A mail-out questionnaire examined symptoms previously associated with vinyl chloride exposure. Assessment of exposure levels was made by analytical measurement and observation. The resulting statistical analysis revealed a dose-response type of relationship between exposure and certain morbidity symptoms.
Suppression of mitogen-induced splenocyte lymphoproliferation and interleukin 2 (IL-2) production can be used as indicators of immunotoxicity. Staphylococcal enterotoxin A (SEA) is both a potent mitogen and the most potent in vitro inducer of IL-2 production that has been described. An in vitro system was used to measure impairment of SEA-induced lymphoproliferation and IL-2 production using splenocytes from female C57BL/6 mice dosed with either cyclosporin A (30 mg/kg/day, 14 days), benzene (220, 440, or 880 mg/kg/day, 14 days), or vehicle. Splenocytes were stimulated with either concanavalin A (con A) or SEA. Benzene- and cyclosporin A-treated mice demonstrated significant decreases in splenocyte proliferation. IL-2 production was determined by incubating splenocyte culture supernatants with IL-2 dependent cytotoxic T-cells (CTLL-2), pulsing with 3H-thymidine, and determining amount of incorporated label. Cell proliferation and IL-2 production were inhibited by both benzene and cyclosporin A, effects more clearly demonstrated using SEA than con A. SEA was a superior mitogen compared to con A in the assays evaluated here.
Whether use of oxygen-rich gasoline additives to reduce air pollution is a cause of acute adverse health effects is an ongoing concern in the United States. Attention has focused in particular on use of methyl tert-butyl ether (MTBE, CAS #1634-04-4) and, despite considerable published research, debate persists regarding its potential for adverse health effects. To better understand the debate, we critically reviewed published and unpublished reports to assess whether differences in methodological approach or quality could explain the variable results reported. We considered studies on acute human health effects of inhalation exposure to MTBE either alone or in gasoline (19 reports) as well as clinical use of parenteral MTBE to dissolve cholesterol gall stones (12 reports). Each study was reviewed from three perspectives (epidemiology, industrial hygiene, and, clinical diagnostics), judged satisfactory, limited adequacy, or unsatisfactory for each criterion, and grouped into one of three categories from most to least adequate in overall methodology. The studies judged most adequate on individual criteria and those with highest overall adequacy found no significant association between MTBE exposure and symptoms. We propose that the persistent debate has been fueled by the findings of methodologically weak hypothesis-generating studies.
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