The Social Economic Implications of a Gasoline Crisis

The Social Economic Implications of a Gasoline Crisis Free Online Research Papers Background Gasoline has been around for ages and is the driving force for much of the world. Gasoline is a mixture of hydrocarbons, although some contain significant quantities of ethanol. In its early days, gasoline was used as a cleaning agent and also as a treatment for lice. Gas became really important once the world started to get into the automobile and aviation period. Some of the first uses of gasoline in automobiles originated during the wars of the early 1900’s and is used everywhere in today’s age. Purpose The purpose of this report is to talk about the economic and social problems that are arising from the recent spike in gasoline prices. Also, it discusses what people can do to help fight against the continual rise in the cost of fuel. Methodology The internet is a tremendous source to use to gather information on a topic, and it proved extremely helpful in obtaining ideas on the problem being discussed in this report. The New York Times online, Wikipedia, Fox News online, and other databases were used to find out valuable information on the topic at hand. Significance Since gasoline is the driving force of the world, it is extremely important to keep and maintain the price of fuel at a reasonable level so that people can afford to drive their automobiles. II. Rising Gasoline Prices The number one reason for the sudden spike in gasoline prices can be easily contributed to the supply and demand curve. The demand for gasoline is up more than ever now, while the supply from the major companies in OPEC is not. According to some sources, the non OPEC countries’ supply of crude oil is dwindling, which is bad for the prices because they are not producing very much oil. This leads to a near monopoly in the oil production factor. Cheap oil, which runs around $60/barrel, may be gone. This summer the average price of a barrel of oil was around $120/barrel. This is a giant leap, a 200% increase, but it really isn’t as bad as it seems. A $120 barrel of oil is still a smaller fraction of the GDP than it was in the 1980’s. Even though many think that this price will shut down the entire world with their energy usage, they are in essence wrong. A major problem with the continual rise in fuel prices is its effect on the average American. The rising cost is putting a drain on a family’s money that could be used for entertainment. Most families live in more rural areas in the suburbs and have to drive a significant distance to travel to work. These long drives put a large drain on their gas tanks. This causes them to spend twice as much as it used to just to travel to work. This may not be as big of a problem as it seems, but these same parents are not getting a raise from work to make up for this deficit. They are not able to do they things as a family that they used to. Another factor that arises from the higher gas prices is the larger cost for the farmers to harvest their crops. A lot of people would not even think about this. They don’t look to the farmers as the producer of all of the items at the grocery store. The cost of fuel is a major factor in how much profit the farmer will make off of the crops that he or she raises. The farmer spends so much money to run their tractors, combines, semis, and trucks. A farmer that was recently interviewed stated that it was going to cost him over $20,000 more this fall to harvest his crops than it did the year before. The higher cost to harvest the crops leads to a direct impact on the cost of the products at the store. Companies have to pay more now to get the same amount of produce that they received originally. Not only does the produce cost more, but the cost of transporting theses goods is rising too. This leads to a direct price hike on the goods at the store. People wonder why they are paying more to go to the grocery than before and don’t understand it. They don’t see that the rise in fuel prices is accountable for a majority of the price increase. This leads to even more spending on families to provide the same food for them to eat. People are spending more money and not getting any more out of it. Not only do the rising gas prices put a damper on families, but it also hurts all transportation in general. Schools also have to spend more money just to drive their buses to pick up students from home, drive to athletic events, and also academic events. High gas prices hurt public transportation as well. They have to spend more to fill up their tanks just like everyone else. For them to keep making their same profits they have to raise the price of fares for citizens to travel with them. A person just can not expect to get the same services as before for the same price when the companies have to pay higher prices for fuel. If they were to do this, they would lose a significant amount of money. This in effect can lead them to going bankrupt after an extended amount of time. The same thing can be said about the airline industry and also tourist attractions. Their costs to operate continue to grow leading them to charge more for a plane ticket to help cover the costs. This then leads to people wanting to not travel as much, which in effect makes those companies lose the revenue that they are used to getting. With the loss of people traveling, the companies have to lay off more people all of the time to try and keep their profits up. II. Lowering Gas Prices There is some hope in sight for everyone. In the couple of months leading up to the election the gas prices have fallen significantly. This is a great relief to many people around the world. Lowering gas prices is a savior to many people. This will ultimately lead to folks having more money in their wallets. In the world today, this is a great thing with the credit crisis going on. So many homes have been foreclosed on due to financial means. This probably isn’t a solution to the problem, but it is a great start. Having more money will allow people to pay off these bills instead of not paying anything at all. The biggest help would be to lower income families and to small family-owned farms. These groups are the people just barely getting by as it is. With the increase in the gas prices it was putting an even larger strain on their already low incomes. Now they are taking a sigh of relief, at least for now. This lower fuel costs will possibly keep them afloat long enough until the government can get the prices under control. III. Who Is At Risk The bad thing about this dilemma is that it affects almost everyone in the world who uses an automobile for anything. Even if you do not use a car or truck for anything it will affect you in same way or another. Any person who drives a car is affected by the soaring gas prices. Whether you drive a long distance or just to the library. It is costing more and more to drive a vehicle. It is affecting many students here at Morehead State University too. Since this campus is like a suitcase college, students packing up and leaving every weekend to go home, it is putting a pinch on their pocketbooks as well. This in effect can actually be better for the campus and surrounding restaurants. With more kids staying around, it leads to them having more business on the weekends. Students will more than likely go out to these companies rather than sitting in their dorms all weekend. The rising gas prices can actually have a good effect on larger cities and metropolitan areas. If less people are out there driving, it will reduce traffic. This is a good thing resulting from the dilemma. With less traffic there is going to be a better chance of having fewer wrecks. Another benefit to less cars being on the road is pollution. There will be less exhaust fumes going up into the atmosphere. This is a great thing for the environment. IV. Conclusion The rising cost of gasoline is a major concern for the US and the World. Recent hikes in the cost of crude oil are having a tremendous impact on everyone. The group that is most vulnerable according to some is the farming industry. Everything that a farmer does with his farm has some use of gasoline involved, whether it is filling up their family cars or to filling their tractors and combines with diesel fuel. Diesel fuel costs around one dollar more per gallon than regular gasoline. People don’t think about all of the factors in the farm that involves gas and diesel fuel. If they are paying more to harvest their crop, then they will have to get more in return on their crops. This leads to a trickle effect onto all of the goods one will buy at the grocery store. As long as the prices stay high then it will be harder and harder for people to live in their comfortable bubble that they are used to living in. Gas prices do not affect only a small portion of society; it affects all. V. Recommendation The hike in gasoline prices has made many think of ways to reduce the impact of the problem. Here is a list of things that are currently happening to help fight the fuel price dilemma. 1. Hybrid cars are being produced and sold now more than ever before. A hybrid car is a basic car that has two different engines. It has the normal gasoline engine and also an electric motor. The hybrid car will run off of the electric motor as long as it is charged. Once the battery runs out it automatically switches over to the gas engine. A good thing about this is that once the gas engine takes over, it begins to charge the electric motor back to running capacity. A bad side to the hybrid car is that it costs significantly more than the average gas powered car, nearly double the price in some instances. It is not the best solution to the problem, but it is a start. 2. Another solution to the rising gas prices is more fuel efficient cars. Most of the big auto makers offer a car that can get 35-40 mpg. The problem with this is that most of these cars are a lot smaller and do not have the large capacity that the SUV owners are accustomed to. 3. A third solution is bio fuels. These are a whole different type of fuel. These include bio-diesel, hydrogen, and vegetable oil. A good thing about these fuels is that they are cheaper to run and also help the environment. They burn much cleaner than a normal gas powered car or truck. BIBLIOGRAPHY Alternative Fuel. Wikipedia. 16 Dec. 2006. 18 Nov. 2008 http://en.wikipedia.org/wiki/Alternative_fuel Ashton, Peter K. (2007). The method behind endless gasoline price spikes. Nieman Watchdog. niemanwatchdog.org/index.cfm?fuseaction=background.viewbackgroundid=187 Dunn, Phillip. Hybrid CarsPros and Cons. Physorg. 19 Jan. 2006. 16 Nov. 2008 physorg.com/news10031.html. Krauss, Clifford. (2008). Rural US Takes Worse Hit as Gas Tops $4 Average. The New York Times Online. nytimes.com/2008/06/09/business/09gas.html?_r=1scp=15sq=gasoline%20crisisst=nyt Lawinski, Jennifer. OPEC Cuts Oil Production in Move to Boost Prices. FoxNews. 24 Oct. 2008. 15 Nov. 2008 . McKay, Steve. High Fuel Prices Effects on Farming. Telephone interview. 10 Oct. 2008. Why Are Gas Prices So High ? ZFacts. 3 Dec. 2007. 15 Nov. 2008

Why do teens use self-injury as a coping mechanism Research Paper

Why do teens use self-injury as a coping mechanism - Research Paper Example It is a fact that as the materialism and modernism are increasing at a fast face all over the globe, the probability of self-injury is also mounting at an astounding pace in the teens. Myriad critical reasons form the bedrock of the self-abusing tendency in teens and a complex and intricate meshwork of crude realities needs to be scrutinized for identifying the major factors. These factors should explain the reason why more and more teenagers are readily seeking refuge in self-injury mechanism. People are oblivious to many distressing realities concerning this issue and this paper is basically an effort to highlight the relation between problems faced by teenagers and increased tendency of self-abusing. Facts and discussion presented in this paper are basically meant to illuminate the reality of the claim that â€Å"more and more teenagers are using self-injury as a coping mechanism because they are unable to relate their aggravated problems to their parents, peers, or teachers beca use of poor self-esteems, low morals, and continuous feelings of guilt and shame.†... It is an unequivocal fact that depression is highly capable of paralyzing one’s thinking, self-assessing, and comprehending abilities. Therefore, one finds oneself eventually trapped in a tight spot where one can neither hear any voice from the outside world that is normal nor translate the inner rushed and psychic emotions that are abnormal into something that could be understood by the people surrounding that person. An increased number of teenagers are selecting self-harm as a way of emotional projection in the hope of coping with horribly bizarre feelings of numbness, shame, regret and for punishing themselves for certain past failures. 3. Inability of parents and teachers to help teenagers increases self-harm incidence: Self-harm is a horrendous and powerful reality that affects all teenagers irrespective of social, racial, ethnic, or economic differences. It is an issue of concern around the globe that what majorly makes most of the distressed and disappointed teenagers seek refuge in self-harm in spite of the presence of parents at homes and teachers at schools. Research suggests that teenagers engage in self-destructive behavior because they find it increasingly difficult to relate their gross problems with their parents as the depression intensifies. With ever-heightening materialistic approach, most of the parents are unable to share more time with their families due to which, teenagers find it impossible to verbally communicate the nature of their problems in the short time their parents spare them. Nearly same is the scenario experienced by such depressed and anguished teenagers at the schools, where owing to increased cultural diversity and number of students, teachers are unable to relate to all the students

Integration of Third Country Nationals in the EU Essay

Integration of Third Country Nationals in the EU - Essay Example In the last 20 years the issue of migration of third world citizens to the European countries has gained particular importance and the member states of the European Union have shown special concern to the matter. The first such move to address the matter was taken in the early 1990's with the treaty of Amsterdam which was first such move of the European Council taken in order to safeguard the social and political rights of third country nationals within the Europe. Such a move along with the ongoing efforts in trying to curtail the immigration in the Europe and tightening the Immigration and Asylum policies was conceived by many observers a stride towards a new culture that will be tolerant, supportive and nondiscriminatory towards the immigrants. Consequently the European Council met in 1999 and drafted a set of procedures at Tampere that guaranteed political rights and a treatment to the third world citizens that would be analogous to EU nationals. The main aim of the conference was to design an integrated policy for the entire European Union. Despite these efforts to homogenize the policies regarding the assimilation of the third world national a number of imperative decisions regarding the employment and other important economic and social aspects were left with the member states and this marked for the insufficiency of the measures to a great extent. One of the factors underlining the varying responses amongst the Europeans has been the d iscrepancy in the level of exposure to the immigrants. Certain have developed a great deal of deal of acumen regarding the issue through continuous interaction with the immigrant inflow for over a long time as compared to these nations a few of the EU member states have only lately been faced with immigration. This factor has resulted in a wide variety of approaches to find a resolution to the matter. As the percentage of the non-Europeans increases and with the every chance of further enhancement in the number the need for a regulated and uniform effort becomes more than significant. Moreover to eliminate the possible threats of discrimination, social exclusion, xenophobia and racism it is extremely vital to make a concerted effort to develop an effective set of policies and procedures regarding the integration of the third country inhabitants. What is Integration This has been subject that has been dealt with respect to a number of principal subject areas including sociology, mathematics and a number of other sciences. Often it has been defined as a term but very seldom has it been looked upon as a concept. Integration as a concept in the context of this subject has been defined as a dynamic, multidimensional process that incorporates mutual socioeconomic, political, legal and cultural accommodation by all immigrants and residents of Member States of the European Union. The basic aim behind the introduction of the phenomenon is to assimilate a universal culture within Europe and to train the third world nationals in the local language, norms, values and to develop them as a permanent fragment, notwithstanding of the color, of the European Society. Importance of Integration to the EU member states Democracy and equality have been popular slogans of the West in the latter part of the 20th century. Realizing that equal contribution by all parties is at the heart of democracy and that

Transformational leadership on World health care Essay Example for Free

Transformational leadership on World health care Essay Introduction   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Transformational leadership can be defined and utilized based on specific or relative circumstances in many varied ways. For one, it can be assessed as the task of simply increasing the efficiency of everyone through a scheme of excellence for the whole company or the improvement of the morale of an individual employee. The main assumption behind this approach is that when employees of a certain company or organization are working their tasks efficiently, the amount and quality of work done are proportionally affected. In essence, employees that are more efficient translate into far greater options and larger benefits. The correlation is thus an important aspect in the leadership skills of the heads of various companies and organizations.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   For the most part, transformational leadership can be used as a tool not only in analyzing the crucial aspects of world health care but also in directly addressing the cases that shape the totality of the events related to the broad scope of global health care. The complexities involved in the cross-continental management and maintenance of the multitude of interrelated functions.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The task of meeting the multiple health care services across the different parts of the world that direly need immediate action calls forth an approach whereby the functioning of the wide number of health care service providers are efficiently met. Transformational leadership, following its basic principle, offers means in which the tasks required in addressing world health care are met. Noting further that transformational leadership aptly disperses the capabilities of the employees and, consequently, the different departments or institutions that comprise the whole of the company, the application of this approach on the various issues that are involved in the global arena of health care may eventually help alleviate the global challenge attached to world health care. A look into transformational leadership   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Transformational leadership, in essence, signifies the role of the â€Å"leader† in directing the rest of his or her subordinates in a fitting manner that will bring about favorable results to the functioning of every employee, department, and of the whole company in the process. However, the apparent effect of the role of the leader on the subordinates in the company can be further observed and analyzed from a closer examination on what makes a leader able to affect his subordinates apart from the boss-subordinate relationship (Antonakis House, 2001).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   One aspect that separates transformational leadership a cut above the rest is that it defines the extent to which a leader is seen as charismatic to his subordinates. The core principle behind this is that leaders should treat their subordinates or employees as individuals who are also capable of thinking for themselves, or individuals who are intellectually stimulating (Tichy Devanna, 2001).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   By treating the lower â€Å"ranks† or departments of the company as entities capable of actually affecting the intellectual direction of the company, the employees will not merely serve as passive elements in the upbringing of the company but as active elements capable of pouring into that intellectual basin their knowledge on the affairs of the company.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The result will be that the efforts of the leader in guiding the direction of the company will be amplified since the employees are treated in a manner in which they are involved in the critical processes. Moreover, a good leader will bring about a heightened sense of life into the company. The role of transformational leadership in world health care   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   World health care has been a primary concern among the international community for the past few years. Many factors are attributed to the growing concern over the issues that are directly related to the problems that beset world health care.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Among the various countries that are in deep need of health care, those that belong to the third-world countries are most notable. Inasmuch as these countries lack the internal capacity to finance and support a growing demand for health care, these nations also have a relatively low means in achieving at least good health for a small fraction of the population. A very limited number of infrastructures and programs that are aimed at addressing the health care issues of these nations amplify the drastic situation even more.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   This is the point wherein the international community has resorted to measures that will seek to address the current health issues that beset the citizens of countries suffering from low-health maintenance. For the most part, the international community has joined efforts in seeking out the best possible means in resolving these global health issues. The consequent effect to this is the creation of various international institutions that operate on the local levels of various countries.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Since the operations of these global institutions are tilted on a multitude of local areas, it is apparent that a number of workers are seen to be handling these local operations. In this light, the role of a transitional leadership is needed to take its shape.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   By having a transitional leadership in the management of all the affairs taken by the various institutions, the possibility of having a full line of efficient institutions can take place. That is, by treating all the employees who will handle the tasks relative to the specific institutions in these international health offices as individuals capable of contributing to the think-tank process, the process will be further stimulated. These individuals, as partakers in the critical thinking process, are further empowered and acquire a higher role in the global effort of resolving world health care issues.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   On the local level, these working individuals can be further guided according to the tasks by relegating a leader whose charisma gives positive effects to the working attitude and philosophy of the employees. Thus, the implementation of health policies from these various international institutions becomes an easy and efficient task in the case where employees have little or no defiance to the implementation of the tasks. Conclusion Far more importantly, transitional leadership allows the development of the employees in terms of their personal growth and in their working attitude. It contributes the international efforts in resolving the issues that beset world health care inasmuch as the international community operates on the local level or in the localities with poor health conditions, especially in communities belonging to the third-world countries. References Antonakis, J., House, R. J. (2001). Transformational Leadership. In B. J. Avolio F. Yammarino (Eds.), Transformational and Charismatic Leadership (pp. 3-66): JAI Press. Bhargava, S. (2003). Transformational Leadership: Value Based Management for Indian Organizations: Sage Publications Pvt. Ltd. Ginter, P. M., Duncan, W. J., Sappington, A. A., Swayne, L. E. (2005). Strategic Management of Health Care Organizations (5 ed.): Blackwell Publishing Incorporated. Porter, M. E., Teisberg, E. O. (2006). Redefining Health Care: Creating Value-Based Competition on Results (1 ed.): Harvard Business School Press. Tichy, N. M., Devanna, M. A. (2001). The Themes, The Protagonists, The Transformational Drama. In Transformational Leader (2 ed., pp. 8): Wiley.

The Evil of Richard the Third :: essays research papers

The Evil of Richard III Shakespeare Richard III was a traitor, a murderer, a tyrant, and a hypocrite. The leading characteristics of his mind are scorn, sarcasm, and an overwhelming contempt. It appears that the contempt for his victims rather than active hatred or cruelty was the motive for murdering them. Upon meeting him he sounds the keynote to his whole character. " I, that am curtailed of this proportion, cheated of feature by dissembling nature, Deform'd, unfinish'd sent before my time Into this word scarce half made up"( 1.1.20-23) The first scene of the play begins with a soliloquy, which emphasizes Richard's physical isolation as he appears alone as he speaks to is audience. The idea of physical isolation is heightened by his references to his deformity such as "rudely stamped ....Cheated of feature by dissembling Nature, deformed unfinished". "( 1.1.21-22). This deformity would be an outward indication to his audience of the disharmony from Nature and viciousness of his spirit. As he hated "the idle pleasure of these days" and speaks of his plots to sent one brother against another, Richard seems socially apart from the figures around him, and perhaps regarded as an outsider or ostracized because of his deformity. His separation his family is emphasized when he says "Dive, thoughts down to my soul"(1.1.41) when he sees his brother approaching. He is unable to share his thought with his own family as he is plotting against them. Thus, we are given hints of his physical, social and spiritual isolation which is developed throughout the play. But despite these hints, he still refers to himself as part of the House of York, shown in the repeated use of "Our" The task which Shakespeare undertook was to mold the hateful constitution of Richard's Moral; character. Richard had to contend with the prejudices arising from his bodily deformity which was considered an indication of the depravity and wickedness of his nature. Richard's ambitious nature, his elastic intellect, and his want of faith in goodness conspire to produce his tendency to despise and degrade every surrounding being and object, even as his own person. He is never sincere except when he is about to commit a murder. "therefore, since I can not prove a lover, To entertain these fair well spoken days, I am determined to be a villain".As a villain Richard must be heartless, he can not let his emotions interfere with his actions.

Historical Development in the Field of Toxicology

Historical Development in the Field of Toxicology And Mechanisms and Factors Responsible for the Entrance of Toxicants in the Human body and their Harmful Effects Jorge D. Rebolledo Columbia Southern University Abstract The purpose of this paper is to make a short historical reference in the field of Toxicology and how this area of science has develop starting from centuries ago until our present. It is also the intention of this paper to explain how the toxics enter our body, how they are absorbed and the mechanisms responsible for that. Introduction As stated by E. Monosson, some define Toxicology as the study of toxic materials, including the clinical, industrial, economic, and legal problems associated with them. Although toxicology—as a formally recognized scientific discipline—is relatively new (with major developments in the mid-1900s), the science itself is thousands of years old. Consider the potential results of early trial and error experiences of hunter-gatherers for whom identifying a toxic plant or animal was a life or death situation. Some of the most poisonous substances known today are naturally produced chemicals including ricin from castor beans or tetrodotoxin from the puffer fish. Early humankinds’ careful observations of such plants or animals with toxic characteristics as frogs, containing curare, were put to use not only for avoidance of toxic substances but for weaponry as well. Many naturally-derived poisons were likely used for hunting, as medicinal (the Egyptians were aware of many such toxic substances as lead, opium and hemlock as early as 1500 BCE). Use extended eventually to political poisonings as practiced, for example, by the early Greeks and Romans. With time, poisons became widely used and with great sophistication. Notable poisoning victims include Socrates, Cleopatra, and Claudius. One of the more interesting stories resulting from a combination of both ancient history and current toxicological research, is the story of King Mithridates, king of Pontus (120-63 BC) who according to toxicology legend was so afraid that he might be a casualty of political poisoning, is said to have concocted a potion from a great number of herbs for his own consumption. It is believed he understood that by consuming small amounts of potential poisons, he might protect himself from any would-be poisoner. That is, he believed in the effectiveness of hormesis. Apparently, his plans worked so well that he gained a name for himself as one so mighty he could not be killed. Unfortunately, it is said that when circumstances were such that he desired to kill himself, he was unable to do so by ingesting poison and had to be run through by a sword instead. Whether or not the story is true, it has led current day scientists to speculate upon the ingredients of his potion. It is believed that some herbs that he may have used, for example, St. Johns Wort could truly have contributed to detoxification of some other poisons. Recent studies have demonstrated that St. Johns Wort (often used as an herbal remedy) can increase the metabolism or breakdown of certain drugs and chemicals. This early story of toxicology relates a very important concept—that all animals have some kind of intrinsic ability for detoxifying a number of naturally-occurring toxicants in small doses (so that, in some cases low doses of chemicals may pass through the body without causing harm. From this we derive the concept of a chemical threshold), and that these processes can be altered by exposure to other chemicals. The question remains as to how adept animals, including humans, are at detoxifying many of the newer industrial chemicals or mixtures of industrial or industrial and natural chemicals. Additionally, it is well known that in some cases, detoxification of chemicals can produce even more toxic compounds. Pre-Industrial Toxicology As declared by E. Monosson, as humans sought to better understand natural compounds that were both beneficial and harmful to them, there was very little if any clear understanding of the fundamental chemical nature of substances. That is, there was no connection between the ‘extract’ and ‘essence’ of a poisonous plant or animal and any one particular chemical that might cause toxicity. In fact, an awareness of chemistry in its modern form did not occur until around the mid to late 1600s. Paracelsus, a physician from the sixteenth century and one of the early â€Å"Fathers of Toxicology† believed that all matter was composed of three â€Å"primary bodies† (sulfur, salt, and mercury). Yet, Paracelsus also coined the now famous maxim of the newly emerging discipline of toxicology: â€Å"All substances are poisons, there is none which is not a poison. The right dose differentiates a poison from a remedy. † (Paracelsus, 1493-1541) This phrase and Paracelsus’ name are committed to memory by hundreds of new toxicology students each year and has become the ‘motto’ of toxicology. Interestingly, if one takes Paracelsus at face value, it appears that in this quote he was referring to substances which served as potential remedies but could be poisonous if taken in high enough concentrations. Most of us are aware of the fact that overdosing can turn remedies to poisons, even with such apparently innocuous drugs as aspirin and Tylenol. Another branch on the toxicology family tree that developed in the sixteenth century, along with the study of drugs and the use of chemicals in hunting and warfare, was occupational toxicology. As humans learned how to remove and exploit such materials as coal, and metals and other minerals, occupational exposures to these chemical substances (and chemicals produced incidentally) resulted. Scientists eventually recognized the linkages among illnesses and exposures to these compounds. Some of the first reports of occupational illness, or diseases caused by activities related to specific occupations, can be found in literature from the mid- to late-1500s. Early occupational observations include the ill effects from lead mining and madness caused by mercury exposure (for example, the saying â€Å"mad as a hatter† was attributed to the common use of mercury in the hat felting process). Later, in the 1700s, Bernardino Ramazzini is credited with bringing to light diseases of tradesmen, including silicosis in stone workers and lead poisoning. In the late 1700s, Sir Percival Potts made one of the more famous observations in toxicology, linking an occupational exposure (in this case soot in chimney sweeps) to cancer of the scrotum. At this point we have discussed the pre-Industrial Revolution developments in toxicology, that were primarily devoted to the study of such naturally-occurring toxicants as the polyaromatic compounds contained in soot and heavy metals, and such toxins as botulinum toxin produced by the bacterium Clostridium botulinum. Toxicology and the Chemical and Industrial Revolution The chemical/Industrial Revolution of the mid-19th century released many naturally-occurring chemicals into the environment in unprecedented amounts. Also, it produced and released new substances unlike any that had existed in the natural world. With the production and use of these chemicals, and the need to protect humans from the toxic effects of industrial chemicals, toxicology eventually evolved to include its modern day branches: pharmacology, pesticide toxicology, general toxicology, and occupational toxicology. Towards the mid-late 20th century, environmental toxicology was developed to specifically address the effects on both humans and wildlife of chemicals released into the environment. A notable difference among the branches of toxicology is that pharmacology, pesticides and even occupational toxicology primarily have focused on the effects of relatively high concentrations of single chemicals. This compares to the relatively low concentrations of several different chemicals or chemical mixtures that are relevant to environmental toxicology. The chemicals considered by the earlier branches of toxicology were, and are, a known quantity. That is, the research was designed to address questions about specific, well-characterized chemicals, exposure conditions, and even concentration ranges rather than complex chemical mixtures. For example, pharmacologists might work with a particular active ingredient (e. g. , salicylic acid or aspirin), and be confident about the route of exposure (oral) and the concentration or dose. This is seldom the case in environmental toxicology, and hazardous waste assessment and cleanup in particular, where chemicals often are present in mixtures, routes of exposure may vary (for example, from oral to dermal to inhalation). Significantly, exposure concentrations prove difficult to determine. Mechanisms and Factors Responsible for the Entrance of Toxicants in the Human body and their Harmful Effects Absorption of toxicants Absorption is the process whereby toxicants gain entrance to the body. Ingested and inhaled materials, nonetheless, are considered outside the body until they cross the cellular barriers of the gastrointestinal tract or the respiratory system. To exert an effect on internal organs a toxicant must be absorbed, although such local toxicity as irritation, may occur. Absorption varies greatly with specific chemicals and with the route of exposure. For skin, oral or respiratory exposure, the exposure dose (or, â€Å"outside† dose) is usually only a fraction of the absorbed dose (that is, the internal dose). For substances injected or implanted directly into the body, exposure dose is the same as the absorbed or internal dose. Several factors affect the likelihood that a foreign chemical or, xenobiotic, will be absorbed. According to E. Monosson, the most important are: †¢ Route of exposure Concentration of the substance at the site of contact †¢ Chemical and physical properties of the substance The relative roles of concentration and properties of the substance vary with the route of exposure. In some cases, a high percentage of a substance may not be absorbed from one route whereas a low amount may be absorbed via another route. For example, very little DDT powder will penetrate the skin whereas a high percentage will be absorbed when it is swallowed. Due to such route-specific differences in absorption, xenobiotics are often ranked for hazard in accordance with the route of exposure. A substance may be categorized as relatively non-toxic by one route and highly toxic via another route. The primary routes of exposure by which xenobiotics can gain entry into the body are: †¢ Gastrointestinal tract: Key in environmental exposure to food and water contaminants and is the most important route for many pharmaceuticals. †¢ Respiratory tract: Key in environmental and occupational exposure to aerial toxicants and some drugs that use this route (i. e. : inhalers). †¢ Skin: Also an environmental and occupational exposure route. A lot of medicines are applied to the skin directly. Other routes of exposure—used primarily for specific medical purposes—are: †¢ Injections (IV, Subcutaneous, Intradermal, Intrathecal) basically used for medications. †¢ Implants (Hormone patches) †¢ Conjunctival instillations (Eye drops) †¢ Suppositories For a toxic to enter the body (as well as move within, and leave the body) it must pass across cell membranes (cell walls). Cell membranes are formidable barriers and major body defenses that prevent foreign invaders or substances from gaining entry into body tissues. Normally, cells in solid tissues (for example, skin or mucous membranes of the lung or intestine) are so tightly compacted that substances cannot pass between them. Entry, therefore, requires that the xenobiotic have some capability to penetrate cell membranes. Also, the substance must cross several membranes in order to go from one area of the body to another. In essence, for a substance to move through one cell requires that it first move across the cell membrane into the cell, pass across the cell, and then cross the cell membrane again in order to leave the cell. This is true whether the cells are in the skin, the lining of a blood vessel, or an internal organ (for example, the liver). In many cases, in order for a substance to reach its site of toxic action, it must pass through several membrane barriers. Cell membranes surround all body cells and are basically similar in structure. They consist of two layers of phospholipid molecules arranged like a â€Å"sandwich† and also known as â€Å"phospholipid bilayer†. Each phospholipid molecule consists of a phosphate head and a lipid tail. The phosphate head is polar so it is hydrophilic (attracted to water). In contrast, the lipid tail is lipophilic (attracted to lipid-soluble substances). The two phospholipid layers are oriented on opposing sides of the membrane so that they are approximate mirror images of each other. The polar heads face outward and the lipid tails inward. The cell membrane is tightly packed with these phospholipid molecules—interspersed with various proteins and cholesterol molecules. Some proteins span across the entire membrane providing for the formation of aqueous channels or pores. Some toxicants move across a membrane barrier with relative ease while others find it difficult or impossible. Those that can cross the membrane, do so by one of two general methods: either passive transfer or facilitated transport. Passive transfer consists of simple diffusion (or osmotic filtration) and is â€Å"passive† in that there is no requirement for cellular energy or assistance. Some toxicants cannot simply diffuse across the membrane. They require assistance that is facilitated by specialized transport mechanisms. The primary types of specialized transport mechanisms are: †¢ Facilitated diffusion †¢ Active transport †¢ Endocytosis (phagocytosis and pinocytosis). Passive transfer is the most common way that xenobiotics cross cell membranes. Two factors determine the rate of passive transfer: †¢ Differences in concentrations of the substance on opposite sides of the membrane (substance moves from a region of high concentration to one having a lower concentration. Diffusion will continue until the concentration is equal on both sides of the membrane); and †¢ Ability of the substance to move either through the small pores in the membrane or through the lipophilic interior of the membrane. Properties of the chemical substance that affect its ability for passive transfer are: †¢ Lipid solubility Molecular size †¢ Degree of ionization (that is, the electrical charge of an atom) Substances with high lipid solubility readily diffuse through the phospholipid membrane. Small water-soluble molecules can pass across a membrane through the aqueous pores, along with normal intracellular water flow. Large water-soluble molecules usually cannot make it through the small pores, although some may diffuse through the l ipid portion of the membrane, but at a slow rate. In general, highly ionized chemicals have low lipid solubility and pass with difficulty through the lipid membrane. Most aqueous pores are about 4 angstrom (A) in size and allow chemicals of molecular weight 100-200 to pass through. Exceptions are membranes of capillaries and kidney glomeruli that have relatively large pores (about 40A) that allow molecules up to a molecular weight of about 50,000 (molecules slightly smaller than albumen which has a molecular weight of 60,000) to pass through. Facilitated diffusion is similar to simple diffusion in that it does not require energy and follows a concentration gradient. The difference is that it is a carrier-mediated transport mechanism. The results are similar to passive transport but faster and capable of moving larger molecules that have difficulty diffusing through the membrane without a carrier. Examples are the transport of sugar and amino acids into red blood cells (RBCs), and into the central nervous system (CNS). Some substances are unable to move with diffusion, unable to dissolve in the lipid layer, and are too large to pass through the aqueous channels. For some of these substances, active transport processes exist in which movement through the membrane may be against the concentration gradient: they move from low to higher concentrations. Cellular energy from adenosine triphosphate (ADP) is required in order to accomplish this. The transported substance can move from one side of the membrane to the other side by this energy process. Active transport is important in the transport of xenobiotics into the liver, kidney, and central nervous system and for maintenance of electrolyte and nutrient balance. Many large molecules and particles cannot enter cells via passive or active mechanisms. However, some may enter, by a process known as endocytosis. In endocytosis, the cell surrounds the substance with a section of its cell wall. This engulfed substance and section of membrane then separates from the membrane and moves into the interior of the cell. The two main forms of endocytosis are phagocytosis and pinocytosis. In phagocytosis (cell eating), large particles suspended in the extracellular fluid are engulfed and either transported into cells or are destroyed within the cell. This is a very important process for lung phagocytes and certain liver and spleen cells. Pinocytosis (cell drinking) is a similar process but involves the engulfing of liquids or very small particles that are in suspension within the extracellular fluid. Gastrointestinal Tract The gastrointestinal tract (GI tract, the major portion of the alimentary canal) can be viewed as a tube going through the body. Its contents are considered exterior to the body until absorbed. Salivary glands, the liver, and the pancreas are considered accessory glands of the GI tract as they have ducts entering the GI tract and secrete enzymes and other substances. For foreign substances to enter the body, they must pass through the gastrointestinal mucosa, crossing several membranes before entering the blood stream. Substances must be absorbed from the gastrointestinal tract in order to exert a systemic toxic effect, although local gastrointestinal damage may occur. Absorption can occur at any place along the entire gastrointestinal tract. However, the degree of absorption is strongly site dependent. Three main factors affect absorption within the various sites of the gastrointestinal tract: †¢ Type of cells at the specific site †¢ Period of time that the substance remains at the site †¢ pH of stomach or intestinal contents at the site. Under normal conditions, xenobiotics are poorly absorbed within the mouth and esophagus, due mainly to the very short time that a substance resides within these portions of the gastrointestinal tract. There are some notable exceptions. For example, nicotine readily penetrates the mouth mucosa. Also, nitroglycerin is placed under the tongue (sublingual) for immediate absorption and treatment of heart conditions. The sublingual mucosa under the tongue and in some other areas of the mouth is thin and highly vascularized so that some substances will be rapidly absorbed. The stomach, having high acidity (pH 1-3), is a significant site for absorption of weak organic acids, which exist in a diffusible, nonionized and lipid-soluble form. In contrast, weak bases will be highly ionized and therefore are absorbed poorly. Chemically, the acidic stomach may break down some substances. For this reason those substances must be administered in gelatin capsules or coated tablets, that can pass through the acidic stomach into the intestine before they dissolve and release their contents. Another determinant that affects the amount of a substance that will be absorbed in the stomach is the presence of food. Food ingested at the same time as the xenobiotic may result in a considerable difference in absorption of the xenobiotic. For example, the LD50 for Dimethline (a respiratory stimulant) in rats is 30 mg/kg (or 30 parts per million) when ingested along with food, but only 12 mg/kg when it is administered to fasting rats. The greatest absorption of chemicals, as with nutrients, takes place in the intestine, particularly in the small intestine (see Figure 9). The intestine has a large surface area consisting of outward projections of the thin (one-cell thick) mucosa into the lumen of the intestine (the villi). This large surface area facilitates diffusion of substances across the cell membranes of the intestinal mucosa. Since the intestinal pH is near neutral (pH 5-8), both weak bases and weak acids are nonionized and are usually readily absorbed by passive diffusion. Lipid soluble, small molecules effectively enter the body from the intestine by passive diffusion. In addition to passive diffusion, facilitated and active transport mechanisms exist to move certain substances across the intestinal cells into the body, including such essential nutrients as glucose, amino acids and calcium. Also, strong acids, strong bases, large molecules, and metals (and some important toxins) are transported by these mechanisms. For example, lead, thallium, and paraquat (herbicide) are toxicants that are transported across the intestinal wall by active transport systems. The high degree of absorption of ingested xenobiotics is also due to the slow movement of substances through the intestinal tract. This slow passage increases the length of time that a compound is available for absorption at the intestinal membrane barrier. Intestinal microflora and gastrointestinal enzymes can affect the toxicity of ingested substances. Some ingested substances may be only poorly absorbed but they may be biotransformed within the gastrointestinal tract. In some cases, their biotransformed products may be absorbed and be more toxic than the ingested substance. An important example is the formation of carcinogenic nitrosamines from non-carcinogenic amines by intestinal flora. Very little absorption takes place in the colon and rectum. As a general rule, if a xenobiotic has not been absorbed after passing through the stomach or small intestine, very little further absorption will occur. However, there are some exceptions, as some medicines may be administered as rectal suppositories with significant absorption. An example, is Anusol (hydrocortisone preparation) used for treatment of local inflammation which is partially absorbed (about 25%). Respiratory Tract Many environmental and occupational agents as well as some pharmaceuticals are inhaled and enter the respiratory tract. Absorption can occur at any place within the upper respiratory tract. However, the amount of a particular xenobiotic that can be absorbed at a specific location is highly dependent upon its physical form and solubility. There are three basic regions to the respiratory tract: †¢ Nasopharyngeal region †¢ Tracheobronchial region †¢ Pulmonary region By far the most important site for absorption is the pulmonary region consisting of the very small airways (bronchioles) and the alveolar sacs of the lung. The alveolar region has a very large surface area (about 50 times that of the skin). In addition, the alveoli consist of only a single layer of cells with very thin membranes that separate the inhaled air from the blood stream. Oxygen, carbon dioxide and other gases pass readily through this membrane. In contrast to absorption via the gastrointestinal tract or through the skin, gases and particles, which are water-soluble (and thus blood soluble), will be absorbed more efficiently from the lung alveoli. Water-soluble gases and liquid aerosols can pass through the alveolar cell membrane by simple passive diffusion. In addition to solubility, the ability to be absorbed is highly dependent on the physical form of the agent (that is, whether the agent is a gas/vapor or a particle). The physical form determines penetration into the deep lung. A gas or vapor can be inhaled deep into the lung and if it has high solubility in the blood, it is almost completely absorbed in one respiration. Absorption through the alveolar membrane is by passive diffusion, following the concentration gradient. As the agent dissolves in the circulating blood, it is taken away so that the amount that is absorbed and enters the body may be quite large. The only way to increase the amount absorbed is to increase the rate and depth of breathing. This is known as ventilation-limitation. For blood-soluble gases, equilibrium between the concentration of the agent in the inhaled air and that in the blood is difficult to achieve. Inhaled gases or vapors, which have poor solubility in the blood, have quite limited capacity for absorption. The reason for this is that the blood can become quickly saturated. Once saturated, blood will not be able to accept the gas and it will remain in the inhaled air and then exhaled. The only way to increase absorption would be to increase the rate of blood supply to the lung. This is known as flow-limitation. Equilibrium between blood and the air is reached more quickly for relatively insoluble gases than for soluble gases. The absorption of airborne particles is usually quite different from that of gases or vapors. The absorption of solid particles, regardless of solubility, is dependent upon particle size. Large particles (>5  µM) are generally deposited in the nasopharyngeal region ((head airways region) with little absorption. Particles 2-5  µM can penetrate into the tracheobronchial region. Very small particles (

The Wonders Of Modern Science And Astronomy - 1581 Words

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