Proximity to Air Pollution Sources Increases Childhood Asthma Attacks

American Journal of Epidemiology 2007 165(8):927-935
Air Pollution Sources and Childhood Asthma Attacks in Cataño, Puerto Rico

Nilsa I. Loyo-Berríos1, Rafael Irizarry2, Joseph G. Hennessey3,4, Xuguang Grant Tao5,6,7 and Genevieve Matanoski6,7

1 Office of Surveillance and Biometrics, Center for Devices and Radiological Health, Food and Drug Administration, US Department of Health and Human Services, Rockville, MD
2 Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
3 Center for Imaging Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD
4 Department of Psychiatry, School of Medicine, Johns Hopkins University, Baltimore, MD
5 Division of Environmental and Occupational Health, School of Medicine, Johns Hopkins University, Baltimore, MD
6 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
7 District of Columbia Cancer Registry, District of Columbia Health Department, Washington, DC

Correspondence to Dr. Nilsa I. Loyo-Berríos, Center for Devices and Radiological Health, Food and Drug Administration, US Department of Health and Human Services, 1350 Piccard Drive, HFZ-541, Rockville, MD 20850 (nilsa.loyo-berrrios@fda.hhs.gov).

Asthma prevalence in the Cataño Air Basin of Puerto Rico is 27% for children aged 13–14 years and 45% for children aged 5–6 years. There is concern that these rates are related to air pollution. The authors conducted a nested case-control study to evaluate whether proximity to air pollution point sources was associated with increased risk of asthma attacks. For 1997–2001, 1,382 asthma-related medical visits (International Classification of Diseases, Ninth Revision, codes 493 and 493.9) in children under 17 were identified through health insurance claims. Controls were children with no asthma attacks who were randomly selected from enrollees in two health insurance companies by incidence density sampling (1:5) and matched to cases on gender, age, insurance company, and event date. The distance from a point source to the subject's residence area represented a surrogate exposure measurement. Odds ratios for a 1-km decrease in distance were obtained by conditional logistic regression. Risk of asthma attack was associated with residing near a grain mill (odds ratio (OR) = 1.35), petroleum refinery (OR = 1.44), asphalt plant (OR = 1.23), or power plant (OR = 1.28) (all p's <>Residence near major air emissions sources (>100 tons/year) increased asthma attack risk by 108% (p <>
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BrooklynDodger(s) comment: This study provides some evidence that increased "air pollution" - nature unspecified - increases the risk of childhood asthma. The Dodger(s) concede(s) this is not a totally settled question and that continuing work in this area is needed.
The Dodger(s) are impressed at the methods - mapping addresses of cases and controls against locations of air pollution sources, which are likely in some kind of geographical data base. This provides a semi-quantitative exposure measure derived at the computer terminal, not pounding the pavement taking measurements. An idea others can use. Quibbling, air emissions don't spread uniformly as the inverse square of distance, they move in a plume. As long as all the heavy statistical and mapping guns were trained on this project, it could have been enhanced by applying a wind fan and plume mapping software to exposure assessment. It might also be feasible to map PM2.5 in the street using real time monitoring equipment, in relation to these sources. That might be looking for the lost keys under a lampost because that's where the light is, but PM2.5 or black carbon is the strongest known candidates for causes. Ozone variation at the ground level in relation to these sources is unlikely.
The sociology of this project interests. There's no institution in Puerto Rico listed on this project. The project was done at the "Mayor of New York for One More Term (so far)" School of Public Health in Baltimore. The first author - likely the doctoral student, likely in epidemiology given the last author - is now affiliated in the DC area outside of environmental health.

Not Asking the Correct Questions About Job Satisfaction

International Journal of Industrial ErgonomicsVolume 39, Issue 1, January 2009, Pages 1-6
Effect of job organization on job satisfaction among shop floor employees in automotive industries in Malaysia
S.Z. Dawala, , , Z. Tahaa and Z. Ismailb
aDepartment of Engineering Design and Manufacture, Faculty of Engineering, University of Malaya, Lembah Pantai 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia
bDepartment of Civil Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia

Abstract
The effect of job organization factors on job satisfaction was examined in two automotive industries in Malaysia. The information was collected from 170 male subjects with the mean age and work experience of 26.8 ± 5.3 years and 6.5 ± 4.9 years, respectively. The results showed that the job satisfaction was significantly related to job organization factors. The potential applications of these findings include methods developed in diagnosing the industrial work, namely, questionnaire design, data collection and statistical analysis to diagnose current industrial work design that affect workers satisfaction. The relationship between job organization factors and job satisfaction was analyzed using statistical methods to determine the correlations and regression model. The model developed highlights that the most significant factors in both automotive companies are job rotation, work method, problem solving and goal setting with adjusted R2 of 0.8 and 0.7 for the two automotive companies.
Relevance to industry
The study highlights methodological developments in determining the effect of job organization factors on job satisfaction in the automotive industries. The findings suggest that job organization factors and job satisfaction are significantly related and it is therefore important to maintain these factors in an automotive industrial environment in order to keep the shop-floor employees motivated.
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BrooklynDodger(s) comment: Work organization results are particularly likely to be influence by cultural factors, especially in what would be considered a rising industrial power. The Dodger(s) are pleased to see that publications from these nations are making their way to the international literature.
That said, factory work is organized in similar fashion everywhere, especially in the automotive industry. A factory workforce is stratified: management; professional (engineers, logistics); technical; clerical; skilled maintenance; mobile occupations (material handling, laborers); fixed production (assemblers, machine operators). These strata have observable differences is work organization, and in particular for the fixed production strata, ergonomic risk and musculoskeletal pain. There are salaried occupations on the "shop floor," but more important there are distinct strata in the hourly occupations on the "shop floor."
The Dodger(s) didn't find any recognition of this in the paper. In particular, the confounding of musculoskeletal pain with fixed production jobs should be taken into account in these job satisfaction surveys.
The Dodger(s) would have preferred that the abstract to recognize that this is a pilot study, and much more, that the direction of the associations be stated.

Medical Myths And Moral Panic

http://www.bmj.com/cgi/content/full/335/7633/1288
BMJ 2007;335:1288-1289 (22 December),
Mixed messages
Medical myths

Rachel C Vreeman, fellow in children’s health services research1, Aaron E Carroll, assistant professor of paediatrics2
1 Children’s Health Services Research, Indiana University School of Medicine, Indianapolis, IN, USA, 2 Regenstrief Institute, Indianapolis, IN, USA

http://www.bmj.com/cgi/content/full/337/dec17_2/a2769

Christmas 2008: Seasonal Fayre
Festive medical myths

BrooklynDodger(s) comment: These are available in full text. Mostly it's just for fun.

But there's a but if a lesson here about framing ideas or myths taking hold without evidence. Two myths among those cited as that sugar causes hyperactivity in children, or eating late causing obesity.These have the aspect of Moral Panic, which promotes believeability. Moral panic is the concept that a deviant or denigrated group is responsible for a bad societal outcome.

Endogenous Carcinogens - Estrogen

New study firmly ties hormone use to breast cancer
By MARILYNN MARCHIONE The Associated Press Saturday, December 13, 2008; 5:47 PM


"SAN ANTONIO -- Taking menopause hormones for five years doubles the risk for breast cancer, according to a new analysis of a big federal study that reveals the most dramatic evidence yet of the dangers of these still-popular pills.
Even women who took estrogen and progestin pills for as little as a couple of years had a greater chance of getting cancer. And when they stopped taking them, their odds quickly improved, returning to a normal risk level roughly two years after quitting.
Collectively, these new findings are likely to end any doubt that the risks outweigh the benefits for most women..."



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BrooklynDodger(s) comment: The Dodger(s) bring(s) this news report to attention to make the point that cancers which appear without exogenous chemical exposure may arise from endogenous chemicals. The most potent risk factor for mammary cancer is being a woman (there are male mammary cancers, it might be that environmental causes of breast cancer are more feasibly studied in males because of lower population rates.) The risk factors for breast cancer quoted in the cancer control literature - late or no childbearing, low exercise, higher BMI, greater height, etc - are modifiers of the main effect.



The post also reminds the Dodger(s) that the common notion of 10-15 year latency for solid tumors applies to initiation stage carcinogens. If removal from exposure for 2 years reduces risk, then 2 years of exposure might be assumed to increase risk measurably. We probably all have some little tumors lurking, just waiting for a chemical to facility expansion of the clone.

Neurotoxic Effects of Injected Manganese Salt

Toxicological Sciences 2009 107(1):156-164;
Manganese Induces Dopaminergic Neurodegeneration via Microglial Activation in a Rat Model of Manganism

Fang Zhao, Tongjian Cai, Mingchao Liu, Gang Zheng, Wenjing Luo1 and Jingyuan Chen1

Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an, China

1 To whom correspondence should be addressed at Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, 17 Changlexi Street, Xi'an, China. Fax: +86-29-84774863. E-mail: jy_chen@fmmu.edu.cn

"Manganese is an essential trace element required for normal development and bodily functions. However, exposure of the brain to excessive amounts of manganese results in neurotoxicity. Although previous studies examining manganese neurotoxicity have focused on neuronal injury, especially direct injury to dopaminergic neurons, the effects of manganese-induced neurotoxicity on glial cells have not been reported. The current study was designed to examine the effect of manganese on microglial activation, and the underlying mechanism of manganese-induced dopaminergic neuronal injury in vivo. We established an animal model of manganism by intrastriatal injection of MnCl2·4H2O into male Sprague-Dawley rats. One day after administration of manganese, a few microglial cells in the substantia nigra (SN) were activated, although the number of tyrosine hydroxylase (TH)–immunoreactive neurons in the SN was unaffected. Seven days after administration of manganese, a marked reduction in the number of TH-immunoreactive neurons was observed in the SN, and the majority of microglial cells were activated. We found that manganese upregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF-) gene expression, as well as iNOS, TNF-, and interleukin-1β (IL-1β) protein levels in the SN. Furthermore, treatment with minocycline, an inhibitor of microglial activation, attenuated microglial activation and mitigated IL-1β, TNF-, and iNOS production as well as dopaminergic neurotoxicity induced by manganese. These results suggested that dopaminergic neurons could be damaged by manganese neurotoxicity, and that the activated microglial cells and their associated activation products played an important role in this neurodegenerative process."

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BrooklynDodger(s) comments: This report comes from an interesting location, a sign that economic development in China is accompanied by ongoing toxicologic research. An important lesson from this paper is that the nervous system and its function include a lot more cells than just neurons. The site of action of a toxic chemical can be the glial cells - which wrap and support the neurons. Tumors arise from glial cells as well, rather than neurons.

Depleting Macrophage both Increases and Decreases Sensitization by Trimellitic Anhydride - A Lesson for Risk Assessment Models

Toxicology and Applied Pharmacology Volume 211, Issue 1 , 15 February 2006, Pages 20-29
Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma
Dingena L. Valstara, Marcel A. Schijfa, Frans P. Nijkampa, Gert Stormb, Josje H.E. Artsc, C. Frieke Kuperc, Nanne Bloksmaa, d and Paul A.J. Henricksa, ,

Abstract
Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.
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BrooklynDodger(s) comment: Trimellitic anhydride hardens epoxy resins, particularly powdered paint. It's a sensitizer and an asthmagen.
http://www.cdc.gov/NIOSH/78121_21.html#Potential%20Occupational%20Exposures
Powdered coatings are attractive to EPA and environmental groups because of low or no VOC, but the problem in the workplace is dust (particulate) control, which is more difficult to control in spray operations than vapor.
TMA has a vapor pressure of 7.6 x 10^-5 Pa @ 25ºC, saturation vapor concentration of about .1 ppm. So we'd be talking particulate here [Can someone please check the Dodger(s) arithmatic?]

Now back to the lesson of posted abstract. Science types like to incorporate "mechanistic" data into exposure-response assessments. In a "Houdini" risk assessment, the goal is to chose a biochemical parameter in the most resistant species or subpopulation for which people are most like the resistant species, and use that parallel to argue for greater human resistence. This makes the risk disappear, or at least get smaller, and allows the regulatory agency or industry to escape from doing anything. Most of these risk assessments are untestable hypotheses, since they estimate population risks in a dose range which can't be directly observed.

An exposure response relationship in a population will be steeper - predict lower low dose risk - if the population is more homogeneous. The Dodger(s) imagine(s) that there's a range of alveolar macrophage populations in the human population. The experiment shows that depending on the end point chosen, depletion - lower levels - either reduces or enhances the gravity of the organisms response. So the assessor could chose an endpoint that either increases or decreases the estimated low dose risk, and therefore lowers or raises the appropriate PEL.

Real Primary Prevention - Smoking Causes Disease, But What Causes Smoking?

Am J Prev Med Volume 36, Issue 1, Pages 9-12 (January 2009)
Postpartum Depressive Symptoms and Smoking Relapse Alicia M. Allen, MPHb, Cheryl B. Prince, PhDa, Patricia M. Dietz, DrPHa

"Background
Smokers with depressive symptoms are more likely to relapse after attempting to quit than those without depressive symptoms. Little is known about the relationship between depressive symptoms and relapse during the postpartum period; thus the aim of the present study is to assess the relationship between postpartum smoking relapse and depressive symptoms.
Methods
Analysis of 2004 Pregnancy Risk Assessment Monitoring System (PRAMS) data from women in 16 states who reported smoking 3 months before pregnancy and reported abstinence from smoking during the last 3 months of pregnancy (n=2566). For women experiencing postpartum depressive symptoms, chi-square tests were computed for homogeneity of distribution between two groups (sustained abstinence versus relapsed) and an OR for relapsing during the postpartum period. Potential confounders, including demographic characteristics, intensity of smoking before pregnancy, and time since delivery, were computed.
Results
Compared to women who did not experience postpartum depressive symptoms, women who did were 1.86 (95% CI=1.31, 2.65) times as likely to relapse during the postpartum period. After adjusting for demographic characteristics, intensity of smoking, and time since delivery, the association decreased slightly (adjusted OR=1.77, 95% CI=1.21, 2.59).
Conclusions
Women who quit smoking during pregnancy may be more likely to relapse if they experience depressive symptoms. Further research is needed into the screening and treatment of postpartum depressive symptoms as a possible method for preventing postpartum smoking relapse."

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BrooklynDodger(s) comment: Health risk behavior, such as smoking, is clearly associated with adverse outcomes. Many health "promotion" messages and programs blame the victim for the adverse outcome because the victim engages in health risk behavior. These messages and programs rely on exhortation as the major intervention.
The Dodger(s) contend(s) that a better strategy is to intervene on the causes of the risk behavior. Stress is widely believed to cause risk behavior, pain should be understood to be a stressor. A series of posts will argue that musculoskeletal pain is a cause of risk behavior and is responsible for health risk behavior. But the plausibility of this argument depends on the generality of the observation that the stressor precedes the risk behavior.
This post quotes a study which observed that newly arising depression or depressive symptoms is associated with smoking relapse. The Dodger(s) consider(s) depression or depressive symptoms to be a form of pain. The Dodger(s) also note that prevalence of smoking in a population depends on the balance between smokers quitting and ex-smokers starting again. Likely there are few newly starting smoking among forty-somethings.

PPE Rule - An Avenue for Chemical Protection in the Absense of an OSHA PEL

http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=FEDERAL_REGISTER&p_id=21370
Clarification of Employer Duty To Provide Personal Protective Equipment and Train Each Employee - 73:75568-75589

"In this rulemaking, OSHA is amending its standards to add language clarifying that the personal protective equipment (PPE) and training requirements impose a compliance duty to each and every employee covered by the standards and that noncompliance may expose the employer to liability on a per-employee basis."
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BrooklynDodger(s) comment: Remarkably, the Bush-Chao OSHA has announced a policy of per instance violations of the PPE standard. This opens a door to forcing protections against chemicals for which there are no PEL's or even in compliance with PEL's.

Per instance citations are a logical escape from the "one size fits all" critique of OSHA enforcement. Large employers which create hazards expose many more workers to those hazards than small employers. The large employers have more knowledge and more resources to abate these violations, it makes no sense that OSHA be permitted to cite only one instance. Per instance citations should not be limited to egregious violations.

Now to PPE. The recent, but not so new, PPE standard requires a formal, documented risk assessment of each job assignment or exposure.

Protective equipment, including ... respiratory devices,... shall be provided, ... wherever it is necessary by reason of hazards of processes or environment, chemical hazards...encountered in a manner capable of causing injury or impairment in the function of any part of the body through absorption, inhalation or physical contact.

1910.132(d)(2) The employer shall verify that the required workplace hazard assessment has been performed through a written certification that identifies the workplace evaluated; the person certifying that the evaluation has been performed; the date(s) of the hazard assessment; and, which identifies the document as a certification of hazard assessment.

OSHA has for years had the authority to cite under the General Duty Clause where an exposure complies with a PEL, but the employer has knowledge that the PEL allows serious physical harm. (UAW v. General Dynamics Land Systems Division, http://www.altlaw.org/v1/cases/420579). OSHA has rarely cited this case and most people and inspectors believe the opposite ("Rarely" is a weasel word for not knowing if there is any instances where the case has been cited. The Dodger(s) know(s) of a case where an OSHRC ALJ opinion says the exact opposite of the DC Court of Appeals.)

The assessment would require attention to exposures with no PEL or in compliance with PEL. So, here's a scenario. A worker suffers significant and disabling pulmonary disease from MWF exposure or diacetyl. Both exposures are known in the industry to cause such serious physical harm from exposures within the PEL (for MWF) or where there is no PEL. The inspector checks the PPE risk assessment. Hazard ignored? violation. Employees not provided appropriate PPE? Violation for each. The multiple violations would generate penalties sufficient to motivate abatement.

Substance Abuse and DUI Arrests - A Lesson for New Year's Eve

Accident Analysis & PreventionVolume 41, Issue 1, January 2009, Pages 191-196

Trends in driving under the influence of drugs: A register-based study of DUID suspects during 1977–2007 Karoliina K. Ojaniemia, , , Tomi P. Lintonenb, c, Antti O. Impinena, Pirjo M. Lillsundea and Aini I. Ostamoa, c
aNational Public Health Institute, Department of Mental Health and Alcohol Research, Mannerheimintie 166, 00300 Helsinki, Finland

"Abstract
Our aim was to describe the incidence and trends of driving under the influence of drugs (DUID) and to examine the main drug findings and their trends in suspected DUID cases in Finland. A register-based study was conducted of all suspected DUID cases during 1977–2007. The data included 31,963 DUID offenders apprehended by the police with a positive finding for illicit/licit drug impairing driving performance. Toxicological results were analyzed in blood and/or urine specimens in one central laboratory. The incidence of suspected DUID cases increased 18-fold during 1977–2007. Most of the suspects were men (89.7%). However, the male–female ratio decreased from 13.9 to 7.3. The mean age decreased from 36.2 years in 1977 to 29.9 years in 2001 but has since reincreased. Most often found substances were benzodiazepines (75.7%), amphetamines (46.0%), cannabinoids (27.7%) and opioids (13.8%). Most common illicit drugs, amphetamines and cannabinoids, started to appear at the end of the 1980s. Poly-drug findings were common (77.1%). Suspected DUID cases have increased sharply after the introduction of a zero tolerance law, especially in regard to amphetamines. DUID is an increasing problem in Finland, and needs serious attention.

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BrooklynDodgers(s) comment: The Dodger(s) suggest(s) that driving while impaired is a health risk behavior, likely to have the same associations or causative factors as driving without a seat belt, speeding, smoking, and obesity. [Obesity is more an outcome than a behavior]. This explains the clustering of risk behaviors. This paper is less informative since it doesn't, as least in the abstract, address the likely greater prevalence of alchohol. Also, it addresses the Finnish cultural and law enforcement environment. Nevertheless, it points to a key contradition of the substance abuse literature. The most common drugs were prescription medications, even if not prescribed. And, half the drugs were amphetamines, which would be expected to improve performance, and which are medications prescribed for military pilots. Much that the Dodger(s) would like to criticize the draconian notion of "zero tolerance" policy, the Dodger(s) note several methods problems which undermine the conclusion of a growing problem.

Ash Hills and Arsenic

http://www.washingtonpost.com/wp-dyn/content/article/2008/12/29/AR2008122902511.html?sub=AR
High Arsenic Levels Found in Water Near Tenn. Ash Spill

By Kristin M. Hall Associated Press Tuesday, December 30, 2008; Page A03

KINGSTON, Tenn., Dec. 29 -- Some water samples near a massive spill of coal ash in eastern Tennessee are showing high levels of arsenic, and state and federal officials Monday cautioned residents who use private wells or springs to stop drinking the water...

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BrooklynDodger(s) comment: Maybe you don't think about coal ash much, the Dodger(s) certainly didn't. What is "clean coal" anyway? The starting point of musing was that whatever stuff is in the coal that doesn't form gaseous combustion products is left behind as ash. And the coal contains whatever was in the trilobites and trees of way back when. Since living creatures contain metals, burned creatures leave behind metal oxides, which yield a high pH. Remember saponification of fats to soaps by soda ash?

But a longer-than-intended wander through google yielded some background information. The Dodger(s) invite corrections and additions to this information.

Most of us know that arsenic is known to be a human carcinogen by inhalation and by ingestion in drinking water. IARC opines "There is sufficient evidence in humans that arsenic in drinking-water causes cancers of the urinary bladder, lung and skin." The full text of this monograph can be found at http://monographs.iarc.fr/ENG/Monographs/vol84/index.php In press accounts, this classification is characterized as "has been linked to cancer" which reads much weaker than an alternative which might be "arsenic in actual drinking water people drink has caused bladder, lung and skin cancer."

The EPA MCL limit for arsenic in drinking water is 10 ppb (10 ug/L) with a goal of zero. There appear to be no EPA limits for arsenic in soil; cleanup levels are triggered by site specific considerations. Most coal ash is fly ash, there is considerable effort to finding what to do with it, although it is not deemed hazardous waste. There's even a "flyashinfo" web site. Which contains some technical papers. http://www.flyash.info/2007/105wang.pdf

According to the site, most fly ash is <>

Formaldehyde - You Get What You Model For

Sensitivity Analysis of Biologically Motivated Model for Formaldehyde-Induced Respiratory Cancer in Humans

Annals of Occupational Hygiene 2008 52(6):481-495; doi:10.1093/annhyg/men038

Kenny S. Crump1,3,*, Chao Chen2, John F. Fox2, Cynthia Van Landingham1 and Ravi Subramaniam2
1 ENVIRON International Corporation, 1900 North, 18th Street, Suite 804, Monroe, LA 71201, USA2 National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Mail Code 8623D, 1200 Pennsylvania Avenue, NW, Washington, DC 20460, USA

"Conolly et al. (2003, 2004) developed biologically motivated models of formaldehyde carcinogenicity in F344 rats and humans based on a two-stage clonal expansion model of cancer. Based on the human model, Conolly et al. (2004) claimed that cancer risks associated with inhaled formaldehyde are deminimis at relevant human exposure levels. However, they did not conduct a sensitivity analysis to evaluate the robustness of this conclusion. Here, we present a limited sensitivity analysis of the formaldehyde human model. We show that when the control animals from the National Toxicology Program (NTP) studies are replaced with control animals only from NTP inhalation studies, estimates of human risk are increased by 50-fold. When only concurrent control rats are used, the model does not provide any upper bound (UB) to human risk. No data went into 20 the model on the effect of formaldehyde on the division rates and death rates of initiated cells. We show that slight numerical perturbations to the Conolly et al. assumptions regarding these rates can be made that are equally consistent with the underlying data used to construct the model, but produce estimates of human risk ranging anywhere from negative up to 10 000 times higher than those deemed by Conolly et al. to be ‘conservative’. Thus, we conclude that estimates of human risk by Conolly et al. (2004) are extremely sensitive to modeling assumptions. This calls into question the basis for the Conolly et al. claim of de minimis human risk and suggests caution in using the model to derive human exposure standards for formaldehyde"
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BrooklynDodger(s) comment: There's something up with formaldehyde at EPA. The Dodger(s) believe this activity responds to a TSCA Section 21 Petition by NRDC asking for a rule; EPA denied the petition but announced an assessment. Previously the Dodger(s) have noted the drastic contrasts between inhalation exposure limits by OSHA, NIOSH, ACGIH, and ATSDR, in the context of Katrina trailers and other domicilary exposures. EPA has not set a reference concentration for formaldehyde, having last published an assessment of formaldehyde in IRIS in 1991 which contains a drinking water limit and a cancer unit risk value.

The EPA 1991 (before IARC reclassified formaldehyde as "KNOWN" to be carcinogenic to humans) assessment was:

B1 (Probable human carcinogen - based on limited evidence of carcinogenicity in humans)

Weight-of-Evidence Narrative: Based on limited evidence in humans, and sufficient evidence in animals. Human data include nine studies that show statistically significant associations between site-specific respiratory neoplasms and exposure to formaldehyde or formaldehyde-containing products. An increased incidence of nasal squamous cell carcinomas was observed in long-term inhalation studies in rats and in mice. The classification is supported by in vitro genotoxicity data and formaldehyde's structural relationships to other carcinogenic aldehydes such as acetaldehyde. This may be a synopsis of the full weight-of-evidence narrative. See IRIS Summary.

Quantitative Estimate of Carcinogenic Risk from Oral Exposure Not Assessed under the IRIS Program.

Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure Inhalation Unit Risk(s) Extrapolation Method 1.3 x10-5 per ug/m3 Linearized multistage procedure, additional risk

The Dodger(s) will discuss this at a later time. You haven't heard the last from the Dodger(s) on formaldehyde (or anything else.) Staff from the Chemical Industry Institute of Toxicology (CIIT), now rebranded as the "Hamner Institute for Life Sciences," had published a risk assessment to compete with the EPA quantitative exposure response relationship. The publication above appears to represented an EPA alternative to the CIIT alternative to the EPA calculations. The key finding was that plausible alternative parameters to the CIIT parameters generated unit risks ranging from less than the CIIT estimate to 10,000 higher.

The Organization formerly Known as CIIT Gets Grant from EPA to Study Asbetos Toxicity

BrooklynDodger(s) comment: Vermiculate in Libby, Montana is a major concern for EPA, especially figuring out remediation in a town likely heavily contaminated. The Libby asbestos is amphibole, like crocidolite and amosite. Most asbestos to which people are and were exposed is a serpentine mineral, crysotile. Increased potency estimates for amphiboles relative to crysotile would much reduce the legacy risks and costs of asbestos. But also trigger greater cleanup efforts in Libby. In addition, estimates increasing the potency of long fibers and suggesting short fibers to be relatively impotent would reduce the legacy risks and costs of brake shoes.

Recently, EPA floated an "approach" to risk assessment that would greatly increase the relative potency of amphiboles and long fibers. The approach was rejected by the EPA Science Advisory Committee, for the second time.

The Dodger(s) will comment on the limited public health value of more mechanistic research on asbestos fiber types in future posts. For now, the Dodger(s) suggest that the more approapriate agency to receive this contract was the National Toxicology Program.


http://www.thehamner.org/docs/Press%20035%20-%20$2%201%20Million%20EPA%20Grant%20to%20Study%20Asbestos%20121908.pdf

The Hamner Institutes for Health Sciences Receives
$2.1 Million Asbestos Research Grant
Environmental Protection Agency Awards Organization Funding To Study Inhaled Vermiculite Fiber

"
The three-year study will include assembling an inhalation exposure system for the exposure of fibers to laboratory animals, conducting range-finding and definitive toxicity studies in rats, and analyzing fiber content of rat tissues following exposure. The study will be led by four key personnel at The Hamner: Darol E. Dodd, Ph.D., DABT; Owen R. Moss, Ph.D; Ed Bermudez, M.S., DABT; and Brian A. Wong, Ph.D."

Exposure to POP's Via Breast Milk

Lifestyle and polybrominated diphenyl ethers in human milk in the United States: A pilot study
Authors: Judy S. LaKind ab; Cheston M. Berlin Jr bc; Jennifer L. Stokes b; Daniel Q. Naiman d; Ian M. Paul b; Donald G. Patterson Jr e; Richard S. Jones e; Sarah Niehser e; Richard Y. Wang e; Larry L. Needham e; Matthew N. Lorber f; Andreas Sjdin e
Affiliations:
Toxicological & Environmental Chemistry, Volume 90, Issue 6 November 2008 , pages 1047 - 1054

"Polybrominated diphenyl ethers (PBDE) are a class of brominated flame retardants with some congeners having the ability to accumulate in body lipids. The incorporation of PBDE in consumer products found primarily in the indoor environment suggests that routes of exposure include inhalation of indoor air and contact with indoor dust. The purpose of this study was to test the hypothesis that lifestyle factors, and in particular the proximity and use of products likely to contain PBDE in the indoor environment, are primarily responsible for levels of PBDE found in human milk. Human milk samples were taken from two populations of lactating women in the same geographic region of the United States: one “typical” of US suburban lifestyle, and the other practicing a traditional Amish lifestyle, which excludes many modern amenities containing PBDE, such as computers and televisions. For a subset of the cohort, persistent organic pesticides and polychlorinated biphenyls (PCB) were also measured in human milk samples. Despite the small number of participants, there is evidence suggestive of Amish women having lower PBDE concentrations in their milk. In addition, the nonsignificant differences in levels of PCBs and pesticides between the two groups of women as compared to the significant differences in levels of PBDE suggest an important route of exposure for PBDE other than diet. Information prepared for study participants is provided to initiate a dialogue on how to best communicate biomonitoring findings to study participants and to the public in general.
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BrooklynDodger(s) comment: The object of this study was to detect exposure to brominated flame retardents. Humans are at the top of the food chain, so bioconcentration would be expected. Mobilization of POP's from lipid stores through the blood to human breast milk is also expected. Obviously the target population of infants is expected the most vulnerable. The paper suggests a human milk monitoring program may be helpful in tracking human exposure to POP's. Another finding less emphasized is that Amish lifestyle conferred no protection against PCB's and pesticides. >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Physical Activity and Breast Cancer - What About Work?

BrooklynDodger(s) comment: Very few chemicals have been associated with increased breast cancer. This is because most non-drug, non-hormonal agents have been found associated with cancer among workers with substantially higher exposure than the general population. However, there are relatively few women in such cohorts, and so little has come from these studies. Another reason may be inferred from this study. The study found that increased physical activity was associated with decreased breast cancer - a frequently observed effect which translates to a blame the victim tone in the standard cancer control literature ("You got cancer because you were lazy.")

Note that modest amounts of physical activity which conferred protection, "The most physically active group (who walked for 1 hour per day and exercised for 1 hour per week)" Compare that with standing and walking 10 hours a day, pounding steel on the assembly line. So women in industrial and construction occupations would be expected to present with a much reduced risk of breast cancer compared to the general population. Studies of industrial cohorts which might observe breast cancer rates close to expected should be considered studies finding an association between the exposure and breast cancer.

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Effect of Physical Activity on Breast Cancer Risk: Findings of the Japan Collaborative Cohort Study


Sadao Suzuki1, Masayo Kojima1, Shinkan Tokudome1, Mitsuru Mori5, Fumio Sakauchi5, Yoshihisa Fujino6, Kenji Wakai2, Yingsong Lin7, Shogo Kikuchi7, Koji Tamakoshi3, Hiroshi Yatsuya4, Akiko Tamakoshi7 for the Japan Collaborative Cohort Study Group
"Purpose: This study aimed to examine prospectively the association between physical activity and breast cancer risk in a non-Western population.
Methods: We analyzed data from the Japan Collaborative Cohort Study, which included 30,157 women, ages 40 to 69 years at baseline (1988-1990), who reported no previous history of breast cancer, and provided information on their walking and exercise habits. The subjects were followed prospectively from enrollment until 2001 (median follow-up period, 12.4 years). Breast cancer incidence during this period was confirmed using records held at population-based cancer registries. The Cox proportional hazards model was used to estimate the hazard ratio (HR) for the association of breast cancer incidence with physical activity.
Results: During the 340,055 person-years of follow-up, we identified 207 incident cases of breast cancer. The most physically active group (who walked for 1 hour per day and exercised for 1 hour per week) had a lower risk of breast cancer (HR, 0.45; 95% confidence interval, 0.25-0.78) compared with the least active group after adjusting for potential confounding factors. The inverse association of exercise on breast cancer was stronger among those who walked for 1 hour per day than those who walked for <1 p =" 0.042).">
Conclusions: Our analysis provided evidence that physical activity decreased the risk of breast cancer. Walking for 1 hour per day and undertaking additional weekly exercise both seemed to be protective against breast cancer, regardless of menopausal status or BMI. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3396–401)

Nanoparticles Penetrate the Intact Skin, Greater Penetration of Damaged Skin

BrooklynDodger(s) comment: Currently a prominent use of nanoparticles is nano sized titanium dioxide (an IARC 2B carcinogen) in skin treatments. Another post noted that these titanium dioxide particles could penetrate the olfactory epithelium and find there way the brain. Here's a study of silver nanoparticles (does anyone know what they might be used for?) penetrating the regular skin in a laboratory study.

This study should be considered hazard identification - at least as far as exposure goes. The next step in the NAS paradigm is dose-response assessment. We need more than two points - intact and damaged - and more than a single application in a laboratory system.

ToxicologyVolume 255, Issues 1-2, 8 January 2009, Pages 33-37

Human skin penetration of silver nanoparticles through intact and damaged skin

Francesca Filon Laresea, , , Flavia D’Agostina, Matteo Croserab, Gianpiero Adamib, Nadia Renzic, Massimo Bovenzia and Giovanni Mainad
"There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes.
Median silver concentrations of 0.46 ng cm−2 (range Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy.
We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

Nuclear Safety and Risk Assessment

BrooklynDodger(s) comments: As pressure mounts for new expansion of nuclear power, the risk assessment battle will resume. The canonical example of public "misperception" of risk is the often published table comparing risk from a nuclear accident to the risk from driving to the grocery store. For the purpose of this blog posting, the Dodger(s) won't address the overall topic.
However, this press account reminds us that any industrial process has all sorts of unanticipated ways it can go wrong... can go wrong... can go wrong....

Nuclear safety left hanging as crane dangled fuel rods
Michigan incident got warning but no fine
BY HUGH McDIARMID JR.FREE PRESS STAFF WRITER
March 18, 2006

"A 110-ton load of nuclear waste dangled for 55 hours above a cooling pool last October as two workers at a southwest Michigan nuclear power plant improperly manipulated a crane that had frozen, federal regulators concluded in a recent review of the incident

"...Under the NRC's worst-case scenario, if the suspended load had accidentally dropped, a fire could have ignited, leading to formation of a radioactive cloud. The cloud could have put thousands of people downwind of the plant -- all the way to Kalamazoo -- at risk of fatal radiation poisoning....

"Sidebar:
The scariest nuclear accident in Michigan was the 1966 partial meltdown of the Fermi 1 nuclear reactor near Monroe that inspired the 1975 book "We Almost Lost Detroit."...
Plant officials maintained that only 1% of the uranium fuel melted, but critics say the plant came close to a runaway reaction that could have killed people for miles around the plant.
No radiation was released, but the plant never returned to useful operation."

Human Ecology in a Declining Economy

BrooklynDodger(s) comment: Sometimes the source is not peer reviewed; this comes from the Detroit Free Press which is almost underwater like the car companies. The Dodger(s) has(have) seen coyotes in riverside Detroit (not the business district, but habited.) The near, or maybe total collapse of the Detroit auto industry exemplifies Chaos theory - moderate to small changes in an adverse direction may be recovered from, but a little push may crash the whole system. The system includes people living nearby the companies and their factories. Chaos also says that once a system crashes, it may never come back to where it was.

This applies to the wildlife around Detroit. Those who said let the companies fail suggest we live in a "dog eat dog" world. There's something else that eats dogs, in this case, coyotes.

The Dodger(s) didn't have time to compare sitesfor this, and, embarrassed by the notion of posting a wikipedia link, provide the following lecture notes

http://nature.berkeley.edu/~bingxu/UU/geocomp/Week8/Chaos.pdf


http://www.freep.com/article/20081221/NEWS05/812210387/?imw=Y

Coyotes clash with humans, small pets in Detroit suburbs
Trapping, shooting considered
BY BILL LAITNER • FREE PRESS STAFF WRITER • December 21, 2008


"Kim Sikand had seen coyotes in her Bloomfield Hills yard, and she had heard city advice to keep pets under watch...

http://www.michigan.gov/images/KenyonLIF_05038Coyote_23439_7.jpg

Diethanolamine Inhibits Brain Development When Applied to the Skin

Brooklyn Dodger(s) comments: DEA ought to be a 2B carcinogen, by skin application, although it's not, for reasons to be discussed in another post. The Dodger(s) interest in DEA relates to its presence in MWF's. But the heat around DEA which fuels mechanistic research is generated by the presence of DEA as an unwanted impurity in skin lotion. One theory is that liver damage and liver cancer in mice follow from choline depletion. Here we have an investigation of developmental disability from DEA applied to the skin.

The effect level in this study is 80 mg/kg/day for 10 days, with 60 mg/kg as a NOEL. The Dodger(s) will context this with the NTP bioassay in another post. So the uncertainty factors of 10 for acute to chronic, 10 for animal to human, and 10 for population variability would generate a RfD of 60 ug/kg/day as a default. [But, is 10 days acute or chronic? the fetus is sensitive for only 10 days or maybe only 1 day within the 10. but there's an effect at 60 mg/kg, just not significant. so maybe the real NOEL is 40]

Now comes a skin lotion, with 1.8 ppm DEA, likely an impurity in a diethanolamide-fatty acid condensate. [Still dirty after all these years?]. The 3 women dosed had plasma levels varying by 3-fold from top to bottom, with 5 nmoles/ml about the mean, compared to 1250 in the 80 mg/kg mice. A ratio of about 250 from the effect level. The Dodger(s) think this is too close.

Hazcomers take note.

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Dose Response Effects of Dermally applied Diethanolamine on Neurogenesis in Fetal Mouse Hippocampus and Potential Exposure of Humans

Corneliu N. Craciunescu, Mihai D. Niculescu, Zhong Guo, Amy R. Johnson, Leslie Fischer, and Steven H. Zeisel

Toxicol. Sci. 2009 107: 220-226;

http://toxsci.oxfordjournals.org/cgi/content/abstract/107/1/220?etoc

"Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline and alters brain development. We previously reported that 80 mg/kg/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. ... Timed-pregnant C57BL/6 mouse dams were dosed dermally from gestation day 7–17 with DEA at 0 (controls), 5, 40, 60, and 80 mg/kg body/day. Fetuses (embryonic day 17 [E17]) from dams treated dermally with 80 mg/kg body/day DEA had decreased neural progenitor cell mitosis at the ventricular surface of the ventricular zone ... Also, this dose of DEA to dams increased rates of apoptosis in E17 fetal hippocampus ... This dose of DEA resulted in accumulation of DEA and its metabolites in liver and in plasma. At doses of DEA less than 80 mg/kg body/day to dams, there were no differences between treated and control groups. In a small group of human subjects, dermal treatment for 1 month with a commercially available skin lotion containing 1.8 mg DEA per gram resulted in detectable plasma concentrations of DEA and dimethyldiethanolamine, [BrooklynDodger(s) comment: risk assessment conclusion implied but not justified] but these were far below those concentrations associated with perturbed brain development in the mouse."

Diesel Particulate - What Part of Probably Carcinogenic Don't You Understand?

BrooklynDodger(s) Comments: Diesel particulate matter is an IARC 2A carcinogen because there is "sufficient" evidence in laboratory studies, but human studies were considered "limited" by the last working group to take it up, in 1989. http://monographs.iarc.fr/ENG/Monographs/vol46/volume46.pdf Despite multiple studies among truck drivers and railroad personnel showing increased lung cancer, including some controlling for smoking, it wasn't enough to pull the trigger on "known." With some justice, it can be argued that there's lots of other junk in the air on the road, gasoline engine exhaust if possibly carcinogenic, there's some evidence for particulate air pollution being associated with increased community cancer. Attributing the excess cancer only to diesel can be criticized.

The study quoted here strengthens the evidence in people, but the wording points to an intermediate step. IARC evaluates "exposure circumstances," and mixtures in addition to particular agents. Maybe a step to consensus is to evaluate the exposure circumstance of truck driving or exposure to vehicle exhaust - evidence for carcinogenicity of these exposures ought to be sufficient.

Emissions from compressed natural gas engines should be bioassayed. Lighter in weight than diesel, but many nanoparticles.
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Environ Health Perspect. 2008 October; 116(10): 1327–1332.


Lung Cancer and Vehicle Exhaust in Trucking Industry Workers


Eric Garshick,1,2 Francine Laden,2,3,4 Jaime E. Hart,2,3 Bernard Rosner,2 Mary E. Davis,3,5 Ellen A. Eisen,6,7 and Thomas J. Smith3

src="http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif" border=0>Abstract


"Background. An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties.
Objectives. We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.
Methods. Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.
Results. Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk.
Conclusions. Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work."

Presence of Diethanolamine in currently used MWF confirmed, skin penetration observed to be predominant mode of exposure.

BrooklynDodger(s) comment: Finnish investigators compared the potential for skin absorption to that of ethanolamine aerosol in machine shops. The first finding was that diethanolamine (DEA) was present in the fluids. [NTP found clear evidence that diethanolamine causes liver cancer and liver disease in mice when applied to the skin. NIOSH found that an MWF caused liver pathology in mice when applied to the skin, likely from DEA content.] The investigators state that 100 times as much DEA was on the skin compared to that inhaled. There is no good quantitative way to estimate historical exposure to ethanolamines by skin absorption in MWF operation. A case of liver disease in a worker exposed to MWF may be due to DEA skin absorption, even if air levels are very low.

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Determination of Occupational Exposure to Alkanolamines in Metal-Working Fluids.

Annals of Occupational Hygiene. 51(2):153-160, March 2007.

Henriks-Eckerman, Maj-Len 1,*; Suuronen, Katri 2; Jolanki, Riitta 2; Riala, Riitta 2; Tuomi, Timo 2

Abstract: Overall exposure to alkanolamines in metal-working fluids (MWFs) in machine shops was studied by determining alkanolamines in air samples and in rinse-off samples from the hands of machinists. Methods for collecting airborne alkanolamines and alkanolamines absorbed to the skin of the hands were developed and tested. The exposure measurements were carried out in nine machine shops. After a 2 h working period the dominant hand of 37 machinists was rinsed with 200 ml of 20% isopropanol for 1 min in a plastic bag. Personal air samples were also collected during the 2 h working period onto acid-treated glass fibre filters. The filter samples were desorbed with methanol and analysed by liquid chromatography with mass spectrometric detection (LC-MS). The rinse-off samples were also analysed for alkanolamines by LC-MS. The median air concentration of monoethanolamine (EA) was 57 [mu]g m-3, diethanolamine (DEA) 64 [mu]g m-3 and triethanolamine (TEA) 6 [mu]g m-3. The workers' overall exposure to alkanolamines was estimated by calculating the amount in inhaled air and the amount on the skin. The median amount of EA on the skin of the dominant hand was 9-43 times the median amount in inhaled air during 2 h exposure. The corresponding ratio for DEA was 100 and for TEA 170. According to this study the exposure to alkanolamines occurs mainly through the skin. EA was the only alkanolamine with a noticeable inhalation uptake compared to the skin uptake. Total exposure to MWFs may be reduced by reducing skin exposure. The hand rinsing method can be used to assess the efficiency of protective gloves.