Saturday, February 28, 2009

Mechanisms of Formaldehyde Respiratory Effects Explored

Toxicology and Applied PharmacologyVolume 233, Issue 3, 15 December 2008, Pages 355-359
Mechanistic and dose considerations for supporting adverse pulmonary physiology in response to formaldehyde
Chad M. Thompsona, , , Ravi P. Subramaniama and Roland C. Grafströmb, c
aNational Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, 8623-P, Washington, DC, 20460, USA
bInstitute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
cVTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, FI-20521 Turku, Finland
Induction of airway hyperresponsiveness and asthma from formaldehyde inhalation exposure remains a debated and controversial issue. Yet, recent evidences on pulmonary biology and the pharmacokinetics and toxicity of formaldehyde lend support for such adverse effects. Specifically, altered thiol biology from accelerated enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione and pulmonary inflammation from involvement of Th2-mediated immune responses might serve as key events and cooperate in airway pathophysiology.
Understanding what role these mechanisms play in various species and lifestages (e.g., child vs. adult) could be crucial for making more meaningful inter- and intra-species dosimetric extrapolations in human health risk assessment.
BrooklynDodger(s) comment: This publication co-authored by EPA again suggests that EPA is laying on ammunition for an upcoming battle over a risk assessment for formaldehyde. Apparently some investigators have generated a controversy over formaldehyde as a risk factor for asthma, so EPA has sought to explore the other side of the argument. Apparently, the mechanistic extrapolation market has been cornered by the other guys in the US, so EPA went to Scandinavia for collaborators.

Friday, February 27, 2009

Some Evidence That Ultrafine Carbon Particles Cause autonomic modulation of the heart and repolarization of the ventricular myocardium.

ECG Parameters and Exposure to Carbon Ultrafine Particles in Young Healthy Subjects.
Zareba, Wojciech1Couderc, Jean Philippe1Oberdörster, Gunter2Chalupa, David1Cox, Christopher3Li-Shan Huang4Peters, Annette5Utell, Mark J.1Frampton, Mark W.1 mark•
Inhalation Toxicology; Mar2009, Vol. 21 Issue 3, p223-233, 11p
The mechanisms underlying the association between air pollution and cardiovascular morbidity and mortality are unknown. This study aimed to determine whether controlled exposure to elemental carbon ultrafine particles (UFP) affects electrocardiogram (ECG) parameters describing heart rate variability; repolarization duration, morphology, and variability; and changes in the ST segment. Two separate controlled studies (12 subjects each) were performed using a crossover design, in which each subject was exposed to filtered air and carbon UFP for 2 hours. The first protocol involved 2 exposures to air and 10 μg/m3 (∼ 2× 106 particles/cm3, count median diameter ∼25 nm, geometric standard deviation ∼1.6), at rest. The second protocol included 3 exposures to air, 10, and 25 μg/m3 UFP (∼ 7× 106 particles/cm3), with repeated exercise. Each subject underwent a continuous digital 12-lead ECG Holter recording to analyze the above ECG parameters. Repeated measures analysis of variance (ANOVA) was used to compare tested parameters between exposures. The observed responses to UFP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFP in comparison to air exposure. In conclusion, transient exposure to 10-25 μ g/m3 ultrafine carbon particles does not cause marked changes in ECG-derived parameters in young healthy subjects. However, trends are observed indicating that some subjects might be susceptible to air pollution, with a response involving autonomic modulation of the heart and repolarization of the ventricular myocardium.
BrooklynDodger(s) Comment: Oberdorster is a leading authority on health effects of inhalation of small particles. Remember that carbon used to be considered inert, but now is a 2B carcinogen, among other respiratory effects. The text of the abstract gives indication of negotiation with the reviewers; whether the conclusion was bargained down or bargained up can't be told. So maybe this is equivocal evidence rather than some evidence for an effect on the heart after 2 hours at 25 ug/M3 in a small sample size of healthy volunteers. ?graduate students?

Thursday, February 26, 2009

Rating Posture: The Bigger the Better

Applied ErgonomicsVolume 40, Issue 3, May 2009, Pages 371-378
Reliability of assessing upper limb postures among workers performing manufacturing tasks

Angela Dartta, , , John Rosecrancea, Fred Gerrb, Peter Chenc, Dan Antond and Linda Merlinob
aColorado State University, Occupational and Environmental Health Section, ERHS, Environmental Health Building, Fort Collins, CO 80523, USA
bUniversity of Iowa, Occupational and Environmental Health, IREH, Iowa City, IA 52245, USA
cColorado State University, Industrial Organizational Psychology, Clark Building, Fort Collins, CO 80523, USA
dEastern Washington University, Department of Physical Therapy, Spokane, WA 99202 USA

The purpose of this study was to determine the inter- and intra-rater reliability of assessing upper limb postures of workers performing manufacturing tasks. Assessment of neck, shoulder, and wrist postures of 20 manufacturing employees was conducted by two raters observing digital video files using Multimedia Video Task Analysis (MVTA). Generalizability theory was used to estimate the inter- and intra-rater reliability. The results demonstrated good to excellent inter-rater reliability for neck and shoulder postures and fair to excellent inter-rater reliability for wrist postures. Intra-rater posture assessment demonstrated good to excellent reliability for both raters in all postures of the neck, shoulder, and wrist. This study demonstrated that posture assessment of manufacturing workers using MVTA is a reliable method.
BrooklynDodger(s) comment: Was this a doctoral project, or a master's essay? Posture assessment for hand work is a challenge in ergonomic studies. Not surprisingly, ratings were more consistent for the big stuff - head and neck - than the wrist. Although these raters did pretty well with the wrist. This provides important support for an ergonomic standard. The Dodger(s) wonder how trained hourly workers would have done.

Wednesday, February 25, 2009

No New Information about Artificial Soccer Fields

Applied ErgonomicsVolume 40, Issue 3, May 2009, Pages 485-490
Amateur football game on artificial turf: Players’ perceptions
Elisabetta M. Zanetti, a,
aDepartment of Industrial and Mechanical Engineering (DIIM), University of Catania, V.le Andrea Doria 6, 95125 Catania, Ct, Italy
The purpose of this study was to establish whether players’ perceptions in football competitions played on artificial turf can be influenced by the pitch under examination, the kind of infill material used, the weather conditions and by player's role in the team.
A multifactorial statistical analysis was made of the results obtained from over 1600 U.E.F.A. questionnaires completed by amateur footballers.
Pitch and weather factors were demonstrated to be relevant to the aspects investigated. Conversely, the players’ role and the infill material were significant for only a few aspects; for each variable, the analysis indicated the most favourable conditions. Overall, the analysis provided insight into amateur players’ favourable feelings about artificial turf, compared with its natural alternative (actually made of earth, without grass in the case of amateur players).
BrooklynDodger(s) Comment: The Dodger(s) click up this abstract because there's a concern - maybe a moral panic - about artificial turf on playgrounds in NYC. The Dodger(s) believe(s) some of this concern is the ideal comparison of turf with grass, rather than the actual comparison of turf with packed earth with a few clumps of grass. The chemical exposure comparison in real life is the offgassing of crumb rubber infill with dust maybe containing silica, although the main contaminant is PM2.5 in NYC air. On the other hand, infill turf is a polymeric mat sprinkled with rubber crumbs layered over a bed of sand. Which is a carcinogen, but not one which outgasses.

The Dodger(s) was (were) chagrined [had to look this up. "Chagrinned" is not allowed. Is it really legitimate to make a noun into a verb like this? Intermet dictionary said it was a transitive verb, but the Dodger(s) can't see that. Did the Steelers chagrin the Cardinals in the Superbowl?] to find no more than a hint of the results in the abstract. Where were the reviewers?

It seems like the players prefer turf to dirt. Better living through chemistry.

Monday, February 23, 2009

Workplace Violence Prevention in Health Care Settings Works

Annals of Epidemiology Volume 19, Issue 2, February 2009, Pages 125-133

Hospital Employee Assault Rates Before and After Enactment of the California Hospital Safety and Security Act
Carri Casteel PhDa, b, , , Corinne Peek-Asa PhDc, d, Maryalice NoceraMSNb, Jamie B. Smith MAb, James Blando PhDe, Suzi Goldmacher MSN, Emily O'Hagan MPHe, David Valiante PhDe and Robert Harrison PhDf
aDepartment of Epidemiology, University of North Carolina at Chapel Hill
bUniversity of North Carolina Injury Prevention Research Center, Chapel Hill
cDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, IA
dUniversity of Iowa Injury Prevention Research Center, Iowa City, IA
eNew Jersey Department of Health and Senior Services, Trenton, NJ
fUniversity of California, San Francisco

This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995.
We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993–1995) and a 6-year post-enactment period (1996–2001) using New Jersey hospitals as a temporal control.
Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment.
Policy may be an effective method to increase safety to health care workers.
BrooklynDodger(s) comment: The Dodger(s) couldn't get the full text to find the most interesting findings, which would have been the actual rates rather than the ratios, were New Jersey and California different, were emergency rooms and psychiatric facilities different? (The Dodger(s) suspect higher rates of assault in custodial facilities.) The reviewers get a demerit for not making the authors put that in the abstract. Injury control research is difficult, but this is a meager data base

Sunday, February 22, 2009

Exposure Response Variation among Differing Diesel Particulate Types

Toxicological Sciences 2009 107(2):522-534;
Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples

Tina Stevens*, Seung-Hyun Cho,, William P. Linak and M. Ian Gilmour,1
* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 Air Pollution and Prevention Control Division, National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831 Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-0026. E-mail:

Numerous studies have demonstrated that diesel exhaust particles (DEP) potentiate allergic immune responses, however the chemical components associated with this effect, and the underlying mechanisms are not well understood. This study characterized the composition of three chemically distinct DEP samples (N, C, and A-DEP), and compared post-sensitization and post-challenge inflammatory allergic phenotypes in BALB/c mice. Mice were instilled intranasally with saline or 150 µg of N-DEP, A-DEP, or C-DEP with or without 20 µg of ovalbumin (OVA) on days 0 and 13, and were subsequently challenged with 20 µg of OVA on days 23, 26, and 29. Mice were necropsied 18 h post-sensitization and 18 and 48 h post-challenge. N-DEP, A-DEP, and C-DEP contained 1.5, 68.6, and 18.9% extractable organic material (EOM) and 47, 431, and 522 µg of polycyclic aromatic hydrocarbons (PAHs), respectively. The post-challenge results showed that DEP given with OVA induced a gradation of adjuvancy as follows: C-DEP A-DEP > N-DEP. The C- and A-DEP/OVA exposure groups had significant increases in eosinophils, OVA-specific IgG1, and airway hyperresponsiveness. In addition, the C-DEP/OVA exposure increased the T helper 2 (TH2) chemoattractant chemokine, thymus and activation-regulated chemokine and exhibited the most severe perivascular inflammation in the lung, whereas A-DEP/OVA increased interleukin (IL)-5 and IL-10. In contrast, N-DEP/OVA exposure only increased OVA-specific IgG1 post-challenge. Analysis of early signaling showed that C-DEP induced a greater number of TH2 cytokines compared with A-DEP and N-DEP. The results suggest that potentiation of allergic immune responses by DEP is associated with PAH content rather than the total amount of EOM.
BrooklynDodger(s) comment: The Dodger(s) need(s) to figure out the provenance of these different diesel exhaust types. The article was not available in full text, at least yet. Since extractable organic matter and PAH were confounded, it's not clear why the authors conclude it's PAH.

Saturday, February 21, 2009

2 Weeks of Modest Levels of Nanoparticles Cause Systemic Immune System Changes

Toxicological Sciences 2007 100(1):203-214;
Pulmonary and Systemic Immune Response to Inhaled Multiwalled Carbon Nanotubes

Leah A. Mitchell*,, Jun Gao*, Randy Vander Wal, Andrew Gigliotti, Scott W. Burchiel* and Jacob D. McDonald,1
* College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131–0001 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 The National Center for Microgravity Research, c/o The NASA-Glenn Research Center, Cleveland, Ohio 44135
1 To whom correspondence should be addressed at Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108. Fax: (505) 348-4980. E-mail:

Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell–dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m3 had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.
BrooklynDodger(s) comment: Investigators demonstrated subtantial effects on immune system from modest, short term exposure to nanoparticles. Hazard identification accomplished- toxic potency established What will be done for potency estimates?

Friday, February 20, 2009

Another Pathway to Non-cancer Nanoparticle Toxicity

American Journal of Respiratory Cell and Molecular Biology. Vol. 40, pp. 349-358, 2009© 2009 American Thoracic Society

Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma

Jessica P. Ryman-Rasmussen1,2, Earl W. Tewksbury2, Owen R. Moss2, Mark F. Cesta1,2,3, Brian A. Wong2 and James C. Bonner1,2
1 Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina; 2 The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina; and 3 Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Correspondence and requests for reprints should be addressed to James C. Bonner, Ph.D., North Carolina State University, Box 7633, Raleigh, NC 27695. E-mail:

Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
BrooklynDodger(s) Comment: This study provides another view of the toxic potential of carbon nanotubes. The small numbers of mice and short exposure time means these data don't support inference of a threshold or no risk without allergic inflammation. The data do support an inference that persons with allergic inflammation might be less resistent to nano particles.

Thursday, February 19, 2009

Injury Control Implications of Surgery Safety Study

A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population
Alex B. Haynes, M.D., M.P.H., Thomas G. Weiser, M.D., M.P.H., William R. Berry, M.D., M.P.H., Stuart R. Lipsitz, Sc.D., Abdel-Hadi S. Breizat, M.D., Ph.D., E. Patchen Dellinger, M.D., Teodoro Herbosa, M.D., Sudhir Joseph, M.S., Pascience L. Kibatala, M.D., Marie Carmela M. Lapitan, M.D., Alan F. Merry, M.B., Ch.B., F.A.N.Z.C.A., F.R.C.A., Krishna Moorthy, M.D., F.R.C.S., Richard K. Reznick, M.D., M.Ed., Bryce Taylor, M.D., Atul A. Gawande, M.D., M.P.H., for the Safe Surgery Saves Lives Study Group

Background Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery.
Methods Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation.
Results The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001).>
Conclusions Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals.

BrooklynDodger(s) comment: Once again, a simple industrial quality control or safety protocol is applied to a health care setting, and proves to drastically improve patient safety and also outcomes, thereby also saving further procedures and money. Likely, compliance with the checklist varied across hospitals and times, thereby reducing effectiveness. That said, the nearly 1% fatality rate after intervention gives the Dodger(s) pause about undergoing surgery.

Wednesday, February 18, 2009

Chemoprevention Fails Again - Selenium and Vitamin E Fail to Prevent Prostate Cancer

JAMA. 2009;301(1):39-51

Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologicand preclinical data indicated the potential of selenium and vitamin E forpreventing prostate cancer.

Objective To determine whether selenium, vitamin E, or both could prevent prostatecancer and other diseases with little or no toxicity in relatively healthy men.

Design, Setting, and Participants A randomized, placebo-controlled trial (Seleniumand Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium vitamin E, and placebo) in a double-blindfashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serumprostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination notsuspicious for prostate cancer.

Interventions Oral selenium (200 $B&L(Bg/d from L-selenomethionine) and matched vitaminE placebo, vitamin E (400 IU/d of all rac- -tocopheryl acetate) and matchedselenium placebo, selenium vitamin E, or placebo placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.Main Outcome Measures Prostate cancer and prespecified secondary outcomes,including lung, colorectal, and overall primary cancer.

Results As of October 23, 2008, median overall follow-up was 5.46 years (range,4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancerwere 1.13 (99% CI, 0.95-1.35; n=473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n=432)for selenium, and 1.05 (99% CI, 0.88-1.25; n=437) for selenium vitamin E vs 1.00(n=416) for placebo. There were no significant differences (all P .15) in any otherprespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P=.06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P=.16) but not in the selenium vitamin E group.

Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
BrooklynDodger(s) Comments: Seems like the bloom will never be off the funding rose for chemoprevention. Imagine what a 35000 person study cost!!! And, starting in 2001 against a backdrop of mostly failed clinical trials of anti oxidant chemoprevention. The trail did not run long enough to evaluate the hazard of these treatments, although it suggests Selenium may increase risks of prostate cancer and type II diabetes. Schadenfreud aside, the anti-oxidant model posits that initiation by oxidant mechanisms is reduced by the treatment. By 55, most men are initiated. So the trial doesn't really test the model. Vitamins are likely good for cancer cells as well as regular cells, so increased cancer is a likely outcome of late stage treatment. The Dodger(s) confess not to know the street doses which gullibles take to prevent cancer, to compare with those in this study.

Monday, February 16, 2009

Biomarkers of Effect Found Associated with Chemical Exposure in a Community Population

Toxicology Letters Volume 184, Issue 2, 30 January 2009, Pages 139-144
Community level exposure to chemicals and oxidative stress in adult population

Yun-Chul Honga, b, Eun-Young Parka, Min-Seon Parkc, Jeong Ah Koc, Se-Young Ohd, Ho Kime, Kwan-Hee Leef, Jong-Han Leemf and Eun-Hee Hag, ,

aDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
bInstitute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
cDepartment of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
dDepartment of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea
eDepartment of Epidemiology and Biostatistics, Seoul National University School of Public Health, Seoul, Republic of Korea
fDepartment of Occupational and Environmental Medicine, Inha University Hospital, Incheon, Republic of Korea
gDepartment of Preventive Medicine, Ewha Womans University Medical School, Seoul, Republic of Korea

Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P <>). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P <> The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.
BrookkynDodger(s) comment: The Dodger(s) generally fear that community survey projects like this will generate spurious null results. So finding an association should be considered of special weight. The investigators identify a pathway from oxidative stress to diabetes. Oxidative stress is relatively easily measured in live people as an intermediate outcome. This broadens the range of conditions which may be caused by occupational or environmental chemical exposures.

Sunday, February 15, 2009

National Health Insurance Coverage Improves Breast Cancer Survival

Annals of EpidemiologyVolume 19, Issue 2, February 2009, Pages 121-124

Breast Cancer Survival in Ontario and California, 1998–2006: Socioeconomic Inequity Remains Much Greater in the United States

Kevin M. Gorey PhD, MSWa, , , Isaac N. Luginaah PhDb, Eric J. Holowaty MDc, Karen Y. Fung PhDd and Caroline Hamm MDe
aSchool of Social Work, University of Windsor, Ontario
bDepartment of Geography, University of Western Ontario, London
cDivision of Preventive Oncology, Cancer Care Ontario, Toronto
dDepartment of Mathematics and Statistics, University of Windsor, Ontario
eWindsor Regional Cancer Center, Ontario

This study re-examined the differential effect of socioeconomic status on the survival of women with breast cancer in Canada and the United States. Ontario and California cancer registries provided 1,913 cases from urban and rural places. Stage-adjusted cohorts (1998–2000) were followed until 2006. Socioeconomic data were taken from population censuses. SES-survival associations were observed in California, but not in Ontario, and Canadian survival advantages in low-income areas were replicated. A better controlled and updated comparison reaffirmed the equity advantage of Canadian health care.
BrooklynDodger(s) Comment: Chemicals are part of the environment, psychosocial stress and class bias are part of the environment, but we EOHS folks forget that social insurance is also part of the environment which determines health outcomes.

Saturday, February 14, 2009

Review of Nanoparticle Toxicity Concludes That Application and Hazard are Tied Together in Physicochemical Properties

Pulmonary applications and toxicity of engineered nanoparticles
J. W. Card, D. C. Zeldin, J. C. Bonner, and E. R. Nestmann
Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L400 - L411.

Because of their unique physicochemical properties, engineered nanoparticles have the potential to significantly impact respiratory research and medicine by means of improving imaging capability and drug delivery, among other applications. These same properties, however, present potential safety concerns, and there is accumulating evidence to suggest that nanoparticles may exert adverse effects on pulmonary structure and function. The respiratory system is susceptible to injury resulting from inhalation of gases, aerosols, and particles, and also from systemic delivery of drugs, chemicals, and other compounds to the lungs via direct cardiac output to the pulmonary arteries. As such, it is a prime target for the possible toxic effects of engineered nanoparticles. The purpose of this article is to provide an overview of the potential usefulness of nanoparticles and nanotechnology in respiratory research and medicine and to highlight important issues and recent data pertaining to nanoparticle-related pulmonary toxicity.
BrooklynDodger(s) comment: This abstract conveys no information, but having saved it, the Dodger(s) need to fill a day's post. The toxic potential of nanoparticles is well established, the equivalent of hazard identification in the NAS Red Book paradigm. No uncertainty left. Potency estimates - exposure response assessment - are grounded in short term exposure studies in laboratories, but can be grounded in potency estimates for diesel particulate matter and carbon black.

Friday, February 13, 2009

p53 - Maybe Genetics Doesn't Load the Gun After All

NATURe RevIewS CanCer voLUMe 9 FeBRUARy 2009 95
p53 polymorphisms: cancer implications
Catherine Whibley*, Paul D. P. Pharoah‡ and Monica Hollstein*

Abstract The normal functioning of p53 is a potent barrier to cancer. Tumour-associated mutations in TP53, typically single nucleotide substitutions in the coding sequence, are a hallmark of most human cancers and cause dramatic defects in p53 function. By contrast,
only a small fraction, if any, of the >200 naturally occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Polymorphisms in the TP53 locus that might have cancer-related phenotypical manifestations are the subject of this Review. Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are also discussed.
BrooklynDodger(s) comment: No highlights here, because the full text doesn't have much fat, although little information. The expression of the p53 gene leads to cell suicide, apoptosis. Something you want in a tumor cell. Defective p53 lets the tumor cell grow in the face of other triggers for apoptosis, so it's logical that p53 mutations are found in tumor cells. The review suggests that few defective p53 genotypes are found in the human population, meaning that it's not a place for specially sensitive populations.

Thursday, February 12, 2009

Reference Values for Indoor Air Problems Orders of Magnitude Less Than PEL's

Airborne Concentrations of Volatile Organic Compounds, Formaldehyde and Ammonia in Finnish Office Buildings with Suspected Indoor Air Problems
Authors: Heidi J. Salonen a; Anna-Liisa Pasanen b; Sanna K. Lappalainen a; Henri M. Riuttala a; Tapani M. Tuomi a; Pertti O. Pasanen c; Beatrice C. Bck a; Kari E. Reijula a
Affiliations: a Finnish Institute of Occupational Health, Helsinki, Finland
b Finnish Institute of Occupational Health, Kuopio, Finland
c Department of Environmental Science, University of Kuopio, Kuopio, Finland

Journal of Occupational and Environmental Hygiene, Volume 6, Issue 3 March 2009 , pages 200 - 209
A database of indoor air concentrations of volatile organic compounds (VOCs) (n = 528), formaldehyde (n = 76), and ammonia (n = 47) in office environments was analyzed to suggest interpretation guidelines for chemical measurements in office buildings with suspected indoor air problems. Indoor air samples were collected for VOCs from 176 office buildings, 23 offices for formaldehyde, and 14 office buildings for ammonia in 2001-2006. Although the buildings had reported indoor air complaints, a walk-through inspection by indoor air specialists showed no exceptional sources of indoor air pollutants. The measurements of chemical pollutants did not indicate any clear reason for the complaints. The geometric mean concentration of total volatile organic compounds (TVOC) was 88 μg m-3 in office rooms and 75 μg m-3 in the open plan offices. The mechanical supply and exhaust ventilation significantly (p <>The highest mean concentration and frequency distributions were determined for the individual VOCs. The most common VOCs found in ≥ 84% of the indoor samples include toluene, xylene (p,m), 1-butanol, nonanal, and benzene. According to concentrations, the most abundant VOCs were 2-(2-ethoxyethoxy)ethanol, acetic acid, 1,2-propanediol, and toluene. The geometric mean concentration of formaldehyde and ammonia in the office buildings was 11 μg m-3 (3-44 μg m-3 and 14 μg m-3 (1-49 μg m-3, respectively. On the basis of statistical analyses, the guideline value indicating a usual concentration of the pollutant in office buildings is 70 μg m-3 for TVOC, 7 μg m-3 for most individual VOCs, 10 μg m-3 for formaldehyde, and 12 μg m-3 for ammonia The guidance value suggested for TVOC is 250 μg m-3, for formaldehyde 15 μg m-3, and for ammonia 25 μg m-3. If the guidance value is exceeded, this may indicate the existence of an exceptional source and the need for additional environmental investigations. The levels should not be used for the evaluation of health risks. The guideline values are applicable in a subarctic climate for modern, urban office buildings.
BrooklynDodger(s) comments: The Dodger(s) appreciate(s) that these investigators are willing to put an index value on exposure levels associated with indoor air complaints, although the Dodger(s) see no clear rational for these values. Formaldehyde at .010 mg/m^3 is equivalent to 0.008 ppm, well below the ATSDR MRL for intermediate duration exposure of 0.03 ppm. An interesting account of an indoor air investigation at the National Center for Health Statistics can be found at

Wednesday, February 11, 2009

Putting a Carcinogen on Your Hair - Diethanolamine in Shampoo

Journal of AOAC INTERNATIONAL Volume: 88 Issue: 2 Page(s): 592-594 March 2005

Determination of Diethanolamine in Shampoo Products Containing Fatty Acid Diethanolamides by Liquid Chromatography with a Thermal Energy Analyzer
Author(s): Hardy J. Chou 1

A liquid chromatography (LC) method using a thermal energy analyzer (TEA) is described for the determination of diethanolamine (DEA) in shampoo products containing fatty acid diethanolamides. DEA was converted to N-nitrosodiethanolamine (NDELA) by dissolving a portion of the product in 6M acetic acid and mixing with sodium nitrite for 1 h at room temperature. The reaction mixture was dried, dissolved in acetone, and analyzed for NDELA by LC-TEA. The recovery of DEA from 2 shampoo products at fortification levels of 25, 250, and 1000 ppm ranged from 70 to 105%. Twenty shampoo products were analyzed by this method, and 19 were found to contain DEA at levels ranging from 140 to 15 200 ppm.
BrooklynDodger(s) comment: NTP bioassays of diethanolamine and diethanolamine fatty acid condensates by skin exposure provided clear evidence of carcinogenicity in male and female mice, but not the rat. Some years ago, IARC relegated DEA to group 3, not classifiable. The working group considered the male and female mouse experiments to be a single study - not so under current rules - and declined to consider the fatty acid condensate studies to be DEA studies. Years later, DEA exposure to much of the population continues.

Tuesday, February 10, 2009

Mechanistic Explanation of Chrome Carcinogenicity - What about other agents?

Toxicology and Applied PharmacologyVolume 235, Issue 1, 15 February 2009, Pages 47-56

Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

Laura M. Beavera, b, Erik J. Stemmyb, c, Stephanie L. Constantb, c, Arnold Schwartzd, Laura G. Littleg, Jason P. Gigleyc, Gina Chuna, b, Kent D. Sugdeng, Susan M. Ceryaka, b, e, f and Steven R. Patiernoa, b, f, ,
aDepartment of Pharmacology and Physiology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
bInstitute of Biomedical Sciences, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
cDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
dDepartment of Pathology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
eDepartment of Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
fGW Cancer Institute, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
gThe University of Montana, Department of Chemistry, 32 Campus Drive, Missoula, MT 59812, USA

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.


BrooklynDodger(s) Comment: This study provides some single dose results for a known human carcinogen in the target organ. Chromate ion appears the active agent. Should all agents which impact survival signaling, apoptosis, be considered carcinogens? At least, would this biological response trigger further study? The Dodger(s) wonder about ferric oxide, which is also an oxidizer.

Monday, February 09, 2009

Low Levels of Arsenic in Drinking Water Causes Irreversible Damage to Lungs to Newborns

Toxicology and Applied PharmacologyVolume 235, Issue 1, 15 February 2009, Pages 105-113

In utero and postnatal exposure to arsenic alters pulmonary structure and function

R. Clark Lantza, b, c, , , Binh Chaua, Priyanka Sarihana, Mark L. Wittenb, d, Vadim I. Pivniouka, e and Guan Jie Chena
aDepartment of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
bSouthwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721, USA
cBIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
dDepartment of Pediatrics, University of Arizona, Tucson, AZ 85724, USA
eArizona Respiratory Center, University of Arizona, Tucson, AZ 85724, USA

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.
BrooklynDodger(s) comments: Risk assessors debate whether cancer causing properties discovered by one route apply (are relevent) to another - inhalation v. ingestion usually. Houdinists default to no relevence. Arsenic became known to be a human carcinogen as a result of inhalation exposure in the workplace causing lung cancer. Then as a result of ingestion of water in the developing world. Now comes laboratory support for human epidemiology. Also, this study shows the potential importance of looking at all stages of life. The Dodger(s) need to search for drinking water bioassays of arsenic. And, it would be nice if the investigators repeated the study with in utero only and perinatal only exposure.

Sunday, February 08, 2009


BrooklynDodger(s) Comments: The Dodger(s) blew it on Sunday. No post.

Saturday, February 07, 2009

"Hostility" makes you fat

American Journal of Epidemiology Volume 169, Number 3 Pp. 347-354
Hostility and Trajectories of Body Mass Index Over 19 Years: The Whitehall II Study
Hermann Nabi, Mika Kivimaki, Séverine Sabia, Aline Dugravot, Mohamed Lajnef, Michael G. Marmot and Archana Singh-Manoux
Correspondence to Dr. Hermann Nabi, INSERM U687, Hôpital Paul Brousse, Bâtiment 15/16, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France (e-mail:

The authors examined the associations of hostility measured in adulthood with subsequent body mass index (BMI; weight (kg)/height (m)2) assessed at 4 time points over a 19-year period (1985–2004) in a United Kingdom cohort study. A total of 6,484 participants (4,494 men and 1,990 women) aged 35–55 years at baseline (1985–1988) completed the Cook-Medley Hostility Scale. BMI was assessed upon medical examination in phases 1 (1985–1988), 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004). Mixed-models analyses of repeated measures showed clear evidence of increasing BMI over follow-up in both sexes. In women, higher levels of hostility were associated with higher BMI at baseline, and this effect remained constant throughout the follow-up period. In men, hostility levels were also strongly associated with BMI at baseline, but results for the interaction between time and hostility also suggested that this association increased over time, with persons in the highest quartile of hostility gaining an excess of 0.016 units (P = 0.023) annually over the follow-up period as compared with persons in the lowest quartile. The authors conclude that the difference in BMI as a function of hostility levels in men is not stable over time.
BrooklynDodger(s) comment: Here's another nugget mined form the Whitehall vein.

[New Yorkers associate Whitehall with reporting to the draft board during the Vietnam War. This Whitehall is in England.]

The Hostility Scale [lots of caps here so far] asks questions which are supposed to measure "Cynicism, Hostile Attributions, Hostile Affect, Aggressive Responding, Social Avoidance." In other words, bad attitude. Assume for the sake of argument this 1950's scale does measure those things. A bad score would indicate an unhappy, suffering person whose future behavior might cause more unhappiness and social isolation - in other words pain. So people in pain gain weight. Probably from inappropriate eating behavior [which is to say, eating]. So this study provides additional evidence that pain causes health risk behavior.

Friday, February 06, 2009

Houdini Alert - Ethyl Benzene Carcinogenicity

Toxicological Sciences 2009 107(2):352-366

Mechanism of Ethylbenzene-Induced Mouse-Specific Lung Tumor: Metabolism of Ethylbenzene by Rat, Mouse, and Human Liver and Lung Microsomes

Shakil A. Saghir1, David L. Rick, E. L. McClymont, Fagen Zhang, Michael J. Bartels and James S. Bus
Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674
1 To whom correspondence should be addressed at Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674. Fax: (989) 638-9863. E-mail: ssaghir{at}

This study was conducted to determine species differences in the metabolism of ethylbenzene (EB) in liver and lung. EB (0.22–7.0mM) was incubated with mouse, rat and human liver and lung microsomes and the formation of 1-phenylethanol (1PE), acetophenone (AcPh), 2-ethylphenol (2EP), 4-ethylphenol (4EP), 2,5-ethylquinone, and 3,4-ethylquinone were measured. Reactive metabolites (2,5-dihydroxyethylbenzene-GSH [2EP-GSH] and 3,4-dihydroxyethylbenzene-GSH [4EP-GSH]) were monitored via glutathione (GSH) trapping technique. None of the metabolites were formed at detectable levels in incubations with human lung microsomes. Percent conversion of EB to 1PE ranged from 1% (rat lung; 7.0mM EB) to 58% (mouse lung; 0.22mM EB). More 1PE was formed in mouse lung than in mouse liver microsomes, although formation of 1PE by rat liver and lung microsomes was similar. Metabolism of EB to 1PE was in the order of mouse > rat > human. Formation of AcPh was roughly an order of magnitude lower than 1PE. Conversion of EB to ring-hydroxylated metabolites was much lower (0.0001% [4EP-GSH; rat lung] to 0.6% [2EP-GSH; mouse lung]); 2EP-GSH was typically 10-fold higher than 4EP-GSH. Formation of 2EP-GSH was higher by lung (highest by mouse lung) than liver microsomes and the formation of 2EP-GSH by mouse liver microsomes was higher than rat and human liver microsomes. Increasing concentrations of EB did lead to a decrease in amount of some formed metabolites. This may indicate some level of substrate- or metabolite-mediated inhibition. High concentrations of 2EP and 4EP were incubated with microsomes to further investigate their oxidation to ethylcatechol (ECat) and ethylhydroquinone (EHQ). Conversion of 2EP to EHQ ranged from 6% to 9% by liver (mouse > human > rat) and from 0.1% to 18% by lung microsomes (mouse >> rat >> human). Conversion of 4EP to ECat ranged from 2% to 4% by liver (mouse > human rat) and from 0.3% to 7% by lung microsomes (mouse >> rat >> human). Although ring-oxidized metabolites accounted for a relatively small fraction of overall EB metabolism, its selective elevation in mouse lung microsomes is nonetheless consistent with the hypothesized mode of action for observed preferential toxicity of EB to the lung in this species.


BrooklynDodger(s) comment: Few employers buy ethyl benzene intentionally, but it constitutes about 1/3 of commercial xylenes, being it weighs the same molecularly. So there's a lot of it around.

IARC classifies EB as 2B: "Ethylbenzene was tested by inhalation exposure in single experiments in mice and rats. In mice, it increased the incidence of lung adenomas in males and of liver adenomas in females. In male rats, it increased the incidence of renal tubule adenomas and carcinomas. An increase in the incidence of renal adenomas was seen in females only after step-sectioning. A study in rats by oral administration could not be evaluated. A metabolite of ethylbenzene, 1-phenylethanol, increased the incidence of renal tubule adenomas in male rats." [Note that IARC considers adenomae as evidence for carcinogenicity, not just carcinomae.]

The renal adenomae in females get EB out of the alpha-2 Houdini machine.

Several volatile organic compounds cause mouse lung tumors but are either less potent or lack this potential in the rat. This gives rise to the Mouse Clara Cell Hypothesis to erase human risk potential, or at least to reduce human potency estimates through parallelogrammation.

The Dodger(s) confess not to have read the full text to determine where in Midland these Dow scientists (Dowagers? some are guys, but a few names are not gender identifiable) got the human lung tissue. Likely from lung biopsies, not usually an indication of good health among donors, and at best a convenience sample not reflecting variation among the human population. [Although, to be fair, neither the lab mouse or rat strains reflect the variation among their species either.]

Thursday, February 05, 2009

More Nanoparticle Hazard Identification - Iron Oxide Added to the List

Toxicol. Sci. 2009 107: 342-351; doi:10.1093/toxsci/kfn245.

Particokinetics and Extrapulmonary Translocation of Intratracheally Instilled Ferric Oxide Nanoparticles in Rats and the Potential Health Risk Assessment
Mo-Tao Zhu*,, Wei-Yue Feng*,1, Yun Wang*,, Bing Wang*, Meng Wang*, Hong Ouyang*, Yu-Liang Zhao* and Zhi-Fang Chai*
* Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China
1 To whom correspondence should be addressed at P.O. Box 918, Beijing 100049, China. Fax: (8610) 88235294. E-mail:
Exposure to nanoparticles has presented potential risks to human cardiorespiratory systems. Pulmonary retention and extrapulmonary redistribution of inhaled nanoparticles have been considered to be important contributing factors of cardiorespiratory diseases. In the present work, 22-nm 59Fe2O3 nanoparticles (radioactive isotope 59Fe-labeled ferric oxide nanoparticles) were intratracheally instilled into the male Sprague-Dawley rats at a dose of 4 mg/rat. Extrapulmonary distribution of 59Fe2O3 in organs and its metabolism in lung, blood, urine, and feces were measured for 50 days of exposure. Phagocytosis and clearance of agglomerated nano-Fe2O3 by monocytes/macrophages were observed by histopathology and inductively coupled plasma-mass spectrometry examination. Our results showed intratracheal-instilled nano-59Fe2O3 could pass through the alveolar-capillary barrier into systemic circulation within 10 min that consisted with one-compartment kinetic model. The nano-59Fe2O3 in the lung was distributed to organs rich in mononuclear phagocytes, including liver, spleen, kidney and testicle. The plasma elimination half-life of nano-59Fe2O3 was 22.8 days and the lung clearance rate was 3.06 µg/day, indicating the systemic accumulation and lung retention had occurred. The deposited nano-Fe2O3 in interstitial lung was probably contributed by the particles escaping from alveolar macrophages phagocytosis and macrophages clearance function overloading. Our results suggest that the effect of Fe2O3 nanoparticles exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanoparticles.
Key Words: ferric oxide nanoparticle; extrapulmonary translocation; particokinetics; lung retention; health risk assessment.
BrooklynDodger(s) comment: By now, the question of whether nanoparticles are absorbed from the respiratory tract, translocated systemically and enter cells should be settled. Yes they can! Toxic potential and potency plausibly has a physical component - independent of chemistry - and a chemical specific component. The Dodger(s) would buy carbon black and titanium dioxide - Group 2B carcinogens - as the baselines for comparison of other species. Iron oxide (not metallic iron) particles might be pretty potent - iron oxide getting loose in the cell likely promotes redox-cycling and oxidative damage.

Welding fume contains iron oxide particles, it would be worthwhile assessing particle size, the time course of particle size and the size distribution of particles reaching the alveolar surface.