New National Study Finds Decrease in Pediatric Injuries Associated with Household Cleaners Children younger than 6 years still at high risk of poisoning

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

The European Food Safety Authority (EFSA) has published an analysis of the levels of dioxins and related substances in food and animal feed. The report, which was prepared by EFSA’s Data Collection and Exposure unit, is based on over 7,000 samples collected by 21 European countries between 1999 and 2008. EFSA was asked by the European Commission to evaluate dioxin contamination levels in relation to maximum levels which have been set for different categories of food and feed in the EU in order to protect consumers.

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.