The purpose of the micronucleus test is to identify substances (liquid or solid) that cause cytogenetic damage which results in the formation of micronuclei containing lagging chromosome fragments or whole chromosomes. An increase in the frequency of micronucleated polychromatic erythrocytes in treated animals is an indication of induced chromosome damage. Animals are exposed to the test substance by an appropriate route (usually by gavage using a stomach tube or a suitable intubation cannula, or by intraperitoneal injection). Bone marrow and/or blood cells are collected, prepared and stained. Preparations are analyzed for the presence of micronuclei. Each treated and control group must include at least 5 analysable animals per sex. Administration of the treatments consists of a single dose of test substance or two daily doses (or more). The limit dose is 2000 mg/kg/body weight/day for treatment up to 14 days, and 1000 mg/kg/body weight/day for treatment longer than 14 days.
Male Chinese hamsters and mice are commonly used. Animals are exposed to the test substance (liquid or solid) by an appropriate route of exposure, usually by gavage or by intraperitoneal injection. Then, they are sacrificed at appropriate times after treatment. Each treated and control group must include at least five analysable males. Test substances are preferably administered once or twice but they may also be administered as a split dose to facilitate administering a large volume of material. Prior to sacrifice, animals are treated with a metaphase-arresting agent. Chromosome preparations are then made from germ cells and stained, and metaphase cells are analyzed for chromosome aberrations. A limit test may be performed if no effects would be expected at a dose of 2000 mg/kg bw/d. Positive results from the in vivo spermatogonial chromosome aberration test indicate that a substance induces chromosome aberrations in the germ cells of the species tested.
The method is based on the repeated oral administration of the substance of interest over a prolonged period (one dose level daily during 90 days). This Test Guideline is intended primarily for use with non-rodents species. The commonly used non-rodent species is the dog (the beagle is frequently used). At least 8 animals (4 female and 4 male) should be used for each test group. Three concentrations, at least, should be used. The test compound is administered in the diet or in the drinking water, by gavage or in capsules. A limit test may be performed if no effects would be expected at a dose of 1000 mg/kg bw/d. The results of this study include: measurements (weighing at least once a week, food/water consumption) and daily (preferably at the same time) and detailed observations (ophtalmological examination, haematology, clinical biochemistry and urinalysis), as well as gross necropsy and histopathology. A properly conducted 90-day subchronic test should provide a satisfactory estimation of a no-effect level.
Males and females of the Parent generation (5-9 weeks old) should be dosed during growth, during their mating, during the resulting pregnancies, and through the weaning of their first generation offspring. The administration of the substance is continued to first generation offspring during their growth into adulthood, mating and production of a second generation (until the weaning). The rat is the preferred species for testing. Each test and control group should contain a sufficient number of animals to yield preferably not less than 20 pregnant females at or near parturition. At least three dose levels and a concurrent control shall be used. It is recommended that the test substance be administered orally (by diet, drinking water or gavage). A limit test may be performed if no effects would be expected at a dose of 1000 mg/kg bw/d. The results of this study include: measurements (weighing, sperm parameters, oestrus cycle parameters and offspring parameters), clinical daily observations, as well as gross necropsy and histopathology. The findings of this two-generation reproduction toxicity study should be evaluated in terms of the observed effects including necropsy and microscopic findings. A properly conducted reproductive toxicity test should provide a satisfactory estimation of a no-effect level and an understanding of adverse effects on reproduction, parturition, lactation, postnatal development including growth and sexual development.
The Test Guideline focuses on rodents and oral administration. Both sexes should be used. For rodents, at least 20 animals per sex per group should normally be used at each dose level, while for non-rodents a minimum of 4 per sex per group is recommended. At least three dose levels should be used in addition to the concurrent control group. Frequency of exposure normally is daily, but may vary according to the route chosen (oral, dermal or inhalation) and should be adjusted according to the toxicokinetic profile of the test substance. The duration of the exposure period should be 12 months. The study report should include: measurements (weighing) and regular detailed observations (haematological examination, urinalysis, clinical chemistry), as well as necropsy procedures and histopathology.
The test is usually based on the incorporation of tritium-labelled thymidine, 3H-TdR, (during 3-8 hours) into the DNA of liver cells which have a low frequency of cells in the S-phase of the cell cycle. The uptake of 3H-TdR is usually determined by autoradiography. Rats are commonly used, and the number of animals should be at least three analysable animals per group. Normally, at least two dose levels are used. A limit test may be performed if no effects would be expected at a dose of 2000 mg/kg bw/d. Test substances are generally administered as a single treatment by gavage using a stomach tube or a suitable intubation cannula. Liver cells are prepared from treated animals 12-16 hours after dosing of animal. After autoradiography, normally 100 cells are scored from each animal from at least two slides. A positive result from the UDS test with mammalian liver cells in vivo indicates that a substance induces DNA damage in mammalian liver cells in vivo that can be repaired by unscheduled DNA synthesis in vitro. A negative result indicates that, under the test conditions, the test substance does not induce DNA damage that is detectable by this test.
This Test Guideline is designed for use with the rat. It is recommended that the test substance be administered orally by gavage. This should be done in a single dose daily to the animals using a stomach tube or a suitable intubation cannula. Each group should be started with at least 10 animals of each sex. Generally, at least three test groups and a control group should be used. Dose levels should be selected taking into account any existing toxicity and (toxico-) kinetic data available. The limit test corresponds to one dose level of at least 1000 mg/kg body weight. The results of this study include measurements (weighing, food/water consumption) and daily detailed observations (including sensory reactivity to stimuli), preferably each day at the same time, as well as gross necropsy and histopathology. The findings of this toxicity study should be evaluated in terms of the observed effects, necropsy and microscopic findings. The evaluation will include the relationship between the dose of the test substance and the presence or absence of observations. Because of the short period of treatment of the male, the histopathology of the testis and epididymus must be considered along with the fertility data, when assessing male reproduction effects.
Cells in suspension or monolayer culture are exposed to, at least four analysable concentrations of the test substance, both with and without metabolic activation, for a suitable period of time. They are subcultured to determine cytotoxicity and to allow phenotypic expression prior to mutant selection. It is recommended to utilise at least 106cells. Cytotoxicity is usually determined by measuring the relative cloning efficiency (survival) or relative total growth of the cultures after the treatment period. The treated cultures are maintained in growth medium for a sufficient period of time, characteristic of each selected locus and cell type, to allow near-optimal phenotypic expression of induced mutations. Mutant frequency is determined by seeding known numbers of cells in medium containing the selective agent to detect mutant cells, and in medium without selective agent to determine the cloning efficiency (viability). After a suitable incubation time, colonies are counted.
Groups of at least 10 male and 10 female rodents are exposed 6 hours per day for 90 days to a) the test chemical at three or more concentration levels, b) filtered air (negative control), and/or c) the vehicle (vehicle control). Animals are generally exposed 5 days per week but exposure for 7 days per week is also allowed. Males and females are always tested, but they may be exposed at different concentration levels if it is known that one sex is more susceptible to a given test chemical. The results of the study include measurement and daily and detailed observations (haematology and clinical chemistry), as well as ophthalmology, gross pathology, organ weights, and histopathology. This Test Guideline allows the flexibility to include satellite (reversibility) groups, interim sacrifices, bronchoalveolar lavage (BAL), lung burden (LB) for particles, neurologic tests, and additional clinical pathology and histopathological evaluations in order to better characterize the toxicity of a test chemical.
Over the years, advances in space technologies have led to the development of increasingly sophisticated military and civil space assets.
Where is the space sector heading now? What are the obstacles to its further development? What are its future prospects? What are the applications that are likely to be successful in the future?
To answer these questions, this report adopted a scenario-based approach to explore the future evolution of major components of the space sector (military space, civil space, commercial space) over the next thirty years. It covers four major factors of change: geopolitical developments, socio-economic developments, energy and the environment, technology.
"Outstanding review, especially useful for the three sophisticated scenarios, useful to many futurists."
Future Survey, August 2004.
In particular it argues that the current governance of international migration is both insufficient and inefficient. Restrictive and non-cooperative migration policies not only affect development in sending countries but also have counterproductive effects in the countries that implement them. Likewise, the lack of integration policies generates costs for society. In this respect, the book focuses on South-South migration and highlights the specific risks of neglecting integration in developing countries. It also analyses the effects of emigration on origin-country labour markets and underlines the externalities of immigration policies in migrant-sending countries.
The book explores the feasibility of implementing a coherent governance framework centred on three complementary objectives: i) a more flexible regulation of international migration flows; ii) a better integration of immigrants in developing countries; and iii) a higher impact of labour mobility on development.
OECD governments are increasingly using environmentally related taxes because they are typically one of the most effective policy tools available. Exploring the relationship between environmentally related taxation and innovation is critical to understanding the full impacts of this policy instrument as well as one potential facet of “green growth.” By putting a price on pollution, do environmentally related taxes spur innovation? What types of innovation result? Does the design of the tax play a critical role? What is the effect of this innovation?
In analysing these questions, this report draws on case studies that cover Japan, Korea, Spain, Sweden, Switzerland, the United Kingdom, Israel and others. It covers a wide set of environmental issues and technologies, as well as the economic and policy contexts. The research methods range from econometric analysis to interviews with business owners and executives. The report also explores the use of environmentally related taxes in OECD countries and outlines considerations for policymakers when implementing these taxes.
Green growth policies can stimulate economic growth while preventing environmental degradation, biodiversity loss and unsustainable natural resource use. The results from this publication will contribute to the Green Growth Strategy being developed by the OECD as a practical policy package for governments to harness the potential of greener growth.
China Education Daily nominated this book as one of the "100 most influential education books for teachers" on December 15, 2011.