John C. Findlay

Health effects of short-term inhalation of nitrogen dioxide and ozone mixtures

Abstract The effects of single and multiple daily 3-hour exposures to nitrogen dioxide (NO 2 ) and ozone (O 3 ) mixtures on the resistance to streptococcal pneumonia were investigated. The concentrations of NO 2 ranged from 1.5 to 5.0 ppm, and those of O 3 , from 0.05 to 0.5 ppm. The effect of a single exposure to the mixture was additive, whereby the excess mortality rates were equivalent to those induced by the inhalation of each individual pollutant. The ability to clear inhaled bacteria from the lungs was diminished in mice exposed to the NO 2 O 3 mixtures for 3 hours. This impairment was manifested by the increased frequency of isolation of Streptococcus from the lungs for up to 6 days after the respiratory challenge. Excess mortalities observed after 20 daily 3-hour exposures suggested that a synergistic effect might be present upon repeated inhalation of pollutant mixtures, that made them more effective in reducing resistance to respiratory infection. The results emphasize the need for the establishment of primary air quality standards for short-term NO 2 exposures.

Effects of repeated exposures to peak concentrations of nitrogen dioxide and ozone on resistance to streptococcal pneumonia

Exposures to various mixtures of nitrogen dioxide (NO2) and ozone (O3) reduced the resistance of mice to streptococcal pneumonia as evidenced by increased mortality rates and shortened survival time. Daily 3-h exposures (5 d/wk) for 2--6 mo to an air pollutant mixture consisting of 940 microgram/m3 (0.5 ppm) NO2 and 196 microgram/m3 (0.1 ppm) O3 were most effective in reducing the resistance to infection. The decrease in resistance to the infection occurred sooner than the mice continued to be exposed to the air pollutants instead of clean air for 14 d after the respiratory challenge with Streptococcus pyogenes aerosol. After 3 mo of exposure to the pollutant mixture, there was some decrease in the ability of mice to clear inhalated streptococci from their lungs. At the same time the total cell count in the fluid lavaged from the lungs of mice was markedly reduced, as were the viability and phagocytic activity of the alveolar macrophages. Exposure to the pollutants combined with challenge with Streptococcus aerosol resulted in marked morphological changes in lung tissues as seen by scanning electron microscopy.

Chronic Toxicity/Oncogenicity Evaluation of 60 Hz (Power Frequency) Magnetic Fields in F344/N Rats

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat.

Chronic Toxicity/Oncogenicity Evaluation of 60 Hz (Power Frequency) Magnetic Fields in B6C3F1 Mice

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in mice. Groups of 100 male and 100 female B6C3F1 mice were exposed to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female B6C3F1 mice received intermittent (1 hr on/1 hr off) exposure to 10 G fields. A small but statistically significant increase in mortality was observed in male mice exposed continuously to 10 G fields; mortality patterns in all other groups of mice exposed to magnetic fields were comparable to those found in sex-matched sham controls. Body weight gains and the total incidence and number of malignant and benign tumors were similar in all groups. Magnetic field exposure did not increase the incidence of neoplasia in any organ, including those sites (leukemia, breast cancer, and brain cancer) that have been identified in epidemiology studies as possible targets of magnetic field action. A statistically significant decrease in the incidence of malignant lymphoma was observed in female mice exposed continuously to 10 G fields, and statistically significant decreases in the incidence of lung tumors were seen in both sexes exposed continuously to 2 G fields. These data do not support the hypothesis that chronic exposure to pure, linearly polarized 60 Hz magnetic fields is a significant risk factor for neoplastic development in mice.

Chronic Exposure to Nitrogen Dioxide

Squirrel monkeys continuously exposed to 1 ppm of nitrogen dioxide (NO2) for 493 days were challenged five times with monkey-adapted influenza A/PR/8/34 virus. All monkeys exposed to NO2 produced serum neutralization antibody within 21 days after virus infection, whereas only one control monkey exposed to filtered air showed comparable response. The differences observed in hemagglutination-inhibition antibody titers, body temperatures, respiratory functions, body weights, and hematological values between the experimental and control monkeys were not significant. Histopathologic examination of lung tissues indicated slight emphysema and thickened bronchial and bronchiolar epithelium only in monkeys exposed to NO2 and challenged with the influenza virus. Transmission election microscopic examination did not disclose any ultrastructural changes that could be attributed to the experimental exposures.

Chronic toxicity of NO2 in squirrel monkeys. 3. Effect on resistance to bacterial and viral infection.

Monkeys were exposed to 10 ppm NO/sub 2/ for 1 month and 5 ppm for 2 months prior to challenge with Klebsiella pneumoniae or influenza virus. Minute respiratory volumes of monkeys exposed to 10 ppm were elevated after 2 weeks and remained high throughout exposure (increase in tidal volume and rate). Challenge reduced minute volume of exposed monkeys but increased volume of control monkeys. With 5 ppm exposure, tidal volume gradually decreased, but respiratory rate increased to maintain minute volume. Subsequent exposure to K. pneumonaie produced death in 25 to 28% of NO/sub 2/-exposed monkeys. Bacterial clearance also was reduced. With viral infection, 6/6 in 10 ppm group died; 1/3 in 5 ppm group died. No controls died in either case.

Effect of exposure to nitrogen dioxide on t and b cells in mouse spleens

Effects of exposure to nitrogen dioxide (NO2) on thymus-derived (T) and bursa-derived (B) cells were studied in albino mice. The mice were exposed continuously 24 hday to 940 μgm3 NO2 and to 188 μgm3 NO2 with daily 3-h peaks 5 daysweek of either 470, 940 or 1880 μgm3 NO2. After 1, 3, 6, 9 and 12 months of exposure, single-cell suspensions were prepared from spleen and incubated with phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS). The PHA and LPS responses from mice exposed to NO2 were generally depressed when compared with those in mice exposed for the same time periods to filtered air.

Chronic Toxicity of NO2 in Squirrel Monkeys

Monkeys were exposed to 10 ppm NO/sub 2/ for 1 month and 5 ppm for 2 months prior to challenge with Klebsiella pneumoniae or influenza virus. Minute respiratory volumes of monkeys exposed to 10 ppm were elevated after 2 weeks and remained high throughout exposure (increase in tidal volume and rate). Challenge reduced minute volume of exposed monkeys but increased volume of control monkeys. With 5 ppm exposure, tidal volume gradually decreased, but respiratory rate increased to maintain minute volume. Subsequent exposure to K. pneumonaie produced death in 25 to 28% of NO/sub 2/-exposed monkeys. Bacterial clearance also was reduced. With viral infection, 6/6 in 10 ppm group died; 1/3 in 5 ppm group died. No controls died in either case.

Chronic Toxicity/Oncogenicity Studies of 60 Hz Magnetic Fields in F344 Rats and B6C3F1 Mice: Final Survival, Body Weight, Clinical Observation, and Gross Pathology Data

The results of a number of epidemiology studies have suggested a positive association between exposure to power frequency magnetic fields and the incidence of several types of malignancy1–3. However, other epidemiology studies of similar design have found no such relationship between magnetic field exposure and cancer risk4,5. Because the epidemiology database for magnetic field exposure and cancer risk is contradictory, it appears unlikely that definitive assessments of human risk associated with magnetic field exposure can be developed on the basis of epidemiology data alone. In cases where the epidemiology data are inconclusive, the importance of studies in experimental animal model systems increases. Well-controlled animal studies permit evaluation of the biological effects of magnetic fields in vivo under tightly controlled exposure conditions, and in the absence of potential confounding variables. The present report provides the results of the in-life component of studies that are designed to evaluate the chronic toxicity and potential oncogenicity of chronic exposure to 60 Hz magnetic fields in F344 rats and B6C3F1 mice.