On Hiatus until 3/5

Going to somewhere with no high speed connection which blocks blogspot.

Silica Damage Progresses After Exposure Ceases

Porter, D. W.; Hubbs, A. F.; Mercer, R.; Robinson, V. A.; Ramsey, D.; McLaurin, J.; Khan, A.; Battelli, L.; Brumbaugh, K.; Teass, A., and Castranova, V.

Progression of lung inflammation and damage in rats after cessation of silica inhalation.

Toxicol Sci. 2004 Jun; 79(2):370-80.


Abstract: Human epidemiologic studies have found that silicosis may develop or progress even after occupational exposure has ended, suggesting that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure. We previously described the time course of rat pulmonary responses to silica inhalation as biphasic, the initial phase characterized by increased but controlled pulmonary inflammation and damage. However, after a threshold lung burden was exceeded, rapid progression of silica-induced pulmonary disease occurred. To test the hypothesis that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure we initiated a study to investigate the relationship between silica exposure, the initiation and progression of silica-induced pulmonary disease, and recovery. Rats were exposed to silica (15 mg/m(3), 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were maintained without further exposure for 36 days to examine recovery. The major findings of this study are: (1) silica-exposed rats were not in pulmonary overload, and lung silica burden decreased with recovery; (2) pulmonary inflammation, damage and lipidosis increased with recovery for rats exposed to silica for 40 and 60 days, but not 20 days; (3) histopathology revealed changes in silica-induced alveolitis, epithelial hypertrophy and hyperplasia, and alveolar lipoproteinosis consistent with bronchoalveolar lavage (BAL) endpoints; and (4) pulmonary fibrosis developed even when exposure was stopped prior to its initial development.

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BrooklynDodger(s) comments: NIOSH labs in Morgantown produce a steady stream of "modest" size inhalation toxicology projects which really illuminate current problems of occupational exposure. For example, the only medline-accessible study of diacetyl, the active ingredient in popcorn workers lung, is from this lab. These labs are a gift from Robert Byrd, although they exist at the cost of closing NIOSH inhalation tox in Cincinnati.

It's unfortunate that these studies aren't followed up by the appropriate 2-year or lifetime bioassays, with larger groups and lower exposure levels. This study actually used substantial numbers of animals, although still modest compared to a high dollar industry bioassay [for example titanium dioxide] and only held animals for 100 days [60 days of exposure plus 36 days of recovery]

The investigators say this was "a study to investigate the relationship between initial silica exposure, the initiation and progression of silica-induced pulmonary disease, and recovery after silica exposure. Three different exposure times were used in this
study, namely 20, 40, and 60 days. These represent exposure times previously determined to result in elevated but controlled inflammation and damage without fibrosis (20 days), the tran-sition from controlled inflammation and damage to rapidly increasing inflammation and damage (40 days), and rapidly increasing inflammation and damage with fibrosis developing (60 days)." [editor could have deleted a sentence here]

The material was Min-U-Sil, particle size averaged less than 2 microns. The mass median aerodynamic diameter of the silica particles averaged 1.78 m (range 1.70 –1.89 m), and the geometric standard deviation averaged 1.93 m (range 1.87–2.00 m). Size is important should have been mentioned in the abstract.

The Dodger(s) further notes that the 15 mg/m3 exposure level must be viewed in context of resistance of the rat to particulate toxicity. The effect level for cigarette smoke carcinogenesis in the rat is about 200 mg/m3, in an extended observation study beyond the 2 year standard.

The Dodger(s) is troubled by references to a "threshold" of exposure for anything, since threshold is equally likely an artifact of small group size and population background rate of an effect. Nevertheless, the investigator's discussion is useful.

Human epidemiologic studies have
found that, even after occupational exposure has ended, silicosis
may develop or progress (Hessel and Sluis-Cremer, 1987;
Hnizdo and Murray, 1998; Hnizdo and Sluis-Cremer, 1993;
Kreiss and Zhen, 1996; Miller et al., 1998; Ng et al., 1987),
suggesting that in humans there maybe a threshold silica burden
above which silica-induced pulmonary disease would
progress without further exposure. A recent study of coal
miners who had relatively low working lifetime dust exposures,
and whose exposures were almost entirely under the
current U.S. exposure limits for coal and silica, determined that
relatively low occupational exposures to silica in mixed dust
are associated with pulmonary responses, including inflammation
and fibrosis (Kuempel et al., 2003). When considered
together, these human studies suggest that relatively low silica
exposures may pose a serious health risk because silica-induced
disease, once initiated even at low threshold lung burdens,
can progress even in the absence of further exposure. The
findings of our rat inhalation model are consistent with the
pattern of pulmonary responses reported in humans and, thus,
add support to this proposal. The similarity in the rat silica
inhalation model presented here and previously reported human
pulmonary responses suggests that this rat model can be
used in future investigations of the mechanisms which may be
responsible for these phenomena (Kuempel et al., 2002).

It's important to extend this work beyond silica to a series of other PSLT particles.

Of Mice [and rats] and Men exposed to cigarette smoke

BrooklynDodger(s) request indulgence for a possible reposting. The Dodger(s) intend a posting on effects of silica exposure at 15 mg/M3, and also on the controversy over titanium dioxide and carbon black carcinogenicity. It's important to establish how resistent rats and mice are to particle carcinogenesis in the bioassay, and why that's important for risk assessment.

The goal is to parallelogramate exposures, man to mouse, epidemiology to bioassay.

Remarkably, it turns out that until 2004, there was not sufficient NTP evidence that cigarette smoke caused cancer in animals. Reproducibly, cigarette smoke caused cancer in hamsters, but larynx not lung cancer. Rats and mice were marginal. But, NTP requires two species. Without human evidence [imagine 1953], cigarettes would not have been "reasonably anticipated."

In the current climate, cigarettes would have been permitted to go into commerce [were they an industrial product] and might have been advocated as a lower toxicity alternative to cigars and pipes.

In 2004, and 2005, bioassays were finally published showing an association between cigarette smoke exposure and lung cancer in rats and mice. BrooklynDodger(s) note the effect level is about 200 mg/M3. Remember that number when people denigrate the bioassay of titanium dioxide at that level, or call 5 mg/M3 a "high" exposure to diesel particulate.

Second, the Dodger(s) notes the 30 month exposure of the rats or the "lifetime" exposure of the mouse. The Ramazzini Institute scientists have been criticized for lifetime exposure, rather than the standard 24 month [and industry advocated 18 month] in the US.

Next time we have an argument about unrealistic exposure levels, remember the cigarette studies.

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Mauderly, J. L.; Gigliotti, A. P.; Barr, E. B.; Bechtold, W. E.; Belinsky, S. A.; Hahn, F. F.; Hobbs, C. A.; March, T. H.; Seilkop, S. K., and Finch, G. L.

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats. Toxicol Sci. 2004 Oct; 81(2):280-92.

Abstract: An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.

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Hutt, J. A.; Vuillemenot, B. R.; Barr, E. B.; Grimes, M. J.; Hahn, F. F.; Hobbs, C. H.; March, T. H.; Gigliotti, A. P.; Seilkop, S. K.; Finch, G. L.; Mauderly, J. L., and Belinsky, S. A.

Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer in B6C3F1 mice through genetic and epigenetic pathways.

Carcinogenesis. 2005 Nov; 26(11):1999-2009.

Abstract: Although cigarette smoke has been epidemiologically associated with lung cancer in humans for many years, animal models of cigarette smoke-induced lung cancer have been lacking. This study demonstrated that life time whole body exposures of female B6C3F1 mice to mainstream cigarette smoke at 250 mg total particulate matter/m(3) for 6 h per day, 5 days a week induces marked increases in the incidence of focal alveolar hyperplasias, pulmonary adenomas, papillomas and adenocarcinomas. Cigarette smoke-exposed mice (n = 330) had a 10-fold increase in the incidence of hyperplastic lesions, and a 4.6-fold (adenomas and papillomas), 7.25-fold (adenocarcinomas) and 5-fold (metastatic pulmonary adenocarcinomas) increase in primary lung neoplasms compared with sham-exposed mice (n = 326). Activating point mutations in codon 12 of the K-ras gene were identified at a similar rate in tumors from sham-exposed mice (47%) and cigarette smoke-exposed mice (60%). The percentages of transversion and transition mutations were similar in both the groups. Hypermethylation of the death associated protein (DAP)-kinase and retinoic acid receptor (RAR)-beta gene promoters was detected in tumors from both sham- and cigarette smoke-exposed mice, with a tendency towards increased frequency of RAR-beta methylation in the tumors from the cigarette smoke-exposed mice. These results emphasize the importance of the activation of K-ras and silencing of DAP-kinase and RAR-beta in lung cancer development, and confirm the relevance of this mouse model for studying lung tumorigenesis.

Hecht, S.S. (2005)

Carcinogenicity studies of inhaled cigarette smoke in laboratory animals: old and new. Carcinogenesis 26, 1488-92.

Abstract: A new study demonstrates that lifetime whole-body exposure of B6C3F1 mice to high doses of cigarette smoke robustly increases lung cancer incidence compared with sham exposed animals. This is the first study to demonstrate a strong effect of inhaled cigarette smoke on lung cancer in an animal model. This commentary attempts to put the new results in perspective with the existing literature on cigarette smoke inhalation studies in animals and discusses strengths, limitations and possible applications of available models.

Indoor Air Health Effects Among Children

Indoor Air Volume 14 Page 59 - August 2004

Volume 14 Issue s7

Dampness in buildings and health (DBH): Report from an ongoing epidemiological investigation on the association between indoor environmental factors and health effects among children in Sweden

C.-G. Bornehag1,2,3, J. Sundell3 and T. Sigsgaard4

Abstract With the aim of identifying health-relevant exposures in buildings, an epidemiological study "Dampness in Buildings and Health" (DBH) started in the year 2000 in Sweden. The health focus of the study is on asthma and allergic symptoms among small children and their parents. The first step in the study was an epidemiological cross-sectional questionnaire on housing and health involving 14,077 preschool children in the county of Värmland in Sweden (March–April 2000). Self-reported moisture-related problems in the building were strongly associated with asthma, allergic symptoms, and airway infections among children and adults. Other factors associated with symptoms among the children were allergic heredity, smoking in the family, male sex, urban living, short breast feeding, pet keeping, daycare attendance, non-farming life and some food habits. The second step in the study was a nested case-control study including 198 children with symptoms and 202 healthy controls. A detailed clinical examination by physicians in parallel with extensive inspections and measurements in the subjects' homes were conducted from October 2001 to April 2002. The influence of selection bias in case-control studies has been studied, and questionnaires on self-reported symptoms and building characteristics have been validated. Identified risk factors for allergic symptoms are, e.g., inspector-observed dampness, a low ventilation rate, endotoxin, Penicillium and phthalates in dust. In the third phase, a 5-year follow-up study will be carried out during 2005. The same questionnaire as used in DBH-phase 1 will be distributed to the 10,852 children/parents who responded to the first questionnaire in 2000. Finally, in a fourth phase, controlled experimental studies in climate chambers and in vitro tests regarding findings from DBH-Phase 2 are planned to be conducted during 2004–08. Practical implications Asthma and allergies among small children are associated with a number of risk factors in the indoor environment. In investigations of building-related health problems many factors have to be considered, including "dampness" emissions from building materials, and ventilation rates.

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[Marie Curie, a new avatar, symbolizing female scientific leadership]

BrooklynDodger(s) comments: Children's environmental health sometimes gets traction where the health of grown-ups slips down the slope. Grown-ups are usually treated as guilty victims of their diet composition, eating, smoking, drinking, and having sex. These guilty behaviors are increasingly advanced as excuses for cutting health insurance. Pediatricians seem more interested in environmental health than most other docs, the Dodger(s) knows of two leading occupational health docs who started as pediatricians, and at least one was denigrated as a "baby doctor" in the occupational setting. Interest in pediatric lead intoxication drove modern understanding of adult occupational lead poisoning. Why childhood asthma rates are going up in the US is mysterious. Air pollution is going down, asthma going up, this observation is used by obstructors of public health to argue against air pollution regulation. Another confusing observation is that early life exposure to biological agents - like a barnyard - seems to protect against asthma in later childhood. But why would pets increase risk and farming decrease? At the same time, a home environment of poverty is associated with more asthma. BrooklynDodger(s) searches for a hypothesis in the impressions that more modern housing has fewer air changes, perhaps more moisture because of home laundries, lint and moisture from clothes dryers. The Dodger(s) will return to this mystery.

More on Ventilation and Childhood Asthma

Indoor Air Volume 15 Page 275 - August 2005 doi:10.1111/j.1600-0668.2005.00372.x

Volume 15 Issue 4

Association between ventilation rates in 390 Swedish homes and allergic symptoms in children

C. G. Bornehag1,2,3, J. Sundell2, L. Hägerhed-Engman1, T. Sigsgaard4

Abstract The aim of the study was to test the hypothesis that a low-ventilation rate in homes is associated with an increased prevalence of asthma and allergic symptoms among children. A total of 198 cases (with at least two of three symptoms: wheezing, rhinitis, eczema) and 202 healthy controls, living in 390 homes, were examined by physicians. Ventilation rates were measured by a passive tracer gas method, and inspections were carried out in the homes. About 60% of the multi-family houses and about 80% of the single-family houses did not fulfill the minimum requirement regarding ventilation rate in the Swedish building code (0.5 air changes per hour, ach). Cases had significantly lower ventilation rates than controls and a dose–response relationship was indicated. Practical Implications A low-ventilation rate of homes may be a risk factor for allergies among children. Families with allergic children should be given the advice to have good ventilation in the home. In investigations, of associations between environmental factors and allergies, the air change rate in homes has to be considered. >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

BrooklynDodger(s) comment: The Dodger(s) again take advantage of new technique for grabbing a table from a pdf.

The public health finding is straightforward, so the Dodger(s) will muse on other things. Actually measuring air movement and presenting the range and central tendency is a great public health value. Boy would it be nice to get this data for the US.

First, it's unfortunate the investigators tabulate the mean rather than the median. The Dodger(s) would be quite surprised if ventilation rates were distributed symmetrically about the mean, so the median would be a better statement of the central tendency.

Second, natural ventilation and the oldest construction - the Dodger(s) assumes windows and doors, provides more air changes than "mechanical exhaust." It's a little unclear what this middle period ventilation and construction was. Even with active exhaust, ventilation is poor.

The ASHRAE book says a room with no windows and no door [we assume] to the outside enjoys 0.5 ACH. ASHRAE air changes include "appropriately cleaned" recirculated air. So natural ventilation may be superior to an office with ASHRAE design criteria of 1 ACH. The Dodger(s) assumes 1 ACH implies a half life of a contaminant of 1 H, not that it's all gone in an hour.

Third, we come back to the conundrum that living an a farm early in life - exposed to all kinds of biologicals - protects against asthma, while living in a damp and moldy apartment, which likely has less of all kinds of biologicals than the farm, and maybe even less than the apartment specific biologicals, agonizes asthma.

More on Writs

[vioxx; not a new avatar]


Jury Rejects Claim That Vioxx Caused Death
Merck Has Now Won 2 of 3 Cases

By Brooke A. Masters
Washington Post Staff Writer
Saturday, February 18, 2006; Page A17

A federal jury in New Orleans yesterday cleared drugmaker Merck & Co. of responsibility in the first federal case involving use of its withdrawn arthritis drug Vioxx.

The eight-member jury deliberated for less than four hours before finding that Merck was not liable for the 2001 heart attack that killed Richard Irvin Jr., who had taken the painkiller for less than a month. The jury agreed that Merck was not negligent, did not provide inadequate warnings about the drugs and did not produce a defective product.

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BrooklynDodger(s) comments: The Dodger(s) is a little concerned about this decision if the jury in fact found that "Merck was not negligent, did not provide inadequate warnings about the drugs and did not produce a defective product." The Dodger(s) general reading is that Merck at the very least pushed for marketing Vioxx beyond those who suffered stomach aches from the cheaper, longer tested alternatives. The NEJM suggests that the original clinical trial report might have been cooked as well. Nevertheless, a plaintiff still has to show that the injury they suffered was caused by Vioxx Looking at the 3 trials so far, the Dodger(s) hope that the plaintiff's bar is testing how weak a case on causality will win. This case had previously hung at 8-1 for no cause.

There is a precedential danger here. WaPo tells us:

The New Orleans case has been closely watched because it was the first of 4,050 federal Vioxx cases to come to trial. U.S. District Judge Eldon E. Fallon, who is overseeing all of the federal cases, has scheduled two more trials in the next few months and has said he hopes to conduct broad settlement talks when all three are finished. [This would seem to be a reason not to go back at the same venue with the same case in front of that particular judge.]

Merck also is defending more than 5,500 state court cases, including one now being tried in Texas.

The victim took Vioxx for one month. It was prescribed over the phone by a son-in-law, several states away. The son in law testified that a warning would have kept him from prescribing.

The judge excluded two plaintiff's witnesses. From the Times article, these appeared to be physicians who had treated the victim. The judge said they were not qualified to opine on whether Vioxx caused the heart attack. The Dodger(s) is conflicted about that. Excluding witnesses is bad news. Probably they were qualified to say they were really surprised the patient kicked the bucket, given their experience with similarly healthy patients. But are they any better biostatistically compared to the cheerleader manufacturer's reps giving away drugs?

These trials are deciding issues which are as complex as the risk assessment phase of a full blown OSHA chemical hazard rulemaking. The jurors are at least as qualified as the lawyer now nominated as Assistant Secretary of Labor for OSHA, or the Secretary of Labor, neither of whom have any science training. But the issues may not be framed, or the plaintiff's experts as credentialed to opine on the issues which are key.

It would be good if the plaintiff's lawyers could control what's going in front of this judge? He's listening to it all, Merck gets to fine tune.

States Writs

Rules Would Limit Lawsuits

U.S. Agencies Seek To Preempt States

By Caroline E. Mayer

Washington Post Staff Writer
Thursday, February 16, 2006; Page D01

The Bush administration is using federal rulemaking to limit consumer rights to seek damages under state laws governing faulty products.

The Consumer Product Safety Commission will vote today on a rule that would restrict such suits in the case of mattresses that catch fire, the most recent rule changes undertaken by several agencies. Last month, the Food and Drug Administration limited consumers' ability to recover damages for injuries from agency-approved drugs

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BrooklynDodger(s) comment: The Dodger(s) can't figure out how a rule by an agency can impact a lawsuit under a state statute. New avatar aside, the Dodger(s) can't claim a law degree.

However, as we look back on the intial flight of Vioxx lawsuits, we think each of those juries was asked to do something in the realm of rulemaking hearing on the risk of taking the medicine. Without agency support, they were asked, among other things, to determine whether the adverse effect was more likely than not the consequence of taking Vioxx. While there was little doubt of Merck's guilt in concealing risks, and marketing Vioxx well beyond the stomach irritation sufferers who were legitimate users, the difficulty of proving that a particular victim suffered the statistical consequences of the exposure was pretty difficult.

We're still mystified about the substance of these rules. What about the role of the industry in setting inadequate rules?

Dogs are good for something

[Probably not a new avatar.]

The Dodger(s) have been accused of hostility to caninity. Here's a positive story of the value of dogging. >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

American Journal of Preventive Medicine
Volume 30, Issue 2 , February 2006, Pages 131-136

Relationships Among Dog Ownership and Leisure-Time Walking in Western Canadian Adults

Shane G. Brown BEd^, and Ryan E. Rhodes PhD

School of Physical Education, University of Victoria, Victoria, British Columbia, Canada

Available online 2 February 2006.

Background

Dog ownership may be an effective tailored intervention among adults for promoting physical activity. This study examined the relationship between walking, physical activity levels, and potential psychological mediators between people who owned dogs and those who did not own dogs in the Capital Region District of Greater Victoria, British Columbia, Canada. Data were collected in September 2004; analyses were conducted in January 2005.

Methods

A random sample of men (n=177) and women (n=174) aged 20 to 80 years participated. Questionnaires were mailed out in 2004 to collect information about demographics, dog ownership, leisure-time walking, physical activity levels, and theory of planned behavior (TPB) constructs.

Results

The analyses revealed that dog owners spent more time in mild and moderate physical activities and walked an average of 300 minutes per week compared to non–dog owners who walked an average of 168 minutes per week. A mediator analysis suggests that dog obligation acts as a mediator between dog ownership and physical activity. Moreover, the theory of planned behavior constructs of intention and perceived behavioral control explained 13% of the variance in walking behavior with an additional 11% variance in walking behavior being explained by dog obligation. Regarding intention to walk, the TPB explained 46% of the variance in intention to walk with dog obligation adding an additional 1% variance.

Conclusions

In this group of Canadians, those who owned a dog participated in more mild to moderate physical activity than those who did not. Acquiring a dog should be explored as an intervention to get people more physically active.

More on Hunting Safety

BrooklynDodger(s) continues to look on hunting safety as a subset of injury control. The Dodger(s) found a reference in the blogosphere that the Cheney party had resumed hunting after a lunch at which beer was consumed.

The Dodger(s) sought a reference to an acceptable blood alcohol level for persons shooting guns, in
Texas or anywhere else. The Dodger(s) were not successful, except for the following reference at the website of a Texas hunting venue:

Hunting Guidelines

There are a few simple requirements and rules to observe while you are enjoying your hunting experience on the Masser Ranch.

• Requirements

  • You must have a valid Texas hunting license, and follow all game laws.

  • You will be required to sign any necessary release forms before being allowed to hunt.

  • You will be required to shoot your weapon at our range before being allowed to hunt.

• Hunting Rules

  • No loaded weapons in camp or in the lodge.

  • No alcohol will be consumed during hunting hours.

  • No shots at running game.

Nanotubes not Just GigaHype

Finally some data, although limited, on engineered nanoparticles. First, the study demonstates some effect of nanotube material. For ball park risk estimation, we'd need to know how some other materials with human evidence, say silica, react in this setting and at what dosing.

This study gives us little to paralleogramate this risk with.


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Muller, J.; Huaux, F.; Moreau, N.; Misson, P.; Heilier, J. F.; Delos, M.; Arras, M.; Fonseca, A.; Nagy, J. B., and Lison, D.

Respiratory toxicity of multi-wall carbon nanotubes.

Toxicol Appl Pharmacol. 2005 Sep 15; 207(3):221-31.


Abstract: Carbon nanotubes focus the attention of many scientists because of their huge potential of industrial applications, but there is a paucity of information on the toxicological properties of this material. The aim of this experimental study was to characterize the biological reactivity of purified multi-wall carbon nanotubes in the rat lung and in vitro. Multi-wall carbon nanotubes (CNT) or ground CNT were administered intratracheally (0.5, 2 or 5 mg) to Sprague-Dawley rats and we estimated lung persistence, inflammation and fibrosis biochemically and histologically. CNT and ground CNT were still present in the lung after 60 days (80% and 40% of the lowest dose) and both induced inflammatory and fibrotic reactions. At 2 months, pulmonary lesions induced by CNT were characterized by the formation of collagen-rich granulomas protruding in the bronchial lumen, in association with alveolitis in the surrounding tissues. These lesions were caused by the accumulation of large CNT agglomerates in the airways. Ground CNT were better dispersed in the lung parenchyma and also induced inflammatory and fibrotic responses. Both CNT and ground CNT stimulated the production of TNF-alpha in the lung of treated animals. In vitro, ground CNT induced the overproduction of TNF-alpha by macrophages. These results suggest that carbon nanotubes are potentially toxic to humans and that strict industrial hygiene measures should to be taken to limit exposure during their manipulation.

Gun Safety Comments

After considerable thought, the Dodger(s) decided the VP shooting his crony was a public health issue related to injury control and unintentional violence. The Dodger(s) wonder whether the reporting delay was related to a question of blood alcohol level? Surely it was not a question of lacking appropriate endorsement of a hunting license. The incident harks back to Tom Friedman's comment noted below. There's a difference between knowing how, or wanting, to pull the trigger, and hitting the right target. >>>>>>>>>>>>>>>>>>>>>>>>>>> EDITORIAL DESK

Osama and Katrina

By THOMAS L. FRIEDMAN (NYT) 872 words
Published: September 7, 2005

On the day after 9/11, I was in Jerusalem and was interviewed by Israeli TV. The reporter asked me, ''Do you think the Bush administration is up to responding to this attack?'' As best I can recall, I answered: ''Absolutely. One thing I can assure you about these guys is that they know how to pull the trigger.''

It was just a gut reaction that George Bush and Dick Cheney were the right guys to deal with Osama. I was not alone in that feeling, and as a result, Mr. Bush got a mandate, almost a blank check, to rule from 9/11 that he never really earned at the polls. Unfortunately, he used that mandate not simply to confront the terrorists but to take a radically uncompassionate conservative agenda -- on taxes, stem cells, the environment and foreign treaties -- that was going nowhere before 9/11, and drive it into a post-9/11 world. In that sense, 9/11 distorted our politics and society.

Paradigmatically Inconvenient Carcinogen

[This post formatting is driving the Dodger(s) nuts.]

The Dodger(s) had assumed the conventional non-carcinogenicity of aspartame because it's a dipeptide of two standard amino acids. It's not that these are nutrients, because vitamins like the chemoprevention studies can increase cancer. It's that these amino acids are substantial parts of diet already, and lots of them around. They are macro nutrients.

However, now we have to rethink. Corn oil causes pancreatic cancer in rats. Shifts in the fat content of diet can alter tumor frequencies. But the Times summary suggests the dosing levels were relatively low compared to shifting sources of caloric intake.

The Ramazzini protocol involves lifetime exposure rather than terminating dosing and the animals at two years.

Although it probably violates copyright, the Dodger(s) couldn't resist the rat in the picture.

http://www.nytimes.com/2006/02/12/business/yourmoney/12sweet.html?_r=1&adxnnl=1&oref=slogin&adxnnlx=1139832763-IsrK11SUkARIAxM16EU1ZAThe Lowdown on Sweet?

By MELANIE WARNER

Published: February 12, 2006

WHEN Dr. Morando Soffritti, a cancer researcher in Bologna, Italy, saw the results of his team's seven-year study on aspartame, he knew he was about to be injected into a bitter controversy over this sweetener, one of the most contentiously debated substances ever added to foods and beverages.

A study conducted at an Italian cancer research center, above, has rekindled the debate on aspartame.

Aspartame is sold under the brand names Nutra-Sweet and Equal and is found in such popular products as Diet Coke, Diet Pepsi, Diet Snapple and Sugar Free Kool-Aid. Hundreds of millions of people consume it worldwide. And Dr. Soffritti's study concluded that aspartame may cause the dreaded "c" word: cancer.

The research found that the sweetener was associated with unusually high rates of lymphomas, leukemias and other cancers in rats that had been given doses of it starting at what would be equivalent to four to five 20-ounce bottles of diet soda a day for a 150-pound person. The study, which involved 1,900 laboratory rats and cost $1 million, was conducted at the European Ramazzini Foundation of Oncology and Environmental Sciences, a nonprofit organization that studies cancer-causing substances; Dr. Soffritti is its scientific director.

Didactic Matter on Indoor Air

A colleague pointed BrooklynDodger(s) to this review, in a journal of which BrooklynDodger(s) was ignorant. The abstract conveys little useful information, but the full text is a good general review with a decent amount of references to the original research.

This is important both in itself, but more important in relation to community air pollution studies. The particle levels are routinely measured by EPA through a network of stations. But the stations are typically in "clean" areas or on roof tops, so as not to be influence by localized point sources. So the relationship of these rooftop data to what people on the ground are breathing outdoors is one issue. The relationship of rooftop to indoor and outdoor air combined is another.

BrooklynDodger(s) expects that the goodness of the correlation would vary with particle size, the smaller the particle the better the correlation. PM10 is mostly crustal dust, PM2.5 and below would be agglomeration, with a peak frequency at around 1 micron.

BrooklynDodger(s) just discovered how to grab a page image out of a pdf and pull it into a blog posting. Whoopee!!!

Above shows penetration into a building based on particle size. It's virtually 100% in the size range of interest.



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Indoor Air 2004; 14 (Suppl 7): 175–183

Indoor particle dynamics

Introduction

Airborne particulate matter (PM) can cause many
deleterious effects. Of concern in indoor environments
are adverse health outcomes and material damage. The
significance of PM as a determinant of indoor air
quality is strongly related to airborne particle concentration,
size distribution, and chemical or biological
composition. In turn, these attributes depend on a suite
of other factors, broadly classified as sources, removal
mechanisms, and transformation processes. In studying
indoor particle dynamics, we seek to elucidate the
causal dependencies of indoor particle concentrations
and fates on the processes that influence them. In this
paper, I first provide an overall framework for thinking
about indoor particle dynamics, and then present a
synopsis of what is known about the key phenomena.

W. W. Nazaroff
University of California, Berkeley, USA
Key words: Deposition; Emissions; Filtration; Material
balance; Penetration; Ultrafine.
Professor William Nazaroff
2108 Shattuck Ave. Rm. 315,
Department of Civil & Environmental Engineering,
2108 Shattuck Avenue #315, University of California,
Berkeley, CA 94720-1716, USA
e-mail: nazaroff@ce.berkeley.edu.



Practical implications
The paper gives a practical overview of issues related to particulate matter indoors, as well as valuable information for understanding filtration and how particles contribute to adverse health effects.

Popping Off About Popcorn Lung (?2)

The Dodger(s) can't figure out if this was previously posted. So, if you remeber it, skip over.

BrooklynDodger(S) comments: Frankly, the picture flips the Dodger out. First, there's something really nasty lurking here. Like concealed data showing that diacetyl, the active ingredient in this butter flavor, was known to be a problem. There's nothing on medline or toxline

Popcorn Lawsuit Settled JOPLIN, Missouri, Jan. 25, 2006 (AP) A butter flavoring manufacturer ordered to pay $20 million to a couple has settled with them out of court, ending the company's appeal of the damage award for lung disease the couple blamed on a chemical in the flavoring product. >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> An obvious question, before EPA and FDA tell us there's no problem with consumer exposure is what's the exposure from cooking popcorn in your microwave? Or, what do you get from spritizing "I can't believe it's not butter" on your toast? Can't be found. The structure of diacetyl is below. Speaking as chemist(s) and toxicologist(s), the Dodger(s) would blow right by this structure without a second thought. So much for structure activity. >>>>>>>>>>>>>>>>>>>>>>>>

Commentation and Glad Handing.

[A new avatar?] [Bayesless]
BrooklynDodger(s) comment: Malcolm Gladwell is hot, as a non-fiction author translating technical subjects for lay audiences. In this case, it's social science type topics. He parallels Suroweicki (sp?), also at the New Yorker, who does business and economics, and may James Glieck who wrote on chaos and other more natural science topics. The Dodger(s) concern is that these guys have "never the played the game" in the disciplines they write about. Unlike Paul Krugman and Steve Gould, for two. Or, the Dodger(s) or the Reveres. Even though no practitioner can have worked on more than a few of the important issues that might be covered in an first year course in chemistry or biology or economics, nevertheless the presentation is grounded in some direct understanding of where the ideas came from. That said, practitioners are often not very good at explaining what's important about their ideas. In a way, a bench scientist writing about stuff away from the scientist's field may be the best commentator.Gladwell's commentaries on auto safety, published in the New Yorker, were mainly wrong. He said the focus on crash survivablity was wrong, emphasized behavior modification, and missed the environmental differences between driving in the US and driving in Europe.

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The Gladwell Effect

http://www.nytimes.com/2006/02/05/books/review/05donadio.html?_r=1&oref=slogin

• 
  

By RACHEL DONADIO

Published: February 5, 2006

"PEOPLE are experience rich and theory poor," the writer Malcolm Gladwell said recently. "People who are busy doing things — as opposed to people who are busy sitting around, like me, reading and having coffee in coffee shops — don't have opportunities to kind of collect and organize their experiences and make sense of them."

---

MALCOLM GLADWELL'S BOOKS

'Blink' (2005): Review | First Chapter

'The Tipping Point' (2000): Review | First Chapter

Slight, shoeless and sporting the large head of curly hair that's become his trademark, Gladwell, a staff writer for The New Yorker, was sitting at the kitchen table of his apartment in a West Village town house. In tones at once laid-back and precise, he was discussing his best-selling books: "The Tipping Point" argues that small actions can spark "social epidemics" — a term he gives a positive connotation; and "Blink a paean to intuitive thinking, makes a case for "thin-slicing," paring down our information intake so we can tune out the static and make fast, sound decisions

EPA and Particles

Am J Respir Crit Care Med Vol 173. pp 365–369, 2006

AJRCCM is the journal of the American Thoracic Society, which is the medical arm of the American Lung Association. The ALA projects a public health orientation, contrasting the American Cancer Society emphasis on being fat, drinking, smoking and eating potato chips.

Anyway, the lead editorial in the new issue is by Rom and Samet. Unfortunately, no abstract, and therefore no medline access to the text, but, in conclusion of a short summary of the evidence:


In the face of the extensive evidence on PM and health and
the strong mandate of the Clean AirAct for public health protection,
the PM NAAQS proposed by Administrator Johnson appear
lax. Based on the same evidence, the American Thoracic
Society and other health organizations have recommended 12
and 25 ug/m3 for the average annual and 24-h PM2.5 standards,
respectively. The proposed, less stringent standard does not protect
the nation’s health, as required by the Clean Air Act.


Again, the importance of these recomendations for OSH practitioners is their implication for occupational environment, where the 24-h standard is something like 10,000 micrograms.

Evisceration by Evaluation

http://www.whitehouse.gov/omb/expectmore/

To paralysis by analysis we can add evisceration by evaluation to the burdens of public health agencies. Each program is rated by OMB according the PART [program assessment rating tool]. OMB negotiates or imposes goals. Programs which are ineffective or results not demonstrated are supposed to be cut. Here's the deal:

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• Programs that are PERFORMING have ratings of Effective, Moderately Effective, or Adequate.
  • Effective. This is the highest rating a program can achieve. Programs rated Effective set ambitious goals, achieve results, are well-managed and improve efficiency.
  • Moderately Effective. In general, a program rated Moderately Effective has set ambitious goals and is well-managed. Moderately Effective programs likely need to improve their efficiency or address other problems in the programs' design or management in order to achieve better results.
  • Adequate. This rating describes a program that needs to set more ambitious goals, achieve better results, improve accountability or strengthen its management practices.

  Programs categorized as NOT PERFORMING have ratings of Ineffective or Results Not Demonstrated.

  • Ineffective. Programs receiving this rating are not using your tax dollars effectively. Ineffective programs have been unable to achieve results due to a lack of clarity regarding the program's purpose or goals, poor management, or some other significant weakness.
  • Results Not Demonstrated. A rating of Results Not Demonstrated (RND) indicates that a program has not been able to develop acceptable performance goals or collect data to determine whether it is performing.
• >>>>>>>>>>>>>>>>>>>>>>>>>>>>

OSHA, MSHA and NIOSH all scored "adequate." FEMA also scored "adequate." For what it's worth here's some choice extracts:

Dept of Health & Human Service

National Bioterrorism Hospital Preparedness Program

Results Not Demonstrated

Dept of Homeland Security	Immigration and Customs Enforcement: Automation Modernization Program	Results Not Demonstrated
Dept of Homeland Security	Preparedness -- Grants and Training Office Assistance to Firefighters Grant Program	Results Not Demonstrated
Dept of Homeland Security	Preparedness -- Grants and Training Office State Homeland Security Grants	Results Not Demonstrated
Dept of Homeland Security	Preparedness -- Infrastructure Protection Cyber Security	Results Not Demonstrated
Dept of Homeland Security	Science and Technology: Threat and Vulnerability, Testing and Assessment	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Air Cargo Security Programs	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Aviation Regulation and Enforcement	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Baggage Screening Technology	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Federal Air Marshal Service	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Flight Crew Training	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Passenger Screening Technology	Results Not Demonstrated
Dept of Homeland Security	Transportation Security Administration: Screener Workforce	Results Not Demonstrated

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By the way, the Departments of Defense and State are largely effective or moderately effective. Guess who's going to be cut? OSHA and NIOSH.
Guess who's going to be increased? DHS

Roadway Fatalities and Speeding

BrooklynDodger(s) is irritated by blame the victim employer driven driving safety programs. So the Dodger(s) begin a series looking at data, moving toward a real public health approach.

Employer [including the Bush OSHA] propaganda exclusively targets seat belt use and drunk driving. The Dodger(s) has also advocates seat belt use and sobriety behind the well. But this campaign wastes time and money, and a diversion of attention.

The Dodger(s) frames a constellation of risk behavior deducible from the high relative risk of roadway fatality: friday and saturday night, alcohol, younger, male, no seat belt, speeding. Yes, it's risk behavior. Public health approaches would try to identify causes driving the risk behavior, and address those causes.

So here's some descriptive data. Time trends might be of some interest, but the Dodger(s) will ignore them for the moment.

Speeding was noted in 1/3 of roadway fatalities.

There's a confounding of drinking and speeding. There's a confounding of weekend nights and speeding. It's unfortunate the report doesn't consider seat belt use as well.

The Dodger(s) are not surprised that rural roads and going around curves are confounding with speeding as well, although that may be a FARS reporting phenomenon.

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DOT HS 809 839

June 2005
Technical Report

Analysis of Speeding-Related
Fatal Motor Vehicle Traffic Crashes

Executive Summary

In 2002, 13,713 fatalities -- about a third of all fatalities that occurred in motor vehicle traffic
crashes were speeding-related, i.e., at least one of the drivers involved in the crash was speeding......about 40 percent of speeding-related fatal crashes occurred while negotiating a curve, while slightly less than 20 percent of non-speeding related fatal crashes occurred under similar roadway geometry... About 41 percent of drivers who were intoxicated (BAC=0.08+) were also speeding as compared to 14 percent for sober drivers. A major proportion of fatal, speeding-related single-vehicle crashes occur on rural roadways.... The western states show a higher proportion of their overall fatalities to be speeding-related as compared to the eastern states.

Between 1983 and 2002, New Jersey had the lowest overall proportion of fatalities that are
speeding-related while South Carolina had the highest such percentage.

Fine Points about Fine Particles

[new avatar]

BrooklynDodger(s) comments: This is a tough post. The Dodger(s) think the most important finding of the last decade is the human health effects from exposure to poorly soluble low toxicity (PSLT) particles. This started with the observation that exposure to diesel particulate matter caused cancer in rats (but not mice.) This gave biological plausibility to repeated studies showing increase cancer among workers exposure to DPM, mostly truck drivers and train drivers. Then, additional bioassay studies showed carbon black - DPM with the PAC's washed off - also caused lung cancer in rats (but not mice). The titanium dioxide - the non-toxic control - cause cancer in rats (but not mice.) Air pollution studies directly observe increase mortality from respiratory and cardiac effects correlated with variation in particulate levels within EPA's current limits. Initially, no one could believe the cardiac effects. Then, laboratory studies showed that fine and ultrafine particles - PR'd as "nanoparticles" - could be shown to penetrate into circulation and show systemic effects in animals and people. A leading experimenter in the area was Gunter Oberdorster. Maybe the leading experimenter in non-cancer effects. Major funding from the Health Effects Institute, published in NIEHS Environmental Health Perspectives. IARC has put this who game in play this February. Carbon black, titanium dioxide and non asbestos talc are the PSLT trifecta. The Dodger(s) jaw(s) dropped to see Oberdorster show as an observer on behalf of the Industrial Minerals Association at this show in Lyons. The Dodger(s) now hold their breath as to the result. >>>>>>>>>>>>>>>>>>>>>>>>> Environ Health Perspect. 2005 Jul;113(7):823-39.

Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles.

Oberdorster G, Oberdorster E, Oberdorster J.

Department of Environmental Medicine, University of Rochester, Rochester, New York 14642, USA. Gunter_Oberdorster@urmc.rochester.edu

Although humans have been exposed to airborne nanosized particles (NSPs; <>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

http://monographs.iarc.fr/past&future/vol93-participants.pdf

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

VOLUME 93: CARBON BLACK, TITANIUM DIOXIDE AND NON-ASBESTIFORM TALC* Lyon, France: 7-14 February 2006
Observers

John Hoskins, Independent Consultant, on behalf of the Titanium Dioxide Panel of the American Chemistry Council (USA) & CEFIC Titanium Dioxide Manufacturers Association (Europe)

Noor Jehan, University of Peshawar, Pakistan Peter Morfeld, RAG Inc., on behalf of the International Carbon Black Association

Kenneth Mundt, ENVIRON Corporation, on behalf of the International Carbon Black Association

Joshua E. Muscat, Penn State Cancer Institute, on behalf of the Industrial Minerals Association-Europe (IMA-EU) & Industrial Minerals Association-North America (IMA-NA)

Günter Oberdörster, University of Rochester Medical Center, on behalf of the Industrial Minerals Association-Europe (IMA-EU) & Industrial Minerals Association-North America (IMA-NA)
David B. Warheit, DuPont Haskell Laboratory, on behalf of the Titanium Dioxide Panel of the American Chemistry Council (USA) & CEFIC Titanium Dioxide Manufacturers Association (Europe)

Science and the Public

Acquantainces of BrooklynDodger(s) have admitted not reading these laboriously posted bits of knowledge because of obscurity of the base information, much less the obscurity of interest.

The problem is that mature science is recondite. That is, best characterised by a word no one knows anyway. Back in the day, when Aristotle was writing physics, anyone could understand what he was writing about, if you could read. Now, the Physical Review, or whatever, is impenetrable.

So with many of the abstracts BrooklynDodger(s) post.

Sorry.

The problem is that when science writers express stuff much better than the sceincers who create the stuff, you wonder if the writers understand fully.

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recondite \REK-uhn-dyt\, adjective:
1. Difficult to understand; abstruse.
2. Concerned with obscure subject matter.

Recondite is from Latin reconditus, past participle of recondere, "to store back," i.e., "out of the way," hence "to hide"; itself from re-, "back, again" + condere, "to put away, to store." Thus, recondite knowledge is "hidden" (because of obscurity or difficulty) from the understanding of the average person.