1,158 results match your criteria International Journal of Toxicology [Journal]


Addendum to Iwai and Hoberman (2014)-Reassessment of Developmental Toxicity of PFHxA in Mice.

Int J Toxicol 2019 Apr 14:1091581819837904. Epub 2019 Apr 14.

3 Integral Consulting Inc, Fayetteville, NY, USA.

This article presents a supplemental data analysis and evaluation of the findings from an oral (gavage) combined developmental and perinatal/postnatal reproduction toxicity study of the ammonium salt of perfluorohexanoic acid (CASRN: 21615-47-4) in Crl: CD-1(ICR) mice. The original study has been cited as supporting a lowest-observed-adverse-effects level of 175 mg/kg/d and no-observed-adverse-effects level of 35 mg/kg/d for developmental effects from perfluorohexanoic acid (PFHxA, CASRN: 307-24-4) in mice. The statistical analysis reported in 2014 was accurate in terms of quantifying statistical significance within phase 2 of the study. Read More

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http://dx.doi.org/10.1177/1091581819837904DOI Listing
April 2019
1 Read

Confounding Factors in the Interpretation of Preclinical Studies.

Int J Toxicol 2019 Apr 11:1091581819837157. Epub 2019 Apr 11.

4 Experimental Pathology Laboratories, Sterling, VA, USA.

A number of issues may arise during the conduct of a study which can complicate interpretation of in vitro and in vivo datasets. Speakers discussed the implications of differing interpretations and how to avoid complicating factors during study planning and execution. Consideration needs to be given to study design factors including defining objectives, consideration of expected pharmacological effects, dose selection and drug kinetics, species used, and vehicle selection. Read More

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http://journals.sagepub.com/doi/10.1177/1091581819837157
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http://dx.doi.org/10.1177/1091581819837157DOI Listing
April 2019
2 Reads

Editor's Note.

Authors:
Mary Beth Genter

Int J Toxicol 2019 Mar/Apr;38(2):87

International Journal of Toxicology.

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http://dx.doi.org/10.1177/1091581819839708DOI Listing

Evaluation of the Toxicity and Neurological Effects of Fulranumab in Adult Cynomolgus Monkeys.

Int J Toxicol 2019 Mar 10:1091581819830980. Epub 2019 Mar 10.

1 Janssen R&D, LLC, Spring House, PA, USA.

Fulranumab, an anti-human nerve growth factor antibody, was evaluated in a series of nonclinical toxicology studies. No treatment effects were observed in adolescent cynomolgus monkeys in standard design, repeat-dose toxicology studies of up to 6 months. Adverse effects on the developing nervous system were observed in offspring of pregnant cynomolgus monkeys treated with fulranumab. Read More

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http://dx.doi.org/10.1177/1091581819830980DOI Listing

Kidney Pathophysiology, Toxicology, and Drug-Induced Injury in Drug Development.

Authors:
Zaher A Radi

Int J Toxicol 2019 Mar 7:1091581819831701. Epub 2019 Mar 7.

1 Pfizer Worldwide Research and Development, Drug Safety R&D, Cambridge, MA, USA.

Anatomically, the kidneys are paired, bean-shaped (in most mammals), excretory organs that lie in the retroperitoneum. High blood flow to the kidneys, together with high oxygen consumption, makes them more vulnerable to exposure, via the circulation, and subsequent injury related to high concentrations of xenobiotics and chemicals. In preclinical drug development and safety assessment of new investigational drugs, changes in kidney structure and/or function following drug administration in experimental laboratory animals need to be put in context with interspecies differences in kidney functional anatomy, physiology, spontaneous pathologies, and toxicopathological responses to injury. Read More

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http://dx.doi.org/10.1177/1091581819831701DOI Listing
March 2019
2 Reads

Editor's Note.

Authors:
Mary Beth Genter

Int J Toxicol 2019 Jan/Feb;38(1)

International Journal of Toxicology.

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http://dx.doi.org/10.1177/1091581819825611DOI Listing
February 2019

A Global Overview of Poison Treatment Apps and Databases.

Int J Toxicol 2019 Mar/Apr;38(2):146-153. Epub 2019 Feb 21.

1 Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Acute poisoning is a serious health problem that is associated with high mortality. Management of acute poisoning cases in the critical care settings is the biggest challenge due to the difficulty in identification of poison involved. Immediate information about the poisoning and its management is crucial in the early diagnosis, treatment, and in the prevention of poisoning complications. Read More

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http://dx.doi.org/10.1177/1091581819827801DOI Listing
February 2019
1 Read

Nonclinical Toxicology and Toxicokinetic Profile of an Oral Lanthionine Synthetase C-Like 2 (LANCL2) Agonist, BT-11.

Int J Toxicol 2019 Mar/Apr;38(2):96-109. Epub 2019 Feb 21.

1 Landos Biopharma Inc, Blacksburg, VA, USA.

BT-11 is an orally active, gut-restricted investigational therapeutic targeting the lanthionine synthetase C-like 2 pathway with lead indications in ulcerative colitis (UC) and Crohn disease (CD), 2 manifestations of inflammatory bowel disease (IBD). In 5 mouse models of IBD, BT-11 is effective at oral doses of 8 mg/kg. BT-11 was also efficacious at nanomolar concentrations in primary human samples from patients with UC and CD. Read More

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http://dx.doi.org/10.1177/1091581819827509DOI Listing
February 2019
4 Reads

Language Consideration and Methodological Transparency in "Systematic" Reviews of Animal Toxicity Studies.

Int J Toxicol 2019 Mar/Apr;38(2):135-145. Epub 2019 Feb 21.

3 Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

This study evaluated the use of non-English literature (NEL) in systematic reviews (SRs) or meta-analyses (MAs) of animal-based toxicity or communicable disease (CD) studies. A secondary goal was to assess how grant funding, country of primary authorship, or study quality reporting influenced the use of NEL in these reviews. Inclusion criteria and data extraction forms were based on a pilot evaluation of a 10% random sample of reviews that were identified from a PubMed search (2006 to May 2017). Read More

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http://dx.doi.org/10.1177/1091581819827232DOI Listing
February 2019
1 Read

Toxicity of Pexacerfont, a Corticotropin-Releasing Factor Type 1 Receptor Antagonist, in Rats and Dogs.

Int J Toxicol 2019 Mar/Apr;38(2):110-120. Epub 2019 Feb 13.

2 Evansville, IL, USA.

Pexacerfont is a corticotropin-releasing factor subtype 1 receptor antagonist that was developed for the treatment of anxiety- and stress-related disorders. This report describes the results of repeat-dose oral toxicity studies in rats (3 and 6 months) and dogs (3 months and 1 year). Pexacerfont was well tolerated in all of these studies at exposures equal to or greater than areas under the curve in humans (clinical dose of 100 mg). Read More

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http://dx.doi.org/10.1177/1091581819827501DOI Listing
February 2019
2 Reads

CDER Experience With Juvenile Animal Studies for CNS Drugs.

Int J Toxicol 2019 Mar/Apr;38(2):88-95. Epub 2019 Feb 10.

2 Division of Psychiatry Products, Center for Drug Evaluation and Research (CDER), Office of New Drugs (OND), US Food and Drug Administration (FDA), Silver Spring, MD, USA.

A survey was undertaken to evaluate juvenile animal studies conducted for drug applications reviewed by the Center for Drug Evaluation and Research between 2009 and 2014. Some conclusions about the nonclinical pediatric safety assessment based on studies performed in support of central nervous system-active compounds are presented here. A total of 44 completed studies from 32 New Drug Applications submitted to the Divisions of Psychiatry and Neurology Products were evaluated. Read More

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http://dx.doi.org/10.1177/1091581818824313DOI Listing
February 2019
10 Reads

Lipoxygenase Protein Expression and Its Effect on Oxidative Stress Caused by Benzidine in Normal Human Urothelial Cell Lines.

Int J Toxicol 2019 Mar/Apr;38(2):121-128. Epub 2019 Feb 10.

1 Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, China.

Metabolic activation of indirect-acting carcinogens in the target organ is an effective mechanism of carcinogenesis. Lipoxygenase (LOX) can co-oxidize the bladder carcinogen benzidine (BZ). However, it is not entirely clear whether BZ is activated and which enzyme is involved in its activation in bladder epithelial cells. Read More

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http://dx.doi.org/10.1177/1091581819827495DOI Listing
February 2019
4 Reads
1.233 Impact Factor

Investigating the Value of Urine Volume, Creatinine, and Cystatin C for Urinary Biomarkers Normalization for Drug Development Studies.

Int J Toxicol 2019 Jan/Feb;38(1):12-22. Epub 2019 Jan 23.

2 Janssen Research & Development, LLC, San Diego, CA, USA.

Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there seems to be no standardized normalization method for analyzing these urinary biomarkers, as some users normalize with urinary creatinine (uCr), urine volume (uVol), or leave biomarker un-normalized. More recently, urinary cystatin C is also emerging as a urinary biomarker normalizer, given some of its characteristics as a glomerular filtration marker. Read More

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http://dx.doi.org/10.1177/1091581818819791DOI Listing
January 2019
1 Read

β- N-methylamino-L-alanine Inhibits Human Catalase Activity: Possible Implications for Neurodegenerative Disease Development.

Int J Toxicol 2019 Mar/Apr;38(2):129-134. Epub 2019 Jan 20.

1 Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa.

The naturally produced, nonprotein amino acid β- N-methylamino-l-alanine (BMAA) has been proposed as a significant contributor to sporadic neurodegenerative disease development worldwide. However, the existing hypothesized mechanisms of toxicity do not adequately explain the role of BMAA in neurodegenerative disease development. There is evidence for BMAA-induced enzyme inhibition, but the effect of BMAA on human stress response enzymes has received little attention, despite the well-described role of oxidative stress in neurodegenerative disease development. Read More

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http://dx.doi.org/10.1177/1091581818821921DOI Listing
January 2019
1 Read

Safety Study of Single-Dose Intravenously Administered DOTA-Siglec-9 Peptide in Sprague Dawley Rats.

Int J Toxicol 2019 Jan/Feb;38(1):4-11. Epub 2019 Jan 20.

2 Turku PET Centre, University of Turku, Turku, Finland.

The peptide-based radioactive compound [Ga]Ga-DOTA-Siglec-9 is a novel agent for imaging of inflammation with positron emission tomography. The drug target of [Ga]Ga-DOTA-Siglec-9 is vascular adhesion protein 1. Previous studies have obtained promising results with [Ga]Ga-DOTA-Siglec-9 in experimental animals. Read More

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http://dx.doi.org/10.1177/1091581818821606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357174PMC
January 2019
1 Read

A Proof-of-Concept Evaluation of JTPc and Tp-Tec as Proarrhythmia Biomarkers in Preclinical Species: A Retrospective Analysis by an HESI-Sponsored Consortium.

Int J Toxicol 2019 Jan/Feb;38(1):23-32. Epub 2018 Dec 19.

1 GREPAQ (Groupe de recherche en pharmacologie animale du Québec), Université de Montréal, St-Hyacinthe, Quebec, Canada.

Introduction:: Based on the ICH S7B and E14 guidance documents, QT interval (QTc) is used as the primary in vivo biomarker to assess the risk of drug-induced torsades de pointes (TdP). Clinical and nonclinical data suggest that drugs that prolong the corrected QTc with balanced multiple ion channel inhibition (most importantly the l-type calcium, Cav1.2, and persistent or late inward sodium current, Nav1. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818813601
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http://dx.doi.org/10.1177/1091581818813601DOI Listing
December 2018
14 Reads

Percutaneous Hepatic Perfusion With Filtered Melphalan for Localized Treatment of Metastatic Hepatic Disease: A Risk Assessment.

Int J Toxicol 2018 Nov 19:1091581818811306. Epub 2018 Nov 19.

4 Aclairo Pharmaceutical Development Group Inc, Vienna, VA, USA.

Regional therapies for metastatic liver disease have garnered interest in recent years due to technological advances in drug delivery. A percutaneous hepatic perfusion (PHP) using a newly developed generation 2 (GEN2) filtration system was designed to mitigate systemic toxicity and cardiovascular risk associated with hepatic blood filtration during hepatic artery infusion of the chemotherapy drug melphalan. The GEN2 system was evaluated in healthy swine, and plasma samples were assessed for clinical chemistry, melphalan toxicokinetics (TK), inflammatory cytokines, catecholamines, hematological, and cardiac biomarkers. Read More

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http://dx.doi.org/10.1177/1091581818811306DOI Listing
November 2018
20 Reads

Toxicity and Mutagenicity Evaluation Following RISUG Contraception Reversal in Rats.

Int J Toxicol 2018 Nov 1:1091581818809473. Epub 2018 Nov 1.

1 Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur, Rajasthan, India.

Reestablishment of fertility, after a male contraceptive method, is of great concern. In this context, RISUG (Reversible Inhibition of Sperm Under Guidance) has been evaluated for its mutagenicity following reversibility with dimethyl sulfoxide (DMSO)/sodium bicarbonate (NaHCO) in Wistar albino rats. Animals were divided into 7 groups, namely, sham-operated control, vas occlusion with RISUG for 90 and 360 days, reversal with DMSO and NaHCO after 90 and 360 days, respectively. Read More

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http://dx.doi.org/10.1177/1091581818809473DOI Listing
November 2018
15 Reads

Long-Term Systemic Treatment With Methamphetamine Causes Retinal Damage in CD1 Mice.

Int J Toxicol 2018 Oct 29:1091581818809356. Epub 2018 Oct 29.

2 Department of Ophthalmology, Shenzhen Second People's Hospital, Shenzhen, People's Republic of China.

As a powerful psychostimulant with high potential for abuse, methamphetamine (Meth) could cause long-lasting abnormalities in retinas. The purpose of this study was to investigate the effects of systemic administration of Meth at low dose on retinal damage and understand the underlying mechanisms of pathology. CD1 mice were treated with 0. Read More

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http://dx.doi.org/10.1177/1091581818809356DOI Listing
October 2018
27 Reads

Embracing Transparency Through Data Sharing.

Int J Toxicol 2018 Oct 3:1091581818803880. Epub 2018 Oct 3.

1 PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.

Low rates of reproducibility and translatability of data from nonclinical research have been reported. Major causes of irreproducibility include oversights in study design, failure to characterize reagents and protocols, a lack of access to detailed methods and data, and an absence of universally accepted and applied standards and guidelines. Specific areas of concern include uncharacterized antibodies and cell lines, the use of inappropriate sampling and testing protocols, a lack of transparency and access to raw data, and deficiencies in the translatability of findings to the clinic from studies using animal models of disease. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818803880
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http://dx.doi.org/10.1177/1091581818803880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291903PMC
October 2018
3 Reads

"Not Everything That Shakes Is a Seizure": Making the Determination of Test Article-Induced Convulsions in Toxicology Studies.

Int J Toxicol 2018 Nov/Dec;37(6):422-433. Epub 2018 Sep 24.

1 Neurobehavioral Sciences Department, MPI Research (A Charles River Company), Mattawan, MI, USA.

Spontaneous unexpected events occasionally develop during the course of rodent preclinical toxicology studies. The presentation of serious adverse events on animal studies may require notification of these events to the Food and Drug Administration if the events are most likely the direct result of test article administration. Classical conditioning of emotional responses may occur over the course of a repeat-dose study and clinical observation calls of "convulsions" are reported to the study director and/or staff veterinarians. Read More

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http://dx.doi.org/10.1177/1091581818796444DOI Listing
March 2019
2 Reads

Editor's Note.

Authors:
Mary Beth Genter

Int J Toxicol 2018 Sep/Oct;37(5):351

International Journal of Toxicology.

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http://dx.doi.org/10.1177/1091581818800031DOI Listing
March 2019
2 Reads

Safety Assessment of PEGs Cocamine and Related Ingredients as Used in Cosmetics.

Int J Toxicol 2018 Sep/Oct;37(2_suppl):10S-60S

5 Executive Director, Cosmetic Ingredient Review Executive Director, Washington, DC, USA.

The Cosmetic Ingredient Review Expert Panel assessed the safety of 47 polyethylene glycols (PEGs) cocamine and related ingredients, which are reported to function mostly as surfactants and antistatic agents. The Panel reviewed the relevant data and developed a framework to satisfy previously identified data deficiencies for this group of materials as well as extend the scope of related materials covered by the analysis. The irritation potential of these ingredients is consistent with the surface active properties that are characteristic of surfactants. Read More

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http://dx.doi.org/10.1177/1091581818794417DOI Listing
February 2019
11 Reads
1.233 Impact Factor

Safety Assessment of PEG-150 Pentaerythrityl Tetrastearate as Used in Cosmetics.

Int J Toxicol 2018 Sep/Oct;37(2_suppl):5S-9S

4 Cosmetic Ingredient Review Executive Director, Washington, DC, USA.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of polyethylene glycol (PEG)-150 pentaerythrityl tetrastearate, which functions as a viscosity-increasing agent-aqueous in cosmetic products and is being used at concentrations up to 5%. Given the chemical structure (large molecule), skin penetration is not likely. The available toxicity data and the low ingredient use concentrations suggest that systemic toxicity would not be likely even if percutaneous absorption were to occur. Read More

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http://dx.doi.org/10.1177/1091581818794457DOI Listing
February 2019
14 Reads
1.233 Impact Factor

Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics.

Int J Toxicol 2018 Sep/Oct;37(2_suppl):61S-94S

4 Cosmetic Ingredient Review Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 14 tocopherols and tocotrienols and concluded these ingredients are safe as used in cosmetics. The tocopherols are reported to function in cosmetics as antioxidants or skin-conditioning agents; in contrast, tocotrienols are not reported to function as an antioxidants in cosmetics but as a light stabilizer, oral care agent, or skin-conditioning agent. The Panel reviewed the new and existing animal and clinical data to determine the safety of these ingredients and found it appropriate to extrapolate the existing information to conclude on the safety of all the tocopherols and tocotrienols. Read More

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http://dx.doi.org/10.1177/1091581818794455DOI Listing
February 2019
8 Reads
1.233 Impact Factor

Paradoxical Protective Effect of Perfluorooctanesulfonic Acid Against High-Fat Diet-Induced Hepatic Steatosis in Mice.

Int J Toxicol 2018 Sep/Oct;37(5):383-392. Epub 2018 Aug 22.

1 Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.

Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant with worldwide bioaccumulation due to a very long half-life. Perfluorooctanesulfonic acid exposure results in significant hepatic effects including steatosis, proliferation, hepatomegaly, and in rodents, carcinogenesis. The objective of this study was to determine whether PFOS exposure exacerbates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis pathogenesis. Read More

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http://dx.doi.org/10.1177/1091581818790934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150807PMC
March 2019
20 Reads

Characterization of the Testicular Toxicity of 3-Nitro-1,2,4-Triazol-5-One and 2,4-Dinitroanisole in Rats ( Rattus norvegicus).

Int J Toxicol 2018 Sep/Oct;37(5):364-372. Epub 2018 Aug 22.

4 US Army Medical Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA.

Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) and dinitroanisole (2,4-dinitroanisole; DNAN), insensitive energetic materials used in explosive formulations, have induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests. To identify the target site of testicular toxicity of NTO and DNAN, Sprague Dawley rats were orally dosed with NTO (500 mg/kg/d) or DNAN (50 or 100 mg/kg/d) in corn oil for 1, 3, 7, or 14 days. Degeneration of germinal epithelium occurred in multiple tubule stages on days 7 and 14 in treated rats. Read More

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http://dx.doi.org/10.1177/1091581818789878DOI Listing
March 2019
4 Reads

How Did I Ever Get Here? The 2018 Mildred S. Christian Award Winner.

Authors:
Linda S Birnbaum

Int J Toxicol 2018 Jul/Aug;37(4):272-275

1 National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, NC, USA.

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http://dx.doi.org/10.1177/1091581818781316DOI Listing
March 2019
2 Reads

Editor's Note.

Authors:
Mary Beth Genter

Int J Toxicol 2018 Jul/Aug;37(4):271

Editor-in-Chief, International Journal of Toxicology.

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http://dx.doi.org/10.1177/1091581818789698DOI Listing
March 2019
3 Reads

Effect of Cyclophosphamide Treatment on Central and Effector Memory T Cells in Mice.

Int J Toxicol 2018 Sep/Oct;37(5):373-382. Epub 2018 Jun 20.

1 Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland.

Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. The important question is whether cyclophosphamide (CP), as immunosuppressive agent used in cancer therapy and in some autoimmune diseases, may act on the memory T-cell population. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818780128
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http://dx.doi.org/10.1177/1091581818780128DOI Listing
March 2019
11 Reads

Quantitative Evaluation of Cytochrome P450 3A4 Inhibition and Hepatotoxicity in HepaRG 3-D Spheroids.

Int J Toxicol 2018 Sep/Oct;37(5):393-403. Epub 2018 Jun 20.

1 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea.

Predicting drug-drug interactions (DDIs) is an important step during drug development to avoid unexpected side effects. Cytochrome P450 (CYP) 3A4 is the most abundant human hepatic phase I enzyme, which metabolizes >50% of therapeutic drugs. Therefore, it is essential to test the potential of a drug candidate to induce CYP3A4 expression or inhibit its activity. Read More

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http://dx.doi.org/10.1177/1091581818780149DOI Listing
March 2019
17 Reads

Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study.

Int J Toxicol 2018 Jul/Aug;37(4):276-284. Epub 2018 Jun 19.

1 West Virginia University Cancer Institute, West Virginia University, Morgantown, WV, USA.

Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident. Read More

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http://dx.doi.org/10.1177/1091581818779038DOI Listing
March 2019
26 Reads

Development of a Phototoxicity Testing Strategy for Accurate Photosafety Evaluation of Pharmaceuticals Based on the Assessment of Possible Melanin-Binding Effects.

Int J Toxicol 2018 Jul/Aug;37(4):296-307. Epub 2018 Jun 13.

1 Charles River Laboratories Den Bosch B.V., DD 's-Hertogenbosch, the Netherlands.

Drug-induced phototoxicity occurs when drugs absorb natural sunlight, leading to chemical reactions causing cellular damage. Distribution to light-exposed tissues is critical and is enhanced by binding to melanin. The International Council on Harmonization S10 guidance document on photosafety evaluation of pharmaceuticals states that although nonpigmented skin tends to be more sensitive than pigmented skin, pigmented skin models should be considered for drugs that bind significantly to melanin. Read More

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http://dx.doi.org/10.1177/1091581818777998DOI Listing
March 2019
4 Reads

Comparative Assessment on Mechanism Underlying Renal Toxicity of Commercial Formulation of Roundup Herbicide and Glyphosate Alone in Male Albino Rat.

Int J Toxicol 2018 Jul/Aug;37(4):285-295. Epub 2018 Jun 11.

2 Department of Pure and Applied Zoology, College of Bioscience, Federal University of Agriculture, Abeokuta, Nigeria.

There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate. We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat. Fifty-six adult male rats randomized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3. Read More

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http://dx.doi.org/10.1177/1091581818779553DOI Listing
March 2019
22 Reads

Behavioral, Pharmacokinetic, and Cardiovascular Evaluation of Candidate Oximes in African Green Monkeys.

Int J Toxicol 2018 Sep/Oct;37(5):352-363. Epub 2018 Jun 7.

1 United States Army Medical Research Institute of Chemical Defense, MD, USA.

Oxime reactivators are critical antidotes after organophosphate pesticide or nerve agent poisoning, directly restoring the function of inhibited acetylcholinesterase. In the continuing search for more broad-spectrum acetylcholinesterase reactivators, this study evaluated one of the leading next-generation oxime reactivators: methoxime, (1,1'-trimethylene bis[4-(hydroxyimino)methyl]pyridinium dichloride (MMB-4). The pharmacokinetics of both salts of MMB-4 (dichloride [2Cl] and dimethanesulphonate [DMS]) were characterized across a range of relevant doses (19, 58, and 116 µmol/kg, intramuscular) in a nonhuman primate model (male African green monkeys), and only subtle differences were observed between the salts. Read More

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http://dx.doi.org/10.1177/1091581818779362DOI Listing
March 2019
5 Reads

Inhibition of Mast Cell Degranulation With Cromolyn Sodium Exhibits Organ-Specific Effects in Polycystic Kidney (PCK) Rats.

Int J Toxicol 2018 Jul/Aug;37(4):308-326. Epub 2018 Jun 3.

1 Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.

Autosomal recessive polycystic kidney disease (ARPKD) is a monogenic disease characterized by development of hepatorenal cysts, pericystic fibrosis, and inflammation. Previous studies show that mast cell (MC) mediators such as histamine induce proliferation of cholangiocytes. We observed robust MC accumulation around liver cysts, but not kidney cysts, in polycystic kidney (PCK) rats (an animal model of ARPKD). Read More

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http://dx.doi.org/10.1177/1091581818777754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027616PMC
March 2019
15 Reads

Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats.

Int J Toxicol 2018 Jul/Aug;37(4):327-334. Epub 2018 Jun 3.

3 Psychiatry Department, Faculty of Medicine, Minia University, Menia, Egypt.

Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin-norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. Read More

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http://dx.doi.org/10.1177/1091581818777470DOI Listing
March 2019
51 Reads
1.233 Impact Factor

Safety Assessment of Polyether Lanolins as Used in Cosmetics.

Int J Toxicol 2018 May/Jun;37(1_suppl):19S-27S

4 Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 39 polyether lanolin ingredients as used in cosmetics. These ingredients function mostly as hair conditioning agents, skin conditioning agent-emollients, and surfactant-emulsifying agents. The Panel reviewed available animal and clinical data, from previous CIR safety assessments of related ingredients and components. Read More

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http://dx.doi.org/10.1177/1091581817740120DOI Listing
February 2019
7 Reads
1.233 Impact Factor

Safety Assessment of Alkyl Betaines as Used in Cosmetics.

Int J Toxicol 2018 May/Jun;37(1_suppl):28S-46S

4 Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 11 alkyl betaines as used in cosmetics. These ingredients are reported to function as hair and skin conditioning agents, antistatic agents, surfactants-cleansing agents, and viscosity-increasing agents in cosmetic products. Although there are data gaps, the shared chemical core structure, similar functions and concentrations of use in cosmetics, and the expected similarities in physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group. Read More

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http://dx.doi.org/10.1177/1091581818773354DOI Listing
February 2019
10 Reads
1.233 Impact Factor

Safety Assessment of Tromethamine, Aminomethyl Propanediol, and Aminoethyl Propanediol as Used in Cosmetics.

Int J Toxicol 2018 May/Jun;37(1_suppl):5S-18S

4 Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of tromethamine, aminomethyl propanediol, and aminoethyl propanediolas used in cosmetics. All 3 ingredients are reported to function in cosmetics as pH adjusters, and tromethamine and aminomethyl propanediol are also reported to function as fragrance ingredients. The Panel reviewed relevant animal and human data related to these ingredients, along with a previous safety assessment of aminomethyl propanediol. Read More

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http://dx.doi.org/10.1177/1091581817738242DOI Listing
February 2019
8 Reads
1.233 Impact Factor

Safety Assessment of Magnesium Sulfate as Used in Cosmetics.

Int J Toxicol 2018 May/Jun;37(1_suppl):47S-54S

4 Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of magnesium sulfate, which functions as a bulking agent in cosmetic products and is reportedly used at concentrations up to 11% and 25% in leave-on and rinse-off products, respectively. The Panel noted that the history of safe medical use of magnesium sulfate provides further confidence that there are no significant toxicity concerns relating to systemic exposure to this ingredient after cosmetic product application. Furthermore, the extensive clinical experience of the Panel, including the results of numerous patch tests, indicates that magnesium salts do not have the potential to induce sensitization. Read More

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http://dx.doi.org/10.1177/1091581818773355DOI Listing
February 2019
4 Reads
1.233 Impact Factor

Safety Assessment of Hydrolyzed Wheat Protein and Hydrolyzed Wheat Gluten as Used in Cosmetics.

Int J Toxicol 2018 May/Jun;37(1_suppl):55S-66S

4 Executive Director, Cosmetic Ingredient Review, Washington, DC, USA.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the product use, formulation, and safety data on hydrolyzed wheat protein and hydrolyzed wheat gluten, which function as skin- and hair-conditioning agents. The Panel determined that data from clinical and laboratory studies were sufficient to demonstrate that these ingredients will not elicit type 1 immediate hypersensitivity reactions in sensitized individuals and will not induce sensitization when the polypeptide lengths of the hydrolysates do not exceed 30 amino acids. The Panel concluded that hydrolyzed wheat gluten and hydrolyzed wheat protein are safe for use in cosmetics when formulated to restrict peptides to an average molecular weight of 3,500 Da or less. Read More

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http://dx.doi.org/10.1177/1091581818776013DOI Listing
February 2019
6 Reads
1.233 Impact Factor

Skin and Eye Irritation Assessment of Oil Palm ( Elaeis guineensis) Leaf Extract for Topical Application.

Int J Toxicol 2018 Jul/Aug;37(4):335-343. Epub 2018 May 7.

1 Malaysian Palm Oil Board, Bandar Baru Bangi, Kajang, Malaysia.

Many types of phytochemicals have been found to be present in oil palm leaf and could potentially be used as functional ingredients for skincare product. However, as of today, there is no published report on hazard identification and safety assessment of oil palm ( Elaeis guineensis) leaf extract (OPLE), particularly on skin and eye irritation. In this study, potential hazard of OPLE on skin and eye irritation was evaluated as an initial step to the safety assessment of OPLE. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818773979
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http://dx.doi.org/10.1177/1091581818773979DOI Listing
March 2019
16 Reads

Investigation of the Genotoxicity of Aluminum Oxide, β-Tricalcium Phosphate, and Zinc Oxide Nanoparticles In Vitro.

Int J Toxicol 2018 May/Jun;37(3):216-222. Epub 2018 May 4.

2 Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.

The aim of this study was to investigate the genotoxicity of aluminum oxide (AlO), β-tricalcium phosphate (β-TCP) (Ca(PO)), and zinc oxide (ZnO) nanoparticles (NPs) that were 4.175, 9.058, and 19. Read More

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http://dx.doi.org/10.1177/1091581818775709DOI Listing
January 2019
7 Reads

Safety Evaluation of Soy Leghemoglobin Protein Preparation Derived From Pichia pastoris, Intended for Use as a Flavor Catalyst in Plant-Based Meat.

Int J Toxicol 2018 May/Jun;37(3):241-262. Epub 2018 Apr 11.

1 Impossible Foods Inc., Redwood City, CA, USA.

The leghemoglobin protein (LegH) from soy ( Glycine max) expressed in Pichia pastoris (LegH preparation, LegH Prep) imparts a meat-like flavor profile onto plant-based food products. The safety of LegH Prep was evaluated through a series of in vitro and in vivo tests. The genotoxic potential of LegH Prep was assessed using the bacterial reverse mutation assay (Ames test) and the in vitro chromosome aberration test. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818766318
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http://dx.doi.org/10.1177/1091581818766318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956568PMC
January 2019
12 Reads

Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease.

Int J Toxicol 2018 Mar/Apr;37(2):144-154

2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Polycystic kidney disease is characterized by the progressive development of kidney cysts and declining renal function with frequent development of cysts in other organs including the liver. The polycystic kidney (PCK) rat is a rodent model of polycystic liver disease that has been used to study hepatorenal disease progression and evaluate pharmacotherapeutic interventions. Biomarkers that describe the cyst progression, liver impairment, and/or hepatic cyst burden could provide clinical utility for this disease. Read More

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http://dx.doi.org/10.1177/1091581818760746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877312PMC
March 2019
18 Reads

Editor's Note.

Authors:
Mary Beth Genter

Int J Toxicol 2018 Mar/Apr;37(2):115

International Journal of Toxicology.

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http://dx.doi.org/10.1177/1091581818767641DOI Listing
March 2019
5 Reads

Ototoxicity: The Radical Drum Beat and Rhythm of Cochlear Hair Cell Life and Death.

Int J Toxicol 2018 May/Jun;37(3):195-206. Epub 2018 Mar 25.

1 Neurobehavioral Sciences Department, MPI Research, Inc., Mattawan, MI, USA.

The function and structure of the auditory information processing system establishes a unique sensory environment for the "perfect storm." The battle between life and death pits the cascade of an apoptotic storm, programmed cell death cascades, against simple cell death (necrosis) pathways. Live or die, the free radical biology of oxygen and hydroxylation, and the destruction of transition metal migration through the mechanical gate sensory processes of the hair cell lead to direct access to the cytoplasm, cytoplasmic reticulum, and mitochondria of the inner workings of the hair cells. Read More

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http://dx.doi.org/10.1177/1091581818761128DOI Listing
January 2019
5 Reads

Genotoxic Effects Due to Exposure to Chromium and Nickel Among Electroplating Workers.

Int J Toxicol 2018 May/Jun;37(3):234-240. Epub 2018 Mar 19.

1 Occupational and Environmental Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Using chromium and nickel for electroplating is important in many industries. This process induces variable adverse health effects among exposed workers. The aim of this study is to detect the genotoxic effects of combined exposure to chromium and nickel among electroplating workers. Read More

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http://dx.doi.org/10.1177/1091581818764084DOI Listing
January 2019
8 Reads

Trichloroethylene Alters Th1/Th2/Th17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity.

Int J Toxicol 2018 Mar/Apr;37(2):155-163. Epub 2018 Mar 19.

1 Institute of Dermatology, Anhui Medical University, Hefei, Anhui, People's Republic of China.

The role of environmental factors in autoimmune diseases has been increasingly recognized. While major advance has been made in understanding biological pathogen-induced autoimmune diseases, chemically triggered autoimmunity is poorly understood. Trichloroethylene (TCE), a common environmental pollutant, has recently been shown to induce autoimmunity. Read More

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http://dx.doi.org/10.1177/1091581818757036DOI Listing
March 2019
20 Reads