Human reflex bronchoconstriction as an adjunct to conjunctival sensitivity in defining the threshold limit values of irritant gases and vapours

The thesis describes studies on acute exposures of human lungs and eyes to irritant gases and vapours and the phsysiological response of these organs. The bronchoactivity of the gases and vapours after inhalation as measured objectively by constant volume ,whole body plethysmograph. The threshold sensitivity of the eyes was assessed subjectively by exposure inside tight fitting goggles. Considerable effort was devoted to the development of methods for the production of known, low concentrations of gases and vapours in air. Sulphur dioxide and ammonia were prepared by static dilution in a Douglas bag. Vapours were produced by continuous generation of vapour at constant temperature and subsequent dilution. Mean dose response curves were obtained for sulphur dioxide and ammonia inhalation by randomised double blind Latin square exposures using twelve subjects and four concentrations for each gas. Examples of other irritants were chosen so as to illustrate the effect of straight and branched chains (ketones), double bonds (aldehydes) and of increasing molecular weight in homologous series. A chlorinated hydrocarbon (trichlorethylene) was also included. The effect of increasinging molecular weight from acetone to the pentanones was an increase in irritancy (acetone and methylethyl ketone are not irritant). The Branched chair pentanone (3-methyl-butan-2-one) was less irritant than the two straight chain isomers. Moving the oxygen atom from the 3- to the 2- position also increased irritancy. Formaldehyde was found to be more irritant than acetaldehyde and acrolein more irritant than either of these; this may be attributed to the presence of the unsaturated double bond crolein. A correlation was found between the threshold of irritancy as measured at the eye and the threshold of bronchoactivity. Further, the evidence suggests that reflex bronchoconstriction may be present at concentrations below those necessary for irritancy at the eye. The implications of these findings are discussed with discussed with reference to the establishment of Threshold Limit Values for industrial exposures. However, although these Experimental findings in volunteers were, it is believed, adequate to support the above conclusion further observations, especially near the threshold level would be necessary before they are used as an adjunct to other physiological responses in establishing the TLVs. A chapter on miscellaneous studies examines the bronchoactivity of methoxytlurane (Penthrane) an anaesthetic and obstetric analgesic. The results indicate that it is a bronchodilator in normal adults. This chapter also includes a comparison of residual volume, obtained by body plethysmography and by the method of helium dilution.