Influence of acid aerosol droplet size on structural changes in the rat lung caused by acute exposure to sulfuric acid and ozone.

To investigate whether aerosol droplet size influences structural changes in the lung produced by short-term, concomitant exposure to ozone and sulfuric acid, groups of 10 rats were exposed 4 hr/day for 2 days to filtered air, 0.6 ppm ozone, 0.5 mg/m3 fine (aerosol mass median diameter (MMD) = 0.3 microm) or ultrafine (MMD = 0.06 microm) sulfuric acid, or a mixture of ozone and 0.5 mg/m3 fine or ultrafine sulfuric acid. The volume percentage of total parenchyma containing markedly to severely injured alveolar septae was measured morphometrically. There were no differences between the ultrafine or fine acid exposure groups and the sham group for any of the morphologic endpoints. Volume percentage of markedly to severely injured tissue was increased in the ultrafine, but not fine, mixture animals when compared with the ozone-only group. In addition, a synergistic interaction between ozone and ultrafine, but not fine, sulfuric acid was found for this endpoint. The bromodeoxyuridine cell labeling index in the periacinar region was greater in the rats exposed to the fine sulfuric acid and ozone mixture than that in rats exposed to ozone alone, and a synergistic interaction between ozone and fine sulfuric acid was found for this end point. None of the exposures produced any changes in ventilatory parameters. Thus, acid aerosol droplet size was found to influence the effect of sulfuric acid in modifying ozone-induced structural changes in the rat lung.

Health hazard labeling for hazard communication in the pharmaceutical industry.

Company health and safety professionals must advise workers of the potential hazards of workplace chemicals. Yet it is difficult to develop one, consistent corporate labeling strategy for worldwide use. This chapter describes one company's approach to devising a corporate policy satisfying all criteria.

Prenatal care and sea fish.

OBJECTIVES: To evaluate the effects of a prenatal nutritional counselling programme about the benefits of increasing dietary intake of sea fish. STUDY DESIGN: A hospital and parity matched observational comparison study. Four-hundred ninety-nine pregnant women, attending selected clinics for antenatal care, before 20 weeks gestation, were offered a 20-min nutritional advice session. They were encouraged to increase the intake of oily sea fish and reduce intake of food rich in transfatty acid. For each woman interviewed a corresponding control was established. MAIN RESULTS: The mean birth weight was slightly higher in the study group (3349 g vs. 3284 g) and the difference persisted after adjusting for gestational age (85 g/week vs. 83 g/week). The rate of delivery before 37 weeks was lower in the study group (7.3% versus 9.5%). The mean neonatal head circumference was greater in the study group (34.7 cm vs. 34.4 cm). CONCLUSION: The effect of advice to increase intake of oily fish warrants further study.

Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits.

Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Amplification of the c-myc oncogene during progression of radiation-induced rat skin tumors.

Evaluation of a large panel of radiation-induced rat skin tumors of diverse size and histological type revealed a correlation between c-myc copy number and tumor size. Both the frequency and degree of c-myc gene amplification were increased in large compared to small carcinomas, but none of the sarcomas examined showed c-myc amplification. Serial biopsies of individual tumors exhibited similar trends of increasing c-myc copy number in later biopsies. In one regressing tumor, the c-myc gene copy number paralleled the growth rate of the tumor during growth and regression. The average time required from tumor appearance to significant gene amplification was close to the average period between tumor appearance and the onset of rapid growth. The data suggest that, rather than being a target gene for the direct early effects of ionizing radiation, c-myc functions as a late-stage progression-related oncogene in this model system.

An experimental model for oncogene activation during tumor progression in vivo.

Tumor progression usually involves a complex pattern of molecular alterations. In many human tumors oncogene amplification or activation has been associated with advanced stages of cancer. Transfection studies have demonstrated the ability of several cellular oncogenes to induce a more malignant phenotype in transformed cells. We have examined the role of c-myc in tumor progression in rat tracheal cell culture, and in rat skin tumors induced by ionizing radiation. In the latter in vivo model, c-myc amplification was found to occur as a function of tumor size. Serial biopsies of growing tumors confirmed the trend toward increased gene copy number with time and stage of progression. This effect was specific for the c-myc gene, in epithelial tumors. Evidence was found for a role of tumor heterogeneity and evolution of tumor cell subpopulations in determining the oncogene activation profile of individual tumors.