TR 055 : Pulmonary Toxicity of Polyalkylene Glycols | December 1997
Polyalkylene glycols (polyglycols; PAG) are a group of polymeric chemicals with a wide range of physicochemical properties and applications. No significant adverse health effects arising from industrial experience over many years have been reported for these chemicals. PAG have low vapour pressures and no adverse effects have been reported following exposure to vapour atmospheres at ambient temperature.
Experimental animal studies involving a range of PAG have revealed, however, that inhalation of aerosols can, in some cases, lead to severe delayed toxic effects in the lung. A review of the data shows that these toxic effects are confined to two areas of PAG chemistry and differ only in severity of the responses seen. In acute toxicity studies certain butanol and water-initiated random 50:50 ethylene oxide-propylene oxide (EO-PO) copolymers of molecular weight 2,900 and greater induce significant toxic changes in the rat lung including congestion, haemorrhage, interstitial pneumonia and Type II pneumocyte hyperplasia; interstitial focal fibrosis occurs after longer exposure. In sub-acute toxicity studies similar though less severe changes are seen in the lung with 1,700 molecular weight copolymers of similar composition; certain block and reverse-block EO-PO copolymers of molecular weight 1,100 and greater show similar, though less severe changes in the lung.
Acute aerosol inhalation toxicity data on other PAG (diol- and triol-initiated polymers and copolymers and copolymers with different proportions of EO and PO) demonstrate that this pattern of lung toxicity is not general for PAG.
The underlying reasons for the apparent specificity in chemical composition responsible for the observed effects have not been demonstrated. Ultrastructural studies conducted after exposure of rats to random copolymers have suggested that the Type I pneumocytes lining the alveoli are the primary target cell. For random copolymers the available information points to the uptake of circulating unmetabolised copolymer into lung epithelial cells by an active transport mechanism.
In view of these findings, it is recommended that inhalation exposure to those PAG copolymers, shown to have adverse lung effects in animal studies, is adequately controlled where there is the possibility of aerosol generation in the workplace.