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Transcriptional profiling of male CD-1 mouse lungs and harderian glands supports the involvement of calcium signaling in acrylamide-induced tumors
Publication date: Available online 21 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Nikolai L. Chepelev, Rémi Gagné, Timothy Maynor, Byron Kuo, Cheryl A. Hobbs, Leslie Recio, Carole L. Yauk Acrylamide (AA) exposure causes increased incidence of forestomach, lung, and Harderian gland tumors in male mice. One hypothesized mode of action (MOA) for AA-carcinogenicity includes genotoxicity/mutagenicity as a key event, possibly resulting from AA metabolism to the direct genotoxic metabolite glycidamide. Alternatively, altered calcium signaling (CS) has been proposed as a central key event ...
Source: Regulatory Toxicology and Pharmacology - February 21, 2018 Category: Toxicology Source Type: research

Corrigendum to “Quantitative analysis of menthol and identification of other flavoring ingredients in capsule cigarettes marketed in Korea” [Regul. Toxicol. Pharmacol. 92C (2018) 420–428]
Publication date: Available online 21 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hyung Soo Kim, Eun Chul Pack, Ye Ji Koo, Ye Jin Lee, Dae Kwan Sung, Seung Ha Lee, Young Soon Kim, Kyeng Hee Kwon, Kyung Min Lim, Dae Yong Jang, Dal Woong Choi (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - February 21, 2018 Category: Toxicology Source Type: research

Acute, subchronic oral toxicity, toxicokinetics, and genotoxicity studies of DFC-2, an antitubercular drug candidate
Publication date: Available online 21 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hoonhee Seo, Hafij Al Mahmud, Sukyung Kim, Md Imtiazul Islam, Kee-In Lee, Young Sig Gil, Ho-Yeon Song The infectious disease tuberculosis remains a serious global health issue and is responsible for nearly 1.8 million deaths every year. In our previous study, DFC-2 was confirmed to show anti-tubercular activity against drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis. To support the safety-in-use of DFC-2 as an anti-tubercular drug, DFC-2 was tested via single- and 28-day repeated-dose oral...
Source: Regulatory Toxicology and Pharmacology - February 21, 2018 Category: Toxicology Source Type: research

A kinetic-based safety assessment of consumer exposure to salicylic acid from cosmetic products demonstrates no evidence of a health risk from developmental toxicity
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): R. Labib, D. Bury, F. Boisleve, G. Eichenbaum, S. Girard, J. Naciff, M. Leal, J. Wong Salicylic acid (SA) has a long history of safe use as ingredient in topical cosmetic products. In 2016, the Committee for Risk Assessment of the European Chemicals Agency proposed to classify SA as a Category 2 reproductive toxicant based on adverse developmental effects in animal toxicity studies. This hazard-based classification (based on mg/kg doses) requires a reassessment of the safety of the current SA concentrations in cosmetic consume...
Source: Regulatory Toxicology and Pharmacology - February 21, 2018 Category: Toxicology Source Type: research

Mutagenicity and genotoxicity studies of aspartame
Publication date: Available online 19 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Akira Otabe, Fumio Ohta, Asuka Takumi, Barry Lynch Two studies were conducted to further assess its mutagenic and genotoxic potential. In a bacterial reverse mutation pre-incubation study, Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2 uvrA were treated with aspartame at concentrations of up to 5000 μg/plate with or without metabolic activation and showed no mutagenic potential. Similarly, in vivo micronucleus testing of aspartame following gavage administration (500&ndas...
Source: Regulatory Toxicology and Pharmacology - February 19, 2018 Category: Toxicology Source Type: research

No subchronic toxicity of multiple herbicide-resistant soybean FG72 in Sprague-Dawley rats by 90-days feeding study
Publication date: Available online 17 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Zixin Xie, Shiying Zou, Wentao Xu, Xu Liu, Kunlun Huang, Xiaoyun He The genetically modified (GM) soybean FG72 contains two exogenous genes: p-hydroxyphenylpyruvate dioxygenase (hppd) and double mutant 5-enol pyruvylshikimate-3-phosphate synthase (2mepsps), endowing the FG72 with the glyphosate and isoxaflutole herbicides resistant abilities for presence of the 2mEPSPS and HPPD W336 proteins. A food safety assessment of GM soybean FG72 was evaluated by a 90-days feeding study using three different dietary concentra...
Source: Regulatory Toxicology and Pharmacology - February 18, 2018 Category: Toxicology Source Type: research

Letter to the editor: "Evaulation of radioisotopic and non-radioisotopic versions of local lymph node assays for subcategorization of skin sensitiers compliant to UN GHS rev 4" by Ha et al., 2017
Publication date: Available online 2 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Susanne Noreen Kolle, Robert Landsiedel (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - February 16, 2018 Category: Toxicology Source Type: research

Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition
Publication date: Available online 15 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Julia Schnorr, Sören Fütterer, Karsten Spicher, Maria Catarinolo, Christoph Schlösser, Harald Enzmann, Peter Langguth Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its’ second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and...
Source: Regulatory Toxicology and Pharmacology - February 16, 2018 Category: Toxicology Source Type: research

Comparative study on some oxidative stress parameters in blood of vitiligo patients before and after combined therapy
Publication date: Available online 14 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): A. Zheleva, G. Nikolova, Y. Karamalakova, E. Hristakieva, R. Lavcheva, V. Gadjeva Currently accepted that oxidative stress is a triggering event in the melanocytic destruction and is probably involved in the etiopathogenesis of vitiligo disease. Despite numerous investigations, contradictory results were reported about the levels of oxidative stress biomarkers measured in the skin and blood of vitiligo patients. By Electron Paramagnetic Resonance spectroscopy (EPR) and spectrophotometry, we have investigated and co...
Source: Regulatory Toxicology and Pharmacology - February 15, 2018 Category: Toxicology Source Type: research

Immunologic effects of chronic administration of tofacitinib, a Janus kinase inhibitor, in cynomolgus monkeys and rats – Comparison of juvenile and adult responses
Publication date: Available online 15 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Mark Collinge, Douglas J. Ball, Christopher J. Bowman, Andrea L. Nilson, Zaher A. Radi, W. Mark Vogel Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3 inhibition impairs gamma common chain cytokine receptor signaling, important in lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus monkey and rat studies were conducted and the impact of tofacitinib on immune parameters (lymphoid tissu...
Source: Regulatory Toxicology and Pharmacology - February 15, 2018 Category: Toxicology Source Type: research

Corrigendum to "Implementing the D4F in a robust model, allowing for enhanced comparison, prioritisation and grouping of NMs" [Regul. Toxicol. Pharmacol. 92 (2018) 207 –212]
Publication date: Available online 13 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): J.J. Scott-Fordsmand, M.J.B. Amorim, P.B. Sørensen (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - February 14, 2018 Category: Toxicology Source Type: research

Impact of exposure factor selection on deterministic consumer exposure assessment
Publication date: Available online 12 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hyunkyung Ban, Ji Young Park, Daeyeop Lee, Kiyoung Lee Deterministic exposure assessment has uncertainty about the selection of input parameters on the resulting estimates. The purpose of this study was to compare inhalation exposures estimated by a specific percentile of each of the three exposure factors in deterministic assessment with population exposure. Exposure to nine household care products, namely a deodorizer, six cleaning products, and two disinfectants were investigated. The population exposures were i...
Source: Regulatory Toxicology and Pharmacology - February 13, 2018 Category: Toxicology Source Type: research

Developmental immunotoxicity is not associated with the consumption of transgenic Bt rice TT51 in rats
In this study, rats from F0, F1, and F2 generations were fed a diet with 60% TT51 rice, MingHui rice, or nominal-origin rice. The study focused on developmental immunotoxicity in F1 and F2 offspring after long-term consumption of TT51. A wide range of immunological parameters was monitored in this two-generation study on reproductive toxicity. The experiments were performed on F1 and F2 offspring at postnatal days 21 and 42. No adverse clinical effects were observed in any of the experimental groups. In addition, histopathology observations and immunotoxicity tests, including hematological indicators, spleen lymphocyte sub...
Source: Regulatory Toxicology and Pharmacology - February 13, 2018 Category: Toxicology Source Type: research

Insulation fiber deposition in the airways of men and rats. A review of experimental and computational studies
Publication date: Available online 11 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): G.D. Nielsen, I.K Koponen The typical insulation rock, slag and glass wool fibers are high volume materials. Current exposure levels in industry (generally ≤ 1 fiber/cm3 with a median diameter ∼1 μm and length ≥10 μm) are not considered carcinogenic or causing other types of severe lung effects. However, epidemiological studies are not informative on effects in humans at fiber levels >1 fiber/cm3. Effects may be inferred from valid rat studies, conducted with rat respirable fibers (di...
Source: Regulatory Toxicology and Pharmacology - February 12, 2018 Category: Toxicology Source Type: research

Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: A literature review
Publication date: Available online 9 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Gerhard Scherer The health risk of tobacco smoking can best be avoided or reduced by not taking up or quitting the habit. The use of new and innovative tobacco (NTPs, e.g. electronic cigarettes) can either be an aid for smoking cessation or, for those who are not able or willing to quit, an alternative for smoking conventional tobacco products. Before the use of an NTP can be regarded as an effective approach in tobacco harm reduction (THR), the implicated risk has to be evaluated by suitable toxicological methods s...
Source: Regulatory Toxicology and Pharmacology - February 10, 2018 Category: Toxicology Source Type: research

Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Judy Strickland, Amy J. Clippinger, Jeffrey Brown, David Allen, Abigail Jacobs, Joanna Matheson, Anna Lowit, Emily N. Reinke, Mark S. Johnson, Michael J. Quinn, David Mattie, Suzanne C. Fitzpatrick, Surender Ahir, Nicole Kleinstreuer, Warren Casey Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the r...
Source: Regulatory Toxicology and Pharmacology - February 10, 2018 Category: Toxicology Source Type: research

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): J.P. Bercu, S.M. Galloway, P. Parris, A. Teasdale, M. Masuda-Herrera, K. Dobo, P. Heard, M. Kenyon, J. Nicolette, E. Vock, W. Ku, J. Harvey, A. White, S. Glowienke, E.A. Martin, L. Custer, R.A. Jolly, V. Thybaud This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previousl...
Source: Regulatory Toxicology and Pharmacology - February 10, 2018 Category: Toxicology Source Type: research

Assessment of tobacco heating product THP1.0. Part 5: In  vitro dosimetric and cytotoxic assessment
In this study, we have assessed aerosol generation and cytotoxicity from two commercially available THPs, THP1.0 and THS, relative to tobacco smoke from 3R4F reference cigarettes, using an adapted Borgwaldt RM20S Smoking Machine. Quantification of nicotine in the exposed cell-culture media showed greater delivery of nicotine from both THPs than from the cigarette. Using Neutral Red Uptake assay, THPs demonstrated reduced in vitro cytotoxicity in H292 human bronchial epithelial cells as compared with 3R4F cigarette exposure at the air–liquid interface (p < 0.0001). Both THPs demonstrated a statis...
Source: Regulatory Toxicology and Pharmacology - February 8, 2018 Category: Toxicology Source Type: research

Assessment of tobacco heating product THP1.0. Part 4: Characterisation of indoor air quality and odour
Publication date: March 2018 Source:Regulatory Toxicology and Pharmacology, Volume 93 Author(s): Mark Forster, John McAughey, Krishna Prasad, Eleni Mavropoulou, Christopher Proctor The tobacco heating product THP1.0, which heats but does not burn tobacco, was tested as part of a modified-risk tobacco product assessment framework for its impacts on indoor air quality and residual tobacco smoke odour. THP1.0 heats the tobacco to less than 240 °C ± 5 °C during puffs. An environmentally controlled room was used to simulate ventilation conditions corresponding to residential, office and hospitality env...
Source: Regulatory Toxicology and Pharmacology - February 8, 2018 Category: Toxicology Source Type: research

Assessment of tobacco heating product THP1.0. Part 1: Series introduction
Publication date: March 2018 Source:Regulatory Toxicology and Pharmacology, Volume 93 Author(s): Christopher Proctor We have recently developed a Tobacco Heating Product (THP) comprising an electrical heating device, commercially known as Glo™, and consumable tobacco rods, commercially known as Kent Neostiks™. We refer to this system as THP1.0; Bright tobacco-flavoured variant THP1.0(T), or THP1.0(M) Menthol-flavoured variant. In this issue, we present a series of seven pre-clinical studies conducted on THP1.0,covering the following aspects of its design, development, safety and toxicological assessment, and a...
Source: Regulatory Toxicology and Pharmacology - February 8, 2018 Category: Toxicology Source Type: research

Mixture risk assessment of selected mainstream cigarette smoke constituents generated from low-yield cigarettes in South Korean smokers
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Eun Chul Pack, Dae Yong Jang, Hyung Soo Kim, Seung Ha Lee, Hae Young Kim, Seok Ho Song, Hoon Sik Cho, Kyeng Hee Kwon, Kun Ho Park, Kyung Min Lim, Dal Woong Choi A total of 38 hazardous constituents in mainstream cigarette smoke of low-yield cigarettes sold in Korea were selected and analyzed using established methods. Risk calculations were performed using risk algorithms employed in previous studies and Korean population-based exposure parameters. The median cumulative incremental lifetime cancer risk of male smokers could va...
Source: Regulatory Toxicology and Pharmacology - February 7, 2018 Category: Toxicology Source Type: research

Assessing the safety of an Ephedrae Herba aqueous extract in rats: A repeat dose toxicity study
In this study, we evaluated the subchronic toxicity of an Ephedrae Herba aqueous extract (EHAE) in male and female F344 rats. The EHAE was administered orally daily at doses of 0, 125, 250, 500, and 1000 mg/kg bw/day for 13 weeks. Toxicological assessment was performed to determine mortality, clinical signs, and changes in body weight, food consumption, ophthalmological, urinary, hematological, and serum biochemical parameters, macroscopic and microscopic evaluations, and organ weights. We found that oral administration of EHAE to F344 rats for 13 weeks resulted in histopathological changes in the kidneys and salivary ...
Source: Regulatory Toxicology and Pharmacology - February 6, 2018 Category: Toxicology Source Type: research

A comparison of fish pesticide metabolic pathways with those of the rat and goat
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Richard C. Kolanczyk, Jose A. Serrano, Mark A. Tapper, Patricia K. Schmieder Ecological risk assessments are often limited in their ability to consider metabolic transformations for fish species due to a lack of data. When these types of evaluations are attempted they are often based on parent chemical only, or by assuming similarity to available mammalian metabolic pathways. The metabolism maps for five pesticides (fluazinam, halauxifen-methyl, kresoxim-methyl, mandestrobin, and tolclofos-methyl) were compared across three sp...
Source: Regulatory Toxicology and Pharmacology - February 6, 2018 Category: Toxicology Source Type: research

Repeated dose 28-day oral toxicity study of a botanical composition composed of Morus alba and Acacia catechu in rats
In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP1306 was considered to be the highest dose tested, 2000 mg/kg/day, both for male and female rats. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - February 6, 2018 Category: Toxicology Source Type: research

Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury
We examined the effect of gender, age, and drug properties on liver events reporting frequency (RF) to assess patient- and drug-related risks for drug-induced liver injury (DILI). We performed a data-mining analysis of the WHO VigiBase™ to 1) identify drugs with gender- and age-biased RF and 2) characterize drug properties using the Liver Toxicity Knowledge Base. Age-, gender-specific Empirical Bayes Geometric Mean of relative reporting ratio of liver events with 90% confidence interval (CI) was calculated for 375 drugs with DILI potential. Forty-one drugs showed an increased RF in women, which had a higher prevalenc...
Source: Regulatory Toxicology and Pharmacology - February 6, 2018 Category: Toxicology Source Type: research

Status of acute toxicity testing requirements and data uses by U.S. regulatory agencies
Publication date: Available online 3 February 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Judy Strickland, Amy J. Clippinger, Jeffrey Brown, David Allen, Abigail Jacobs, Joanna Matheson, Anna Lowit, Emily N. Reinke, Mark S. Johnson, Michael J. Quinn, David Mattie, Suzanne C. Fitzpatrick, Surender Ahir, Nicole Kleinstreuer, Warren Casey Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these ...
Source: Regulatory Toxicology and Pharmacology - February 4, 2018 Category: Toxicology Source Type: research

Food and feed safety of DAS-444 Ø6-6 herbicide-tolerant soybean
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Rod A. Herman, Ricardo D. Ekmay, Barry W. Schafer, Ping Song, Brandon J. Fast, Sabitha Papineni, Guomin Shan, Daland R. Juberg DAS-444Ø6-6 soybean was genetically engineered (GE) to withstand applications of three different herbicides. Tolerance to glufosinate and glyphosate is achieved through expression of the phosphinothricin acetyltransferase (PAT) and double-mutated maize 5-enolpyruvyl shikimate-3-phosphate synthase (2mEPSPS) enzymes, respectively. These proteins are expressed in currently commercialized crops and ...
Source: Regulatory Toxicology and Pharmacology - January 29, 2018 Category: Toxicology Source Type: research

Biotherapeutics in non-clinical development: Strengthening the interface between safety, pharmacokinetics-pharmacodynamics and manufacturing
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Peter Ulrich, Guenter Blaich, Andreas Baumann, Rajni Fagg, Adam Hey, Andrea Kiessling, Sven Kronenberg, Rikke Hvid Lindecrona, Silke Mohl, Wolfgang F. Richter, Jay Tibbitts, Flavio Crameri, Lucinda Weir Biological drugs comprise a wide field of different modalities with respect to structure, pharmacokinetics and pharmacological function. Considerable non-clinical experience in the development of proteins (e.g. insulin) and antibodies has been accumulated over the past thirty years. In order to improve the efficacy and the safe...
Source: Regulatory Toxicology and Pharmacology - January 29, 2018 Category: Toxicology Source Type: research

Toxicological evaluation of 3 ′-sialyllactose sodium salt
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Daehee Kim, Rit Bahadur Gurung, Wonmin Seo, Albert W. Lee, Jinsuk Woo The safety of 3′-sialyllactose (3′-SL) sodium salt was evaluated by testing for gene mutations, in vivo and in vitro clastogenic activity, and animal toxicity in beagle dogs and rats. The results of all mutagenicity and genotoxicity tests were negative, indicating that 3′-SL does not have any mutagenic or clastogenic potential. The mean lethal dose (LD50) of 3′-SL sodium salt was well above 20 g/kg body weight (bw) in rats. A dose e...
Source: Regulatory Toxicology and Pharmacology - January 29, 2018 Category: Toxicology Source Type: research

Toxicity assessment of the extractables from multi-layer coextrusion poly ethylene bags exposed to pH=5 solution containing 4% benzyl alcohol and 0.1  M sodium acetate
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Jingcong Zhuang, Xuebin Xing, Di Wang, Zhenxia Du, Jianfeng Wang, Yan Dong, Wenlian Yu, Sajid Hussain Siyal A non-target analysis was developed for the analysis of extractables from multi-layer coextrusion bags exposed to 4% benzyl alcohol solution and 0.1 M sodium acetate at pH = 5 for defined periods (15 day, 45 day and 90 day) according to manufacturer instructions based on the ultra-performance liquid chromatography (UPLC) quadrupole-time of flight mass spectrometry (Q-TOF MS). In order to confirm the extractables, p...
Source: Regulatory Toxicology and Pharmacology - January 29, 2018 Category: Toxicology Source Type: research

Biomonitoring Equivalents for interpretation of urinary iodine
Publication date: April 2018 Source:Regulatory Toxicology and Pharmacology, Volume 94 Author(s): Sean M. Hays, Devika Poddalgoda, Kristin Macey, Lesa Aylward, Andy Nong Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Dise...
Source: Regulatory Toxicology and Pharmacology - January 29, 2018 Category: Toxicology Source Type: research

Antinociception of the spirocyclopiperazinium salt compound LXM-15 via activating α7 nAChR and M4 mAChR and inhibiting CaMKIIα/cAMP/CREB/CGRP signalling pathway in mice
This study first reported that intragastric administration of LXM-15 produced significant analgesic effect, which may be related to the activation of α7 nicotinic acetylcholine receptor and M4 muscarine acetylcholine receptor, and thereby inhibiting CaMKIIα/cAMP/CREB/CGRP signalling pathway. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 17, 2018 Category: Toxicology Source Type: research

Combining machine learning models of in vitro and in vivo bioassays improves rat carcinogenicity prediction
This study demonstrates the novelty of a combined approach for IVRC prediction, with higher performance than existing software. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 15, 2018 Category: Toxicology Source Type: research

The classification of azodicarbonamide (ADCA) as a respiratory sensitiser; adding to the weight of evidence
Publication date: Available online 11 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hille Suojalehto, Jean-Luc Malo, Paul Cullinan (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 15, 2018 Category: Toxicology Source Type: research

Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria
Publication date: Available online 12 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Lois Haighton, Ashley Roberts, Brandon Walters, Barry Lynch The current review assessed cancer studies of aspartame based on a quality appraisal using the Klimisch grading system. Nine studies having complete histopathology were included: three 2-year studies by Searle; three transgenic mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A tenth study limited to brain tumors was not rated. None were determined as Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP...
Source: Regulatory Toxicology and Pharmacology - January 15, 2018 Category: Toxicology Source Type: research

Absence of toxicity in Swiss mice following treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin: Acute and repeated-dose toxicity study
Publication date: Available online 13 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Gláucio Barros Saldanha, Glaucia Barros Saldanha, Marina Rebeca Soares Carneiro de Sousa, George Laylson da Silva Oliveira, Ana Paula dos Santos C.L. da Silva, Jorge M. David, Juceni Pereira David Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4-arylcoumarin and neoflavene, have been the subject of a number of studies with respect to their therapeutic potential and, despite promising in vitro, ex vivo and in vivo pharmacological activities, there is a lack of studies demonstra...
Source: Regulatory Toxicology and Pharmacology - January 15, 2018 Category: Toxicology Source Type: research

Analysis of refuse-to-file policy for generic drug application in Taiwan
Publication date: Available online 9 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): I-Chen Sun, Churn-Shiouh Gau Generic drugs are accounted for majority of medicinal products. To reduce the unnecessary review for incomplete dossiers of generic drugs, Taiwanese government launched a refuse-to-file (RTF) procedure since 2017. The present study aimed to examine the outcome of RTF procedure by analyzing application characteristic, RTF rate and deficiencies found in the submitted dossiers. Descriptions of administrative information, chemistry, manufacturing and controls, bioequivalence study, and compar...
Source: Regulatory Toxicology and Pharmacology - January 10, 2018 Category: Toxicology Source Type: research

Evaluation of 30% DAS-444 Ø6-6 soybean meal in a subchronic rat toxicity study
Publication date: Available online 6 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Sabitha Papineni, Julie K. Passage, Ricardo D. Ekmay, Johnson Thomas Event DAS-444Ø6-6 soybean is genetically modified (GM) to provide tolerance to 2,4-diclorophenoxyacetic acid (2,4-D), glyphosate, and glufosinate herbicides through expression of the AAD-12, 2mEPSPS, and PAT proteins, respectively. DAS-444Ø6-6 soybeans were evaluated for safety in subchronic rat feeding studies. The results from two previous subchronic rat feeding studies evaluating diets formulated with 20% inclusion of DAS-444Ø...
Source: Regulatory Toxicology and Pharmacology - January 7, 2018 Category: Toxicology Source Type: research

An evaluation of the fixed concentration procedure for assessment of acute inhalation toxicity
Publication date: Available online 6 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Fiona Sewell, Ian Ragan, Ian Indans, Tim Marczylo, Nigel Stallard, David Griffiths, Thomas Holmes, Paul Smith, Graham Horgan Acute inhalation studies are conducted in animals as part of chemical hazard identification and for classification and labelling. Current methods employ death as an endpoint (OECD TG403 and TG436) while the recently approved fixed concentration procedure (FCP) (OECD TG433) uses fewer animals and replaces lethality as an endpoint with evident toxicity. Evident toxicity is the presence of clinica...
Source: Regulatory Toxicology and Pharmacology - January 6, 2018 Category: Toxicology Source Type: research

Quantitative analysis of menthol and identification of other flavoring ingredients in capsule cigarettes marketed in Korea
Publication date: Available online 6 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Hyung Soo Kim, Eun Chul Pack, Ye Ji Koo, Ye Jin Lee, Dae Kwan Sung, Seung Ha Lee, Young Soon Kim, Kyeng Hee Kwon, Kyung Min Lim, Dae Yong Jang, Dal Woong Choi Currently, capsule cigarettes have been introduced by tobacco industries and their sales have increased exponentially. However, the capsule flavoring ingredients and their safety are still unknown. Although the contents of menthol and other ingredients directly added to cigarettes have been determined extensively, no analogous study exists for menthol-containin...
Source: Regulatory Toxicology and Pharmacology - January 6, 2018 Category: Toxicology Source Type: research

Determination of developmental toxicity of zebrafish exposed to propyl gallate dosed lower than ADI (acceptable daily intake)
Publication date: Available online 3 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Alper Baran, Mine Köktürk, Muhammed Atamanalp, Saltuk Buğrahan Ceyhun Propyl gallate (PG) is an antioxidant substance widely used in cosmetics, pharmaceutical and food industries. The aim of this study was to evaluate the potential toxic effect of PG injected to zebrafish embryos. To this end, zebrafish embryos were exposed to PG with 0, 1, 10 and 50 ppm concentrations which are lower than ADI and were monitored at 24, 48, 72 and 96 hpf. Survival rate, hatching rate and malformations were evaluated durin...
Source: Regulatory Toxicology and Pharmacology - January 4, 2018 Category: Toxicology Source Type: research

Structure activity relationship (SAR) toxicological assessments: The role of expert judgment
This report outlines and defines analog rating rules for several compound categories. While not comprehensive, the exercises demonstrate the development of rules for categories with a large spread in molecular weight and alkyl chain length and explains the advantages that we see in this approach compared to relying solely on a computational approach or an unstructured expert judgement approach. These rules may be incorporated into analog searching work flows to define boundaries for analogs “suitable” for read-across. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - January 4, 2018 Category: Toxicology Source Type: research

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?
Publication date: Available online 4 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Andrew Van Cott, Charles E. Hastings, Robert Landsiedel, Susanne Kolle, Stefan Stinchcombe In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formula...
Source: Regulatory Toxicology and Pharmacology - January 4, 2018 Category: Toxicology Source Type: research

Primary study on the toxic mechanism of vanadyl trehalose in Kunming mice
Publication date: Available online 4 January 2018 Source:Regulatory Toxicology and Pharmacology Author(s): Pingzhe Jiang, Qiqi Liu, Zaizhong Ni, Qian Wei, Xiaodan Li, Shuguang Xing, Deling Kong, Minggang Li It has been shown that vanadyl trehalose could lower blood glucose but show mild toxicity to the stomach and intestine in diabetic Kunming mice. We analysed antioxidant levels, pro-inflammatory cytokine expression, apoptosis factors and intestinal microflora alteration to explore the mechanism of vanadyl trehalose toxicity in Kunming mice. The results revealed that oral administration of vanadyl trehalose at tested dos...
Source: Regulatory Toxicology and Pharmacology - January 4, 2018 Category: Toxicology Source Type: research

A reappraisal on metformin
Publication date: Available online 30 December 2017 Source:Regulatory Toxicology and Pharmacology Author(s): Tuğba Adak, Afshin Samadi, Ayşe Zeynep Ünal, Suna Sabuncuoğlu This review investigates the different biological effect of Metformin (MET) in different conditions. MET is an oral antidiabetic drug used for the treatment of type 2 diabetes mellitus (T2DM) particularly in overweight people. The main mechanism of action of the MET is inhibition of hepatic glucose production and reduction of insulin resistance. In addition to its antidiabetic effects, MET is also found to be related with the risk for development...
Source: Regulatory Toxicology and Pharmacology - December 30, 2017 Category: Toxicology Source Type: research

Treatment of β-thujaplicin counteracts di(2-ethylhexyl)phthalate (DEHP)-exposed vascular smooth muscle activation, inflammation and atherosclerosis progression
Publication date: Available online 27 December 2017 Source:Regulatory Toxicology and Pharmacology Author(s): Mei Fen Shih, Kuang-Hung Pan, Chia-Chyuan Liu, Chia-Rui Shen, Jong Yuh Cherng The initiation of atherosclerosis involves up-regulation of molecules such as E-selectin, VCAM-1, and ICAM-1. The progression of atherosclerosis is linked to proliferation and migration of vascular smooth muscle cell via MMP-2 and MMP-9 activities. However, the etiology of atherosclerosis concerning plasticizers is unknown. We evaluated β-thujaplicin in preventing the development of atherosclerosis in a model induced by pro-inflammat...
Source: Regulatory Toxicology and Pharmacology - December 28, 2017 Category: Toxicology Source Type: research

Safety assessment of methanolic extract of Terminalia chebula fruit, Terminalia arjuna bark and its bioactive constituent 7-methyl gallic acid: In vitro and in vivo studies
Publication date: Available online 28 December 2017 Source:Regulatory Toxicology and Pharmacology Author(s): N. Suganthy, S. Muniasamy, G. Archunan Terminalia chebula and Terminalia arjuna were widely used in traditional medicine for the treatment of memory impairment, inflammatory disorders and as an anti-aging agent. However, reports regarding their safety aspects are lacking. Hence, the present study was carried out to investigate the toxicity of methanolic extracts of Terminalia chebula fruit (TCF), Terminalia arjuna bark (TAB) and its bioactive constituent 7- Methyl gallic acid (7MG) under in vitro and in vivo condit...
Source: Regulatory Toxicology and Pharmacology - December 28, 2017 Category: Toxicology Source Type: research

Acute and sub-chronic toxicological studies of the iridoid glycosides extract of Lamiophlomis rotata (Benth.) Kudo in rats
This study was aimed to evaluate the safety of IGLR using acute and sub-chronic toxicity study methods on Sprague-Dawley rats. In acute toxicity test, IGLR caused slight diarrhea in three dose groups and a decreased of RBC and increased of MCH and Ret (P < .05) were observed in 16 g/kg group. In sub-chronic toxicity study, unscheduled deaths occurred in 1 and 3 rats at 0.40 and 1.00 g/kg groups, respectively. A slight diarrhea was observed in 1.00 g/kg group. Hemolytic anemia was the main toxicity effects of IGLR found in 0.40 and 1.00 g/kg groups, with a significant decrease of RBC, HGB (P < ...
Source: Regulatory Toxicology and Pharmacology - December 27, 2017 Category: Toxicology Source Type: research

Applicability of surface sampling and calculation of surface limits for pharmaceutical drug substances for occupational health purposes
Publication date: Available online 27 December 2017 Source:Regulatory Toxicology and Pharmacology Author(s): Camille Jandard, Helena Hemming, Maarten Prause, Claudia Sehner, Markus Schwind, Marc Abromovitz, Ester Lovsin Barle Within the context of Occupational Hygiene (OH), surface sampling has been employed as a method to assess surface levels of Active Pharmaceutical Ingredients (APIs). There are potentially a number of reasons surface samples are collected including assessing potential health risks, housekeeping and cleaning effectiveness. There are no internationally accepted standards relating to collecting or interp...
Source: Regulatory Toxicology and Pharmacology - December 27, 2017 Category: Toxicology Source Type: research

Subchronic toxicity and genotoxicity studies of Antrodia mushroom β-glucan preparation
The objective of the present study was to investigate adverse effects, if any, of β-glucan (∼65% pure) from A. cinnamomea in subchronic toxicity and mutagenicity studies. In the subchronic toxicity study, Sprague Dawley rats (12/sex/group) were followed Organization for Economic Cooperation and Development (OECD) test guideline with Good Laboratory Practice (GLP) application, and were administered (gavage) Antrodia mushroom β-glucan preparation at dose levels of 0, 500, 1000 and 2000 mg/kg body weight (bw)/day for 90 days. Treatment with β-glucan preparation did not result in any toxicologically signif...
Source: Regulatory Toxicology and Pharmacology - December 27, 2017 Category: Toxicology Source Type: research