New substances added to HHS Report on Carcinogens

The U.S. Department of Health and Human Services today added eight substances to its Report on Carcinogens, a science-based document that identifies chemicals and biological agents that may put people at increased risk for cancer.

The industrial chemical formaldehyde and a botanical known as aristolochic acids are listed as known human carcinogens. Six other substances — captafol, cobalt-tungsten carbide (in powder or hard metal form), certain inhalable glass wool fibers, o-nitrotoluene, riddelliine, and styrene — are added as substances that are reasonably anticipated to be human carcinogens. With these additions, the 12th Report on Carcinogens now includes 240 listings. It is available at 12th Report on Carcinogens.

“Reducing exposure to cancer-causing agents is something we all want, and the Report on Carcinogens provides important information on substances that pose a cancer risk,” said Linda Birnbaum, Ph.D., director of both the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP). “The NTP is pleased to be able to compile this report.”

John Bucher, Ph.D., associate director of the NTP added, “This report underscores the critical connection between our nation’s health and what’s in our environment.”

The Report on Carcinogens is a congressionally mandated document that is prepared for the HHS Secretary by the NTP. The report identifies agents, substances, mixtures, or exposures in two categories: known to be a human carcinogen and reasonably anticipated to be a human carcinogen. A listing in the Report on Carcinogens does not by itself mean that a substance will cause cancer. Many factors, including the amount and duration of exposure, and an individual’s susceptibility to a substance, affect whether a person will develop cancer.

Once a substance is nominated by the public or private sector and selected for consideration, it undergoes an extensive evaluation with numerous opportunities for scientific and public input. There were at least six opportunities for public input on each substance. The NTP used established criteria to evaluate the scientific evidence on each candidate substance under review. The NTP drew upon the scientific expertise of several federal agencies, including the National Institutes of Health, Centers for Disease Control and Prevention, Agency for Toxic Substances and Disease Registry, U.S. Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Consumer Product Safety Commission, and Occupational Safety and Health Administration.

“The strength of this report lies in the rigorous scientific review process,” said Ruth Lunn, Dr.P.H., director of the NTP Office of the Report on Carcinogens. “We could not have completed this report without the significant input we received from the public, industry, academia, and other government agencies.”

A detailed description of each substance listed in the Report on Carcinogens is included in the new report.

Two known human carcinogens:

Aristolochic acids have been shown to cause high rates of bladder or upper urinary tract cancer among individuals with kidney or renal disease who consumed botanical products containing aristolochic acids. Aristolochic acids are a family of acids that occur naturally in some plant species. Despite a warning issued in 2001 by the U.S. Food and Drug Administration that advised consumers to discontinue use of any botanical products containing aristolochic acids, they can still be purchased on the Internet and abroad, and may be found as a contaminant in herbal products used to treat a variety of symptoms and diseases, such as arthritis, gout, and inflammation.

Formaldehyde was first listed in the 2nd Report on Carcinogens as a substance that was reasonably anticipated to be a human carcinogen, after laboratory studies showed it caused nasal cancer in rats. There is now sufficient evidence from studies in humans to show that individuals with higher measures of exposure to formaldehyde are at increased risk for certain types of rare cancers, including nasopharyngeal (the nasopharnyx is the upper part of the throat behind the nose), sinonasal, as well as a specific cancer of the white blood cells known as myeloid leukemia. Formaldehyde is a colorless, flammable, strong-smelling chemical that is widely used to make resins for household items, such as composite wood products, paper product coatings, plastics, synthetic fibers, and textile finishes. Formaldehyde is also commonly used as a preservative in medical laboratories, mortuaries, and some consumer products, including some hair straightening products.

Six substances reasonably anticipated to be human carcinogens:

Captafol was found to induce cancer in experimental animal studies, which demonstrated that dietary exposure to captafol caused tumors at several different tissue sites in rats and mice. Captafol is a fungicide that had been used to control fungal diseases in fruits, vegetables, ornamental plants, and grasses, and as a seed treatment. It has been banned in the United States since 1999, but past exposures may still have an effect on health.

Cobalt-tungsten carbide (in powder and hard metal form) showed limited evidence of lung cancer in workers involved in cobalt-tungsten carbide hard metal manufacturing. Cobalt-tungsten carbide is used to make cutting and grinding tools, dies, and wear-resistant products for a broad spectrum of industries, including oil and gas drilling, as well as mining. In the United States, cobalt-tungsten hard metals are commonly referred to as cemented or sintered carbides.

Certain inhalable glass wool fibers made the list based on experimental animal studies. Not all glass wool or man-made fibers were found to be carcinogenic. The specific glass wool fibers referred to in this report have been redefined from previous reports on carcinogens to include only those fibers that can enter the respiratory tract, are highly durable, and are biopersistent, meaning they remain in the lungs for long periods of time. Glass wool fibers generally fall into two categories for consumers: low-cost, general purpose fibers, and premium, special purpose fibers. The largest use of general purpose glass wool is for home and building insulation, which appears to be less durable and less biopersistent, and thus less likely to cause cancer in humans.

o-Nitrotoluene is listed because experimental animal studies showed tumor formation at many different tissue sites in rats and mice. o-Nitrotoluene is used as an intermediate in the preparation of azo dyes and other dyes, including magenta and various sulfur dyes for cotton, wool, silk, leather, and paper. It is also used in preparing agricultural chemicals, rubber chemicals, pesticides, petrochemicals, pharmaceuticals, and explosives. Workers in the United States are likely exposed to o-nitrotoluene through the skin or from breathing it during production and use. o-Nitrotoluene has also been detected in air and water near facilities that produce munitions, and near military training facilities.

Riddelliine has been found to cause cancer of the blood vessels in rats and mice, leukemia and liver cancer in rats, and lung tumors in mice. This botanical should not be confused with the drug Ritalin, prescribed for the treatment of attention deficit hyperactivity disorder. Riddelliine is found in certain plants of the genus Senecio, a member of the daisy family, grown in sandy areas in the western United States and other parts of the world. Some common names for Senecio plants are ragwort and groundsel. Riddelliine-containing plants are not used for food in the United States, and have no known commercial uses. However, at least 13 Senecio species have been identified that are used in herbal medicines or possibly as food in other parts of the world. Exposure in humans could result from eating or drinking herbal medicine or teas, honey, or foods contaminated by parts of Senecio plants or after consuming products from animals that have fed on the plants.

Styrene is on the list based on human cancer studies, laboratory animal studies, and mechanistic scientific information. The limited evidence of cancer from studies in humans shows lymphohematopoietic cancer and genetic damage in the white blood cells, or lymphocytes, of workers exposed to styrene. Styrene is a synthetic chemical used worldwide in the manufacture of products such as rubber, plastic, insulation, fiberglass, pipes, automobile parts, food containers, and carpet backing. People may be exposed to styrene by breathing indoor air that has styrene vapors from building materials, tobacco smoke, and other products. The greatest exposure to styrene in the general population is through cigarette smoking. Workers in certain occupations may potentially be exposed to much higher levels of styrene than the general population.

The Report on Carcinogens, Twelfth Edition, is prepared by the National Toxicology Program, an interagency program headquartered at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

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The NTP was established in 1978. The program was created as a cooperative effort to coordinate toxicology testing programs within the federal government, strengthen the science base in toxicology, develop and validate improved testing methods, and provide information about potentially toxic chemicals to health, regulatory, and research agencies, scientific and medical communities, and the public. The NTP is headquartered at the NIEHS. For more information about the NTP, visit http://ntp.niehs.nih.gov.

NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit  http://www.niehs.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Related Articles:

• Norway proposes to prohibit four hazardous substances in consumer products
• Submissions sought on Review of Organophosphate Insecticide Dichlorvos
• United Nations urged to ban Mercury Fillings

Every year in the United States, there are more than 1.2 million poison exposures among children younger than 6 years. In recent decades, household cleaning products have consistently been one of the leading sources of pediatric poisoning. A new study conducted by the Center for Injury Research and Policy of The Research Institute at Nationwide Children’s Hospital found that from 1990-2006, an estimated 267,269 children younger than 6 years were treated in U.S. hospital emergency departments for injuries attributable to household cleaning products. During the 17-year study period, researchers noted a 46 percent decrease in the number of injuries.

Data from the study, being released online August 2 and appearing in the September issue of Pediatrics, show that most of the household cleaner-related injuries were poisonings, with children ages 1-3 years accounting for the majority (72 percent) of the injuries. Bleach was the cleaning product most commonly associated with injury (37.1 percent). While approximately one-third of the injuries occurred through contact with the cleaning product, the more frequent means was ingestion (62.7 percent), and spray bottles were the most common storage container (40.1 percent).

“Interestingly, spray bottles were the only major storage source that increased over the study period,” said study lead author Lara McKenzie, PhD, principal investigator at the Center for Injury Research and Policy at Nationwide Children’s Hospital. “Although rates of household cleaner-related injuries from regular bottles and original containers decreased during the study period, spray bottle injury rates remained constant. This area is worthy of further research.”

The good news is that the number of injuries decreased almost by half during the study period, but the bad news is that there were still nearly 12,000 children younger than 6 years who suffered injuries from household cleaning products in 2006.

“Young children are curious about their surroundings and tend to explore their environment by putting things in their mouths,” said Dr. McKenzie, also a faculty member of The Ohio State University College of Medicine. “This general sense of inquisitiveness, combined with increased mobility, the ubiquitous nature of household cleaning products and the ease of accessibility, place young children at high risk of injury.”

Parents and caregivers must do their part to prevent childhood poisonings. According to Heath Jolliff, DO, associate medical director of the Central Ohio Poison Center at Nationwide Children’s Hospital, parents should store poisonous substances in locked cabinets, out of sight and reach of children.

“It’s important to only purchase cleaners with child-resistant packaging, keep all products in their original containers and properly dispose of leftover or unused products,” Dr. Jolliff, also a faculty member at OSU College of Medicine, said.

Parents should also know what to do if they suspect their child has come in contact with a poison. Dr. Jolliff advises to immediately contact the Poison Center at 1-800-222-1222 (this national number will direct callers to their local Poison Center), unless the child is unconscious, not breathing, or having seizures, in which case parents should call 9-1-1.

This is the first published study using nationally representative data to examine poisonings from household cleaning products among children younger than 6 years for an extended time period. Data for this study were collected from the National Electronic Injury Surveillance System (NEISS), which is operated by the U.S. Consumer Product Safety Commission. The NEISS dataset provides information on consumer product-related and sports and recreation-related injuries treated in hospital emergency departments across the country.

Reference:

Nationwide Children’s Hospital, New National Study Finds Decrease in Pediatric Injuries Associated with Household Cleaners Children younger than 6 years still at high risk of poisoning, Columbus, OH – 8/2/2010.

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Further Articles about Children’s Health:

• Oil Spill: Kids in the Gulf
• Pesticides in kids linked to ADHD- Attention-Deficit/Hyperactivity Disorder, study finds
• Our Planet – Our Children – How are your Children doing?
• EPA releases Guide to help Scientists understand Children Exposure to Pollutants
• Common Plastics Chemicals linked to ADHD Symptoms

Dioxins and similar compounds, such as dioxin-like polychlorinated biphenyls (PCBs), include a range of toxic substances which are formed by burning – e.g. through waste incineration or forest fires – and some industrial processes. Their presence in the environment has declined since the 1970s, following concerted efforts at the EU level.

Dioxins are found at low levels in many foods. They do not cause immediate health problems, but long-term exposure to high levels of dioxins has been shown to cause a range of effects, including cancer. Their persistence and the fact that they accumulate in the food chain, notably in animal fat, therefore continues to cause some safety concerns.

The highest average levels of dioxins and dioxin-like PCBs in relation to fat content were observed for liver and liver products from animals. The highest average levels in relation to total product weight were for fish liver and products derived from fish liver. In animal feed, the highest average levels were found in fish oil.

Overall, 8% of the samples exceeded the different maximum levels set out in EU legislation. However, some of these samples clearly originated from targeted sampling during specific contamination episodes. There were also large variations between different groups of food and feed in terms of the proportion of samples which exceed maximum levels.

The report concludes that no clear trend can be established regarding changes in background levels of dioxins and related substances in food and feed over time, as there were increases in some categories but decreases in others. Furthermore, occasional contamination episodes and a lack of information on which samples resulted from targeted or random sampling make it difficult to assess such trends.

The current EU method for measuring overall dioxin levels is based on toxicity values for different types of dioxins recommended by the World Health Organisation (WHO) in 1998. EFSA was also asked to assess the impact on total dioxin levels of using toxicity values set out in WHO recommendations from 2005, which downgraded the relative toxicity of certain types of dioxins. The report finds that using the new values would reduce overall dioxin levels by 14%, although the extent of this reduction was very different across food and feed categories.

Finally, the report recommends continuous random testing of a sufficient number of samples in each food and feed group to ensure accurate assessments of the presence of dioxins and dioxin-like PCBs.

Author; EFSA, EFSA publishes European overview of dioxin levels in food and feed, March 31, 2010

• Full Report
• Results of the monitoring of dioxin levels in food and feed
• European Commission – Food Contaminants – Dioxins and PCBs

WASHINGTON – The U.S. Environmental Protection Agency today released a user-friendly document to help risk assessors understand how children are exposed to pollution. The document, titled “Highlights of the Child-Specific Exposure Factors Handbook” serves as a quick-reference guide to the more comprehensive “Child-Specific Exposure Factors Handbook” published by EPA in 2008. It will serve as an additional resource for those who work on children’s health issues, which the agency has been highlighting during Children’s Health Month.

EPA developed the reference guide to provide important information necessary for answering questions about exposure through drinking water, breathing, and eating foods, such as:

• How much exposure to environmental pollutants might children get if they live or play near contaminated sites?
• How much dirt from a child’s hands might s/he inadvertently eat?
• How much of a child’s exposure to various pollutants might come from skin contact?
• Which age groups (childhood life stages) may inhale or ingest the most and thus may be at higher risks?

More information on the documents:

• http://www.epa.gov/childexpfactors/highlights
• http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=200445

Reference: EPA Releases Guide to Help Scientists Understand Children’s Exposure to Pollutants, Release date: 10/27/2009

This article aims to describe essential conditions and starting-points for the monetary evaluation of environmentally attributable diseases. Furthermore, a cost calculation within a scenario analysis is conducted for Germany. 

To calculate the costs of environmental health effects we chose a disease-specific perspective. The national statistics of the Federal Statistical Office and the World Health Report burden of disease estimates were used to identify the most important disease categories for Germany. Based on an extensive literature research in computerized databases and the publications of national and international institutions, available costs of illness studies for Germany as well as environmental attributable fractions (EAFs) were identified. Based on these data environmental health costs were calculated with a top-down approach. 

Direct and indirect environmental costs of illness add up to 15-62 billion euro (2006) per year depending on the specific scenario. From our results a tentative scheme is deduced of how the monetary environmental burden of specific diseases is composed and how it can be assigned to major environmental exposures and economic sectors which can be used in setting intervention priorities and evaluating intervention efficiency. 

Within this article, we were able to calculate environmental health costs for Germany based on available, easy to access data and deduce implications for environmental policy decision-making. However, there are restrictions in data quality, as the aetiology of some diseases with respect to environmental impacts is not very well documented and data has not been collected particularly for Germany. 

Reference:   Haucke F, Brückner U., First approaches to the monetary impact of environmental health disturbances in Germany, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Germany, Health Policy. 2009 Sep 8.

Information about some members (mainly TRPV1, TRPV3 and TRPA1) of the large group of receptors of the TRP ion channel family

I want to introduce you to some of the receptors of the TRP (transient receptor potential) ion channel family. Please keep in mind that I am not a scientist and that English is not my mother tongue.

There will be two parts. In the first part today you will find general information about several receptors of the TRP family and the role these receptors play in regard to environmental irritants and MCS. In the second part you will find a list of substances which are able to activate these receptors.

Information about different receptors of the TRP family

TRPV1

The most information can be found about the TRPV (vanilloid) subgroup and TRPA1.

The TRPV1 receptor is broadly expressed in all “port of entry” tissues (e.g., skin, gut, airways, conjunctiva) and the various cell types linings such tissues (i.e., keratinocytes, epithelia, endothelia, etc.). In addition TRPV1 receptors were found in various peripheral nonneuronal tissues (e.g., kidney, lung, testis, pancreas, spleen, liver, stomach, vascular smooth muscle, placenta, cornea, uterus, bladder). It exists in many areas of the CNS like hypothalamus, hippocampus, frontal cortex, motor neurons of the spinal cord and in CNS cells involved in inflammation (e.g. astrocytes, microglia). (Veronesi et al. (2006)

TRPV1 is gated not only by vanilloids such as capsaicin, but also by noxious heat, acidosis and intracellular lipid mediators such as anandamide, lipoxygenase products and various pro-algesic pathways.

If you read “vanilloid” it is likely that you are thinking of a piece of cake or vanilla ice cream. In addition to such a sweet food, vanillin can be found when paper becomes old (the smell of old books). But in contrast to your expectation vanilloids are substances, which are often hot and pungent like capsaicin in chillies. I am sure you know that burning sensation in your mouth if you have eaten something hot and spicy. This feeling of pain is caused by SP (substance P), which the TRPV1 releases together with neurokinin A [NKA], and calcitonin-gene-related-peptide [CGRP], which are leading to an inflammatory response.

In addition various cell types, including mast cells, epithelial cells, and immune cells, have been shown to release pro-inflammatory cytokines (e.g., IL1beta, IL6, IL8, and TNF) in response to SP, CGRP, and NKA. (Veronesi 2006)

After a while SP is used up and the result is that you will feel a reduction of pain (desensitization). Because of this mechanism capsaicin is sometimes used as a treatment in medicine.

The problem with this is, that damage or even the death of cells, mentioned in several articles, can take place:

“Cell death was characterized by cytoplasmic swelling, coalescence contents and eventual lysis” (Berkley Molecular Neurobiology Student Manuscripts- Term Paper Code 53)

“After using capsaicin, the inflammatory reaction and lipid peroxidation may affect cellular functions and lead to cell death.” (Richeux et al. 2000)

“Activation of the capsaicin receptor (VR1 or TRPV1) in bronchial epithelial cells by capsaicinoids and other vanilloids promotes pro-inflammatory cytokine production and cell death.” (Reilly 2005)

“We show that activation of the intracellular subpopulation of TRPV1 causes endoplasmic reticulum (ER) stress and cell death in human bronchial epithelial and alveolar cells.” (Thomas et al. 2007)

“In conclusion, the TRPV1 receptor is active in the brain microvasculature and has its permeability-increasing effect via substance P. It also plays a role in the immediate blood-brain barrierr disruption following ischaemia-reperfusion.” (Hu et al. 20005)

“Activation of TRPV1 excites sensory neurons and induces the accumulation of intracellular Ca2+. This results in excessive mitochondrial Ca2+ loading and subsequent mitochondrial disruption, leading to neuronal cell death.”(Kim 2006)

“We recently reported that cytochrome c release from damaged mitochondria and caspase-3 activation are required for TRPV1-mediated neurodegeneration in mesencephalic cultures.” (Kim 2006)

TRPV3

The TRPV3 receptor is another member of the TRPV family. It behaves in a similar way as TRPV1. It can be activated by substances like camphor, carvacrol and thymol.

In the article by Vogt-Eisele et al. 2007 terpenoids in essential oils, which are used cosmetically, were studied as agonists for TRPV3.

TRPA1

TRPA1 can be activated by allyl isothiocyanate, which you can find in mustard oil (cabbage, cress…) or by the thiosulfinate allicin (garlic and onions).

TRPA1, also plays an important role in modulating nociceptor excitability and neurogenic inflammation in the setting of tissue injury. Bradykinin is produced in response to tissue injury, inflammation and ischemia and it binds to the PLC-coupled receptors on sensory neurons. It causes acute pain through immediate excitation of nociceptors like TRPA1, followed by a longer sensitization of thermal and mechanical stimuli. This hypersensitization is produced through PLC-mediated potentiation of TRPV1. TRPA1 is often coexpressed with TRPV1. (Bautista et al. 2006)

TRPM2

Peroxynitrite and other reactive species induce oxidative DNA damage and activate poly(ADP-ribose) polymerase 1 (PARP-1).

Overactivation of PARP-1 depletes its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to functional impairment or death of cells, as well as up-regulation of various proinflammatory pathways (Pacher, Szabo 2008)

TRPM2 is gated by (PARP-1). (Pacher, Szabo 2008)

TRPM8

This receptor is responsible for sensing cool temperatures. If you eat menthol, it gives you a cool feeling, which is created by the activation of this receptor.

These receptors play a role in regard to environmental toxins and in MCS

I want to share now a few quotes in regard to sensitization of the receptors with you.

“In general, sensitization may be governed by a change in conformation status of the receptor or ion channel itself, rendering an enhanced activation state. Sensitization may further be governed by increased expression of functional receptors on the cell surface.” (Veronesi and Oortgiesen 2006)

“In particular, upregulation of TRPV1 is often produced after exposure to proinflammatory agents, thus suggesting the general hypothesis that under inflammatory circumstances, a ‘sensitized’ TRPV1 can be activated by agonist concentrations much lower than those tested under conventional experimental conditions.” (Geppetti 2004)

“Furthermore, activation by one ligand can potentiate the response to a second activator.” (Kauer 2008)

In several articles researchers of different teams looked at environmental irritants and their role in activation/sensitization of these receptors:

Toxicologists have reported an initiating role for TRPV1 in mediating airway inflammation (e.g., hyperresponsiveness, asthma) caused by chemical irritants and air pollutants (e.g., particulate matter, ozone, pesticides (Veronesi et al., 2001 )). Identifying this receptor as a common responder to multiple chemical toxicants could explain how diverse pollutants and inhaled substances produce the respiratory dysfunction associated with environmental contaminants. (Veronesi and Oortgiesen 2006)

In the article by Andre et al. (2008) is mentioned that unsaturated aldehydes (mainly acrolein and crotonaldehyde) in cigarette smoke stimulated TRPA1 and caused airway neurogenic inflammation.

Acrolein is present in tear gas, vehicle exhaust, and smoke from burning vegetation, including tobacco products. Acrolein can induce apnea, shortness of breath, cough, airway obstruction, and mucous secretion. It is also a toxic metabolite of cyclophosphamide and ifosfamide, chemotherapeutic agents widely used in the treatment of cancer, severe arthritis, multiple sclerosis, and lupus. (Bautista et al. 2006)

Shiba et al. (2009) found out that phthalate esters are able to activate TRPV1 and TRPA1 receptors.

Macpherson showed in 2007 that formaldehyde activates the ion channel TRPA1. In addition it was discovered that the endogenous aldehyde hydroxynonenal is able to activate TRPA1, too.

It is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress and it promotes acute pain, neuropeptide release, and neurogenic inflammation. (Trevisani 2007)

Cyclohexanone is known to activate TRPV1 and it is used as an intermediate in the production of nylon, fungicices, herbicides, paint thinners and lubricant oils. (Silver et al. 2006)

But the most important work was done by Pall and Anderson (2004). They investigated the role of many substances especially solvents and VOCs in regard to the TRP ion channels and they mention in their article 12 points, which provide the support that TRPVs plays a role in MCS. Here are a few examples:

• Chemicals, which stimulate the TRP receptors are similar to the diversity to chemicals in MCS.
• TRPVs increase NO and stimulate NMDA receptors.
• Substance P is increased on vanilloid stimulation and it is elevated in MCS
• Neurogenic inflammation is caused by the activation of TRPVs and it plays a role in MCS

Professor Pall describes the connection between the receptors of the TRP family, NO and the NMDA receptor as follows:

“The vanilloid receptor (TRPV1 or VR1), widely distributed in the central and peripheral nervous system, is activated by a broad range of chemicals similar to those implicated in Multiple Chemical Sensitivity (MCS) Syndrome. The vanilloid receptor is reportedly hyperresponsive in MCS and can increase nitric oxide levels and stimulate N-methyl-D-aspartate (NMDA) receptor activity, both of which are important features in the previously proposed central role of nitric oxide and NMDA receptors in MCS. Vanilloid receptor activity is markedly altered by multiple mechanisms, possibly providing an explanation for the increased activity in MCS”(Pall and Anderson 2004)

While I worked on this subject I had the feeling I looked through a keyhole. I was able to see some parts of the room in front of me, but other parts I was not able to see. I am convinced that during the next years more parts of the “room” will be discovered and we will get a bigger view in which in additional areas, these receptors play a role and maybe even more substances will be discovered by which these receptors are activated.

Author: Namid

References:

First I want to give you a few additional links to articles, which I found helpful:

Geppetti, P., et al. (2006). The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol. 2006 Mar 8;533(1-3):207-14.

Geppetti et al (2004).: Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. British Journal of Pharmacology (2004) 141, 1313-1320

If you want to read more about the role of these receptors in diseases I would recommend that you read Nilius et al.:Transient Receptor Potential Cation Channels in Disease. Physiol. Rev. 87: 165-217, 2007

It contains several good figures like: fig. 7 – TRPV1, fig.8 – TRPA1, fig. 11- respiratory tract.

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• Veronesi, B., Oortgiesen, M. (2006). The TRPV1 Receptor: Target of Toxicants and Therapeutics. Toxicological Sciences 2006 89(1):1-3
• Berkley Molecular Neurobiology Student Manuscripts. The cellular mechanism of capsaicin and its role as an excitatory neurotoxin – Term Paper Code: 53
• Richeux, F., Cascante, M., Ennamany, R., Sanchez, D., Sanni, A., Saboureau, D., Creppy,E. E. (2000). Implications of oxidative stress and inflammatory process in the cytotoxicity of capsaicin in human endothelial cells: lack of DNA strand breakage. Toxicology. 2000 May 19;147(1):41-9.
• Reilly, C. A., Johansen, M. E., Lanza, D. L., Lee J., Lim, J. O., Yost,G. S.(2005). Calcium-dependent and independent mechanisms of capsaicin receptor (TRPV1)-mediated cytokine production and cell death in human bronchial epithelial cells. J Biochem Mol Toxicol. 2005;19(4):266-75.
• Thomas, K. C., Sabnis, A. S., Johansen, M. E., Lanza, D. L., Moos, P.J., Yost, G. S., Reilly C. A. (2007). Transient Receptor Potential Vanilloid 1 Agonists Cause Endoplasmic Reticulum Stress and Cell Death in Human Lung Cells. J Pharmacol Exp Ther. 2007 June; 321(3): 830-838.
• Hu, D.-E., Easton, A. S., Fraser, P. A. (2005). TRPV1 activation results in disruption of the blood-brain barrier in the rat. Br J Pharmacol. 2005 October; 146(4): 576-584.
• Kim, S. R., Kim, S. U., Oh, U., Jin, B. K. (2006). Transient Receptor Potential Vanilloid Subtype 1 Mediates Microglial Cell Death In Vivo and In Vitro via Ca2+-Mediated Mitochondrial Damage and Cytochrome c Release. The Journal of Immunology, 2006, 177: 4322-4329.
• Geppetti, P., Materazzi, S., Nicoletti, P. (2006). The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol. 2006 Mar 8;533(1-3):207-14.
• Vogt-Eisele, A.K., Weber, K., Sherkheli, M. A., Vielhaber, G., Panten, J., Gisselmann, G., Hatt, H. (2007). Monoterpenoid agonists of TRPV3. British Journal of Pharmacology (2007) 151, 530-540
• Bautista, D. M., Jordt, S.-E., Nikai, T., Tsuruda, P. R., Read, A. J., Poblete, J., Yamoah, E. N., Basbaum, A. I., Julius, D. (2006). TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents.Cell Volume 124, Issue 6, 24 March 2006, Pages 1269-1282
• Pacher, P., Szabo C. (2008). Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol. 2008 Jul;173(1):2-13
• Geppetti, P., Trevisani, M. (2004). Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Br J Pharmacol. 2004 Apr;141(8):1313-20
• Kauer, J. A., (2008). TRPV1:hot new channels in the brain. Future Neurology Vol. 3, No. 5, Pages 507-510
• Shiba, T., Maruyama, T., Watanabe, T., et al. (2009). TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity. Journal of neuroimmunology
• Macpherson, L. J., Xiao, B., Kwan, K.Y., Petrus, M.J., Dubin, A.E., Hwang, S., Cravatt, B., Corey, D.P., Patapoutian, A. (2007). An ion channel essential for sensing chemical damage. J Neurosci. 2007 Oct 17;27 (42):11412-5 17942735
• Trevisani, M., Siemens, J., Materazzi, S., Bautista, D. M., Nassini, R., Campi, B., Imamach, N., Andre, E., Patacchini, R., Cottrell, G. S., Gatti, R., Basbaum, A.I., Bunnett, N. W., Julius, D., Geppetti, P. (2007). 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2007 August 14; 104(33): 13519-13524
• Silver, W. L. et al. 2006: TRPV1 Receptors and Nasal Trigeminal Chemesthesis. Chemical Senses 2006 31(9):807-812.
• Pall, M. L., Anderson, J. H., 2004. The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity. Arch Environ Health 59:363-375.

The disease MCS – Multiple Chemical Sensitivity (ICD-10 T78.4) is mentioned at the Thesaurus “Safety and Health at Work”, alphabetical Part, Status May 2009, as: 

Multiple Chemical Sensitivity (B02.19.00)     

At the systematic Part MCS – Multiple Chemical Sensitivity is found at the category B02:  

“Work related Disease and Occupational Disease/Disease”  

integrated in Part:  

• B02.19 Other Disease 
• B02.19.00 Multiple Chemical Sensitivity  

Chronic Fatigue Syndrome (CFS) is integrated analogue.  

MCS is not classified as a mental disease

To clear up occurring doubts, it is to point out that MCS – Multiple Chemical Sensitivity is not integrated into chapter B02.15: Mental diseases, Depression, Neurosis, Post traumatic Stress Disorder or psychosomatic diseases. 

Thesaurus “Safety and Health at Work”

The Thesaurus offers a quick overview on the broad group of themes “Safety and Health at Work”. It contains about 3 500 main keywords and is the joining of the keywords from the two previous Thesauri “Safety at Work” and “Occupational Medicine”. The Thesaurus is based on the practical work of the Library group, documentation at the content development and their research of technical literature. It is a tool for documentation.   

The Thesaurus is intended for all who search for literature about “Safety and Health at Work”. It is supportive for prearrangement of research inquiries at the data pool LITDOK and can be helpful for searching in topic related databases.  

Author: Silvia K. Müller, CSN – Chemical Sensitivity Network, July 23, 2009  

Reference:  Thesaurus „Sicherheit und Gesundheit bei der Arbeit“ Alphabetischer Teil, Systemischer Teil, Dortmund/Berlin/Dresden 2009. 

The Maine Department of Environmental Protection (DEP) and the Maine Center for Disease Control and Prevention (CDC) announce the publication of Maine’s List of Chemicals of High Concern. Publishing the list of about 1700 chemicals is the first step toward implementing Maine’s new Toxic Chemicals in Children’s Products law.

The law aims to make children’s products safer and less toxic. Maine DEP and CDC have taken the first step, which is to identify and list chemicals known to governments as causing cancer and other health concerns.

“Increasing public awareness of toxic chemicals and their presence in children’s products will promote the use of safer chemicals in Maine and move us toward our long term goal of protecting the public and the environment,” said DEP Commissioner David Littell. “We also hope this list will prove helpful to businesses, including manufacturers, as they work to improve the chemical safety of their products.”

The CHC list was compiled from existing government lists which identified chemicals that are known to pose specific health threats including those that cause cancer. Some of the commonly recognized chemicals on the list include: lead, mercury, formaldehyde, and bisphenol A.

“Far too often we are forced to confront the risks and benefits of chemicals in products only after we discover they are present in children’s bodies at levels of possible concern,” said Dr. Dora Anne Mills, State Health Officer and Director of the Maine Center for Disease Control and Prevention. “We need to be assured that children’s products are safe from toxic chemicals when they are put on the market. The Maine CHC list is an important first step toward that critical goal.”

In the past, Maine and other states have targeted specific chemicals or products. The CHC listing takes a more holistic approach – it sets up a process to, prioritize, access chemical information, and replace some of the harmful chemicals in children’s products. The law gives the state the authority to phase out the use of dangerous chemicals in children’s products when safer alternatives are effective and available at a comparable cost.

Next year, the DEP and CDC will begin to look more closely at these chemicals, the extent of their use, the level of exposure to children, and documented presence in the human body or environment. The law required the DEP to move at least two “priority chemicals” forward for further scrutiny and possible regulatory action.

Maine is one of several states to implement news laws to reduce toxic chemicals in consumer products. Maine is the first state to publish a List of Chemicals of High Concern.

• Maine’s List of Chemicals of High Concern
• Chemicals of High Concern, Complete List of about 1 700 Chemicals in pdf format

Reference:Department of Environmental Protection Maine, State Takes First Step in Protecting Children from Toxic Chemicals, Identifies Dangerous Chemicals, July 17, 2009

Today, WHO publishes its first guidelines on indoor air quality, addressing dampness and mould. (1) They are the result of a rigorous two-year review of the currently available science by 36 leading experts worldwide, coordinated by the WHO Regional Office for Europe. The authors conclude that occupants of damp or mouldy buildings, both private and public, have up to a 75% greater risk of respiratory symptoms and asthma. The guidelines recommend the prevention or remediation of dampness- and mould-related problems to significantly reduce harm to health.

“As people spend most of their daily lives in homes, offices, schools, health care facilities or other buildings, the quality of the air they breathe indoors is critical for their health and well-being,” says Dr Srdan Matic, Unit Head, Noncommunicable Diseases and Environment at the WHO Regional Office for Europe. “For the first time, these guidelines offer guidance to public health and other authorities on how to ensure safety and healthy conditions in buildings. We believe that this work will contribute to improving the health of people around the world.”

The book is the first in a series of WHO guidelines on indoor air quality. They are intended for worldwide use, to protect health under various environmental, social and economic conditions. Future publications addressing selected chemicals and combustion products are being prepared. Together, the guidelines will comprise the first-ever comprehensive evidence-based recommendations to tackle indoor air pollution, one of the major causes of death and disease worldwide.

Globally, about 1.5 million deaths each year, mostly among women and children in developing countries, are associated with the indoor combustion of solid fuels. In the European Union (EU) alone, combustion, chemicals from building materials and dampness cause an annual loss of over 2 million years of healthy life due to premature death or to chronic diseases, such as asthma and cardiovascular diseases.

In many EU countries, 20-30% of households have problems with dampness. Strong evidence indicates that this is a risk to health. In damp conditions, hundreds of species of bacteria and fungi grow indoors and emit spores, cell fragments and chemicals into the air. Exposure to these contaminants is associated with the incidence or worsening of respiratory symptoms, allergies, asthma and immunological reactions. Children are particularly susceptible. According to recent evidence, 13% of childhood asthma in developed countries in the WHO European Region could be attributable to damp housing.

Knowledge of indoor air pollutants is the key to enabling action to prevent related health effects and maintain clean air. Many of these actions are beyond the power of individual building users and occupants, and must be taken by public authorities. The guidelines recommend measures to ensure that buildings are well designed, constructed and maintained, and to make adequate housing and occupancy policies. Building owners are responsible for providing healthy workplaces or living environments, free of moisture and mould, by ensuring adequate insulation. Occupants are responsible for managing the use of water, heating and ventilation to avoid excess humidity.

“In the absence of clear evidence, building standards and regulations have not sufficiently targeted prevention and control of excess moisture. The new guidelines are essential, as they provide reference criteria for what constitutes healthy indoor air,” concludes Dr Michal Krzyzanowski, Regional Adviser, Noncommunicable Diseases and Environment at the WHO Regional Office for Europe, and the leader of the WHO project to draw up the guidelines. “More than 100 studies on the health effects of damp environments were reviewed in the preparation process. This body of evidence forms the basis of the guidelines and provides a solid foundation for action.”

Full Report: Indoor Air Quality Guidelines on Dampness and Mould

The Regional Office web site offers further information on air quality and health.

Reference: WHO guidelines on indoor air quality: dampness and mould. Copenhagen, WHO Regional Office for Europe, 2009, accessed 16 July 2009.

The Centers for Disease Control and Prevention announced today the launch of the Web-based Environmental Public Health Tracking Network, a surveillance tool that scientists, health professionals, and – for the first time – members of the public can use to track environmental exposures and chronic health conditions.

“The ability to examine many data sets together for the first time has already resulted in faster responses to environmental health issues. We believe the Tracking Network holds the potential to shed new light on some of our biggest environmental health questions,” said Howard Frumkin, M.D., M.P.H., DrPh., director, of CDC’s National Center for Environmental Health.

The web-based tool unites vital environmental information from across the country, including air and water pollutants and information for some chronic conditions, including asthma, cancer, childhood lead poisoning and heart disease into one resource.

While scientists know exposures such as air particle pollution and lead contribute to illnesses, many environmental and health connections remain unproven since detailed health and environmental data existed in separate silos until now.

“The Tracking Network is the foundation we need to make better environmental health decisions and help prevent chronic illnesses, such as asthma, cancer, and heart disease,”said Michael McGeehin, Ph.D., director, Division of Environmental Hazard and Health Effects of CDC’s National Center for Environmental Health.

CDC funds projects in California, Connecticut, Florida, Maine, Maryland, Massachusetts, Missouri, New Hampshire, New Jersey, New Mexico, New York, Oregon, Pennsylvania, Utah, Washington, Wisconsin, and New York City.

To date, their projects have led to 73 public health actions to control potential illnesses from environmental exposures. For example, the Utah Department of Health received a call from a citizen concerned about cases of cancer in his neighborhood. In the past, a similar call would have prompted a study that would have taken up to a year to complete, with most of that time spent waiting for data. In less than a day, the Utah Tracking Program was able to let this resident know that the likelihood of cancer in his area was no greater than in the state as a whole.

Massachusetts ranks third in the United States for prevalence of asthma. When Massachusetts Tracking staff conducted asthma surveillance and indoor quality assessments in schools, a significant association between mold/moisture and the prevalence of asthma was found. Based on tracking data, Massachusetts staff are working with school officials to correct mold/moisture problems and to enact policy changes for reducing mold and moisture in schools.

In March 2009, CDC received additional funding from Congress to expand environmental public health tracking to five more locations. Awards will be made and announced later this summer. Over time, CDC hopes to expand the Tracking Network across all 50 states, and track additional environmental hazards and health conditions to build a more complete picture of environmental public health.

CDC’s Tracking Network is the result of collaboration with 17 local and state health departments; federal partners, including the National Aeronautics and Space Administration, the National Cancer Institute, the U.S. Environmental Protection Agency and the U.S. Geological Survey; and organizations including the American Public Health Association, Association of State and Territorial Health Officials, Council of State and Territorial Epidemiologists, National Association of County and City Health Officials, National Environmental Health Association, National Association of Health Data Organizations and the National Association for Public Health Statistics and Information Systems.

For more information please visit the Tracking Network at www.cdc.gov/ephtracking

Watch the YouTube video at http://www.youtube.com/user/CDCStreamingHealth

Reference: U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, July 7, 2009

Photo: CDC, James Gathany