Defined approaches to classify agrochemical formulations into EPA hazard categories developed using EpiOcularTM reconstructed human corneal epithelium and bovine corneal opacity and permeability assays.

Many sectors have seen complete replacement of the in vivo rabbit eye test with reproducible and relevant in vitro and ex vivo methods to assess the eye corrosion/irritation potential of chemicals. However, the in vivo 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 EpiOcularTM 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. Presented here are the results from testing 29 agrochemical formulations, which were evaluated against the United States Environmental Protection Agency's (EPA) pesticide classification system, and assessed using orthogonal validation, rather than direct concordance analysis with the historical in vivo rabbit eye data. Scientific confidence was established by evaluating the methods and testing results using an established framework that considers fitness for purpose, human biological relevance, technical characterisation, data integrity and transparency, and independent review. The in vitro and ex vivo methods used in the DAs were demonstrated to be as or more fit for purpose, reliable and relevant than the in vivo rabbit eye test. Overall, there is high scientific confidence in the use of these DAs for assessing the eye corrosion/irritation potential of agrochemical formulations.

Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides.

Background: 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. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum.Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method.Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study).Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.

'Whose life are They Going to Save? It's Probably Not Going to be Mine!' Living With a Life-Shortening Condition During the Coronavirus (COVID-19) Pandemic: A Grounded Theory Study of Embodied Precarity.

This article explores the experiences of young adults with a life-shortening condition in the first wave of the Coronavirus (COVID-19) pandemic in the UK. It presents the findings from an inclusive qualitative research study using constructivist grounded theory which aimed to examine the unintended consequences of pandemic control measures (lockdown and 'shielding') on this population. Purposive and theoretical sampling methods were used to recruit young adults with a life-shortening condition, employing a range of recruitment methods such as social media, advertising in newsletters and snowballing. Twenty-six young adults (aged 22-40 years), with a wide range of life-shortening conditions participated in the study. Seventeen participants were female and nine male. The majority identified as White British/Other and the remainder as Black British (2), Mixed Race (2) or Latin American (1). Data were generated iteratively using in-depth guided interviews and analysed collectively by an inclusive research team using the constant comparative method. The article explores a theory of embodied precariousness of living with a life-shortening condition during the first wave of the Coronavirus pandemic in relation to three categories: the rationing of life-saving treatment, the deterioration of health and retraction of healthcare provision, and the disruption of typical care arrangements. The findings show that the pandemic control measures introduced to keep people safe have intensified the precarity of this group promoting inequalities in healthcare and health outcomes. The article identifies some implications for practice to support the future management of unexpected and unwanted change.

Performance of the GHS Mixtures Equation for Predicting Acute Oral Toxicity.

Acute oral toxicity classifications are based on the estimated chemical dose causing lethality in 50 % of laboratory animals tested (LD50). 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. The goal of this study was to evaluate the concordance of LD50s predicted using the GHS Mixtures Equation and LD50s from the in vivo test results. Using the EPA classification system, concordance was 55 % for the full dataset (N = 671), 52 % for agrochemical formulations (N = 620), and 84 % for antimicrobial cleaning products (N = 51). Most discordant results were from substances LD50 > 2000 mg/kg (limit test) or 2000 < LD50 < 5000 mg/kg that were predicted as LD50 > 5000 mg/kg. A supplementary analysis combining all formulations with an LD50 > 500 mg/kg produced a concordance of 82 %. The lack of more toxic formulations in this dataset prevented a thorough evaluation of the GHS equation for such substances. Accordingly, our results suggest the GHS equation is helpful to predict the toxicity of mixtures, particularly those with lower toxicity.

Challenging norms: Making non-normative choices in childbearing. Results of a meta ethnographic review of the literature.

OBJECTIVE: Women have the right to make choices during pregnancy and birth that sit outside clinical guidelines, medical recommendations, or normative expectations. Declining recommended place or mode of birth, routine intervention or screening can be considered 'non-normative' within western cultural and social expectations around pregnancy and childbirth. The aim of this review is to establish what is known about the experiences, views, and perceptions of women who make non-normative choices during pregnancy and childbirth to uncover new understandings, conceptualisations, and theories within existing literature. METHODS: Using the meta-ethnographic method, and following its seven canonical stages, a systematic search of databases was performed, informed by eMERGe guidelines. FINDINGS: Thirty-three studies met the inclusion criteria. Reciprocal translation resulted in three third order constructs - 'influences and motivators', 'barriers and conflict and 'knowledge as empowerment'. Refutational translation resulted in one third order construct - 'the middle ground', which informed the line of argument synthesis and theoretical insights. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The findings of this review suggest that whilst existing literature from a range of high-income countries with similar healthcare systems to the UK have begun to explore non-normative decision-making for discrete episodes of care and choices, knowledge based, theoretical and population gaps exist in relation to understanding the experiences of, and wider social processes involved in, making non-normative choices across the UK maternity care continuum.

'Coping quite well with a few difficult bits': living with disfigurement in early adolescence.

Facial disfigurement affects approximately one in 500 children and young people in the UK. Four mothers and their four children aged 11-13 years who have a facial disfigurement were recruited through the charity Changing Faces, in order to examine the perspectives and concerns of adolescents and their mothers, and how they live with their disfigurement. Semi-structured interviews were analysed using Interpretative Phenomenological Analysis. The implications for research and practice in health psychology are discussed, and in particular the support and intervention of friends, constant vigilance and practical assistance from mothers, and the individual characteristics of the child are highlighted for further consideration.

Representations of autism: implications for community healthcare practice.

The work presented in this paper is part of a larger project in which online asynchronous discussion groups were employed to examine how a range of contributors--including people with autism, parents of people with autism, and professionals working within the field of autism--view and understand autism. In this paper, we focus on the voices of people with autism. The terminology used in the paper takes its lead from the writings of people with autism, who frequently use the term 'AS' to refer to autistic spectrum and Asperger syndrome and 'NT', which refers to neurologically typical people without autism. We examine a key theme identified in the online discussion groups--the representation of individuals with autism as occupying a separate world of autism. In doing so, we question an apparent goal of therapeutic interventions--to bring people with autism out of their 'separate world' and integrate them into a more typically 'social world'. We present an alternative understanding of autism that argues for valuing diversity and viewing autism as a difference rather than a deficit. We will discuss some of the implications that this may have for working with people with autism in health and social care practice.

Role of peer support for people with a spinal cord injury.

Spinal cord injuries can result in significant physiological and psychological challenges for patients. Nurses have an important role in the rehabilitation of people with a spinal cord injury, as does the provision of peer support by people who are 'living well' after experiencing a spinal cord injury. AIM: To explore peer support and whether it can have an effective role in a multidisciplinary team approach to supporting a patient with a spinal cord injury. METHOD: This was an independent evaluation that used an online survey, a focus group and telephone interviews to elicit the views of respondents about the Spinal Injury Association (SIA) peer support service in England and Wales. There were four groups of respondents: people with a spinal cord injury; their family and friends; peer support officers; and nurse specialists and other healthcare practitioners. FINDINGS: It was identified that peer support officers were valued for their ability to provide a positive role model for people with a spinal cord injury. Healthcare practitioners involved in the care of people with a spinal cord injury also appreciated the training and support they received from peer support officers. CONCLUSION: This evaluation demonstrated that peer support officers were regarded as an important element of a multidisciplinary team approach to managing the care of those who had experienced a spinal cord injury. Peer support officers were also considered a valuable source of information and education, particularly for healthcare practitioners working in settings where spinal cord injury was not a common presentation.

Smokers' representations of their own smoking: a q-methodological study.

Little work has addressed how smokers represent their own smoking rather than smoking in general. Research has identified a huge number of variables that contribute to smoking, yet not much is known about how smokers 'make sense' of these and construct explanations of the factors that contribute to their own smoking. This study used Q-methodology to investigate smokers' own representations of their smoking behaviour. Analysis revealed four main factors: smoking as a social tool; the dual identity smoker; reactionary smoking; and smoking as a social event. We argue that an understanding of the diversity of smokers' representations and explanations of their own smoking could play a useful role in developing more effective targeted interventions.

Constructing an autistic identity: AS voices online.

Excerpts from current research with people who have autism using online discussion groups are provided. Two major themes emerged that focus on "expert" knowledge of autism and identity. In contrast to the image of people with autism being unable to speak for themselves, our research on chat rooms has demonstrated that these individuals are finding a voice in an online environment, and the Internet may be a powerful tool in enabling this voice to be heard. The challenge that experiential knowledge poses to scientific knowledge is discussed in light of diagnosis, and the positive nature of an autism spectrum (AS) identity is highlighted as a common thread in discussions.