Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats

In an attempt to examine the interaction of man-made mineral fibres with benzo[a]pyrene (B[a]P), homozygous X-lacI transgenic F344 rats were intratracheally treated with rock (stone) wool RWI and glass wool MMVF 10 fibres together with B[a]P. To analyze the induction of gene mutations by fibres and B[a]P in lung, single doses of 1 and 2 mg fibres/animal or multiple doses of 2 mg fibres/animal were administered weekly on 4 consecutive weeks (total dose 8 mg/animal). B[a]P (10 mg/animal) was administered either simultaneously with fibres (for single dose treatment with fibres) or together with the last fiber treatment (for multiple dose treatment with fibres). Animals were scarified 4 weeks after the last treatment. Benzo[a]pyrene administered simultaneously with RW1 fibres exhibited a strong synergistic effect on mutagenicity, the observed mutant frequency (MF) being more than three-fold higher than the net sum of the MF induced after separate administration of both agents. Our data suggest that DNA adducts induced by simultaneous B[a]P and fiber treatment lead to a strong increase in mutatant frequencies.     

Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients

The traditional “safety factor”; method has been used for years to establish occupational exposure limits (OELs) for active ingredients used in drugs. In the past, a single safety factor was used to address all sources of uncertainty in the limit setting process. The traditional 100‐fold safety factor commonly used to derive an acceptable daily intake value incorporates a default factor of 10 each to account for interindividual variability and interspecies extrapolation. Use of these defaults can lead to overly conservative health‐based limits, especially when they are combined with other (up to 10‐fold) factors to adjust for inadequacies in the available database. In recent years, attempts have been made to quantitate individual sources of uncertainty and variability to improve the scientific basis for OELs. In this paper we discuss the science supporting reductions in the traditional default uncertainty factors. A number of workplace‐specific factors also support reductions in these factors. Recently proposed alternative methodologies provide a framework to make maximum use of preclinical and clinical information, e.g., toxicokinetic and toxicodynamic data, to reduce uncertainties when establishing OELs for pharmaceutical active ingredients.     

Dose limits for occupational exposure to ionising radiation and genotoxic carcinogens: a German perspective

This paper summarises the view of the German Commission on Radiological Protection (“Strahlenschutzkommission”, SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current dose limits followed by a discussion of the detriment used by ICRP as a measure for stochastic health effects. Studies on radiation-induced cancer are reviewed because this endpoint represents the most important contribution to detriment. Recent findings on radiation-induced circulatory disease that are currently not included in detriment calculation are also reviewed. It appeared that for detriment calculations the contribution of circulatory diseases plays only a secondary role, although the uncertainties involved in their risk estimates are considerable. These discussions are complemented by a review of the procedures currently in use in Germany, or in discussion elsewhere, to define limits for genotoxic carcinogens. To put these concepts in perspective, actual occupational radiation exposures are exemplified with data from Germany, for the year 2012, and regulations in Germany are compared to the recommendations issued by ICRP. Conclusions include, among others, considerations on radiation protection concepts currently in use and recommendations of the SSK on the limitation of annual effective dose and effective dose cumulated over a whole working life.     

Man-made mineral (vitreous) fibres: evaluations of cancer hazards by the IARC Monographs Programme

Man-made vitreous (glass-like) fibres are non-crystalline, fibrous inorganic substances (silicates) made primarily from rock, slag, glass or other processed minerals. These materials, also called man-made mineral fibres, include glass fibres (used in glass wool and continuous glass filament), rock or stone wool, slag wool and refractory ceramic fibres. They are widely used for thermal and acoustical insulation and to a lesser extent for other purposes. These products are potentially hazardous to human health because they release airborne respirable fibres during their production, use and removal. Man-made mineral fibres and man-made vitreous fibres have been the subject of reviews by IARC Monographs Working Groups in 1987 and 2001, respectively, which resulted in evaluations of the carcinogenic hazard to humans from exposure to these materials. These reviews and evaluations have been published as Volumes 43 and 81 of the IARC Monographs series [IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 43, Man-made Mineral Fibres and Radon (1988); IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 81, Man-made Vitreous Fibres (2002)]. The re-evaluation in 2001 was undertaken because there have been substantial improvements in the quality of the epidemiological information available on the carcinogenicity to humans of glass fibres, continuous glass filament and rock/slag wool. The new evaluations have addressed the limitations of earlier cohort studies, particularly concerning the lack of adjustment with respect to concomitant risk factors such as smoking and other sources of occupational exposure. In addition, the evaluation of the evidence for carcinogenicity of glass fibres to experimental animals has been refined, by making a distinction between insulation glass wool and special-purpose glass fibres. The results of the evaluations in 1987 and 2001 are thus different in several aspects. In this paper, the reviews and evaluations of the carcinogenic hazards of exposure to man-made mineral fibres (MMMF, Monograph volume 43, [1]) and man-made vitreous fibres (MMVF, Monograph volume 81, [2]) are summarised, and the differences explained. In particular, the considerations of the respective IARC Monographs Working Groups (1987, 2001) in reaching their conclusions are discussed in some detail.     

Biological durability and oxidative potential of man-made vitreous fibres as compared to crocidolite asbestos fibres

In this study we investigated relationships between redox properties and biodurability of crocidolite asbestos fibres and three different man-made vitreous fibres (MMVF): traditional stone wool fibres (MMVF 21), glass fibres (MMVF 11) and refractory ceramic fibres (RCF). Each fibre type was incubated up to 22 weeks in four different incubation media: gamble solution (GS) pH 5.0 and pH 7.4, representing blood plasma without proteins, and surfactant-like solution (SLS) pH 5.0 and pH 7.4. During incubation time aliquots of incubation mixtures were removed and analysed in a biochemical model reaction, mimicking activated phagocytes. In addition, changes of fibre morphology and chemical composition were examined using SEM- and EDX-technology. In the presence of crocidolite asbestos fibres and MMVF 21 the formation of OH*-radicals according to the Haber-Weiss sequence could be demonstrated, whereas MMVF 11 and RCF showed no reactivity. Crocidolite asbestos fibres exhibited a significant higher activity compared with the stone wool fibres at the onset of incubation. The oxidative capacities of these fibre types were shown to depend on both specific surface area and iron content. The oxidative potentials of crocidolite asbestos fibres as well as MMVF 21 were not constant during incubation over several weeks in each incubation medium. The reactivities showed sinoidal curves including reactivities much higher than those at the onset of incubation time. These irregular changes of oxidative capacity may be explained by changes of the redox state of fibre surface-complexed iron. Furthermore our results showed clear differences between incubation of fibres in GS and SLS, respectively, indicating that phospholipids play an important part in fibre dissolution behaviour and oxidative reactivity. In conclusion we suggest, that biodurability testing procedures should not exclusively concentrate on dissolution rates of fibres. They should include fibre characteristics concerning known pathogenic mechanisms to evaluate the real toxic potential of the fibre type looking at. Secondly we suggest, that phospholipids should be constituents of incubation liquids used for standardised fibre biodurability test procedures thus representing more realistic incubation conditions.     

Effect of intratracheal fibres exposure on the rat lung

The changes in antioxidant status of rat lung after intratracheal instillation of stone-wool and glass fibres were studied. The animals were exposed to 2 or 8 mg of fibres for 4 or 16 weeks, the bronchoalveolar lavage was performed and the activity of superoxide dismutase, glutathione peroxidase and the total amount of glutathione was estimated both in tissue and in cell free fraction of bronchoalveolar lavage and the ascorbic acid was determined in lung tissue. The results showed the higher burden by stone-wool. Most changes were detected in groups exposed to higher dose of fibres for shorter time period, the most sensitive parameter was superoxide dismutase. The lung tissue was studied also by light microscopy and transmission electron microscopy.     

Upper limits of temperature for growth inChlorella (Chlorophyceae)

The upper limit of temperature for growth is a species-specific character in the genusChlorella. The limits of 14Chlorella species range from 26–30°C (C. saccharophila) to 38–42°C (C. sorokiniana), withC. fusca var.vacuolata (34°C) andC. kessleri (34–36°C) assuming an intermediate position. Thus, there is no wide gap in the temperature limits between the normal (“low-temperature”) species ofChlorella and the “high-temperature” species,C. sorokiniana.     

Consideration on a limit for lifetime occupational radiation exposure

Annual dose limits in occupational radiation exposure are merely a secondary constraint in addition to the primary rule of dose reduction and justification. The limits may, therefore, be reached only in rare, special cases. However, in principle, there might be cases in which the annual limit is continuously exhausted throughout a working life; a high total dose of 0.8 Sv could then be reached. In view of this possibility, there have been considerations of an added restriction by limiting the lifetime occupational dose to 0.4 Sv. The implications of such lifetime doses are considered, and it is shown that an exposure up to the maximum of 0.8 Sv will lead to the need for compensation, if a leukaemia were to occur in the exposed worker. A lifetime dose of 0.4 Sv equally spread over a working life will not lead to the critical value of the probability of causation in excess of 0.5. Nevertheless, it could cause such critical values when it is accumulated during shorter periods. More decisive than the probabilities of causation are, however, the absolute numbers of excess cases of leukaemia due to the occupational exposure. It is seen that less than one excess case would be expected if a group of 100 workers were all exposed to the maximum of 0.8 Sv. Since lifetime doses of 0.8 or 0.4 Sv will be accumulated in very few cases and only with special justification, there appears to be little need to introduce a further limit of lifetime exposure in addition to the current annual limit. Received: 15 November 1997 / Accepted in revised form: 1 April 1998     

The development of advanced cellulosic fibres

For the majority of the last century, commercial routes to regenerated cellulose fibres have coped with the difficulties of making a good cellulose solution by using an easy to dissolve derivative (e.g. xanthate in the case of viscose rayon) or complex (e.g. cuprammonium rayon). For the purposes of this paper, advanced cellulosic fibres are defined as those made from a process involving direct dissolution of cellulose. The first examples of such fibres have now been generically designated as lyocell fibres to distinguish them from rayons, and the first commercial lyocell fibre is Courtaulds' Tencel.     

An evaluation of several methods for assessing the effects of occupational exposure to radiation

Several methods for the analysis of occupational radiation exposure data, including procedures based on Cox's proportional hazards model, are presented and evaluated. Issues of interest include the contribution of an external control, the effective handling of highly skewed exposure data, and the potential for detecting effects in populations occupationally exposed to radiation. Expressions for evaluating the power of various procedures are derived and applied to data from the Hanford population in order to determine power curves for detecting leukemia effects, with both additive and multiplicative linear models being used. It is found that the introduction of an external control can increase power, although not when an overall adjustment factor must be estimated from the data or when death rates for the study population are substantially lower than those for the control population. It is also found that very little power is lost if exposures are grouped. Finally, the power calculations indicate, as expected, that in analyses of occupationally exposed populations, such as the Hanford workers, there is very little chance of detecting radiation effects at the levels of our current estimates. However, power is reasonably good for detecting effects that are 10 to 15 times larger.     

Succession and soil development in man-made coastal ecosystems at the Baltic Sea

By the creation of Køge Bay Seaside Park in 1978 the opportunity was given to study the establishment of vegetation and primary succession in a man-made coastal area. As the soil consists of marine material from the Baltic Sea, no organic matter or seedbank was present. The first steps of primary succession were followed in 1980, when the initial inventories of flora immigration and soil development were carried out in coastal grasslands and plantings. The surveys were repeated in 1992 and 1993. Except for the planted woody species and a few sown grasses, all other species of plants have reached the area through natural dispersal of diaspores. The total number of species in the permanent plots has increased from 26 in 1980 to 91 in 1993. The results indicate that this number will continue to increase in the coming years until a certain level. Then it will probably decrease as a result of competition from woody species, unless the vegetation is kept in a steady state by disturbances or management. Today the area is very far from the initial situation, and the off-shore barrier has changed towards a landscape dominated by small groves and grasslands of an urban common type.     

Cytogenetic investigation of occupational exposure to epichlorohydrin.

Cytogenetic evaluation of peripheral lymphocytes from 93 workers currently exposed to epichlorohydrin has revealed an increase in aberration rates as compared to that of a 75-person group seen for preemployment examination. Statistically significant differences were found in the distribution of individuals with chromatid breaks, chromosome breaks, severely damaged cells, and total abnormal cells. These results confirm the observations of Kucerova et al. in a similar occupational group.     

Exploring the limits of benzimidazole DNA-binding oligomers for the hypoxia inducible factor (HIF) site

The vascular endothelial growth factor (VEGF) and its receptors have been implicated as key-factors in tumor angiogenesis and are major targets in cancer therapy. New oligomers which mimic the architecture of DNA-binding polyamides have been designed to target the hypoxia inducible factor (HIF-1) binding site on the promoter of VEGF gene. These oligomers incorporate an increasing number of six–five fused rings such as hydroxybenzimidazole–imidazole, benzimidazole–pyrrole, benzimidazole–chlorothiophene, and imidazopyridine–pyrrole, and bind the VEGF hypoxia response element (HRE) 5′-TACGT-3′ with high affinity and selectivity.     

Investigations on DNA damage and frequency of micronuclei in occupational exposure to electromagnetic fields (EMFs) emitted from video display terminals (VDTs)

The potential effect of electromagnetic fields (EMFs) emitted from video display terminals (VDTs) to elicit biological response is a major concern for the public. The software professionals are subjected to cumulative EMFs in their occupational environments. This study was undertaken to evaluate DNA damage and incidences of micronuclei in such professionals. To the best of our knowledge, the present study is the first attempt to carry out cytogenetic investigations on assessing bioeffects in personal computer users. The study subjects (n = 138) included software professionals using VDTs for more than 2 years with age, gender, socioeconomic status matched controls (n = 151). DNA damage and frequency of micronuclei were evaluated using alkaline comet assay and cytochalasin blocked micronucleus assay respectively. Overall DNA damage and incidence of micronuclei showed no significant differences between the exposed and control subjects. With exposure characteristics, such as total duration (years) and frequency of use (minutes/day) sub-groups were assessed for such parameters. Although cumulative frequency of use showed no significant changes in the DNA integrity of the classified sub-groups, the long-term users (> 10 years) showed higher induction of DNA damage and increased frequency of micronuclei and micro nucleated cells.     

Temperature limits to early development of the New Zealand sea urchin Evechinus chloroticus (Valenciennes, 1846)

Seawater temperature is an important environmental factor for the early life stages of marine invertebrates. In this study we evaluated and described the effects of temperature during early development of E. chloroticus, identifying the optimum temperature range and upper thermal limit for successful development. The temperature range evaluated was between 15–24 °C which included the normal seawater temperatures during the spawning season in northern New Zealand, as well as the highest temperature projected by the IPCC for this region due to global warming (1–3 °C by the year 2100). Gametes from several females and males were used in the experiment. Fertilization was carried out at different temperatures and development was monitored at different time points after fertilization in each temperature. The development rate of E. chloroticus increased with an increase in seawater temperature. However, at temperatures higher than 21.5 °C the amount of abnormal development reached ∼30%. The optimum temperature for early development was between 15–21 °C, whereas the upper thermal limit was ∼24 °C. Therefore, early development of E. chloroticus is negatively affected by an increase in seawater temperature of ∼3–4 °C above current seawater temperature levels in northern New Zealand. The thermal sensitivity of early life stages of E. chloroticus could affect survival rates during early development of this species in a global warming scenario, which could impair recruitment in populations which are exposed to higher temperatures, leading to possible distributional shifts of this species.