Monday, December 5, 2016

American Association of Poison Control Centers

Lindsay Pasquale
Blog
American Association of Poison Control Centers
The American Association of Poison Control Centers duty is to help prevent and treat poison exposures. They are available at all times of the day, every day, and to contact them the number is 1-800-222-1222. The service is open to anyone seeking information, and to help. In 2014 there were 663,305 calls regarding prevention, safety, education, administrative, and caller referral.

The poison center Managing Directors mostly are PharmDs or RNs with American Board of Applied Toxicology (ABAT) board certification in clinical toxicology. There is a lot of specialized training involved. Poison center managing directors are responsible for patients care information service operations, clinical education, and staff instruction. Poison control centers are highly trained and knowledgeable.

Poison exposure causing death in five year olds or younger were mostly coded as “unintentional” and those over 12 years old were mostly “intentional”. Children five and younger typically don’t know right from wrong, it is very dangerous for them to be near any type of poison. For example, cleaning material stored in cabinets, if it’s not locked or put away children have easy access to it. By the age of 12, kids should know better and know what could be potentially dangerous. The children younger than three years old were involved in 35.6% of exposures and children younger than six years old are accounted for about half of all human exposures, 47.7%. Most of the human exposures were acute cases. One and two year olds are most likely to get poisoned, which isn’t much of a surprise knowing how that age group tends to put everything they can get a hold of in their mouth. This leads to ingestion, the consumption of a substance this normally taken through the mouth into the gastrointestinal tract, which is the major pathway to being poisoned. Children do not know any better so it is crucial to limit the exposure.

I experienced poison as a child when I was about five years old. I was with my family watching the firework show at a festival on the fourth of July. The glow sticks quickly grabbed my attention and I have quite a few around my neck and wrist. The night ended shortly when one broke open in my mouth due to chewing on it, even though my mother told me not to. I immediately told my mom what happened and began to wash my mouth out with water until we got home. She called poison control and I wasn’t the only child that did this that night. They said I would be fine and to keep rinsing my mouth out. This was a perfect example of how easy it is for children to poison themselves.

The reason for human exposure was mostly unintentional, but also with unintentional general, therapeutic error, and unintentional misuse. Children under five years old was unintentional while most fatalities in adults 20 years old or older we intentional.


Analgesics, also known as pain killers create the largest percentage of calls. There are different forms of analgesics such as, narcotic and non-narcotic. For adults, overdose and poisoning in result of painkillers are the most common calls.   

   













Dose/Response Relationship

Lindsay Pasquale

Blog
Dose Response Relationship

The dose response relationship describes the change in effects on some sort of organism caused by different levels of exposure, or doses, to a stressor, usually a chemical, after a certain exposure time. This could apply to individuals or a population. Dose response helps determine safe and hazardous levels and dosage. It generally depends on the exposure time and exposure route. A dose response curve is used to relate the magnitude of the stressor which includes, the concentration of the pollutant, amount of drug, temperature, intensity of radiation, to the response of the receptor.

There are two types of dose response curves, one describes the graded responses of an individual to varying doses of the chemical and one that describes the distribution of responses to different doses in a population of people. The dose is represented on the X-axis and the response is represented on the y-axis. Threshold is an important aspect of dose response relationships. The threshold is the magnitude or intensity of that must be exceeded for a certain reaction, result, or condition to occur. The human body is able to take some toxic insult and still remain healthy. It’s important to identify a level of exposure to a chemical at which there is no effect to determine thresholds when possible. It’s based on acute responses, such as death, which is more easily determined. Chemicals that cause cancer or other chronic responses are more difficult to determine. When the threshold is difficult to determine toxicologists look at the slope of the dose response curve to give them information about the toxicity of a chemical.

Exposure to poisons can be intentional or unintentional, the effects of the exposure to poisons vary with the dose, or amount of exposure. The measurements used for expressing levels of contamination in the environment are usually parts per million (ppm), or parts per billion (ppb). Those are extremely small quantities. Another commonly used measures of toxicity is the LD50, the lethal dose for 50 percent of the animals tested of a poison, and is usually expressed in milligrams of a chemical per kilogram of body weight (mg/kg). A chemical with a large LD 50 is practically nontoxic, a chemical with a small LD50 is far more dangerous. The danger or risk of adverse effect of chemicals is mostly determined by how they are used, not by the toxicity of the chemical itself.

The more potent the poison is, the less it will take to kill, the less potent the poison is, the more it takes to kill. The potency of a poison is a measure of its strength compared to other poisons. It is often compared using signal words such as danger, warning, or caution. It can also be expressed in categories such as highly toxic, moderately toxic, slightly toxic, or nontoxic.


The threshold limit value (TLV), is the airborne concentration of the chemical expressed in ppm, that produces adverse effects in workers exposed for five days per week, eight hours per day. The TLV is usually set to prevent minor toxic effects (skin or eye irritations). 



  


Phase I and II Biotransformation

Lindsay Pasquale

Blog
Phase I and II Biotransformation

Phase I of metabolism is the introduction of a pair of modification or functional group in a drug molecule such that it becomes more polar. There are different types of Phase I metabolism reactions; oxidation, reduction, and hydrolysis. First, oxidation is the introduction of OH enzymes; mixed function oxidase, monooxygenases, cytochrome, association with reductase enzyme, in other words contains NADPH. Examples of oxidative enzymes are Flavin containing monooxygenases; nucleophilic atoms. Secondly, alcohol dehydrogenases; alcohols to aldehydes and ketones. Lastly, aldehyde dehydrogenases; which are aldehydes to carboxylic acids. Reduction interacts with the reducing agents, Azo- and Nitro-reductions can be catalyzed. This process happened by the enzymes of intestinal flora. And also by cytochrome P450, usually known as the oxidizing enzyme, has the capacity to reduce xenobiotic under low anaerobic or oxygen conditions. Reduction participates in the role of intestinal microbial flora in biotransformation. Hydrolysis is a chemical reaction of a compound with water, usually resulting in the formation of one or more compounds. Epoxide Hydrolase (EH) is detoxifying enzyme for epoxides, it’s the formation of diols. Epoxide can be present in many tissues; epoxides are electrophilic which tend to bind to proteins or to nucleic acids. The role of EH in biotransformation of benzoapyrene is the inactivation, and the conversion of benzoapyrene to tumorigenic diol epoxide.

The chemical role of Phase II reactions in biotransformation is the process of an organic acid, acetyl, or methyl group is conjugated to the molecule at a preexisting functional group or at a functional group acquired in phase I biotransformation. Phase II includes; glucuronidation, sulfation, conjugation with glycine, conjugation with glutathione, acetylation, and methylation. Glucuronide conjugation is the acid from glucose, that reduces toxicity and sometimes produce carcinogenic substances. Excretion in the kidney or bile depending on conjugate size. This process includes xenobiotics and also endogenous substances. Sulfate conjugation has the ability to decrease toxicity, it is readily excreted by urine. The most common sulfo group is sulfotransferase, the transferring of enzymes that catalyze the transfer of a sulfo group from a donor molecule to an acceptor alcohol or amine. Lastly in the sulphate conjugation, PAPS limits the pathway. Acetylation is the water solubility of parent molecule and their excretion. It masks the functional group of parent from getting involved in conjugations. Methylation reaction makes slightly less soluble. It masks available functional groups, different types include; O-methylation, N-methylation, and S-methylation.


Phase I is the parent drug that is altered by introducing or exposing a functional group. Drugs that are transformed by the reaction of this phase usually loose pharmacological activity. Phase I reactions convert inactive, prodrugs to biologically active metabolites. Reaction products have the possibility to be directly excreted in the urine, or react with endogenous compounds o form water soluble conjugates. Phase II is a parent drug that participates in conjugation reactions that form covalent linkage between a parent compound functional group and glucuonic acid, sulfate, glutathione, amino acid, an acetate. The organ for biotransformation is the liver, but other organs participate in metabolism.





Sunday, December 4, 2016

IEUBK Model

Lindsay Pasquale

Blog
IEUBK Model

The Integrated Exposure Uptake Biokinetic (IEUBK) model is commonly used to estimate blood lead concentrations of children who have been exposed. The model calculates the probability that the child’s blood lead concentration will exceed the selected level of concern. This model can be used as a risk assessment tool. It can be useful for remediation strategies for lead in the human environment. The purpose of this model is to predict the likely blood lead distribution for children given the exposure to lead at the site, and the probability that children exposed to lead in that environment will have blood lead concentrations exceeding a health- based level of concern, according to EPA. The IEUBK model has previously been used by the Environmental Protection Agency as one of its methods for developing the National Ambient Air Quality Standard for lead and the National Primary Drinking Water Regulation for lead.

Validation is important, there are many factors to which makes something valid. To determine that, the model is biologically and physically plausible and consolidates the best available data. The model uses numerically accurate, and the accuracy of the computer codes have been verified. Lastly, the IEUBK model provides useful comparisons of model output with real world data.

The IEUKB model is structured so that the environmental concentration blood lead relationship in children is established through four distinct components: exposure, uptake, biokinetics, and blood lead distributions. The four model components just stated are designed to run as distinct but interrelated modules according to NCBI. The exposure/intake dose is expressed in micro-grams of lead per day, all based on media specific lead concentrations and consumption rates; cubic meters of air inhaled per day, grams of soil ingested per day, liters of water per day. The uptake component estimates the transfer of lead through the body, the gastrointestinal tract or lungs to the blood in micro-grams per day in children. Now the biokinetic component, which estimates the transfer of absorbed lead between blood and other vital tissues and its elimination through excretory pathways. In addition, the outcomes are calculated in various time fractions for the period of 0 to 84 month old children. The probability distribution component produces graphic illustration of the probability exceeding blood levels over the level of concentration.

The model is a product of many years of development within the US EPA. This is a tool for making accelerated calculations and recalculations of a complicated set of equations that include a extensive number of exposure, uptake, and biokinetic parameters. Lead is one of the most common toxic chemicals found at Superfund sites. EPA’s data shows that lead is among the most frequently used contaminant in the scoring of the sites with the Hazard Ranking Systems. The IEUKB model results can be used as a useful tool to assist in determining site specific cleanup levels.


I think this is a very useful tool for lead exposures. It’s frightening knowing how destructible it can be to children and how easy it can be to get exposed to high levels. It’s all around us even when we think it’s not. 






Wednesday, November 30, 2016

Biological Poisons

Lindsay Pasquale

Blog
Biological Poisons

Poisons are harmful to living organisms. The famous saying “the dose makes the poison” relates to this very well because we are able to handle a certain amount of a substance but there is a point to where it becomes poisonous. That’s why we have standards by Occupational Safety and Health (OSHA) agency or Environmental Protection Agency (EPA), if a company is working with a poisonous substance there is a standard of how much you are able to be exposed before it becomes harmful. Some poisons are manufactured by humans, others such as biological poisons are produced by bacteria, fungi, protists, plants, and animals.

There are three different ways to get exposed by poisons; absorption through the skin, inhalation into the lungs, and ingestion in the gut. Our skin has an important job of forming a barrier against many poisons, but it provides a route of entry for liquids. Inhalation provides a route of entry into the bloodstream for volatile molecules. There are some enzymes and acids that enable some ingestion poisons from entering. After exposure, most poisons toxic effects come quickly.

Treatment is available but not guaranteed for every poison. Antidotes is a common treatment available for a few poisons. Treatment focuses on removing the poison from the body and maintain respiration and circulation until the effects are reduced as the compound excretes over time.

The major agricultural chemicals are pesticides, which include insecticides, herbicides, fungicides, fumigants and rodenticides. Herbicides is a chemical which is commonly used to kill plants. The potential of this chemical to produce toxicity in humans is low. A high dose of this can cause muscular and neurological symptoms. Warfarin is an anticoagulant drug used as a rodent poison. Originally, it was a drug to treat thromboembolism, a disease caused by blood clots. The restriction caused by blood clotting by warfarin can lead to internal bleeding. Since it can induce internal bleeding, it is also used as rodenticide. Alar, is used as a plant growth regulator to improve the appearance and shelf life of apples. But the use of alar has decreased because of the harms it may cause. There were concerns that it may cause tumors in children who eat the apples.


General air pollutants include sulfur dioxide, nitrogen oxides, and carbon monoxide. Sulfur dioxide is an acidic pollutant that irritates the respiratory tract. If it irritates the throat, it will cause a harsh cough and may result in a shortness of breath, lung edema, or pneumonia. Nitrogen oxides are oxidizing pollutants; it can also cause respiratory irritation. It tends to be more irritant to the lung rather than the upper respiratory tract. Lastly, carbon monoxide is an asphyxiating pollutant that binds to hemoglobin more strongly that oxygen. Tissues lack oxygen which result in many toxic effects. The human brain is especially sensitive to lack of oxygen, in result most of the symptoms are neurological. Asphyxiation is the term that describes lack of oxygen, which is what carbon monoxide is. 







Environmental Pollutants

Lindsay Pasquale

Blog
Environmental Pollutants

Pollution is the contamination to the natural environment that can have harmful effects. Environmental pollutants have become a real problem once the industrial revolution took off. Environmental pollution happens when the environment cannot process or neutralize harmful by products created by humans, poisonous gas emissions for example. This is extremely important because of the negative effects pollutants has on the earth like clean air and clean water.

Technology facilitated by businesses has become one of the main causes of deterioration of natural resources. Think of when you are driving, the semi-truck in front of you has black smoke pouring out of it pipes. You look to your right and see smoke stacks with huge smoke clouds above them, and a chemical plant is right next to the river. Does that worry anyone these days? We see environmental pollutants in front of our eyes every day. Business take a part in this by division of labor, cheaper production cost, overproduction, overconsumption, over pollution.

Pollution is increasing every year at a high rate, the five basic types of pollution is air, water, soil, noise, and light. Air is said to be the most harmful type of pollution in our environment. China is suffering bad from bad air quality due to coal combustion and other factors. They are hardly able to see in front of them, it looks like a constant area of smoke or fog. Air pollution can be caused by multiple sources; trucks, buses, cars, trains, Sulphur dioxide, carbon monoxide, or nitrogen oxides. It can be a leading factor in lung cancer, asthma, allergies, or any other breathing complications. Chlorofluorocarbons (CFC), is released from common house hold items like refrigerators, air conditioners, deodorants, and insect repellant which is slowly damaging the atmosphere and depleting the ozone layer leading to global warming.

Waste products released into bodies of water such as lakes, rivers, or oceans has deeply affected the marine life. Industries are not the only source of polluting these areas, humans are a huge participator as well. Humans pollute water by garbage, ashes, or any household items. You will find that in some rural areas people will bathe, cook and clean in the same water, making the quality even worse. Water pollution can indirectly pollute soil by runoff and leaching ground water.

Noise pollution includes the noise of aircrafts, cars, buses, trucks, loud speakers, industry noise, and are all extremely harmful to the environment. Motor vehicles are responsible for almost all of the unwanted noise worldwide.

Soil pollution leads to damaging farms and the crops grown on them. Acid rain, polluted water, fertilizers and many more are the cause of this. Chemical are released by spill or underground storage take leakage which release heavy contaminants.


I feel that environmental pollution is escalating very quickly and changes aren’t being made to help. Everyone is used to their everyday lifestyle and people aren’t realizing the harm they are actually doing. Businesses only care about money and not many seem to care about how badly they are polluting the air. I can only see it getting worse in the future and eventually it will catch up to us.





Cancer

Lindsay Pasquale

Blog
Cancer

Cancer is a huge topic of research and discussion in today’s world. Cancer is the process of when the body’s cells begin to divide without stopping and spread into surrounding tissues. The human body is made up of trillions of cells and cancer is capable of starting anywhere. When cancer begins to develop, cells become more abnormal, old or damaged cells survive when they should die, and new cells form when they are not supposed to. The extra cells divide without stopping and could form growths, also known as tumors. There are many cancers that form solid tumors, but cancers of blood such as leukemia’s, generally do not create solid tumors. Cancerous tumors can spread into or invade nearby tissues. The tumors grow and some cells break off and travel to different places in the body.

Cancer is a genetic disease that is caused by changes in genes that control the way our cells function, including how they grow and divide. Genetic changes that cause cancer can be passed down through generations. It can also occur in someone lifetime by certain exposures. Some factors that cause cancer include exposure to, chemicals in tobacco smoke, or radiation such as ultraviolet rays from the sun. The three main types of genetic changes that lead to cancer are proto-oncogenes, tumor suppressor genes, and DNA repair genes. These can be known as the “drivers” of cancer.

Metastasis is the process by which cancer cells spread to other parts of the body, and metastatic is when cancer spreads from where it first started in the body by traveling through the lymph system. Metastatic cells generally look the same as the original cancer cell under a microscope. Treatment isn’t always guaranteed to save a life, but it can prolong the lives of some people. The goal of treatment for metastatic cancer is to control the growth or to relieve symptoms caused by the cancer. This tumor can cause severe damage to a person’s body and affect how it functions.


The three stage process of carcinogenesis consist of Initiation, Promotion and Progression stages. The first step is Initiation, which involves damage to the genome. It can be caused by damaged DNA, or damages to chromosomes. The driver of this step is oxidative stress, but other types of damaging events are capable of occurring. The second stage Promotion, is a long process that starts with one damaged cell that has a growth advantage. The two key aspects to this stage is that it is a stage of cellular growth, and of progressive genomic damage to these multiplying cells, making them unstable. It is driven by chronic inflammation, which contributes to the growth of a tumor. The last stage, Progression, is characterized by karyotypic instability and malignant growth. Molecular targets during this process include; proto-oncogenes, cellular oncogenes, and tumor suppressor genes. Many of these genetic changes have been identified in the developing process of colon cancer. The genetic material of the tumor is more fragile and prone to addition mutations.