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Repeat dose and reproductive toxicity of thrombopoietin mimic peptide in Sprague-Dawley rats
In this report, we evaluated the potential toxicity of TMP in repeat-dose toxicity and reproductive/developmental toxicity studies (segment Ⅰ, Ⅱ, Ⅲ). TMP was administered subcutaneously to Sprague-Dawley (SD) rats at 5, 15 or 50 mcg/kg. In repeat-dose toxicity study, the rats were administrated three times a week for 26 week with a 4-week recovery. TMP could produce anti-drug antibodies and induce platelet counts increase, megakaryocyte proliferation. While platelet counts decreased gradually and returned to normal after 4 weeks in male rats. Other significant findings included myelofibrosis of bone marrow, hepatic e...
Source: Regulatory Toxicology and Pharmacology : RTP - February 11, 2024 Category: Toxicology Authors: Shidong Qiu Yuji Liang Xiaobo Wang Xiue Li Guoyue Wei Peng Xiao Suling Teng Peilu Sun Lei Song Zenglin Zhao Yanling Mu Source Type: research

Chronic aquatic toxicity assessment of diverse chemicals on Daphnia magna using QSAR and chemical read-across
Regul Toxicol Pharmacol. 2024 Feb 5;148:105572. doi: 10.1016/j.yrtph.2024.105572. Online ahead of print.ABSTRACTWe have modeled here chronic Daphnia toxicity taking pNOEC (negative logarithm of no observed effect concentration in mM) and pEC50 (negative logarithm of half-maximal effective concentration in mM) as endpoints using QSAR and chemical read-across approaches. The QSAR models were developed by strictly obeying the OECD guidelines and were found to be reliable, predictive, accurate, and robust. From the selected features in the developed models, we have found that an increase in lipophilicity and saturation, the pr...
Source: Regulatory Toxicology and Pharmacology : RTP - February 7, 2024 Category: Toxicology Authors: Ankur Kumar Vinay Kumar Probir Kumar Ojha Kunal Roy Source Type: research

Pre-clinical safety assessment of biotechnologically produced lacto-N-tetraose (LNT)
In this study, the preclinical safety of LNT produced by the Escherichia coli K-12 E2083 production strain was assessed. LNT was negative in both the bacterial reverse mutation assay and the in vitro micronucleus assay, demonstrating the absence of genotoxic potential for this substance. In the OECD 408 guideline compliant 90-day oral toxicity study rat, LNT did not induce any adverse effects in any treatment group up to and including the highest dose tested, and no LOAEL could be determined. Therefore, the no-observed-adverse effect level (NOAEL) is set at the highest dose level tested, i.e. a dietary level of 5 % (w/w), ...
Source: Regulatory Toxicology and Pharmacology : RTP - February 5, 2024 Category: Toxicology Authors: Hester van der Woude Sylvia M J G Pelgrom Carin Buskens Roy Hoffmans Nora Krajcs Dianne J Delsing Source Type: research

Adverse effects in traditional and alternative toxicity tests
Regul Toxicol Pharmacol. 2024 Feb 1;148:105579. doi: 10.1016/j.yrtph.2024.105579. Online ahead of print.ABSTRACTChemical safety assessment begins with defining the lowest level of chemical that alters one or more measured endpoints. This critical effect level, along with factors to account for uncertainty, is used to derive limits for human exposure. In the absence of data regarding the specific mechanisms or biological pathways affected, non-specific endpoints such as body weight and non-target organ weight changes are used to set critical effect levels. Specific apical endpoints such as impaired reproductive function or ...
Source: Regulatory Toxicology and Pharmacology : RTP - February 3, 2024 Category: Toxicology Authors: Patience Browne Katie Paul Friedman Kim Boekelheide Russell S Thomas Source Type: research

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern
Regul Toxicol Pharmacol. 2024 Jan 28;148:105569. doi: 10.1016/j.yrtph.2024.105569. Online ahead of print.ABSTRACTThe Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile...
Source: Regulatory Toxicology and Pharmacology : RTP - January 29, 2024 Category: Toxicology Authors: Isabelle Lee Cesar Scrochi Olive Chon Mary Ann Cancellieri Ambarnil Ghosh John O'Brien Brendan Ring Cronan McNamara Anne Marie Api Source Type: research

Is schedule IV suvorexant an appropriate reference drug of abuse to use in preclinical abuse liability testing in the rat?
Regul Toxicol Pharmacol. 2024 Jan 27;148:105570. doi: 10.1016/j.yrtph.2024.105570. Online ahead of print.ABSTRACTThe abuse potential of novel CNS-active drug candidates with low specificity for known receptors involved in abuse might be complex to test preclinically relative to an appropriate reference drug of abuse. Suvorexant, a Schedule IV dual orexin receptor antagonist was investigated for its potential use as a reference drug in Drug Discrimination Learning (DDL) studies. Firstly, toxicokinetic properties of suvorexant were determined in male and female rats after single oral doses of 160 and 325 mg/kg in MC and PEG4...
Source: Regulatory Toxicology and Pharmacology : RTP - January 29, 2024 Category: Toxicology Authors: Greet B A Teuns Michela Tessari Source Type: research

Derivation of no significant risk levels for three lower acrylates: Conclusions and recommendations from an expert panel
Regul Toxicol Pharmacol. 2024 Jan 26;148:105567. doi: 10.1016/j.yrtph.2024.105567. Online ahead of print.ABSTRACTA panel of toxicology, mode of action (MOA), and cancer risk assessment experts was engaged to derive no-significant-risk-levels (NSRLs) for three lower acrylates: methyl acrylate (MA), ethyl acrylate (EA), and 2-ethylhexyl acrylate (2EHA) using the best available science, data, and methods. The review was structured as a five-round, modified Delphi format, a systematic process for collecting independent and deliberative input from panel members, and it included several procedural elements to reduce potential so...
Source: Regulatory Toxicology and Pharmacology : RTP - January 28, 2024 Category: Toxicology Authors: C R Kirman P J Boogaard J S Bus V L Dellarco K Shao B R Stern S M Hays Source Type: research

In Memoriam: Michael "Mike" Steven Denison 1954-2022
Regul Toxicol Pharmacol. 2024 Jan 25:105566. doi: 10.1016/j.yrtph.2024.105566. Online ahead of print.NO ABSTRACTPMID:38278690 | DOI:10.1016/j.yrtph.2024.105566 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - January 26, 2024 Category: Toxicology Authors: Martin van den Berg Source Type: research

Can "Hazard-Cost-Effectiveness Analysis" improve the risk management of chemicals under REACH?
Regul Toxicol Pharmacol. 2024 Feb;147:105561. doi: 10.1016/j.yrtph.2024.105561. Epub 2024 Jan 19.ABSTRACTCost-Effectiveness Analysis (CEA) is a decision-making framework to prioritize policy decisions for chemicals. Differences in hazard profiles among chemicals are not integrated in CEA under the EU REACH Regulation, which could limit its relevance. Another concern is that two different economic decision support methods (CEA for chemicals considered as PBTs or vPvBs from a regulatory perspective and Cost Benefit Analysis (CBA) for others) are used under REACH. To address this situation, we define "Hazard" CEA by integrati...
Source: Regulatory Toxicology and Pharmacology : RTP - January 21, 2024 Category: Toxicology Authors: Jean-Marc Brignon Jean-Christophe Vergnaud Sandrine Andres Enrico Mombelli Tsarafara Rambolarimanana Source Type: research

Systematic update to the mammalian relative potency estimate database and development of best estimate toxic equivalency factors for dioxin-like compounds
This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets). REP quality and relevance for these data was assessed via application of a consensus-based weighting framework. Using Bayesian dose-response modeling, available data were modeled to produce standardized dose/concentration-response Hill curves. Study quality and REP data were synthesized via Bayesian meta-analysis to i...
Source: Regulatory Toxicology and Pharmacology : RTP - January 20, 2024 Category: Toxicology Authors: S Fitch A Blanchette L C Haws K Franke C Ring M DeVito M Wheeler N Walker L Birnbaum K I Van Ede E C Antunes Fernandes D S Wikoff Source Type: research

Identification of true chemical respiratory allergens: Current status, limitations and recommendations
Regul Toxicol Pharmacol. 2024 Feb;147:105568. doi: 10.1016/j.yrtph.2024.105568. Epub 2024 Jan 14.ABSTRACTAsthma in the workplace is an important occupational health issue. It comprises various subtypes: occupational asthma (OA; both allergic asthma and irritant-induced asthma) and work-exacerbated asthma (WEA). Current regulatory paradigms for the management of OA are not fit for purpose. There is therefore an important unmet need, for the purposes of both effective human health protection and appropriate and proportionate regulation, that sub-types of work-related asthma can be accurately identified and classified, and th...
Source: Regulatory Toxicology and Pharmacology : RTP - January 16, 2024 Category: Toxicology Authors: Mark A Pemberton Josje He Arts Ian Kimber Source Type: research

Prioritization of chemicals in personal care products based on persistent, bioaccumulative and toxic (PBT) potential: An Indian perspective
Regul Toxicol Pharmacol. 2024 Feb;147:105563. doi: 10.1016/j.yrtph.2024.105563. Epub 2024 Jan 10.ABSTRACTNumerous organic ingredients present in Personal care products (PCPs) are being detected in sewage which has a high potential to impact the environment. These compounds are called as Emerging contaminants (ECs) or Contaminants of emerging concern. However, the information on the source and occurrence of ECs present in PCPs is very minimal. Specifically, information on the persistence (P), bioaccumulation (B) and toxicity (T) is very scarce. The determination of PBT properties is a complex task given the magnitude of che...
Source: Regulatory Toxicology and Pharmacology : RTP - January 12, 2024 Category: Toxicology Authors: Abirami Balakrishnan Varshini Senthilkumar Sowmiya Rajan Jeyakumaran Jabez John Kevin Vinodh Uthradevi Kannan Balakrishnan Paramasivam Source Type: research

Comprehensive safety assessment of serendipity berry sweet protein produced from Komagataella phaffii
Regul Toxicol Pharmacol. 2024 Feb;147:105562. doi: 10.1016/j.yrtph.2024.105562. Epub 2024 Jan 6.ABSTRACTSerendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays...
Source: Regulatory Toxicology and Pharmacology : RTP - January 8, 2024 Category: Toxicology Authors: Elaine L Freeman Rachel Ward Mary M Murphy Tina Wang Jason Ryder Source Type: research