The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals : consequences for occupational and environmental medicine

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5′-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

Possible impact of human CYP2E1 polymorphisms on the metabolism of acrylonitrile

Case reports of human accidental poisonings point to significant individual differences in human acrylonitrile metabolism and toxicity. A cohort of 59 persons with industrial handling of low levels of acrylonitrile has repetitively been studied from 1994 through 1999 as part of a medical surveillance programme. The analyses included adduct determinations of N-terminal N-(cyanoethyl)valine in haemoglobin and genotypings of the following cytochrome P-450 2E1 (CYP2E1) polymorphisms: G-1259C and C-1019T (two subjects heterozygous), A-316G (three subjects heterozygous), T-297A (15 subjects heterozygous), G-35T (eight subjects heterozygous), G4804A (two subjects heterozygous), T7668A (six subjects heterozygous). N-(Cyanoethyl)valine adduct levels were, if any, only slightly influenced by smoking and mainly determined by the external acrylonitrile exposures. The individual means and medians of N-(cyanoethyl)valine levels over the entire observation period were compared with the CYP2E1 variants (Wilcoxon rank sum test). No influences of the investigated CYP2E1 polymorphisms on the N-(cyanoethyl)valine levels appeared at the 5% level. However, there was a trend, at a level of P≃0.1, pointing to higher acrylonitrile-specific adduct levels in persons with the A-316G mutation. Higher adduct levels would be compatible with a slower CYP2E1-mediated metabolism of acrylonitrile and with lower extents of toxification to cyanide.

Exploring the re-criminalising of OHS breaches in the context of industrial death

Since the 1980s the calls for further criminalisation of organisational conduct causing harm to workers, the public and the environment have intensified in Australia, Canada and England and Wales.' One focal point of this movement has been the criminal law's response to organisations (and their personnel) failing to comply with occupational health and safety ('OHS') standards, particularly when physical harm (death and serious injury) has resulted from those breaches. Some governments have responded with proposals to enable manslaughter prosecutions to be initiated 'more effectively' against organisations causing the deaths of workers or, in some cases, members of the public (Archibald et al, 2004; Haines and Hall, 2004; Hall et al, 2004; Tombs and Whyte, 2003). In Australia governments have also increased monetary penalties for regulatory OHS offences, a few have introduced other contemporary organisational sanctions, and some have initiated OHS prosecutions more vigorously and with larger fines.

The implications of de‐collectivist industrial relations laws and associated developments for worker health and safety in Australia, 1996–2007

The institutional and regulatory interlinkages between industrial relations (IR) and occupational health and safety (OHS) are seldom explored in the IR literature. This article begins to address this gap by examining regulatory initiatives in Australia during a period of neoliberal government. It examines the laws enacted by the federal government during this period and events and cases arising from these laws that go some way to illustrating their effects. Evidence is also drawn from detailed research on a number of state OHS inspectorates between 2004 and 2006. It is argued that de-collectivist changes to IR laws exacerbated problems posed by the growth of flexible work arrangements and a drop in union density, weakening participatory provisions in OHS laws and promoting work arrangements that undermined OHS standards. The study provides evidence of the implications of a divergence in the trajectory of IR and OHS laws and the importance of better integrating worker protection laws.

Statistics critical in securing our food supply

“World food security … is at its lowest in half a century,” wrote Julian Cribb FTSE, a wellknown consultant in science communication and founding editor of www.sciencealert. com.au in the lead article in the 2008 ATSE Focus magazine issue entitled “Food for the world: the nation’s challenge”. Food security continues to be a key national and international concern and it is pleasing to see this issue of Focus again exploring aspects of the topic with the aim of continuing to raise awareness of issues and influencing relevant policy decisions. Statistics (or statistical science, more broadly) has been critical to the information and decision-making value chain needed to optimise agriculture and the food supply chain. The key steps are most often addressed by multidisciplinary research groups including statisticians in collaboration with life and physical scientists, agri-industry personnel and other relevant stakeholders.

Suicide, statistics and the coroner: A comparative study of death investigations

Australia has a significantly higher suicide rate than England. Rather than accepting that this ‘statistical fact’ is a direct reflection of some positivist truth, this paper begins with the premise that how suicide is counted depends upon what counts as suicide. This study involves semi-structured interviews with coroners both in Australia and England, as well as observations at inquests. Important differences between the two coronial systems include: first, quite different logics of operation; second, the burden of proof for reaching a finding of suicide is significantly higher in England; and third, the presence of family members at English inquests results in far greater pressure being brought to bear upon coroners. These combined factors result in a reduced likelihood of English coroners reaching a finding of suicide. The conclusions are twofold. First, this research supports existing criticisms of comparative suicide statistics. Second, this research adds theoretical weight to criticisms of positivist analyses of social phenomena.

Computation of Mathematical Models for Complex Industrial Processes

Designed for undergraduate and postgraduate students, academic researchers and industrial practitioners, this book provides comprehensive case studies on numerical computing of industrial processes and step-by-step procedures for conducting industrial computing. It assumes minimal knowledge in numerical computing and computer programming, making it easy to read, understand and follow. Topics discussed include fundamentals of industrial computing, finite difference methods, the Wavelet-Collocation Method, the Wavelet-Galerkin Method, High Resolution Methods, and comparative studies of various methods. These are discussed using examples of carefully selected models from real processes of industrial significance. The step-by-step procedures in all these case studies can be easily applied to other industrial processes without a need for major changes and thus provide readers with useful frameworks for the applications of engineering computing in fundamental research problems and practical development scenarios.

A new approach to spatial data interpolation using higher-order statistics

Interpolation techniques for spatial data have been applied frequently in various fields of geosciences. Although most conventional interpolation methods assume that it is sufficient to use first- and second-order statistics to characterize random fields, researchers have now realized that these methods cannot always provide reliable interpolation results, since geological and environmental phenomena tend to be very complex, presenting non-Gaussian distribution and/or non-linear inter-variable relationship. This paper proposes a new approach to the interpolation of spatial data, which can be applied with great flexibility. Suitable cross-variable higher-order spatial statistics are developed to measure the spatial relationship between the random variable at an unsampled location and those in its neighbourhood. Given the computed cross-variable higher-order spatial statistics, the conditional probability density function (CPDF) is approximated via polynomial expansions, which is then utilized to determine the interpolated value at the unsampled location as an expectation. In addition, the uncertainty associated with the interpolation is quantified by constructing prediction intervals of interpolated values. The proposed method is applied to a mineral deposit dataset, and the results demonstrate that it outperforms kriging methods in uncertainty quantification. The introduction of the cross-variable higher-order spatial statistics noticeably improves the quality of the interpolation since it enriches the information that can be extracted from the observed data, and this benefit is substantial when working with data that are sparse or have non-trivial dependence structures.

Phenotyping cotton ovule fibre initiation with spatial statistics

Yield in cultivated cotton (Gossypium spp.) is affected by the number and distribution of fibres initiated on the seed surface but, apart from simple statistical summaries, little has been done to assess this phenotype quantitatively. Here we use two types of spatial statistics to describe and quantify differences in patterning of cotton ovule fibre initials (FI). The following five different species of Gossypium were analysed: G. hirsutum L., G. barbadense L., G. arboreum, G. raimondii Ulbrich. and G. trilobum (DC.) Skovsted. Scanning electron micrographs of FIs were taken on the day of anthesis. Cell centres for fibre and epidermal cells were digitised and analysed by spatial statistics methods appropriate for marked point processes and tessellations. Results were consistent with previously published reports of fibre number and spacing. However, it was shown that the spatial distributions of FIs in all of species examined exhibit regularity, and are not completely random as previously implied. The regular arrangement indicates FIs do not appear independently of each other and we surmise there may be some form of mutual inhibition specifying fibre-initial development. It is concluded that genetic control of FIs differs from that of stomata, another well studied plant idioblast. Since spatial statistics show clear species differences in the distribution of FIs within this genus, they provide a useful method for phenotyping cotton. © CSIRO 2007.

Statistics at play

Three core components in developing children’s understanding and appreciation of data — establish a context, pose and answer statistical questions, represent and interpret data — lay the foundation for the fourth component: use data to enhance existing context.

Vision-based operations of a large industrial vehicle : autonomous hot metal carrier

Hot metal carriers (HMCs) are large forklift-type vehicles used to move molten metal in aluminum smelters. This paper reports on field experiments that demonstrate that HMCs can operate autonomously and in particular can use vision as a primary sensor to locate the load of aluminum. We present our complete system but focus on the vision system elements and also detail experiments demonstrating reliable operation of the materials handling task. Two key experiments are described, lasting 2 and 5 h, in which the HMC traveled 15 km in total and handled the load 80 times.