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This study aims to (1) analyze the level of financial and non-financial feasibility of oil palm and rice farming, (2) analyze the sensitivity level of oil palm and rice farming, (3) determine the comparability of the feasibility of oil palm and rice farming and to know what is the most profitable in Lubuk Pinang District, Mukomuko Regency, Bengkulu Province. The data used in this study are primary data and secondary data. The sampling of oil palm farmers in this study used a stratified random sampling technique, while the rice farmers used accidental sampling techniques. The data analysis technique used in this study is the analysis of the Present Net Value (NPV) and Net B / C Ratio. The results showed that from a financial perspective, oil palm and rice farming in Lubuk Pinang District, Mukomuko Regency, Bengkulu Province, were declared feasible to continue; this can be seen from the NPV and B / C Ratio values. The NPV value in oil palm farming is IDR 44,682,270.66, while the NPV in rice farming is IDR 168,218,082.21. The Net B / C Ratio in oil palm farming was 2.31, while the Net B / C Ratio value in rice farming was 6.94. From a non-financial perspective, oil palm and rice farming are considered feasible due to the availability of production factors for both farms, such as seeds, labor, and other production inputs.

The assessment of disability-related costs among children remains a largely under-researched subject with related questions rarely included in surveys. This paper addresses this issue through a unique mixed methods study conducted in the Philippines combining a nationally representative survey and in-depth interviews with families and health professionals. To quantify the extra costs associated with disabilities, the research used the standard of living approach, whereby expenditure levels of families with children with and without disabilities were compared in relation to different measures of living standards. The results find consistent evidence of high extra costs among households that have children with disabilities and point to health expenses as the leading source. Using an asset index as the indicator of living standards, a child with a disability is estimated to require between 40% and 80% extra expenditure to reach the same living standard of other children. However, the size of extra costs is substantially higher when the measure of the standard of living relies on a broader set of deprivations. In such cases, higher estimates of extra costs are likely to be the result of the lack of an inclusive environment. Critically, this points to the need to provide not only financial support but also inclusive services, especially in health and education.

To inform the development of global wastewater monitoring systems, we surveyed programmes in 43 countries. Most programmes monitored predominantly urban populations. In high-income countries (HICs), composite sampling at centralised treatment plants was most common, whereas grab sampling from surface waters, open drains, and pit latrines was more typical in low-income and middle-income countries (LMICs). Almost all programmes analysed samples in-country, with an average processing time of 2·3 days in HICs and 4·5 days in LMICs. Whereas 59% of HICs regularly monitored wastewater for SARS-CoV-2 variants, only 13% of LMICs did so. Most programmes share their wastewater data internally, with partnering organisations, but not publicly. Our findings show the richness of the existing wastewater monitoring ecosystem. With additional leadership, funding, and implementation frameworks, thousands of individual wastewater initiatives can coalesce into an integrated, sustainable network for disease surveillance?one that minimises the risk of overlooking future global health threats.

The assessment of disability related costs among children remains a largely under-researched subject with related questions rarely included in surveys. This paper addresses this issue through a unique mixed methods study conducted in the Philippines combining a nationally representative survey and in-depth interviews with families and health professionals. To quantify the extra costs associated with disability the research used the standard of living approach, whereby expenditure levels of families with children with and without disabilities are compared in relation to different measures of living standards. The results find consistent evidence of high extra costs among households that have children with disabilities and point to health expenses as the leading source. Using an asset index as the indicator of living standards, a child with disability is estimated to require between 40 and 80% extra expenditure to reach the same living standard of other children. However, the size of extra costs is substantially higher when the measure of standard of living relies on a broader set of deprivations. In such cases, higher estimates of extra costs are likely to be the result of the lack of an inclusive environment. Critically, this points to the need not only to provide financial support, but also inclusive services, especially in health and education.

The Dynamic Energy Budget theory (DEB) enables ecotoxicologists to model the effects of chemical stressors on organism life cycles through the coupling of toxicokinetic-toxicodynamic (TK-TD) models. While good progress has been made in the application of DEB-TKTD models for aquatic organisms, applications for soil fauna are scarce, due to the lack of dedicated experimental designs suitable for collecting the required time series effect data. Enchytraeids (Annelida: Clitellata) are model organisms in soil ecology and ecotoxicology. They are recognised as indicators of biological activity in soil, and chemical stress in terrestrial ecosystems. Despite this, the application of DEB-TKTD models to investigate the impact of chemicals has not yet been tested on this family. Here we assessed the impact of the pyrethroid insecticide cypermethrin on the life cycle of Enchytraeus crypticus. We developed an original experimental design to collect the data required for the calibration of a DEB-TKTD model for this species. E. crypticus presented a slow initial growth phase that has been successfully simulated with the addition of a size-dependent food limitation for juveniles in the DEB model. The DEB-TKTD model simulations successfully agreed with the data for all endpoints and treatments over time. The highlighted physiological mode of action (pMoA) for cypermethrin was an increase of the growth energy cost. The threshold for effects on survival was estimated at 73.14 mg kg

People with Methamphetamine Use Disorder (PwMUD) spend substantial time and resources on substance use, which hinders their ability to explore alternate reinforcers. Gold-standard behavioural treatments attempt to remedy this by encouraging action towards non-drug reinforcers, but substance use often persists. We aimed to unravel the mechanistic drivers of this behaviour by applying a computational model of explore/exploit behaviour to decision-making data (Iowa Gambling Task) from 106 PwMUD and 48 controls. We then examined the longitudinal link between explore/exploit mechanisms and changes in methamphetamine use 6 weeks later. Exploitation parameters included reinforcement sensitivity and inverse decay (i.e., number of past outcomes used to guide choices). Exploration parameters included maximum directed exploration value (i.e., value of trying novel actions). The Timeline Follow Back measured changes in methamphetamine use. Compared to controls, PwMUD showed deficits in exploitative decision-making, characterised by reduced reinforcement sensitivity, U = 3065, p = 0.009, and less use of previous choice outcomes, U = 3062, p = 0.010. This was accompanied by a behavioural pattern of frequent shifting between choices, which appeared consistent with random exploration. Furthermore, PwMUD with greater reductions of methamphetamine use at 6 weeks had increased directed exploration (β = 0.22, p = 0.045); greater use of past choice outcomes (β = -0.39, p = 0.002) and greater choice consistency (β = -0.39, p = 0.002). Therefore, limited computational exploitation and increased behavioural exploration characterise PwMUD's presentation to treatment, while increased directed exploration, use of past choice outcomes and choice consistency predict greater reductions of methamphetamine use.

A new single scattering adjoint transport capability was implemented in Framework for REsearch in Nuclear ScIence and Engineering (FRENSIE). The Evaluated Electron Data Library (EEDL) was used to g...

The assessment of chemical mixture toxicity is one of the major challenges in ecotoxicology. Chemicals can interact, leading to more or less effects than expected, commonly named synergism and antagonism respectively. The classic ad hoc approach for the assessment of mixture effects is based on dose-response curves at a single time point, and is limited to identifying a mixture interaction but cannot provide predictions for untested exposure durations, nor for scenarios where exposure varies in time. We here propose a new approach using toxicokinetic-toxicodynamic modelling: The General Unified Threshold model of Survival (GUTS) framework, recently extended for mixture toxicity assessment. We designed a dedicated mechanistic interaction module coupled with the GUTS mixture model to i) identify interactions, ii) test hypotheses to identify which chemical is likely responsible for the interaction, and finally iii) simulate and predict the effect of synergistic and antagonistic mixtures. We tested the modelling approach experimentally with two species (Enchytraeus crypticus and Mamestra brassicae) exposed to different potentially synergistic mixtures (composed of: prochloraz, imidacloprid, cypermethrin, azoxystrobin, chlorothalonil, and chlorpyrifos). Furthermore, we also tested the model with previously published experimental data on two other species (Bombus terrestris and Daphnia magna) exposed to pesticide mixtures (clothianidin, propiconazole, dimethoate, imidacloprid and thiacloprid) found to be synergistic or antagonistic with the classic approach. The results showed an accurate simulation of synergistic and antagonistic effects for the different tested species and mixtures. This modelling approach can identify interactions accounting for the entire time of exposure, and not only at one time point as in the classic approach, and provides predictions of the mixture effect for untested mixture exposure scenarios, including those with time-variable mixture composition.

IntroductionBesides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking.GoalsTo summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID.MethodsWe performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized.Results6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high.ConclusionsWe could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.

Neonicotinoids are currently licensed for use in 120 countries, making accurate nontarget species sensitivity predictions critical. Unfortunately, such predictions are fraught with uncertainty, as sensitivity is extrapolated from only a few test species and neonicotinoid sensitivities can differ greatly between closely related taxa. Combining classical toxicology with de novo toxicogenomics could greatly improve sensitivity predictions and identify unexpectedly susceptible species. We show that there is a >30-fold differential species sensitivity (DSS) for the neonicotinoid imidacloprid between five earthworm species, a critical nontarget taxon. This variation could not be explained by differential toxicokinetics. Furthermore, comparing key motif expression in subunit genes of the classical nicotinic acetylcholine receptor (nAChR) target predicts only minor differences in the ligand binding domains (LBDs). In contrast, predicted dissimilarities in LBDs do occur in the highly expressed but nonclassical targets, acetylcholine binding proteins (AChBPs). Critically, the predicted AChBP divergence is capable of explaining DSS. We propose that high expression levels of putative nonsynaptic AChBPs with high imidacloprid affinities reduce imidacloprid binding to critical nAChRs involved in vital synaptic neurotransmission. This study provides a clear example of how pragmatic interrogation of key motif expression in complex multisubunit receptors can predict observed DSS, thereby informing sensitivity predictions for essential nontarget species.

Current methods to assess the impact of chemical mixtures on organisms ignore the temporal dimension. The General Unified Threshold model for Survival (GUTS) provides a framework for deriving toxicokinetic–toxicodynamic (TKTD) models, which account for effects of toxicant exposure on survival in time. Starting from the classic assumptions of independent action and concentration addition, we derive equations for the GUTS reduced (GUTS-RED) model corresponding to these mixture toxicity concepts and go on to demonstrate their application. Using experimental binary mixture studies with Enchytraeus crypticus and previously published data for Daphnia magna and Apis mellifera, we assessed the predictive power of the extended GUTS-RED framework for mixture assessment. The extended models accurately predicted the mixture effect. The GUTS parameters on single exposure data, mixture model calibration, and predictive power analyses on mixture exposure data offer novel diagnostic tools to inform on the chemical mode of action, specifically whether a similar or dissimilar form of damage is caused by mixture components. Finally, observed deviations from model predictions can identify interactions, e.g., synergism or antagonism, between chemicals in the mixture, which are not accounted for by the models. TKTD models, such as GUTS-RED, thus offer a framework to implement new mechanistic knowledge in mixture hazard assessments.

Nanomaterials (NMs) are thermodynamically unstable by nature, and exposure of soil organisms to NMs in the terrestrial environment cannot be assumed constant. Thus, steady-state conditions may not apply to NMs, and bioaccumulation modeling for uptake should follow a dynamic approach. The one-compartment model allows the uptake and elimination of a chemical to be determined, while also permitting changes in exposure and growth to be taken into account. The aim of the present study was to investigate the accumulation of Ag from different Ag NM types (20 nm Ag0 NMs, 50 nm Ag0 NMs, and 25 nm Ag2 S NMs) in the crop plant wheat (Triticum aestivum). Seeds were emerged in contaminated soils (3 or 10 mg Ag/kg dry soil, nominal) and plants grown for up to 42 d postemergence. Plant roots and shoots were collected after 1, 7, 14, 21, and 42 d postemergence; and total Ag was measured. Soil porewater Ag concentrations were also measured at each sampling time. Using the plant growth rates in the different treatments and the changing porewater concentrations as parameters, the one-compartment model was used to estimate the uptake and elimination of Ag from the plant tissues. The best fit of the model to the data included growth rate and porewater concentration decline, while showing elimination of Ag to be close to zero. Uptake was highest for Ag0 NMs, and size did not influence their uptake rates. Accumulation of Ag from Ag2 S NMs was lower, as reflected by the lower porewater concentrations. Environ Toxicol Chem 2021;40:1861-1872. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Verification and validation tests have been performed for the single scattering Evaluated Electron Data Library (EEDL) implemented in the Framework for Research in Nuclear ScIence and Engineering (...

Excessive adiposity (particularly visceral fat mass) increases the risks of developing metabolic syndrome. Women have lower deposit of visceral fat than men, and this pattern becomes diminished postmenopausally, but the underlying mechanism remains largely unknown. Here, we show that the gender difference in visceral fat distribution is controlled by an estradiol–autophagy axis. In C57BL/6J and wild-type control mice, a higher visceral fat mass was detected in the males than in the females, which was associated with lower expression of estrogen receptor α (ERα) and more active autophagy in males vs. females. However, deletion of ERα normalized autophagy activity and abolished the gender difference in visceral adiposity. In line with the adiposity-reducing effect of the ERα–autophagy axis, we found that downregulation of ERα and increased autophagy activity were required for adipogenesis, while induction of estradiol signaling dampened autophagy and drastically prevented adipogenesis. Mechanistically, the estradiol-ERα signaling activated mTOR, which phosphorylated and inhibited ULK1, thereby suppressing autophagy and adipogenesis. Together, our study suggests that the lower visceral adiposity in the females (vs. the males) arises from a more active estradiol-ERα signaling, which tunes down autophagy and adipogenesis. USDA USDA: National Institute of Food and Agriculture Hatch Project 1007334 National Institutes of Health NIH: R18DK091811 NIH: 1R01AT007077

The Washington Group questions (WGQ) on functioning have been widely promoted as the go-to tool for disability data collection. Designed for use by government, the WGQ have been adopted by non-government organizations (NGOs) for use in programming. However, little is known about how the WGQs are being used by NGOs or how use may be contributing to disability inclusion. Method: This paper describes exploratory research on the use of the WGQ in NGO programming. An online survey provided an overview of adoption followed by semi-structured interviews from a purposive sample to explore data collection, analysis, and use. Results: Thematic analysis showed limited inclusion outcomes directly attributable to use of the WGQ, adoption driven by individual champions rather than systematically across organizations, and challenges in data collection resulting in a wide range of prevalence rates. What information the WGQ can realistically contribute to programs was also overestimated. However, the process of using the WGQ was raising awareness on disability inclusion within program teams and communities. Conclusion: Acknowledging differences in emerging use by NGOs beyond the WGQ’s intended purpose, alongside promoting a flexible and staged approach to adoption and use in programming, may improve utility and disability inclusion outcomes over time.

The scale of variation in species sensitivity to toxicants has been theoretically linked to mode of action. Specifically, it has been proposed there will be greater variations for chemicals with a putative specific biological target than for toxicants with a non-specific narcotic mechanism. Here we test the hypothesis that mode of action is related to variation in sensitivity in a specifically designed experiment for species from a single ecologically important terrestrial taxa, namely earthworms. Earthworm toxicity tests were conducted with five species for four chemicals, providing a series of increasingly complex modes of action: a putative narcotic polycyclic aromatic hydrocarbon (fluoranthene), and three insecticides (chlorpyrifos, cypermethrin, imidacloprid) with known neuronal receptor targets. Across all the chemicals, the standard epigeic test species Eisenia fetida and Lumbricus rubellus, were generally among the two least sensitive, while the endogenic Aporrectodea caliginosa and Megascolecidae Amynthas gracilis were generally more sensitive (never being among the two least sensitive species). This indicates a potential for bias in the earthworm ecotoxicology literature, which is dominated by studies in epigeic Lumbricidae, but contains few endogeic or Megascolecidae data. Results confirmed the lowest range of variation in sensitivities for effects on reproduction was for fluoranthene (2.5 fold). All insecticides showed greater variation for species sensitivity (cypermethrin: 7.5 fold, chlorpyrifos: 10.3 fold, imidacloprid: 31.5 fold) consistent with the specific mechanisms of the pesticides. Difference in toxicodynamics, based on mode of action specificity and receptor complexity was reflected in the magnitude of sensitivity variation. However, measurements of tissue concentrations also indicated the potential importance of toxicokinetics in explaining species sensitivity variations for chlorpyrifos and cypermethrin.

Threats to wild and managed insect pollinators in Europe are cause for both ecological and socio-economic concern. Multiple anthropogenic pressures may be exacerbating pollinator declines. One key pressure is exposure to chemicals including pesticides and other contaminants. Historically the honey bee (Apis mellifera spp.) has been used as an ‘indicator’ species for ‘standard’ ecotoxicological testing but it has been suggested that it is not always a good proxy for other types of eusocial and solitary bees because of species differences in autecology and sensitivity to various stressors. We developed a common toxicity test system to conduct acute and chronic exposures of up to 240 h of similar doses of seven chemicals, targeting different metabolic pathways, on three bee species (Apis mellifera spp., Bombus terrestris and Osmia bicornis). We compared the relative sensitivity between species in terms of potency between the chemicals and the influence of exposure time on toxicity. While there were significant interspecific differences that varied through time, overall the magnitude of these differences (in terms of treatment effect ratios) was generally comparable (< 2 fold) although there were some large divergences from this pattern. Our results suggest that A. mellifera spp. could be used as a proxy for other bee species provided a reasonable assessment factor is used to cover interspecific variation. Perhaps more importantly our results show significant and large time dependency of toxicity across all three tested species that greatly exceeds species differences (> 25 fold within test). These are rarely considered in standard regulatory testing but may have severe environmental consequences, especially when coupled with the likelihood of differential species exposures in the wild. These insights indicate that further work is required to understand how differences in toxicokinetics vary between species and mixtures of chemicals.

Aim: To survey dietitians on their knowledge and practices regarding vitamin D (VitD) intake, sources, supplementation and effect on disease state.

The effects of exposure to different levels of ionising radiation were assessed on the genetic, epigenetic and microbiome characteristics of the “hologenome” of earthworms collected at sites within the Chernobyl exclusion zone (CEZ). The earthworms Aporrectodea caliginosa (Savigny, 1826) and Octolasion lacteum (Örley, 1881) were the two species that were most frequently found at visited sites, however, only O. lacteum was present at sufficient number across different exposure levels to enable comparative hologenome analysis. The identification of morphotype O. lacteum as a probable single clade was established using a combination of mitochondrial (cytochrome oxidase I) and nuclear genome (Amplified Fragment Length Polymorphism (AFLP) using MspI loci). No clear site associated differences in population genetic structure was found between populations using the AFLP marker loci. Further, no relationship between ionising radiation exposure levels and the percentage of methylated loci or pattern of distribution of DNA methylation marks was found. Microbiome structure was clearly site dependent, with gut microbiome community structure and diversity being systematically associated with calculated site-specific earthworm dose rates. There was, however, also co-correlation between earthworm dose rates and other soil properties, notably soil pH; a property known to affect soil bacterial community structure. Such co-correlation means that it is not possible to attribute microbiome changes unequivocally to radionuclide exposure. A better understanding of the relationship between radionuclide exposure soil properties and their interactions on bacterial microbiome community response is, therefore, needed to establish whether these the observed microbiome changes are attributed directly to radiation exposure, other soil properties or to an interaction between multiple variables at sites within the CEZ.

This chapter describes Disaster Risk Reduction (DRR) capacity building activities with disabled people’s organizations (DPOs) in four hazard risk provinces in Indonesia. Established as part of an Australian Aid supported development research initiative, the project was implemented in the last years of the Hyogo Framework for Action by the Centre for Disability Research and Policy, University of Sydney and Arbeiter-Samariter-Bund Deutschland e.V, Indonesia and Philippines Office. As in other regions, participation in DRR by Indonesian DPOs was highly limited under the HFA. With the Sendai Framework for DRR (SFDRR) now recognizing persons with disabilities as key stakeholders, there is a need to broaden knowledge on the role of DPOs in DRR. While the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) refers to situations of risk, the related article has received little attention from DPOs due to multiple competing priorities. Similarly, DRR actors have rarely engaged with the disability sector. The SFDRR calls for greater collaboration between these two groups. This chapter outlines core features of the capacity building initiative and the impact of the programme on equipping Indonesian DPOs to engage within DRR. We describe how capacity building initiatives contributed to increased collaboration between disability and DRR actors, providing a practical model for supporting DPOs as policy advocates in other regions and countries. Disability-inclusive DRR recognizes the importance of collaboration to reduce and prevent risk. As the chapter illustrates, the resources to achieve this are far closer at hand than the DRR community previously thought.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of

To survey dietitians on their knowledge and practices regarding vitamin D (VitD) intake, sources, supplementation and effect on disease state.An online survey was disseminated to members of the Dietitian Association Australia via the weekly online state newsletter during April 2015. Response rate was 3%, with 134 respondents completing the survey. The survey included questions about knowledge and current practices. Descriptive statistics were used to analyse the results.Dietitians have good knowledge regarding dietary sources of VitD and roles in the body, but there is confusion around supplement doses for treatment and prevention of deficiency and sun exposure guidelines.Dietitians are well positioned to provide patients with advice on VitD supplementation and sun exposure practices, but not all are confident to provide this care. There is a need for clear and well-disseminated guidelines for VitD management by dietitians.

The chapter argues that although risk and vulnerability are central to the disaster risk reduction (DRR) community’s collective endeavours, to date scant attention has been paid to the most at-risk within our work. Disability is a cross-cutting issue that significantly increases risk for individuals who are often already living with exclusion. While many DRR interventions claim to be participatory in their approach, interventions that recognise and respond to the needs of people with disability remain paradoxically few.

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepato toxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.