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R Binns

Publications and source records attributed to R Binns.

33 records · Page 2Linked to original sources

Inhalation toxicity studies on cigarette smoke. V. Deposition of smoke particles in the respiratory system of rats under various exposure conditions.

This paper describes a dosimetry experiment on rats which was designed to make a contribution towards the optimisation of exposure conditions for inhalation toxicology studies with smoke aerosols. The main conclusions drawn from the work are: (i) Under continuous exposure conditions the deposition of total particulate matter (TPM) in the respiratory system and carboxyhaemoglobin (COHb) levels in blood were linearly dependent on the concentration of smoke in the exposure chamber. (ii) Intermittent exposure gave relatively lower TPM deposition compared to continuous exposure, even after allowing for differences in actual exposure times. (iii) For arithmetically equivalent exposure levels, short exposure to high concentration gave greater TPM deposition than long exposures to low smoke concentrations. (iv) There was a good correlation between lower respiratory system (LRS) and lung deposition of TPM and blood COHb level for both continuous and intermittent exposure conditions. These findings are discussed in relation to the conduct of inhalation studies with tobacco smoke.

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Inhalation toxicity studies on cigarette smoke (VI). 6-week comparative experiments using modified flue-cured cigarettes: histopathology of the lung.

Rats were exposed twice daily for 6 weeks to diluted smoke derived from cigarettes with a range of deliveries of particulate matter. The inhaled smoke reached the alveolar surface, increased the size and number of free macrophages and provoked epithelial metaplasia but did not appear to alter the lymphoid reaction to spontaneous infection. The hypertrophy of the macrophages was typically alveolar and their hyperplasia was directly proportional to the particulate delivery of cigarettes smoked. Alveolar metaplasia was incipient, developed characteristically near the respiratory bronchiole in close association with macrophage clusters and only in rats exposed to smoke from cigarettes with the highest delivery of particulate matter.

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Inhalation toxicity studies on cigarette smoke (VII). 6-week comparative experiments using modified flue-cured cigarettes: histopathology of the conducting airways.

Rats were exposed twice daily for 6 weeks to diluted smoke derived from cigarettes with a range of deliveries of particulate matter. The inhaled smoke caused squamous metaplasia and keratinising hyperplasia in the larynx and goblet cell hyperplasia in the nasal cavity, trachea and intrapulmonary bronchus. Squamous metaplasia occurred in the larynx of almost all rats exposed to smoke but never in their tracheas or bronchi. The degree of reaction observed for the other responses, except goblet cell hyperplasia in the trachea, was positively related, by quantitative microscopy, to the particulate delivery of cigarettes. These findings, together with other smoke-induced changes which occur in the pulmonary alveoli, provide a basis for the short-term bioassay of inhalation toxicity of cigarette smoke.

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Inhalation toxicity studies on cigarette smoke (VIII). 6-week comparative experiments using modified flue-cured cigarettes: general toxicology.

Details are given of studies carried out to compare the inhalation toxicity to rats of smoke from cigarettes modified to give a range of deliveries of particulate matter. Dosimetry work showed that under conditions similar to those used for subsequent toxicity experiments, smoke particulates deposited in the lower respiratory system within the approximate dose range of 500--700 microgram TPM/g lung tissue. Respiratory monitoring showed that the response of animals to a range of smoke exposure conditions was similar and did not change during the course of the experiments. This observation was confirmed by monitoring of blood carboxyhaemoglobin levels after exposure to smoke. During exposure to smoke the rate of respiration decreased to approximately 40% of the pre-exposure rate. Tidal volume, after an initial slight decrease, showed a progressive increase throughout the smoke exposure period. Bodyweight gain was reduced in those animals subjected to smoke exposures. True sham-smoked animals showed a body weight gain intermediate between that of smoke and cage control rats. The clear indications of such between-group differences in response to treatment, coupled with the indicators of consistent dosing of animals under the defined exposure conditions, form a sound basis for the interpretation of terminal pathology.

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Inhalation toxicity studies on cigarette smoke. IV. Expression of the dose of smoke particulate material applied to the lungs of experimental animals.

Calculations of total particulate matter (TPM) dose applied to the lungs of animals are made from experimental dosimetry data. TPM dose levels achieved in a number of species following exposure to smoke are related to body weight, lung weight and alveolar surface areas of these animals. The dosage levels achieved in animals are compared with estimate of TPM dose retained by a smoker. Cigarette dosage equivalents to which animals are subjected can be calculated on the basis of these comparisons. The validity of making such extrapolations from animal dosimetry data to the human exposure situation is discussed.

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Methacholine: a 7-day inhalation toxicity study with primates.

The acute and sub-acute inhalation toxicity of methacholine to cynomolgus monkeys was assessed by exposure of animals to an aerosol of a 2% solution of the material in sterile saline. The acute response was characterized by a decrease in tidal volume, increase in respiratory rate, a fall in dynamic compliance and an increased pulmonary resistance. Onset of the acute response was rapid, reached a peak after 2-3 min of exposure and recovery appeared to be complete after 30 min following termination of an exposure. The sub-acute inhalation toxicity of methacholine was assessed by single daily aerosol exposure of primates to graded doses of the compound for 7 days. Pre- and post-exposure measurements of haematology and blood biochemistry, urinalysis, blood gas analysis and ECG showed no changes which could be attributed to exposure to methacholine. Nor were treatment-related histopathological changes observed in exposed animals. Distinct changes were seen in the mechanical characteristics of the lungs of exposed animals. Pulmonary resistances, measured on the day following final exposure, were increased in all animals exposed to the methacholine aerosol. During 9 weeks following the last of the daily exposures, increased pulmonary resistance values persisted in the animals retained for this period, although there was some indication of a gradual return to pre-exposure resistance values.

Aerosols↗

Animal inhalation studies with tobacco smoke.

An outline is given of the techniques that have been used for exposure of small and large experimental animals to tobacco smoke. The effects of tabacco smoke inhalation on a wide range of biological systems have been investigated, and some important published studies have been noted. Much early work on tobacco smoke was equivocal because of the unsatisfactory exposure techniques, and the poor quality of animals used. Exposure techniques, particularly for small animals, are improving and more recent publications indicate an increased awareness of the special problems of working with tobacco smoke. At this time, however, exposure techniques anty of different tobacco smokes are essentially at the mid-development stage.

Aerosols↗

Inhalation toxicity studies on cigarette smoke II. Tobacco smoke inhalation dosimetry studies on small laboratory animals.

A newly developed exposure system has been used to carry out smoke dosimetry studies on rats, mice, hamsters and guinea pigs. In all species, smoke total particulate matter (TPM) deposited in significant amounts in the lower respiratory system (LRS) at dose levels ranging from 0.515 to 1.710 mg TPM/g respiratory tissue. Nasal deposition of smoke particulates did occur in all of the species examined. The significance of these dosimetry data in relation to the conduct of long-term comparative inhalation toxicity studies with tobacco smoke is discussed.

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Inhalation toxicity studies on cigarette smoke III. Tobacco smoke inhalation dosimetry study on rats.

Smoke inhalation dosimetry studies have been carried out on rats, using a new exposure system. A range of cigarettes, tobacco types and smoke concentrations was used. Penetration of smoke into the lungs was clearly demonstrated, and loads of total particulate matter (TPM) of up 1 mg were detected in the lower respiratory system of rats. The mass of TPM deposited was affected by the smoke concentration during exposure. Deposition of TPM in the head of the rat was low in relation to total respiratory system deposition. A pattern of predominantly lung deposition was achieved under the conditions used for this series of experiments. This pattern was not affected by changes in smoke dilution level, cigarette or tobacco type.

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