Assessment of priority tobacco additives per the requirements of the EU Tobacco Products Directive (2014/40/EU) part 1: Background, approach, and summary of findings
Publication date: Available online 21 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Simms Liam, Clarke Anna, Paschke Thilo, Manson Andrew, Murphy James, Stabbert Regina, Esposito Marco, Ghosh David, Roemer Ewald, Martinez Javier, Freiesleben Jarl, Kim Hyo-Keun, Lindegart Thomas, Scharfe Marc, Vincze Istvan, Vlachos Panagiotis, Wigotzki Diane, Pollner Gwen, Lutz RolfAbstractThis publication is part of a series of 3 publications and describes the non-clinical and clinical assessment performed to fulfill the regulatory requirement per Art. 6 (2) of the EU Tobacco Products Directive 2014/40/EU under whi...
Source: Regulatory Toxicology and Pharmacology - February 22, 2019 Category: Toxicology Source Type: research

A case study on the application of an expert-driven read-across approach in support of quantitative risk assessment of p,p’-dichlorodiphenyldichloroethane
Publication date: Available online 19 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Lucina E. Lizarraga, Jeffry L. Dean, J. Phillip Kaiser, Scott C. Wesselkamper, Jason C. Lambert, Q. Jay ZhaoAbstractDeriving human health risk estimates for environmental chemicals has traditionally relied on in vivo toxicity databases to characterize potential adverse health effects and associated dose-response relationships. In the absence of in vivo toxicity information, new approach methods (NAMs) such as read-across have the potential to fill the required data gaps. This case study applied an expert-driven read-...
Source: Regulatory Toxicology and Pharmacology - February 21, 2019 Category: Toxicology Source Type: research

Effect of acute exposure in swiss mice (Mus musculus) to a fibrinolytic protease produced by Mucor subtilissimus UCP 1262: An histomorphometric, genotoxic and cytological approach
Publication date: Available online 18 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Marllyn Marques da Silva, Tamiris Alves Rocha, Danielle Feijó de Moura, Cristiano Aparecido Chagas, Francisco Carlos Amanajás de Aguiar Júnior, Noêmia Pereira da Silva Santos, Renata Vitória Da Silva Sobral, Jéssica Miranda do Nascimento, Ana Cristina Lima Leite, Lorenzo Pastrana, Romero Marcos Pedrosa Brandão Costa, Thiago Pajeú Nascimento, Ana Lúcia Figueiredo PortoAbstractThe fibrinolytic enzyme produced by Mucor subtilissimus UCP 1262 was obtained by s...
Source: Regulatory Toxicology and Pharmacology - February 19, 2019 Category: Toxicology Source Type: research

28-Day somatic gene mutation study of 1-bromopropane in female Big Blue® B6C3F1 mice via whole-body inhalation: Support for a carcinogenic threshold
Publication date: Available online 16 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Mark Stelljes, Robert Young, Jeff WeinbergAbstractA 2-year inhalation rat and mouse cancer study by the National Toxicology Program (NTP) on 1-bromopropane, a brominated solvent most commonly used as a vapor degreaser, showed significant increase in tumors in the lung of female mice and in the large intestine of male and female rats. The most sensitive endpoint was lung tumors in female mice. Mice of both sexes had hyperplasia and inflammation of the nose and showed regeneration of lung tissue. The NTP assumed that t...
Source: Regulatory Toxicology and Pharmacology - February 16, 2019 Category: Toxicology Source Type: research

Toxicological assessment compilation of selected examples of raw materials for homeopathic medicinal products
Publication date: Available online 13 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Marie-Luise Buchholzer, Marion Kirch, Christiane Kirchner, Werner KnoessAbstractThe considerable number of homeopathic medicinal products (HMP) on the German market and the staggering breadth of active substances of various origin along with the specific legal requirements of adequate safety principles posed the need to compile data on toxicologically evaluated raw materials. In line with the European regulatory framework, HMP applications must consider appropriate safety standards in analogy to conventional human me...
Source: Regulatory Toxicology and Pharmacology - February 14, 2019 Category: Toxicology Source Type: research

Evaluation of developmental toxicity of Methyl Chloride (Chloromethane) in rats, mice, and rabbits
Publication date: Available online 10 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Josje Arts, Marco Kellert, Lynn Pottenger, Josianne Theuns-van VlietAbstractMethyl Chloride (MeCl; Chloromethane) is a high production volume chemical (>1000 t/a) and is used as an industrial solvent. Based on cardiac lesions reported in developmental toxicity studies in mice, but not in rats, manufacturers decided to classify MeCl as a developmental toxicant, cat. 2. Recently, the European Chemical Agency required a developmental toxicity study in a non-rodent species. No developmental toxicity was observed in ...
Source: Regulatory Toxicology and Pharmacology - February 11, 2019 Category: Toxicology Source Type: research

Acute toxicity and genotoxicity evaluations of Nattokinase, A promising agent for cardiovascular diseases prevention
Publication date: Available online 8 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Hao Wu, Huan Wang, Feng Xu, Jiepeng Chen, Lili Duan, Fengjiao ZhangAbstractCardiovascular diseases (CVDs) are the leading cause of death in the world; however, current agents for CVDs prevention are still limited. Owing to the serious bleeding risk of Aspirin, FDA recently recommended against it from preventing first heart attacks. Nattokinase (NK), a serine protease possessing many key beneficial effects on cardiovascular system, is being pursued as a promising alternative agent. In light of this, the safety profile ...
Source: Regulatory Toxicology and Pharmacology - February 9, 2019 Category: Toxicology Source Type: research

Regulatory effect of decreasing therapeutic duplication of respiratory drugs using a prescription database between 2012 and 2015
Publication date: Available online 8 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Hyesung Lee, Inmyung Song, Sun Mi Shin, Han Eol Jeong, Eui-Kyung Lee, Ju-Young ShinAbstractDuplicative drug use increases the risk of adverse drug reactions and expends healthcare resources unnecessarily. No epidemiological evidence of the prevalence of therapeutic duplication (TD) involving respiratory system drugs exists. Therefore, we describe the prescription patterns of these drugs and estimate changes in TD rates following implementation of a new regulation in 2013. A time-series analysis using national healthca...
Source: Regulatory Toxicology and Pharmacology - February 9, 2019 Category: Toxicology Source Type: research

A 90-day subchronic toxicology screen of genetically modified rice Lac-3 and its effects on the gut microbiota in Sprague-Dawley rats
Publication date: Available online 7 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Xueqin Zhang, Tongtong Zhang, Jingni Shi, Shiying Zou, Mingzhang Guo, Xiaoyun He, Daichang Yang, Xiaohong MeiAbstractA 90-day subchronic toxicology screen of genetically modified (GM) rice Lac-3 expressing human lactoferrin (hLF) and its effects on the gut microbiota were studied in comparison to non-GM rice fed to Sprague-Dawley (SD) rats. Three different dietary concentrations (17.5%, 35% and 70%, w/w) of the GM rice or its corresponding non-GM rice were used. Additionally, the phylotypes of gut microbiota in the co...
Source: Regulatory Toxicology and Pharmacology - February 8, 2019 Category: Toxicology Source Type: research

Subacute toxicity and toxicokinetics study of DHP107, an oral paclitaxel formulation with once-weekly dosing in mice
In conclusion, the target organs were determined to be the reproductive and hematopoietic organs in male mice, suggesting of sex difference and the NOAEL of DHP107 was established to be 
Source: Regulatory Toxicology and Pharmacology - February 7, 2019 Category: Toxicology Source Type: research

Editorial Board
Publication date: March 2019Source: Regulatory Toxicology and Pharmacology, Volume 102Author(s): (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - February 7, 2019 Category: Toxicology Source Type: research

Toxicology study of long-term administration of rhKGF-2 eye drops on rabbit corneas
In this study, we used New Zealand white rabbits to study possible toxic effects of ocular administration of recombinant human keratinocyte growth factor-2 eye drops. Animals in the medium- and high-dose groups had some ocular irritant reactions during the course of drug administration; however this reaction was harmless to the cornea and it ended up when administration was stopped. Serum biochemistries were largely unaffected by treatment. Pathological examinations were unremarkable. We found that over-dosed administration of these eye drops caused some ocular irritation, but this irritant reaction was harmless to the eye...
Source: Regulatory Toxicology and Pharmacology - February 6, 2019 Category: Toxicology Source Type: research

Toxicological comparison of cigarette smoke and e-cigarette aerosol using a 3D in vitro human respiratory model
Publication date: Available online 2 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Lukasz Czekala, Liam Simms, Matthew Stevenson, Nicole Tschierske, Anna G. Maione, Tanvir WaleleAbstractWith the growing prevalence of e-cigarettes as an alternative to conventional cigarettes amongst smokers worldwide, there is a need for new methods to evaluate their relative toxicological profile as part of a safety assessment. Initiatives to replace, reduce and refine animal testing have led to developments of new methodologies utilizing organotypic, in vitro tissue models. Here we use a respiratory epithelial mode...
Source: Regulatory Toxicology and Pharmacology - February 2, 2019 Category: Toxicology Source Type: research

Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria
Publication date: Available online 2 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Lois Haighton, Ashley Roberts, Tomas Jonaitis, Barry LynchAbstractGiven the widespread use of the low-calorie sweetener aspartame over the last 30 years, the current work was undertaken to evaluate aspartame epidemiology studies looking at cancer endpoints against quality appraisal criteria. The quality appraisal tool used was from the National Heart, Lung and Blood Institute (NHLBI) of the National Institute of Health. Studies identified included nine case-control studies and five prospective cohort studies. Most stu...
Source: Regulatory Toxicology and Pharmacology - February 2, 2019 Category: Toxicology Source Type: research

Approval of modified-release products by FDA without clinical efficacy/safety studies: A retrospective survey from 2008 to 2017
Publication date: Available online 1 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Yi-Lin Wang, Yi-Ting Chang, Shih-Ying Yang, Ya-Wen Chang, Mei-Hsien Kuan, Chien-Lung Tu, Hui-Chun Hong, I-Chun Lai, Churn-Shiouh Gau, Li-Feng HsuAbstractIn principle, approval of a modified-release (MR) drug product is based on evidence from pharmacokinetic (PK) and/or pharmacodynamic studies and clinical efficacy/safety studies. The purpose of this survey is (i) to explore the number of new drug applications (NDAs) of MR drug products, approved by the FDA, employ the PK study as a bridge to already-approved immediate...
Source: Regulatory Toxicology and Pharmacology - February 1, 2019 Category: Toxicology Source Type: research

Emission level of seven mainstream smoke toxicants from cigarette with variable tobacco leaf constituents
Conclusions] The results showed that seven toxicants were significantly influenced by leaf position and location, and closely correlated with leaf components, such as potassium, malate and alkaloid contents. The results provide useful and comprehensive information on the affecting factors and correlating leaf constituents for the variations of seven smoke toxicants.Graphical abstract (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 31, 2019 Category: Toxicology Source Type: research

An evaluation of the USEPA Proposed Approaches for applying a biologically based dose-response model in a risk assessment for perchlorate in drinking water
Publication date: Available online 29 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Harvey H. Clewell, P. Robinan Gentry, C. Eric Hack, Tracy Greene, Rebecca A. ClewellAbstractThe United States Environmental Protection Agency's (USEPA) 2017 report, “Draft Report: Proposed Approaches to Inform the Derivation of a Maximum Contaminant Level Goal for Perchlorate in Drinking Water”, proposes novel approaches for deriving a Maximum Contaminant Level Goal (MCLG) for perchlorate using a biologically-based dose-response (BBDR) model. The USEPA (2017) BBDR model extends previously peer-reviewed per...
Source: Regulatory Toxicology and Pharmacology - January 30, 2019 Category: Toxicology Source Type: research

Improving risk assessment approaches for chemicals with both endogenous and exogenous exposures
Publication date: Available online 28 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): William H. Farland, Angela Lynch, Neeraja K. Erraguntla, Lynn H. PottengerAbstractTo conduct risk assessments of exogenous chemicals for which there are also endogenous exposures, knowledge of the chemistry and biology of both types of exposures need to be integrated into problem formulation and carried through to risk characterization. This issue is framed in a risk assessment context, highlighting the importance of quantifying increments of dose from all sources of the same or similar chemicals interacting with biol...
Source: Regulatory Toxicology and Pharmacology - January 29, 2019 Category: Toxicology Source Type: research

Acute and sub-chronic 90-day oral toxicity study of Perilla seed oil in rodents and Beagle dogs
In conclusion, the “no observed adverse effect level” (NOAEL) of oral administration of PSO for 90 days in Beagle dogs was considered to be 3 g/kg/d.Graphical abstract (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 29, 2019 Category: Toxicology Source Type: research

A study in a rat initiation-promotion bladder tumour model demonstrated no promoter/progressor potential of dapagliflozin
In conclusion, dapagliflozin does not act as promoter or progressor of bladder cancer in a validated bladder cancer model in rats. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 25, 2019 Category: Toxicology Source Type: research

A comprehensive toxicological safety assessment of an extract of Ageratum conyzoides
Publication date: Available online 23 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Philip A. Palmer, Bryson A. Jessica, Amy E. Clewell, John R. Endres, Gábor Hirka, Adél Vértesi, Erzsébet Béres, Róbert Glávits, Ilona Pasics SzakonyinéAbstractA battery of toxicological studies was conducted to aid in the safety assessment of an ethanolic extract of Ageratum conyzoides for use as an ingredient in food. In accordance with internationally accepted standards, a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, an in...
Source: Regulatory Toxicology and Pharmacology - January 24, 2019 Category: Toxicology Source Type: research

Toxicologic evaluation of repetitive 4-week intravenous injections of midkine antisense oligonucleotide nanoliposomes in rats
Publication date: Available online 22 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Jing Chen, Jing Zhong, Pingping Niu, Limin Xu, Linfu Zhou, Honghai Wu, Chao Chen, Licheng DaiAbstractMidkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we report the 4-week sub-chronic toxicity of MK-ASODN nanoliposomes in SD rats. The adverse effects included loss of body weight gain and food consumption, peri-rhinal bleeding, piloerection, peri-anal filth, and kidney, liver, spleen, thymus, lung, and inject...
Source: Regulatory Toxicology and Pharmacology - January 23, 2019 Category: Toxicology Source Type: research

Human health safety studies of a new insecticide: Dissipation kinetics and dietary risk assessment of afidopyropen and one of its metabolites in cucumber and nectarine
Publication date: Available online 18 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Jun Xie, Yunxi Zheng, Xingang Liu, Fengshou Dong, Jun Xu, Xiaohu Wu, Mingshan Ji, Yongquan ZhengAbstractTo preliminarily study the law of natural dissipation and the relation to human health of a new insecticide (afidopyropen), the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method and a UHPLC-MS/MS system were used to extract and detect the afidopyropen and its metabolite (M440I007) from cucumber and nectarine. The limits of quantitation (LOQs) of both target compounds in two matrixes were reduced to 0....
Source: Regulatory Toxicology and Pharmacology - January 18, 2019 Category: Toxicology Source Type: research

Effective tool for assessment of the quality of barrier creams - relationships between rheological, textural and sensory properties
Publication date: Available online 18 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Agnieszka Kulawik-Pióro, Anna Ptaszek, Joanna KrukAbstractThe efficiency of barier creams (BC) in the prevention of occupational skin diseases is closely related to their mechanical, rheological but also sensory properties. The measurement procedure we elaborated, which simulates the spreadability conditions on the skin and evaluation whether the structure reconstruction occurs (hysteresis loop test, shear rate dependence of normal force), allows the assessment of the effectivness of the BC in terms of mechanic...
Source: Regulatory Toxicology and Pharmacology - January 18, 2019 Category: Toxicology Source Type: research

Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible
Publication date: Available online 18 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): John E. Doe, Alan R. Boobis, Vicki Dellarco, Penelope A. Fenner-Crisp, Angelo Moretto, Timothy P. Pastoor, Rita S. Schoeny, Jennifer G. Seed, Douglas C. WolfAbstractDevelopments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either “carcinogens” or “non-carcinogens”. The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three cat...
Source: Regulatory Toxicology and Pharmacology - January 18, 2019 Category: Toxicology Source Type: research

Consumer protection provided by the European medical device and cosmetic legislation for condoms and lubricants
Publication date: Available online 16 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): B. Desmedt, M. Vanhamme, C. Vanhee, V. Rogiers, E. DeconinckAbstractPersonal lubricants and lubricants used in condoms contain a number of ingredients which are also present in cosmetic products. They have to comply with the medical device regulation (745/2017). It is assumed that they provide the same level of consumer protection, if not more, as foreseen in the legal framework of cosmetics (1223/2009). In the current study we developed an analytical method capable of identifying and quantifying 15 ingredients, commo...
Source: Regulatory Toxicology and Pharmacology - January 17, 2019 Category: Toxicology Source Type: research

Measurement uncertainty for the potency estimation by rapid microbiological methods (RMMs) with correlated data
Publication date: Available online 14 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Alessandro Morais Saviano, Ricardo J.N. Bettencourt da Silva, Felipe Rebello LourençoAbstractRecently, rapid microbiological methods (RMM) have often been used to determinate the potency of antibiotic drugs. Since all the standard and sample preparations are assayed into the same analytical conditions, it is expected that the correlations among the inhibitions zone sizes are not negligible. However, the procedures adopted in uncertainty estimations do not consider the correlation of data. The aim of this work w...
Source: Regulatory Toxicology and Pharmacology - January 15, 2019 Category: Toxicology Source Type: research

Challenges in working towards an internal threshold of toxicological concern (iTTC) for use in the safety assessment of cosmetics: Discussions from the Cosmetics Europe iTTC Working Group workshop
Publication date: Available online 15 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Corie A. Ellison, Karen L. Blackburn, Paul L. Carmichael, Harvey J. Clewell, Mark T.D. Cronin, Bertrand Desprez, Sylvia E. Escher, Steve S. Ferguson, Sébastien Grégoire, Nicola J. Hewitt, Heli M. Hollnagel, Martina Klaric, Atish Patel, Sabrina Salhi, Andreas Schepky, Barbara G. Schmitt, John F. Wambaugh, Andrew WorthAbstractThe Threshold of Toxicological Concern (TTC) is an important risk assessment tool which establishes acceptable low-level exposure values to be applied to chemicals with limited toxico...
Source: Regulatory Toxicology and Pharmacology - January 15, 2019 Category: Toxicology Source Type: research

Authors' response to the letter to the editor by Jowsey et al.
Publication date: Available online 3 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Olivier Sanvido, Kaspar Schmid, Rex E. FitzGerald, Nicolas Roth, Martin F. Wilks, Peter Bormann, Nancy B. Hopf (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 11, 2019 Category: Toxicology Source Type: research

Fitness for purpose and stability assessment of long-chain polyunsaturated fatty acids in chicken tissues
Publication date: Available online 9 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Gerald Patrick Dillon, Alexandros Yiannikouris, Walter Brandl, Cathy Cardinall, Wendy Yuan, Colm Anthony MoranAbstractThe global popularity of chicken in human diets make it an obvious choice for enrichment with DHA and LC-PUFA. There is presently a need for a robust method for the analysis of chicken tissues and where the fitness for purpose of the method has been demonstrated. The purpose of this paper is to present the validation of the AOAC method 996.06 on five different chicken tissues; breast, thigh, skin, kidne...
Source: Regulatory Toxicology and Pharmacology - January 10, 2019 Category: Toxicology Source Type: research

Perfluorohexanoic acid toxicity, part I: Development of a chronic human health toxicity value for use in risk assessment
Publication date: Available online 9 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Anthony L. Luz, Janet K. Anderson, Philip Goodrum, Judi DurdaAbstractPerfluorohexanoic acid (PFHxA) is a short-chain, six-carbon perfluoroalkyl acid (PFAA) and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used globally today. The transition to short-chain fluorotelomer-based products as a cornerstone in replacement fluorochemistry has raised questions regarding potential human health risks associated with exposure to fluorotelomer-based substances and th...
Source: Regulatory Toxicology and Pharmacology - January 10, 2019 Category: Toxicology Source Type: research

Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops
This study was designed to assess the preclinical toxicity of antipyrine combined with lidocaine hydrochloride ear drops (ALED) and support the clinical trials of ALED in clinical settings in China. All the experiments including acute toxicity in rodents, skin sensitization toxicity in guinea pigs, skin irritation toxicity in rabbits and chronic toxicity in rats were performed according to China Food and Drug Administration (CFDA) guidelines. The maximum tolerated dose (MTD) of ALED administration for mice and rats was over (400 g antipyrine plus 100 g lidocaine hydrochloride)/kg and (240 g andtipyrine plus 60 g li...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

Isopsoralen induces different subchronic toxicities and metabolomic outcomes between male and female Wistar rats
Publication date: Available online 8 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Yue Zhang, Xiao-mei Yuan, Yue-fei Wang, Miao-miao Jiang, Ya-nan Bi, Ying Liu, Wei-ling Pu, Lei Song, Ju-yang Huang, Li-kang Sun, Zhi-xing Zhou, Kun ZhouAbstractIsopsoralen is a major active and quality-control component of Fructus Psoraleae, but lacks a full safety evaluation. We evaluated the oral toxicity of isopsoralen in Wistar rats treated for 3 months at doses of 0, 3.5, 7.0, and 14 mg/kg. Additionally, the plasma metabolomics of isopsoralen in male and female rats treated for 3 months at doses of 0 and...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

Target animal safety testing of an oral salicylanilide suspension, oxyclozanide, for the treatment of fascioliasis in bovine in China
Publication date: Available online 8 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Zhen Dong, Jichao Sun, Yubin Bai, Weiwei Wang, Yueming Zhu, Bing Li, Fusheng Cheng, Xiaojuan Wei, Enliang Song, Haijian Cheng, Fugui Jiang, Xuzheng Zhou, Jiyu ZhangAbstractThe aim of this study was to determine the potential toxicity risk of an oxyclozanide suspension to the target animal, bovine. In this experiment, 32 Simmental beef cattles were fattened and fed a full-price diet without antimicrobial agents. The test cattle were divided into 4 groups, which were treated with 0, 1, 3, and 5 times the recommended dosa...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

Perfluorohexanoic acid toxicity, part II: Application of human health toxicity value for risk characterization
Publication date: Available online 8 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Janet K. Anderson, Anthony L. Luz, Philip Goodrum, Judi DurdaAbstractPerfluorohexanoic acid (PFHxA) is a short-chain, six-carbon PFAA and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used in the United States, Europe and Japan today. With the shift towards short-chain PFAA chemistry, uncertainties remain regarding human health risks associated with current exposure levels. Here, we present a critical review and assessment of data relevant to human health...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge
Publication date: Available online 8 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Douglas C. Wolf, Samuel M. Cohen, Alan R. Boobis, Vicki L. Dellarco, Penelope A. Fenner-Crisp, Angelo Moretto, Timothy P. Pastoor, Rita S. Schoeny, Jennifer G. Seed, John E. DoeAbstractDevelopments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell ...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

Science peer review for the 21st century: Assessing scientific consensus for decision-making while managing conflict of interests, reviewer and process bias
Conclusions: By careful consideration of science peer review design elements we have shown that: 1) panel participation can be broadened to include scientists who would otherwise not participate; 2) panel diversity can be managed in an unbiased manner without adverse impacts to panel expertise; 3) results obtained from independent concurrent panels are shown to be reproducible; and 4) there are benefits of collecting input from expert panels via a structured format (i.e., survey) with respect to characterization of consensus, identification of hidden sources of bias, and identification of potential outlier participants. (S...
Source: Regulatory Toxicology and Pharmacology - January 9, 2019 Category: Toxicology Source Type: research

The use of Genomic Allergen Rapid Detection (GARD) assays to predict the respiratory and skin sensitising potential of e-liquids
In this study, we used the Genomic Allergen Rapid Detection (GARD) testing strategy to predict and compare the respiratory and skin sensitising potential of three experimental and two commercial e-liquids. These novel, myeloid cell-based assays use changes in the transcriptional profiles of genomic biomarkers that are collectively relevant for respiratory and skin sensitisation. Our initial results indicate that the GARD assays were able to differentiate and broadly classify e-liquids based on their sensitisation potential, which are defined mixtures. Further studies need to be conducted to assess whether and how these ass...
Source: Regulatory Toxicology and Pharmacology - January 8, 2019 Category: Toxicology Source Type: research

Response to the comments of Natsch and Landsiedel on my paper “Is a combination of assays really needed for non-animal prediction of skin sensitization potential? Performance of the GARD (genomic allergen rapid detection) assay in comparison with OECD guideline assays alone and in combination.”
Publication date: Available online 7 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): David W. Roberts (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 8, 2019 Category: Toxicology Source Type: research

Letter to the editor regarding the article by Roberts, 2018
Publication date: Available online 7 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Andreas Natsch, Robert Landsiedel (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 8, 2019 Category: Toxicology Source Type: research

Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans
Publication date: Available online 8 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Samuel M. Cohen, Alan R. Boobis, Vicki L. Dellarco, John E. Doe, Penelope A. Fenner-Crisp, Angelo Moretto, Timothy P. Pastoor, Rita S. Schoeny, Jennifer G. Seed, Douglas C. WolfAbstractOver 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bi...
Source: Regulatory Toxicology and Pharmacology - January 8, 2019 Category: Toxicology Source Type: research

Short commentary on NDMA (N-nitrosodimethylamine) contamination of valsartan products
We present information and discuss various elements of this phenomenon including: actions taken by regulatory agencies, source of the nitrosamine impurities, range of possible risk assessments based mainly on ICH M7 criteria, epidemiological assessment and analytical aspects. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 8, 2019 Category: Toxicology Source Type: research

Pharmacokinetics and four-week repeated-dose toxicity of hyaluronic acid and ketorolac combination following intra-articular administration in normal rats
In conclusion, repeated IA administration of HA/KL combination was tolerated well in normal rats, encouraging future studies of IA injection of HA/KL combination on osteoarthritis-induced animal models and even patients. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 4, 2019 Category: Toxicology Source Type: research

Safety evaluation of the oils extracted from edible insects (Tenebrio molitor and Pachymerus nucleorum) as novel food for humans
This study presents the acute and subacute (28 days) toxicological profile of the oil extracted from TM and PN larvae. The TM and PN larvae have all essential amino acids and the oils extracted from them fostered a considerable reduction in cholesterol and glucose levels of the treated rats. The experiments suggested that the TM and PN oils have low toxicity since it did not cause any lethality as well as no changes in hematological parameters. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 4, 2019 Category: Toxicology Source Type: research

Percutaneous permeability of 1-phenoxy-2-propanol, a preservative in cosmetics
In this study, Franz diffusion method was used to determine the percutaneous penetration of PP using the dorsal skin of rats. Each formulation of shampoo or cream, 113.6 mg/cm2, was applied to a donor compartment of Franz diffusion cell for 24 h. Receptor fluid was collected at 0, 1, 2, 4, 8, 12, and 24 h following dermal application. Remaining formulation was removed with a cotton swab after last sampling. Using tape stripping method, stratum corneum was removed. PP in epidermis and dermis was extracted in PBS for 24 h. The concentration of PP from the swab, stratum corneum, and epidermis and dermis samples was de...
Source: Regulatory Toxicology and Pharmacology - January 4, 2019 Category: Toxicology Source Type: research

The effect of Cynara scolymus (artichoke) on maternal reproductive outcomes and fetal development in rats
Publication date: Available online 3 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): André Tadeu Gotardo, Maria Izabel da Silva Mattos, Isis Machado Hueza, Silvana Lima GórniakAbstractCynara scolymus (C.scolymus) is a plant employed worldwide as an herbal medicine. However, there is a paucity of data related to the evaluation of its toxicity in commercial preparations; thus, the aim of this study was to evaluate the possible teratogenic effect of the dry extract of C.scolymus leaves in Wistar rats. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 2.0 or 4.0 g/k...
Source: Regulatory Toxicology and Pharmacology - January 4, 2019 Category: Toxicology Source Type: research

Response to the letter to the editor by Jowsey et al. (Skin sensitization risk assessment for plant protection products: The applicability of sensitization assessment factors)
Publication date: Available online 3 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Olivier Sanvido, Kaspar Schmid, Rex E. FitzGerald, Nicolas Roth, Martin F. Wilks, Peter Bormann, Nancy B. Hopf (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 3, 2019 Category: Toxicology Source Type: research

Skin sensitization risk assessment for plant protection products: The applicability of sensitization assessment factors
Publication date: Available online 3 January 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Ian R. Jowsey, Leona Merolla, Philip A. Botham (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 3, 2019 Category: Toxicology Source Type: research

Biomonitoring Equivalents (BEs) for tetrabromobisphenol A
Publication date: Available online 26 December 2018Source: Regulatory Toxicology and PharmacologyAuthor(s): Sean M. Hays, Christopher R. KirmanAbstractTetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed by measuring TBBPA in the blood of humans. Here, we derive Biomonitoring Equivalents (BEs) for TBBPA to interpret these, and future biomonitoring results for TBBPA in humans. The available toxicity risk values (TRVs) for TBBPA were all based on toxicology studies in rats. Several studies have been conducted i...
Source: Regulatory Toxicology and Pharmacology - December 27, 2018 Category: Toxicology Source Type: research

The reliability of an environmental epidemiology meta-analysis, a case study
Publication date: Available online 24 December 2018Source: Regulatory Toxicology and PharmacologyAuthor(s): S. Stanley Young, Mithun Kumar Acharjee, Kumer DasAbstractClaims made in science papers are coming under increased scrutiny with many claims failing to replicate. Meta-analyses are questionable when based on data from observational studies which are often unreliable. We examine the reliability of the base studies used in an air quality/heart attack meta-analysis and the resulting meta-analysis. A meta-analysis study that includes 14 observational air quality/heart attack studies is examined for its statistical reliab...
Source: Regulatory Toxicology and Pharmacology - December 25, 2018 Category: Toxicology Source Type: research