RESUMO
BACKGROUND: Gallbladder cancer is rare, but cancers detected incidentally after cholecystectomy are increasing. The aim of this study was to review the available data for current best practice for optimal management of incidental gallbladder cancer. METHODS: A systematic PubMed search of the English literature to May 2018 was conducted. RESULTS: The search identified 12 systematic reviews and meta-analyses, in addition to several consensus reports, multi-institutional series and national audits. Some 0·25-0·89 per cent of all cholecystectomy specimens had incidental gallbladder cancer on pathological examination. Most patients were staged with pT2 (about half) or pT1 (about one-third) cancers. Patients with cancers confined to the mucosa (T1a or less) had 5-year survival rates of up to 100 per cent after cholecystectomy alone. For cancers invading the muscle layer of the gallbladder wall (T1b or above), reresection is recommended. The type, extent and timing of reresection remain controversial. Observation time may be used for new cross-sectional imaging with CT and MRI. Perforation at initial surgery had a higher risk of disease dissemination. Gallbladder cancers are PET-avid, and PET may detect residual disease and thus prevent unnecessary surgery. Routine laparoscopic staging before reresection is not warranted for all stages. Risk of peritoneal carcinomatosis increases with each T category. The incidence of port-site metastases is about 10 per cent. Routine resection of port sites has no effect on survival. Adjuvant chemotherapy is poorly documented and probably underused. CONCLUSION: Management of incidental gallbladder cancer continues to evolve, with more refined suggestions for subgroups at risk and a selective approach to reresection.
Assuntos
Colecistectomia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Complicações Pós-Operatórias/terapia , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/estatística & dados numéricos , Conversão para Cirurgia Aberta/estatística & dados numéricos , Humanos , Achados Incidentais , Laparoscopia/efeitos adversos , Laparoscopia/estatística & dados numéricos , Metástase Neoplásica , Inoculação de Neoplasia , Complicações Pós-Operatórias/patologia , Prognóstico , Reoperação/estatística & dados numéricos , Medição de RiscoRESUMO
Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g., naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.
Assuntos
Campos de Petróleo e Gás , Poluentes Químicos da Água , Alberta , Ácidos Carboxílicos , Lipídeos , Compostos OrgânicosRESUMO
STUDY DESIGN: Prospective cohort controlled trial design. OBJECTIVES: (i) To investigate mood benefits of adding group cognitive behaviour therapy (group-CBT) to standard spinal cord injury (SCI) inpatient rehabilitation (SR) that included access to antidepressant medication and individually delivered CBT on demand. (ii) To determine whether those with elevated depressive mood during inpatient rehabilitation significantly improve. SETTING: SCI rehabilitation and community settings in New South Wales, Australia. METHODS: Participants included 50 adults with SCI who completed SCI rehabilitation that included group-CBT compared with 38 participants who also completed SCI rehabilitation that did not contain group-CBT. Comprehensive assessment occurred after admission, within 2 weeks of discharge and 12 months post-injury. Multivariate repeated measures analyses were conducted to examine differences between groups and over time. RESULTS: The addition of group-CBT to SR did not result in significant improvement in mood. However, participants with clinically elevated depressive mood assessed during inpatient rehabilitation experienced significant reductions in depressive mood when assessed in the community regardless of CBT dosage. Anxiety correlated with mood while no sociodemographic/injury factors correlated with mood at any time period except education level. CONCLUSION: There were no mood advantages over time of adding group-CBT to inpatient SCI rehabilitation that contains individually delivered CBT on demand and access to antidepressant medication. However, findings showed those with elevated depressive mood during inpatient rehabilitation significantly improved when assessed in the community; however, their levels of depressive mood remain high. Future research should investigate the efficacy of providing individual preferences for managing depression in people with SCI.
Assuntos
Depressão , Traumatismos da Medula Espinal/psicologia , Adolescente , Adulto , Afeto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/terapia , Terapia Cognitivo-Comportamental , Depressão/terapia , Escolaridade , Feminino , Humanos , Vida Independente , Pacientes Internados/psicologia , Masculino , Pessoa de Meia-Idade , Reabilitação Neurológica , Psicoterapia de Grupo , Traumatismos da Medula Espinal/reabilitação , Resultado do Tratamento , Adulto JovemRESUMO
The UK Defence Medical Service's Pre-Hospital Emergency Care (PHEC) capability includes rapid-deployment Medical Emergency Response Teams (MERTs) comprising tri-service trauma consultants, paramedics and specialised nurses, all of whom are qualified to administer emergency care under extreme conditions to improve the survival prospects of combat casualties. The pre-deployment training of MERT personnel is designed to foster individual knowledge, skills and abilities in PHEC and in small team performance and cohesion in 'mission-specific' contexts. Until now, the provision of airborne pre-deployment MERT training had been dependent on either the availability of an operational aircraft (eg, the CH-47 Chinook helicopter) or access to one of only two ground-based facsimiles of the Chinook's rear cargo/passenger cabin. Although MERT training has high priority, there will always be competition with other military taskings for access to helicopter assets (and for other platforms in other branches of the Armed Forces). This paper describes the development of an inexpensive, reconfigurable and transportable MERT training concept based on 'mixed reality' technologies-in effect the 'blending' of real-world objects of training relevance with virtual reality reconstructions of operational contexts.
Assuntos
Serviços Médicos de Emergência , Medicina Militar/educação , Treinamento por Simulação , Humanos , Manequins , Reino UnidoRESUMO
STUDY DESIGN: Group cohort design. OBJECTIVES: To determine the influence of spinal cord injury (SCI) and neurological level on heart rate variability (HRV) and associations with fatigue. SETTING: SCI rehabilitation outpatient and community settings in New South Wales, Australia. METHODS: Participants included 45 adults with SCI living in the community and 44 able-bodied controls. Socio-demographic, neurological injury, psychological, HRV and eye blink variables were assessed. Multivariate analysis of variance and post hoc protected t-tests were used to determine differences in HRV and fatigue as a function of the neurological level. Pearson's correlation analysis was used to determine the relationships between these factors. RESULTS: Participants with SCI had significantly reduced sympathetic activity. Those with tetraplegia had lowered sympathetic activity compared with those with paraplegia and able-bodied controls. Neither were differences in parasympathetic activity found between groups nor were there any significant differences found for the time domain or non-linear domains. Higher levels of fatigue were found in the SCI sample, and participants with tetraplegia had higher fatigue levels compared with those with paraplegia. Fatigued participants were more likely to have altered autonomic function-that is, reduced sympathetic activity. CONCLUSIONS: Higher levels of neurological impairment in people with SCI are more likely to result in disordered cardiovascular control involving reduced sympathetic activity, whereas elevated fatigue was found to be associated with increased sympathetic dysfunction. Findings highlight the need to address risks associated with this dysfunction, such as improved HRV and fatigue screening for people with SCI and improved education on cardiovascular risk factors.
Assuntos
Fadiga/etiologia , Frequência Cardíaca/fisiologia , Doenças do Sistema Nervoso/etiologia , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Austrália , Piscadela/fisiologia , Estudos de Coortes , Eletrocardiografia , Eletroculografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças do Sistema Nervoso/diagnóstico , Exame Neurológico , Pacientes Ambulatoriais , Características de ResidênciaRESUMO
STUDY DESIGN: This is a longitudinal design study. OBJECTIVES: The objective of this study was to determine factors that predict resilience in people with spinal cord injury (SCI) at discharge from inpatient rehabilitation and after reintegration into the community 6 months post discharge. SETTING: This study was conducted in SCI rehabilitation units and the community in New South Wales, Australia. METHODS: Participants included 88 adults with SCI admitted over almost 3 years into three SCI Units in Sydney. Standardized self-report and clinician-based measures were used. Longitudinal assessment occurred up to 6 months post discharge. Sociodemographic, injury and psychological variables were assessed at admission, before discharge and 6 months post discharge. Standard multiple regression was used to determine factors that predict resilience at discharge from hospital and 6 months post discharge. RESULTS: Almost 70% of the participants were classified as resilient at discharge and 66% after 6 months of living in the community. Multiple factors significantly predicted resilience at discharge and 6 months post discharge, including self-efficacy, low levels of negative mood and lower functional independence, whereas social support and low severity of secondary conditions trended to significance. Demographic and injury variables did not contribute significantly. CONCLUSION: Self-efficacy and low levels of negative mood states strongly contribute to resilience. The determination of these predictors will assist in improving rehabilitation programs to strengthen the resilience of people with SCI. However, given that 40-44% of the variance in resilience was explained by the group of factors entered, future longitudinal research is needed to determine not only whether resilience correlates but also whether these associations change over time.
Assuntos
Resiliência Psicológica , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pacientes Internados/psicologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Alta do Paciente , Prognóstico , Autoeficácia , Autorrelato , Índice de Gravidade de Doença , Apoio Social , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Resultado do Tratamento , Adulto JovemRESUMO
STUDY DESIGN: Cross-section design. OBJECTIVES: The development of reliable screen technology for predicting those at risk of depression in the long-term remains a challenge. The objective of this research was to determine factors that classify correctly adults with spinal cord injury (SCI) with depressed mood and to develop a diagnostic algorithm that could be applied for prediction of depressed mood in the long-term. SETTING: SCI rehabilitation unit, rehabilitation outpatient clinic and Australian community. METHODS: Participants included 107 adults with SCI. The assessment regimen included demographic and injury variables, negative mood states, pain intensity, health-related quality of life and self-efficacy. Participants were divided into those with 'normal' mood versus those with elevated depressed mood. Discriminant function analysis (DFA) was then used to isolate factors that in combination, best classify the presence or absence of depressed mood. RESULTS: At the time of assessment, 24 participants (22.4%) had elevated depressed mood. DFA identified six factors that discriminated between those with depressed mood (P<0.01) and those with normal mood, explaining 61% of the variance. Factors consisted of pain intensity, mental health, emotional and social functioning, self-efficacy and fatigue. DFA correctly classified 91.7% (n=22 of 24) of those with depressed mood and 95.2% (n=79 of 83) of those without. Demographic, injury and physical health function variables were not found to discriminate depressed mood. CONCLUSION: Clinical implications of applying a diagnostic algorithm for detecting depression in adults with SCI are discussed. Prospective research is needed to test the predictive efficacy of the algorithm.
Assuntos
Algoritmos , Depressão/diagnóstico , Depressão/etiologia , Análise Discriminante , Traumatismos da Medula Espinal/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicologia , Estatística como AssuntoRESUMO
Microbial contamination in surface waters has become a worldwide cause for concern. As efforts are made to reduce this contamination, monitoring is integral to documenting and evaluating water quality improvements. Autosamplers are beneficial in such monitoring efforts, as large data sets can be generated with minimized effort. The extent to which autosamplers can be utilized for microbial monitoring is largely unknown due to concerns over contamination. Strict sterilization regimes for components contacting the water being sampled are difficult, and sometimes logistically implausible, when utilizing autosamplers. Field experimentation showed contamination of fecal coliform in autosamplers to be more of a concern than that of Escherichia coli. Further study in a controlled laboratory environment suggested that tubing configuration has a significant effect on residual E. coli concentrations in sampler tubing. The amount of time that passed since the last sample was collected from a given sampler (antecedent dry weather period - DWP) tubing was also a significant factor. At a DWP of 7 days, little to no contamination was found. Thus, simple protocols such as providing positive drainage of tubing between sample events and programming samplers to include rinses will reduce concerns of contamination in autosamplers.
Assuntos
Contaminação de Equipamentos , Microbiologia da Água/normas , Monitoramento Ambiental , Escherichia coli/isolamento & purificaçãoRESUMO
PURPOSE: In the new era of revalidation, there is an increasing need to measure surgical outcome objectively. We apply a graphical method, the Variable Life Adjusted Display (VLAD), to esophagogastric resection for malignancy. This technique charts the cumulative difference between expected and actual risk-adjusted mortality over time, allowing observation of performance trends irrespective of case-mix. METHODS: P-POSSUM was applied retrospectively to 182 consecutive patients who underwent resection for esophageal or gastric malignancy in a district general hospital. The primary outcome measured was 30-day mortality. RESULTS: A total of 168 patients were eligible for inclusion, with a median age of 68 years. The overall 30-day mortality rate was 4.2% compared with 7.1% as predicted by P-POSSUM. The resulting VLAD plot demonstrates an upward trend of better than predicted surgical performance. CONCLUSIONS: VLAD has been hereby applied to esophagogastric surgery and has graphically demonstrated risk-adjusted trends in a single general surgeon's performance. For qualitative comparative purposes, including recertification, VLAD is judged to be a simple, directly interpretable, and useful technique for monitoring surgical performance.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/normas , Gastrectomia/normas , Risco Ajustado/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Competência Clínica , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Feminino , Gastrectomia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Neoplasias Gástricas/mortalidade , Resultado do TratamentoRESUMO
There is a need to develop effective stormwater filters for passive (without any addition of chemicals or energy) and effective removal of pathogens in order to mainstream stormwater harvesting. This study focuses on the development of coated granular activated carbon (GAC) filtration material in order to develop filters for effective removal of pathogens from urban stormwater. Several laboratory trials were performed to gauge the effectiveness of the filters, which use a mixture of the zinc-sulphate-heptahydrate coated GAC and sand, on the removal of Escherichia coli (E. coli) from semi-natural stormwater. On average, a 98% removal of the inflow concentration of E. coli was achieved. Furthermore, there was also an improvement of approximately 25% in the removal of phosphorous. However, it was found that the treated material was leaching zinc. It was important to determine whether the observed removal of E. coli was indirectly caused by the sampling methodology. The results showed that the inactivation of the E. coli in the collected sample was small compared with the inactivation which actually occurred within the filter. This provides much promise to the filter, but the presence of zinc in the outflow demonstrates the need for further investigation into the stabilisation of the coating process.
Assuntos
Carvão Vegetal/química , Carvão Vegetal/economia , Purificação da Água/métodos , Sulfato de Zinco/química , Escherichia coli/isolamento & purificação , ChuvaRESUMO
OBJECTIVE: It has been recommended that carotid endarterectomy should be carried out within fourteen days of the index event if maximum stroke prevention benefit is to be achieved. The aim of this study was to see whether this target was being met in our region and where in the pathway delays occurred. METHODS: This was a retrospective review of all patients (n=75) undergoing carotid endarterectomy in 2006 in a regional vascular unit. Eleven patients were excluded as the timing of onset of symptoms was unclear, leaving 64 patients for further analysis. RESULTS: The median time-interval from onset of symptoms to surgery was 47 days (interquartile range 32-65 days). Five of 64 patients (4.5%) had a carotid endarterectomy within 14 days. Median time from onset of symptoms to presentation to health services was one day (IQR 0-7 days), from presentation to health services to neurovascular clinic was 16 days (IQR 10-23 days), from neurovascular clinic to vascular surgery clinic was 13 days (IQR 9-24 days), and from vascular surgery clinic to operation was 13 days (IQR 8-22 days). Fifteen of the 51 patients (29%) attending a neurovascular clinic and five of the 57 patients (9%) attending a vascular surgery clinic were seen within 14 days. CONCLUSION: The fourteen-day target is difficult to achieve due to the number of steps in the referral pathway. This delay may be jeopardising outcome. Reduction in the delay to surgery would require a multi-disciplinary approach and should involve education of the general public.
Assuntos
Amaurose Fugaz/prevenção & controle , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Fidelidade a Diretrizes , Ataque Isquêmico Transitório/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Amaurose Fugaz/diagnóstico , Amaurose Fugaz/etiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estudos de Coortes , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/etiologia , Masculino , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta , Estudos Retrospectivos , Escócia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
A previous 'in house' validation study showed that the SMI assay can be used as an alternative to the in vivo Draize eye irritation test. The aim of this multi-centre study with four participating laboratories was to assess the transferability and inter-laboratory variability of the assay using 20 reference chemicals covering the whole irritancy range. The eye irritation potency of the chemicals was assessed by measuring the amount of mucus produced during a 60-min contact period with a 1% dilution, and a second 60-min treatment with a 3.5% dilution. After each contact period the protein release from the mucosal surface was measured. Linear discriminant equations were used to convert the results into the corresponding EU eye irritation categories (NI, R36 and R41). All the non-irritants were predicted correctly by the four laboratories resulting in a 100% specificity. For the R36 compounds a correct classification rate of 89% (VITO) and 100% (SPL, JNJ and UGent) was obtained. The R41 compounds were classified correctly in 78% of the cases for VITO, 89% for SPL and JNJ and 100% for UGent. We can conclude that the SMI assay is a relevant, easily transferable and reproducible alternative to predict the eye irritation potency of chemicals.
Assuntos
Alternativas ao Uso de Animais , Olho/efeitos dos fármacos , Irritantes/toxicidade , Moluscos/fisiologia , Muco/metabolismo , Pele/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Olho/patologia , Irritantes/classificação , L-Lactato Desidrogenase/análise , Muco/enzimologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Pele/metabolismo , Testes de ToxicidadeRESUMO
OBJECTIVE: To determine the extent of daytime sleepiness in adults with spinal cord injury (SCI) and investigate the contribution of fatigue and autonomic function to sleepiness status. METHODS: Participants included 45 adults with SCI attending outpatient services or living in the community and 44 able-bodied controls. The Oxford Sleep Resistance Test (OSLER) was used to assess daytime sleepiness, while eye blink rate duration (electrooculography) and the Iowa Fatigue Scale assessed fatigue. Heart rate variability (HRV) was used to assess autonomic function. Survival analysis (Kaplan Meier) was used to estimate the rate of loss in participation in the OSLER task, as a measure of daytime sleepiness. Repeated measures ANOVA was used to determine HRV differences between groups. Regression analysis was used to establish factors that contributed to daytime sleepiness. RESULTS: Participants with high lesions ("T3 and above") had significantly increased daytime sleepiness. OSLER results revealed only 33% of those with high lesions remained awake during the task. Those with high lesions also had significantly reduced sympathetic activity while no differences in parasympathetic activity were found between groups. Lesion completeness had no effect. Standardized variation in heart rate, slow eye blinks, low frequency HRV and self-reported fatigue contributed to daytime sleepiness. CONCLUSION: Neurological lesions at "T3 or above" have an increased risk of daytime sleepiness, impacting on independence in daily functional tasks and work performance. Autonomic imbalance alters cardiovascular control, affecting health and wellbeing. The interaction of these factors requires further investigation.
Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Fadiga/etiologia , Sonolência , Traumatismos da Medula Espinal/complicações , Doenças do Sistema Nervoso Autônomo/patologia , Fadiga/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Assessment of ocular irritancy is an international regulatory requirement in the safety evaluation of industrial and consumer products. Although many in vitro ocular irritation assays exist, alone they are incapable of fully categorizing chemicals. The objective of CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for eye irritation assessment that can lead to complete replacement of the in vivo Draize rabbit eye test (OECD TG 405). A set of 80 reference chemicals was tested with seven test methods, one method was the Slug Mucosal Irritation (SMI) test method. The method measures the amount of mucus produced (MP) during a single 1-hour contact with a 1% and 10% dilution of the chemical. Based on the total MP, a classification (Cat 1, Cat 2, or No Cat) is predicted. The SMI test method correctly identified 65.8% of the Cat 1 chemicals with a specificity of 90.5% (low over-prediction rate for in vivo Cat 2 and No Cat chemicals). Mispredictions were predominantly unidirectional towards lower classifications with 26.7% of the liquids and 40% of the solids being underpredicted. In general, the performance was better for liquids than for solids with respectively 76.5% vs 57.1% (Cat 1), 61.5% vs 50% (Cat 2), and 87.5% vs 85.7% (No Cat) being identified correctly.
Assuntos
Olho/efeitos dos fármacos , Gastrópodes , Irritantes/classificação , Irritantes/toxicidade , Mucosa/efeitos dos fármacos , Testes de Toxicidade/métodos , AnimaisRESUMO
Assessment of ocular irritation is a regulatory requirement in safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as stand-alone assays. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed to assess the reliability of eight in vitro test methods and computational models as well as establishing an optimal tiered-testing strategy. For three computational models (Toxtree, and Case Ultra EYE_DRAIZE and EYE_IRR) performance parameters were calculated. Coverage ranged from 15 to 58%. Coverage was 2 to 3.4 times higher for liquids than for solids. The lowest number of false positives (5%) was reached with EYE_IRR; this model however also gave a high number of false negatives (46%). The lowest number of false negatives (25%) was seen with Toxtree; for liquids Toxtree predicted the lowest number of false negatives (11%), for solids EYE_DRAIZE did (17%). It can be concluded that the training sets should be enlarged with high quality data. The tested models are not yet sufficiently powerful for stand-alone evaluations, but that they can surely become of value in an integrated weight-of-evidence approach in hazard assessment.
Assuntos
Olho/efeitos dos fármacos , Irritantes/classificação , Irritantes/toxicidade , Modelos Biológicos , Animais , Simulação por Computador , Relação Quantitativa Estrutura-Atividade , Coelhos , Testes de ToxicidadeRESUMO
Assessment of acute eye irritation potential is part of the international regulatory requirements for safety testing of chemicals. In the last decades, many efforts have been made in the search for alternative methods to replace the regulatory in vivo Draize rabbit eye test (OECD TG 405). Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. The main objective of the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for serious eye damage and eye irritation assessment that can lead to complete replacement of OECD TG 405. A set of 80 reference chemicals (e.g. balanced by important driver of classification and physical state), was tested with seven test methods. Based on the results of this project, three different strategies were suggested. We have provided a standalone (EpiOcular ET-50), a two-tiered and three-tiered strategy, that can be used to distinguish between Cat 1 and Cat 2 chemicals and chemicals that do not require classification (No Cat). The two-tiered and three-tiered strategies use an RhCE test method (EpiOcular EIT or SkinEthic™ EIT) at the bottom (identification No Cat) in combination with the BCOP LLBO (two-tiered strategy) or BCOP OP-KIT and SMI (three-tiered strategy) at the top (identification Cat 1). For our proposed strategies, 71.1% - 82.9% Cat 1, 64.2% - 68.5% Cat 2 and ≥80% No Cat chemicals were correctly identified. Also, similar results were obtained for the Top-Down and Bottom-Up approach.
Assuntos
Olho/efeitos dos fármacos , Irritantes/classificação , Irritantes/toxicidade , Testes de Toxicidade/métodos , Animais , Bovinos , Gastrópodes , HumanosRESUMO
Assessment of ocular irritancy is an international regulatory requirement in the safety evaluation of industrial and consumer products. Although many in vitro ocular irritation assays exist, alone they are incapable of fully categorizing chemicals. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium was developed to assess the reliability of eight in vitro test methods and establish an optimal tiered-testing strategy. One assay selected was the Short Time Exposure (STE) assay. This assay measures the viability of SIRC rabbit corneal cells after 5min exposure to 5% and 0.05% solutions of test material, and is capable of categorizing of Category 1 and No Category chemicals. The accuracy of the STE test method to identify Cat 1 chemicals was 61.3% with 23.7% sensitivity and 95.2% specificity. If non-soluble chemicals and unqualified results were excluded, the performance to identify Cat 1 chemicals remained similar (accuracy 62.2% with 22.7% sensitivity and 100% specificity). The accuracy of the STE test method to identify No Cat chemicals was 72.5% with 66.2% sensitivity and 100% specificity. Excluding highly volatile chemicals, non-surfactant solids and non-qualified results resulted in an important improvement of the performance of the STE test method (accuracy 96.2% with 81.8% sensitivity and 100% specificity). Furthermore, it seems that solids are more difficult to test in the STE, 71.4% of the solids resulted in unqualified results (solubility issues and/or high variation between independent runs) whereas for liquids 13.2% of the results were not qualified, supporting the restriction of the test method regarding the testing of solids.
Assuntos
Córnea/citologia , Irritantes/classificação , Irritantes/toxicidade , Testes de Toxicidade/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , CoelhosRESUMO
Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. The objective of the CON4EI project was to develop tiered testing strategies for eye irritation assessment. A set of 80 reference chemicals (38 liquids and 42 solids) was tested with eight different methods. Here, the results obtained with the EpiOcular™ Eye Irritation Test (EIT), adopted as OECD TG 492, are shown. The primary aim of this study was to evaluate of the performance of the test method to discriminate between chemicals not requiring classification for serious eye damage/eye irritancy (No Category) and chemicals requiring classification and labelling. In addition, the predictive capacity in terms of in vivo drivers of classification (i.e. corneal opacity, conjunctival redness and persistence at day 21) was investigated. EpiOcular™ EIT achieved a sensitivity of 97%, a specificity of 87% and accuracy of 95% and also confirmed its excellent reproducibility (100%) from the original validation. The assay was applicable to all chemical categories tested in this project and its performance was not limited to the particular driver of the classification. In addition to the existing prediction model for dichotomous categorization, a new prediction model for Cat 1 is suggested.
Assuntos
Olho/efeitos dos fármacos , Irritantes/classificação , Irritantes/toxicidade , Testes de Toxicidade/métodos , Alternativas aos Testes com Animais , Opacidade da Córnea/induzido quimicamente , Humanos , Reprodutibilidade dos TestesRESUMO
Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies.
Assuntos
Epitélio Corneano/efeitos dos fármacos , Irritantes/classificação , Irritantes/toxicidade , Testes de Toxicidade/métodos , Alternativas aos Testes com Animais , Humanos , Reprodutibilidade dos TestesRESUMO
Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. In the past, several prospective and retrospective validation studies have taken place in the area of serious eye damage/eye irritation testing. Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. A very important aspect to ensure development of successful alternative test methods and/or strategies for serious eye damage/eye irritation testing is the selection of appropriate reference chemicals. A set of 80 reference chemicals was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project, in collaboration with Cosmetics Europe, from the Draize Reference Database published by Cosmetics Europe based on key criteria that were set in their paper (e.g. balanced by important driver of classification and physical state). The most important goals of the CON4EI project were to identify the performance of eight in vitro alternative tests in terms of driver of classification and to identify similarities/differences between the methods in order the build a successful testing strategy that can discriminate between all UN GHS categories. This paper provides background on selection of the test chemicals.