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- Evaluation of Developmental and Reproductive Toxicity in Rabbits for
MB-102, a Fluorescent Tracer Agent Designed for Real-Time Measurement of
Glomerular Filtration Rate-
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Authors: Joseph E. Bugaj, Richard B. Dorshow
Abstract: International Journal of Toxicology, Ahead of Print.
The fluorescent tracer, MB-102, has been designed for the direct, real-time measurement of glomerular filtration rate. Previous studies, both in vitro and in vivo (rats, rabbits and dogs), were conducted to assess potential toxicity including single dose toxicity, mutation assay, chromosomal aberration assay, phototoxicity, local tolerance study, micronuclease assay, hERG channel changes, CNS and cardiovascular safety. The results of these studies led to a safety/toxicology profile for this agent deemed sufficient by the FDA to conduct Phase I and Phase II human clinical studies. In this paper we report on maternal toxicity and the potential effects on embryo-fetal development and the toxicokinetics of MB-102 administered daily via intravenous (bolus) injection into pregnant rabbits during the period of organogenesis gestation day 7-19. Assessment of toxicity was based on mortality, clinical observations, body weight, food consumption, reproductive performance and necropsy and cesarean section findings. Blood samples were collected for toxicokinetic evaluation. No test article findings were noted in any of these studies. The only clinical findings observed were the discoloration of skin, eyes or pelage in the 2 higher dose groups, which were considered related to the color and fluorescent properties of MB-102 and were deemed non-adverse. Exposure, as assessed by Cmax and AUC(0-6) increased in a dose dependent manner from 4.5 to 113 mg/kg/day. No accumulation of the test article was noted after multiple doses were administered. Thus, intravenous administration of MB-102 was not associated with any adverse developmental or reproductive toxicities in pregnant rabbits.
Citation: International Journal of Toxicology
PubDate: 2022-06-27T01:28:06Z
DOI: 10.1177/10915818221111331
- Tumor-Inhibitory Effects of Zerumbone Against HT-29 Human Colorectal
Cancer Cells-
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Authors: Fezzeh Memari, Farshad Mirzavi, Mohammad Jalili‐Nik, Amir R. Afshari, Ahmad Ghorbani, Mohammad Soukhtanloo
Abstract: International Journal of Toxicology, Ahead of Print.
Colorectal cancer (CRC) is the second cause of cancer-associated death globally. Recently, herbal medicinal products and, in particular, zerumbone have been widely studied and used for cancer treatment as they induce significant anti-cancer effects. However, there is limited information about the anti-cancer effects of zerumbone in CRC. Therefore, we aimed to investigate the in vitro anti-cancer effects of the zerumbone in CRC, focusing on cell apoptosis and migration. Anti-proliferative and anti-migratory effects of zerumbone on HT-29 cells were evaluated using MTT and scratch wound healing assay, respectively. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of migration and apoptosis-related genes. Apoptosis and cell cycle distribution were evaluated by flow cytometry. The intracellular level of reactive oxygen species (ROS) was measured using a ROS assay kit. Additionally, matrix metalloproteinase-2/-9 (MMP-2/-9) activity was determined using gelatin zymography. Zerumbone suppressed the viability of the HT-29 cells dose-dependently while having less cytotoxicity on normal NIH/3T3 cells. Zerumbone induced apoptosis in HT-29 cells and arrested the cell cycle in the G2/M phase. These effects were associated with alteration in the expression of apoptosis-related genes (up-regulation of Bax and down-regulation of Bcl-2 genes). Zerumbone also enhanced the generation of ROS in HT-29 cells. Furthermore, zerumbone significantly inhibited the migration of HT-29 cells and decreased MMP-2/-9 mRNA expression and activity. Our findings provide a potential use for zerumbone to induce apoptosis and suppress metastasis in HT-29 cells; thus, it could be developed as a promising natural agent for future CRC therapy.
Citation: International Journal of Toxicology
PubDate: 2022-06-20T03:17:09Z
DOI: 10.1177/10915818221104417
- Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal
Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity
Study in Rats-
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Authors: Bernard S. Buetow, Gregg D Cappon, Laura M. Aschenbrenner, Lawrence Updyke, Vince R. Torti, Mark Evans, Shana R. Dalton, Steven Bailey, Christopher J. Bowman
Abstract: International Journal of Toxicology, Ahead of Print.
Bococizumab is an anti-PCSK9 monoclonal antibody that was intended for the treatment of hypercholesterolemia. After reviewing the 6-month rat toxicity study data, in which there was a low spontaneous tumor incidence, unrelated to bococizumab administration, the U.S. FDA granted a carcinogenicity waiver request based on a weight-of-evidence assessment of low carcinogenic risk. Subsequently, after reviewing 6-month rat toxicity study data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted. The resulting 2-year carcinogenicity study demonstrated no bococizumab-related increase in tumors, confirming the weight-of-evidence evaluation and alleviating concerns regarding the carcinogenic potential. Here we report the scientific and regulatory background that led to the request for a rat carcinogenicity study, the feedback on the design of the carcinogenicity study, and the results from this study which affirmed the original weight-of-evidence assessment of low carcinogenic risk.
Citation: International Journal of Toxicology
PubDate: 2022-06-08T05:03:28Z
DOI: 10.1177/10915818221106397
- Safety Assessment of Skin and Connective Tissue-Derived Proteins and
Peptides as Used in Cosmetics-
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Authors: Christina L. Burnett, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 19 skin and connective tissue-derived proteins and peptides, which are reported to function mainly as skin and/or hair conditioning agents in cosmetics. The Panel reviewed the relevant data provided and concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.
Citation: International Journal of Toxicology
PubDate: 2022-06-07T05:16:19Z
DOI: 10.1177/10915818221104783
- Protein-Ligand Identification and In Vitro Inhibitory Effects of Cathine
on 11 Major Human Drug Metabolizing Cytochrome P450s-
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Authors: Sharoen Y. M. Lim, Jason Siau Ee Loo, Mustafa Alshagga, Mohammed A. Alshawsh, Chin E. Ong, Yan Pan
Abstract: International Journal of Toxicology, Ahead of Print.
Cathine is the stable form of cathinone, the major active compound found in khat (Catha edulis Forsk) plant. Khat was found to inhibit major phase I drug metabolizing cytochrome P450 (CYP) enzyme activities in vitro and in vivo. With the upsurge of khat consumption and the potential use of cathine to combat obesity, efforts should be channelled into understanding potential cathine-drug interactions, which have been rather limited. The present study aimed to assess CYPs activity and inhibition by cathine in a high-throughput in vitro fluorescence-based enzyme assay and molecular docking analysis to identify how cathine interacts within various CYPs’ active sites. The half maximal inhibitory concentration (IC50) values of cathine determined for CYP2A6 and CYP3A4 were 80 and 90 μM, while CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2 and CYP3A5 showed no significant inhibition. Furthermore, in Ki analysis, the Lineweaver-Burk plots depicted non-competitive mixed inhibition of cathine on both CYP2A6 and CYP3A4 with Ki value of 63 and 100 μM, respectively. Cathine showed negligible time-dependent inhibition on CYPs. Further, molecular docking studies showed that cathine was bound to CYP2A6 via hydrophobic, hydrogen and π-stacking interactions and formed hydrophobic and hydrogen bonds with active site residues in CYP3A4. Both molecular docking prediction and in vitro outcome are in agreement, granting more detailed insights for predicting CYPs metabolism besides the possible cathine-drug interactions. Cathine-drug interactions may occur with concomitant consumption of khat or cathine-containing products with medications metabolized by CYP2A6 and CYP3A4.
Citation: International Journal of Toxicology
PubDate: 2022-06-04T10:06:10Z
DOI: 10.1177/10915818221103790
- Evaluation of Pharmaceuticals for DNA Damage in the Chicken Egg
Genotoxicity Assay (CEGA)-
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Authors: Tetyana Kobets, Jian-Dong Duan, Esther Vock, Ulrich Deschl, Gary M. Williams
Abstract: International Journal of Toxicology, Ahead of Print.
DNA damage is an established initiating event in the mutagenicity and carcinogenicity of genotoxic chemicals. Accordingly, assessment of this endpoint is critical for chemicals which are being developed for use in humans. To assess the ability of the Chicken Egg Genotoxicity Assay (CEGA) to detect genotoxic pharmaceuticals, a set of 23 compounds with different pharmacological and reported genotoxic effects was tested for the potential to produce nuclear DNA adducts and strand breaks in the embryo-fetal livers using the 32P-nucleotide postlabeling (NPL) and comet assays, respectively. Due to high toxicity, two aneugens, colchicine and vinblastine, and an autophagy inhibitor, hydroxychloroquine, could not be evaluated. Out of the 20 remaining pharmaceuticals, 10 including estrogen modulators, diethylstilbestrol and tamoxifen, antineoplastics cyclophosphamide, etoposide, and mitomycin C, antifungal griseofulvin, local anesthetics lidocaine and prilocaine, and antihistamines diphenhydramine and doxylamine, yielded clear positive outcomes in at least one of the assays. The antihypertensive vasodilator hydralazine and antineoplastics streptozotocin and teniposide, produced only DNA strand breaks, which were not dose-dependent, and thus, the results with these 3 pharmaceuticals were considered equivocal. No DNA damage was detected for 7 compounds, including the purine antagonist 6-thioguanine, antipyretic analgesics acetaminophen and phenacetin, antibiotic ciprofloxacin, antilipidemic clofibrate, anti-inflammatory ibuprofen, and sedative phenobarbital. However, low solubility of these compounds limited dosages tested in CEGA. Overall, results in CEGA were largely in concordance with the outcomes in other systems in vitro and in vivo, indicating that CEGA provides reliable detection of DNA damaging activity of genotoxic compounds. Further evaluations with a broader set of compounds would support this conclusion.
Citation: International Journal of Toxicology
PubDate: 2022-06-04T07:53:24Z
DOI: 10.1177/10915818221093583
- Increasing the Reuse of Protein Non-Naïve Nonhuman Primates in
Pharmaceutical Drug Discovery and Development: An Overview and Industry
Position on the Challenges and Benefits-
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Authors: Charles Mattis, Natalie Bratcher, Monika Burns, Christopher Carosino, Christina de Zafra, R. Marcus Fancher, Katrin Georgi, Candace Graff, Renee R. Hukkanen, Colena Johnson, Yanbin Lao, Amber Lange, Donna Lee, Michelle Lepherd, Sean Maguire, Mantas Malisauskas, Melinda Manuel, Sonia Miranda, Lori Reed, Rosemary Santos, Brian Sayers, David Shaw, David Shuster
Abstract: International Journal of Toxicology, Ahead of Print.
The IQ Consortium NHP Reuse Working Group (WG) comprises members from 15 pharmaceutical and biotechnology companies. In 2020, the WG developed and distributed a detailed questionnaire on protein non-naïve NHP reuse to the WG member companies. The WG received responses from key stakeholders including principal investigators, facility managers, animal welfare officers and research scientists. This paper’s content reflects the consolidated opinion of the WG members and the questionnaire responses on the subject of NHP reuse within nonclinical programs at all stages of research and development. Many of the pharmaceutical companies represented in the working group or participating in the questionnaire have already achieved some level of NHP reuse in their nonclinical programs, but the survey results suggested that there is significant potential to increase NHP reuse further and a need to understand the considerations involved in reuse more clearly. The WG has also focused carefully on the inherent concerns and risks of implementing protein non-naive NHP reuse and has evaluated the best methods of risk assessment and decision-making. This paper presents a discussion on the challenges and opportunities surrounding protein non-naïve NHP reuse and aims to stimulate further industry dialogue on the subject and provide guidance for pharmaceutical companies to establish roadmaps and decision trees enabling increased protein non-naïve NHP reuse. In addition, this paper represents a solid basis for collaborative engagement between pharmaceutical and biotechnology companies with contract research organizations (CROs) to discuss how the availability of protein non-naïve NHP within CROs can be better leveraged for their use within nonclinical studies.
Citation: International Journal of Toxicology
PubDate: 2022-06-03T06:03:31Z
DOI: 10.1177/10915818221101791
- Shp2 in Alveolar Macrophages Regulates Macrophage I Phenotype in Acute
Lung Injury-
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Authors: Dawei Wang, Qiumei Cao
Abstract: International Journal of Toxicology, Ahead of Print.
Macrophage play important role in acute lung injury (ALI). This study aims to explore the possible role of Shp2 in regulating macrophage 1 (M1) in ALI progression. ALI was induced in rats by intravenous injection of lipopolysacharide (LPS). Lentivirus was used to knock down Shp2 expression. Lungs from LPS-induced ALI rats were evaluated by H&E staining and wet/dry lung weight ratio (W/D ratio) measurement. The expression of inflammatory cytokines IL-1β, TNF-α and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. The expressions of M1 biomarker (iNOS) and macrophage 2 (M2) biomarker (Arg-1) in lung tissues and macrophages were measured by immunofluorescence and western blot. The ratio of M2/M1 was detected by flow cytometry. Inflammatory cytokines were highly expressed in ALI rat models, in which elevated expression of iNOS and decreased Arg-1 expression were detected. Shp2 was found to be highly expressed in lung tissues of ALI rat models. LPS treatment in NR8383 cells lead to increased M1 phenotype and elevated expression of Shp2. Suppression on Shp2 expression can counteract the LPS-induced effect and further attenuate ALI progression. Evidence collected from ALI rat and cell models showed that suppression Shp2 expression in macrophages can inhibit M1 phenotype to attenuate ALI progression.
Citation: International Journal of Toxicology
PubDate: 2022-06-02T12:51:08Z
DOI: 10.1177/10915818221105227
- Book Review
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Authors: Stephen J Newsholme
Abstract: International Journal of Toxicology, Ahead of Print.
Citation: International Journal of Toxicology
PubDate: 2022-06-02T10:41:38Z
DOI: 10.1177/10915818221106034
- Repeated-Dose Toxicity, Biodistribution, and Shedding Assessments With a
ChAd155 Respiratory Syncytial Virus Vaccine Candidate Evaluated in Rabbits
and Rats-
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Authors: Alan H. Stokes, Camille Planty, Johanne Pion, Philippe Ancian, Alexandra Rogue, Carine Bansard, Jérémy Silvano, Dominique Papineau, Nawel Ben Abdeljelil, Giulietta Maruggi, Haifeng Song, Catherine Spickler, Karine Blouin, Guillaume Dubois, Luis-Alexander Rodriguez, Judith Baumeister, Ann-Muriel Steff, Eric Destexhe
Abstract: International Journal of Toxicology, Ahead of Print.
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTI) in infants, and toddlers and vaccines are not yet available. A pediatric RSV vaccine (ChAd155-RSV) is being developed to protect infants against RSV disease. The ChAd155-RSV vaccine consists of a recombinant replication-deficient chimpanzee-derived adenovirus (ChAd) group C vector engineered to express the RSV antigens F, N, and M2-1. The local and systemic effects of three bi-weekly intramuscular injections of the ChAd155-RSV vaccine was tested in a repeated-dose toxicity study in rabbits. After three intramuscular doses, the ChAd155-RSV vaccine was considered well-tolerated. Changes due to the vaccine-elicited inflammatory reaction/immune response were observed along with transient decreases in platelet count without physiological consequences, already reported for other adenovirus-based vaccines. In addition, the biodistribution and shedding of ChAd155-RSV were also characterized in two studies in rats. The distribution and persistence of the ChAd155-RSV vaccine candidate was consistent with other similar adenovector-based vaccines, with quantifiable levels of ChAd155-RSV observed at the injection site (muscle) and the draining lymph nodes up to 69 days post administration. The shedding results demonstrated that ChAd155-RSV was generally not detectable in any secretions or excreta samples. In conclusion, the ChAd155-RSV vaccine was well-tolerated locally and systemically.
Citation: International Journal of Toxicology
PubDate: 2022-06-02T03:14:29Z
DOI: 10.1177/10915818221101788
- Book Review
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Authors: William J. Brock
Abstract: International Journal of Toxicology, Ahead of Print.
Citation: International Journal of Toxicology
PubDate: 2022-06-01T03:30:29Z
DOI: 10.1177/10915818221106032
- Safety Assessment of Plant-Derived Proteins and Peptides as Used in
Cosmetics-
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Authors: Christina L. Burnett, Ivan J. Boyer, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 19 plant-derived proteins and peptides, which function mainly as skin and/or hair conditioning agents in personal care products. The Panel concluded that 18 plant-derived proteins and peptides are safe as used in the present practices of use and concentration as described in this safety assessment, while the data on Hydrolyzed Maple Sycamore Protein are insufficient to determine safety.
Citation: International Journal of Toxicology
PubDate: 2022-05-23T11:58:23Z
DOI: 10.1177/10915818221100700
- Comprehensive Nonclinical Safety Assessment of Nirmatrelvir Supporting
Timely Development of the SARS-COV-2 Antiviral Therapeutic, Paxlovid™-
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Authors: Jean G. Sathish, Siddhartha Bhatt, Jamie K. DaSilva, Declan Flynn, Stephen Jenkinson, Amit S. Kalgutkar, Maggie Liu, Balasubramanian Manickam, Jason Pinkstaff, William J. Reagan, Norimitsu Shirai, Ahmed M. Shoieb, Madhu Sirivelu, Saurabh Vispute, Allison Vitsky, Karen Walters, Todd A. Wisialowski, Lawrence W. Updyke
Abstract: International Journal of Toxicology, Ahead of Print.
COVID-19 is a potentially fatal infection caused by the SARS-CoV-2 virus. The SARS-CoV-2 3CL protease (Mpro) is a viral enzyme essential for replication and is the target for nirmatrelvir. Paxlovid (nirmatrelvir co-administered with the pharmacokinetic enhancer ritonavir) showed efficacy in COVID-19 patients at high risk of progressing to hospitalization and/or death. Nonclinical safety studies with nirmatrelvir are essential in informing benefit-risk of Paxlovid and were conducted to support clinical development. In vivo safety pharmacology assessments included a nervous system/pulmonary study in rats and a cardiovascular study in telemetered monkeys. Potential toxicities were assessed in repeat dose studies of up to 1 month in rats and monkeys. Nirmatrelvir administration (1,000 mg/kg, p.o.) to male rats produced transient increases in locomotor activity and respiratory rate but did not affect behavioral endpoints in the functional observational battery. Cardiovascular effects in monkeys were limited to transient increases in blood pressure and decreases in heart rate, observed only at the highest dose tested (75 mg/kg per dose b.i.d; p.o.). Nirmatrelvir did not prolong QTc-interval or induce arrhythmias. There were no adverse findings in repeat dose toxicity studies up to 1 month in rats (up to 1,000 mg/kg daily, p.o.) or monkeys (up to 600 mg/kg daily, p.o.). Nonadverse, reversible clinical pathology findings without clinical or microscopic correlates included prolonged coagulation times at ≥60 mg/kg in rats and increases in transaminases at 600 mg/kg in monkeys. The safety pharmacology and nonclinical toxicity profiles of nirmatrelvir support clinical development and use of Paxlovid for treatment of COVID-19.
Citation: International Journal of Toxicology
PubDate: 2022-05-21T08:14:51Z
DOI: 10.1177/10915818221095489
- Evaluation of Pulmonary Effects of 3-D Printer Emissions From
Acrylonitrile Butadiene Styrene Using an Air-Liquid Interface Model of
Primary Normal Human-Derived Bronchial Epithelial Cells-
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Authors: Mariana T. Farcas, Walter McKinney, Jayme Coyle, Marlene Orandle, W. Kyle Mandler, Aleksandr B. Stefaniak, Lauren Bowers, Lori Battelli, Diana Richardson, Mary A. Hammer, Sherri A. Friend, Samantha Service, Michael Kashon, Chaolong Qi, Duane R. Hammond, Treye A. Thomas, Joanna Matheson, Yong Qian
Abstract: International Journal of Toxicology, Ahead of Print.
This study investigated the inhalation toxicity of the emissions from 3-D printing with acrylonitrile butadiene styrene (ABS) filament using an air-liquid interface (ALI) in vitro model. Primary normal human-derived bronchial epithelial cells (NHBEs) were exposed to ABS filament emissions in an ALI for 4 hours. The mean and mode diameters of ABS emitted particles in the medium were 175 ± 24 and 153 ± 15 nm, respectively. The average particle deposition per surface area of the epithelium was 2.29 × 107 ± 1.47 × 107 particle/cm2, equivalent to an estimated average particle mass of 0.144 ± 0.042 μg/cm2. Results showed exposure of NHBEs to ABS emissions did not significantly affect epithelium integrity, ciliation, mucus production, nor induce cytotoxicity. At 24 hours after the exposure, significant increases in the pro-inflammatory markers IL-12p70, IL-13, IL-15, IFN-γ, TNF-α, IL-17A, VEGF, MCP-1, and MIP-1α were noted in the basolateral cell culture medium of ABS-exposed cells compared to non-exposed chamber control cells. Results obtained from this study correspond with those from our previous in vivo studies, indicating that the increase in inflammatory mediators occur without associated membrane damage. The combination of the exposure chamber and the ALI-based model is promising for assessing 3-D printer emission-induced toxicity.
Citation: International Journal of Toxicology
PubDate: 2022-05-19T06:19:50Z
DOI: 10.1177/10915818221093605
- Safety Assessment of Hydroxyethyl-3,4-Methylenedioxyaniline HCl as Used in
Cosmetics-
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Authors: Laura N Scott, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Hydroxyethyl-3,4-Methylenedioxyaniline HCl, which is reported to function as a hair dye ingredient. The Panel reviewed relevant data provided in this safety assessment, and concluded that Hydroxyethyl-3,4-Methylenedioxyaniline HCl is safe for use as a hair dye ingredient in the present practices of use and concentrations described in this report. The Panel cautions that this ingredient should not be used in cosmetic products in which N-nitroso compounds can be formed.
Citation: International Journal of Toxicology
PubDate: 2022-05-16T07:47:43Z
DOI: 10.1177/10915818221099897
- Safety Assessment of Ethers and Esters of Ascorbic Acid as Used in
Cosmetics-
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Authors: Wilbur Johnson, Ivan J. Boyer, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 7 ethers and esters of ascorbic acid, which collectively function as antioxidants, skin-conditioning agents, skin protectants, fragrance ingredients, and skin bleaching agents in cosmetic products. The Panel reviewed relevant data relating to the safety of these ingredients, and concluded that the ethers and esters of ascorbic acid are safe in the present practices of use and concentration, as described in this safety assessment.
Citation: International Journal of Toxicology
PubDate: 2022-05-13T09:00:50Z
DOI: 10.1177/10915818221093545
- Safety Assessment of L-β-Aminoisobutyric Acid (L-BAIBA): Subchronic
Toxicity Study in Sprague Dawley Rats-
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Authors: Devanand Shanmugasundaram, Qiru Fan, Mingru Wang, Ronghua Yi, Ou Wang
Abstract: International Journal of Toxicology, Ahead of Print.
L-3-Aminoisobutyric acid (L-BAIBA) is an endogenous compound in human metabolism when thymine and valine undergo catabolism. L-BAIBA represents one of the two isomers of BAIBA in biological systems. BAIBA has been shown to reduce body fat percentage via an increase in fatty acid oxidation and a decrease in hepatic lipogenesis. However, no toxicological effects of L-BAIBA in animals or humans have been established. The present study was designed to evaluate the safety and toxic potentials of this compound, where L-BAIBA was administered orally to Sprague Dawley rats at 100, 300, and 900 mg/kg/day for 90 days. No treatment-related adverse effects were observed in any of the treatment groups. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of L-BAIBA was 900 mg/kg/day.
Citation: International Journal of Toxicology
PubDate: 2022-05-13T08:15:51Z
DOI: 10.1177/10915818221094487
- Safety Assessment of Carbonate Salts as Used in Cosmetics
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Authors: Wilbur Johnson, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Lillian J. Gill, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 6 carbonate salts which function as absorbents, bulking agents, opacifying agents, pH adjusters, buffering agents, abrasives, and oral care agents in cosmetic products. The Panel reviewed relevant data relating to the safety of these ingredients, and concluded that these carbonate salts are safe in the present practices of use and concentration in cosmetics when formulated to be non-irritating.
Citation: International Journal of Toxicology
PubDate: 2022-05-09T04:46:04Z
DOI: 10.1177/10915818221087202
- Safety Assessment of Rosa canina-derived Ingredients as Used in Cosmetics
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Authors: Wilbur Johnson, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Lillian J. Gill, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 12 Rosa canina-derived ingredients, which are reported to function as skin conditioning agents, fragrance ingredients, cosmetic astringents, anti-acne agents, abrasives, humectants, and exfoliants in cosmetic products. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching cumulative levels that may be hazardous to consumers. The Panel reviewed relevant data relating to the safety of these ingredients and concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating and non-sensitizing.
Citation: International Journal of Toxicology
PubDate: 2022-05-07T03:52:55Z
DOI: 10.1177/10915818221080088
- Safety Assessment of Bovine Milk Proteins and Protein Derivatives as Used
in Cosmetics-
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Authors: Christina L. Burnett, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 16 bovine milk proteins and protein-derived ingredients, which function mainly as skin and hair conditioning agents in personal care products. The Panel reviewed relevant data provided in this safety assessment, and concluded that these ingredients are safe in the present practices of use and concentration.
Citation: International Journal of Toxicology
PubDate: 2022-05-05T01:03:49Z
DOI: 10.1177/10915818221098137
- Safety Assessment of Hydrofluorocarbon 152a as Used in Cosmetics
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Authors: Christina L. Burnett, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Lillian J. Gill, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Hydrofluorocarbon 152a, which functions as a propellant in personal care products. The Panel reviewed relevant data provided in this safety assessment, and concluded that Hydrofluorocarbon 152a is safe in the present practices of use and concentration described in this safety assessment.
Citation: International Journal of Toxicology
PubDate: 2022-04-19T08:46:56Z
DOI: 10.1177/10915818221083516
- Safety Assessment of 1-Hydroxyethyl 4,5-Diamino Pyrazole Sulfate as Used
in Cosmetics-
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Authors: Christina L. Burnett, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Lillian J. Gill, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 1-Hydroxyethyl 4,5-Diamino Pyrazole Sulfate, which functions as an oxidative hair dye ingredient. The Panel reviewed relevant data provided in this safety assessment, and concluded that 1-Hydroxyethyl 4,5-Diamino Pyrazole Sulfate is safe in the present practices of use and concentration in oxidative hair dye formulations.
Citation: International Journal of Toxicology
PubDate: 2022-04-18T11:37:08Z
DOI: 10.1177/10915818221082093
- Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in
Cosmetics-
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Authors: Monice M. Fiume, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, Lillian J. Gill, Bart Heldreth
Abstract: International Journal of Toxicology, Ahead of Print.
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 46 butyl polyoxyalkylene ethers that share a common structural motif, namely a butyl chain (4 carbon alkyl chain) bound to a polyoxyalkylene (PPG, PEG, or both); 23 of these ethers were previously reviewed by the Panel, and 23 are reviewed herein for the first time. Most of the butyl polyoxyalkylene ethers have several functions in cosmetics, but the most common reported functions include hair conditioning agent and skin conditioning agent, and many reportedly function as solvents. Upon review of new data, including frequency and concentration of use, and data from previous Panel reports and on read-across analogs, the Panel concluded that these ingredients are safe in the present practices of use and concentration in cosmetics when formulated to be non-irritating.
Citation: International Journal of Toxicology
PubDate: 2022-02-11T03:57:37Z
DOI: 10.1177/10915818211059697
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