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Biomedical subjects

A D Jones

Publications and source records attributed to A D Jones.

At least 127 records · Page 7Linked to original sources

Effects of electrostatic charge on the pathogenicity of chrysotile asbestos.

Two groups of 48 rats of the AF/HAN strain were exposed for one year to respirable dust clouds of UICC chrysotile asbestos at a dose level of 10 mg/m3. One group was treated with dust carrying the normal electrostatic charge produced during dust generation, whereas the other was exposed to dust discharged by exposure to ionising radiation from a thallium-204 source. After dusting most animals were retained for their full life span. At the end of the dusting period those animals treated with normally charged dust had significantly more chrysotile retained in their lungs than animals exposed to discharged dust. Subsequently, animals treated with normally charged dust developed more pulmonary fibrosis and more pulmonary tumours. These findings suggest that the charge carried by airborne fibres should be taken into account when considering the health risks from exposure to chrysotile. Highly charged fibres are more likely to be deposited in lung tissue and thus constitute a greater hazard.

Animals↗

Pulmonary clearance of UICC amosite fibres inhaled by rats during chronic exposure at low concentration.

Clearance of UICC amosite asbestos from the lungs during chronic--that is, repeated--exposure was investigated by using the scanning electron microscope to measure lung burdens from rats which had inhaled amosite asbestos at an approximately constant concentration of 0.1 mg/m3 or, equivalently, 20 fibres/ml for seven hours a day, five days a week for up to 18 months. The lung burdens were compared with previous results for higher exposure concentrations of 1 and 10 mg/m3. Those previous lung burdens had been measured using other analytical methods (infrared spectrophotometry) that were not suitable for the new lower lung burdens. Taken together, these results showed lung burdens rising pro rata with exposure concentration and exposure time. This accumulation of lung burden has been described by a kinetic model that takes account of the sequestration of material at locations in the lung from where it cannot be cleared. Unlike some earlier models in which lung burdens eventually reach a plateau with equilibrium between deposition and clearance during chronic exposure, this sequestration model shows lung burdens continuing to rise with exposure time. The latest results reported here support the application of such a model to lower exposure concentrations closer to those of asbestos in workplaces.

Animals↗

Comparisons of the pathogenicity of long and short fibres of chrysotile asbestos in rats.

Long-term inhalation and intraperitoneal injection studies were undertaken with laboratory rats treated with a specially prepared short-fibre sample of Canadian chrysotile asbestos. This was compared, at an equal mass dose, to dust generated from the same chrysotile batch so as to contain the highest possible number of long fibres. The long-fibre cloud contained roughly five times more fibres greater than 5 micron in length as seen by phase contrast optical microscopy (PCOM). For increasing lengths, the ratio between the dust clouds increased progressively, reaching over 80: 1 for fibres greater than 30 microns in length. Rats treated with long-fibre chrysotile developed six times more advanced interstitial fibrosis (asbestosis) than animals treated with short-fibre chrysotile and three times more pulmonary tumours. At the end of the 12-month dusting period, three times more short chrysotile than long had been retained in the rat lung tissues. During the following 6 months, however, the short-fibre chrysotile was removed from the lungs much more rapidly than the long. Following intraperitoneal injection at a mass dose of 25mg of dust, both long and short chrysotile produced mesotheliomas in more than 90% of rats. At a dose level of 2.5mg of dust, the short-fibre chrysotile produced mesotheliomas in only one-third as many rats as the long-fibre dust which still produced mesotheliomas in more than 90% of animals injected. At a dose level of 0.25mg of dust, the short-fibre chrysotile produced no mesotheliomas while the long-fibre chrysotile still produced these tumours in 66% of rats. In the two highest doses, where short-fibre chrysotile produced mesotheliomas, the mean tumour induction period was significantly longer than for tumours produced by long chrysotile.

Animals↗

The effect of electrostatic charge on the aspiration efficiencies of airborne dust samplers: with special reference to asbestos.

An experimental investigation has been conducted into the effects of electrostatic charge, carried by the dust particles and by the sampler itself, on the sampling of airborne dusts. Experiments covering both personal and static sampling and a range of sampler types were carried out in the laboratory for both fibrous asbestos and isometric silica gel dusts. Experiments also were carried out in the spinning shop of an asbestos textile factory. The results showed that the aspiration efficiency of the sampler always is reduced as the charge on the sampler increases, independently of the type of sampler and of whether it is used as a static or personal sampler. The effect is most marked when sampling takes place in calm air. It is concluded from the results that, for the levels of charge reached by samplers in most practical situations, the effects on aspiration efficiency will be small. Possible exceptions to this might occur, however, in workplace environments where relative humidity is very low, and charge levels of the sampler (or on the worker wearing the sampler) can become high.

Air Pollutants, Occupational↗

High-performance liquid chromatographic column switching method for the determination of hydroxyproline in meat and meat products.

A method is described for the determination of 4-hydroxyproline in meat and meat products. The amino acid is converted to a sensitive fluorescent derivative with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Chromatography of other (unwanted) amino acid derivatives is avoided by column switching, thereby shortening analysis time. The method is suitable for routine analysis and is applicable to the entire range of 4-hydroxyproline levels normally encountered in meat and meat products (0.05-12.5%).

Animals↗

Effects of the inhalation of dusts from calcium silicate insulation materials in laboratory rats.

The effects of respirable dust from three commercially produced calcium silicate insulation materials were examined in laboratory rats by long-term inhalation and injection techniques. These calcium silicate products have been used as replacements for asbestos in the insulation of the engine rooms of ships, and the particle size distribution of the dust clouds generated for the experimental study closely matched those found in ships during the installation of this type of material. One year of exposure to a dust cloud of 10 mg/m3 of respirable dust had no discernible effect on the length of survival of treated animals compared to controls. No pulmonary lesions were found that appeared associated with the inhalation of calcium silicate per se, but one sample did contain significant amounts of quartz and this did produce a few small pulmonary nodules. While two small pulmonary neoplasms, one malignant and one benign, were found in dusted animals, neither was the cause of death, and the incidence was not significantly different from the control group where no tumors were found. One peritoneal mesothelioma was found in an animal from one of the inhalation groups, but this was considered to be a spontaneous tumor as none of over 100 animals injected intraperitoneally with 25 mg of calcium silicate developed these tumors. While the white blood cell count of dusted animals, compared to controls, was significantly raised in all treated groups at the end of the dusting period, these figures were within the published normal ranges for laboratory rats. It was concluded that the three tested calcium silicate products were harmless to the rats of this species at the doses tested.

Animals↗

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

Animals↗

Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process.

Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenic and carcinogenic and there were no significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average 10% of all lung tissue. In the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types.

Animals↗

Inhalation studies on the effects of tremolite and brucite dust in rats.

Samples of commercially used asbestos, especially chrysotile, are frequently contaminated by small amounts of other fibrous minerals. Among these are tremolite and brucite although pure tremolite is also produced commercially in relatively small quantities. In order to determine how harmful commercially exploited tremolite might be in comparison with other asbestos types and to explore the possibility that small amounts of tremolite and brucite as contaminants could significantly affect the pathogenicity of industrially used chrysotile, long-term animal inhalation and injection studies using rats were undertaken with what were considered to be mineralogically pure samples of these minerals. Rats treated with tremolite developed very high levels of pulmonary fibrosis as well as 16 carcinomas and two mesotheliomas in a group of 39 animals. Tremolite thus proved to be the most dangerous mineral that we have studied. Animals treated with 'brucite' developed moderate levels of pulmonary fibrosis and two carcinomas. Both tremolite and brucite produced mesotheliomas in greater than 90% of animals following i.p. injection. However, it was found that the supposedly pure brucite in fact contained 10% chrysotile, a level of contamination that could well have been responsible for the pathological changes found in both inhalation and intraperitoneal injection studies. The greatest care should be exercised by industry in handling tremolite or materials contaminated with it.

Air Pollutants, Occupational↗

Kinetics of deposition and clearance of inhaled mineral dusts during chronic exposure.

New inhalation studies have been carried out with rats exposed to UICC (Union International Contre le Cancer) amosite asbestos, with the main aim of further elucidating the factors the influence the accumulation of dust in the lung during prolonged chronic exposure. The results show that, for exposure times beyond a few weeks, the lung burden rises linearly and does not level off as predicted by simple models based on ideas taken from the 1966 report of the Task Group on Lung Dynamics. Furthermore, the lung burden is found to scale directly in proportion to the exposure concentration in a way that seems to contradict the overload hypothesis stated earlier. Nevertheless, the general pattern exhibited by our results for asbestos is markedly similar to that found elsewhere for rats inhaling diesel fume, leading to the suggestion that it is general (and not specific to fibrous dust); and the hypothesis that, whereas overload of clearance can take place at high lung burdens after exposure has ceased, it is cancelled by the sustained stimulus to clearance mechanisms provided by the continuous challenge of chronic exposure. The linearity of the increase in lung burden is explained in terms of a kinetic model involving sequestration of some inhaled material to parts of the lung where it is difficult to clear. The particular sequestration model favoured is one where, the longer a particle remains in the lung without being cleared, the more likely it will be sequestrated (and therefore less likely cleared). It is believed that such ideas may eventually be useful in forming exposure-dose relations for epidemiology.

Animals↗

An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats.

Two types of experiments were carried out to examine the effects of deposition and clearance on the accumulation in the lungs of rats of inhaled fibres of UICC amosite. In the first experiment the mass lung burdens of the dust in question were measured as a function of the time at which animals were killed after the cessation of the six week exposure period, and in the second the masses were measured for rats removed from exposure and killed at intervals during the exposure period itself. The experimental conditions were chosen to complement those of earlier work. Taken together with the results of that earlier work, the new results provide the basis for a simple mathematical model of the kinetics of deposition and clearance which appears to account for the major observed trends. Most significantly, there is strong evidence for an overload of clearance at high lung burdens (exceeding about 1500 micrograms/rat), in which a breakdown occurs of the intermediate rate clearance mechanisms (time constants of the order of 12 days). This hypothesis is supported for inhaled asbestos dust, quartz dust, and diesel fume by results obtained elsewhere. Biological explanations for the clearance overload hypothesis are at present speculative, involving discussion of the role of the macrophage in pulmonary clearance. It is believed that the clearance overload hypothesis could have possible consequences for people occupationally exposed to airborne dusts.

Animals↗

Th determinants of birth weight.

Presented are the results of multivariate regression analysis of the variations in birth weight of term babies associated with the socioeconomic, physical, and medical factors recorded in obstetric case notes at a London teaching hospital. The results show that the sex of the baby, parity, maternal smoking during the pregnancy, maternal height, weight, marital status, and race, and gestation (after allowing for the foregoing characteristics) were all important and significant factors. Socioeconomic status, per se, was not, nor was age. In particular, the results negate the suggestion that the loss of birth weight associated with smoking during the pregnancy might be due to the smoker, rather than to smoking itself. The results indicate that moderate smoking (one to 15 cigarettes per day) causes a loss of 107 gm, and that heavy smoking (16+) causes a loss of 158 gm, after all other factors have been taken into account. An investigation of how these figures would be affected by failing to control for one or more of the other factors led to the conclusion that the estimates of the loss of birth weight as a result of smoking in completely uncontrolled studies may be reasonably accurate, whereas the estimates in partially controlled studies are probably biased.

Adolescent↗