Coarse Particles and Dust Storm Mortality
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In a paper titled "Episodes of High Coarse Particle Concentrations Are Not Associated with Increased Mortality," Schwartz et al. (1) concluded that "coarse particles from windblown dust are not associated with mortality risk." The authors seem to have overlooked the medical literature on the health effects of the historic U.S. dust storms of the dust bowl in 1935 (2-4). Brown et al. (2) reported that
the dust ... was exceedingly irritating to the respiratory tract and materially increased the number of deaths from pneumonia and other complications.... The storm that will be longest remembered came [to Dodge City, Kansas] on the afternoon of Sunday [April] the 14th at 2:40 p.m.... No fatalities are known.
They concluded that
The "immediate" effects are shown in the [delayed] increase in morbidity and mortality from the acute infections of the respiratory tract.
Schwartz et al. (1) restricted their analysis to mortality occurring on "the day of the dust storm or the following day." Therefore, they may have not observed any delayed rise in mortality that could have occurred later because of the "immediate" exacerbation of acute respiratory infections in highly susceptible individuals, such as those with preexisting chronic obstructive pulmonary disease. Furthermore, improvements in modern medical treatments, such as the replacement of the sulfa drugs of the mid-1930s by penicillin and other drugs, could delay a mortal outcome beyond the lag observed in the 1930s.
David T. Mage
U.S. Environmental Protection Agency
National Center for Environmental Assessment/Environmental
Media Assessment Group
Research Triangle Park, North Carolina
E-mail: Mage.David@epa.gov
References and Notes
1. Schwartz J, Norris G, Larson T, Sheppard L, Claiborne C, Koenig J. Episodes of high coarse particle concentrations are not associated with increased mortality. Environ Health Perspect 107:339-342 (1999).
2. Brown EG, Gottlieb S, Laybourn RL. Dust storms and their possible effects on health--with special reference to the dust storms in Kansas in 1935. Public Health Rep 50:1369-1383 (1935).
3. Blue JA. Dust--its effect on man from a medical standpoint with special reference to the dust bowl. South Med J 31:1101-1106 (1938).
4. Svobida L. An Empire of Dust. Caldwell, ID:The Caxton Printers, Ltd., 1940;99-105.
Dust Storms: Schwartz's Response
In response to our paper reporting no excess risk of death in Spokane following dust storms when compared to appropriately chosen controls (1), Mage cites an article from the 1930s that anecdotally reports high rates of respiratory illness during the dust bowl period in the Midwest. This period, which coincided with the Great Depression, was a period of extreme social and economic stress. Since our paper was published, a reanalysis of three diary studies by Neas and Schwartz (2) has reported that lung function and lower respiratory symptoms were associated with fine particles but not coarse particles. Gold et al. (3) reported that heart rate variability is associated with fine particles but not coarse particles. These new results confirm our findings, which are also supported by the toxicology studies cited in our paper. Based on this evidence, I find the anecdotal reports from the 1930s unconvincing.
Joel Schwartz
Harvard School of Public Health
Boston, Massachusetts
E-mail: jschwrtz@hsph.harvard.edu
References and Notes
1. Schwartz J, Norris G, Larson T, Sheppard L, Claiborne C, Koenig J. Episodes of high coarse particle concentrations are not associated with increased mortality. Environ Health Perspect 107:339-342 (1999).
2. Neas LM, Schwartz J. Fine particles are more strongly associated than coarse particles with acute respiratory health effects in schoolchildren. Epidemiology (in press).
3. Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, Allen G, Verrier M, Cherry R, Verrier R. Ambient pollution and heart rate variability. Circulation (in press).
Uterotrophic Activity of a "Phytoestrogen-Free" Rat Diet
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Thigpen et al. (1) recently discussed the phytoestrogen content of a range of commercially available rodent diets and the effect they could have on the outcome of reproductive toxicity and endocrine disruption studies. They suggested that careful attention should be given to the use of the casein-based and phytoestrogen-free diet AIN-76A (Research Diets, Inc., New Brunswick, NJ) in such studies. Their letter was primarily in response to a paper by Boettger-Tong et al. (2) in which the sensitivity of the rodent uterotrophic assay was reduced by the use of a diet containing phytoestrogens, leading to increased control uterine weights.
We previously described how we had changed our weanling rat diet from PCD to RM1 (both from Special Diet Services Ltd., Witham, Essex, UK) to decrease control uterine weights and thereby to increase the sensitivity of the uterotrophic assay (3). That change led to a reduction in the mean uterine weight of 24-day-old control rats from 33.7 ± 7.0 mg (mean ± SD; n = 155) to 28.3 ± 6.1 mg (n = 371). Treatment of these control rats with the antiestrogen Faslodex (AstraZeneca, Alderley Park, Macclesfield, UK) reduced uterine weights further to 18.3 ± 2.4 mg (n = 23), indicating low levels of phytoestrogens in the RM1 diet or the presence of prepubertal levels of estradiol.
Inspired by the letter from Thigpen et al. (1), we mounted a study in which pregnant rats are being fed one of four different diets throughout pregnancy and until weaning. We plan to observe sentinel developmental landmarks and reproductive organ weights. The diets under study are RM3/RM1 (3), AIN-76A (1), Purina 5001 (1), and a global diet containing no soy or alfalfa (Harlan UK, Bicester, Oxfordshire, UK). As a pilot study to the above comparative diet study, we exposed 21-day-old (weanling) female Alpk rats to our usual RM1 diet or to AIN-76A diet for 3 days, as in our standard usual uterotrophic assay (3). We also exposed a group of animals on the AIN-76A diet to the antiestrogen Faslodex. Animals were killed on postnatal day 24 and uterine weights were determined. The animals on the AIN-76A diet had heavier uteri than those on the standard diet, an increase that was abolished by concomitant treatment with the antiestrogen. The effect was confirmed in a larger repeat study (blotted uterine weights were 26.1 ± 6.7 mg for RM1 and 45.4 ± 22.3 mg for AIN-76A, with no statistically significant difference in the terminal body weights of the two groups; groups included 30 animals, and similar differences were also seen for dry uterine weights).
We have no explanation for the increases in uterine weight observed for the animals on the AIN-76A diet. These increases were substantial; one of the animals on the AIN-76A diet had a uterine weight typical for that of an estradiol-treated animal (136.8 mg blotted weight). There is no obvious source of estrogens in the AIN-76A diet from the specifications provided by the manufacturers. Thigpen et al. (1) noted that no phytoestrogens have been detected in this diet [the subsequently derived diets AIN-93G and AIN-93M have soybean oil added (4)]. An earlier paper by Thigpen et al. (5) showed that this same AIN-76A diet increased uterus to body weight ratios in weanling CD-1 mice as compared to animals maintained on Purina Chow 5002. The authors noted that it was unclear what substances were responsible for that increase in uterine weights (5).
The present findings indicate the need for careful pilot studies before changes are made to laboratory animal diets. They also indicate that the estrogenic activity of rodent diets cannot be determined solely by reference to their reported phytoestrogen/soy content. The most subtle estrogenic effects yet reported for synthetic estrogens, the increases in male mouse prostate weight reported by vom Saal and his colleagues (6-9), were observed in animals fed Purina chow 5001, a diet identified by Thigpen et al. (1) as being the richest in phytoestrogens among those to which they referred. The choice of rodent diets for use in endocrine-disruption studies should receive urgent coordinated attention.
John Ashby
Helen Tinwell
Jenny Odum
AstraZeneca Central Toxicology Laboratory
Alderley Park, Macclesfield
Cheshire, United Kingdom
E-mail: John.Ashby@ctl.zeneca.com
References and Notes
1. Thigpen JE, Setchell KDR, Goelz MF, Forsythe DB. The phytoestrogen content of rodent diets [Letter]. Environ Health Perspect 107:182-183 (1999).
2. Boettger-Tong H, Murthy L, Chiappetta C, Kirkland JL, Goodwin B, Adlercreutz H, Stancel GM, Makela S. A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environ Health Perspect 106:369-373 (1998).
3. Odum J, Lefevre PA, Tittensor S, Paton D, Harris CA, Beresford NA, Sumpter JP, Ashby J. The rodent uterotrophic assay: critical protocol features, studies with nonylphenol and comparison with a yeast estrogenicity assay. Regul Toxicol Pharmacol 25:176-188 (1997).
4. Reeves PG, Nielsen FH, Fahey GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939-1951 (1993).
5. Thigpen JE, Li L-A, Richter CB, Lebetkin EH, Jameson CW. The mouse bioassay for the detection of estrogenic activity in rodent diets. Lab Anim Sci 37:602-605 (1987).
6. Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect 105:70-76 (1997).
7. vom Saal FS, Cooke PS, Buchanan DL, Palanza P, Thayer KA, Nagel SC, Parmigiani S, Welshons WV. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior. Toxicol Ind Health 14:239-260 (1998).
8. vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Parmigiani S, Welshons WV. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci USA 94:2056-2061 (1997).
9. Welshons WV, Nagel SC, Thayer KA, Judy BM, vom Saal FS. Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenestrogens increases adult prostate size in mice. Toxicol Ind Health 15:12-25 (1999).
Last Updated: December 29, 1999
