Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: Intratracheal administration in hamsters

Objectives-It was hypothesised from an epidemiological investigation that a formula change from Acramin FWR (a polyurea) to Acramin FWN (a polyamideamine) had led to severe pulmonary disease in textile printing sprayers in Spain and Algeria. To verify this, the pulmonary toxicity of the components of the paint systems involved was assessed in experimental animals. Methods-Individual components and relevant mixtures, diluted in phosphate buffered saline, were given by intratracheal instillation of 2 ml/kg to hamsters. Pulmonary toxicity was assessed on days 3, 7, 14, 28, and 92 after a single intratracheal instillation, by histology and by measuring wet and dry lung weight, protein concentration, the activities of lactate dehydrogenase, alkaline phosphatase, beta-N-acetyl-glucosaminidase, and gamma-glutamyltransferase, inflammatory cell number and distribution in bronchoalveolar lavage fluid (BALF), and hydroxyproline content in dried lung tissue. Results-Based on the doses that killed 50% of the animals (LD(50)s), the various components were found to be 10 to 1250 times more toxic when given intratracheally than when given orally (according to reported oral LD(50)s in rats). Acramin FWN, Acramin FWR, Acrafix FHN, or their mixtures caused lung damage. Protein concentration, enzyme activities, total cell number, and percentage of polymorphonuclear neutrophils were increased in BALF during the first week after intratracheal instillation. Lung weights remained high for at least a month. Histology showed inflammatory cell infiltration and subsequent fibrosis with collagen deposition. This finding was confirmed by an increased hydroxyproline content in dried lung tissue. Acramoll W did not show toxic effects. Conclusions-The study suggests that there is no major difference, in hamsters, between the acute intratracheal toxicity of Acramin FWR and that of Acramin FWN. Consequently, there is no simple toxicological explanation for the epidemiological hypothesis. However, the pulmonary toxicity of these non-irritant polymeric compounds is surprisingly high. The Ardystil disaster and these results should serve as a strong warning that conventional toxicity testing of chemicals does not necessarily protect workers against respiratory toxicity.