of propaquizafop in rats
The objective of the present investigation was to evaluate the dependency of early key events leading to liver tumors on PPARα activation in wildtype (WT) compared to PPARα-knockout (KO) rats following 2 weeks exposure to 75, 500 and 1000 ppm propaquizafop in the diet. In WT rats, both WY-14643 (50 mg/kg bw/day) and propaquizafop (dose-dependently) induced marked increases in liver weights, correlating with liver enlargement and hepatocellular hypertrophy, along with increased CYP4A and acyl-CoA oxidase mRNA expression and enzyme activities versus controls, while in KO rats liver weight was mildly increas...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research

The sub-chronic toxicity of a naphthenic hydrocarbon solvent in rats
Publication date: Available online 6 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Juan-Carlos Carrillo, M. David Adenuga, Fayaz Momin, Richard H. Mckee Cycloalkanes/naphthenes are constituents of complex hydrocarbon solvents, and hence an understanding of their toxicological profile is critical to establish safe limits for occupational exposures to these solvents. Although naphthenes are structurally related to and share a common metabolic fate with the straight and branched chain analogues, some toxicokinetic differences have been noted. The acute central nervous system response to volatile naphthe...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research

An innovative investigative approach to characterize the effects observed in a combined fertility study in male and female rats
Publication date: Available online 7 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Jianxun Xie, Juergen Funk, Martin Bopst, Giorgio Ottaviani, Noel Downes, Scott Hackford, Loris Villabruna, Georg Schmitt, Paul Barrow This paper describes the characterization of male- and female-mediated effects in a standard ICH rat fertility and early embryonic development study with a discontinued clinical small molecule. In the standard study, the test item had no effect on the number of treated females becoming pregnant, but litter sizes were reduced at the high dose level. In the treated male rats, increased inc...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research

In vitro percutaneous penetration of silver nanoparticles in pig and human skin
In this study, the effects of surface charge, dose, and cosmetic vehicle on the penetration of silver nanoparticles (AgNPs) into pig and human skin were compared. AgNPs (20 nm) with varying surface-charges (polyethylene glycol (PEG; neutral), citrate (CIT; negative), and branched polyethylenimine (bPEI; positive) were dosed onto skin in in vitro diffusion cells using an aqueous solution and an oil-in-water emulsion formulation. Samples were analyzed by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscope (TEM) to assess AgNP skin penetration. The results showed that neutral and posit...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research

An open-label, randomized, four-treatment crossover study evaluating the effects of salt form, acetaminophen, and food on the pharmacokinetics of phenylephrine
Publication date: Available online 7 April 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Cathy K. Gelotte Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter (OTC) medicines. Previously marketed prescription products contained phenylephrine tannate, an extended-release salt, which allowed dosing every 8–12 h. Given the regulatory history that cold medicines marketed before 1962 had limited supporting clinical data, and with widespread replacement of pseudoephedrine by phenylephrine in OTC products over the last ten years, the need for contemporary studies grew. This ex...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research

Criteria for grouping of manufactured nanomaterials to facilitate hazard and risk assessment, a systematic review of expert opinions
Publication date: June 2018 Source:Regulatory Toxicology and Pharmacology, Volume 95 Author(s): Nina Elisabeth Landvik, Vidar Skaug, Benedicte Mohr, Jos Verbeek, Shanbeh Zienolddiny With the emergence of nanotechnology the number of manufactured nanomaterials (MNM) in production and use is constantly increasing. Exposure of workers to MNM is of concern, because still much is unknown about health effects. MNM may have different properties, testing of each material is time consuming and costly. Experts have proposed various approaches to categorize MNM to facilitate risk assessment of human health effects based on shared pr...
Source: Regulatory Toxicology and Pharmacology - April 12, 2018 Category: Toxicology Source Type: research