Showing papers in "IARC scientific publications in 1980"

Cooperative Programme on Short-Term Assays for Carcinogenicity in Japan

Abstract: This entry consists of charts noting mutagenicity or carcinogenicity of 182 compounds examined under a project of the Japanese Ministry of Health and Welfare using Salmonella typhimurium TA100 and TA98, Bacillus subtilis, hamster lung fibroblast cells, human embryo fibroblasts, bone-marrow cells, and silk worms.

Asbestos retention in human respiratory tissues: comparative measurements in lung parenchyma and in parietal pleura.

Abstract: Asbestos fibres in respiratory tissues from 29 cases diversely exposed to asbestos dusts have been characterized, sized and counted using a transmission electron microscope. Comparison of data obtained by measurement of fibres in lung parenchyma and in parietal pleura samples showed the following: -- In each case, the proportion of chrysotile fibres (as opposed to amphiboles) was higher in parietal pleura than in lung parenchyma. (The proportion of chrysotile in pleura was greater than 90% in 30 of the 40 samples.) -- Fibres encountered in parietal pleura were shorter than those in the parenchyma. -- There was no evident correlation between numerical concentrations of fibres in lung parenchyma and those in parietal pleura. This study has shown that characteristics of asbestos retention in parietal pleura cannot be derived from measurements in lung parenchyma. On the basis of the cases analysed here, who were exposed to mixed types of asbestos dust, chrysotile seems to be the asbestos type retained almost exclusively in parietal pleural tissues. These findings might be taken into account when assessing the risk of pleural diseases (especially mesothelioma) attributable to each type of asbestos fibre.

The incidence of pneumoconiosis, mesothelioma and other respiratory cancer in men engaged in mining and milling crocidolite in Western Australia.

Abstract: Previous employees of a mining company, engaged in mining of crocidolite at Wittenoom Gorge in Western Australia between 1943 and 1966, have been traced to determine their incidence of asbestos-related diseases. Of 6200 male employees, 220 (3.5%) have developed pneumoconiosis and 26 have developed pleural mesothelioma. No cases of peritoneal mesothelioma have been identified. Prior to 1978, 60 men had died from respiratory cancer other than mesothelioma, compared with 38.25 expected from the mortality experience of all Western Australian males. The incidence of pneumoconiosis and mesothelioma and the mortality from other respiratory cancer all increased with duration of employment, interval from first employment, and level of occupational exposure, indicating a strong relationship between intensity of asbestos exposure and these diseases. The mortality ratio for respiratory cancer, excluding mesothelioma (1.57), was nearly twice that for all nonrespiratory causes of death, suggesting a two-fold increase in mortality from respiratory cancer compared with all Western Australian males. Variation of mortality from respiratory cancer by duration of employment and occupational exposure suggests that at least 30% of respiratory cancer deaths other than mesothelioma may be due to asbestos exposure. The major part of this excess is accounted for by respiratory cancer occurring in men with previously diagnosed pneumoconiosis.

Toward a classification scheme for degrees of experimental evidence for the carcinogenicity of chemicals for animals.

Abstract: A classification scheme is proposed for degrees of experimental evidence for the carcinogenicity of chemicals for animals. The classification stems from the suggestions of an IARC Working Group that the evaluation of bioassays include consideration of whether an increase in malignant tumours occurred and whether it occurred to an unusual degree or in multiple experiments. We extended the evaluative process to chemical experiments with no evidence of carcinogenicity and gave increased emphasis to results from more than one animal species. Although the proposed classification was developed for a group of NCI bioassays which were similar in design and conduct, it may provide a general framework for the evaluation of carcinogenesis bioassays and stimulate development and application of evaluative methods.

The consequences of exposure to asbestos dust in a wartime gas-mask factory.

Abstract: This further study of wartime gas-mask workers who were exposed to asbestos dust has shown that among those who worked with crocidolite there is a considerable excess of cases of mesothelioma, a more modest excess of bronchial carcinoma, but no excess of any other type of malignant disease. A dose-response relationship is established in the mesothelioma and bronchial carcinoma patients. It is not possible to base any conclusions on the limited data available for the small number of people exposed to chrysotile for a maximum period of five months. We believe that the identification and measurement of fibres in autoptic lung tissue from patients with accurately known occupational histories of asbestos dust exposure is useful, and a similar study on a population exclusively exposed to chrysotile would be of considerable interest.

Mutagenic activity of chemicals previously tested for carcinogenicity in the National Cancer Institute bioassay program.

Abstract: Twenty-six chemicals treated in long-term carcinogenicity bioassays were tested for mutagenicity in the Salmonella/microsome plate assay. Of the eight chemical reported as being noncarcinogenic in animals, five were not mutagenic and three induced a mutagenic response. Thirteen chemicals were carcinogenic in either rats, mice or both species. Ten of these were positive in the mutagenicity assay, and three were negative. Four chemicals were suspect as far as the carcinogenicity results were concerned, and three were negative. The results obtained in vivo with one compound were inconclusive, and the mutagenicity results were negative.

Animal experiments on biological effects of mineral fibres.

Abstract: The papers presented in this session are summarized. Although asbestos fibres produce tumours in a number of animal species tested, rats appear to be the most susceptible, in terms of latent period and numbers of tumours produced. The deposition, translocation and clearance of different types of fibres in the lung have been investigated in a number of experiments, and it has been shown that many of them migrate more readily than was previously thought; their penetration into the gut was the object of further investigation. The syncarcinogenicity with asbestos of various substances, such as benzo[a]pyrene, N-nitrosodiethylamine, cigarette smoke or radiation, is described. Experiments on the different carcinogenicities of different fibres are summarized; although it is pointed out that there is much controversy in this area. A hypothesis is presented whereby the carcinogenic potency of a fibre is dependent on various size parameters, based on length, diameter and length:diameter ratio. On the basis of this hypothesis, the carcinogenic potency of short fibres may be weak, but many short fibres may induce a tumour as easily as a few long fibres. Finally, a plea is made for a far greater number of well-defined standard samples of asbestos and man-made mineral fibres than exists at present, since there are currently great difficulties in comparing and interpreting results.

Roentgenographic lung changes, asbestosis and mortality in a Belgian asbestos-cement factory.

Abstract: Annual chest radiographs, work history and mortality of 1,973 workers in an asbestos-cement factory were correlated with age and with duration and level of dust exposure. Degree of radiographic lung change was significantly related to fibre-years of exposure in the case of small lung opacities, pleural adhesions and pleural thickening. For 29 cases of asbestosis diagnosed between 1963 and 1977, a highly significant dose-response relationship was found. In comparison with national mortality rates, there was an excess of deaths due to cancer of the gastrointestinal tract, although there was no relationship to fibre-years.

The pathology and mineral content of lungs in cases of mesothelioma in the United Kingdom in 1976

Abstract: A study was made of 93 cases of mesothelioma who died in 1976 in the United Kingdom. Lung tissue was available for mineral fibre analysis from 86 of these cases, and also from 29 cases of cerebrovascular disease and 27 cases of bronchial carcinoma, matched for place of death, age and sex with the mesothelioma cases. It was observed that: (1) mesothelioma patients had more amphibole fibres in their lungs than did control cases; (2) chrysotile fibres were not present in greater numbers in the mesothelioma patients than in the control cases; (3) four of the mesothelioma cases had no amphibole fibres in their lungs; two of these had chrysotile fibres, and the other two had no asbestos fibres; and (4) 30 cases of mesothelioma had no chrysotile fibres in their lungs.

Dimensions of airborne asbestos fibres.

Abstract: Systematic measurements were made of the dimensions of fibres found in the air in mines and mills for crocidolite, amosite and chrysotile. Samples were collected on membrane filters and examined in light, transmission electron and scanning electron microscopes. The proportion of short fibres was shown to decrease with extent of processing, especially for amosite. No airborne fibres had a diameter greater than 3 micrometers, and all would therefore be capable of reaching the pulmonary alveoli. It was shown that for the same airborne mss of the different varieties of asbestos, fewer amosite fibres would be present than crocidolite or chrysotile fibres. Most of the fibres to which workers are exposed are short and thin. It was also shown that the choice of analytical method and the limits of fibre dimension that can be observed are critical. Thus, fibres greater than 5 micrometers which are visible in the light microscope represent only a small proportion of the total fibre count, and transmission electron microscopic methods can lead to under-reporting of long fibres.

Occurrence of volatile nitrosamines in food: a survey of the West German market.

Abstract: More than 3000 food samples from the West German market have been analysed for volatile nitrosamines. N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) in concentrations above 0.5 micrograms/kg were found in only 3 and 2% of the samples, respectively. N-Nitrosodimethylamine (NDMA) was detectable in 30% of the samples and 6% of them were found to contain more than 5 micrograms/kg. Consumption data given in the "Nutritional Report, 1976" allow calculation of the average daily intake of volatile nitrosamines from food. Intakes for West German males are 1.1 micrograms/day for NDMA and 0.1 micrograms/day for NPYR. With regard to NDMA, the relative contributions are 64% for beer, 10% for meat and meat products and 25% for all other foods (150 types). NDMA in beer originates in the malt, where it is formed during kilning (drying). Technological improvements to eliminate NDMA contamination of beer are reported.

Chemical studies on tobacco smoke LXVIII. Analysis of volatile and tobacco-specific nitrosamines in tobacco products.

Abstract: The yields of volatile N-nitrosamines in cigarette smoke are primarily dependent upon the nitrate content of the tobacco and, to some extent, on the protein content. Cellulose acetate tips, such as those found on most commercial filter cigarettes, selectively remove at least 70% of the volatile N-nitrosamines, independently of the pH of the weakly acidic or weakly alkaline smoke. So far, three tobacco-specific N-nitrosamines have been detected in tobacco and tobacco smoke. During tobacco processing and smoking, N'-nitrosonornicotine is formed by nitrosation of nicotine and, to a minor degree, by nitrosation of nornicotine, whereas 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone originates from oxidative nitrosation of nicotine. N'-Nitrosoanatabine is formed by nitrosation of the second most abundant tobacco alkaloid, anatabine. The tobacco-specific N-nitrosamines in the smoke arise partly from the tobacco by transfer and partly by nitrosation of the alkaloids during smoking (pyrosynthesis). Preliminary results indicate that cellulose acetate filter tips may selectively remove considerable amounts of the nonvolatile nitrosamines from the smoke.

Metabolism of N-nitrosodimethylamine.

Abstract: NDMA and NDEA are metabolized by a microsomal enzyme system that requires NADPH and oxygen. This metabolism leads to an unstable product which decomposes to yield a reactive alkylating species. This species is too reactive chemically to influence significantly organs other than those in which it was generated. Alkylation of cellular components, particularly DNA, is a critical event in the initiation of tumours by these carcinogens. The greatest capacity to metabolize these nitrosamines to alkylating agents is found in the liver, but other organs, including the oesophagus, lung and kidney, are also capable of activation. These organs may be more susceptible to alkylation than the liver because they have a lesser ability to catalyse the removal of 06-alkylguanine from their DNA. However, orally administered doses of NDMA and the NDMA formed by nitrosation reactions within the gastrointestinal tract are rapidly absorbed from the upper part of the small intestine and carried to the liver in the portal blood supply. When small doses are given in this way, the capacity of the liver to metabolize the carcinogen is sufficient that the nitrosamine is effectively cleared in a 'first-pass' effect, leaving very little to interact with other organs. This has two important consequences: firstly, levels of NDMA found in peripheral blood may be significantly lower than those expected on the basis of total dietary exposure because of the rapid metabolism and effective clearance of the carcinogen by the liver; secondly, physiological factors leading to reduction of the metabolic activation in the liver may result in more of the carcinogen being metabolized other tissues and in a greater risk of cancer developing in those tissues.

Lung cancer mortality in relation to measured dust levels in an asbestos textile factory.

Abstract: A cohort of 255 men who entered this factory since the beginning of 1951, when routine dust sampling weas initiated, have been followed up to the end of 1978. Eight (1.62 expected) died of lung cancer over 20 years after first exposure (P less than 0.001). Earlier estimates of dust levels hve been revised to correspond to modern counting methods, and the average cumulative exposure of this cohort is now estimated to have been 200-300 fibres/ml-years. No deaths have yet been attributed to asbestosis, but a separate study of this group has reported that 10 of these men have been certified as asbestotic. An earlier analysis of lung cancer, mesothelioma and asbestosis incidence in men employed prior to 1951 suggested a dose-response relationship for lung cancer in relation to static sampler dust measurements that was probably approximately correct, but it is not clear whether personal sampling wound give similar results.

Further studies on the occurrence of volatile and non-volatile nitrosamines in foods.

Abstract: Approximately 250 samples of various foods, such as cured meat products, fried bacon, cooked-out bacon fats, baby foods containing meats, tomato products, cooked pizza, powdered and evaporated milk, mushrooms and different varieties of alcoholic beverages, were analysed by GLC-TEA for the presence of volatile nitrosamines. The levels detected in cured meat products (both cooked and uncooked) were very low, and both their incidence (at greater than 1 microgram/kg) and concentrations were much lower than those observed in a 1974 survey. The levels of N-nitrosopyrrolidine (NPYR) in fried bacon and cooked-out bacon fats were also somewhat lower than those observed at the end of 1976, but the decrease may not be significant. Traces (mean, 1.5 micrograms/kg) of N-nitrosodimethylamine (NDMA) were detected in 21 of 22 samples of beers and ales. Most of the remaining foods gave negative results, excepting the skim milk powders, which contained minute traces (mean, 0.4 micrograms/kg) of NDMA. An HPLC-TEA method was developed for the analysis of N-nitrosoproline (NPRO) and N-nitrososarcosine (NSAR) in raw and fried bacon. A study of the heat-induced decarboxylation of these nitrosamino acids suggests that these compounds are heat-labile and would not be expected to occur in fried foods at significant levels. Their presence, however, may lead to the formation of traces of NPYR and NDMA during frying at lower temperatures.

Occurrence, formation and precursors of N-nitroso compounds in the Japanese diet.

Abstract: A survey has been made of volatile nitrosamines in 123 fermented foods. These included salt-fermented vegetables, soy sauce, "miso", Japanese "sake" and other fermentation products. No appreciable amount, or only trace quantities, of NDMA and NPYR were detected in vinegar, "sake", wines and whiskies, while minute quantities of NDMA were detected in 31 out of 33 beer samples, where the levels ranged from traces to 13.8 micrograms/l, with an average of 5.1 micrograms/l. The nitrosamine content of salt-dried fish apparently increased when these products were broiled in a city gas range. A method for the determination of N-alkylureas in foods has been developed. A total of 57 food samples, both uncooked and broiled in a gas range or fried, were analysed. No alkylureas could be detected in these samples.

Comparison of length-dependent cytotoxicity of inhalable asbestos and man-made mineral fibres.

Abstract: Fibres of various defined length distributions were tested in vitro and in vivo. Tumour cells with phagocytic ability were used as the in vitro test system. DNA and protein synthesis and cell proliferation and enzyme release (LDH) were determined. Using gravimetrical and numerical doses in cultures, good indications of the toxicity of single fibres were found. It was possible to demonstrate clear-cut relationships between fibre length and cytotoxicity. In this test system, the toxicity of fibres increases with increasing length. The results of the cell experiments also furnish important indications of the doses of fibrous dusts to be used in animal tests and of the possibility of comparing different fibres with each other, especially with respect to the numerical or gravimetrical quantification of fibre fractions. Amosite, chrysotile, crocidolite and glass fibres of three or four different length spectra were tested.

Lung cancer risk associated with manufacture of asbestos-cement products.

Abstract: The mortality experience of a cohort of 5645 Louisiana asbestos-cement workers with a minimum follow-up of 20 years was related to total dust, duration and concentration of exposure and fibre type Excess respiratory cancer risk was detected in workers with moderate and heavy asbestos dust exposure, but no excess risk occurred in categories of lower exposure Mortality due to all other causes was normal Both duration and level of exposure were shown to contribute to risk; both variables exhibited levels at which no excess mortality was detected Workers exposed to both chrysotile and crocidolite appeared to be at greater risk of respiratory malignancy than those with exposure to chrysotile only

Biological effects of attapulgite.

Abstract: Some clay minerals occur naturally in a fibrous or lath-like crystal state as attapulgite and sepiolite. Because of their sorptive and colloidal properties, attapulgite and sepiolite have numerous industrial applications, mainly as additives in oil-drilling muds, in chemical fertilizers, pesticides, paints, adhesive products, bleaching agents, cosmetic compounds and phytosanitary products. World consumption of each is over one million tons annually. Acid-treated attapulgite is used in the composition of certain drugs used for the treatment of gastrointestinal diseases. Such drugs available commercially in France were analysed for their mineral content by transmission electron microscopy and found to contain attapulgite fibres [mean length: 0.9 micrometers (0.1-3.6); mean diameter: 0.05 micrometers (0.01-0.5)]. The haemolytic activities of a Spanish attapulgite sample and of three samples of drugs sold in France were greater or similar to that of UICC chrysotile asbestos. Attapulgite fibres were encountered in large quantities in the lung washing fluid of a patient suffering from lung fibrosis who had been exposed recently for three years during the processing of attapulgite material. Attapulgite fibres were also found in a urine sample from a patient who had ingested 6-9 g/day of an attapulgite drug for six months.

A comparison of the pathological effects in rats of the UICC reference samples of amosite and chrysotile with those of amosite and chrysotile collected from the factory environment.

Abstract: Inhalation studies were undertaken in rats to compare the pathogenic effects of samples of UICC amosite and chrysotile with those of amosite and chrysotile samples collected from the factory environment. Fibre length and diameter studies on the four dust samples showed that the UICC chrysotile cloud contained more long fibres than factory chrysotile, although the factory fibres tended to be thicker. The factory amosite cloud contained more long fibres than UICC amosite, but again the factory fibres were thicker. The factory dusts contained considerable amounts of impurities; in spite of this, the lung dust content of asbestos at the end of 12 months' dusting was higher with factory dusts than with UICC material. The UICC chrysotile and factory chrysotile produced similar levels of interstitial fibrosis, but the factory dust produced fewer malignant lung tumours. The factory amosite produced much more interstitial fibrosis than UICC amosite, but neither amosite cloud produced any malignant pulmonary tumours. These results are discussed in relation to current theories on the importance of fibre dimensions in the pathogenesis of lung disease.

Progression of asbestos radiographic abnormalities: relationships to estimates of dust exposure and annual decline in lung function.

Abstract: The determinants of radiographic worsening were examined in a cohort of 244 asbestos-cement manufacturing workers. Progression of irregular small opacities was related to higher average and cumulative dust exposures. Progression of pleural thickening or pleural plaques was related to length of exposure and time since first exposure, but not to average or cumulative exposure. Larger declines in forced vital capacity and forced expiratory volume (one second) were related to larger cumulative dust exposures and to progression of irregular small opacities and pleural thickening. Progression of pleural calcification was not associated with significantly declines in lung function. Changes in lung diffusing capacity did not correlate with measures of dust exposure or with progression of radiographic abnormalities.

Cytogenetic effects of Rhodesian chrysotile on human lymphocytes in vitro.

Abstract: Cytogenetic studies were carried out on human lymphocytes from nine subjects; cells were incubated with Rhodesian chrysotile fibres (10 micrograms/ml) for 48 and 72 hours. After treatment, chromosome alterations were twice as frequent, and chromosome breaks showed the highest percentage increment. We focussed our attention on chromosome breaks, since they are typically induced by ionizing radiation and by chemical carcinogens, and in particular alkylating agents. Since asbestos strongly adsorbs proteins and since indications exist that the interaction may be selective, we consider that this type of interaction may be the cause of cytogenetic damage induced in vitro by asbestos.

Fibrous glass: carcinogenicity and dimensional characteristics.

Abstract: Pleural responses in rats after the implantation of 17 samples of fibrous glass allowed Stanton et al. (1977) to formulate a statistical interpretation of the relationship between the carcinogenicity of this material and its dimensional characteristics. Using the data from that study, a new statistical approach has been developed, using correspondence analysis, multiple regression on the length and diameter of the fibres and simple regression on the average aspect ratio of the fibres, i.e., their average length:diameter ratio. Relationships obtained indicate that carcinogenicity is a continuous, increasing function of the aspect ratio of the fibres, and thus show that it is not possible to separate the effects of the two variables, length and diameter. A hypothesis is presented according to which the fibres could act as an active support for the transformation of adsorbed precarcinogenic molecules. This role would be dependent on the dimensional characteristics of the fibres.

Effect of length on the clearance of fibres from the lung and on body formation.

Abstract: Studies of the effect of fibre length on lung clearance have shown that fibres less than 5 micrometers in length are removed more efficiently than are longer fibres. The probability of body formation occurring increases with fibre length. It appears possible that thin fibres of given length are coated less readily than thick fibres, but further work is required to substantiate this.

The comparative effects of three chrysotiles by injection and inhalation in rats.

Abstract: Three samples of chrysotile, UICC Canadian chrysotile, a grade 7 Canadian chrysotile and a super fine sample (SFA) also from a Canadian mine, were compared in animal experiments using rats of the Wistar strain. All the materials contained impurities. The average length and diameter of the fibres contained in the UICC chrysotile cloud were less than for the other two chrysotiles, but the higher fibre count meant that the UICC cloud contained more fibres of all lengths. In the first experiment, groups of 48 rats were injected intrapleurally with 20 mg of respirable dust. Mesotheliomas occurred with all samples; 18 with SFA, 13 with grade 7, and five with UICC chrysotile. In the second experiment, rats were exposed to a respirable cloud of about 1 mg/m3 for 35 hours a week. Groups of 48 rats were exposed for three months, 24 for six months and 24 for 12 months. Malignant lung tumours occurred with all the dusts; 10 with UICC chrysotile, 4 with SFA, and 1 with grade 7. However, only one of these tumours, obtained with SFA, was a mesothelioma.