Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Environmental Protection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1987

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC publication No. 13. The need for biological risk assessment in reaching decisions about carcinogens.

The prudent assumption that carcinogen bioassays in rodents predict for human carcinogenicity is examined. It is suggested that in certain cases, as for example the induction of tumors against a high incidence in controls, or in situations in which high dose toxicity may be a critical factor in the induction of cancer, the probability that animal bioassays predict for humans may be low. The term 'biological risk assessment' is introduced to describe that part of risk assessment concerned with the relevance of specific animal results to the induction of human cancer. Biological risk assessment, which is almost entirely dependent on an understanding of carcinogenesis mechanisms, is an important addition to present mathematical modeling used to predict the effects of animal carcinogens that have been demonstrated after high dose exposure, to the effects of the much smaller doses to which humans are perceived to be exposed. Evidence for the conclusions reached by biological risk assessment may sometimes be supported by a careful review of human epidemiological data.

Animals↗
PubMed1988

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC working paper No. 5. Genotoxicity tests as predictors of carcinogens: an analysis.

Differences between the results of numerical validation studies comparing in vitro and in vivo genotoxicity tests with the rodent cancer bioassay are leading to the perception that short-term tests predict carcinogenicity only with uncertainty. Consideration of factors such as the pharmacokinetic distribution of chemicals, the systems available for metabolic activation and detoxification, the ability of the active metabolite to move from the site of production to the target DNA, and the potential for expression of the induced lesions, strongly suggests that the disparate sensitivity of the different test systems is a major reason why numerical validation is not more successful. Furthermore, genotoxicity tests should be expected to detect only a subset of carcinogens, namely genotoxic carcinogens, rather than those carcinogens that appear to act by non-genetic mechanisms. Instead of relying primarily on short-term in vitro genotoxicity tests to predict carcinogenic activity, these tests should be used in a manner that emphasizes the accurate determination of mutagenicity or clastogenicity. It must then be determined whether the mutagenic activity is further expressed as carcinogenicity in the appropriate studies using test animals. The prospects for quantitative extrapolation of in vitro or in vivo genotoxicity test results to carcinogenicity requires a much more precise understanding of the critical molecular events in both processes.

Animals↗
PubMed1989

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 17. Can a mechanistic rationale be provided for non-genotoxic carcinogens identified in rodent bioassays?

In a recent survey of the results of the National Cancer Institute/National Toxicology Program's Carcinogenesis Bioassay Program, Ashby and Tennant (1988) drew attention to the high proportion of carcinogens that were non-genotoxic insofar as their response to the Salmonella-microsome test was concerned. The present review contrasts these findings with what is known mechanistically about non-genotoxic carcinogens that affect the tissues which are considered to be particularly prone to non-genotoxic tumor induction. Excessive and often thresholded increases in cellular proliferation in the affected tissues appear to be one common feature in tumor induction by these agents, which act either through cytotoxicity followed by regeneration or through hormone-mimetic action. It is suggested that a weight of the evidence approach on a chemical by chemical basis is necessary to decide the relevance of these agents to the human situation.

Animals↗
PubMed1990

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/1. Mutational events in the etiology of arteriosclerotic plaques.

The arteriosclerotic plaque is the lesion most often associated with cardiovascular disease, which is the leading cause of death in North America and Western Europe. Plaques are composed of cells (mostly smooth muscle cells but also macrophages and some lymphocytes) and formed elements (cellular debris, collagen, elastin, glycosaminoglycans, lipid droplets, cholesterol crystals and sometimes calcium deposits). Proliferation of smooth muscle cells is essential to plaque formation and development. Most theories of plaque development have viewed this proliferation as a secondary event following an initiating stimulus (e.g., endothelial injury). According to this view, the proliferating smooth muscle cells are otherwise identical to the large number of non-proliferating smooth muscle cells in the artery wall. The 'monoclonal' hypothesis of plaque formation presents a fundamentally different view; namely, that the cell proliferation critical to plaque development follows the stable transformation of smooth muscle cells and that the plaques can therefore be viewed as benign smooth muscle cell tumors of the artery wall. Environmental agents, including viruses and chemicals that have been previously associated with cell transformation and tumorigenesis may therefore also contribute directly to plaque development. Data are provided from in vivo and in vitro studies in support of this proposition. Evidence is also presented that in standardized assays human and animal plaque DNAs elicit responses similar to those elicited by tumor DNAs. Thus, both plaque formation and tumorigenesis may share common mechanisms.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis--a review of the epidemiological evidence.

This paper reviews the epidemiological literature of relevance for the hypothesis that somatic mutation is involved in the formation of the atherosclerotic plaque. Assuming that somatic mutations are involved in atherogenesis, one would expect at least some of the risk factors for cancer and for atherosclerosis to be identical. Therefore, the review covers the correlated occurrence of cancer and atherosclerotic disease. Special interest is given to populations at high risk of cancer, including subpopulations with certain genetic diseases, and populations exposed to certain carcinogenic environmental agents including ionizing radiation, vinyl chloride monomer (VCM), arsenic, tobacco, and various industrial combustion effluents containing polycyclic aromatic hydrocarbons (PAHs). Exposure to combustion effluents from burning of tobacco or fuel is associated with an increased risk of cancer and atherosclerotic disease. Combustion effluents constitute a complex mixture of potentially hazardous agents, however, and the observed correlation of cancer and atherosclerosis among exposed persons cannot be unambiguously interpreted as evidence of a common etiology of the two groups of diseases. For ionizing radiation, arsenic, and VCM there is suggestive evidence that these agents possess an atherogenic effect beside their well-known carcinogenic properties. Both arsenic and VCM seem to have a specific affinity to the vascular bed causing various lesions including angiosarcomas and atherosclerotic plaques. Regarding ionizing radiation, the atherogenic effects seem to be localized to heavily irradiated fields. Beside the carcinogenic and atherogenic effects, exposure to arsenic, VCM, and ionizing radiation brings about an increase in the incidence of mutations and chromosomal aberrations. A theory involving somatic mutation in the pathogenesis of the atherosclerotic plaque could be consistent with the observed biological effects of ionizing radiation, arsenic, and VCM. The scant data from families with certain inherited diseases may also be consistent with an involvement of the genome in the pathogenesis of atherosclerosis. In conclusion, there is strong epidemiological evidence that several factors associated with an increased risk of cancer are also associated with an increased risk of atherosclerosis.

Arsenic↗
PubMed1990

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/3. Animal studies suggesting involvement of mutagen/carcinogen exposure in atherosclerosis.

It is very important to elucidate the causative agents of atherosclerosis because coronary heart disease and cerebrovascular disease are the main causes of death in the developed countries. The evidence for a monoclonal origin of atherosclerotic plaques in humans prompted the study of the involvement of mutagens/carcinogens in the development of atherosclerosis. Polycyclic hydrocarbons, including 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene, were shown to act as initiators and/or accelerators in atherosclerotic plaque formation in the chicken, pigeon and mouse. Radiation and oxygen radicals were also demonstrated to be involved in the development of atherosclerosis in animals.

Amines↗
PubMed1990

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 1/2. A multi-factor ranking scheme for comparing the carcinogenic activity of chemicals.

A scheme for ranking the quantitative activity of chemical carcinogens is described. This activity scheme uses as its base, dose potency measured as TD50, the chronic dose rate that actuarially halves the adjusted percentage of tumor-free animals at the end of the study (Gold et al., Environ. Health Perspect., 67, 161-200, 1986). The TD50 is converted into an inverse log scale, a decile scale, and then adjusted by weighting factors that describe other parameters of carcinogenic activity. These factors include positive or negative weightings for: the induction of tumors at tissues or organs associated with high historical control tumor incidences; the induction of tumors at multiple sites; the induction of tumors in both sexes of the species; and the induction of tumors in more than one species. These factors were chosen as they represented qualitative descriptions of the general specificity or non-specificity of chemicals with regard to the activity in rodents and have some bearing on the potential activity of chemicals in humans. In order to construct a measure to express the inactivity of chemicals towards the induction of cancer, a measure analogous to the TD50 has been developed: the highest average daily dose or HADD. The HADD is the highest average daily dose in mg chemical/kg body weight administered in a chronic cancer study and that did not induce a statistical increase in tumors. HADD values were similarly converted to log decile units and adjusted by weighting factors according to lack of activity in both sexes of a species, and the lack of activity in more than one species. In order to explore the use of this multi-factor activity scheme for both carcinogens and non-carcinogens, a group of 142 chemicals was selected that had been tested according to an oral dosing protocol in two sexes of two species of rodents and whose data was peer-reviewed and available for this analysis. This data came from the National Toxicology Program/National Cancer Institute Bioassay Technical Reports. Three activity ranking schemes were developed: the Carcinogen Activity-F344 Rat, an activity scheme based on cancer data obtained with the F344 rat; the Carcinogen Activity-B6C3F1 Mouse, an activity scheme based on cancer data obtained with the B6C3F1 mouse, and the Carcinogen Activity-Combined, an activity scheme based on selecting data from both the F344 rat and the B6C3F1 mouse. This selection was based on the most sensitive rodent responding to the carcinogenic activity of active chemicals and the least sensitive rodent responding to the toxic effects of inactive chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1990

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 10. A new approach to germinal mutation surveillance: pair-wise evaluation of component elements in unidentified multiple congenital abnormalities.

In the Hungarian population-based surveillance of germinal mutations, 3 indicator conditions of offspring are being followed, namely 15 sentinel anomalies, Down syndrome and unidentified multiple congenital abnormality. The latter is discussed here as a possible indicator of germinal dominant gene and chromosomal mutations. The component congenital abnormalities of unidentified multiple congenital abnormalities are classified into 45 groups. The component congenital abnormalities were reduced to pairs. A pair is a set of 2 independent component congenital abnormalities in index patients with 2 or more congenital abnormalities. Baseline figures of all component congenital abnormality pairs in 3722 unidentified multiple congenital abnormalities were determined in the study period 1973-1982. The observed data for 1983 were compared with expected occurrences based on baseline figures. This pair-wise evaluation of component elements within unidentified multiple congenital abnormalities seems to be an adequate surveillance method to detect any time cluster of congenital abnormality pairs due to environmental factors including germinal mutagens.

Abnormalities, Multiple↗
PubMed1991

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 18. Review of the genotoxicity and carcinogenicity of antischistosomal drugs; is there a case for a study of mutation epidemiology? Report of a task group on mutagenic antischistosomals.

One of the interests of ICPEMC is to identify situations in which the possible induction of inherited defects in man by mutagen exposure could actually be studied. The large-scale use of mutagenic drugs in field programmes against schistosomiasis, mainly during the 1970's, was considered a possible case. An ICPEMC task group approached the problem by (1) updating the genetic toxicology data base for antischistosomal drugs, and (2) reviewing possible study areas. Expertise was combined from genetic toxicology, mutation epidemiology and tropical medicine. It was considered that: (a) if any, hycanthone would be the most appropriate candidate drug for study; (b) it would be virtually impossible to meet the basic requirements of an appropriate mutation epidemiology study, in endemic countries; (c) as more defined genetic endpoints would be selected (e.g. sentinel phenotypes) the required large sample sizes would seem prohibitive, since documentation on past programmes is limited and local demography would render the reliable tracking of substantial numbers of offspring of treated persons an almost impossible task; (d) in most endemic countries proper diagnosis and registration of inherited defects is largely lacking; (e) the problems encountered in demonstrating inherited effects in humans after heavy or chronic exposure to established animal mutagens such as ionizing radiation and cancer chemotherapy, in combination with the ambiguous nature of the animal germ cell data with hycanthone, do not particularly warrant large expectations; (f) since non-mutagenic antischistosomal drugs are now in use, the problem is academic and of low priority in the endemic countries whose medical and research resources are often limited. Thus, studying offspring of hycanthone-treated people to demonstrate the mutagenic potential of the drug in man is not a viable enterprise.

Animals↗
PubMed1991

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 19. The classification of carcinogens identified in the rodent bioassay as potential risks to humans: what type of substance should be tested next?

The relevance of rodent cancer bioassay data to humans is discussed in relation to the needs of regulatory agencies. The usefulness of in vivo and in vitro genotoxicity testing in this connection is also discussed. In the case of rodent carcinogens that do not elicit genotoxicity, it is suggested that homeostatic imbalance, cell proliferation, and other processes may play a major role in tumor development and its importance to the possible ability of the test agent to induce human cancer. These possibilities need to be evaluated on a case by case basis. The methods by which chemicals are selected for the rodent cancer bioassay are also discussed and it is pointed out that naturally-occurring constituents of human foods should in future receive greater priority as a consequence of anticipated changes resulting from biotechnology.

Animals↗
PubMed1993

International Commission for Protection Against Environmental Mutagens and Carcinogens. Power frequency electric and magnetic fields: a review of genetic toxicology.

Epidemiologic studies have reported a modestly increased risk of childhood leukemia associated with certain electric power wire configurations. Since cancer likely involves DNA damage, this review discusses the evidence of direct and indirect genetic toxicity effects for both electric and magnetic fields at 50- and 60-Hz and miscellaneous pulsed exposures. Exposure conditions vary greatly among different end points measured, making comparisons and conclusions among experiments difficult. Although most of the available evidence does not suggest that electric and/or magnetic fields cause DNA damage, the existence of some positive findings and limitations in the set of studies carried out suggest a need for additional work.

Animals↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the maintenance of genetic stability.

DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases.

Animals↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and operationally non-genotoxic carcinogens.

A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect. Oxidative DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewed for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidative DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with aging are the result of the accumulation of lesions resulting from unrepaired oxidative DNA damage.

Animals↗