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.