Unraveling How Membrane Nanostructure Changes Impact the Eye Irritation of Nonionic Alkyl Ethoxylate Surfactants.

Nonionic surfactants used in agri-spraying processes may cause varying degrees of corneal irritation when they come in direct contact with farmers' eyes, and the exact irritations are thought to be determined by how surfactants interact with corneal cell membranes. However, how nonionic surfactants interact with cell membranes at the molecular and nano levels remains largely unexplored. In this study, the interactions between nonionic surfactants (alkyl ethoxylate, CE) and lipid membranes were examined by membrane permeability measurement, quartz crystal microbalance with dissipation, dual polarization interferometry, confocal laser scanning microscopy, and neutron reflection, aiming to reveal complementary structural features at the molecular and nano levels.

Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny - Part IV: the ECETOC and CLE Proposal for a Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS).

Following the European Commission Endocrine Disruptor Criteria, substances shall be considered as having endocrine disrupting properties if they (a) elicit adverse effects, (b) have endocrine activity, and (c) the two are linked by an endocrine mode-of-action (MoA) unless the MoA is not relevant for humans. A comprehensive, structured approach to assess whether substances meet the Endocrine Disruptor Criteria for the thyroid modality (EDC-T) is currently unavailable. Here, the European Centre for Ecotoxicology and Toxicology of Chemicals Thyroxine Task Force and CropLife Europe propose a Function-Related euroevelopmental oxicity esting and ssessment cheme (Thyroid-NDT-TAS).

Weakly supervised anomaly detection coupled with Fourier transform infrared (FT-IR) spectroscopy for the identification of non-normal tissue.

The detection and classification of histopathological abnormal tissue constituents using machine learning (ML) techniques generally requires example data for each tissue or cell type of interest. This creates problems for studies on tissue that will have few regions of interest, or for those looking to identify and classify diseases of rarity, resulting in inadequate sample sizes from which to build multivariate and ML models. Regarding the impact on vibrational spectroscopy, specifically infrared (IR) spectroscopy, low numbers of samples may result in ineffective modelling of the chemical composition of sample groups, resulting in detection and classification errors.

Predictive liver lipid biomarker signature of Acetyl-coenzyme A carboxylase inhibitor related developmental toxicity in non-pregnant female Han Wistar rats - Lipidomics biomarker discovery and validation.

Introduction: Acetyl-coenzyme A carboxylase (ACCase) inhibition is an attractive herbicide target. However, issues with fetal developmental toxicity identified at the late stages of the development process can halt progression of previously promising candidates.

Objectives: To select and verify predictive lipid biomarkers of ACCase inhibition activity in vivo using liver samples obtained from early stage 7 day repeat dose studies in non-pregnant female Han Wistar rats that could be translated to developmental toxicity endpoints discovered during late-stage studies to provide an early screening tool.

Scientific and Regulatory Policy Committee Best Practices: Recommended ("Best") Practices for Informed (Non-blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies.

This article describes the Society of Toxicologic Pathology's (STP) five recommended ("best") practices for appropriate use of informed (non-blinded) versus masked (blinded) microscopic evaluation in animal toxicity studies intended for regulatory review. (1) Informed microscopic evaluation is the default approach for animal toxicity studies. (2) Masked microscopic evaluation has merit for confirming preliminary diagnoses for target organs and/or defining thresholds ("no observed adverse effect level" and similar values) identified during an initial informed evaluation, addressing focused hypotheses, or satisfying guidance or requests from regulatory agencies.

Infrared micro-spectroscopy coupled with multivariate and machine learning techniques for cancer classification in tissue: a comparison of classification method, performance, and pre-processing technique.

The visual detection, classification, and differentiation of cancers within tissues of clinical patients is an extremely difficult and time-consuming process with severe diagnosis implications. To this end, many computational approaches have been developed to analyse tissue samples to supplement histological cancer diagnoses. One approach is the interrogation of the chemical composition of the actual tissue samples through the utilisation of vibrational spectroscopy, specifically Infrared (IR) spectroscopy.

An evaluation of carcinogenicity predictors from short-term and sub chronic repeat-dose studies of agrochemicals in rats: Opportunities to refine and reduce animal use.

The aim of this study was to examine whether short term, repeat dose, rat studies provide sufficient information about potential carcinogenicity to enable predictions about the carcinogenic potential of agrochemicals to be made earlier in compound development. This study aimed to identify any correlations between toxicity findings obtained for short term rat studies (28 day and 90 day) and neoplastic findings obtained from 24 month rat carcinogenicity studies for agrochemical compounds (18 compounds) tested in Han Wistar and Sprague Dawley rats. The macroscopic pathology, microscopic pathology, hematology, biochemistry, organ weights, estrogen receptor activation and genotoxicity results were examined.

Research Relevant Background Lesions and Conditions: Ferrets, Dogs, Swine, Sheep, and Goats.

Animal models provide a valuable tool and resource for biomedical researchers as they investigate biological processes, disease pathogenesis, novel therapies, and toxicologic studies. Interpretation of animal model data requires knowledge not only of the processes/diseases being studied but also awareness of spontaneous conditions and background lesions in the model that can influence or even confound the study results. Species, breed/stock, sex, age, anatomy, physiology, diseases (noninfectious and infectious), and neoplastic processes are model features that can impact the results as well as study interpretation.

Species differences in phenobarbital-mediated UGT gene induction in rat and human liver microtissues.

Species differences in hepatic metabolism of thyroxine (T4) by uridine diphosphate glucuronosyl transferase (UGT) and susceptibility to thyroid hormone imbalance could underlie differences in thyroid carcinogenesis caused by hepatic enzyme inducers in rats and humans. To investigate this hypothesis we examined profiles of hepatic UGT induction by the prototypical CAR activator phenobarbital (PB) in rat and human liver 3D microtissues. The rationale for this approach was that 3D microtissues would generate data more relevant to humans.

Comparison of the predictive nature of the Genomic Allergen Rapid Detection (GARD) assay with mammalian assays in determining the skin sensitisation potential of agrochemical active ingredients.

Alternatives to mammalian testing are highly desirable to predict the skin sensitisation potential of agrochemical active ingredients (AI). The GARD assay, a stimulated, dendritic cell-like, cell line measuring genomic signatures, was evaluated using twelve AIs (seven sensitisers and five non-sensitisers) and the results compared with historical results from guinea pig or local lymph node assay (LLNA) studies. Initial GARD results suggested 11/12 AIs were sensitisers and six concurred with mammalian data.

Opinion on Current Use of Non-Blinded Versus Blinded Histopathologic Evaluation in Animal Toxicity Studies.

The Society of Toxicologic Pathology (STP) explored current institutional practices for selecting between non-blinded versus blinded histopathologic evaluation during Good Laboratory Practice (GLP)-compliant, regulatory-type animal toxicity studies using a multi-question survey and STP-wide discussion (held at the 2019 STP annual meeting). Survey responses were received from 107 individuals representing 83 institutions that collectively employ 589 toxicologic pathologists. Most responses came from industry (N = 46, mainly biopharmaceutical or contract research organizations) and consultants (N = 24).

Long-term exposure to commercially available sunscreens containing nanoparticles of TiO2 and ZnO revealed no biological impact in a hairless mouse model.

Background: The application of sunscreen is a critical component of a sun-safe strategy, however the possibility of unexpected, adverse outcomes resulting from long-term use of sunscreens containing nanoparticles of titanium dioxide (TiO2) and zinc oxide (ZnO) has not yet been examined. Here, immune-competent hairless mice were exposed over a 36-week period to weekly topical applications of sunscreens containing nanoparticles of ZnO or TiO2, or no metal oxide nanoparticles, with or without subsequent exposure to ultraviolet radiation (UVR). Control groups received no sunscreen applications, with or without UVR.

Histopathological analysis of the respiratory tract.

The basic anatomy of the mouse respiratory system is similar to that of other mammals and can be usefully examined under the light microscope in phenotyping studies, inhalation toxicity studies, and studies involving mouse models of human disease. In many studies, however, only the lungs are examined, leaving the possibility that phenotypic information from the majority of the conducting airways is lost. This unit provides standard approaches for tissue collection at necropsy and subsequent selection of a range of respiratory tissues for histological and pathological analysis.

Spontaneous nonneoplastic lesions in control Syrian hamsters in three 24-month long-term carcinogenicity studies.

Information about the incidence of spontaneously occurring, nonneoplastic background findings in Syrian hamsters is essential if Syrian hamsters are to be used for toxicity studies. Male and female Syrian hamsters of the strain Han:AURA from the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) breeding colony were maintained as control animals for carcinogenicity studies and were examined for the presence of nonneoplastic background findings either when they died or when the study was terminated. The nonneoplastic background lesions observed at an incidence of >50% (high), >25% (moderate), and >10% (low) in either male or female animals or in both sexes in one or more long-term studies are detailed.

Proceedings of the 2013 National Toxicology Program Satellite Symposium.

The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Portland, Oregon, in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion.

The Incidence of Lymphoplasmacytic Gastritis in the Fundus and Antrum of Cynomolgus Monkey ( Macaca fascicularis ) Stomachs.

Lymphoplasmacytic gastritis is a concern for toxicological pathologists reading preclinical, non-human primate toxicity studies because subtle gastric changes which could be treatment-related may be masked and gastritis lesions may be confused with treatment-related effects and thus a gastric finding may be incorrectly assigned as a treatment-related lesion. This paper discusses the incidence of lymphoplasmacytic gastritis in cynomolgus monkeys at a contract research organization. The incidence of lymphoplasmacytic gastritis in the fundus and antrum of control cynomolgus monkeys on 18 non-gastric compound studies, was scored.

Spontaneous neoplastic lesions in control Syrian hamsters in 6-, 12-, and 24-month short-term and carcinogenicity studies.

Male and female Syrian hamsters of the strain Han: AURA from the Fraunhofer Institute for Toxicology and Experimental Medicine breeding colony were maintained as control animals for five toxicity/carcinogenicity studies and were examined for the presence of neoplastic disease either when they died or when the study terminated. In total, 250 male animals and 250 female animals in three carcinogenicity studies were analyzed as well as the results of a 6-month study (fifty males and fifty females) and a 12-month study (fifty males and fifty females). In the 24-month studies, in the male animals, twenty-five organs were affected with malignant and benign tumors.

Prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in Australasia over a 5-y period.

Viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. The presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. Here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from Australasia submitted to a rodent health monitoring laboratory (Cerberus Sciences) from 2004 to 2009.

Posttransplant lymphoproliferative disorder associated with primate gamma-herpesvirus in cynomolgus monkeys used in pig-to-primate renal xenotransplantation and primate renal allotransplantation.

Background: A series of immunosuppressed cynomolgus monkeys were used in porcine-to-primate and primate-to-primate renal transplantation. In a number of animals nodal and extranodal lymphomas as well as areas of lymphoid hyperplasia in multiple organs (posttransplant lymphoproliferative disorder, PTLD) were recorded.

Methods: PTLD was characterized with respect to manifestation sites, histopathology, immunophenotype, and association with primate Epstein Barr-like Virus by in situ hybridization and quantitative polymerase chain reaction.