Investigation of quality review issues and the association with application characteristics for new drug applications in first-cycle reviews
Publication date: Available online 22 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Jhih-Siang Liou, Lin-Chau ChangAbstractQuality, essential in the drug development and approval process, was demonstrated to be a major reason leading to multiple reviews for New Drug Applications (NDAs) submitted to the United States Food and Drug Administration (USFDA). The present study aimed at systematically investigating quality deficiencies described in the first-cycle NDA reviews of the approved drug products to identify the types of concerns and the association between the occurrence of quality deficiencies and...
Source: Regulatory Toxicology and Pharmacology - August 23, 2019 Category: Toxicology Source Type: research

Acute and sub-acute oral toxicity studies of standardized extract of Nasturtium officinale in Wistar rats
Publication date: Available online 19 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): M. Clemente, M.D. Miguel, K.B. Felipe, C. Gribner, P.F. Moura, A.G.R. Rigoni, L.C. Fernandes, J.L.S. Carvalho, I. Hartmann, M.T. Piltz, R. Henneberg, D.P. Montrucchio, O.G. MiguelAbstractNasturtium officinale (watercress) is a perennial dicotyledonous plant, rich in vitamins, minerals and chemical compounds. The leaves of this plant, which contain glucosinolate, are used for its diuretic and hypoglycemic effects. The purpose of the study was to investigate the safety of the standardized extract of Nasturtium officinale...
Source: Regulatory Toxicology and Pharmacology - August 20, 2019 Category: Toxicology Source Type: research

Classification or non-classification of substances with positive tumor findings in animal studies: A guidance by the German MAK commission
Publication date: Available online 18 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Britta Laube, Sandra Michaelsen, Veronika Meischner, Andrea Hartwig, Bernd Epe, Michael SchwarzAbstractOne of the important tasks of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (known as the MAK Commission) is in the evaluation of a potential for carcinogenicity of hazardous substances at the workplace. Often, this evaluation is critically based on data on carcinogenic responses seen in animal studies and, if positive tumor responses have been observed, th...
Source: Regulatory Toxicology and Pharmacology - August 19, 2019 Category: Toxicology Source Type: research

The 21st Century movement within the area of skin sensitization assessment: From the animal context towards current human-relevant in vitro solutions
Publication date: Available online 17 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Renato Ivan de Ávila, Malin Lindstedt, Marize Campos ValadaresAbstractIn a regulatory context, skin sensitization hazard and risk evaluations of manufactured products and their ingredients (e.g. cosmetics) are mandatory in several regions. Great efforts have been made within the field of 21st Century Toxicology to provide non-animal testing approaches to assess the skin allergy potential of materials (e.g. chemicals, mixtures, nanomaterials, particles). Mechanistic understanding of skin sensitization process thr...
Source: Regulatory Toxicology and Pharmacology - August 19, 2019 Category: Toxicology Source Type: research

Dissipation rates and residue levels of diflubenzuron and difenoconazole on peaches and dietary risk assessment
Publication date: Available online 17 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Maofeng Dong, Lin Ma, Xiuping Zhan, Jianbo Chen, Lanqi Huang, Weimin Wang, Li ZhaoAbstractThe dissipation kinetics, residue levels, and potential risks of diflubenzuron and difenoconazole on peaches were investigated under open field conditions. Two years of field trials were carried out in Shanghai, China, and the half-lives of diflubenzuron and difenoconazole on peaches ranged from 4.4 to 25d. Their terminal residue concentrations on peaches were 0.022–5.7 mg/kg after three of the tested sampling intervals. B...
Source: Regulatory Toxicology and Pharmacology - August 19, 2019 Category: Toxicology Source Type: research

Data derived Extrapolation Factors for developmental toxicity: A preliminary research case study with perfluorooctanoate (PFOA)
Publication date: Available online 16 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Michael L. Dourson, Bernard Gadagbui, Chijioke Onyema, Patricia M. McGinnis, Raymond G. YorkAbstractGuidelines of the United States Environmental Protection Agency (EPA, 1991) and the International Programme on Chemical Safety (IPCS, 2005) suggest two different default positions for dosimetric extrapolation from experimental animals to humans when the dosimetry of the critical effect is not known. The default position of EPA (1991) for developmental toxicity is to use peak concentration (or Cmax) for this dosimetric ex...
Source: Regulatory Toxicology and Pharmacology - August 17, 2019 Category: Toxicology Source Type: research

Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development
Publication date: Available online 16 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Paul Baldrick, James W. Hutchings, Matthew D. Heath, Murray A. SkinnerAbstractPQ Birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. It consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to L-tyrosine in its microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). A nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity...
Source: Regulatory Toxicology and Pharmacology - August 17, 2019 Category: Toxicology Source Type: research

Metabolomics as read-across tool: An example with 3-aminopropanol and 2-aminoethanol
Publication date: Available online 14 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): S. Sperber, M. Wahl, F. Berger, H. Kamp, O. Lemke, V. Starck, T. Walk, M. Spitzer, B.v RavenzwaayAbstractRead-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their ‘Read-Across Assessment Framework’ (Raaf, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants f...
Source: Regulatory Toxicology and Pharmacology - August 16, 2019 Category: Toxicology Source Type: research

Opinion of the Scientific Committee on Consumer safety (SCCS) – Opinion on the safety of cosmetic ingredient salicylic acid (CAS 69-72-7)
Publication date: Available online 8 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): SCCS, Ulrike Bernauer, Laurent Bodin, Qasim Chaudhry, Pieter Coenraads, Maria Dusinska, Janine Ezendam, Eric Gaffet, Corrado Lodovico Galli, Berit Brunstad Granum, Eirini Panteri, Vera Rogiers, Christophe Rousselle, Maciej Stepnik, Tamara Vanhaecke, Susan Wijnhoven, A. Koutsodimou, A. Simonnard, W. Uter, Eirini Panteri (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - August 10, 2019 Category: Toxicology Source Type: research

Letter to the editor regarding the article “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 5 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Andy Forreryd, Henrik Johansson, Tim Lindberg, Kathrin Zeller, Malin Lindstedt (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - August 7, 2019 Category: Toxicology Source Type: research

Reproductive and developmental toxicity screening of polyhexamethylene guanidine phosphate by oral gavage in rats
Publication date: Available online 6 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Jinsoo Lee, Ji-Seong Jeong, Sang Yun Kim, Wan-Jung Im, Young-Jun Shin, Kyuhong Lee, Seong-Jin Choi, Yongju Heo, Eun Ju Jeong, Sang-Yoon Nam, Wook-Joon YuAbstractPolyhexamethylene guanidine phosphate (PHMG-P) has effective antimicrobial activity against various microorganisms and has been widely used as a biocide in commercial products. However, its use as a humidifier disinfectant has provoked fatal idiopathic lung disease in South Korea, especially in pregnant or postpartum women and their young children. PHMG-P-relate...
Source: Regulatory Toxicology and Pharmacology - August 7, 2019 Category: Toxicology Source Type: research

Scientific assessments in European food law: Making it future-proof
Publication date: Available online 3 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Alie de BoerAbstractEuropean food laws increasingly use scientific evidence to protect consumers from hazards and to prevent the use of misleading information. In this article, the use of risk assessment in European food law is analysed and the implications of the recently adopted adjustments to the EU's General Food Law are reviewed. The risk analysis cycle that has been implemented in many authorisation decisions of the European Commission has resulted in the increased level of public health protection since 2002. The...
Source: Regulatory Toxicology and Pharmacology - August 4, 2019 Category: Toxicology Source Type: research

Comparative pharmacokinetic and biodistribution study of two distinct squalene-containing oil-in-water emulsion adjuvants in H5N1 influenza vaccines
ConclusionsThis study demonstrates a rapid decline of AS03 from the quadriceps muscles of mice as compared to conventional SQ/W emulsion adjuvant, with an increased transfer to mechanistically relevant tissues such as local lymph nodes. Systemic tissue exposure to potential toxicological target tissues was very low. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - August 3, 2019 Category: Toxicology Source Type: research

Elemental impurities in pharmaceutical products adding fuel to the fire
Publication date: Available online 31 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): M. Maithani, R. Raturi, P. Sharma, V. Gupta, P. BansalAbstractThe pharmaceuticals may generate impurities at various stages of development, transportation and storage which make them risky to be administered. Thus, it is essential that these impurities must be detected and quantified. However, their presence as impurities in finished products is virtually unavoidable, even under GMP conditions. Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentra...
Source: Regulatory Toxicology and Pharmacology - August 1, 2019 Category: Toxicology Source Type: research

Towards quantitative read across: Prediction of Ames mutagenicity in a large database
Publication date: Available online 30 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Romualdo BenigniAbstractIn silico chemical safety assessment can support the evaluation of hazard and risk following potential exposure to a substance, thus stimulating an increased interest for the use of Structure-Activity based approaches by regulatory authorities, particularly QSAR and Read Across. Whereas the longer history of QSAR led to recognize the crucial requirements for predictivity, there are still challenges faced by adopting Read Across to a larger extent in a regulatory setting, namely standardization and...
Source: Regulatory Toxicology and Pharmacology - July 31, 2019 Category: Toxicology Source Type: research

Nonclinical safety assessment of PF614: A novel TAAP prodrug of oxycodone for chronic pain indication
Publication date: Available online 27 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Ps Joshi, N. Sanakkayala, L. Kirkpatrick, Ps TerseAbstractPF614, a novel trypsin activated abuse protection (TAAP) prodrug of oxycodone, is being studied as chronic pain analgesic with extended release and abuse resistant properties. A series of nonclinical safety studies were conducted to support PF614 introduction to clinical trials. Ames assays (PF614 and its metabolites), comet assay (PF614 ≤ 50 mg/kg/day oral gavage in rats) and micronucleus assay (PF614 ≤ 175 mg/kg/day oral gavage in rats) were ne...
Source: Regulatory Toxicology and Pharmacology - July 28, 2019 Category: Toxicology Source Type: research

Exaggeration of health risk of congener alcohols in unrecorded alcohol: does this mislead alcohol policy efforts?
Publication date: Available online 20 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Dirk W. Lachenmeier, Stephan G. Walch, Jürgen Rehm (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - July 21, 2019 Category: Toxicology Source Type: research

Integrated in silico and in vitro genotoxicity assessment of thirteen data-poor substances
This study demonstrates the application of genotoxic potency analysis for prioritizing further investigations.Graphical abstract (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - July 21, 2019 Category: Toxicology Source Type: research

Can be the health risk from consumption of unrecorded fruit spirits containing alcohols other than ethanol ruled out?
Publication date: Available online 20 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Orsolya Bujdosó, László Pál, Attila Nagy, Ervin Árnyas, Róza Ádány, János Sándor, Martin McKee, Sándor Szűcs (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - July 21, 2019 Category: Toxicology Source Type: research

Control performance of fish short term reproduction assays with fathead minnow (Pimephales promelas)
Publication date: Available online 19 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): James R. Wheeler, Pablo Valverde-Garcia, Mark CraneAbstractThe fish short-term reproduction assay (FSTRA) is an in vivo screen to assess potential interactions with the fish endocrine system. After a 21-day exposure period vitellogenin (VTG) and secondary sexual characteristics are measured in males and females. Egg production and fertility are also monitored daily throughout the test. This paper presents data from 49 studies performed to satisfy test orders from the United States Environmental Protection Agency's Endocr...
Source: Regulatory Toxicology and Pharmacology - July 19, 2019 Category: Toxicology Source Type: research

Statistical analysis of the reproducibility and predictive capacity of MCTT HCE™ eye irritation test, a me-too test method for OECD TG 492
Publication date: Available online 17 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Song-E. Lim, Donghwan Lee, SeungJin Bae, Kyung-Min LimAbstractWe aimed to conduct additional statistical analysis of the reproducibility and predictive capacity of MCTT HCE™ eye irritation test (EIT), a me-too test method for OECD TG 492 with the data generated during the validation study in which 30 reference chemicals were tested in three repeated runs by three independent laboratories. We evaluated the within-laboratory reproducibility (WLR) and the between-laboratory reproducibility (BLR) through tabulation and...
Source: Regulatory Toxicology and Pharmacology - July 18, 2019 Category: Toxicology Source Type: research

Percutaneous penetration of drugs applied in transdermal delivery systems: An in vivo based approach for evaluating computer generated penetration models
Publication date: Available online 18 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Anne J. Keurentjes, Howard I. MaibachAbstractHuman skin is a viable pathway for administration of therapeutics. Transdermal delivery systems (TDS) have been approved by the US-FDA since 1981. To enable the risk assessment of dermal exposure, predictive mathematical models are used. In this work the accuracy of predicted flux of the models is compared to experimental human in vivo data of drugs applied in US-FDA approved TDS. A database of pharmacokinetic data of drugs applied in TDS was used and updated. Three mathematic...
Source: Regulatory Toxicology and Pharmacology - July 18, 2019 Category: Toxicology Source Type: research

Acute oral toxicity and repeated dose 28-day oral toxicity studies of MIL-101 nanoparticles
Publication date: Available online 17 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Chia-Hung Liu, Hsien-Chun Chiu, Hsiang-Ling Sung, Jyun-Yi Yeh, Kevin C.W. Wu, Shing-Hwa LiuAbstractMetal-organic frameworks (MOFs) nanoparticles are a class of porous crystalline materials constructed from the bonding metal ions or clusters linked with organic ligands to form frameworks. MIL-101(Cr), one of the most representative MOFs, is a three-dimensional chromium terephthalate-base porous material consisted of chromium (III)-trimers cross-linked by 1,4-benzene dicarboxylate. The present study focused on determining ...
Source: Regulatory Toxicology and Pharmacology - July 18, 2019 Category: Toxicology Source Type: research

Determination of offspring NOAEL for zeta-cypermethrin using internal exposure data from rat developmental neurotoxicity studies
The objectives of the current study were to determine the toxicokinetics (TK) of zeta-cypermethrin in postnatal day (PND) 11, 21 and 90 rats after gavage doses and use the internal exposure data from the DNT and TK studies to calculate an offspring NOAEL in mg/kg/day during lactation. The DNT studies showed that zeta-cypermethrin is not a developmental neurotoxicant. The NOAEL for maternal and offspring was determined to be 125 ppm (9.0 and 21.4 mg/kg/day for dams during gestation and lactation, respectively), based on systemic toxicity of reductions in maternal body weight, body weight gains and food consumption and o...
Source: Regulatory Toxicology and Pharmacology - July 18, 2019 Category: Toxicology Source Type: research

An FDA oncology analysis of toxicities associated with PBD-containing antibody-drug conjugates
We examined 15 ADCs with PBD-dimer payloads and a DAR of 2 and concluded that dose limiting toxicities in animals and in humans are generally related to the payload. Both the payloads and the ADCs had pro-inflammatory responses causing severe toxicities that were at times of low incidence, making it difficult to assess a cause-effect relationship. Due to their low incidence, single-patient cohorts may not detect these events and such design may not be suitable in first-in-human (FIH) trials. The commonly proposed approach by the sponsors for FIH dose selection was 1/6th highest non-severely toxic dose (HNSTD) in monkeys. T...
Source: Regulatory Toxicology and Pharmacology - July 18, 2019 Category: Toxicology Source Type: research

Use of social media to establish vapers puffing behaviour: Findings and implications for laboratory evaluation of e-cigarette emissions
Publication date: Available online 13 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Kevin McAdam, Anna Warrington, Alice Hughes, David Adams, Jennifer Margham, Carl Vas, Pete Davis, Sandra Costigan, Christopher ProctorAbstractThe recent growth in e-cigarette use has presented many challenges to Public Health research, including understanding the potential for e-cigarettes to generate toxic aerosol constituents during use. Recent research has established that the way e-cigarettes are puffed influences the magnitude of emissions from these devices, with puff duration the dominant driving force. Standardis...
Source: Regulatory Toxicology and Pharmacology - July 14, 2019 Category: Toxicology Source Type: research

Allergenicity prediction of novel and modified proteins: Not a mission impossible! Development of a Random Forest allergenicity prediction model
In conclusion, the model developed in this study improves the predictability of the allergenicity of new or modified food proteins, as demonstrated for insect proteins. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - July 14, 2019 Category: Toxicology Source Type: research

A weight of evidence approach to investigate potential common mechanisms in pesticide groups to support cumulative risk assessment: A case study with dinitroaniline pesticides
Publication date: Available online 10 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Jeremy A. Leonard, Mark Nelms, Evisabel Craig, Monique Perron, Hannah Pope-Varsalona, Sarah Dobreniecki, Anna Lowit, Yu-Mei TanAbstractIn 2016, the United States Environmental Protection Agency's (EPA) Office of Pesticide Programs published guidelines for establishing candidate common mechanism groups (CMGs) for cumulative risk assessment (CRA) weight-of-evidence-based screenings. A candidate CMG is a group of chemicals that may share similar structure, apical endpoints, and/or mechanistic data that suggest the potential...
Source: Regulatory Toxicology and Pharmacology - July 12, 2019 Category: Toxicology Source Type: research

Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid
Publication date: Available online 8 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Liqiang Gu, Munong Ma, Yuan Zhang, Lijiang Zhang, Sheng Zhang, Mincong Huang, Majuan Zhang, Yanfei Xin, Gaoli Zheng, Suhong ChengAbstractTo investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously admin...
Source: Regulatory Toxicology and Pharmacology - July 9, 2019 Category: Toxicology Source Type: research

An investigation of the acute central nervous system effects of n-decane
Publication date: Available online 9 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Richard H. McKee, Craig S. Nessel, Juan-Carlos CarrilloAbstractAcute central nervous system (CNS) depression is the most sensitive toxicological effect associated with aliphatic hydrocarbon exposure. No observed effect levels for the CNS effects of aliphatic constituents decrease with increasing carbon number to C10 (Lammers et al., 2011; McKee et al., 2011), whereas constituents with carbon numbers > C10 do not produce CNS effects at maximally attainable vapor concentrations (Nilsen et al., 1988). Accordingly, as ...
Source: Regulatory Toxicology and Pharmacology - July 9, 2019 Category: Toxicology Source Type: research

Low-level radon exposure and lung cancer mortality
ConclusionsAt low indoor radon exposure levels, reverse (negative) LRCs between radon exposure level and lung cancer mortality predominate. The strengths of these associations vary with local demographics.Graphical abstract (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - July 4, 2019 Category: Toxicology Source Type: research

Next tier in vitro and in vivo nonclinical studies further elucidating the safety and toxicity profile of MB-102, a novel fluorescent tracer agent for measurement of glomerular filtration rate
Publication date: Available online 2 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Richard B. Dorshow, Joseph E. BugajAbstractMB-102 was designed for measurement of real-time glomerular filtration rate (GFR). Previously reported in vitro and in vivo nonclinical studies clearly demonstrated negligible toxicity, resulting in FDA clearance for First-in Human, proof of concept clinical studies. The next tier of safety and toxicity studies are reported herein.MB-102 did not demonstrate any phototoxic potential in a BALB/c 3T3 mouse fibroblast study. Co-administration of MB-102 and iohexol resulted in pharmac...
Source: Regulatory Toxicology and Pharmacology - July 3, 2019 Category: Toxicology Source Type: research

Residue behavior and dietary risk assessment of chlorothalonil and its metabolite SDS-3701 in water spinach to propose maximum residue limit (MRL)
Publication date: Available online 29 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Hongfang Lin, Shengming Zhao, Xueqi Fan, Yecheng Ma, Xingling Wu, Yue Su, Jiye HuAbstractDietary risk assessment generally combines food consumption data and the concentration of pesticide by using the risk quotient (RQ) method. Chlorothalonil is the second popular fungicide in the world, and its residue and risk assessment in water spinach remain unknown. In this paper, the field trials of chlorothalonil in water spinach were operated under good agricultural practice (GAP) in China to human health protective. The dissip...
Source: Regulatory Toxicology and Pharmacology - July 1, 2019 Category: Toxicology Source Type: research

An update on the animal studies conducted for biosimilar approvals – Regulatory requirement vs actual scenario
Publication date: Available online 26 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Parag Pipalava, Ronak Patel, Miten Mehta, Meghana Dahiya, Inderjeet Singh, Vinu JoseAbstractNonclinical animal studies are considered as an integral part of biosimilar development program to demonstrate similarity and safety. We have compiled, reviewed and summarized animal studies conducted for European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) submission from 2006 till December 2018. The commonest animal studies conducted included repeat-dose toxicity study along with toxicokinetic,...
Source: Regulatory Toxicology and Pharmacology - June 27, 2019 Category: Toxicology Source Type: research

Corrigendum to “Is there any difference between the health risk from consumption of recorded and unrecorded spirits containing alcohols other than ethanol? A population-based comparative risk assessment” [Regul. Toxicol. Pharmacol. 106 (2019) 334–345]
Publication date: Available online 26 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Orsolya Bujdosó, László Pál, Attila Nagy, Ervin Árnyas, Róza Ádány, János Sándor, Martin McKee, Sándor Szűcs (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 27, 2019 Category: Toxicology Source Type: research

Safety assessment of Weissella confusa – A direct-fed microbial candidate
In conclusion, the toxicological studies performed confirmed W. confusa to be safe, making it a good candidate as a direct-fed microbial product. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 27, 2019 Category: Toxicology Source Type: research

Health risk assessment for pediatric population associated with ethanol and selected residual solvents in herbal based products
In this study, 48 herbal based products (41 for the pediatric population) were analyzed for the presence of ethanol and residual solvents. Ethanol was not detected in only 12% of the products designed for infants or toddlers aged under 2, and not quantified in only 5 of 14 ‘alcohol free’ products. Actual content was higher than labeled in six out of 11 samples with specified ethanol quantity. WHO proposed requirement for ethanol content in products intended for use in children under the age of 6 (
Source: Regulatory Toxicology and Pharmacology - June 24, 2019 Category: Toxicology Source Type: research

Exposure assessments in reproductive and developmental toxicity testing: An IQ-DruSafe industry survey on current practices and experiences in support of exposure-based high dose selection
Publication date: Available online 20 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Paul A. Andrews, Mary Ellen McNerney, Joseph J. DeGeorgeAbstractThe draft ICH S5(R3) guideline includes an exposure-based endpoint as an option for selecting the high dose in developmental and reproductive toxicity (DART) studies. In 2016, IQ DruSafe conducted an anonymous survey to identify industry practices and experiences related to pharmacokinetic assessments in DART studies in order to facilitate a pragmatic data-driven approach to development of an acceptable multiple of the clinical exposure to be proposed for do...
Source: Regulatory Toxicology and Pharmacology - June 21, 2019 Category: Toxicology Source Type: research

Peanut leaf extract has antioxidant and anti-inflammatory activity but no acute toxic effects
This study aimed to examine the phytochemical composition of peanut leaf hydroalcoholic extract (PLHE) and describe its potential toxic effects and antioxidant and anti-inflammatory properties. The qualitative chemical analysis of PLHE by UHPLC-ESI-HRMS allowed the identification of eight metabolites types (totaling 29 compounds). The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay revealed that PLHE had strong antioxidant effects; it also exhibited nitric oxide (NO)-scavenging capacity. Human peripheral blood mononuclear cells (PBMCs) exposed to PLHE showed no reduced cell viability or increased free double-stranded DNA, NO, ...
Source: Regulatory Toxicology and Pharmacology - June 19, 2019 Category: Toxicology Source Type: research

Testing developmental toxicity in a second species: are the differences due to species or replication error?
This study shows that differences in NOAELs or LOAELs (N(L)OAELs) observed between rat and rabbit developmental toxicity studies performed according to OECD guidelines could just as well be caused by study replication errors, and not necessarily by differences in species sensitivity. This conclusion follows from an analysis of a database with rat and rabbit developmental toxicity studies for over 1000 industrial chemicals, pesticides, veterinary drugs and human pharmaceuticals, which included 143 compounds with multiple oral rat studies and 124 compounds with multiple oral rabbit studies.Our analysis confirms earlier findi...
Source: Regulatory Toxicology and Pharmacology - June 19, 2019 Category: Toxicology Source Type: research

Mechanistic relationship between biodegradation and bioaccumulation. Practical outcomes
This article addresses this relationship in searching for BOD threshold below which no vB and B chemicals could be observed. It was found that the regulatory criteria for persistency could be used for identification of not vB and B chemicals. In addition, fish liver metabolism is determined as the most significant factor in reducing of maximum bioaccumulation potential of the chemicals. It was found that parameters associated with the models simulating fish metabolism could be also used for identification of not vB and B chemicals. (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 19, 2019 Category: Toxicology Source Type: research

Proposal of GHS sub-categorization criteria for LLNA: BrdU-ELISA (OECD TG442B)
In this study, we re-analyzed the existing data of 32 sensitizers classified in the 1A or 1B categories of the GHS, and attempted to determine optimal criteria for GHS sub-categorization using LLNA: BrdU-ELISA. Consequently, the optimal criterion for the GHS sub-categorization was determined to be 6% when using EC1.6, showing the correct outcomes (%) for GHS 1A and GHS 1B category chemicals were 92.3 and 84.2 for all 32 chemicals, respectively. When excluding 2-mercaptobenzothiazole which may cause strain specific low response in this assay system, the correct outcomes (%) for GHS 1A chemicals was 100. Further work would b...
Source: Regulatory Toxicology and Pharmacology - June 18, 2019 Category: Toxicology Source Type: research

Distribution of fluoride contamination in drinking water resources and health risk assessment using geographic information system, northwest Iran
Publication date: Available online 18 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Mahmood Yousefi, Sahar Ghalehaskar, Farzaneh Baghal Asghari, Afshin Ghaderpoury, Mohammad Hadi Dehghani, Mansour Ghaderpoori, Ali Akbar MohammadiAbstractThis paper considers exposure to the concentration of fluoride in drinking water resources of Showt city in West Azerbaijan Province in, Iran, and its related potential health risk assessment issues to the resident populations. For this purpose, 88 drinking water samples were analyzed in 2016 by using the spectrophotometric method. Non-carcinogenic health risks due to F ...
Source: Regulatory Toxicology and Pharmacology - June 18, 2019 Category: Toxicology Source Type: research

Editorial Board
Publication date: August 2019Source: Regulatory Toxicology and Pharmacology, Volume 106Author(s): (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 18, 2019 Category: Toxicology Source Type: research

Biosafety of unmodified ultrafine gold particles (AuPs) upon interacting with human blood components before systemic use
Publication date: Available online 14 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Farhat Naz, Amit Kumar Dinda, Renu Saxena, Veena KoulAbstractUltrafine gold particles (AuPs) can be emerged as a good candidate in the field of drug delivery as well as in imaging applications. However, little attention has been paid to detailed study of nanoparticle's interaction with blood components before systemic use. An investigation into the interaction of ultrafine AuPs with blood components is must for its clinical application. In present study, the interaction of ultrafine sized AuPs (2 ± 0.5 nm, 5...
Source: Regulatory Toxicology and Pharmacology - June 14, 2019 Category: Toxicology Source Type: research

Assessment of hypolipidemic, anti-inflammatory and antioxidant properties of medicinal plant Erica multiflora in triton WR-1339-induced hyperlipidemia and liver function repair in rats: A comparison with fenofibrate
Publication date: Available online 11 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Rihab Khlifi, Aida Lahmar, Zaineb Dhaouefi, Zahar Kalboussi, Mouna Maatouk, Soumaya Kilani-Jaziri, Kamel Ghedira, Leila Chekir-GhediraAbstractHyperlipidemia is a serious health threat that has been linked to oxidative stress and systemic inflammation, causing among many other disorders essentially liver disease. The current study was conducted to evaluate the antihyperlipidemic, antioxidant and anti-inflammatory potential of methanol leaf extract from Erica multiflora (M-EML). Triton WR-1339-induced hyperlipidemic rats w...
Source: Regulatory Toxicology and Pharmacology - June 12, 2019 Category: Toxicology Source Type: research

Investigation of number of replicate measurements required to meet cigarette smoke chemistry regulatory requirements measured under Canadian intense smoking conditions
Publication date: Available online 12 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Alison Eldridge, Tatiana Betson, Marcos Vinicius Gama, Graham Errington, Kevin McAdamAbstractThere has been increased interest in recent years in regulatory reporting of cigarette smoke toxicants. There is a great deal of diversity in current regulatory standards around the world in terms of the identities of regulated toxicants, and the number of replicate analyses stipulated for their measurement. Furthermore, analytical methods developed collaboratively by several organisations and intended for regulatory analysis gen...
Source: Regulatory Toxicology and Pharmacology - June 12, 2019 Category: Toxicology Source Type: research

Genetic toxicology in silico protocol
Publication date: Available online 11 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Catrin Hasselgren, Ernst Ahlberg, Yumi Akahori, Alexander Amberg, Lennart T. Anger, Franck Atienzar, Scott Auerbach, Lisa Beilke, Phillip Bellion, Romualdo Benigni, Joel Bercu, Ewan D. Booth, Dave Bower, Alessandro Brigo, Zoryana Cammerer, Mark T.D. Cronin, Ian Crooks, Kevin P. Cross, Laura Custer, Krista DoboAbstractIn silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals...
Source: Regulatory Toxicology and Pharmacology - June 12, 2019 Category: Toxicology Source Type: research

Opinion of the Scientific Committee on consumer safety (SCCS) – Final opinion on the safety of fragrance ingredient Acetylated Vetiver Oil (AVO) - (Vetiveria zizanioides root extract acetylated) - Submission III
Publication date: Available online 6 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): SCCS ScientificCommitteeonConsumerSafetyAbstractOn the basis of the safety assessment carried out using a conservative approach, the SCCS considers the use of Acetylated Vetiver Oil (AVO) with 1% alpha-tocopherol as a fragrance ingredient in cosmetic leave-on and rinse-off type products safe at the concentrations proposed by IFRA.Acetylated Vetiver Oil (AVO) contains some constituents that belong to the chemical group of aldehydes and ketones that are known to be reactive towards biological entities, such as DNA and prote...
Source: Regulatory Toxicology and Pharmacology - June 7, 2019 Category: Toxicology Source Type: research

Opinion of the Scientific Committee on Consumer safety (SCCS) – Opinion on Ethylzingerone - ‘Hydroxyethoxyphenyl Butanone’ (HEPB) - Cosmetics Europe No P98 - CAS No 569646-79-3 - Submission II (eye irritation)
Publication date: Available online 4 June 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): SCCS, U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, E. Ezendam, C.L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, A. Simonnard, W. Uter, Tamara Vanhaecke (Source: Regulatory Toxicology and Pharmacology)
Source: Regulatory Toxicology and Pharmacology - June 5, 2019 Category: Toxicology Source Type: research