725
WR, Gray PHK. Catalogue of Egyptian antiquities in the British Museum Vol I: mummies and human remains 2. London: British Museum, 1968. 6 Arriaza B, Allison M, Gerszten E. Maternal mortality in pre-Columbian Indians in Anca, Chile. Am J Phys Anthropol 1988; 77: 35-41. 7. De Jonge N, Gryseels B, Hilberath GW, Polderman AM, Deelder AM. Detection of circulating anodic antigen by ELISA for seroepidemiology of schistosomiasis mansoni. Trans R Soc Trop Med Hyg 1988; 82: 591-94. 8. Isherwood I, Jarvis H, Fawcitt RA. Radiology of the Manchester mummies In: David AR, ed. Manchester Museum mummy project. Manchester: Manchester University Press, 1979: 25-64 5. Dawson
Plasticisers and bronchial hyperreactivity SIR,-Di-(2-ethylhexyl)phthalate (DEHP) is a widely used plasticiser in polyvinylchloride (PVC) plastics, which may contain up to 40% of the
compound. DEHP and its hydrolysis product mono(2-ethylhexyl)phthalate (MEHP) have become widespread environmental contaminants, being found in foods, soil, plants, bacteria, and the atmosphere, and few of us escape exposure.1 Exposure to DEHP will be especially high in workers in DEHP manufacture and in patients receiving frequent blood transfusions. Plasma stored for 21 days in PVC bags contained up to 8 mg DEHP/dl, and patients receiving multiple blood transfusions are at increased risk of adverse pulmonary effects such as microemboli and hypersensitivity.2 Intravenous administration of DEHP in rats causes pulmonary haemorrhage and inflammmation of the lungs.2 DEHP is extensively hydrolysed in the gut to MEHP and has no toxic effects after oral administration. A variety of tissue esterases can hydrolyse DEHP. Good absorption and hydrolysis are likely following most routes of administration. The inhalation of DEHP has been associated with pulmonary oedema and bronchial Asthma 4 Asthma is characterised by pulmonary inflammation and increased (non-specific) bronchial hyperreactivity. Clinically, this hyperreactivity is observed with lower levels of non-specific stimuli (such as histamine and methacholine) causing the same bronchoconstriction. Pharmacologically non-specific bronchial hyperreactivity is the resultant of "hypersensitivity", characterised by an increase in log ECso (effective concentration inducing 50% of greatest effect), and "hyperreactivity", defmed as an increase in maximal response.S We have studied the pharmacological effects of DEHP, MEHP, and phthalic acid on rat tracheal tissue. Neither DEHP nor phthalic acid, at concentrations of up to 1 mmol/1, affected smooth muscle tone or methacholine-induced contraction of tracheal muscle. 0.1 mmol/1 MEHP, however, induced hypersensitivity to methacholine (table). DEHP and MEHP inhibit protein kinase6 the enzyme involved in the muscarinic receptor transduction pathway.? Protein kinase C inhibitors such as 1(5isoquinolinylsulphonyl)2-methylpiperazine (H7) decrease peak responses to methacholine (table) but do not induce hypersensitivity. The increase in ECso after addition of MEHP is therefore probably explained by protein kinase C inhibition. The absence of similar effect for DEHP might be explained by its high lipophilicity, rendering it unable to reach its sites for action.
MEAN
Results
EC50 VALUES AND
MAXIMAL RESPONSES
of at least 8 experiments (and SEM) in four animals Blank recorded before incubation, control dose-response curves were recorded after incubation for 30 min with solvent Muscarinic receptor responses were measured wIth methacholine *P
WR, Gray PHK. Catalogue of Egyptian antiquities in the British Museum Vol I: mummies and human remains 2. London: British Museum, 1968. 6 Arriaza B, Allison M, Gerszten E. Maternal mortality in pre-Columbian Indians in Anca, Chile. Am J Phys Anthropol 1988; 77: 35-41. 7. De Jonge N, Gryseels B, Hilberath GW, Polderman AM, Deelder AM. Detection of circulating anodic antigen by ELISA for seroepidemiology of schistosomiasis mansoni. Trans R Soc Trop Med Hyg 1988; 82: 591-94. 8. Isherwood I, Jarvis H, Fawcitt RA. Radiology of the Manchester mummies In: David AR, ed. Manchester Museum mummy project. Manchester: Manchester University Press, 1979: 25-64 5. Dawson
Plasticisers and bronchial hyperreactivity SIR,-Di-(2-ethylhexyl)phthalate (DEHP) is a widely used plasticiser in polyvinylchloride (PVC) plastics, which may contain up to 40% of the
compound. DEHP and its hydrolysis product mono(2-ethylhexyl)phthalate (MEHP) have become widespread environmental contaminants, being found in foods, soil, plants, bacteria, and the atmosphere, and few of us escape exposure.1 Exposure to DEHP will be especially high in workers in DEHP manufacture and in patients receiving frequent blood transfusions. Plasma stored for 21 days in PVC bags contained up to 8 mg DEHP/dl, and patients receiving multiple blood transfusions are at increased risk of adverse pulmonary effects such as microemboli and hypersensitivity.2 Intravenous administration of DEHP in rats causes pulmonary haemorrhage and inflammmation of the lungs.2 DEHP is extensively hydrolysed in the gut to MEHP and has no toxic effects after oral administration. A variety of tissue esterases can hydrolyse DEHP. Good absorption and hydrolysis are likely following most routes of administration. The inhalation of DEHP has been associated with pulmonary oedema and bronchial Asthma 4 Asthma is characterised by pulmonary inflammation and increased (non-specific) bronchial hyperreactivity. Clinically, this hyperreactivity is observed with lower levels of non-specific stimuli (such as histamine and methacholine) causing the same bronchoconstriction. Pharmacologically non-specific bronchial hyperreactivity is the resultant of "hypersensitivity", characterised by an increase in log ECso (effective concentration inducing 50% of greatest effect), and "hyperreactivity", defmed as an increase in maximal response.S We have studied the pharmacological effects of DEHP, MEHP, and phthalic acid on rat tracheal tissue. Neither DEHP nor phthalic acid, at concentrations of up to 1 mmol/1, affected smooth muscle tone or methacholine-induced contraction of tracheal muscle. 0.1 mmol/1 MEHP, however, induced hypersensitivity to methacholine (table). DEHP and MEHP inhibit protein kinase6 the enzyme involved in the muscarinic receptor transduction pathway.? Protein kinase C inhibitors such as 1(5isoquinolinylsulphonyl)2-methylpiperazine (H7) decrease peak responses to methacholine (table) but do not induce hypersensitivity. The increase in ECso after addition of MEHP is therefore probably explained by protein kinase C inhibition. The absence of similar effect for DEHP might be explained by its high lipophilicity, rendering it unable to reach its sites for action.
MEAN
Results
EC50 VALUES AND
MAXIMAL RESPONSES
of at least 8 experiments (and SEM) in four animals Blank recorded before incubation, control dose-response curves were recorded after incubation for 30 min with solvent Muscarinic receptor responses were measured wIth methacholine *P
