3,929 results match your criteria Regulatory Toxicology and Pharmacology [Journal]


Toxicological assessment compilation of selected examples of raw materials for homeopathic medicinal products.

Regul Toxicol Pharmacol 2019 Feb 13. Epub 2019 Feb 13.

Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.

The 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 medicinal products. This review presents an option for a systematic and scientifically substantiated approach for regulatory use. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.02.007DOI Listing
February 2019

Evaluation of developmental toxicity of Methyl Chloride (Chloromethane) in rats, mice, and rabbits.

Regul Toxicol Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Triskelion, Utrechtseweg 48, 3704, HE, Zeist, the Netherlands.

Methyl 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.02.001DOI Listing
February 2019
1 Read

Acute toxicity and genotoxicity evaluations of Nattokinase, a promising agent for cardiovascular diseases prevention.

Regul Toxicol Pharmacol 2019 Feb 8;103:205-209. Epub 2019 Feb 8.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, PR China. Electronic address:

Cardiovascular 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.02.006DOI Listing
February 2019
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Regulatory effect of decreasing therapeutic duplication of respiratory drugs using a prescription database between 2012 and 2015.

Regul Toxicol Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea. Electronic address:

Duplicative 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.02.003DOI Listing
February 2019

A 90-day subchronic toxicology screen of genetically modified rice Lac-3 and its effects on the gut microbiota in Sprague-Dawley rats.

Regul Toxicol Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Beijing, 100083, China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, P.R, Beijing, 100083, China. Electronic address:

A 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. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193005
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http://dx.doi.org/10.1016/j.yrtph.2019.02.005DOI Listing
February 2019
2 Reads

Subacute toxicity and toxicokinetics study of DHP107, an oral paclitaxel formulation with once-weekly dosing in mice.

Regul Toxicol Pharmacol 2019 Feb 7;103:196-204. Epub 2019 Feb 7.

Department of Toxicological Evaluation and Research, Korea Institute of Toxicology (KIT), Daejeon, Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon, Republic of Korea. Electronic address:

DHP107, an oral formulation of paclitaxel, is effectively and systemically absorbed in intestinal endothelial cells. Although the in vivo efficacy of DHP107 has been reported, the potential toxicity of DHP107 has not been evaluated. Therefore, this study was conducted to evaluate the toxicity and toxicokinetics of DHP107 orally administered to ICR mice at 25, 50, and 100 mg/kg via once-weekly dosing for six weeks. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193004
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http://dx.doi.org/10.1016/j.yrtph.2019.02.004DOI Listing
February 2019
2 Reads

Toxicology study of long-term administration of rhKGF-2 eye drops on rabbit corneas.

Regul Toxicol Pharmacol 2019 Feb 5;103:189-195. Epub 2019 Feb 5.

Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address:

Keratinocyte growth factor -2 promotes corneal repair. Its mechanism of action involves regulating regeneration and migration of corneal cells, as well as activating corneal limbal stem cells. However, KGF-2 being a carcinogenic growth factor and its potential adverse effect in over dosage long-term treatment had not yet been reported. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.02.002DOI Listing
February 2019

Toxicological comparison of cigarette smoke and e-cigarette aerosol using a 3D in vitro human respiratory model.

Regul Toxicol Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Imperial Brands PLC, 121 Winterstoke Road, Bristol, BS3 2LL, UK.

With 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 model, EpiAirway, to examine the biological effects of nicotine-containing blu PLUS + e-cigarettes, with or without blueberry flavoring, in comparison to conventional cigarette smoke. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.036DOI Listing
February 2019

Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria.

Regul Toxicol Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Intertek Regulatory & Scientific Consultancy, 2233 Argentia Rd., Suite 201, Mississauga, ON, L5N 2X7, Canada.

Given 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.033DOI Listing
February 2019

Approval of modified-release products by FDA without clinical efficacy/safety studies: A retrospective survey from 2008 to 2017.

Regul Toxicol Pharmacol 2019 Feb 1;103:174-180. Epub 2019 Feb 1.

Center of Consultation, Center for Drug Evaluation (CDE), Taipei, Taiwan. Electronic address:

In 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-release drug products without conducting their own clinical efficacy/safety studies; and (ii) to understand the type of PK studies are required for such NDAs. To this end, we surveyed the approved records of MR drug products from 2008 to 2017 from the Drug@FDA website, and filtered pertinent information from FDA's assessment reports. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.037DOI Listing
February 2019

Emission level of seven mainstream smoke toxicants from cigarette with variable tobacco leaf constituents.

Regul Toxicol Pharmacol 2019 Jan 30;103:181-188. Epub 2019 Jan 30.

Molecular Genetics Key Laboratory of China Tobacco, Guizhou Academy of Tobacco Science, Guiyang 550081, PR China. Electronic address:

[Introduction] Seven smoke constituents, including hydrogen cyanide (HCN), ammonia (NH), phenol, benzo[α]pyrene (B[a]P), carbon monoxide (CO)¸ crotonaldehyde, and 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK), are proposed be the most relevant constituents for smoking-related diseases. [Methods] Different combinations of leaf stalk positions, varieties and locations were used to create variable chemistry of cigarette filler and smoke. Experimental cigarettes were measured for emission level of seven smoke toxicants and content of seventy-three filler components. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.032DOI Listing
January 2019

An evaluation of the USEPA Proposed Approaches for applying a biologically based dose-response model in a risk assessment for perchlorate in drinking water.

Regul Toxicol Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

ToxStrategies, Research Triangle Park, NC, USA.

The 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 perchlorate models to describe the relationship between perchlorate exposure and thyroid hormone levels during early pregnancy. Our evaluation focuses on two key elements of the USEPA (2017) report: the plausibility of BBDR model revisions to describe control of thyroid hormone production in early pregnancy and the basis for linking BBDR model results to neurodevelopmental outcomes. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.028DOI Listing
January 2019

Acute and sub-chronic 90-day oral toxicity study of Perilla seed oil in rodents and Beagle dogs.

Regul Toxicol Pharmacol 2019 Jan 28. Epub 2019 Jan 28.

Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Key Laboratory of Structure-based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Perilla seeds are used as food and traditional medicine in China. This study aimed to investigate the toxicity profile of Perilla seed oil (PSO), which is the main constituent of Perilla seeds in rodents and Beagle dogs. No significant treatment-associated toxicity or mortality was observed at PSO dosages of up to 50 g/kg and 20 g/kg in KM mice and Wistar rats, respectively, suggesting that PSO was well tolerated by the experimental rodents. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.035DOI Listing
January 2019
2 Reads

Improving risk assessment approaches for chemicals with both endogenous and exogenous exposures.

Regul Toxicol Pharmacol 2019 Jan 28;103:210-215. Epub 2019 Jan 28.

Olin Corporation (retired), Midland, MI, 48674, USA; LHP Tox Consult, LLC, Midland, MI, 48640, USA.

To conduct risk assessments of exogenous chemicals for which there are also endogenous exposures, knowledge of the chemistry and biology of both types of exposures needs 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 biological targets; understanding the influence of endogenous chemical concentrations on disease risk; and assessing total dose to targets in evaluating risk from incremental environmental exposures. Examples of recent assessments illustrate the importance of addressing this issue. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.029DOI Listing
January 2019

A study in a rat initiation-promotion bladder tumour model demonstrated no promoter/progressor potential of dapagliflozin.

Regul Toxicol Pharmacol 2019 Jan 25;103:166-173. Epub 2019 Jan 25.

Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden. Electronic address:

Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is indicated to improve glycaemic control in adults of type 2 diabetes. In nonclinical studies, dapagliflozin was neither genotoxic nor carcinogenic. However, in some clinical studies, an increased incidence of bladder cancer was observed in the dapagliflozin group vs. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.031DOI Listing
January 2019
1 Read

A comprehensive toxicological safety assessment of an extract of Ageratum conyzoides.

Regul Toxicol Pharmacol 2019 Jan 23;103:140-149. Epub 2019 Jan 23.

Toxi-Coop Zrt., Magyar Jakobinusok tere 4/B, H-1122, Budapest, Hungary. Electronic address:

A 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 vivo mammalian micronucleus test, and a 90-day repeated-dose oral toxicity study in rats were performed. In the first three applied test systems, no evidence of mutagenicity, clastogenicity or genotoxicity was revealed. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.027DOI Listing
January 2019
1 Read
2.031 Impact Factor

Toxicologic evaluation of repetitive 4-week intravenous injections of midkine antisense oligonucleotide nanoliposomes in rats.

Regul Toxicol Pharmacol 2019 Jan 22;103:130-139. Epub 2019 Jan 22.

Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, 198 Hongqi Road, Huzhou, 313000, PR China. Electronic address:

Midkine 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 injection site lesions at high doses. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.030DOI Listing
January 2019
2 Reads

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.

Regul Toxicol Pharmacol 2019 Jan 18;103:150-157. Epub 2019 Jan 18.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address:

To 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 0.0001 mg/kg. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.025DOI Listing
January 2019
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Effective tool for assessment of the quality of barrier creams - relationships between rheological, textural and sensory properties.

Regul Toxicol Pharmacol 2019 Jan 18;103:113-123. Epub 2019 Jan 18.

Department of Engineering and Machinery in Food Industry, Faculty of Food Technology, University of Agriculture in Krakow, ul. Balicka 122, 30-149, Krakow, Poland.

The 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 mechanical resistance and its adhesion to the skin surface. In this thesis an effort was made to define the impact of the human factor - the product application on skin - on the efficiency of medical devices for cutaneous use. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.026DOI Listing
January 2019
2 Reads

Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible.

Regul Toxicol Pharmacol 2019 Jan 18;103:124-129. Epub 2019 Jan 18.

Syngenta Crop Protection, LLC, Greensboro, NC, 27419, USA.

Developments 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 categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.024DOI Listing
January 2019
2 Reads

Consumer protection provided by the European medical device and cosmetic legislation for condoms and lubricants.

Regul Toxicol Pharmacol 2019 Jan 16;103:106-112. Epub 2019 Jan 16.

Medicines and Health Products, Sciensano, Juliette Wytsmanstraat 14, 1050, Brussels, Belgium.

Personal lubricants and lubricants used in condoms contain a number of ingredients which are also present in cosmetic products. These have to comply to the medical device regulation (745/2017) which should 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, commonly found in lubricants and cosmetics. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.022DOI Listing
January 2019
2 Reads

Measurement uncertainty for the potency estimation by rapid microbiological methods (RMMs) with correlated data.

Regul Toxicol Pharmacol 2019 Mar 14;102:117-124. Epub 2019 Jan 14.

Departamento de Farmácia, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, Av. Prof. Lineu Prestes, 580, 05508-000, São Paulo, Brazil. Electronic address:

Recently, 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.023DOI Listing
March 2019
2 Reads

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.

Regul Toxicol Pharmacol 2019 Jan 15;103:63-72. Epub 2019 Jan 15.

European Commission, Joint Research Centre, Ispra, Italy.

The 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 toxicological data. One of the logical next steps in the continued evolution of TTC is to develop this concept further so that it is representative of internal exposures (TTC based on plasma concentration). An internal TTC (iTTC) would provide threshold values that could be utilized in exposure-based safety assessments. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193001
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http://dx.doi.org/10.1016/j.yrtph.2019.01.016DOI Listing
January 2019
5 Reads

Editorial.

Regul Toxicol Pharmacol 2019 Feb;101:A1-A2

Laboratory of Drug Metabolism and Pharmacokinetics Showa Pharmaceutical University Machida, Tokyo, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.yrtph.2018.12.015DOI Listing
February 2019
1 Read

Fitness for purpose and stability assessment of long-chain polyunsaturated fatty acids in chicken tissues.

Regul Toxicol Pharmacol 2019 Jan 9;103:93-99. Epub 2019 Jan 9.

Alltech SARL, Rue Charles Amand, 14500, Vire, France. Electronic address:

The 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. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193001
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http://dx.doi.org/10.1016/j.yrtph.2019.01.014DOI Listing
January 2019
4 Reads

Perfluorohexanoic acid toxicity, part I: Development of a chronic human health toxicity value for use in risk assessment.

Regul Toxicol Pharmacol 2019 Jan 9;103:41-55. Epub 2019 Jan 9.

Integral Consulting Inc., 200 Harry S. Truman Parkway, Suite 330, Annapolis, MD, 21401, USA.

Perfluorohexanoic 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 therefore, PFHxA. Here, we present a critical review of data relevant to such a risk assessment, including epidemiological studies and in vivo and in vitro toxicity studies that examined PFHxA acute, subchronic, and chronic toxicity. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.019DOI Listing
January 2019
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Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops.

Regul Toxicol Pharmacol 2019 Jan 8;103:34-40. Epub 2019 Jan 8.

Naval Medical Research Institute, Second Military Medical University, 880 Xiangyin Road, Shanghai, 200433, China. Electronic address:

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 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 lidocaine hydrochloride)/kg, respectively. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.018DOI Listing
January 2019
2 Reads
2.031 Impact Factor

Science peer review for the 21st century: Assessing scientific consensus for decision-making while managing conflict of interests, reviewer and process bias.

Regul Toxicol Pharmacol 2019 Jan 8;103:73-85. Epub 2019 Jan 8.

SciPinion LLC., Bozeman, MT 59715, USA.

Science peer review plays an important role in the advancement and acceptance of scientific information, particularly when used to support decision-making. A model for science peer review is proposed here using a large, multi-tiered case study to engage a broader segment of the scientific community to support decision making on science matters, and to incorporate many of the design advantages of the two common forms of peer review (journal peer review, science advisory panels). This peer review consisted of a two-tiered structure consisting of seven panels (five review panels in Tier 1, two review panels in Tier 2), which focused on safety data for a modified risk tobacco product (MRTP). Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.003DOI Listing
January 2019
1 Read

Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge.

Regul Toxicol Pharmacol 2019 Jan 8;103:86-92. Epub 2019 Jan 8.

Parker Doe LLP, Carpenter Court, Maple Road, Bramhall, Stockport, Cheshire, SK7 2DH, UK. Electronic address:

Developments 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 and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193002
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http://dx.doi.org/10.1016/j.yrtph.2019.01.021DOI Listing
January 2019
7 Reads

Target animal safety testing of an oral salicylanilide suspension, oxyclozanide, for the treatment of fascioliasis in bovine in China.

Regul Toxicol Pharmacol 2019 Jan 8;103:21-33. Epub 2019 Jan 8.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), China. Electronic address:

The 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 cattle 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 dosage through continuous intermittent oral administration at intervals of 2 days. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.012DOI Listing
January 2019
10 Reads

Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans.

Regul Toxicol Pharmacol 2019 Jan 8;103:100-105. Epub 2019 Jan 8.

Syngenta Crop Protection, LLC, Greensboro, NC, 27419, USA.

Over 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 bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.017DOI Listing
January 2019
6 Reads

Perfluorohexanoic acid toxicity, part II: Application of human health toxicity value for risk characterization.

Regul Toxicol Pharmacol 2019 Jan 8;103:10-20. Epub 2019 Jan 8.

Integral Consulting Inc., 200 Harry S. Truman Parkway, Suite 330, Annapolis, MD, 21401, USA.

Perfluorohexanoic 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 risk assessment to today's short-chain PFAA chemistry. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.020DOI Listing
January 2019
2 Reads

Isopsoralen induces different subchronic toxicities and metabolomic outcomes between male and female Wistar rats.

Regul Toxicol Pharmacol 2019 Jan 8;103:1-9. Epub 2019 Jan 8.

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, 300193, China; Ministry of Education Key Laboratory of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address:

Isopsoralen 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. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193001
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http://dx.doi.org/10.1016/j.yrtph.2019.01.010DOI Listing
January 2019
7 Reads
2.031 Impact Factor

Letter to the editor regarding the article by Roberts, 2018.

Regul Toxicol Pharmacol 2019 Mar 7;102:115-116. Epub 2019 Jan 7.

BASF SE, RB/TB - Z470, D-67056, Ludwigshafen, Germany.

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193000
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http://dx.doi.org/10.1016/j.yrtph.2019.01.005DOI Listing
March 2019
2 Reads
2.031 Impact Factor

The use of Genomic Allergen Rapid Detection (GARD) assays to predict the respiratory and skin sensitising potential of e-liquids.

Regul Toxicol Pharmacol 2019 Jan 7;103:158-165. Epub 2019 Jan 7.

Imperial Brands PLC, 121 Winterstoke Road, Bristol, BS3 2LL, UK.

Electronic cigarettes (e-cigarettes) are an increasingly popular alternative to combustible tobacco cigarettes among smokers worldwide. A growing body of research indicates that flavours play a critical role in attracting and retaining smokers into the e-cigarette category, directly contributing to declining smoking rates and tobacco harm reduction. The responsible selection and inclusion levels of flavourings in e-liquids must be guided by toxicological principles. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.001DOI Listing
January 2019
2 Reads

Short commentary on NDMA (N-nitrosodimethylamine) contamination of valsartan products.

Regul Toxicol Pharmacol 2019 Jan 8. Epub 2019 Jan 8.

David P Elder Consultancy, Hertford, UK. Electronic address:

A range of generic valsartan products have been found to be contaminated with nitrosamines (principally N-nitrosodimethylamine; NDMA). 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.007DOI Listing
January 2019
1 Read

Percutaneous permeability of 1-phenoxy-2-propanol, a preservative in cosmetics.

Regul Toxicol Pharmacol 2019 Jan 3;103:56-62. Epub 2019 Jan 3.

College of Pharmacy, Dankook University, 119 Dandae-ro, Cheonan, Chungnam, 31116, Republic of Korea. Electronic address:

1-Phenoxy-2-propanol (PP) is used as a preservative in cosmetics. PP is currently permitted to be used to up to 1% in cosmetic formulations in Korea and Europe. For risk assessment, percutaneous absorption is a crucial factor, but dermal absorption of PP has not yet been reported. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193000
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http://dx.doi.org/10.1016/j.yrtph.2019.01.002DOI Listing
January 2019
9 Reads

Authors' response to the letter to the editor by Jowsey et al.

Regul Toxicol Pharmacol 2019 Jan 3. Epub 2019 Jan 3.

University of Lausanne, Institute for Work and Health (IST), Route de la Corniche 2, CH-1066, Epalinges-Lausanne, Switzerland. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S02732300193000
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http://dx.doi.org/10.1016/j.yrtph.2019.01.008DOI Listing
January 2019
7 Reads

Pharmacokinetics and four-week repeated-dose toxicity of hyaluronic acid and ketorolac combination following intra-articular administration in normal rats.

Regul Toxicol Pharmacol 2019 Mar 3;102:79-89. Epub 2019 Jan 3.

College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam, 330-714, South Korea. Electronic address:

Intra-articular (IA) injection of hyaluronic acid (HA) in combination with nonsteroidal anti-inflammatory drugs, such as ketorolac (KL), have been clinically investigated to provide more rapid and profound pain relief in patients with osteoarthritis. However, its safety, local tolerance, and potential for pharmacokinetic interaction have not been assessed. In this study, the pharmacokinetics and toxicity of a combination of HA and KL were evaluated in normal rats following four-week repeated-dose injection. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.011DOI Listing
March 2019
7 Reads

Safety evaluation of the oils extracted from edible insects (Tenebrio molitor and Pachymerus nucleorum) as novel food for humans.

Regul Toxicol Pharmacol 2019 Mar 3;102:90-94. Epub 2019 Jan 3.

Faculty of Engineering, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil. Electronic address:

Increased concerns about ensuring food safety motivated the exploration of insects as an alternative protein source. It has been reported that Tenebrio molitor (TM) and Pachymerus nucleorum (PN) larvae are great protein and lipid sources with considerable concentrations of unsaturated fatty acids. Nevertheless, little attention has been given to the safety of using these edible insects. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.013DOI Listing
March 2019
1 Read

The effect of Cynara scolymus (artichoke) on maternal reproductive outcomes and fetal development in rats.

Regul Toxicol Pharmacol 2019 Mar 3;102:74-78. Epub 2019 Jan 3.

Research Centre for Veterinary Toxicology (CEPTOX) - Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 05508-270, SP, Brazil. Electronic address:

Cynara 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2019.01.004DOI Listing
March 2019
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Skin sensitization risk assessment for plant protection products: The applicability of sensitization assessment factors.

Regul Toxicol Pharmacol 2019 Jan 3. Epub 2019 Jan 3.

Syngenta Product Safety, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK.

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http://dx.doi.org/10.1016/j.yrtph.2019.01.009DOI Listing
January 2019
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Biomonitoring Equivalents (BEs) for tetrabromobisphenol A.

Regul Toxicol Pharmacol 2019 Mar 26;102:108-114. Epub 2018 Dec 26.

Summit Toxicology, L.L.P., Bozeman, MT, USA.

Tetrabromobisphenol 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2018.12.014DOI Listing
March 2019
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The reliability of an environmental epidemiology meta-analysis, a case study.

Regul Toxicol Pharmacol 2019 Mar 24;102:47-52. Epub 2018 Dec 24.

Claims 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. Read More

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http://dx.doi.org/10.1016/j.yrtph.2018.12.013DOI Listing
March 2019
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Histopathology re-examination of the NTP toxicity/carcinogenicity studies of tert-butyl alcohol to identify renal tumor and toxicity modes of action.

Regul Toxicol Pharmacol 2019 Mar 24;102:65-73. Epub 2018 Dec 24.

LyondellBasell, Houston, TX, 77010, USA.

Tert-butyl alcohol (TBA) targets the rat kidney following repeated exposures, including renal tubule tumors. The mode of action (MOA) of these tumors, concluded by a pathology working group, involves both alpha2u-globulin nephropathy (α2u-gN) and exacerbated chronic progressive nephropathy (CPN), but has been disputed and an undefined MOA proposed. This study further reviews the histology slides of male and female rat kidneys from the NTP drinking water 13-week toxicity and 2-year carcinogenicity studies, including the 15-month interim sacrifice group. Read More

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http://dx.doi.org/10.1016/j.yrtph.2018.12.011DOI Listing
March 2019
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Reflections on the progress towards non-animal methods for acute toxicity testing of chemicals.

Regul Toxicol Pharmacol 2019 Mar 20;102:30-33. Epub 2018 Dec 20.

National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), Gibbs Building, 215 Euston Road, London, NW1 2BE, UK.

The acute toxicity 'six-pack' is a suite of tests for hazard identification and risk assessment, primarily conducted for the classification and labelling of industrial chemicals and agrochemicals. The 'six-pack' is designed to provide information on health hazards likely to arise from short-term exposure to chemicals via inhalation, oral and dermal routes, including the potential for eye and skin irritation/corrosion and skin sensitization. The component tests of the 'six-pack' currently rely heavily on the use of experimental animals. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300183031
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http://dx.doi.org/10.1016/j.yrtph.2018.12.008DOI Listing
March 2019
13 Reads
2.031 Impact Factor

Pharmaceutical industry perspective on combination toxicity studies: Results from an intra-industry survey conducted by IQ DruSafe Leadership Group.

Regul Toxicol Pharmacol 2019 Mar 19;102:40-46. Epub 2018 Dec 19.

Pfizer Inc., 10646 Science Center Drive, San Diego, CA, 92121, USA.

Interest in developing combination products to overcome drug resistance and treat complex diseases is growing. However, ambiguity remains around the value of combination toxicity studies to support combination products. Therefore, the IQ* DruSafe Leadership Group surveyed member companies to evaluate industry experience with combination toxicity strategies, study designs and their impact on clinical development. Read More

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http://dx.doi.org/10.1016/j.yrtph.2018.12.012DOI Listing
March 2019
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Corrigendum to "Combined effect of benzophenone-2 and ultraviolet radiation promote photogenotoxicity and photocytotoxicity in human keratinocytes". [Regul. Toxicol. Pharmacol. 95 (2018) 298-306].

Regul Toxicol Pharmacol 2019 Feb 18;101:201-202. Epub 2018 Dec 18.

Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Post. Box 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.

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http://dx.doi.org/10.1016/j.yrtph.2018.12.005DOI Listing
February 2019
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Histological analyses of the Ishii (1981) rat carcinogenicity study of aspartame and comparison with the Ramazzini Institute studies.

Regul Toxicol Pharmacol 2019 Mar 18;102:23-29. Epub 2018 Dec 18.

Intertek Scientific & Regulatory Consultancy, 2233 Argentia Road, Suite 201, Mississauga, Ontario, L5N 2X7, Canada.

Researchers from the Ramazzini Institute have reported that lifespan dosing of rats with aspartame treatment is associated with an increased overall incidence of malignant tumors, including leukemias/lymphomas, transitional cell carcinomas of the renal pelvis/ureter, and malignant schwannomas of the peripheral nerves. Other carcinogenicity studies conducted on aspartame have shown no such carcinogenic potential in any organ system. Additional data to assess the carcinogenic potential of aspartame, especially in relation to the publications of the Ramazzini Institute, were obtained from a third-party histological evaluation of tissues from a carcinogenicity study previously conducted to assess the potential for aspartame to induce tumors of the brain. Read More

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http://dx.doi.org/10.1016/j.yrtph.2018.12.010DOI Listing
March 2019
2 Reads