Biomedical subjects

C E O'Neil

Publications and source records attributed to C E O'Neil.

5 recordsLinked to original sources

PubMed1992

Abnormal lung function in polyurethane foam producers. Weak relationship to toluene diisocyanate exposures.

Exposures to toluene diisocyanate (TDI) were studied for effects on respiratory health of workers in two plants manufacturing polyurethane foams. Intensive personal monitoring was used to characterize job exposures. Of 4,845 12-min personal samples, 9% exceeded 5 ppb and 1% exceeded 20 ppb. Initial questionnaire and spirometry were obtained in 386 workers (88.7% of target population). Current smoking was associated with lower mean FEV1 and FEF25-75, but percent predicted (% pred) means were normal in all smoking categories. Multiple regression showed significant adverse effects of cumulative TDI exposure on initial level of FVC and FEV1 of current smokers, and an effect at borderline significance (p less than 0.063) on FEF25-75 over all smoking categories. Logistic regression showed that chronic bronchitis was more prevalent among those with higher cumulative exposures, after controlling for smoking, age, and sex. Methacholine (MCh) reactivity was associated with reduced airway function, -8.5% pred for FEV1 and -20.0% pred for FEF25-75. In 227 with adequate follow-up, the slopes of annual change were abnormal, for example, FEV1 of -67 ml/yr in current and -53 ml/yr in never smokers. Men had worse FEV1 declines than did women, -71 ml/yr versus -43 ml/yr. TDI exposure, lifetime or concurrent, had no significant effect on slopes, despite its demonstrated effects on initial level of lung function and on prevalence of chronic bronchitis.

Adult↗

PubMed1979

Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)-sensitive workers.

Workers with "sensitivity" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.

Aerosols↗

PubMed1977

The in vitro effect of toluene diisocyanate on lymphocyte cyclic adenosine monophosphate production by isoproterenol, prostaglandin, and histamine: a possible mode of action.

Toluene diisocyanate (TDI) significantly inhibits the rise in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) that follows in vitro incubation of human lymphocytes with 6.7 x 10(-3) M isoproterenol and 1 x 10(-6) M prostagladin E1 (p less than 0.05). TDI has no significant effect on th production of lymphocyte cAMP following incubation with histamine (1 x 10(-3) M). The inhibitory action of TDI is greatest at a concentration of 3.3 x 10(-4) M and diminishes as the TDI concentration is increased or decreased. TDI also caused four- to fivefold stimulation of lymphocyte cAMP, an effect that is maximal at 1 x 10(-3) M, a concentration which has no significant inhibitory effect on stimulation of cAMP by isoproterenol or prostagladin E1. Conversely, 3.3 x 10(-4) M TDI, which inhibits cAMP production by isoproterenol and prostaglandin, has little stimulatory effect itself on cAMP production. This evidence suggests that TDI might induce obstructive airways disease through pharmacologic mechanisms and that TDI may be acting as a partial agonist.

Asthma↗

PubMed1977

Toluene diisocyanate pulmonary disease: immunopharmacologic and mecholyl challenge studies.

Selected workers exhibiting clinical "sensitivity" to toluene diiosocyanate (TDI) (wheezing, cough, and dyspnea upon entering a TDI-containing area) were studied for : (1) in vitro TDI-induced leukocyte histamine release; (2) determination of cyclic 3',5' adenosine monophosphate (cAMP) levels of lymphocytes exposed to TDI; (3) effect of TDI on the isoproterenol-induced increase of lymphocyte cAMP levels: and (4) acetyl-beta-methylcholine (mecholyl) inhalation challenge. TDI did not induce histamine release from leukocytes of "sensitive" or "nonsensitive" individuals, nor were lymphocyte cAMP levels affected by in vitro TDI exposure, TDI did, however, diminish in vitro stimulation of cAMP by isoproterenol. This effect, seen with cells of "sensitive" and "nonsensitive" individuals, appeared to be dose-dependent; there were no significant differences between the two groups. When challenged with mecholyl, 7 of 10 "sensitive" but only 1 of 10 "nonsensitive" individuals showed a greater than 20% decrease in FEV1. These results suggest that TDI-induced obstructive airways disorders may be associated with altered beta-adrenergic function.

Administration, Intranasal↗

PubMed1977

Longitudinal study of workers employed in the manufacture of toluene-diisocyanate.

Workers at a toluene-diisocyanate manufacturing plant were studied longitudinally to determine the effects of the chemical on their health. Studies included health questionnaire, pulmonary function, environmental monitoring, and immunologic testing. Workers reporting increased lower respiratory symptoms were from the nonsmoker group. Environmental monitoring showed frequent excursions of toluene-diisocyanate concentrations above the threshold limiting value. There was poor correlation between area and personal exposure levels. No exposure-related decline of pulmonary function was demonstrable. Immunologic studies showed development of a positive skin test to a toluene-diisocyanate-human serum albumin conjugate by some persons and an increasing incidence of toluene-diisocyanate-specific IgE antibodies as measured by a radioallergosorbent test. Toluene-diisocyanate did not induce histamine release from leukocytes in vitro but did diminish the in vitro stimulation of cyclic adenosine monophosphate by isoproterenol. Most of the clinically sensitive persons demonstrated adverse bronchial response when challenged by inhalation of toluene-diisocyanate. This response was dose dependent in some persons. When challenged with Mecholyl, clinically sensitive persons showed greater reactivity of airways than nonsensitive persons.

Antibodies↗