Diesel v. Cigarettes

Okay, BrooklynDodger concedes this paper comes from the "Phillip Morris Research Center." Nevertheless, it illustrates how toxic diesel particulate is, compared to a premier substance which at low exposure levels [0.05 mg/m3 or less] is known to be a human carcinogen.

Inhalation Toxicology is not available to BrooklynDodger in full text, so this blog is abstract based, which may include distortions the editor and reviewers were too distracted to find.

Exposures were 3 and 10 mg/M3. In the rat, 10 mg/M3 for mainstream smoke is probably not an effect level for lung tumors. For diesel, it is an effect level.

For the final endpoint "the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5% in the high RASS [cigarette] groups, and 46% in the high DEE [diesel] groups (sexes combined)."

[It would be nice to see NTP style mortality adjusted statistics. This would determine whether the high sidestream smoke group was elevated or not, and would permit a comparison to the direct smoke study from Lovelace. Except Lovelace only does the mortality adjusted [more sensitive and more specific] method when it's contracting to NTP.]

The other biochemical measures all were positive with diesel and marginal to negative with cigarette smoke.

Diesel at these exposure levels in the rat is about equally potent with washed carbon black. There's a camp which argues diesel carcinogenicity at these levels is a particle effect, not an effect of the goo on the outside of the particle. Traditionally cigarette carcinogenesis research focuses on the genotoxic goo on the outside of the smoke particle, not the particle itself. But the cigarette particle is way less potent than the diesel particle.

It will certainly be difficult to get the cigarette toxicology guys to refocus on particles, having spent so much time with the goo.

If we allow for the particle effect in these rat bioassays [mice and hamsters are more resistent and don't get much], for both agents, what does that say for human exposures? Is there a threshold for the particle effect? Community air pollution research suggests no, at least down to 15 micrograms.



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Inhalation Toxicology
Volume 17, Number 11 / October 2005
549 - 576

Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Walter Stinn A1, Ashok Teredesai A1, Erwin Anskeit A1, Klaus Rustemeier A1, Georg Schepers A1, Peter Schnell A1, Hans-Juergen Haussmann A1, Richard A. Carchman A2, Christopher R. E. Coggins A3, Wolf Reininghaus A1
A1 Philip Morris Research Laboratories GmbH, Cologne, GermanyA2 Philip Morris USA Research Center, Richmond, Virginia, USAA3 Carson Watts Consulting, King, North Carolina, USA

Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs → lung “overload” → pulmonary inflammation → tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.

What's the MSDS for "soft soap."

Michigan Center for "Risk Science and Communication." or some such. BrooklynDodger taxonomizes risk communication into two branches, national policy risk communication and situation specific risk communication.

National policy is about how the exposure health threat that has political momentum to get some public health intervention launched is aimed at a smaller risk than something which is legally tolerated. Phthalates in pacifiers compared to sky diving or speeding on a downhill, curving country road at night in the rain after a few beers and not wearing a seatbelt.

Situation specific is about formaldehyde vapor from the insulation in your house. That's about whether you move out and file a lawsuit - vaporizing your investment against tough sell litigation - or just get over it and live or die with the exposure. That's the soft soap metaphor.

Here's the Center's Debut:


The Center for Risk Science and Communication inaugural symposium:
'Calculation to Communication'
Promoting informed decision-making about health risks.
Thursday and Friday September 15-16, 2005

University of Michigan School of Public Health
Ann Arbor, Michigan

Here are some hazardous ingredients, each more than 1% of the program:

Thursday, September 15, 2005
8:00 a.m. - Registration and Continental Breakfast


1:45 p.m. - Colloquium: 'Risk Science and the National Landscape' John Graham, Ph.D., Administrator, Information and Regulatory Affairs, Office of Management and Budget, The Executive Office of the President

4:45 p.m. Roundtable and Q&A Discussion with the afternoon participants moderated by Teresa Bowers, Ph.D., Principal, Gradient Corporation

6:00 p.m. Reception and Banquet with John Henshaw, M.P.H., Assistant Secretary of Labor for Occupational Safety and Health, 2001–2004. Registration required.
Friday, September 16, 2005

9 a.m. Keynote Address by John H. Marburger III, Science Advisor to the President and Director of the Office of Science and Technology Policy, The White House

9:45 a.m. - 1:00 pm 'Poorly Characterized Environmental Risks' A moderated discussion with:
John Butenhoff, Ph.D., Corporate Toxicology and Regulatory Services, 3M

Edward Calabrese, Ph.D., Professor of Toxicology, Environmental Health Sciences Program, University of Massachusetts School of Public Health and Health Sciences

[Mr. Hormesis]

Melvin Andersen, Ph.D., Division Director of Computational Biology, CIIT Centers for Health Research

Dennis Paustenbach, Ph.D, President and Founder, ChemRisk, Inc.

Census Tract Epidemiology Strikes [out] Again

BrooklynDodger blogged previously about census tracting for vermiculate in New Jersey. Here's an uncontroverted attempt to quell concerns about explosives residues and nuclear processing in Missouri. BrooklynDodger questions whether enough stuff from the feared facility could get far enough to measurably perturb mortality in the target zip codes or county. So a null finding would likely be uninformative whether the leakage, which could still be, in EPAese, an "unreasonable risk to public health" and an association would likely be with something other than the targeted leakage.

Nevertheless, BrooklynDodger was bored enough to search for the actual report. Findings were variously headlined as "no cancer cluster", "are not higher," are "not higher than normal."

Somewhat, this turns on combining races in all analyses, and combining all races and genders in some of the key analyses. BrooklynDodger questions this increasingly common practice. Gender is a "real" thing, race is a reification of real social and hypothetical genetic ecological differences between populations. But population rates by race widely diverge. Transparent public health practice would identify the most concerning evidence in a race-gender group in addition to stating the investigators' strongest beliefs on the correct data set on which to base a conclusion.

Which brings BrooklynDodger to that strongest number. Leukemia mortality among males in St. Charles country was 99 observed, 82 expected. BrooklynDodger's statistical website calculates an SMR of 1.21, CI = 0.99-1.47. Ratios in females were weaker but still greater than 1.0.

So what's a risk communicator to do? [U of M is running a big symposium on risk communication. What's the MSDS for soft soap when the ingredients include John Graham and Dennis Paustenbach?]

"Not higher" without qualifiers [weasel words?] is sketchy. "Not higher than NORMAL" is still pretty sketchy. "Not signficantly different" would convey more information if it were not significantly "higher," but obviously would draw a follow up question from the great unwashed.

Fact is, the study maybe ruled out an excess greater than 47% among the men.

Persons concerned about radiation would be better served by measuring radiation, not that hard to do and with a substantial data base for assessing risk. Those concerned with past exposure to explosives residues would have to put their faith in toxicology.

PS: The Missouri public health web page leads with "Alternatives to Abortion."

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For Immediate Release:July 28, 2005
Contact:Nanci GonderOffice of Public Information573-751-6062
State health department study finds leukemia rates are not higher inWeldon Spring area
An investigation by the Missouri Department of Health and SeniorServices has determined the number of leukemia cases in St. CharlesCounty is not higher than normal. The investigation was conducted inresponse to concerns expressed by citizens in the Weldon Springcommunity about cancer – primarily childhood leukemia – and pastchemical contamination in the area.

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http://www.dhss.mo.gov/DataAndStatisticalReports/weldonspringcancerreport.pdf

Analysis of Leukemia Incidence (1996-2000) and Mortality (1994-2002) Data
in St. Charles County, and Weldon Spring and Surrounding Areas

Summary: In this study, the observed number of incident cases of leukemia in St. Charles County, Weldon Spring and its surrounding ZIP codes during 1996-2000 were compared with the expected number of cases based on the incidence rates for the State of Missouri during the same period; the observed number of leukemia deaths during 1994-2002 were also compared with the expected numbers of death based on the leukemia mortality rates for the State of Missouri during the same period. This study found that leukemia incidence rates during 1996-2000 and mortality rates during 1994-2002 in St. Charles County, Weldon Spring and its surrounding ZIP codes were not significantly different from that of the State of Missouri; the incidence rates for cancers that may be associated with exposure to radiation sources (such as sunlight, x-rays, gamma rays and other naturally occurring or man made sources of radiation) or result from a number of other genetic, lifestyle or unknown risk factors during 1996-2000 and mortality rates during 1994-2002 in St. Charles County were not significantly higher than that in the State of Missouri during the same periods.

Models of cancer - Tobacco Smoke

BrooklynDodger reminds the reader that the importance of mechanistic models is whether they suggest that high dose cancer risks persist at substantially lower exposure levels.

The best human example is tobacco smoke. Given the current close to consensus that environmental tobacco smoke causes cancer, it would appear that high to low dose persistance of risk exists for at least this carcinogen. For smokers, the risk is visible confirmed to the general population. For ETS exposed it's a risk compare to no ETS exposed lung cancer. This might be a 100 fold range of risk against at 1000 fold range of exposure.

Carcinogens are frequently dichotomized in two dichotomies: genotoxic and non-genotoxic; initiators and promoters. Genotoxicity is generally considered equivalent to initiation, and to have no threshold. There may be other mechanisms of initiation other than genotoxicity, receptor based, which also lack a threshold.

Promotors are imagined not to operate by a genotoxic mechanism - the metaphor is irritation or toxicity such as to promote cell proliferation. In turn, irritation is imagined to have a threshold.

So, here it's suggested the tobacco smoke is mostly a promoter. So, what carcinogenic insult is it promoting? The investigators suggest that it's promoting itself, but the environment contains many other lung carcinogens - diesel, silica for two ubiquitants.

The investigators conclude promotion is the primary mechanism for tobacco smoke. Since tobacco smoke has not threshold, then promotion may have no threshold either, in the only human systems in which it's been tested.

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Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1171-81.

Multistage carcinogenesis and lung cancer mortality in three cohorts.

Hazelton WD, Clements MS, Moolgavkar SH.


Fred Hutchinson Cancer Research Center, Public Health Sciences Division, M2-B500, 1100 Fairview Avenue North, Box 19024, Seattle, WA 98109-1024, USA. hazelton@fhcrc.org

Experimental evidence indicates that tobacco smoke acts both as an initiator and a promoter in lung carcinogenesis. We used the two-stage clonal expansion model incorporating the ideas of initiation, promotion, and malignant conversion to analyze lung cancer mortality in three large cohorts, the British Doctors' cohort and the two American Cancer Society cohorts, to determine how smoking habits influence age-specific lung cancer rates via these mechanisms. Likelihood ratio tests indicate that smoking-related promotion is the dominant model mechanism associated with lung cancer mortality in all cohorts. Smoking-related initiation is less important than promotion but interacts synergistically with it. Although no information on ex-smokers is available in these data, the model with estimated variables can be used to project risks among ex-smokers. These projected risks are in good agreement with the risk among ex-smokers derived from other studies. We present 10-year projected risks for current and former smokers adjusted for competing causes of mortality. The importance of smoking duration on lung cancer risk in these cohorts is a direct consequence of promotion. Intervention and treatment strategies should focus on promotion as the primary etiologic mechanism in lung carcinogenesis.

Philosophy of Asbestos Science

BrooklynDodger here mixes theoretical or philosophical concerns for authority in risk assessment with the actual case of asbestos.

The Dodger perviously commented that original research generates the aggregate which requires the cement of a paradigm to be concrete knowledge. Those who mine the aggregate may not have the temperment to extend and apply the paradigm, or see the paradigms' weaknesses. The full text of the abstract is presented here to show how little the "little picture" might be to risk managers, who are lawyers and congress people [congress people are also usually lawyers, unless they are physicians like Frist and Coburn, who are really reactionary.]

Now to the risk policy point. The big debate in asbestos risk assessment is ABC [anything but chrysotile] and OAB [only amphoboles are bad]. The same Houdini risk assessment types who denigrate epidemiology in relation to fine particles inflate epidemiology in relation to potency of various mineral types.

Biological plausibility for this contrast would be found in animal toxicity experiments, then moved to the biochemical level.

One theory for why chrysotile [the main type used, clean white asbestos from the Great White North] is less toxic [which it isn't] is the mineral content of the surface. The iron metaphor for oxidative stress [will be discussed later]. This study shows, BrooklynDodger thinks, that treating chrysotile to put more iron on the surface, like the amphiboles, makes it less toxic, not more toxic.

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Toxicology and Applied Pharmacology Volume 206, Issue 3 , 15 August 2005, Pages 356-364

Different cellular responses evoked by natural and stoichiometric synthetic chrysotile asbestos

Elena Gazzanoa, b, Elisabetta Forestic, Isidoro Giorgio Lescic, Maura Tomatisb, d, Chiara Rigantia, b, Bice Fubinib, d, Norberto Roveric and Dario Ghigoa, b, , aDipartimento di Genetica, Biologia e Biochimica-Sezione di Biochimica, Università di Torino, Via Santena 5/bis-10126 Torino, ItalybCentro Interdipartimentale “G. Scansetti”, Università di Torino, ItalycDipartimento di Chimica “G. Ciamician”, Università di Bologna, Via Selmi 2, ItalydDipartimento di Chimica IFM, Università di Torino, via P. Giuria 7, Italy

Abstract
The carcinogenic potency of asbestos, including chrysotile, is well established. Several physico-chemical features of the fibers appear implied, such as fibrous habit, size, crystallinity, morphology, and surface active metal ions, where free radical generation may take place. In contrast to other asbestos forms, iron is not a stoichiometric component of chrysotile, but is only present together with other extraneous ions as a magnesium- and silicon-replacing contaminant. To determine the role played by contaminating ions and morphological features of the fibers, a stoichiometric chrysotile with constant structure and morphology was synthesized in hydrothermal conditions. Free radical generation and the effects of these fibers on human lung epithelial A549 cells have been compared to that elicited by a well known toxic natural chrysotile (UICC A, from Rhodesia). After a 24-h incubation, the natural, but not the synthetic, form exerted a cytotoxic effect, detected as leakage of lactate dehydrogenase. Homolytic rupture of a CH bond and lipoperoxidation in A549 cells took place in the presence of the natural, but not of the synthetic, chrysotile. Antioxidant systems were also affected differently. The pentose phosphate pathway and its regulatory enzyme glucose 6-phosphate dehydrogenase were markedly inhibited only by the natural specimen, which also caused a depletion of intracellular reduced glutathione in A549 cells. These results suggest that metal ions, fiber size and state of the surface play a crucial role in the oxidative stress caused by chrysotile asbestos. Stoichiometric synthetic fibers may thus be proposed as a reference standard (negative control) for toxicological studies.

Money Tox - More on Cambridge Environmental (revised)

BrooklynDodger recently blogged about a review paper discounting risks of particle pollution [abstracted below], now spreading like a virus through the internet as an abstract in Regulatory Toxicology and Pharmacology.

This post was initially going to be a piece of free floating hostility simply attacking the enterprise, but BrooklynDodger recanted, believing these posts should mostly be foundationed by an abstract.

Another paper by the same authors was found:


Clin Occup Environ Med. 2004 Aug;4(3):481-96, vi.

Chlorinated hydrocarbon solvents.

Armstrong SR, Green LC.

Cambridge Environmental Inc., 58 Charles Street, Cambridge, MA 02141, USA. armstrong@cambridgeenvironmental.com

Chlorinated hydrocarbon solvents, such as trichloroethylene and 1,1,1-trichloroethane, have been used widely in many industries because of their ready ability to dissolve oils, greases, and other materials, their low acute toxicity, and their non-flammability. Although these materials share certain toxicologic, functional, and chemical similarities, important differences exist. These differences largely explain why certain solvents, once common, are no longer in use and why others have become more widely used over time. This article reviews the properties, toxicologic effects of interest, workplace limits, and use history of the most common chlorinated hydrocarbon solvents

BrooklynDodger wonders at the editors of this publication printing an abstract that conveys no information. Actually, in this case, the literature is better served by not propagating the authors' brief over medline.

What's the paradigm, as the Dodger tries to trash the quality of Cambridge Environmental's work?

A high school student can download abstracts, even full papers, and collect quotations supporting one or another view. The point of PhD school is that practitioners can't understand the work unless they have done the work, written and published as well. The authority of a review stands on whether the reviewer has done original original research in the field relevant to the review. But not many original researchers write reviews, and then largely after they have become statespersons of science.

There's a reason why textbook writers, even at the college level, are frequently not muchers, has beens or never weres from the perspective of original research. [Graduate textbooks tend to be compendia of review articles, in turn compendia of abstracts.]

The problem of intellectual synthesis arises because an individual's research generates particles of knowledge, which are meaningless unless held together with the cement of a paradigm to create concrete knowledge [that's a pretty good metaphor, particles should really be aggregate]. The practitioner who may be successful at generating data within a paradigm may not be able to narrate the paradigm or be conversant with the gaps in the paradigm.

For a research university, the key to admission to the faculty is some record of original research. To a degree, conversing with paradigm and its discontents generates quality research. But poor teaching is common, and few scientists are conversant with the notion of paradigm and incommensurability.

In public health areas, the data-synthesis problem intensifies because the work is interdisciplinary, and the key disciplines change from issue to issue. In a mortality study, is absence of exposure-response a consequence of uncertainty in response [epidemiology-biostatistics] or exposure [industrial hygiene]? In a bioassay, does a marginally significant result come from variation in pathologists readings or is it a real departure from historical control rates? Has the author of the review sat in the meeting where co-investigators argued over the conclusion of a single project?

Back to the matter at hand. Where do these people get off with getting their reviews into the peer reviewed literature?

Green LC, Armstrong SR.

Particulate matter in ambient air and mortality: toxicologic perspectives.
Regul Toxicol Pharmacol. 2003 Dec;38(3):326-35.

Green and Armstrong appear as co-authors on one other review found by medline, a description of health effects of chlorinated solvents with an uniformative abstract. However, the provenance of that paper is found below.

Clin Occup Environ Med. 2004 Aug;4(3):481-96, vi. Review.

Armstrong SR, Green LC.

Chlorinated hydrocarbon solvents.

Through the magic of google, the Dodger found Cambridge Environmental, its named staff, and its list of products. The staff includes previously known heavy hitters from the right side of the plate, Crouch and Charnley.

Green is a "senior scientist" and president of the Cambridge Environmental. BrooklynDodger, being an older person, questions whether a 1975 bachelors degree [there is a PhD, but the bachelors is a measure of age] without a university appointment is really "senior." Cambridge sports another "senior scientist" without even a masters degree. "LC Green" is not that easy to search on medline, but the Dodger found no original research in toxicology. Armstrong has a masters degree, usually not enough to get published.

http://www.cambridgeenvironmental.com/projects.htm http://www.cambridgeenvironmental.com/people/armstrong/sarah.htm http://www.cambridgeenvironmental.com/people/green/laura.htm

The review of chlorinated hydrocarbon toxicity would appear to be a recycling of this project:

Cambridge Environmental helped a defendant successfully argue a Daubert motion by showing that the scientific testimony of the plaintiff’s causation witness was unreliable. The case had been brought by a young woman what had contracted leukemia and sued the manufacturer of the cleaning fluid, perchloroethylene, used in the dry-cleaning shop where she had briefly worked, claiming that exposure to perchloroethylene had caused her cancer. We took the lead in preparing a joint expert affidavit signed by one of our staff, an epidemiologist, and a hematologist that strongly criticized the scientific method used by the plaintiff’s expert epidemiologist. We offered detailed testimony before the judge and the physician-scientist she had appointed to assist her. The case was dismissed on summary judgment.

The Cambridge environmental website also recounts another regulatory brief which made the literature:

"A private company sponsored our research on the potency of asbestos as a cause of lung cancer. Existing estimates of this parameter had not been updated to account for results from about a decade of epidemiologic research; and prior attempts to combine epidemiologic studies were only semi-quantitative. We assimilated dose-response data from fifteen groups of asbestos-exposed workers detailed in 22 publications, using maximum likelihood techniques to obtain measures of the relationship between cumulative exposure to asbestos and relative risk of lung cancer. Our meta-analysis (Lash, Crouch, and Green, Occup. Environ. Med. 54:254-263, 1997) explored sources of heterogeneity in the dose-response coefficient, generating a potency estimate under a fixed-effect model and another under a random effects model. These estimates were 24-fold smaller and fourfold smaller, respectively, than the OSHA (1986) estimate relied upon for rule-making."

Money Tox - Particles, and the streets of Cambridge are Paved with Gold

BrooklynDodger couldn't get the full text of the abstracted paper below, so the Dodger can't tell you who sponsored the work, if it were disclosed. The Dodger guesses it's API.

As with the API sponsored Moogavkar paper blogged recently, the sum is, they read the literature on particle toxicology, and don't buy it. Eerily, they end with the tag "not supported by the weight of scientific evidence, although other bases for regulating PM may be justifiable. " Molgavkar said "The Agency could argue that the Science raises concerns about current levels of air pollution, and that reduction of ambient fine particulate matter mass, if it could be achieved without an increase in the level of the ultrafines, could have positive effects on human health. If the Agency justifies a particulate matter mass standard on these grounds then the debate over the form and level of the standard will, for all practical purposes, belong strictly in the Policy arena."


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Regul Toxicol Pharmacol. 2003 Dec;38(3):326-35.

Particulate matter in ambient air and mortality: toxicologic perspectives.

Green LC, Armstrong SR.Cambridge Environmental, 58 Charles Street, Cambridge, MA 02141, USA. Green@CambridgeEnvironmental.com

U.S. regulations that set standards for acceptable concentrations of respirable particulate matter (PM) in outdoor air, particularly total fine particulate matter (PM(2.5)), are based largely on the belief that current concentrations cause death and illness, and that reducing these concentrations will save lives. Because the mortality risk estimates from important observational epidemiologic studies are extremely weak, derived from studies unable to control for relevant confounding causes, and inconsistent by location, toxicologic and clinical information is necessary to judge the likelihood and degree to which such findings are causal. Toxicologic data on typical forms of pollution-derived PM strongly suggest that current ambient concentrations in the U.S. are too small to cause significant disease or death. We review here the results of inhalation studies using concentrated ambient particles, diesel engine exhaust particulate matter, and sulfate and nitrate salts, and find no evidence that moderate concentrations are lethal. The expectation that lives will be saved by reducing ambient PM(2.5) in the U.S. is not supported by the weight of scientific evidence, although other bases for regulating PM may be justifiable.

mega rat - no threshold

In addition to the mega mouse study recently posted, a second attempt at establishing or refuting a threshold was launched in England. Richard Peto [of Peto and Doll] was first author. The investigators found "no indication of any "threshold."

This essential finding had little impact on the low dose extrapolation debate, and is close to forgotten.

Cancer Res. 1991 Dec 1;51(23 Pt 2):6415-51.

Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study.

Peto R, Gray R, Brantom P, Grasso P.
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, United Kingdom.

Four thousand eighty inbred rats were maintained from weaning on various different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA). The principal aim was to characterize the dose-response relationship for the effects of these agents on esophageal cancer (NDEA) or on various types of liver cancer (NDEA and NDMA), although NDEA also caused a few tumors of the nasopharynx and NDMA also caused a few tumors of the lung. The numbers of tumors of mesenchymal and Kupffer cells in the liver were too few to allow easy characterization of the dose-response relationships, and although NDMA induced large numbers of bile duct neoplasms, NDEA did not. Thus, the four principal dose-response relationships studied were of NDEA on esophageal or liver cells and of NDMA on bile duct or liver cells. At doses sufficiently high for the median time to death from the disease of interest to be estimated, relationships were observed of the general form (Dose rate) x (median)n = constant where n was about 2.3 for the first three relationships and about 1 for the last one (NDMA on liver cell tumors). By contrast, at doses sufficiently low for longevity to be nearly normal (median survival about 2.5 years), there remained no material dependence on the dose rate of the age distribution of the induced neoplasms. At these low dose rates, the number of liver (but not of esophageal) neoplasms induced by treatment was simply proportional to the dose rate. This finding is not surprising, since the background incidence of liver (but not of esophageal) neoplasms was appreciable. The linear relationship observed at low dose rates (below 1 ppm) suggests that under these experimental conditions, among rats allowed to liver their natural life span, a dose of 1 ppm of NDEA or NDMA in the drinking water will cause about 25% to develop a liver neoplasm, a dose of 0.1 ppm will cause about 2.5% to do so, and a dose of 0.01 ppm will cause about 0.25% to do so, etc., with no indication of any "threshold." (At these low dose rates, the incidence of liver neoplasms appears likely to exceed greatly that of esophageal neoplasms.) In addition, even quite low dose rates of the test agents caused a variety of nonneoplastic liver abnormalities (e.g., hyperplastic nodules, or shrinkage of hepatocytes) at a frequency roughly proportional to the dose rate.

Money Tox - Fine Particle Environmental Exposure Standard

BrooklynDodger follows Regulatory Toxicology and Pharmacology, otherwise known as the Journal of Corporate Risk Reviews and Briefs.

Well, that's not totally fair, there's some scholarship published there as well. However, the impact of the journal is that some meta-analyses [arguably new scholarship] and other reviews appear with the imprint of peer review to be included in reviews at IARC and NTP.

So, here comes, in advance of the new EPA review on particle limits, something which falls rhetorically outside the lines. The abstract begins "I review the rationale for the Environmental Protection Agency's 1996 fine particle standard..." This review was sponsored by the American Petroleum Institute. It's not clear from what regulatory venue it's recycled.

Suresh Moolgavkar may actually have the weight to start a scholarly paper with "I," since he has a carcinogenesis extrapolation model named for him, the "two-stage clonal expansion model." [Actually, the two-stage model has more parameters than the "linearized multi-stage model."] Even so, the convention of scholarly writing is that there is no "I" in expert.

Moolgavkar is correct that in 1996, there was little toxicological support for the finding of increased cardiovascular mortality associated with particulate exposure. The lynch pin epidemiology appeared only in 1993. However, it's not totally balanced to invoke epidemiology since 1996 to evaluate the staff paper, and ignore the wealth of toxicology since 1996. Toxicology, spurred by epidemiology, has provided biological plausibility to the epidemiological findings.

Moogavkar's problems with the epidemiology boil down to not believing the statistical methods, which for those of us who don't do that kind of work, are black boxes. The two-stage model is another black box.

A nice quote about human data was extracted from the full text:

Another striking example of the limitations of observational epidemiological studies is provided by the experiencewith anti-oxidants and cancer and heart disease. Based on observational epidemiology studies, experimental evidence and biological plausibility, anti-oxidants were widely considered to be promising chemo-preventiveagents for both cancer and heart disease (Blocket al., 1992; Omenn, 1998; Omenn et al., 1996). Yet large randomized clinical trials of a combination of anti-oxidants,b-carotene and retinol, indicated that these supplementsconferred no protection against lung cancer among high risk groups (Omenn et al., 1996). Theauthors concluded, ‘‘. . . the combination of beta caroteneand vitamin A had no benefit and may have had anadverse effect on the incidence of lung cancer and onthe risk of death from lung cancer, cardiovascular disease,and any cause in smokers and workers exposed to asbestos.’’ Very recently a meta-analysis (Miller et al.,2005) of randomized clinical trials of another anti-oxidant,vitamin E, concluded that high doses of this vitamin ‘‘may increase all-cause mortality and should be avoided.’’

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Regulatory Toxicology and Pharmacology 42 (2005) 123–144

Comment

A review and critique of the EPA's rationale for a fine
particle standard

Suresh H. Moolgavkar
Sciences International, Inc., King Street Station, 1800 Diagonal Road, Suite 500, Alexandria, VA 22314, USA

I review the rationale for the Environmental Protection Agency's 1996 fine particle standard, which was based almost entirely on the epidemiological data with neither support from Toxicology nor understanding of mechanism. While many epidemiological papers available in 1996 reported associations between ambient particles and adverse effects on human health, many others did not and the evidence fell far short of supporting a causal association between particle mass concentration and human health.

The literature appearing after 1996 further complicates the picture. The large studies that have appeared after 1996, such as National Mortality Morbidity and Air Pollution Study, and the reanalyses of the American Cancer Society II study, report risks that are substantially smaller than the risks reported in the 1996 Criteria Document and Staff Paper. Moreover, concerns about confounding by weather, temporal trends and co-pollutants remain unresolved. Other issues having to do with model choice have resurfaced as a
result of reanalyses of critical data to address a glitch in a widely used software package for time-series epidemiology studies of air pollution.

Finally, contemporary examples show that the results of observational epidemiology studies can be seriously biased, particularly when estimated risks are small, as is the case with studies of air pollution. The Agency has largely ignored these issues. I conclude that a particle mass standard is not defensible on the basis of a causal association between ambient particle mass and adverse effects on human health. Such a standard may be justifiable on the basis of the precautionary principle, however.

The Agency could argue that the Science raises concerns about current levels of air pollution, and that reduction of ambient fine particulate matter mass, if it could be achieved without an increase in the level of the ultrafines, could have positive effects on human health. If the Agency justifies a particulate matter mass standard on these grounds then the debate over the form and level of the standard will, for all practical purposes, belong strictly in the Policy arena.

Vitamin A, bronchial metaplasia, and Asbestos

The Vitamin A chemoprevention study rained down money on occupational health research, in the NCI's hope of finding an alternative to reducing exposure for cancer prevention. To be fair, it would be nice to have some palliative to give to former asbestos workers or smokers.

As BrooklynDodger's readers will know, Vitamin A actually potentiated carcinogenicity of past asbestos and smoking, and the study was stopped. The study yielded valuable data in the control or placebo arm.

This paper came before the fall.

Apparently bronchial metaplasia, on biopsy, was considered a precursor to lung cancer. The paper is in the period before full text internet access, so the Dodger has read but the abstract. It would appear bronchial metaplasia was rare, in this super high risk cohort for lung cancer. The investigators buy a marginally significant result with a lower odds ratio, than a higher odds ratio which fails to achieve statistical significance.


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Am J Clin Nutr. 1998 Sep;68(3):630-5.

Dietary vitamin A and prevalence of bronchial metaplasia in asbestos-exposed workers.

Mayne ST, Redlich CA, Cullen MR.Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA. Susan.Mayne@Yale.Edu

... Bronchial biopsies were obtained from 49 asbestos workers... Results indicated that workers with metaplasia reported consuming a significantly lower intake of total vitamin A ... than did subjects without metaplasia ... Logistic regression analyses showed that higher intakes of retinol ... provitamin A carotenoids ... and total vitamin A ... were associated with a nonsignificant reduction in the OR for metaplasia (highest quartile compared with lowest quartile, adjusted ORs). Current smoking ... and former smoking ...were associated with a nonsignificant increase in the OR for bronchial metaplasia compared with never smoking. Greater airway obstruction...was associated with an increased OR for metaplasia (OR: 2.86; 95% CI: 1.09, 7.69). These results suggest that a higher (ie, above the median) intake of vitamin A from foods decreases the risk of bronchial metaplasia in workers occupationally exposed to asbestos.

Digital Vibration Threshold - Maybe an early sign of risk

Validation studies of risk assessment tools in ergonomics reliably rank jobs within the limits of statistical power and a limited time window. The goal is identifying a level of stressors which x percent of the exposed population can tolerate for 30 years. or some shorter career.

The obstacle is that workstations [jobs] change within a year, workers move from job to job, injuries and pain experienced in an observed job may come from previous jobs, previously injured workers may be in lower stressor jobs, etc.

Probably the complaints of newly exposed workers is the most reliable measure of long term risk. But workers notoriously under report physical problems. This is because a worker is usually in the job which the worker likes better than any other job they can get, under a union contract or management dictated assignment system. A complaint will gain the worker nothing at all, or may gain a restriction into a job the worker didn't want.

The other problem with symptoms or complaints is the meat vs gristle issue. What hurts is muscle [meat], which has lots of innervation compared to connective tissue [gristle]. Muscle recovers from over exertion by building more strength and endurance; discomfort is reduced by conditioning. The muscle is strong enough to pull on the connective tissue with enough force to damage that tissue. As the connective tissue becomes inflamed, it squeezes or otherwise irritates a nerve, which causes pain or numbness. Which comes first may be determined by where the pain receptor neurons a located in the nerve bundle.

Maybe digital vibration threshold is an early early indicator of impact on the nerves, a response to sub-acute exposures which will predict damage from chronic exposure. In addition, DVT might be a continuous variable, easier to manage for exposure response.

DVT in response to vibration would not be interesting. DVT in response to "awkward postures" may be considered the increased muscle force and connective tissue impact of that force caused by the awkward posture applied to the same external force.

BrooklynDodger notes that correlations with certain risk factors may disappear in a particular cohort if there is no or little variation in that risk factor. For example, if repetition is about the same in all the jobs, then repetition disappears as a risk factor in the cohort.


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Ergonomics. 2005 Jan;48(1):66-77.

Digital vibration threshold testing and ergonomic stressors in automobile manufacturing workers: a cross-sectional assessment.

Gold JE, Punnett L, Cherniack M, Wegman DH.

Department of Work Environment, University of Massachusetts, Lowell, MA 01854, USA.

... Reduced sensitivity to vibration in the fingertips (a function of nerve integrity) has been found in those exposed to segmental vibration, to hand force, and in office workers. The objective of this study was to determine whether an association exists between digital vibration thresholds (VTs) and exposure to ergonomic stressors in automobile manufacturing. Interviews and physical examinations were conducted in a cross-sectional survey of workers (n = 1174). ... VTs were separately associated with hand force, vibration as felt through the floor (whole body vibration), and with an index of multiple exposures in both tool users and non-tool users. Additional associations with contact stress and awkward upper extremity postures were found in tool users. Segmental vibration was not associated with VTs. ...

RFC paper informs views of asbestos

A side debate in the particle and lung cancer world is whether there is something special about asbestos fibers, or whether all fibers are equally dangerous. This debate arose when BrooklynDodger was being taught that asbestos caused fibrosis and lung cancer, while silica only fibrosis. That's no longer true, but the long fiber-short fiber-durable fiber paradigm continues.

This population overall suffered exposures pretty much in the line of asbestos standards of the time, although definitely elevated compared to the current 0.1 fiber/cc limit. The current asbestos rule is aimed at a cumulative exposure of about 4.5 fiber years.

The study found that 8% of workers with 20 year latency had pleural changes, compared to 2.7 % overall. This suggests that the under 20 year latency group must have a prevalence of 1.3% or nearly a 6 fold risk for 20 year latency compared to under 20 years.

Cumulative exposure was dichotomized at 135 fiber/months, which is a bit more than 10 fiber-years. It yielded a 6-fold risk of pleural changes, which backs down to a signficant risk of pleural changes down to vanishing levels of exposure.

Had BrooklynDodger been reviewing this paper, the Dodger would have ballisticed over "irregular opacities...showed a nonsignificant elevated OR in regard to cumulative fiber exposure of 4.7 (95% CI, 0.97 to 23.5). CONCLUSIONS: RCF are significantly associated with pleural changes that were predominantly pleural plaques, but have not resulted in a statistically significant increase in interstitial changes." To the contrary, there is a big odds ratio and a huge upper bound discounted because of reached a lower CI of 0.03 less than 1.00.

Quoting exposure data, for those who join the Dodger in thinking this is an important detail:

From 1987 to 1988, the range of time-weighted average exposure
estimates were 0.01 to 1.04 fibers per cubic centimeter for the
blanket line, 0.03 to 0.61 fibers per cubic centimeter for dry
fabrication, 0.01 to 0.27 fibers per cubic centimeter for wet
fabrication, 0.01 to 0.47 fibers per cubic centimeter for furnace
operations, and 0.02 to 0.62 fibers per cubic centimeter for
maintenance.
...Historical exposure data were available at two plants for calculating pre-1987 in-plant exposures.1...Overall, exposures over time have decreased.
The maximum exposure estimate was 10 fibers per cubic centimeter
in the 1950s for carding in a textile operation;
subsequent engineering changes reduced this estimated exposure to 1
fiber per cubic centimeter.

Chest. 2002 Jun;121(6):2044-51.

A longitudinal study of chest radiographic changes of workers in the refractory ceramic fiber industry.

Lockey JE, LeMasters GK, Levin L, Rice C, Yiin J, Reutman S, Papes D.Division of Occupational and Environmental Medicine, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.

...Chest radiographs were obtained every 3 years... Exposure metrics were ... duration and latency in a production job, and cumulative exposure (fiber-months per cubic centimeter). .. The ... survey included 625 current workers at five manufacturing sites and 383 former workers at two of the five sites. ... Pleural changes were seen in 27 workers (2.7%). Of workers with > 20 years of latency from initial production job or 20 years of duration in a production job, 16 workers (8.0%) and 5 workers (8.1%) demonstrated pleural changes, respectively. Results from the cumulative exposure analysis (> 135 fiber-months per cubic centimeter) demonstrated a significant elevated odds ratio (OR) of 6.0 (95% confidence interval [CI], 1.4 to 31.0). The incidence of irregular opacities at profusion categories > or = 1/0 was similar to other nonspecified dust-exposed worker populations at 1.0%, and showed a nonsignificant elevated OR in regard to cumulative fiber exposure of 4.7 (95% CI, 0.97 to 23.5). CONCLUSIONS: RCF are significantly associated with pleural changes that were predominantly pleural plaques, but have not resulted in a statistically significant increase in interstitial changes.

Noise and music teachers

Back when the OSHA noise standard was being enforced, when employers were being cited for lack of engineering controls, it became fashionable to divert attention from occupational noise exposure to rock and roll. Later, there was a boomlet in boom boxes and walkmen. This paper notes that even in high toned music settings, there can be damage to hearing. Over the last decade, it's been shown that hearing loss begins at 80 dBA, not 85 or 90.

Music may generate higher measurements on a noise meter than ordinary garbage noise, because pure tones may not interfere as the mixed frequencies of white noise.

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J Occup Environ Hyg. 2004 Apr;1(4):243-7.

Noise exposure of music teachers.

Behar A, MacDonald E, Lee J, Cui J, Kunov H, Wong

W.Sensory Communication Group, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. behar@sympatico.ca

Noise exposure of 18 teachers from 15 schools was measured using noise dosimeters. The equivalent continuous noise level (L(eq)) of each teacher was recorded during single activities (classes) as well as for the entire day, and a normalized 8-hour exposure, termed the noise exposure level (L(ex)) was also computed. The measured L(eq) exceeded the 85-dBA limit for 78% of the teachers. L(ex) exceeded 85 dBA for 39% of the teachers. Limited recommendations on how to reduce the noise exposures are provided. The need for a hearing conservation program has also been emphasized.

Hearing loss and solvents

The target of this investigation is how neurological damage from chemical exposure can most easily be measured. In the '80's, investigators notioned that standard psychological or other neurobehavioral tests could be adminstered to workers exposed to chemicals, to give quantitative measures to symptoms, or to reveal effects before symptoms were felt.

BrooklynDodger has the impression that this plan failed. Significant deficits on these tests are not seen at levels of exposure where the participants are definitely "buzzed." After all, bars are frequently equipped with pool tables, dart boards and pinball machines, and some blackjack players are successful in the face of free drinks.

Another line of investigation is to exploit a quantitative measure of neurological function with no cognitive aspect. There's a literature on color vision and solvent exposure. This paper finds an effect on audiometry.

J Occup Environ Med. 2005 Mar;47(3):212-8.

Effects of concurrent noise and jet fuel exposure on hearing loss.

Kaufman LR, LeMasters GK, Olsen DM, Succop P.
Rocky Mountain Center for Environmental and Occupational Health, University of Utah, 391 Chipeta Way, Salt Lake City, UT 84108, USA. LauraKaufman@world.oberlin.edu

...Noise-exposed subjects, with or without jet fuel exposure, underwent hearing tests. Work histories, recreational exposures, protective equipment, medical histories, alcohol, smoking, and demographics were collected by questionnaire. Jet fuel, solvent, and noise exposure data were collected from records. Fuel exposure estimates were less than 34% of the OSHA Threshold Limit Values. ...Subjects with 3 years of jet fuel exposure had a 70% increase in adjusted odds of hearing loss (OR = 1.7; 95% CI = 1.14-2.53) and the odds increased to 2.41 (95% CI = 1.04-5.57) for 12 years of noise and fuel exposure. CONCLUSIONS: These findings suggest that jet fuel has a toxic affect on the auditory system.

Mega mouse study - First look, no threshold

BrooklynDodger returns to yesteryear, before quantitative risk assessment became dominant. In those days, the issue was threshold for carcinogenesis by chemicals. Threshold means there is region where there is NO exposure-response relationship for a chemical - increasing doses below the threshold cause no increased response. If no threshold, then any reduction in exposure will bring a reduced risk, and the only zero risk is zero exposure.

[Quantitative risk assessment, fought vigorously by public health advocates, later came to drive protective OSHA and EPA standards. This force opponents of public health advocates to adopt a new methodology, the Houdini risk assessment, which adds untestable mechanistic hypotheses to reduce or eliminate predicted risks...a commentary for another day.]

A buzz surrounded the "mega mouse study," portrayed as a central mission of the National Center for Toxicological Research (NCTR); NCTR was the Pine Bluff, Arkansas, biological warfare center converted to peaceful use.

Mega-mouse recognized that treatment groups must be large to detect lower rates of response. The 50 animal bioassay can observe statistically significant results at a 10% incidence rate against a zero background, the ED10. The mega-mouse study aimed at finding an ED01, which now the Dodger can't figure is 1% or 0.1%. Probably 1%, given the background rate of these tumors in control animals. Even at 1/1000, the effect is 3 orders of magnetude above the 1/1,000,000 then talked about as the "virtually safe dose." Instead of the million mice implied, "only" 25,000 were used.

Unfortunately, the study compound, a model carcinogen, was a material of no commerical importance, therefore no application of this data other than theoretical was possible.

The answer was, initial models of the data, found no threshold for one site [liver], and maybe or maybe not a threshold for the other site, bladder. That's what NCTR published.

The results had no impact on the debate over threshold.

Subsequently, other statisticians [or the same biostatisticians moved to other institutions] remodeled this data to assert there was a threshold. Check ED01 on pub med.

PS: an early OSHA transcipter [coke oven] misheard and published the term "biased statistician."

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J Environ Pathol Toxicol. 1980;3(3 Spec No):17-34.

Effects of dose and time in a long-term, low-dose carcinogenic study.

Littlefield NA, Farmer JH, Gaylor DW, Sheldon WG.

...Mice were exposed for up to 33 months to low doses of 2-acetylaminofluorene (2-AAF)... urinary bladder neoplasms and liver neoplasms, resulted in 2 different types of dose response relationships. Although bladder neoplasms exhibited a minimum effect level (or a nonlinear response) for specific conditions, the total results were consistent with a "no threshold concept." The late appearing liver neoplasms displayed a nearly linear type response that extrapolated directly to zero dose. ... a positive response was noted at the next lower dose as time was extended. Discontinuing dosing and sacrificing at 18 and 24 months also demonstrated the effects of exposure to the carcinogen 2-AAF. Induction of bladder neoplasms was shown to occur early in the study, but was dependent upon the continuous presence of 2-AAF. The liver neoplasms appeared very late in the study but were shown to be induced at a very early point in the exposures and did not require the continuous presence of the carcinogen in order to develop. A standard 18 month bioassay study, if conducted under the same conditions, would have classified this chemical as a weak acting carcinogen.

Nothing Hurts Like Pain

The CDC and corporate campaign to blame illnesses on the victims, through health risk behavior, devotes no attention to identifying causes of health risk behavior [other than the sins of sloth and gluttony.] BrooklynDodger hypothets that pain, as a subset of psychosocial stress, causes health risk behavior, including smoking, eating too much, drinking too much, driving after drinking too much, and driving badly even when not drinking too much.

The workforce studied appears to be a clerical technical professional executive sample. Even there, the prevalence of "pain" complaints is 30%. From the abstract, the Dodger, who hasn't read the full paper, it's not clear how the investigator could separate pain as a symptom of poor physical health, rather than a cause, so the association with pain is not surprising.

Four days a month is actually about 20% of workdays lost or impaired.


Working In Pain Takes Toll(Page 1 of 2)July 15, 2005

(CBS/AP)Employees reporting the highest level of pain were also more likely to report one or more accidents at work in the last year compared with healthy employees.

(WebMD) Nearly one in three workers suffers from pain that affects not only their health but their productivity as well, according to a new study. Researchers surveyed employees of a major Fortune 500 company and found nearly 30 percent were in pain beyond the normal everyday aches and pains, like toothaches or muscle sprains.

Lost productivity due to performing at less than 100 percent on the job (presenteeism) as well as missing work days (absenteeism) amounted to about four days a month for those in pain compared with less than half a day for healthy employees. Researchers say the findings confirm that pain in the workplace is a major cause of lost productivity that merits greater attention by employers

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J Occup Environ Med. 2005 Jul;47(7):658-70.

The burden of pain on employee health and productivity at a major provider of business services.

Allen H, Hubbard D, Sullivan S.
The Harris Allen Group, Brookline, Massachusetts 02446, USA.
harris-allen@msn.com

An electronic survey was conducted in late 2004, which produced a reasonably representative national sample of 1039 active employee respondents. A total of 28.6% of respondents met the study definition for pain. Pain was linked to: 1) drops of more than 45% and 23%, respectively, in Overall Physical and Mental Health; 2) a fivefold increase in health-induced limitations in work performance; and 3) nearly three and two thirds workdays lost to presenteeism and absenteeism over a 4-week period. ... The prevalence of pain and its impact on those with the condition combine to make it an area of much opportunity for improving workforce health and productivity. Musculoskeletal diseases offer a promising initial target for corporate intervention.

Hospital Acquired Infections

Data Show Scourge of Hospital Infections

<By Ceci Connolly
Washington Post Staff Writer
Wednesday, July 13, 2005; Page A01

Nearly 12,000 Pennsylvanians contracted infections during a hospital stay in 2004, costing an extra $2 billion in care and at least 1,500 preventable deaths, according to state figures released yesterday that officials say represent a conservative measure of one of the deadliest problems in modern medicine. As the first state to collect data on hospital-acquired infections, Pennsylvania has put hard numbers on a troubling phenomenon that until now has only been estimated. Even so, the true infection rate and cost is probably much higher, the report's authors said, because of underreporting by many hospitals. The actual tally could be as high as 115,000 infections, based on billing claims the hospitals submitted to insurers, the report said. "Pennsylvania is 4 percent of the population, which means you may have an additional 100 people dying per day" nationwide because of hospital-acquired infections, said Marc P. Volavka, executive director of the Pennsylvania Health Care Cost Containment Council, the agency that issued the report. "That comes to an additional $50 billion" in medical charges in the United States annually, he said

Instead of cutting off malpractice rights, and denying care, the health care system could do something about medical errors. Actually, this report identifies a system problem which adds cost, kills people, etc, which requires an exposure based abatement system.

BrooklynDodger took the trouble to find the original report and skim it. The reporter neglected to mention that these reports were limited to medical device related infections. Although pneumonia is identified, it's only respirator acquired pneumonia. These are only a fraction of total infections, such as pneumonia or MRSA.

Surgical masks - More Comfortable, Only Problem Is, They Don't Work

Finally, vindication for BrooklynDodger's dentist. For years we have argued about the worthless surigical masks worn by BD's D and staff; dentist maintains a filtering facepiece respirator makes him short of breath. The Dodger scoffed. Now comes a study showing actually heart rate effects comparing "N95 respirators" to "surgical masks." And it shows that surgical masks - which permit the wearer to inhale and exhale through the leaks - are less demanding and more comfortable than an N95.

The Dodger couldn't get the full text, and so can't figure what a "nanotreated" surgical mask [whatever that is] might be - let's assume it's a surgical mask with some kind of effective filter media. The Dodger also couldn't confirm whether or not the N95's had exhalation valves, although the Dodger suspects more not than likely. For all the inside out sampling, the investigators neglected to mention effectiveness in the abstract; the Dodger suspects it's not in the paper either

Infection control folks still don't get it that the main problem is fit, not filtration. Personally, BrooklynDodger doubts that microbes are riding on fine particles, although it would be nice to see some data on what's floating in the isolation unit.

On another matter, the Dodger is pleased that colleagues in the offshore world are making up for the declining output of American occupational health and safety science. The International Archives are making up for the near disappearance of the combined AIHA-ACGIH journal.


International Archives of Occupational and Environmental Health
Volume 78, Number 6
July 2005
Pages: 501 - 509
Short Communication

Effects of wearing N95 and surgical facemasks on heart rate, thermal stress and subjective sensations
Y. Li1 , H. Tokura1, Y.P. Guo1, A.S.W. Wong1, T. Wong2, J. Chung2 and E. Newton1
(1)
Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
(2)
School of Nursing, The Hong Kong Polytechnic University, Kowloon, Hong Kong

Five healthy male and five healthy female participants performed intermittent exercise on a treadmill while wearing the protective facemasks in a climate chamber controlled at an air temperature of 25°C and a relative humidity of 70%. The subjects had significantly lower average heart rates when wearing nano-treated and untreated surgical facemasks than when wearing nano-treated and untreated N95 facemasks, ...the outer surface temperature of both surgical facemasks was significantly higher ... the microclimate and skin temperatures inside the facemask were significantly lower than those in both N95 facemasks... significantly higher absolute humidity outside the surface...... The absolute humidity inside the surgical facemask was significantly,... rated significantly lower for perception of humidity, heat, breath resistance and overall discomfort than both N95 facemasks. The ratings for other sensations, including feeling unfit, tight, itchy, fatigued, odorous and salty, that were obtained while the subjects were wearing the surgical facemasks were significantly lower...

Quantitative Risk Assessment for Coke Oven Emissions

BrooklynDodger was following one line of papers, and was distracted to another. Here's a heavily modeled risk assessment for lung cancer associated with coke oven emissions, based on data in people.

The assessment is based on the two-stage clonal expansion model, which is claimed to be more mechanistically based than the linearized multi-stage model [more arbitrary parameters.] Moolgavkar even has this model named after himself. BrooklynDodger, for the moment, abstains on whether the EPA estimate [6.2, in units to be discussed below], or Moolgavkar's new calculation [1.5] is correct. However, back of the envelope calculations based on the later number instruct, as would a 4-fold multiplier.

The unit risk number is in units of cases per 10,000, cradle to grave exposure at 1 microgram per cubic meter. The OSHA limit is 150 micrograms per cubic meter. People in this environment in the past were exposed far above the OSHA limit, and now are certainly pushing that value.

So, taking a 70 year life span, a 45 year occupational exposure, and multiplying by the OSHA limit, we get 1.4% of exposed workers dying of lung cancer. EPA's less modeled rates predict about 6% mortality at the OSHA limit.

So this paper provides one more example of how high a risk of occupational disease from long term chemical exposure OSHA standards leave behind.


Risk Anal. 1998 Dec;18(6):813-25.

Estimation of unit risk for coke oven emissions.

Moolgavkar SH, Luebeck EG, Anderson EL.

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.

In 1984, based on epidemiological data on cohorts of coke oven workers, USEPA estimated a unit risk for lung cancer associated with continuous exposure from birth to 1 microgram/m3 of coke oven emissions, of 6.2 x 10(-4). This risk assessment was based on information on the cohorts available through 1966. Follow-up of these cohorts has now been extended to 1982 and, moreover, individual job histories, which were not available in 1984, have been constructed. In this study, lung cancer mortality in these cohorts of coke oven workers with extended follow-up was analyzed using standard techniques of survival analysis and a new approach based on the two stage clonal expansion model of carcinogenesis. The latter approach allows the explicit consideration of detailed patterns of exposure of each individual in the cohort. The analyses used the extended follow-up data through 1982 and the detailed job histories now available. Based on these analyses, the best estimate of unit risk is 1.5 x 10(-4) with 95% confidence interval = 1.2 x 10(-4)-1.8 x 10(-4).

Census Tract Epidemiology Reports are Hazardous to Your [mental] Health

Census tract mortality studies aimed at confirming or denying a facility chemical emission threat to health repeat the same error over and over and over.

These are death certificate-based mortality studies. Quantitative extrapolation of mortality risk from agents such as asbestos demonstrate that large excess risk would not be observed by the method, and that excess risk observed by the method would not be due to the emissions.

Possibly mesothelioma cases could be observed in such a study. [Over much of the period, and possibly now, there is no ICD code for mesothelioma, and therefore death certificates would not be coded for it in state death registries.] Possibly, x-ray evidence of pleural plaques in a sample of residents could observe an effect of the facility. Probably a soil sampling study could detect the presence of asbestos contamination. But census tract mortality would not find a problem.

OSHA estimates a 6 per 100 lifetime risk of cancer [mostly lung cancer] from a 45 year working career exposed to 0.1 fiber/cc of asbestos. Thus, 4.5 fiber-years. Which is approximate doubling from population risk for males, and more than doubling for females. Possibly a statistically significant result could be observed at a 2 per 100 lifetime attributable risk at an excess of 30% if the expected deaths from lung cancer were upwards of 100, which translates into expected death from all causes upwards of 2000 in this cohort.

The actual ATSDR report found 276 lung cancer deaths among men, a rate ratio 0f 1.07, with an upper confidence interval of 1.20 [that is, results rule out with 95% confidence a risk as high as 1.20]. Combining races would tend to reduce the SIR based on the expected cases, since the lung cancer mortality rate among blacks is higher than whites.

For mesotheliomas, there were 6 observed vs. about 10 expected; while the SIR was .6 or so, the UCI was 1.23. [Unclear how the investigators got mesothelioma diagnosis from death certficates.]

So, contrary to the stated conclusion, the ATSDR study found an increase in lung cancer, not statistically significant, but only suceeded in ruling out a 20% excess which translates to a lifetime risk of 1.2 per 100. This translates back to a .07 fiber-year exposure.

There is some reassurance that the mesotheliomas were not in excess.


Second report finds minimal cancer risk

Friday, July 08, 2005

By DARRYL R. ISHERWOOD Staff Writer

HAMILTON - State health officials have determined that townshipwide, residents face no increased risk of cancer or other disease from the operation of the W.R. Grace and Co. Zonolite plant, which processed asbestos-laden ore for more than 40 years. ]

But state officials admit that the recent study, conducted on the entire population of Hamilton, does not present as valuable a picture of the health risks as a more narrowly focused study completed in conjunction with federal health officials in March.

This latest report, issued by the state Department of Health and Senior Services late last month, confirms what federal health regulators said three months ago: despite years of processing vermiculite contaminated with tremolite asbestos, the former insulation plant on Industrial Drive did not significantly raise the risk of cancer and other asbestos-related illnesses among township residents.

"(The) results do not indicate that asbestos-related outcomes for Hamilton as a whole have been impacted by potential asbestos exposure from the Zonolite/W.R. Grace facility," said the report, which was issued to the township's health officer.

Michael Berry, the health department scientist [sic] who conducted the study, said that while the report was good news, it was not as accurate as the study done in March. That study looked at Trenton, Lawrence and Hamilton residents who lived within one mile of the plant.

"The problem with the municipalwide study is Hamilton is a very large town and though there may have been significant exposures in the nearby neighborhoods, we certainly had no reason to believe that all or most of Hamilton was affected," Berry said.

Berry said because of Hamilton's size - the township covers 40 square miles - studying health effects of residents who live miles from the plant served little purpose. But in order to be consistent with a national effort to study the health risks in communities where the vermiculite was shipped, Hamilton was included in the state's report.

Another limitation of the study, Berry said, is that it focused only on Hamilton mailing addresses, but there are many areas of the township that have Trenton addresses, which could skew the sample.

That possibility would have been addressed in the March study, which did not limit itself to Hamilton residents, but rather to the people who lived closest to the plant.

Migration is also a weakness of both the recent study and the one completed in March, he said. Residents who moved and were diagnosed with an asbestos-related disease in a different area of the state or country would not fall within either report.

There could be a migration both into and out of a study area," Berry said. "But we hope it would average out."
The study was conducted using cancer and health data from seven New Jersey municipalities that all reportedly received vermiculite ore from a mine in Libby, Mont., that was later found to be contaminated with the deadly form of asbestos.
The report included cancer statistics from 1986 through 1995 and mortality rates from asbestos-related diseases from 1979 through 1998.

Control of Fine Particle Exposures

The Dodger encountered Indoor Air, a journal previously unknown, while browsing medline for more grist for the fine particle mill.

The paper finds that a 27% reduction in fine particle exposure can be achieved by adding filtration for forced air ventilation systems.

Finland by building code requires particle filtration in recirculating ventilation systems, both residential and occupational buildings. This paper is detailed, and refers to previous publications, so the Dodger couldn't find a description of the filtration in the ventilation systems in the buildings studied. [The Dodger will go back through this series, because it includes a lot of data on personal vs. community exposure measurements. That's for another post.]

Commonly used filters for ventilation vary widely in efficiency, from 25 to 67%. It would be surprising if there were any 95% filters in this sample, although Finland can be surprising. The Dodger suggests that much of the collection efficiency against fine particles in these systems results from impaction of drawing air through a more complicated path rather than the filter itself.

In addition, fine particles preferentially penetrate filters. Minimum filter efficiency is at 0.3 microns. PM2.5 is a standard measure because of instrumental considerations, but the bulk of the mass in PM 2.5 is really PM 1.0. Particle numbers will bulk up at lower diameters. Therefore, it is unlikely that the full potential for improved filtration has been found.

Measuring real world reductions is needed to account for air infiltration outside of the ventilation system. An obvious next step would be designing or modifying a commercially available or viable building system with the aim of capturing in the PM 1.0 range, putting it into a real residential building, and measureing the result.

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Indoor Air. 2005 Aug;15(4):246-56.

Reduction potential of urban PM mortality risk using modern ventilation systems in buildings.

Hanninen OO, Palonen J, Tuomisto JT, Yli-Tuomi T, Seppanen O, Jantunen MJ.
KTL, Centre for Environmental Health Risk Analysis, Kuopio, Finland.

While waiting for technological breakthroughs in emission controls, the current work assesses the exposure reductions achievable by a complementary means: efficient filtration of supply air in buildings. For this purpose infiltration factors for buildings of different ages are quantified using Exposures of Adult Urban Populations in Europe Study (EXPOLIS) measurements of indoor and outdoor concentrations in a population-based probability sample of residential and occupational buildings in Helsinki, Finland. These ... compare exposures in the current scenario with an alternative scenario, where the distribution of ambient PM(2.5) infiltration factors in all residential and occupational buildings are assumed to be similar to the subset of existing occupational buildings using supply air filters. In the alternative [filtration equipped] scenario exposures to ambient PM(2.5) were reduced by 27%. ... The estimated exposure reductions suggest that correctly defined building codes may reduce annual premature mortality by hundreds in Finland and by tens of thousands in the developed world altogether.

Larry Brown's Hip: Occupational Injury?

BrooklynDodger is struck by this crossover of work related musculoskeletal disorders, medical malpractice and return to work legal issues.

Not to put too pendantic a point on it, the headline "diagnosis" [newspaper post below] might be more precisely "prognosis." The Dodger presumes there's a diagnosis, if there was a surgery to correct the bladder problem, there was a diagnosis to collect the insurance.

There's a decent literature on physical activity and osteoarthritis of the hip, leading to hip replacement surgery. Probably easy to mount a case-control study with good occupational histories from someone who specializes in hip replacements, although it might be hard to identify controls from the same practice. Ignoring occupation, the Dodger expects that an exposure response relationship for runners could be easily derived.

It's kind of a no-brainer to think Larry Brown would be at high risk: a playing career followed by decades of running up and down the floor during practice. Another study, quantitative lower extremity physical activity of participants and coaches in various sports; other than chess, baseball is probably least active [even with pitchers and catchers], football next, soccer and then basketball the most. Another study, using a cohort of player's association members.

Having defined the risk, which of Larry Brown's employers is responsible for the injury? It seems unfair to the Pistons to absorb all the cost of the surgery of a 64 year old employee with as many prior employers as Larry Brown, not to mention the high school on Long Island, University of North Carolina, and all the sanctioned and non-sanctioned pick up games Larry played.

Below we find that nerve damage is a "rare" side effect of the hip replacement surgery. The Dodger concedes it's more of a reach to diagnose nerve damage impacting urination from a sports page article than for Dr. Frist to rule out persistent vegetative state from a videotape. But let's assume that's what Larry Brown has, and that it's secondary to physical trauma to the nerve during surgery. Quality theory tells us that if it's a 1% side effect, then it's outside the normal distribution of results, therefore a special cause rather than a system cause result. Which equates to malpractice.

Now comes the return to work problem. Millions saw Larry Brown at work on TV. He was doing the job. If he were to claim disability, and try to collect workers comp, they'd show that tape to the referee [workers' comp judge, not the striped shirt kind] and get Larry disqualified, just like the worker who can do 1/2 hour in the garden once a week but can't sustain 10 hours of pounding steel on the assembly line.

Maybe the economic solution is that the Pistons sue the hip replacement surgeon for the $18 million they would have to pay to buy Larry Brown out.

>>>>>>>>>>>>>>>>>>>>
Uncertain diagnosis drags on
Brown in the dark on agent talking to Dumars
July 5, 2005
BY PERRY A. FARRELLFREE PRESS SPORTS WRITER

Larry Brown's future remains cloudy. And it might not clear up today.
Brown's agent, Joseph Glass, planned to have a phone conversation with Joe Dumars, the Pistons' president of basketball operations, today. But Glass said Monday the conversation will just be an update about Brown's condition.

He also said it wouldn't involve a possible buyout by Brown from the remaining three years of his contract with the Pistons.

Brown, who is vacationing in the Hamptons with his family, said Monday, "I don't know anything about that" conversation.

Brown said he isn't healthy and doesn't know when he'll be better.


J Arthroplasty. 2004 Jun;19(4 Suppl 1):104-7.

Neurovascular injury: avoiding catastrophe.

Barrack RL.Tulane University Health Sciences Center, Department of Orthopaedic Surgery, New Orleans, Louisiana 70112, USA.

Major neurovascular injury is the least common, but most distressing, complication of total hip arthroplasty (THA). The keys to minimizing the incidence of these complications are recognizing patients at risk and knowledge of the relevant anatomy. Partial sciatic palsy is the most common nerve injury. At least partial recovery can be expected in 70% to 80% of cases, with the remainder frequently displaying dissatisfaction with their surgery. Vascular injury is most frequently associated with the use of screws for fixation of structural grafts, acetabulur components, and protrusio rings or cages. An understanding of the acetabular quadrant system is crucial in minimizing these potentially catastrophic complications.

Orthopedics. 2004 Jan;27(1):73-81; quiz 82-3.

Current overview of neurovascular structures in hip arthroplasty: anatomy, preoperative evaluation, approaches, and operative techniques to avoid complications.

Rue JP, Inoue N, Mont MA.Department of Orthopedic Surgery, The Johns Hopkins Medical Institutions Baltimore, MD, USA.

Total hip arthroplasty is a common and relatively safe procedure with consistently good results. Despite its popularity and excellent results, THA is a major operation with several major neurovascular structures within reach of retractors, scalpel blades, drills, screws, and reamers. A thorough knowledge of their anatomic location and proximity to the operative field, along with a basic understanding of the principles of vascular surgery can help avoid potentially devastating consequences. Specifically, the surgeon should avoid placement of screws in the anterior-superior quadrant, be vigilant when placing retractors, and avoid excessive tension on the sciatic nerve.