Current methods for cancer risk assessment are resource-intensive and not feasible for most of the thousands of untested chemicals. In earlier studies, we developed a new approach methodology (NAM) to identify liver tumorigens using gene expression biomarkers and associated tumorigenic activation levels (TALs) after short-term exposures in rats. The biomarkers are used to predict the six most common rodent liver cancer molecular initiating events.
View Article and Find Full Text PDFBackground: Children with Disinhibited Social Engagement Disorder (DSED) have specific difficulties with indiscriminate sociability, yet little is known about their broader social competencies as DSED tends not to be identified within samples in the wider 'maltreatment literature.'
Aim: To systematically review the literature to determine the social competencies of children with DSED.
Methods: A comprehensive search following PRISMA guidelines was undertaken using PsycINFO, Medline, Embase, and Cumulative Index to Nursing & Allied Health.
Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations.
View Article and Find Full Text PDFInhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced.
View Article and Find Full Text PDFThe United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides.
View Article and Find Full Text PDFMany sectors have seen complete replacement of the rabbit eye test with reproducible and relevant and methods to assess the eye corrosion/irritation potential of chemicals. However, the rabbit eye test remains the standard test used for agrochemical formulations in some countries. Therefore, two defined approaches (DAs) for assessing conventional agrochemical formulations were developed, using the EpiOcular Eye Irritation Test (EIT) [Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 492] and the Bovine Corneal Opacity and Permeability (OECD TG 437; BCOP) test with histopathology.
View Article and Find Full Text PDFFolia Phoniatr Logop
June 2024
Introduction: This study examined the utility of multiple second formant (F2) slope metrics to capture differences in speech production for individuals with dysarthria and healthy controls as a function of speaking rate. In addition, the utility of F2 slope metrics for predicting severity of intelligibility impairment in dysarthria was examined.
Methods: Twenty three speakers with Parkinson's disease and mild to moderate hypokinetic dysarthria (HD), 9 speakers with various neurological diseases and mild to severe ataxic or ataxic-spastic dysarthria (AD), and 26 age-matched healthy control speakers (CON) participated in a sentence repetition task.
Objective: Digital health tools are increasingly being recognised as effective interventions in monitoring chronic health conditions. This systematic review addressed how digital health is currently utilised in patients with head and neck cancer as an adjunct to care.
Method: Studies of the development or evaluation of an eHealth, telemedicine or telemonitoring tool were eligible.
Progress in developing new tools, assays, and approaches to assess human hazard and health risk provides an opportunity to re-evaluate the necessity of dog studies for the safety evaluation of agrochemicals. A workshop was held where participants discussed the strengths and limitations of past use of dogs for pesticide evaluations and registrations. Opportunities were identified to support alternative approaches to answer human safety questions without performing the required 90-day dog study.
View Article and Find Full Text PDFIntroduction: Isothiazolinones (ITs) are widely used as antimicrobial preservatives in cosmetics and as additives for preservation of consumer and industrial products to control bacteria, fungi, and algae. Although they are effective biocides, they have the potential to produce skin irritation and sensitization, which poses a human health hazard. In this project, we evaluated nonanimal defined approaches (DAs) for skin sensitization that can provide point-of-departure estimates for use in quantitative risk assessment for ITs.
View Article and Find Full Text PDFDespite the impacts of neurodegeneration on speech function, little is known about how to comprehensively characterize the resulting speech abnormalities using a set of objective measures. Quantitative phenotyping of speech motor impairments may have important implications for identifying clinical syndromes and their underlying etiologies, monitoring disease progression over time, and improving treatment efficacy. The goal of this research was to investigate the validity and classification accuracy of comprehensive acoustic-based articulatory phenotypes in speakers with distinct neurodegenerative diseases.
View Article and Find Full Text PDFObjective: Parkinson's Disease (PD) is associated with both motor and non-motor problems, such as cognitive impairment. Particular focus in this area has been on the relationship between language impairment and decline in other cognitive functions, with the literature currently inconclusive on how the nature and degree of language impairment relate to cognition or other measures of disease severity. In addition, little information is available on how language problems identified in experimental task set-ups relate to competency in self-generated language paradigms such as picture description, monologues or conversations.
View Article and Find Full Text PDFBackground: Progressive ataxias frequently lead to speech disorders and consequently impact on communication participation and psychosocial wellbeing. Whilst recent studies demonstrate the potential for improvements in these areas, these treatments generally require intensive input which can reduce acceptability of the approach. A new model of care-ClearSpeechTogether-is proposed which maximises treatment intensity whilst minimising demands on clinician.
View Article and Find Full Text PDFRobust and efficient processes are needed to establish scientific confidence in new approach methodologies (NAMs) if they are to be considered for regulatory applications. NAMs need to be fit for purpose, reliable and, for the assessment of human health effects, provide information relevant to human biology. They must also be independently reviewed and transparently communicated.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
August 2022
U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives.
View Article and Find Full Text PDFDL-glufosinate ammonium (DL-GLF) is a registered herbicide for which a guideline Developmental Neurotoxicity (DNT) study has been conducted. Offspring effects included altered brain morphometrics, decreased body weight, and increased motor activity. Guideline DNT studies are not available for its enriched isomers L-GLF acid and L-GLF ammonium; conducting one would be time consuming, resource-intensive, and possibly redundant given the existing DL-GLF DNT.
View Article and Find Full Text PDFRodent cancer bioassays have been long-required studies for regulatory assessment of human cancer hazard and risk. These studies use hundreds of animals, are resource intensive, and certain aspects of these studies have limited human relevance. The past 10 years have seen an exponential growth of new technologies with the potential to effectively evaluate human cancer hazard and risk while reducing, refining, or replacing animal use.
View Article and Find Full Text PDFBackground: Progressive ataxias are complex disorders that result in a wide variety of symptoms. Whilst we currently have a relatively good understanding of the symptom patterns associated with the various types of ataxia, and how these diseases progress over time, their impact on the person with ataxia is less well understood. In addition, little is known about how carers, friends and families are affected by them.
View Article and Find Full Text PDFTop dose selection for repeated dose animal studies has generally focused on identification of apical endpoints, use of the limit dose, or determination of a maximum tolerated dose (MTD). The intent is to optimize the ability of toxicity tests performed in a small number of animals to detect effects for hazard identification. An alternative approach, the kinetically derived maximum dose (KMD), has been proposed as a mechanism to integrate toxicokinetic (TK) data into the dose selection process.
View Article and Find Full Text PDFDysprosody is a hallmark of dysarthria, which can affect the intelligibility and naturalness of speech. This includes sentence accent, which helps to draw listeners' attention to important information in the message. Although some studies have investigated this feature, we currently lack properly validated automated procedures that can distinguish between subtle performance differences observed across speakers with dysarthria.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
October 2021
Acute oral toxicity classifications are based on the estimated chemical dose causing lethality in 50 % of laboratory animals tested (LD). Given the large number of pesticide registration applications that require acute toxicity data, an alternative to the in vivo test could greatly reduce animal testing. The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Mixtures Equation estimates the acute toxicity of mixtures using the toxicities of mixture components.
View Article and Find Full Text PDFThere are multiple and eye irritation and corrosion test methods that are available as internationally harmonized test guidelines for regulatory use. Despite their demonstrated usefulness to a broad range of substances through inter-laboratory validation studies, they have not been widely adopted for testing agrochemical formulations due to a lack of concordance with parallel results from the traditional regulatory test method for this endpoint, the rabbit eye test. The inherent variability of the rabbit test, differences in the anatomy of the rabbit and human eyes, and differences in modelling exposures in rabbit eyes relative to human eyes contribute to this lack of concordance.
View Article and Find Full Text PDFDermal toxicity is driven by the ability of a substance to penetrate the skin. The “triple pack” approach, which combines in vivo rat, in vitro rat, and in vitro human data, is used to calculate an estimated human dermal absorption factor (DAF). To assess the feasibility of deriving a DAF using only in vitro data, we retrospectively evaluated agrochemical formulations to compare the DAF derived from each individual method to the DAF generated from the triple pack approach.
View Article and Find Full Text PDFInt J Lang Commun Disord
September 2020
Background: There is increasing recognition of the impact that dementia has upon swallowing and at mealtimes, and the significant effect this can have on people with dementia's health and well-being. However, there remains a paucity of evidence for assessment and intervention practices for dysphagia and mealtime difficulties. Furthermore, there is a limited understanding of how speech and language therapists (SLTs) support people with these dementia-related issues and what are the barriers and facilitators to practice.
View Article and Find Full Text PDFFolia Phoniatr Logop
December 2021
Introduction: Children with dysarthria due to cerebral palsy (CP) can experience problems manipulating intensity, fundamental frequency, and duration to signal sentence stress in an utterance. Pauses have been identified as a potential additional cue for stress-marking, which could compensate for this deficit.
Objective: This study aimed to determine whether children use pauses to signal stress placement, and whether this differs between typically developing children and those with CP.
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